3D printing has experienced a tremendous development in recent decades on the technological as well as material side. However, most 3D printable materials are restricted in one aspect: They produce static 3D geometries, unable to respond or adapt to their environment – limiting in this way their applicability for smart technologies where a dynamic behavior is needed. To overcome this issue, the concept of “4D printing” emerged, where the incorporation of time as fourth dimension in 3D geometries enables new features such as responsiveness or adaptivity towards external stimuli. The simplest strategy to access such 4D structures is the utilization of smart polymeric materials for ink design, which can respond to external stimuli on-demand. In particular, the use of shape memory polymers (SMP) – one of the promising materials investigated in this thesis – is suitable for this purpose. Although the concept (and use) of SMP has already been investigated at the macroscale, the microscale is only scarcely explored. Taking one step further, this work presents – in the first part - a novel SMP ink system offering printability of thermoresponsive structures at macro- and microscale using light-based techniques namely digital light processing (DLP) and two-photon laser printing (2PLP). In particular, formulations based on designed SMP ink system are designed and adapted to fulfill requirements of each technique. At both size regimes (macro and micro) excellent printability as well as shape memory properties are demonstrated. Especially the microformulation is considered as promising system for applications in future fields such as microrobotics, biomedical therapies or smart microsensors. In a further work, push-pull azo dye species are incorporated into the SMP formulation giving access to light responsive 4D architectures fabricated at high resolution using DLP. By exploitation of the dyes’ photothermal effects, new features are achieved. Translation towards light as stimulus allows excellent spatial control during shape recovery and access to a multiplicity of intermediate shapes. Last, investigating another aspect of 4D printing, “living” radical polymerization features are incorporated in 3D microstructures permitting the generation of 3D geometries, enabling precise setting of their properties for customized applications. In particular, dormant alkoxyamine bonds were integrated during 2PLP fabrication, allowing postmodification by network decrosslinking via nitroxide exchange reaction (NER) and by chain extension with styrene via nitroxide-mediated polymerization (NMP). Remarkable changes in mechanical properties and size are achieved, giving in this way access to precisely manufacturable and adjustable microscopic geometries –relevant for areas and fields where customized precise architectures are of highest necessity.
The prostate-specific membrane antigen (PSMA) has proven to be a promising target for diagnostic and therapeutic purposes. Although this biological target is well-recognized for prostate cancer, the expression of PSMA is not only restricted to prostate cancer. It is also expressed in many tumor types derived from the endothelial cells of tumor blood vessels. This thesis explores the development of inhibitors for specific targeting of PSMA. These inhibitors are small molecules that contain the Glu-NH-CO-NH-Lys moiety as binding motif, which was already shown to bind to PSMA with high affinity. The novel synthesized compounds were designed using PSMA-617 as reference. PSMA-617, bearing the linker moieties 2-naphthyl-L-alanine and 4-(aminomethyl) cyclohexanecarboxylic acid still the standard structure with respect to pharmacokinetics and internalization efficiency. Improvement of the linker moieties connected to alternative chelating agents to form stable complexes with copper radio-isotopes, in particular the theranostic pair 64Cu and 67Cu was one aim of the project. 64Cu represents an alternative in case where short-term PET imaging is not possible and it also allows the dosimetry of therapeutic 67Cu as an alternative to 177Lu. In the second part of this thesis, PSMA ligands were developed for labelling with lead radio-isotopes; for this study, the radioisotope 203Pb was used as an imaging agent to obtain an approximation for the dosimetry with 212Pb, a radionuclide that represents an in vivo alpha generator. In the last part of the project, a series of PSMA ligands that comprise a benzyl group in the chelator moiety was developed to further optimize the clinically established radiopharmaceutical PSMA- 617. These compounds were evaluated in vitro in the PSMA expressing cell line, C4-2 and in vivo in tumor bearing mice. Among the compounds evaluated, CA003, CA012, CA028 and CA030 were the most promising ones, as demonstrated by their high PSMAspecific cellular uptake and low kidney uptake. The performance of the novel compounds was assessed in first patient studies resulting in clear visualization of the cancer and metastatic lesions with high contrast.
Keywords: prostate-specific membrane antigen (PSMA), prostate cancer, PSMAinhibitors, PET imaging, endo-radiotherapy.
This thesis focuses on the properties and applications of ultrathin poly(ethylene glycol) (PEG) films and freestanding nanosheets, fabricated by thermally-induced crosslinking of amine/epoxy decorated STAR-PEG precursors. In addition, my research was also extended to another kind of molecular films – self-assembled monolayers (SAMs), for which the performance of a model aromatic-aliphatic tripodal SAM on Au(111) in the context of electron beam lithography (EBL) and fabrication of carbon nanomembranes (CNMs) – another kind of nanosheets – was tested.
As the first subproject, the effect of ultraviolet (UV) light (254 nm) on the PEG films was explored. UV irradiation was shown to result in progressive decomposition of the PEG material followed by desorption of released fragments, while preserving the original chemical composition and properties of the films, which offers potential for 3D patterning of PEG materials with retaining bioinert and hydrogel properties. As the second subproject, the effect of molecular weight (MW) of the precursors (2000-20000 g/mol) on the properties of the PEG films and nanosheets was studied. These systems exhibited pronounced biorepulsive, hydrogel, and elastic properties which varied with the MW. The MW affected in particular the swelling behavior and permeability of the PEG films as well as elastic properties of the PEG nanosheets. As the following subproject, the effect of other relevant parameters, such as a deviation from the equilibrium 1:1 composition of the precursors and electron and UV (additional studies) treatment were studied. In particular, the elasticity and stability of the PEG nanosheets were found to be strongly deteriorated by electron irradiation. In contrast, UV irradiation (254 nm) did not affect their elastic properties, in agreement with my previous results on this subject. Within the further subprojects, PEG films were used as a porous and bioinert matrix for DNA sensing, relying on immobilization and hybridization of single-stranded DNA (ssDNA) in the PEG matrix. The immobilization of the probe ssDNA was based on either NHS-ester-amine or thiol-epoxy linkage to the free amine or epoxy groups in the specifically prepared PEG matrix, respectively. In both cases, efficient immobilization of the probe ssDNA and high selectivity and hybridization efficiency of the resulting 3D ssDNA arrays with respect to the target strands were demonstrated. As a suitable transduction technique for the DNA sensing, requiring no ssDNA labeling, electrochemical impedance spectroscopy was employed.
Within a further subproject, a series of thin (80-100 nm) PEG-fullerene (C60) composite films were prepared by immersion, one-pot, and reflux methods. These films exhibited distinct optical and electrochemical properties of C60, merged with some favorable characteristics of the PEG matrix, resulting, in particular, in good electrochemical conductivity and high elasticity. It was demonstrated that these films can be detached from the primary substrate to form free-standing composite nanosheets, having potential for various applications such as flexible electronics, photodetectors, and electrochemical biosensors.
The final subproject was the electron-beam-induced treatment of a triptycene-based SAM (Trip-T1). Upon electron irradiation, this monolayer was found to exhibit behavior similar to that of monopodal aromatic monolayers, showing a clear dominance of intermolecular crosslinking. It was demonstrated that the Trip-T1 SAM can serve as a negative resist in EBL, similar to the reference, monopodal benzylthiol (PT1) SAM. Finally, robust and defect-free CNMs could be successfully fabricated from the Trip-T1 SAM, which, however, required a somewhat higher dose (80 mC/cm2) than for the reference PT1 monolayer (40 mC/cm2). These CNMs correspond to the low limit of material density for such objects.
This thesis deals with the design and characterization of self-assembled monolayers (SAMs) in the context of organic and molecular electronics.
The use of silicon compounds in challenging molecular transformations usually requires their activation by more reactive species, or a preceding transformation in reactive cationic or low-valent states. Only in the second half of the past decade, bis(perhalocatecholato)silanes (1X, X = F, Cl, Br) were reported as the first silane Lewis superacids – incorporating silicon in a neutral form and its natural oxidation state. Still, this burgeoning substance class suffers from drawbacks attributed to required donorcoordination, self-aggregation, poor solubility, or labile substituents. The present contribution describes strategies toward a second-generation of neutral silicon Lewis superacids exhibiting improved properties and an enhanced reactivity. First, a heuristic structure-effect relation between steric modification of the ligand and the final composition of the silicon species is derived by means of suitable model systems. The found relation is applied in the rational design of electron-withdrawing ligands, ultimately resulting in the new representatives bis(tetra(trifluoromethyl)catecholato)silane (1CF3) and bis(nonafluoro-N-phenyl-ortho-amidophenolato)silane (2). Both show an increased reactivity in comparison to their structural predecessors 1X, with no indication on the detrimental self-aggregation. Computations and experiments underlined that 1CF3 ranks among the strongest neutral Lewis acids currently accessible in the condensed phase. It thus enabled catalytic transformations that have never been mediated by a neutral silane. In cooperative action with 1,2,2,6,6-pentamethylpiperidine (pmp), the enhanced properties of 2 allowed the isolation of a hydridosilicate directly synthesized from H2 for the first time. This singularity provoked a first examination on the role of a tetrahedrally coordinated Lewis acid in the H2 cleavage as hallmark FLP reaction. Moreover, spontaneous, FLP type C–H silylations with 2/pmp leading to anionic silicates are described, which are reversible upon addition of a silaphilic donor. The thermodynamic stability of the silicates incited the assignment of an activation attribute as merely context dependent. Tangentially, a protocol for a catalytic C−C bond formation between N-heterocycles and acrylonitrile was derived. Overall, this work documents the guided evolution of the advancement of neutral, silicon Lewis superacids, now with an extended reactivity portfolio including more challenging bond activations. The here presented findings contribute to the fundamental understanding of the molecular chemistry of silicon – the second most abundant element in the earth’s crust.
The study of main-group species for catalysis has emerged in recent years as an active field of study, promising a sustainable alternative to the precious transition metals, whose use comes attached with concerns of toxicity, abundance and costs. Through strategic choice of substituents, typically inactive p-block elements may be activated for challenging bond activations. Rigid, bidentate catecholate and amidophenolate scaffolds were identified as suitable ligands for this purpose, and their impact on germanium and phosphorus compounds studied in this work. In the first part, perhalogenated bis(catecholato)germanes were prepared, characterized and shown by theory and experiment to be the first neutral germanium Lewis superacids, entirely stable in water. Additionally, they are active catalysts for a wide variety of reactions. At phosphorus, catecholates propelled the element typically used as Lewis base to new heights of Lewis acidity. Theoretical and experimental scaling methods ranked the newly prepared catecholato-phosphonium ions among the strongest, isolable Lewis acids. The high Lewis acidity was achieved even without requiring perhalogenation or multiple charges, and energy decomposition analysis assigned structural constraint as the key contributing factor. Aside from being highly active Lewis acid catalysts, the juxtaposition of electrophilic phosphorus and nucleophilic oxygen facilitated phosphorus-ligand cooperative bond activations. This way, inert C(sp2)-H, as well as Si-H bonds were cleaved, and cooperative addition of alkynes and alkenes was observed. Further control over the electronic and steric profiles of the spirophosphonium ions was asserted with amidophenolate substituents, which allowed isolation of the strongest, monocationic phosphonium ion yet, as well as ligand-cooperative activation of alkynes and alkenes following a different mechanism. Combination of both substituents gave phosphonium ions with Lewis acidity dependent structures, which could activate CH bonds by a frustrated Lewis pair-type mechanism. Lastly, a series of structurally constrained phosphenium ions based on pyridylmethylamidophenolate ligands was prepared and characterized. Tuning the substituents of the ligand periphery enabled reversible oxidative addition of even unactivated arenes such as benzene, which was unprecedented reactivity for main-group compounds. The mechanism of the reaction was elucidated by computations and a cooperative C-H deprotonation identified as key step
N-heteropolycycles are a class of aromatic compounds, in which C–H units of polycyclic aromatic hydrocarbons (PAHs) are substituted with N-atoms. These compounds are considered to be promising organic semiconductors with high potentials for the use as functional materials in (opto)electronic applications such as field-effect transistors and photovoltaic cells. For these applications, performance of a device is particularly dependent on the properties of the organic semiconductor at its interface with the metal electrodes. Therefore, gaining insights into the adsorption geometry and the electronic structure of N-heteropolycycles at the organic/metal interface and within their thin films are essential in improving and optimizing the device performance. In this thesis, this goal is achieved for various N-heteropolycyclic compounds by using two characterisation methods, high-resolution electron energy-loss spectroscopy (HREELS) and temperature-programmed desorption (TPD), in combination with density functional theory (DFT) calculations.
In the presented studies, all of the investigated molecules, at all coverages adopt a planar adsorption geometry relative to the substrate surface. By assigning the energies of the lowest excited singlet states (S) as well as the first triplet states (T1), it is found that N-introduction can effect the electronic structure of N-heteropolycycles in three ways, namely narrowing the optical gap (S0 → S1 transition), shifting the S0 → T1 transition to a higher energy and inducing a pronounced rise in the intensity of the α - band (S0 → S2 transition), in comparison to parent PAHs. Next, it is shown that the electronic structure of N-heteropolycycles can be fine-tuned by core substitution with halogens and aromatic groups, which results in a reduction of the transition energies of singlet and first triplet states. Subsequently, it is demonstrated that structural variation via connecting different moieties of N-heteropolycycles also leads to the narrowing the optical gap. Finally, it is determined that electron donating N-heteropolycycles in combination with well-known electron accepting molecules in donor/acceptor (D/A)-systems form charge transfer (CT)-complexes.
Chronic kidney diseases (CKDs) affect a huge population world-wide, where most of these patients do not know they are suffering from a CKD until the later stage. At this point, the treatment options available often lead to poor quality of life without full recovery of the kidney’s functioning. The current clinical diagnostic techniques are expensive, cumbersome, invasive and many-a-times not accurate. This creates a need for an early detection way. Glomerular filtration rate (GFR) to date is still the most used parameter for diagnosing kidney diseases. Nevertheless, tubular secretion and reabsorption play as much a role in healthy functioning of the kidney as does the filtration. The primary focus of this thesis has been to synthesise novel fluorescent markers for evaluating all three physiological processes of the kidneys. This would help diagnosing function-/location-specific abnormality in kidneys. These markers are tested for their use together in evaluating the three kidney functions simultaneously using a transcutaneous device. The detection can be done in parallel with multiple light-emitting diodes (LEDs), or successively. Since the ideal goal would be to measure all the kidney parameters together in a patient, the absorbance and emission wavelength for each marker is designed to be significantly different to evaluate each function distinctly. Fluorescently labelled cyclodextrin (ABZWCY-HβCD) was chosen as a GFR marker in the red-NIR region. The secretion markers have been designed analogous to the known organic anion transporter (OAT) substrates in the blue-green region of the visible light of the electromagnetic spectrum. Fluorescent glucose molecules have been designed as reabsorption markers in the near-infrared (NIR) region. All these functional markers altogether pave way for a wholesome, rapid, and non-invasive technique for kidney diagnosis at an early stage. In addition, fluorescent markers that can assist in kidney imaging were developed, to study its histology using confocal and light sheet microscopy. Fluorescent water-soluble chitosan was developed as a tool for staining kidney vasculature, allowing us to visualise pre- and post-glomerular capillaries along with large blood vessels. Preliminary results on all the markers show scope for their future biomedical application.
During the last three decades, the field of theoretical and computational chemistry has evolved rapidly, promoted by the increasing availability of computational power inherent in modern CPUs and cluster structures. This development has expressed itself in a particular manner in the formulation of modern state-of-the-art electronic structure methods in the frameworks of, for instance, the Algebraic Diagrammatic Construction scheme or Coupled Cluster. Application of these methods to the calculation of molecular excitation energies and properties that describe the most fundamental processes of light-matter interaction, has been established as a profound and reliable tool for experimentalists within chemistry and molecular sciences. This work, which is spilt into three main parts, presents the implementation as well as benchmarking of novel electronic structure methods for the Algebraic Diagrammatic Construction scheme (ADC) as well as Unitary Coupled Cluster (UCC). In the first part, an implementation and benchmark study for the calculation doubly-ionized as well as double electronically-attached states for ADC, termed DIP-ADC and DEA-ADC, respectively, up to third order is presented. The implementation was executed in the Q-Chem program package, benchmark studies included the comparison of states to Full CI data for DIP as well as EOMDIP-CCSD and EOMDEA-CCSD. For both schemes, the third-order methods DIP-ADC(3) as well as DEA-ADC(3) proved to produce results which are in a remarkable good agreement to the corresponding EOM-CCSD method. As for the second part, a benchmark study on core excitation energies in the framework of Unitary Coupled Cluster was presented. To this end, the Core-valence separation approximation was applied to the second-and third-order UCC schemes for electron excitations. It was shown that CVS-UCC is very suitable in the computation of X-ray spectra, similar to CVS-ADC, which has been studied before by Wenzel et al. and that it provides reliable data for the description and simulation of energetically high-lying core excitations. The last part of this work features an implementation of an automated code generator for Unitary Coupled Cluster as it was realized by Leitner et al. for the computation of electronically excited states on a ADC(4) level. Working equations for a UCC3-x scheme (in similarity to UCC2-x with an extended description of the doubles/doubles block of the secular matrix) as well as a full UCC4 for the calculation of electronically-excited states and properties are presented, together with an improved ground-state description, termed UCC4+5[s,t] that includes fifth-order terms. At the end of this work, all results for the three presented topics are summarized in detail, accompanied by a short outlook of what could include future work and development.
Characterisation, compression and shaping of mid-infrared (MIR) pulses are demonstrated in an acousto-optic modulator (AOM) shaper based setup. Characterisation of the pulses’ spectral phase is accomplished via an AOM shaper based variant of dispersion scan (d-scan). By a combination of d-scan and an evolutionary algorithm, broadband MIR pulses centred at 3.2 µm are compressed to below 50 fs FWHM autocorrelation. The shaping and characterisation capabilities of the setup are demonstrated by imprinting and retrieving a set of spectral phases of increasing complexity on compressed broadband MIR pulses. Moreover, the effect of excitation of the C=N=N stretching vibration on the photoreaction of 2-diazo-1-naphthol-5-sulfonate dissolved in methanol is investigated. The C=N=N stretch mode is excited up to at least v=3 by ultrafast MIR pulses. Molecular dissociation in the electronic ground state is not observed. Vibrational excitation decays within 20 ps. Experiments on vibrationally mediated photodissociation show that vibrational pre-excitation increases the photoreaction’s quantum yield by at least 10% compared to excitation of the molecule by a mere ultraviolet pulse. This is explained by an increased Franck-Condon overlap of the edge of the electronic ground state’s potential energy surface with the reactive part of the potential energy surface of the electronic excited state.
Living organisms build upon semi-flexible biopolymers to confer structural integrity and functionality to cells. Semi-flexible (bio-)polymers assemble into hierarchical networks governed by an interplay between entropic and enthalpic effects. The assembled network features a non-linear response to mechanical load, like strain-stiffening and compression-softening. This non-linearity stems from the many-body nature at the microscale, which significantly influences the behaviour at the mesoscale. Due to the lack of non-generic scale-bridging models, the response of semi-flexible (bio-)polymer networks to mechanical stress is not yet fully understood. The aim of this thesis is thus to explore major molecular deformation mechanisms of semi-flexible (bio-)polymer networks by large-scale yet chemically informed molecular dynamics simulations. We developed coarse-grained models for two semi-flexible (bio-)polymers with similar persistence lengths, namely poly(para-phenylene ethynylene)s (PPEs) and collagen, using the Martini 3 force field to perform molecular dynamics simulations under force and to identify locations of high-force concentration with bonds being prone to rupture. Our Martini 3 models largely capture key structural, mechanical and thermodynamic observables from atomistic simulations and experiments from the literature, including interchain packing, mechanical bending stiffness and solvation properties. We show that the entanglement of PPEs in large-scale bulk assemblies increases with polymer chain length. We further observe that long-chain PPE networks under shear-flow form shear bands with extreme shear rates in the fast band, that is, where rupture forces are highest and bonds are likely to fail. Also, we built atomistic structural models for collagen microfibrils with a tuneable crosslink density and combined Martini 3 with Gō-like potentials to find an increase in microfibrillar stretching with decreasing number of crosslinks. Our Martini 3 collagen model is suited to capture the force-stretching of collagen microfibrils from all-atom simulations, performed in collaboration with the Riken institute in Kobe. The two newly developed coarse-grained models for the semi-flexible PPE and collagen complement experiments by predicting bond rupture events in the large-scale assembled polymer networks. They push the frontier of molecular dynamics simulations more close to realism, that is, to their actual biological or synthetic counterparts, and will in future allow probing micrometer sized systems of various structural configurations.
This thesis mainly aims to investigate the influence of side chain modifications on the properties of imine based organic cage compounds. A series of [2+3] isostructural POCs with n-butyl, perfluorinated n-butyl, and partially fluorinated n-butyl groups, is synthesized by precursor modification strategy and the structure-property relationship between the degree of fluorination of the alkyl chains and gas sorption properties for perfluorocarbons (PFCs) is studied in detail. The cage with fluorinated side chains shows excellent selectivities for PFCs over N2 (e.g., SH = 41475 for c-C4F8 vs N2), due to fluorine-fluorine interactions. This strategy extends to introducing n-fluorinated alkyl chains of different lengths from perfluoromethyl to perfluorohexyl into [2+3] POCs. The impact of chain lengths on gas uptakes and selectivities for PFCs, sulphur hexafluoride (SF6), and nitrogen trifluoride (NF3) over not only N2 but also O2 or CO2 is explored. The cage with perfluoropentyl chains displays outstanding selective adsorption properties for these fluorinated gases (F-gases) over N2 or O2, while the cage with perfluorobutyl chains still remained the most selective for F-gases over CO2 (e.g., SH = 19631 for c-C4F8 vs CO2). Moreover, the solid packing of POCs significantly influences gas sorption. [2+3] POC with perfluoromethyl groups exhibits different porous and non-porous polymorphic forms, influenced by crystallographic packing and the orientation of middle flexible phenyl groups in terphenyl units. The specific surface of [2+3] POC can be significantly enhanced by elongated π systems of terphenyl units and the optimization of activation conditions. Lastly, a series of [4+4] truncated tetrahedral nitrogen-rich POCs, synthesized from prochiral tripyrroltrialdehyde and side chain-modified amines, reveals face-oriented polyhedra in the crystalline state through X-ray crystallography.
Natural materials are composed of a limited number of molecular building blocks, e.g. amino acids, carbohydrates), and their exceptional properties are governed by their intricate hierarchical structure on multiple length scales. While 3D printing has emerged as the standard method for the precise fabrication of minute devices, this level of precision is unattainable with current state-of-the-art materials for 3D printing. A common method of obtaining such nanoscale structure in systematic systems exploits the potential for polymers to self-assemble under certain conditions. One important class of polymers which has the ability to form self-assembled structures at a scale of 5- 50 nm are amphiphilic block copolymers. They are tunable over a broad variety of morphologies, ranging from micelles and vesicles to continuous network structures, which can form in both undiluted melt or solution. While these properties have been extensively investigated in 2D films, they have not yet been exploited to generate 3D structures entailing high resolution features, complex geometries and a controlled nanostructure. To that end, in the current PhD thesis, new self-assembled printable materials based on block copolymers (BCPs) that enable precise control of the nanostructure in 3D are investigated. In particular, well-defined BCPs consisting of a poly(styrene) block and a poly(methacrylate)-based copolymer decorated with printable units are selected as suitable self-assembling materials. A broad library of BCPs with different compositions and molecular weight is synthesized using controlled radical polymerization. A subsequent extensive investigation of the phase behavior before and after the functionalization is performed using SAXS, SEM, and SNOM. Lamellar, cylindrical and gyroid morphologies are observed dependent on the composition as well as the molecular weight, allowing the phase diagram of the system to be generated. The dependency of the domain spacing d on the molecular weight of the polymer is found to be described by a power law, which is in accordance with that published for other systems both experimentally as well as in theory. The synthesized library of BCPs is then utilized to create printable formulations for the fabrication of complex 3D microstructures using two-photon laser printing. By fine-tuning the BCP composition and solvent in the formulations, the fabrication of precise 3D nano-ordered structures is demonstrated for the first time. Hereby, the key achievement is a controlled nano-order within the entirety of the 3D structures. To show this, imaging of the cross-sections of the 3D printed samples is performed, enabling visualization also from the inside. A detailed view of both lamellar as well as cylindrical morphology, dependent on the polymer design, is presented. The morphologies are fitting well with those found in the respective bulk polymer analysis, as well as SAXS measurements of the printing ink formulation.
This guide provides a detailed step-by-step procedure for the dispersion of (6,5) single-walled carbon nanotubes by shear force mixing with the conjugated polymer PFO-BPy in organic solvents. All processes presented here were developed in the Zaumseil group at Heidelberg University since 2015 and represent best practices to the best of our knowledge. In addition to the detailed instructions, we discuss potential pitfalls and problems, that we have encountered over eight years of operation and show how to solve them. This also includes a detailed description of how to maintain and service a shear force mixer to ensure long operation lifetime. Finally, we show how to expand our process to the dispersion other nanotube chiralities in electronic-grade quality and how to treat dispersions for subsequent processing (e.g., thin film deposition or functionalization).
Die vorliegende Dissertation beschäftigt sich mit zwei neuen Wegen, die elektronische Struktur von Übergangsmetallkomplexen mit redoxaktiven Guanidin-Liganden (GFA) zu steuern: durch die Einführung einer sekundären Koordinationssphäre sowie durch Homokonjugation. Die Kombination dieser Ligandenklasse als starke Elektronendonoren mit redoxaktiven Übergangsmetallen führt zur Möglichkeit intramolekularer Elektronenübertragungen von den Liganden auf die Metallatome. Besonders in CuII-Komplexen wurden solche Prozesse bereits intensiv untersucht und es konnten mehrere Einflussfaktoren wie die Elektronendonorstärke des Liganden, die Art der Coliganden, sowie der Lösungsmittelpolarität und der Temperatur gefunden werden. Der Fokus lag stets auf der primären Koordinationssphäre der Liganden mit dem Metallatom. Durch den Einbau einer [18]Krone-6-Funktion als Rückgrat eines redoxaktiven Bisguanidin-Liganden gelang in dieser Arbeit die Einführung einer sekundären Koordinationssphäre. In einem CuCl2-Komplex konnte ein valenztautomeres Gleichgewicht beobachtet werden. Erstmalig konnte gezeigt werden, dass die Einlagerung von Kalium- und Barium-Ionen in den Kronenether zu einer drastischen Änderung der elektronischen Struktur führt und weit über eine typische anodische Verschiebung des Redoxpotentials des Liganden hinausgeht. Die Koordination der Ionen initiiert einen intramolekularen Elektronen-transfer vom Metallatom auf den Liganden. Auch in einfach oxidierten CoII-Komplexen wurde der Einfluss auf deren elektronische Struktur untersucht, wobei unabhängig von der Metall-Einlagerung in den Kronenether ein Lösungsmitteleinfluss beobachtet werden konnte. Darüber hinaus konnte dieses neue Ligandensystem auf Dibenzo-Kronenether erweitert werden. So gelang die Synthese neuer Tetraguanidine, in denen zwei o-Bisguanidinobenzol-Einheiten über eine sekundäre Koordinationssphäre verknüpft sind. Besonders interessant ist hierbei die Vergrößerung des Kronenethers zu [24]Krone-8, wobei quantenchemische Untersuchungen zeigen, dass die elektronische Struktur von Metallkomplexen durch die Koordination eines linearen Moleküls durch den Makrozyklus gesteuert werden kann. Weitere experimentelle Untersuchungen könnten den GFA den Weg in die supramolekulare Chemie ebnen. Des Weiteren wurde in dieser Arbeit der Einfluss der Homokonjugation in GFA-Verbindungen untersucht. So wurden erstmalig Hexaguanidino-Triptycen-Derivate synthetisiert, in denen drei o-Bisguanidinobenzol-Einheiten durch diese Art der Konjugation in Wechselwirkung stehen. Das Cyclovoltammogramm zeigt drei reversible Zwei-Elektronen-Oxidationen, was im Einklang mit der Abhängigkeit dieser Einheiten aufgrund der elektronischen Kopplung durch die Homokonjugation steht. Zweifache Oxidation führt zu paramagnetischen Salzen, welche intensive π π*-Übergänge mit Charge-Transfer-Charakter im sichtbaren-NIR-Spektralbereich aufweisen. Detaillierte magnetometrische Messungen (SQUID, ESR) neuer CoII-Komplexe zeigen einen elektronischen high-spin Grundzustand mit neun ungepaarten Elektronen. Partielle Oxidation der Komplexe führt zu ähnlichen ligandenzentrierten elektronischen Übergängen wie bei den freien Liganden. Im Gegensatz dazu konnten diese Beobachtungen mit bereits bekannten Hexaguanidino-Triphenylen-Verbindungen nicht gemacht werden. Dadurch konnte gezeigt werden, dass die elektronische Kopplung durch die Homokonjugation einen entscheidenden Einfluss auf die optischen Eigenschaften und somit die elektronische Struktur solcher Verbindungen hat.
Lysosomes are membrane-bound organelles that act as a central hub for the recycling of biomolecules derived from cellular processes such as autophagy, endocytosis, among others. Lysosomal dysfunction is often linked to severe pathologies such as lysosomal storage disorders (LSDs), which are characterized by the aberrant accumulation of substrates, such as lipids. While cholesterol efflux from lysosomes is well-understood, the transport of other biologically active lipids such as sphingosine remain unknown. This knowledge gap is attributed to a lack of functional tools to manipulate and investigate lipids within living cells and on a single organelle level. The recent development of organelle-targeted caging groups, photoaffinity labeling and in combination with biorthogonal reactions represents a valuable and non-invasive way to identify new protein interactors of single lipid species while acquiring an exquisite spatial-temporal control. This work presents the development, characterization and application of a method to investigate the previously enigmatic export of sphingosine from lysosomes. To this end, We have synthesized lysosome-targeted photoactivatable sphingosine (Lyso- pacSph) and lysosome-targeted photoactivatable cholesterol (Lyso-pacChol) that combine existing technologies such as photoaffinity labeling and a lysosome-targeted photoremovable caging group. In this way, the lyso-probes allow their controlled release within the lysosome using a flash of light. Their remaining modifications enable the study of their trafficking and metabolism as well as the capture of their unique lysosomal interactome. Excitingly, known cholesterol transporters, such as the abundant lysosomal protein SCARB2/LIMP-2 and Niemann-Pick type C1 (NPC1) were also identified as sphingosine interactors. Additionally, I show that both proteins play similar roles in sphingosine transport from lysosomes. Absence of either protein resulted in delayed sphingosine metabolism as observed by thin-layer chromatography as well as prolonged lysosomal localization of the sphingosine probe as shown in fluorescence microscopy experiments. The latter method also allowed me to analyze the impact of an approved drug for NPC, miglustat, on subcellular sphingosine and cholesterol trafficking. Additionally, artificial elevation of sphingosine levels in WT cells created a cholesterol export defect reminiscent of NPC disease, pointing towards a direct and causative role of sphingosine in the pathobiochemistry of this disease. Overall, the developed method presents a powerful tool to investigate the actions of biologically active lipid species with subcellular precision. This will likely inspire the generation of similar tools targeting different lipids and other organelles, thus contributing to a more detailed understanding of the intricacies of lipid-mediated signaling events.
In der vorliegenden Arbeit wird die Stoffklasse der Lanthanoidborohydride mithilfe von paramagnetischer NMR-Spektroskopie untersucht und dabei der Anteil an Fermi und pseudo contact shift an der chemischen Verschiebung bestimmt. Weiterhin werden Versuche zur Darstellung heteroleptischer Lanthanoid-Doppeldeckerverbindungen mit Phthalocyanin- und Cyclopentadienylliganden durchgeführt, die zur Darstellung einer gut löslichen Tripeldeckerverbindung bestehend aus einem Lanthanoid-Doppeldecker und einer Cyclopentadienyl-Zink-Einheit führt. Zur Untersuchung der Sauerstoffreduktion wird ein gut löslicher vierfach koordinierter Eisen-Phthalocyaninkomplex synthetisiert, der sich aufgrund seiner freien axialen Koordinationsstellen in Lösung sehr reaktiv gegenüber Sauerstoff und anderen Reagenzien zeigt. Die axiale Koordination von Lösungsmittelmolekülen wird mittels Kristallstrukturanalyse, sowie anhand paramagnetischer NMR-Daten nachgewiesen. Durch Reaktion mit Chlorierungsreagenzien kann reversibel eine einfach und zweifach chlorierte Eisen-Phthalocyaninverbindung erhalten werden. Bei der zweifach chlorierten Verbindung wurde der Phthalocyaninligand einfach oxidiert, sodass ein ligandzentriertes Radikal resultiert, welches charakteristische paramagnetische NMR-Verschiebungen aufweist. Bei der Reaktion mit Ammoniak oder Isonitrilverbindungen werden axial substituierte diamagnetische Verbindungen erhalten, welche sich oxidationsstabil zeigen und bei höheren Temperaturen zurück in die Ausgangsverbindung überführt werden können. In Gegenwart von Luftsauerstoff wird die Bildung einer Eisenhydroxoverbindung beobachtet und deren Bildung durch Kristallstrukturdaten bestätigt. Die Kinetik der Bildungsreaktion wird mittels UV-VIS-Spektroskopie untersucht und aus der Messung in verschiedenen Lösungsmitteln, sowie aus der Reaktion mit Wasserstofftransferreagenzien Rückschlüsse auf den Reaktionsmechanismus gezogen. Die Reversibilität der Oxidation und damit eine Eignung als Katalysator für die Sauerstoffreduktion wird untersucht und kann durch Erhitzen der Verbindung erreicht werden.
The objective of this thesis was the synthesis and characterization of larger (aza)acenes (> pentacenes) and their radical anions. The thesis focuses on the stabilization of azaacenes by positioning the silylethynyl groups adjacent to the central pyrazine / pyrazinopyrazine rings, which renders azaacenes immune to Diels-Alder reactions, butterfly dimerization and endoperoxide formation (Figure 1). Six (aza)heptacenes containing 0, 2, 4 or 6 nitrogen atoms and four triisopropylsilyl (TIPS) ethynyl substituents were synthesized. The position of the four TIPS ethynyl substituents determines the (aza)heptacenes’ stability. The symmetric 7,16-diaza-6,8,15,17-tetrakis (triisopropylsilylethynyl)heptacene (DAH1), in which the two nitrogen atoms occupy the central ring and the four TIPS-ethynyl substituents fill the four positions in the two directly adjacent rings, is much more stable than any hitherto reported (aza)heptacenes and survives several weeks in solution on the benchtop according to UV-Vis studies. Thin film transistors with μe = 0.042 cm2V-1 s-1 were produced for DAH1. The tetraazaheptacene (TAH) is also reasonably stable (> 7 d), but hexaazaheptacene (HAH) is such a strong oxidant that undergoes spontaneous reduction (≈ 5 d) according to UV-Vis studies. A series of 5,8,13,16-tetraethynyl-6,7,14,15-tetraazahexacenes were synthesized – all were persistent in solution. Upon crystallization, the derivatives with TIPS ethynyl substituents equilibrate into their didehydrotetrazecines (cyclic biscarbodiimide) isomers in the solid state. This solid-state ring opening is enforced by the bulk of the substituents, crystal packing energy and aromaticity given in terms of Clar sextets – with increasing steric bulk the crystal lattice itself enforces ring opening. This process is fully reversible, upon dissolution, the steric force disappears and the bis-carbodiimides revert into the azaacene form. The reversible rearrangement process was also observed in the pentacene and heptacene congeners.
Two-photon laser printing (2PLP) is a disruptive three-dimensional (3D) printing technique that can afford structural fabrication at the submicrometer scale. Apart from constructing static 3D structures, research in fabricating dynamic ones, known as "4D printing”, is becoming a burgeoning field. 4D printed structures exhibit adaptability or tunability towards their environment through the control of an external stimulus. In contrast to the rapid growth in macroscale fabrication, progress in microprinted actuators has only been scarcely reported. Liquid crystal elastomer (LCE) stands out among the promising classes of smart materials for fabricating microrobotics or microactuators due to its distinct anisotropic property, which enables the printed structures to exhibit automated reversible movements upon exposure to stimuli without environmental limitations. Nevertheless, the use of 2PLP for the manufacture of 4D printed LCE microstructures with high versatility and complexity have presented some challenges, limiting their implementation in final applications. This thesis aims to overcome two main obstacles faced in this regard: first, the limitation of two-photon printable stimuli-responsive materials; and second, the lack of a facile approach for aligning liquid crystal (LC) within three dimensions. The first part of this thesis aims on expanding the library of materials used for implementing light responsiveness into LC microstructures, as light provides a higher degree of temporal and spatial control compared to other stimuli. The initial approach has involved incorporation of acrylate-functionalized photoresponsive molecules, such as azobenzene and the donor-acceptor Stenhouse adduct (DASA), into a LC ink using a conventional synthetic method. However, several challenges, such as compatibility with the LC ink, have prevented the achievement of 4D printing via 2PLP. The second approach is based on post-modifying printed LC structures and successfully fabricated microactuators with five different photoresponsive features by individually incorporating each light-absorbing molecule. Furthermore, LC microactuators that exhibit distinct actuation patterns under different colors of light were fabricated by simultaneously implementing orthogonal photoresponsive molecules. The second project presented in this thesis focuses on developing a new strategy to induce alignment domains in a more flexible manner, with the aim of spatially tailoring the LC topology of the 3D printed microstructures. This is achieved by microprinting 3D scaffolds based on polydimethylsiloxane (PDMS) to manipulate the alignment directions of LC molecules. Taking advantage of 2PLP to fabricate arbitrary scaffolds, LC alignments, including planar and radial patterns, could be introduced freely and simultaneously in three-dimensional space with varying degrees of complexity. The applicability of this alignment approach was demonstrated by fabricating responsive LC microstructures within different PDMS environments, and distinct actuation patterns were observed. Overall, these two breakthroughs have unveiled a wide array of new potentials for the utilization of responsive LC microsystems with tunable functionalities and customizable actuation responses, that can be applied across various domains and applications.
Photophysical and-chemical processes make use of light as strongly quantized energy source, rendering mechanisms possible, which involve excited states that are thermally unavailable. This puts them at the heart of many exciting and promising technologies from photovoltaics to photocatalysis and photodynamic therapy. In this work, several strategies to tuning these excited states are rationalized by ultrafast transient absorption and impulsive vibrational spectroscopy, applied to two different classes of samples. Firstly, the excited-state dynamics of two iron(II) complexes are investigated for the tuning effect of solvent choice and ligand design. They toggle on and off the involvement of metal-centered (MC) excited states acting as loss channels for desired metal-to-ligand charge transfer (MLCT) states. Impulsive vibrational spectroscopy is established as suitable method for identifying MLCT-MC transitions in [Fe(bpy)(CN)4]2-, a well-known reference sample. The method is then applied to an iron(II)N-heterocyclic carbene complex and identifies an ultrafast MLCT-MC branching in this promising dye-sensitizer candidate. Secondly, the photophysics and -chemistry of triphenylamine is thoroughly investigated for the influences of solvent, the oxygen content therein and enforced planarity. In n-hexane, triphenylamine is converted to N-phenylcarbazole, with oxygen playing an intricate double role. The conversion is stopped completely by planarization due to the cancellation of p-orbital preorientation. In chloroform, ultrafast electron transfer to the solvent dominates the photochemistry, producing the radical cation leading to chromophore dimerization.
Histone deacetylase 10 (HDAC10) stands out among the eleven zinc-dependent hydrolases of the histone deacetylase family as the only polyamine deacetylase. It exhibits remarkable substrate specificity for N-acetylputrescine and N8 acetylspermidine over N1 acetylspermidine and shows no activity on acetyllysine residues. Although the role of selective polyamine deacetylation in health and disease is enigmatic, HDAC10 received little attention from medicinal chemists and no selective inhibitors suitable as chemical probes were available prior to this study. To address this deficiency, I developed the first well-characterized selective chemical probes for HDAC10 with unprecedented selectivity over other HDAC isozymes. The inhibitors were designed to imitate HDAC10’s polyamine substrates without also binding HDAC6, its closest relative. Insertion of an amino group into the hexyl linker moiety of the approved drug Vorinostat (SAHA) at the γ-position to the hydroxamic acid transformed SAHA from an unselective pan-inhibitor into a selective HDAC10 inhibitor. I further optimized the aza-SAHA scaffold in a medicinal chemistry campaign, which yielded DKFZ-748, a chemical probe for HDAC10 with a 22 nM IC50 against HDAC10 in cells and >500-fold selectivity over HDAC6, as well as Class I enzymes (HDAC1, 2, 3, 8). Selectivity and potency were validated by biochemical and cellular target engagement assays. Furthermore, cells treated with DKFZ-748 showed only accumulation of the polyamine substrates, but not hyperacetylation of HDAC6 or Class I substrates. Potency of the aza-SAHA derivatives could be rationalized with HDAC10 co-crystal structures and selectivity within the entire target landscape of HDAC drugs was demonstrated. Moreover, DKFZ-748 was successfully applied in a polyamine-limited in vitro tumor model, where it enabled HeLa cell growth inhibition, but showed no toxicity under other circumstances. With potent and selective HDAC10 binders at hand, I transitioned from occupancy-driven pharmacology of inhibitors to the event-driven pharmacology of targeted degraders that can remove HDAC10 in cells via induced proteasomal degradation, including potential scaffolding functions of the HDAC10 protein. I demonstrated targeted degradation of HDAC10 using pan-inhibitor-based compounds as a proof of principle, and established a solid-phase synthesis of aza-SAHA-based degraders. These are promising candidates for the selective degradation of HDAC10, based on the excellent selectivity profile of the aza-SAHA derivatives. Furthermore, in a separate approach, I investigated new scaffolds for selective HDAC10 inhibition based on a compound library screen. This part of the project aimed to develop selective HDAC10 inhibitors without the use of amino hydroxamic acids, which opens new therapeutic applications for HDAC10 inhibition beyond cancer therapy.
In dieser Arbeit wird die Synthese, Charakterisierung und Postfunktionalisierung von schwefelhaltigen Makrozyklen beschrieben. Die Makrozyklen wurden aus Monomeren erhalten und in weiteren Reaktionen eingesetzt, um Cyclophane mit einem reinen Kohlenwasserstoffrückgrat zu erzielen. Diese Synthesestrategie wurde als Alternative zu den bekannten Herstellungsmethoden durch die Wittig-Umlagerung, die McMurry-Reaktion, sowie der Wurtz-Reaktion untersucht. Über dynamisch kovalente Chemie konnten aus Dithiolen makrozyklische Disulfide erhalten werden. Diese Disulfide wurden in einer neu entwickelten Schwefelextrusion mit N-heterozyklischen Carbenen umgesetzt und somit in Thioether überführt. Als alternative Syntheseroute ist eine irreversible nukleophile Substitutionsreaktion betrachtet und mit der zweistufigen Synthese verglichen worden. Beide Routen wiesen unterschiedliche Vor- und Nachteile auf und führten zur Darstellung von Mischungen der angestrebten Makrozyklen, welche durch Recycling-Gel-Permeationschromatografie aufgetrennt werden konnten. Auf diesen Wegen war es möglich vier homologe Reihen mit insgesamt 16 makrozyklischen Disulfiden, sowie fünf homologe Reihen von insgesamt 26 makrozyklischen Thioethern zu isolieren und zu charakterisieren. Als größte Kongenere wurden ein alternierender Benzyl-Aryl-Thioether mit 14 benzoiden Einheiten und ein Tridecamer aus dibenzylischen, hexasubstituierten Benzoleinheiten isoliert. Diese wiesen in 1H DOSY-Messungen einen solvodynamischen Durchmesser von 2.12 nm bzw. 2.60 nm auf und stellen die größten bisher verzeichneten Makrozyklen ihrer Art hinsichtlich Anzahl monomerer Einheiten dar. Zur Postfunktionalisierung der schwefelhaltigen Makrozyklen, zu solchen mit reinem Kohlenwasserstoffrückgrat, wurden erfolgreiche Experimente hinsichtlich der Oxidation zu Sulfonen bis hin zu einem Nonamer, sowie Photolyse, Ramberg-Bäcklund-Umlagerung und Sulfon-Pyrolyse durchgeführt. Ein Sulfon-Tetramer konnte erfolgreich in einer thermogravimetrischen Analyse-Apparatur zum entsprechenden Cyclophan in 38% Ausbeute pyrolysiert werden. Durch Einsatz der Ramberg-Bäcklund-Umlagerung gelang zudem der Nachweis der Transformation einer Reihe von Sulfon-Trimer bis zum Hexamer zu den entsprechenden Cyclophanen mit Kohlenstoff-Kohlenstoff-Doppelbindungen.
In this thesis, conversion type anode materials including transition metal oxides (MoO3, MoO2,WOx), disulfides (WS2) and the insertion reaction-based carbides with MXene-structure (Ti3C2,Nb2C, V2C), as well as their composites, were investigated as potential anode materials for next generation lithium ion batteries (LIBs). MXenes were prepared by an selective etching-based process. When used as anode materials forLIBs, the synthesized MXenes electrodes exhibit excellent cycling stability due to their high electronic conductivity, layered structure as well as good mechanical properties. In order toimprove the specific capacity (<300 mAh g-1) of the MXenes, composites based on Nb2C- andV2C-MXenes and conversion-based high-capacity anode materials (MoO2 and MoO3) were produced. The here presented MoO3/Nb2C was synthesized by a ball-milling method and MoO2/C/V2C by an electrostatically assisted hydrothermal method. Crucial experimental parameters for the ball-milled MoO3/Nb2C (ball-milling time, ball-milling speed, and mass ratio of components) were varied to optimize the morphology and thus the battery performance. The best properties are obtained for MoO3/Nb2C composite synthesized with a mass ratio of 1:1 where a capacity of 261 mAh g-1 is found after 300 cycles at a current density of 100 mA g-1. The uniquely structured hydrothermally synthesized MoO2/C/V2C composites consist of uniformly distributed MoO2 in the hierarchical V2C/C structure. When used as anode materials for LIBs, the composites show outstanding cycling stability and superior rate capability with, e.g., 96% capacity retention (605 mAh g-1) at a high current density of 1000 mA g-1 after 400 cycles. Lastly, carbon-coated tungsten oxides based on low-cost carbon sources (CTAB or PVP) were synthesized by a hydrothermal, carbonization process. An additional sulfurization process yielded carbon-coated disulfides. When used as anode materials for LIBs, the CTAB-assisted tungsten oxide carbon composite (c-WOx/C), tungsten disulfide carbon composite (c-WS2/C), and mixedphase (c-WOx/C-WS2/C) electrodes show outstanding cycling stability and rate performance compared to pristine ones. Particularly, the c-WS2/C electrode shows superior long-term cycle stability of 97% retention after 500 cycles at a high current density of 500 mA g-1. Similarly, the PVP-assisted WS2/C (p-WS2/C) electrode displays a capacity retention of 80% after 500 cycles. This work, therefore, presents a scalable and low-cost route to prepare carbon-coated tungsten oxide and disulfide for high performance LIBs, which can be extended for the preparation of other carbon-coated metal-based materials.
Hepatitis B führt zu über achthunderttausend Toten pro Jahr und stellt somit eine der bedeutendsten Erkrankungen der Menschheit dar. Mit Hepatitis D co-infizierte Patienten leiden unter der schwersten Form der Hepatitis. Hepatitis D kann jedoch seit kurzem mit dem Eintrittsinhibitor Myrcludex B (Handelsname: Hepcludex®) effizient behandelt werden. Diese nahezu nebenwirkungsfreie Therapie könnte eventuell noch weiter verbessert werden, da Myrcludex B zusätzlich zur Virusaufnahme auch die Wiederaufnahme von Gallensäuren, die eigentliche Funktion des NTCP, inhibiert. Die Aufnahme von Hepatitis B in Hepatozyten wird über NTCP vermittelt. Da dieser Rezeptor auch Gallensäuren bindet, wurden im Rahmen dieser Arbeit verschiedene Gallensäure-Peptid-Konjugate synthetisiert. Hierbei wurden monomere und dimere Gallensäuren verwendet und der Einfluss verschiedener Linker und Konformationen an der Bindestelle genauer untersucht. Die Peptidsequenz wurde vom Goldstandard Myrcludex B abgeleitet, zudem wurden weitere HBV-Genotypen charakterisiert. Um aussagekräftige Struktur-Wirkungsbeziehungen zu erhalten, wurden über 165 verschiedene Peptide und Gallensäure-Peptid-Konjugate synthetisiert und im ersten Schritt auf ihre HDV-Infektionsinhibition untersucht. Die chimären Substanzen erzielen hervorragende Effizienzen. Mit HBVpreS/2-21-yK-LCA und HBVpreS/2-21-yK-DCA, den beiden besten Substanzen, werden die inhibitorischen Eigenschaften von Myrcludex B erreicht. Für das Erreichen hoher inhibitorischer Aktivitäten müssen jedoch enge strukturelle Voraussetzungen eingehalten werden, beispielsweise führt die Verwendung von D-Lysin in der Verknüpfungsstelle zu einer zehnfach verringerten Effizienz. Da die beiden Substanzen diese Aktivität mit einer deutlich verkürzten Peptidsequenz erreichen, bieten sie, bei vereinfachtem synthetischem Zugang, großes Potential bezüglich einer Verbesserung der Pharmakokinetik. Zudem belegen physikochemischen Charakterisierungen ihre generelle Eignung als Medikamente. In weiteren in vitro-Untersuchungen konnte eine hohe Stabilität der beiden Gallensäure-Peptid-Konjugate gezeigt werden. Zudem waren weder Cytotoxizität noch hämolytische Eigenschaften beobachtbar. Die hervorragenden Daten in vitro konnten mit dem Erhalt der nahezu exklusiven Anreicherung in der Leber in vivo bestätigt werden. Somit stellen diese Substanzen aussichtsreiche Kandidaten für die zukünftige Weiterentwicklung als Medikamente dar.
Biological cells sense the mechanical properties of their surrounding environment and adapt their shape and function. Moreover, the mechanical properties of cells and tissues tightly correlate with their functions. The main thrust of this thesis is to quantitatively determine the mechanical proper- ties of cells and cell-repellent coating materials by the combination of unique experimental techniques by covering different spatio-temporal domains. In chapter 7 the viscoelastic shape relaxation of malaria-infected human red blood cells with a di- ameter of about 10 μm was monitored by the combination of a custom-designed microfluidic device and a high-speed imaging platform under collaboration with Prof. Dr. M. Lanzer (Center for Inte- grative Infectious Diseases, Heidelberg University). Using the binarised cell rims extracted from the live-cell images, the shape recovery of red blood cells upon the ejection from the narrow constriction was monitored with a time resolution of 30 μs per frame. The mechanical responses of the malaria- infected red blood cells were monitored through the entire life cycle of parasites. The systematic comparison of the red blood cells with genetically mutated hemoglobin (hemoglobinopathie) with normal red blood cells indicated a less pronounced change in the relaxation time in hemoglobinopa- thetic red blood cells, which might correlate with delayed protein synthesis in hemoglobinopathetic red blood cells. In chapter 8 the film elastic properties and internal structures of the monolayers of oligoethylene glycol-based dendrons for the coating of iron-oxide nanoparticles were studied by the combination of high energy X-ray reflectivity and high-speed atomic force microscopy. To achieve higher film sta- bility in blood stream, the dendrons, synthesized by the group of Prof. Dr. Felder-Flesch (Institut de Physique et Chimie des Materiaux , Univ. Strasbourg) were coupled to the oxide surface via two phosphonate groups. The interfacial force measurements were performed on planar silicon dioxide surfaces instead of iron oxide nanoparticle surfaces due to the technical limitations. The internal structures of dendron monolayers in water were probed by high energy specular X-ray reflectivity. An analytical model considering the transition from a soft layer to a hard layer was introduced to cal- culate the Young’s modulus from nm-thick monolayers. To gain deeper insights into the interfacial force interactions, the coarse-scale surface force-distance curves were measured by a cell-sized particle attached to an atomic force cantilever cantilever, while the size and distribution of nanoscopic pin- ning centers were monitored by fast force mapping with a pixel rate of 200 Hz. The capability of the dendron coating to prevent the platelet aggregation was assessed by observing the non-specific adhesion of human platelets on dendron-coated substrates. The dynamic uptake and localisation of fluorescent dendron-coated iron oxide nanoparticles into hypoxic mouse breast cancer cells was tracked using fluorescence imaging and cryo-transmission electron microscopy. Together, these meth- ods revealed a continuous uptake of iron oxide nanoparticles into in intracellular compartments such as endosomes via endocytosis. The iron oxide particles were found either agglomerated or as single nanoparticles.
Interatomic or intermolecular Coulombic decay (ICD) is an efficient relaxation pathway on the femtosecond timescale, where after inner-valence ionization of an atom or molecule, the initial vacancy is filled by an outer-valence electron and the excess energy is transferred radiationlessly to its neighbor, leading to its ionization. In this thesis, ICD-related phenomena are studied. Therefore, the work is divided into two main parts. Part I treats the new decay channel double ICD (dICD), where after the relaxation of the system, the excess energy exceeds the double ionization threshold of the neighboring species, resulting in its double ionization. We derive an asymptotic and perturbative expression for the dICD decay width as an indicator of efficiency. In Part II, nuclear dynamics during ICD and pre-ICD in NeKr and ArAr dimers are investigated focusing on different aspects. In pre-ICD, the excess energy is only sufficient for the excitation of the neighboring atom or molecule and additional energy has to be provided for its ionization. While the study about NeKr dimers undergoing ICD mostly concentrates on interference effects, the main goal of the pre-ICD in ArAr dimers study is to understand the nuclear motions and their appearance in the corresponding spectrum.
Der Epidermale Wachstumsfaktor-Rezeptor (EGFR) ist ein wichtiges Target für die Bildgebung und Therapie bei einer Vielzahl von malignen Veränderungen. Derzeit sind jedoch noch keine Bildgebungsagenzien auf der Basis von Peptiden für diesen Rezeptor vorhanden. Im Rahmen dieser Arbeit wurden Multimere (Homodi- und Homotetramer) des literaturbekannten Peptidliganden GE11 hinsichtlich ihrer EGFR-spezifischen Interaktion hergestellt und überprüft. Da sie meist überlegene Bindungseigenschaften verglichen mit denen der jeweiligen Monomeren aufweisen und aufgrund unterschiedlicher Liganden an verschiedene Rezeptoren binden können, wurde zusätzlich ein Heterodimer bestehend aus αVβ3-spezifischem c(RGDfK) und GE11 synthetisiert und ebenfalls untersucht. Des Weiteren wurden die literaturbekannten Peptide CPP, D4, EGBP, GE11, P1, P2, Pep11 und QRH sowie drei neue Peptide, Teilsequenzen des hEGF, EGF5-21, EGF13-32, EGF32 43, auf ihre Eignung als Basis für potentielle monomere Radiotracer für die PET/CT (Positronen-Emissions-Tomographie/Computer Tomographie) untersucht. Die Peptide wurden mit einem PEG5 Linker und dem Chelator NODA-GA funktionalisiert, um die Vergleichbarkeit der Ergebnisse untereinander zu garantieren, wonach die Substanzen mit [68Ga]Ga3+ markiert und in vitro bezüglich ihrer Serumstabilität, ihres 1 Octanol/WasserpH7.4-Verteilungskoeffizienten (logD(7.4)), Internalisierung in und EGFR-Bindungsaffinität an EGFR-überexprimierenden humanen Epithelkarzinomzellen A431 charakterisiert wurden. Die Peptidsynthese erfolgte an fester Phase nach Fmoc-Strategie, wobei die Vorteile einer ultraschallunterstützten oder mechanischen Kupplung anhand der Synthese des Heterodimers überprüft wurden. Die Markierungen mit [68Ga]Ga3+ wurden mittels analytischer Radio-HPLC verifiziert und ergaben nicht-optimierte molare Aktivitäten von 25 – 111 GBq/mymol mit radiochemische Reinheiten von ≥ 97%. Die radiomarkierten Peptide wiesen für die PET/CT geeignete logD(7.4)-Werte zwischen 2.17 ± 0.21 und 4.01 ± 0.13 und Serumsstabilitäten mit Halbwertszeiten von 62 bis zu 8078 min auf. In den in vitro-Evaluierungen an A431-Zellen konnte für keine der Substanzen eine EGFR-spezifische Internalisierung nachgewiesen werden. Ferner konnte in Konzentrationen bis zu 1 mM keine der Substanzen [125I]I-hEGF in kompetitiven Bindungsstudien von dem EGFR verdrängen. Unter den gleichen Bedingungen demonstrierten [125I]I-hEGF und hEGF eine hohe EGFR-spezifische Aufnahme in und Bindung an die A431-Zellen (33.6 ± 0.9% nach 1 h, reduzierbar auf 1.9 ± 0.2% durch Blockierung) und Affinität an dieselbe Zellinie (IC50-Wert: 15.2 ± 3.3 nM). Die Ergebnisse zeigen, dass 68Ga-markierte GE11-basierte Mono-, Homodi-, Homotetra- und Heterodimere wie auch 68Ga-markierte Monomere basierend auf den aktuell literaturbekannten Liganden zur EGFR-spezifischen Bildgebung nicht aussichtsreich ist und eine Entwicklung oder Identifizierung besser geeigneter Peptide, welche eine ausreichend starke Interaktion mit dem EGFR demonstrieren, erfolgen muss.
Patellamides are a group of cyclic peptides, found in the sea squirt (ascidian) Lissoclinum patella. These macrocycles are produced by the obligate symbiotic cyanobacterium Prochloron didemni in large quantities but their biological function remains unclear. Due to the rigid backbone of patellamides and various possible coordination sites, the complexation behavior with different metal ions has been studied in the past. The highest affinity and a wide range of catalytic properties were found with copper(II) ions. The resulting complexes show an extremely efficient carbonic anhydrase activity as well as phosphoesterase, glucosidase, and β-lactamase activity. However, the existence and structure of copper(II)-patellamide complexes in the organism have not directly been confirmed experimentally so far. This work explores possible biological functions of patellamides, focusing on the detection of copper(II)-patellamide complexes in biological samples and testing hypotheses concerning their bioactivity. To obtain synthetically produced patellamides in appropriate quality and quantity, a new method for the synthesis of natural patellamides has been developed. For biological investigations, a field excursion to Heron Island, Queensland, Australia was undertaken, to collect colonies of Lissoclinum patella. A key observation is that injecting copper(II) into the living organism leads to a significant increase in the concentration of different patellamides. Furthermore, copper K-edge XAS measurements of the biological samples suggest that most of the copper within the organism is indeed bound as copper(II). Interestingly, with algae of the genus Nannochloropsis spp. it was observed that, while metal-free patellamides appear to have little effect on the algae, together with copper(II) they can have strong effects: while a rapid death of the algae at high copper(II) concentrations (0.5 mM copper, 0.05 mM patellamide) was observed, no adverse effects and a higher photosynthesis rate were observed at the physiological, low copper(II) concentrations (0.015 mM copper, 0.05 mM patellamides). Based on these and previously published results, it is hypothesized that a main biological function is as a carbonate transporter from the cloacal cavity into the Prochloron cells.
Their high ambipolar charge carrier mobilities and narrowband emission in the near-infrared make semiconducting single-walled carbon nanotubes (SWCNTs) a promising material for optoelectronic devices. The controlled low-level decoration of SWCNTs with covalently bound sp3 defects gives rise to red-shifted luminescence and single-photon emission, thus strongly expanding their application potential. While the spectroscopic properties of sp3-functionalized SWCNT dispersions under optical excitation are already well-understood, little research efforts have been directed at the impact of luminescent defects on charge transport as well as defect population and emission in thin films and under electrical excitation. A fundamental understanding of these aspects is a prerequisite for the realization of light-emitting devices based on functionalized SWCNTs.
This thesis demonstrates high ambipolar charge carrier mobilities and red-shifted defect-state electroluminescence in light-emitting field-effect transistors with randomly oriented networks of functionalized SWCNTs as active layers. The results imply that luminescent defects act as shallow trapping potentials for charge carriers that still allow for fast detrapping at room temperature, thus explaining the moderate decrease in network mobilities upon functionalization. Time-resolved terahertz spectroscopy corroborates the impact of these defects on the intrinsic nanotube conductivity and provides further evidence that charge transport in semiconducting SWCNT networks, as opposed to the widespread belief, is not solely determined by the inter-nanotube junctions.
To achieve better control over the spectroscopic properties of SWCNT thin films deposited on surfaces, substrate passivation with a cross-linked polymer is demonstrated to reduce peak broadening and suppress sideband emission that is assigned to the uncontrolled formation of lattice defects through nanotube–substrate interactions. The realization of pristine and sp3-functionalized SWCNT network transistors with near-intrinsic electroluminescence on passivated substrates showcases the compatibility of the developed method with standard semiconductor processing steps and device fabrication. Moreover, the selective introduction of luminescent defects with a larger spectral red-shift pushes the electroluminescence from SWCNT networks further towards telecommunication wavelengths and highlights their potential for optoelectronic applications such as electrically-pumped single-photon sources.
Die vorliegende Dissertation befasst sich mit der Entwicklung und Evaluierung von bifunktionellen Chelatoren und untergliedert sich in zwei verschiedene Projekte. 89Zr, das in der Immuno-PET von großer Bedeutung ist, wird in klinischen Studien über Desferrioxamin B (DFO) komplexiert. Jedoch weist [89Zr]Zr-DFO-Komplex eine geringe kinetische Inertheit auf, sodass eine Reihe neuer 89Zr-Chelatoren entwickelt wurde. Ziel des Hauptprojektes war der direkte Vergleich von sechs potenziellen Chelatoren DFO, DFO*, CTH36, 3,4,3-(LI-1,2-HOPO), DOTA-GA und NOTA-GA hinsichtlich der kinetischen Inertheit der gebildeten [89Zr]Zr-Komplexe sowie ihrer in vivo-Pharmakokinetik. Um die effiziente Konjugation mit einem gewünschten Biomolekül mittels iEDDA unter milden Bedingungen zu gewährleisten, wurden die Chelatoren mit einem Tetrazin funktionalisiert. Die Bestimmung der Radiomarkierungseigenschaften der Chelatoren und kinetischen Inertheit der gebildeten 89Zr-Komplexe erfolgte zunächst unter Verwendung des Peptids, c(RGDfK) (13), das als Modellbiomolekül diente. Während DFO-, DFO*-, CTH36- und 3,4,3-(LI-1,2-HOPO)-c(RGDfK) bei milden Reaktionsbedingungen radiomarkiert werden konnten, wurde keine [89Zr]Zr-Inkorporation für das DOTA-GA- und NODA-GA-Derivat erzielt. In den EDTA-Challenge-Versuchen demonstrierten [89Zr]Zr-DFO* und [89Zr]Zr-3,4,3-(LI-1,2-HOPO) eine hohe kinetische Inertheit und stellten damit geeignete Kandidaten für die in vivo-Evaluierung dar. DFO, DFO* und 3,4,3-(LI-1,2-HOPO) wurden mittels iEDDA an den Antikörper Cetuximab gebunden, radiomarkiert und in einem HT-29-tumortragenden Mausmodell mittels Kleintier-PET/CT untersucht. Hierbei wurde die hohe kinetische Inertheit der Komplexe [89Zr]Zr-DFO* und [89Zr]Zr-3,4,3-(LI-1,2-HOPO) im Vergleich zu [89Zr]Zr-DFO, resultierend in einer geringeren Knochenanreicherung und einem höherem Tumor-zu-Hintergrundverhältnis, bestätigt. [89Zr]Zr-DFO* wies gegenüber [89Zr]Zr-3,4,3-(LI-1,2-HOPO) ein vorteilhaftes pharmakokinetisches Profil mit einer geringeren Anreicherung in Leber und Milz auf. DFO* ist daher der vielversprechendste Kandidat für den Einsatz in der humanen Immuno-PET. Ziel des Nebenprojektes dieser Arbeit war die Synthese und Evaluierung des bifunktionellen Chelators CB-DO2A-GA, welcher eine Alternative zu den etablierten Chelatoren für 68Ga darstellt. Nach der erfolgreichen Synthese des Chelators wurde dieser hinsichtlich seiner Radiomarkierungseigenschaften, kinetischen Inertheit des gebildeten Komplexes und Serumstabilität mit den Chelatoren DOTA, NODA-GA und DOTA-GA verglichen. Hierfür wurden die Chelatoren mit dem Peptid TATE biofunktionalisiert. Im Gegensatz zu den etablierten Chelatoren war die Radiomarkierung von CB-DO2A-GA-TATE nur wenig effektiv, jedoch wies der [68Ga]Ga-CB-DO2A-GA-Komplex eine hohe Serumstabilität und kinetische Inertheit gegenüber DTPA auf. Folglich stellt CB-DO2A-GA einen geeigneten Chelator zur Bildung von positiv geladenen 68Ga-Komplexen dar.
Advances in nanoscopy techniques have enabled the visualization of the cellular interior and its dynamics in nanoscale detail. Their success relies on availability of suitable fluorescent probes with well-distinguishable on and off states, complementing the specific demands and requirements of each application. Thus, the design and optimization of fluorescent dyes with corresponding bioconjugation and labeling strategies is essential for future discoveries aided by nanoscopy. In this thesis, photoswitchable, photoactivatable and cleavable dyes, in combination with different labeling strategies —from affinity probes to small molecules— were characterized for their applications in nanoscopy techniques. As photoswitchable probes, bioconjugates of diarylethenes with different photophysical and photochemical properties were applied in SMLM, RESOLFT and MINFLUX nanoscopy. Nanobody bioconjugates of a slow-switching red- shifted thienyl-substituted diarylethene, decorated with multiple carboxylic acid groups, were utilized in SMLM to demonstrate the impact of linkage error in the apparent width of vimentin filaments. MINFLUX nanoscopy was conducted with the diarylethene as the photoswitchable marker. Faster-switching phenyl-substituted diarylethenes decorated with non-charged polar solubilizers were investigated and triphenylphosphonium-bearing derivatives were applied in live-cell confocal imaging of mitochondria. By combining the antibody conjugates of a phenyl and a thienyl-substituted diarylethene, two-color fixed-cell confocal and SMLM imaging was enabled, despite partial spectral overlap, yet divergent photoactivation properties. In RESOLFT nanoscopy a series of trimethylammonium-substituted diarylethenes with different linker lengths were applied. In supramolecular complex assembly with cucurbit[7]uril, the probes exhibited improved photofatigue resistance and enhanced fluorescence brightness. As photoactivatable probes, HaloTag-reactive derivatives of a rhodamine,carborhodamines and a siliconrhodamine with emission spectra ranging from green to far red were applied in live-cell labeling. Images of NUP96 and vimentin proteins were acquired via MINFLUX nanoscopy and analyzed to investigate their performance, revealing superior apparent labeling efficiency and low single-digit nanometer resolution. For click labeling, a series of live-cell compatible photoactivatable xanthones bearing tetrazine moieties were investigated in SMLM and MINFLUX nanoscopy. Linkage-error-free labeling via genetic code expansion was exemplified in comparison with different labeling strategies targeting vimentin filaments. In a non-light mediated approach, a chemically cleavable dithiol linker was incorporated in a fluorophore–nanobody–fluorescent protein assembly exhibiting FRET, and was examined by confocal microscopy, FLIM and STED techniques. Chemical cleavage was utilized for multiplexing with one fluorophore for imaging different cellular structures. These results, involving a wide range of fluorescent probes with divergent (photo)physical and (photo)chemical properties, present an overview of their applicability in nanoscopy — including strengths and weaknesses in a range of currently most utilized techniques, as well as insights into upcoming challenges, possible improvements and solutions.
The overexpression of Fibroblast Growth Factor 2 (FGF2) is a well-known phenotype in a number of different cancer types. It acts as a very potent pro-angiogenic mitogen promoting tumour angiogenesis as well as plays a major role in tumour cell survival promoting chemo-resistance. An usual feature of FGF2 is the pathway by which it is exported from cells. Instead of being secreted through the classical ER/Golgi-dependent pathway, FGF2 is transported into the extracellular space by direct translocation across the plasma membrane. The underlying mechanism is based on the formation of lipidic membrane pores, a pathway that has been classified as type I unconventional protein secretion (UPS Type I). While a number of therapeutics have been developed targeting FGF2 signaling in cancer cells, the elucidation of the molecular mechanism of FGF2 secretion in the last two decades opened up unique opportunities to block the biological function of FGF2 under pathophysiological conditions. A number of cis- and trans-acting factors driving FGF2 secretion have been identified with (i) the Na/K-ATPase that recruits FGF2 at the inner plasma membrane leaflet, (ii) Tec Kinase that directly binds and phosphorylates FGF2, (iii) the membrane lipid phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] that triggers FGF2 oligomerization and pore formation and (iv) cell surface heparan sulfate proteoglycans that capture and disassemble FGF2 oligomers at the outer plasma membrane leaflet as the final step of this secretory process. While the specific role of Tec Kinase remains to be established, it has been demonstrated that RNAi-mediated down-regulation of Tec Kinase inhibits unconventional secretion of FGF2. Recently, small molecule inhibitors have been identified that block both physical interactions between FGF2 and Tec Kinase and FGF2 secretion from cells. They are of special interest for treating cancer types that develop FGF2-dependent chemo-resistance towards otherwise effective drugs such as FLT3 inhibitors in acute myeloid leukemia (AML). The goal of this thesis was to improve the potency of FGF2/Tec inhibitors using a medicinal chemistry approach. Starting from the most potent compound, more than 130 analogues were synthesized. All compounds were tested in FGF2/Tec protein-protein interaction assays to determine their inhibitory potential. In total, thirteen compounds were identified with improved IC50 values compared to the original FGF2/Tec inhibitor. These compounds were further evaluated in cell-based assays determining their influence on FGF2 secretion. Amongst this set of compounds, two compounds were identified exerting a stronger secretion phenotype compared to the original FGF2/Tec inhibitor. Furthermore, through the structural design of the newly synthesized compounds, valuable insight was obtained into the structure-activity relationship (SAR) of the small molecule inhibitors described here. This information will be of high value in future studies aiming at the optimization of this class of FGF2/Tec inhibitors with the final goal of developing a potent drug candidate blocking the biological function of FGF2 under pathophysiological conditions.
Tris(catecholato)silicate dianions, a compound class that is already known for over a century, can be readily prepared by reacting sand with catechol under basic conditions. Strikingly, the two-electron-oxidized derivative – silicon tris(perchloro)dioxolene 1Cl – has been recently accessed, representing a thermally stable, neutral triplet diradical and the first non-metal complex with redox-active and mixed-valence substituents. In the present work, the redox properties of 1Cl are investigated and by the synthesis of the corresponding monoradical anion [1Cl]•−, the redox series of tris(catecholato)silicates in general is completed. With cyclic voltammetry the redox potentials E1/2 = 0.43 V and 0.88 V (vs. Fc/Fc+) were finally determined. Comparing the redox potentials of 1Cl with free tetrachloro-o-benzoquinone, a tremendous shift of about 1.2 V becomes apparent. Moreover, 1Cl is applicable as efficient redox catalyst. By varying the quinone ligands and the silicon source, further homo- and heteroleptic derivatives are prepared. Variable temperature EPR measurements disclose the existence of diradicals with a triplet ground state. With a more profound understanding of the monomeric species, the synthesis is extended to higher nuclearity. A straightforward approach is established by introducing substituted 2,5-dihydroxy-p-benzoquinone (H2dhbqY) as [dhbqY][Na@15c5]2 (Y = Cl, Br, Ph, NO2) salts and mixing with bis(catecholato)silanes 2X (X = Cl, Br, CF3, iPr) to obtain the dinuclear species [4X,Y][Na@15c5]2, which are robust to coordinating environments. By selective combination of more electron-rich 2X and electron-poor dhbq linkers diradicaloid complexes [4X,Y]2− (X = Cl, iPr and Y = Cl, Br, NO2) were obtained and characterized. The opposite extreme with the smallest diradical character was accomplished by combining electron-poor 2CF3 and electronrich dhbqPh. The underlying design principle is further disclosed by computational analyses. Conclusively, this one-step protocol grants access to dimeric silicon polyoxolenes with control over and fine-tuning of the spin ground state. Lastly, preliminary results are obtained for the trimeric structures by implementing the six-fold deprotonated tritopic linker 2,3,6,7,10,11-hexahydroxytriphenylene (H6hhtp) with 2Cl. The results gathered in this work present a fundamental understanding of silicon-bridged polyoxolenes and thus are valuable extensions based on a non-metal main group element to known works based on transition metals.
In a world of increasing energy consumption and man-made global warming, the knowledge of electronic and structural properties of organic materials is crucial for their implementation and use in innovative (smart) devices since those determine device performance. Herein, the electronic and structural properties of new promising materials are studied in detail utilising advanced laser spectroscopic techniques. Considering optoelectronic devices such as organic field effect transistors and solar cells, the metal/organic interface plays an important role for device performance. Therefore, the electronic properties of an n-type semiconducting N-substituted pentacene derivative and its change at higher layer thicknesses in contact with a metal electrode is studied via two-photon photoemission spectroscopy as well as the adsorption and desorption properties via temperature-programmed desorption. Several molecular electronic states such as the highest occupied and the lowest unoccupied molecular orbital as well as the optical gap are thereby determined quantitatively. Developing optoelectronic devices further, smart devices covering more complex needs can be achieved by implementing multiresponsive mixtures reacting in differentiated ways to light, which acts as sustainable external stimulus with high spatio-temporal resolution. Hence, the switching behaviour of a mixture of two individually as well as simultaneously addressable photoswitches is researched in detail. Furthermore, the investigated mixture is 3D printable allowing fast and easy implementation in 3D structures. The photoswitches are a push-pull azobenzene derivative and a first generation donor-acceptor Stenhouse adduct absorbing longer wavelengths in the visible region of the spectrum compared to the azobenzene derivative. All steps of the trans-to-cis isomerisation of the former and the linear-to-closed isomerisation of the latter photoresponsive molecule are studied as well as the respective back reactions with special emphasis on the environmental influence and the impact of the photoswitches on each other. Therefore, several techniques, such as femtosecond transient absorption, temperature dependent kinetic visible absorption and kinetic infrared absorption spectroscopy, are used to gain a full picture. Dynamic effects of the environment and the photoswitches on each other are thereby found such that individual switching of both molecules takes place with minor impacts on each other in the mixture. Other 3D printable materials are diblock copolymers exhibiting microphase separation such as a derivative of a standard diblock copolymer for high-resolution nanolithography with additional functional groups allowing 3D printing. The lamellar structure and its regularity is studied by means of a scattering-scanning near-field optical microscope before and after 3D printing upon which a polymeric network is formed. Before printing, lamellae are thereby found whereas the printing process needs to be optimised to maintain this structure after 3D printing.
Most resources of modern computer clusters are locked behind the need for a high degree of parallel efficiency, having millions of processing units on heterogeneous hardware, e.g. having both CPUs and GPUs. Post-HF wave function-based methods offer a high accuracy while having high computational scaling and memory requirements. Their need for storing, transforming, manipulating, and communicating their underlying high-dimensional quantities makes them a bad fit for modern computer architecture.
The second-order Møller-Plesset perturbation theory (MP2) is a commonly used method to recover the electron correlation energy that the Hartree-Fock method is missing. Its computational scaling is O(N^5) (N representing the number of atomic orbitals), as its two-electron integrals have to be transformed from their atomic orbital representation to their molecular orbital representation, and its memory requirements scale with O(N^4).
This thesis applies the ideas of a quadrature scheme to the MP2 method to arrive at a lower scaling form that is embarrassingly parallel. The full Q-MP2 energy integral scales with O(P^2OV) (spatial grid points P, occupied molecular orbitals O, virtual molecular orbitals V) with its largest entity needing O(PN^2) memory. In this thesis, an efficient implementation in the form of the open-source libqqc library is presented. The setup of the integration grids is the deciding factor of the accuracy of the Q-MP2 method. To investigate this a benchmark of small molecules is shown, consisting of seven molecules, three basis sets, and 28 different grid combinations. All but the smallest grid combinations are shown to be within the magnitude of the target chemical accuracy, with only four points on the one-dimensional integration grid being necessary. The error of the spatial grid falls asymptotically with the number of grid points, with the third smallest grid of 20 radial and 38 angular points being chosen for further tests as it is the smallest well-behaved one. The total single-node performance, measured as the number of floating point operations performed per second compared to the theoretical maximum, of the different variants of the algorithm is found to be below 15%. The algorithm is memory bound. The parallelisation strategy shows near-perfect load balancing over the computational nodes. The single-node parallel efficiency is shown to be superlinear for large systems, as a higher percentage of memory can be stored in low-level and fast memory caches with an increasing number of cores. This trend is followed at the multi-node level, which was investigated for up to 960 cores/20 nodes on the JUSTUS 2 computer cluster.
Future optimisation strategies will be focused on optimising the integration grids to lower the number of necessary integration grid points, integral screening, better utilisation of temporal locality, and exploitation of matrix sparsity. Finally, the quadrature scheme was extended to coupled-cluster theory (Q-CC2) and the algebraic-diagrammatic construction scheme for the polarisation propagator (Q-ADC(2)). For the latter method, the computational scaling associated with the solution of the particle-hole state was lowered from originally O(N^5) to O(P^2OV^2 ) and the memory requirement can be additionally lowered from O(N^4) to O(PN^2) by folding of the doubles space into the singles space. Compared to the performance of Q-MP2, a future implementation is expected to have a better single-node performance as more computational work needs to be done per memory transaction, and to have similar parallel efficiency as little additional node-to-node communication is necessary.
The fluorescence-based nanoscopy methods MINFLUX and MINSTED are currently revolutionizing the field of imaging and single molecule tracking by achieving molecular spatial precision with low photon numbers. Using a polymer-based in vitro assay with strongly reduced fluorescence background, I identified MINFLUX-compatible spontaneously blinking fluorophores by quantifying their blinking properties. Due to the spontaneous blinkers being live-cell compatible and having few milliseconds short on-events, I expect them to advance the imaging field by drastically accelerating MINFLUX measurements. The main focus of this work, however, is the application of the nanoscopy methods MINFLUX and MINSTED for tracking of the motor protein kinesin-1. Requiring an only ~1 nm small fluorophore as label, they are inherently less artefact-prone than established techniques which require the attachment of comparatively large beads for a similar spatio-temporal resolution. With an improved interferometric MINFLUX approach, we successfully resolved regular steps and substeps of the kinesin-1 stalk and heads. By discovering that ATP binds to the motor in the one-head-bound state and is hydrolyzed in the two-head-bound state, we aim to solve a long-standing controversy in the field. Furthermore, we deduced that when the rear head of kinesin-1 detaches from the microtubule, it rotates around its front into a rightward-displaced unbound state. In conjunction with an observed stalk rotation, I concluded the motor to walk in a symmetric hand-over-hand fashion. Finally, we successfully resolved the stepping of kinesin-1 with MINSTED, confirming many findings from the MINFLUX experiments and observing motor sidestepping and protofilament switching. These findings will prove helpful in developing treatments for diseases linked to malfunction of kinesins. Beyond that, this thesis establishes MINFLUX and MINSTED for the tracking of dynamic biological processes on the single molecule level.
In dieser Arbeit wird untersucht, wie Nanopartikel mit Zellmembranmodellen interagieren und welche Faktoren Einfluss auf die Nanotoxizität nehmen. Hierfür werden Zellmembransysteme sowie die zugehörigen Modelle für deren Beschreibung präsentiert, wobei die Komplexität im Laufe der Arbeit zunimmt. Dabei stehen die Zellmembranen von Eukaryoten im Mittelpunkt, aber auch die Membranen von Prokaryoten werden thematisiert. Das Ausgangssystem ist aus DMPC aufgebaut, wobei eukaryotische Zellmembranen durch das Einbauen von Cholesterol modelliert und für die Simulation von prokaryotischen Zellmembranen geladene Lipide verwendet werden. Neben den Auswirkungen der Zellmembranzusammensetzung wird die Beeinflussung der Systeme durch die Änderung der Temperatur, des verwendeten Salzes und der Ionenstärke sowie durch die Zugabe von Nanopartikeln untersucht. Bereits an Luft können verschiedene Charakteristika des Systems, wie beispielsweise die Oberflächenstruktur, Bilagenanzahl und Bilagendicke der Oligolipidbilagensysteme, untersucht werden. In wässriger Umgebung werden die lösungsmittelinduzierten Veränderungen der Struktur und Stabilität des Gesamtsystems genauso untersucht wie der Einfluss von Temperaturänderungen. Zudem wird in der wässrigen Umgebung die Interaktion zwischen den Oligolipidbilagen und Nanopartikeln untersucht. Durch die wässrige Umgebung können Salze in die Lösung eingebracht werden, wodurch die biologische Relevanz des Systems zunimmt und der Einfluss der Ionenstärke auf die Charakteristika des Systems untersucht werden kann. Zudem ist von besonderem Interesse, in welcher Form die Zugabe von Salzen die Interaktion von verschiedenen Zellmembranmodellen mit Nanopartikeln beeinflusst. Neutronenreflexions- und Röntgenreflexionsmessungen stehen bei dieser Arbeit als experimentelle Methoden im Vordergrund. Diese werden jedoch durch eine Vielzahl weiterer Messmethoden, wie dynamische Differenzkalorimetrie, Rasterkraftmikroskopie und Ellipsometrie, ergänzt, sodass ein differenziertes Gesamtbild der Systeme entsteht.
In Chapter 2, multi-substituted alkenes are accessible by a gold-catalyzed acyloxyalkynylation of ynamides with ethynylbenziodoxolones (EBXs) in an atom-economic fashion. The EBX reagents act as bifunctional reactants providing both the nucleophilic carboxylate as well as the alkynyl entity. Overall this cascade involves the formation of an alkynyl Au(III) species, stereoselective C(sp)-C(sp2) bond formation and C-O coupling at the alkynyl position of the ynamides. The introduced method features mild conditions and wide substrate scope. A number of tetrasubstituted amide enol 2-iodobenzoates bearing diverse functionalities were prepared in good to excellent yield. DFT calculations exlain the observed regioselectivity. The synthetic potential of the sequence was further documented by a number of selected follow-up transformations. In Chapter 3, Tetrasubstituted alkenes including the ester and ether group, is of great interest in chemistry and material sciences. A variety of tetrasubstituted enol ether 2-iodobenzoate derivatives were prepared in good yields at room temperature through a gold-catalyzed acyloxyalkynylation of ynol ethers with ethynylbenziodoxolones (EBXs), which act as bifunctional reactants in an atom-economic fashion. Furthermore, the mechanism involves an in situ formed alkynyl Au(III) species and a gram-scale reaction was efficiently conducted. In Chapter 4, an efficient method for the construction of highly functionalized new spirooxindolocarbamates from a gold-catalyzed cycloaddition reaction of terminal alkyne and ynamides with isatin-derived ketimines is described. This protocol features easily accessible starting materials and good functional group compatibility enabling the introduction of various functionalized alkyne groups into cyclic carbamates. Gram-scale synthesis and proposed mechanism are also presented.
In Chapter 2, a gold-catalyzed reaction of a bromoalkyne with anthranils to synthesis α-ketoamides is covered. In this reaction, two equivalents nitrene are used to functionalize a C-C triple bond by gold catalysis. Subsequently one equivalent nitrene remains in the amide function of the desired product, while the other equivalent of nitrene is eliminated during the hydrolysis process as an amine. This particular hydrolysis of the intermediate α-iminoimidoyl halides opens access to α-ketoamides for a wide range of haloalkynes. In Chapter 3, a one-step gold-catalyzed hydroamination of alkynes with hydroxylamine-O-sulfonic acid (HOSA) is reported. In this reaction, the limits that traditional synthesis of oximes is highly dependent on carbonyl compounds, is overcome, which expands the diversity of accessible oximes. Green chemistry metrics for this facile reaction are also calculated, this process shows 100% carbon efficiency.
The thesis is focused on 1,10-phenanthroline (phen)-assisted homogeneous oxidative gold catalysis using hydrogen peroxide (H2O2) as oxidant. It is an unprecedented oxidative gold catalysis strategy with an ideal “benefit balance”, not just as a more attractive substitute of common methodologies, but as an extraordinary reaction system. The efficient constructions of 3-alkynylbenzofurans, 1,3-diynes and polyynes were possible by this catalytic system (Au/phen/H2O2). The thesis considers the significant advantages (ideal “benefit balance”) and challenges (no-report) of H2O2 as an oxidant for oxidative gold catalysis. In the first part (Chapter 2), we focused on exploring the possibility of oxidative gold catalysis using H2O2 as oxidant and the potential application value of this reaction system. We discovered that bidentate N-ligands (phen) can effectively promote the oxidation of AuI to AuIII in the presence of H2O2. Furthermore, a set of experiments with stoichiometric gold(I) complexes demonstrated that this catalytic system can be applied for homogeneous gold-catalyzed C(sp2)-C(sp) and C(sp)-C(sp) cross-coupling reactions. The gold-catalyzed cyclization-functionalization is a powerful approach to construct high-value organic molecules. However, current strategies mainly rely on expensive external oxidants or pre-functionalized substrates, which exhibit low atom economy and high costs. To circumvent these drawbacks, in the second part (Chapter 3), we focused on investigating the use of this catalytic system for efficient gold-catalyzed cyclization-functionalizations. A direct construction of 3-alkynylbenzofurans from terminal alkynes was possible by this gold-catalyzed process. Green and inexpensive oxidants, simple gold catalysts, mild reaction conditions, high atom economy, remarkable selectivity, wide substrate scope, broad functional group compatibility and a facile gram-scale synthesis make this alkynylative cyclization method practical for many forms of cyclization reactions. In contrast to prior methods neither pre-functionalized alkynes nor expensive external oxidants are needed. Conjugated 1,3-diynes are unique carbon frameworks which are widely found in natural products, biologically active molecules and functional materials. Considering the importance of synthetic methods for conjugated diynes, especially unsymmetrical 1,3-diynes, we next focused on investigating the use of this catalytic system for a gold-catalyzed cross-coupling of terminal alkynes. An efficient synthesis of unnsymmetrical 1,3-diynes from terminal alkynes via this new gold catalytic system was developed (Chapter 4). A wide range of substrates, including several complex molecules and marketed drugs, were transferred with excellent functional group tolerance. Furthermore, the catalyst system was applied at a gram scale and an extension towards the synthesis of polyynes via a relay strategy was possible. Considering the importance of polyynes in chemical and materials research, and tedious synthesis procedure of the current strategy. In the fourth part (Chapter 5), we focused on exploring gold-catalyzed C(sp)–C(sp) cross-coupling of alkynylsilanes using H2O2 as oxidant. Through this catalytic system, 1,3-diynes and polyynes can be successfully prepared from ethynyltrimethylsilanes without pre-functionalization or deprotection. Compared with current synthetic strategies towards polyynes, our method greatly improves the synthetic efficiency, provide new ideas for the synthesis of polyynes.
Thermoresponsive hydrogels such as poly(N-isopropylacrylamide) (pNIPAM) are highly interesting materials for generating soft actuator systems. Whereas the material has so far mostly been used in macroscopic systems, we here demonstrate that pNIPAM is an excellent material for generating actuator systems at the micrometer scale. Two-Photon Direct Laser Writing was used to precisely structure thermoresponsive pNIPAM hydrogels at the micrometer scale based on a photosensitive resist. We systematically show that the surface- to-volume ratio of the microactuators is decisive to their actuation efficiency. The phase transition of the pNIPAM was also demonstrated by nanoindentation experiments. We observed that the mechanical properties of the material can easily be adjusted by the writing process. Finally, we found that not only the total size and surface structure of the microactuator plays an important role, but also the crosslinking of the polymer itself. Our results demonstrate for the first time a systematic study of pNIPAM-based microactuators, which can easily be extended to systems of microactuators that act cooperatively, e.g., in microvalves.
This thesis describes the synthesis of interlocked giant [8+12] organic cages and the systematic investigations of the catenation mechanism. By tuning the substituents of the building blocks and the length of linkers, a series of monomeric cages with different volumes and structures were designed and synthesized. Based on these monomeric cages, four major factors in the catenation process were studied: 1. The effects of the size and cavity volume of the monomeric cage on catenation tendency (Chapter 3.1). Three types of triptycene triamine and two dialdehyde linkers were utilized to construct six catenanes and two organic cages. By investigating the relationship between the formation of catenanes and the size of monomeric cages, it was found, when the difference between the volume of the cage and its cavity is smaller, the monomeric cages tend to be interlocked more. 2. The structural effects on catenation (Chapter 3.2). To further figure out the driving force of catenation, several dialdehyde linkers with varied substituents were used to build monomeric cages. Experimental results showed that the structural changes of the monomeric cages significantly influenced the catenation results. 3. Solvent effects (Chapter 3.3). To explore the solvent effects on the catenation, a solvent screening was conducted for the synthesis of catenanes. Moreover, the solvent mixtures and several corresponding combinations were also investigated. 4. Synthesis of polycatenanes (Chapter 3.4). According to the studies of solvents and structural effects in previous chapters, the rational synthesis and isolation of dimer, trimer, and tetramer could be achieved by adjusting the ratio of solvent mixtures, type of building blocks, and the equivalents of linkers. In addition, an ongoing project about obtaining single crystals of metal-assisted covalent organic frameworks (MSOFs) was shown in Chapter 4. The idea is to prepare the metal-organic frameworks (MOFs) single crystals first and then transform them into MSOFs single crystals by post-modification. Two approaches were designed and the corresponding MOFs were synthesized, unfortunately, only nanocrystals of MOFs were obtained currently.
Die Implementierung von redoxaktiven Liganden in Koordinationsverbindungen stellt ein aktuelles und schnell wachsendes Forschungsgebiet sowohl in der katalytischen Chemie als auch in den Materialwissenschaften dar. Die Ähnlichkeit der Elektronentransferprozesse in entsprechenden Komplexen zu biologischen Prozessen, welche in einer Vielzahl von Redoxenzymen ablaufen, liefert eine Inspiration für die Entwicklung ähnlicher Systeme. Vor diesem Hintergrund beschäftigt sich die vorliegende Dissertation mit der Verwendung redoxaktiver Bis- und Tetraguanidinliganden in der Übergangsmetallchemie, speziell in Cobaltkomplexen. Eine umfassende Untersuchung der elektronischen Strukturen der verschiedenen Redoxzustände der Komplexe durch eine Vielzahl analytische Methoden steht im Zentrum dieser Arbeit. Der erste Teil der vorliegenden Arbeit beschreibt die Synthese und Untersuchung eines neuen Tetraguanidinliganden auf Naphthalinbasis. Das dargestellte System zeigt neben einer reversiblen Oxidierbarkeit in einem 2-Elektronenoxidationschritt eine für diese Ligandensysteme erstmals beobachtete Fluoreszenz in protonierter Form. Weiterhin konnte durch Umsetzung des Liganden mit N-Halogeno-Succinimid/Phthalimid eine Substitution der aromatischen Wasserstoffatome unter selektiver Bildung des 3,7-Dihalogeno-4,8-Disuccinimido/Phthalimido-Produktes erreicht werden. Die umfassend untersuchte Komplexchemie des Ligandensystems unter Darstellung einer Reihe von Übergangsmetallkomplexen (ZnII, CuII, PdII, CoII) bildet den Abschluss dieses Kapitels. Motiviert durch die Ergebnisse cyclovoltammetrischer Messungen der synthetisierten Cobaltacetylacetonato-Komplexe wurde das Co(acac)2-System im zweiten Teil dieser Arbeit auf die Stoffklasse der Bisguanidinliganden übertragen. Die Verwendung von unterschiedlichen Liganden mit verschiedenen Redoxpotentialen und der Möglichkeit zur Ausbildung intramolekularer Wechselwirkungen ergibt ein breites Feld an Komplexverbindungen mit faszinierender Redoxchemie. Für alle dargestellten acac-Komplexe verläuft der erste Redoxschritt metallzentriert und es werden diamagnetische CoIII-Komplexe erhalten. Für die Komplexe mit vollständig alkylierten Bisguanidinsubstituenten verläuft der zweite Redoxschritt dann ligandenzentriert und es werden CoIII-Komplexe mit radikalischem Bisguanidinliganden erhalten. Für einen Komplex, welcher einen unvollständig alkylierten Bisguanidinliganden mit freien NH-Funktionen beinhaltet, kommt es im zweiten Oxidationsschritt zu einem Redox-Induzierten Intramolekularen Elektronentransfer (RIET) durch Stärkung der intramolekularen Wasserstoffbrückenbindungen in dem erhaltenen CoII-Komplex mit dikationischem Bisguanidinliganden. Diese Reaktion stellt das erste Beispiel für einen durch die Stärkung von Wasserstoffbrückenbindungen ausgelösten RIET dar. Mittels Substitution der acac-Coliganden durch die Lewis-Basischeren Hexafluoroacetylacetonato-Coliganden lässt sich das Ergebnis der Redoxprozesse gezielt steuern. Für diese Komplexe laufen beide Redoxschritte ligandenzentriert ab. Ein monokationischer CoII-Komplex mit radikalischem Bisguanidinliganden wurden mittels paramagnetischer NMR-Spektroskopie untersucht und die Art der magnetischen Wechselwirkungen der Spinzentren bestimmt. Aufgrund der leichten Anpassbarkeit der Redoxpotentiale der Bisguanidinliganden konnte für einen zweifach oxidierten Trifluoracetyalcetonato-Komplex, welcher einen Bisguanidinliganden mit hohem Redoxpotential (E1/2 (1) = –0.17 V) aufweist, eine lösungsmittelabhängige Redoxisomerie beobachtet werden. Eine Kombination aus Tieftemperatur-ESR-Experimenten und UV-vis-Messungen konnte das exklusive Vorliegen des CoIII-Isomers mit radikalischem Bisguanidinliganden in Dichlormethan zeigen. In Acetonitril und Tetrahydrofuran liegt dagegen fast ausschließlich das CoII-Redoxisomer mit dikationischem Bisguanidinliganden vor. Eine Substitution der Coliganden durch redoxaktive Dioxolenliganden führte zu Komplexen mit vier Redoxzentren, wodurch eine facettenreiche Redoxchemie ermöglicht wird. Es konnte gezeigt werden, dass sich die elektronische Struktur der Komplexe durch die Wahl der Coliganden gezielt beeinflussen lässt. Die Verwendung von Di-tertbutyl-Dioxolenliganden ergibt CoII-Komplexe mit neutralem Bisguanidinliganden und zwei Semichinoncoliganden. Der Einsatz der elektronenärmeren Tetrachloro-Dioxolen-Coliganden führt in Folge der Komplexierung zu einen zweifachen intramolekularen Elektronentransfer und es werden CoIII-Komplexe mit radikalischem Bisguanidinliganden und zwei Catecholato-Coliganden erhalten. Die Verwendung redoxaktiver Guanidinliganden in der Cobaltchemie in Kombination mit der Variation der Coliganden ermöglicht also eine gezielte Steuerung von Elektronentransferprozessen und ebnet den Weg für eine vielfältige Redoxchemie mit einer Vielzahl von Anwendungsmöglichkeiten.
Die Prävalenz von Alkohol in der heutigen Gesellschaft ist unumstritten, wodurch sich vielfältige Fragestellungen ergeben, welche oftmals nicht alleinig durch die Messung einer Blutalkoholkonzentration beantwortet werden können. Aufgrund dessen nahm die Bedeutung von spezifischen Abbauprodukten des Ethanols, auch Alkoholbiomarker genannt, in den letzten Jahren stetig zu, da ein Alkoholkonsum durch deren Messung deutlich länger nachweisbar ist. Dafür ist eine verlässliche und robuste Analytik der verschiedenen Biomarker zur Beantwortung diverser Fragestellungen, z.B. im Rahmen der Abstinenzkontrolle, unerlässlich. Aus diesem Grund war das Ziel dieser Arbeit die Entwicklung, Etablierung, Validierung und Anwendung einer neuartigen und spezifischen Multimethode zum Nachweis diverser Alkoholbiomarker wie Ethylglucuronid, Ethylsulfat, N-Acetyltaurin und 16:0/18:1 Phosphatidylethanol. Nach einer erfolgreichen Methodenentwicklung und -validierung entsprechend der Richtlinien der GTFCh konnten alle vier Biomarker mit einer sehr guten Intensität und Reproduzierbarkeit qualitativ nachgewiesen und quantitativ bestimmt werden. Anschließend wurde die Methode im Rahmen verschiedener Studien angewendet, um forensisch und analytisch verwertbare Ergebnisse zu gewinnen. Es ergaben sich Anwendungsgebiete aus der Leichentoxikologie, Pharmakokinetik sowie der klinischen Diagnostik. Zusätzlich wurde geklärt, inwieweit eine Anwendung von NAcT als Alkoholbiomarker sinnvoll ist, wobei die erhaltenen Ergebnisse eine Anwendung nicht unterstützen. Um die Eignung der Methode zur Untersuchung von postmortalem Blut zu testen, wurden 31 Proben gemessen, in denen zuvor hohe Blutalkoholkonzentrationen nachgewiesen werden konnten. Die hierdurch ermittelten Ergebnisse bestätigten die Anwendbarkeit der Methode für postmortales Probenmaterial. Aufgrund der Bestimmung mehrerer Alkoholbiomarker kann eine Alkoholisierung vor dem Tod von einer durch postmortal gebildetes EtOH verursachten Verfälschung der BAK unterschieden werden. Durch die parallele Bestimmung der drei Alkoholbiomarker Ethylglucuronid, Ethylsulfat und 16:0/18:1 Phosphatidylethanol steigt die Aussagekraft der erhobenen Ergebnisse. Zusätzlich wurden zwei Trinkversuche am Institut für Rechts- und Verkehrsmedizin in Heidelberg durchgeführt, in welchem Probanden eine individuelle Alkoholmenge aufgenommen haben, um eine vorgegebene Blutalkoholkonzentration zu erreichen. Über den ersten Versuchstag und einem Zeitfenster von sieben Tagen wurden in definierten Abständen Blut- und Urinproben erhoben, um die Verlässlichkeit der entwickelten Multimethode und die Pharmakokinetiken der einzelnen Biomarker zu untersuchen. Ein weiteres Ziel dieses Studiendesigns war die Ermittlung eines physiologischen Grundwertes für N-Acetyltaurin, da diese Substanz im menschlichen Körper endogen gebildet wird. Es konnte belegt werden, dass N-Acetyltaurin den Ansprüchen eines Biomarkers zum Nachweis eines Alkoholkonsums nicht gerecht werden kann, da die individuellen Schwankungen zu stark sind und keine nachvollziehbare Pharmakokinetik aufgezeigt werden konnte. Im Gegensatz hierzu konnte für die bereits etablierten Biomarker Ethylglucuronid und Ethylsulfat erneut bestätigt werden, dass diese in der Matrix Urin eine entsprechend gute Möglichkeit bieten, in Abhängigkeit von der aufgenommenen Dosis, einen vorangegangen Alkoholkonsum verlässlich nachzuweisen. Der Biomarker 16:0/18:1 Phosphatidylethanol, welcher nur in Vollblut nachgewiesen werden kann, deckt ein noch größeres Nachweisfenster ab und kann auch ein einmaliges, länger zurückliegendes Trinkgeschehen belegen. Dieser Biomarker ist bisher in der forensischtoxikologischen Analytik in Deutschland zum Nachweis einer Alkoholabstinenz nicht etabliert. Mittels der im Rahmen dieser Arbeit validierten Methode ist es nun möglich, den Biomarker 16:0/18:1 Phosphatidylethanol im Rahmen des Abstinenzprogrammes am IRVM analytisch zu bestimmen und in die Beurteilung mit einfließen zu lassen. In einem weiteren Projekt wurde die neu entwickelte Methode zum Nachweis der drei anwendbaren Biomarker im Entzugskontext verwendet. Das Kollektiv bestand aus Blutproben, die zu Beginn und Ende eines Entzugsaufenthaltes im Krankenhaus Salem abgenommen und auf ihre Biomarkerkonzentrationen untersucht wurden. Dabei konnte gezeigt werden, dass Ethylglucuronid und Ethylsulfat innerhalb der Klinikaufenthalte unabhängig von dem Parameter der Lebersteifigkeit im Blut komplett abgebaut wurden. Da Phosphatidylethanol in den Erythrozytenmembranen akkumuliert und nur sehr langsam abgebaut wird, war dieser Biomarker auch zum Ende des Entzugs bei nahezu allen Patienten nachweisbar. Im Falle dieses Alkoholbiomarkers konnte durch einen Kruskal-Wallis-Test gezeigt werden, dass es keinen Zusammenhang zwischen dem Abbau und der Lebersteifigkeit gab. Zusammenfassend lässt sich feststellen, dass die in dieser Arbeit entwickelte analytische Multimethode vielfältige Möglichkeiten bietet, um ein sehr breites Spektrum von Fragestellungen im Bereich der Forensischen Toxikologie beantworten zu können.
In dieser Arbeit wird der erste chirale polyzyklische aromatische Kohlenwasserstoff (PAK) mit einer Affensattel-Topologie präsentiert. Aufbauend auf einem präparativ leicht zugänglichen Truxenvorläufer ist der Affensattel-PAK in nur drei Schritten erhältlich. Durch Verwendung weiterer, funktionalisierter Präkursoren wurde eine Serie von zwölf Derivaten isoliert und charakterisiert. Festkörperstrukturen bestätigten zweifelsfrei die dreidimensionale Form der Moleküle, die durch die enthaltenen fünf-, sechs- und achtgliedrigen Ringe hervorgerufen wird und die Verbindungen so zu einem Ausschnitt aus Mackay-artigen Strukturen macht. Bedingt durch die Krümmung weisen die Zielverbindungen eine dreifache axiale Chiralität auf. Die Trennung der Enantiomere, Charakterisierung dieser über CD-Spektroskopie und die Untersuchung der Racemisierung zeigten Halbwertszeiten von wenigen Millisekunden bis hin zu mehreren Tagen. Zudem gelang es erste Versuche zur Synthese Mackay-artiger Käfigverbindungen durchzuführen, die wichtige Erkenntnisse lieferten. Ein tieferer Einblick in die Eigenschaften der gekrümmten PAKs gelang durch den isosteren Austausch dreier CH-Gruppen gegen Stickstoff. Dessen Auswirkungen wurden im Detail untersucht und führten zu einer Stabilisierung der Enantiomere hin zu einer Halbwertszeit von zwei Monaten. Weiterführend gelang die Entwicklung einer Umlagerung, die zu einem chiralen molekularen Korb führte, dessen Enantiomere bei Raumtemperatur nicht mehr racemisieren. Die experimentellen Ergebnisse wurden durch eine Vielzahl an quantenchemischen Rechnungen unterstützt und erweitert.
Ein zweiter Truxenvorläufer bildete die Basis, auf der die Darstellung eines Systems mit drei Azuleneinheiten gelang. Synthetische Schwierigkeiten auf dem Weg zur Zielverbindung konnten umgangen und so zusätzlich ein ketofunktionalisierter PAK erhalten werden, der zwei separierbare Diastereomere bildet. Der Azulen-PAK stellt aufgrund der enthaltenen fünf- und siebengliedrigen Ringe ein Modell eines Graphendefektes dar und wurde hinsichtlich seiner fotophysikalischen und elektrochemischen Eigenschaften untersucht sowie mit isomeren Verbindungen verglichen. Eine Bestätigung der Strukturen aller drei Zielverbindungen mittels Röntgenstrukturanalyse gelang ebenso. Erste Experimente zur Postfunktionalisierung wurden durchgeführt, sodass zukünftige Projekte darauf aufbauen können.
Nonadiabatic quantum dynamics plays an important role in a wide range of chemical reactions and femtochemistry experiments. However, numerically converged simulations are typically only affordable for small size systems because the computational efforts generically increase exponentially. This thesis is devoted to the theoretical analysis of two candidates of simulation methods for large size systems, linearized phase space methods and quantum simulations.
Linearized phase space methods, for instance, fully linearized methods, partially linearized methods, and symmetrical quasi-classcial windowing, approximate the quantum dynamics as the classical dynamics, and quantum effects are accounted for by Monte Carlo sampling of the initial quantum phase space. The major drawback is that the sampling of independent phase space trajectories neglects quantum coherence and interference. For condensed phase simulations, this limitation fortunately is only minor. Different linearized phase space methods are mainly characterized by the initial electronic phase space selections, and it is believed that the choice of electronic phase space determines the accuracy of the method. While there are lots of numerical results to support this argument, a rigorous theoretical analysis is still outstanding. Rewriting fully and partially linearized methods in a unified expression, we establish a rigorous measure of the short-time accuracy, the intra-electron correlation, which has a close connection to the initial electronic phase space. The methods with correct intra-electron correlation are more accurate in the short-time region for various chemical motivated models than the methods with a wrong one. For various popular linearized phase space methods, including many fully and partially linearzied methods, we also give either a proof of correct intra-electron correlation sampling or an explicit violation example. Our theoretical analysis gives an explanation of the accuracy order of linearized phase space methods reported in the literature. Moreover, the intra-electron correlation can be a guideline for the development future linearized phase space methods.
Further, we introduce the generalized discrete truncated Wigner approximation (GDTWA), which is a well-established linearized phase space method in the field of quantum lattice models, into chemistry. The GDTWA uses the Wootters' discrete phase space for electrons, which can sample the intra-electron correlation correctly for diagonals states. We reformulate the GDTWA in the unified expression of linearized phase space methods, which shows that the GDTWA is a fully--partially hybrid method. With the help of this reformulation, we not only reduce the computational efforts, but also demonstrate a reduced zero-point energy accounting without an explicit zero-point energy parameter in the GDTWA. Numerical benchmarks on scattering models and linear vibronic coupling models show a robust performance on various chemical motivated models. Also, we develop two GDTWA, approach I and II, for a particle in gauge vector potentials. Theoretical analysis shows that the two approaches favor the simulation of synthetic gauge field and on-the-fly simulation of molecular dynamics in the adiabatic representation, respectively. Our numerical results of ultracold atoms, linear vibrionic coupling models as synthetic gauge fields, as well as on-the-fly simulations of linear vibronic coupling models confirm the analysis.
To overcome the difficulty of simulating quantum mechanics arising from exponentially increasing Hilbert space, quantum simulations use controllable quantum devices which obey the rule of quantum mechanics. Nowadays, the imperfect controls of quantum devices have a huge impact on the accuracy of the simulations. Specifically, when the errors of the implementations break symmetries of the system, simulation results could even be qualitatively wrong. We rigorously develop an experimentally feasible linear penalty method to suppress the symmetry-breaking errors. Numerical benchmarks of the lattice gauge theory and the hydrogen molecule show good performances on protections of symmetries, local observables, and wave functions.
Our theoretical analysis on both linearized phase space methods and quantum simulations illustrate the possibilities of simulating large size systems with large potential for applications in quantum chemistry and related areas.
The construction of individual synthetic cells has been developed to achieve processes ranging from recapitulating cell division to mechanosignalling. Taken a step further, another promising implementation of synthetic cell research is the construction of artificial tissues comprising synthetic cells. These artificial tissues have the potential to form a communication network between the synthetic cells to transmit and respond to chemical or mechanical signals. In conjunction with natural tissue, this functioning could support signal transduction and thus aid in creating hybrid systems that will ultimately influence the fundamental understanding of tissue form and functioning. In this thesis, I described the first steps towards building an artificial tissue that consists of giant unilamellar vesicles (GUVs)-based synthetic cells. In the process of charge-mediated GUV production, block copolymer surfactants consisting of PEG and PFPE were used to stabilize water-in-oil droplets that provide the charged scaffold to generate GUVs in the first place. These polymer-based surfactants have a major impact on the overall GUV production yield which is currently recognized as the major technical challenge in the field. Therefore, the first part of my thesis is dedicated to comparing different synthesis routes to achieve surfactants with desired properties. Subsequently, several functional surfactants have been synthesized: 1) a positively charged surfactant that allows electrostatically-mediated GUV formation; 2) a photoliable surfactant, which should enable a light-induced GUV release from water-in-oil droplet templates; and 3) a fluorescent surfactant for labeling the surfactant layer. In the second part of this thesis, I focused on introducing biomimetic interactions between GUVs as well as between GUVs and natural cells. Towards this end, a pH-mediated generation of GUVs with improved release efficiency was explored. These GUVs were biofunctionalized and used for the bottom-up assembly of biomimetic cell adhesion and interaction modules: 1) mimicking epithelial cell interactions through the implementation of adherens junctions between GUVs via E-cadherin proteins; 2) GUV-substrate adhesion through the reconstitution of integrins in the GUVs membrane; and 3) implementation of droplet-based microfluidics for the reconstitution of actin cytoskeleton within GUVs to move towards linking intercellular mechanical signaling and synthetic cell mobility for future applications. Additionally, I showed how adherens junctions and substrate adhesion could be mimicked by DNA-mediated interactions. Finally, a hybrid system consisting of synthetic and natural cells was constructed and analyzed with respect to the interaction between GUVs and HEK cells. Through the use of newly synthesized surfactants, droplet-based microfluidics, and pH-mediated GUV assembly and their efficient biofunctionalization , I was able for the first time to build an extensive network of synthetic cells and hybrid cellular system. This research establishes the foundation for reliable and reproducible production of large numbers of stable populations of GUV-based synthetic cells with pre-determined biomimetic functions and represents a substantial step towards building an artificial tissue. In future, mechanical and biochemical signal transduction can be potentially enabled by transmembrane linkages to the cytoskeleton, leading to the implementation of the advanced bioinspired hybrid cellular systems for biomedical applications.
In den letzten Jahren haben sich N-Heteropolyzyklen zu vielversprechenden Kandidaten für Anwendungen in der organischen Elektronik entwickelt. Zu diesem Zweck ist ein tiefgehendes Verständnis der niederenergetischen elektronischen Anregungs- und Emissionscharakteristika von entscheidender Bedeutung. Die kontrollierte Bildung schwach gebundener van-der-Waals-Dimere und die Charakterisierung ihrer optischen Eigenschaften stellen dabei wichtige Bausteine für den Einblick in die Natur intermolekularer Wechselwirkungen dar. In dieser Arbeit wurde auf die Matrixisolations-Technik zurückgegriffen, mit der hochaufgelöste Infrarot-, Absorptions- und Emissionsspektren von niedrig konzentrierten Analytsubstanzen bei 4 K in festem Neon erhalten wurden. Durch kontrollierte Variation aggregationsfördernder Parameter (Temperatur und Konzentration) konnte zwischen Monomer- und Dimerspektren differenziert werden. Anhand des kleinen Modellsystems Pyridin gelang die gezielte Bildung und detaillierte Charakterisierung des doppelt Wasserstoff-verbrückten, vollständig planaren Pyridin-Dimers in Neon. Die Aufklärung der Struktur erfolgte durch Analyse der Frequenzverschiebungen im Infrarot-Bereich bei Dimerisierung im Zusammenspiel mit quantenchemischen Rechnungen und wird gestützt durch Isotopenexperimente an Pyridin-d5. Die elektronischen Anregungsspektren von Tetracen und zweier im Grundgerüst Stickstoff-substituierter Derivate wurden hinsichtlich ihres Verhaltens unter aggregationsfördernden Bedingungen untersucht. Im Falle von Tetracen wurden erstmals Hinweise auf die Bildung von Dimeren bei höheren Konzentrationen in Form von J-Aggregaten gefunden. Zusätzliche niederenergetische Anregungsbanden im Spektrum der Stickstoff-Derivate von Tetracen konnten durch Intensitätsverstärkungen durch Wechselwirkungen mit dipolverbotenen Übergängen im Rahmen des Herzberg-Teller-Modells vibronischer Kopplung erklärt werden. Es wurden ebenfalls hochaufgelöste Absorptions- und Fluoreszenzspektren von Pentacen und 6,13-Diazapentacen in festem Neon aufgenommen. Begleitende quantenchemische Rechnungen ermöglichten die Zuordnung spezifischer schwingungsaufgelöster Signale zu den entsprechenden Normalmoden. Darüber hinaus gelang erstmals der spektroskopische Nachweis der Bildung von van-der-Waals-Dimeren beider Spezies. Diese Dimere weisen signifikant unterschiedliche optische Eigenschaften auf, die auf die Veränderung der elektronischen Struktur durch die formale Einführung von sp2-hybridisierten Stickstoffatomen in das molekulare Rückgrat zurückgeführt werden.
Networks of polymersorted semiconducting single-walled carbon nanotubes (SWNTs) exhibit ideal properties for electrolyte-gated transistors, such as high charge carrier mobilities and a porous morphology. In combination with many electrolytes, such as ionic liquids, the porosity enables volumetric charge accumulation in these networks, comparable to ion-permeable polymers in electrochemical transistors (ECTs). However, the performance of polymer-wrapped SWNTs in water-gated transistors, which are an important component of bioelectronics, is limited by the hydrophobicity of commonly used wrapping-polymers. This limitation is overcome within this thesis by exchanging the hydrophobic wrapping-polymer with an equivalent polymer that features hydrophilic oligoethylene glycol side chains. High performance water-gated transistors with large volumetric capacitances are demonstrated, employing aerosol-jet printed hydrophilic polymer/SWNT hybrids. Furthermore, slow ionc motion in ion-gel-gated dense SWNT networks is studied and implemented as an approach to create artificial synapses, which show promising behavior for the development of neuromorphic devices. The properties of the presented prototypes suggest that future device generations should contain a mixed network of semiconducting and metallic SWNTs as the gating material and avoid all parasitic capacitances by passivation in order to obtain non-volatile device operation. These findings expand the applicability of solution processed SWNT networks for bioelectronics and brain-inspired computing.
Die vorliegende Arbeit beschäftigt sich mit der Synthese C3-symmetrischer, chiraler Derivate des Tribenzotriquinacens (TBTQs) und deren Verwendung als molekulare Bausteine für Imin-Käfigverbindungen. TBTQ-Derivate sind aufgrund ihrer rigiden, schüsselförmigen Struktur und ihrer ungewöhnlichen orthogonalen Geometrie, interessante Vorläuferverbindungen für die Synthese großer, diskreter organischer Moleküle. Der Grundstein dieser Arbeit bildet eine Iridium-katalysierte Borylierung von TBTQ mit einer beispiellosen Selektivität für das C3-symmetrische Produkt (Ergebnisse basierend auf meiner Masterarbeit). Die Umwandlung der Boronsäureester in andere funktionelle Gruppen ermöglichte die Synthese diverser C3-symmetrischer TBTQ-Derivate im Gramm-Maßstab. Von diesen wurde für die C3-symmetrischen Trihydroxy-TBTQs eine sehr effiziente, lösungsmittelkontrollierte Racematspaltung entwickelt. Die durch Formylierung der Trihydroxy-TBTQs erhältlichen Salicylaldehyde wurden als Bausteine für die Synthese riesiger, kubischer [8+12]-Iminkäfige verwendet (din = 3.3 3.5 nm), und die chirale Selbstsortierung dieser Käfige wurde untersucht. Von 23 theoretisch möglichen Käfigisomeren wurden ausschließlich die enantiomerenreinen und ein meso-Käfig gebildet, welche beide eindeutig durch Einkristallstrukturanalyse charakterisiert werden konnten. Weiterhin konnte durch die Wahl eines geeigneten Lösungsmittels der meso Käfig selektiv erhalten werden. In unpolaren Lösungsmitteln wurde beobachtet, dass der enantiomerenreine [8+12]-Käfig ein vierfach verriegeltes Catenan bildet, welches eindeutig durch Einkristall¬struktur¬analyse charakterisiert werden konnte. Die Catenierung wird in erster Linie durch schwache Wasserstoff¬brücken¬bindungen getrieben und kann durch das Lösungsmittel gesteuert werden. Austausch-Experimente mit deuterierten Käfigbausteinen zeigten, dass das Catenan durch Verketten von zwei präformierten Käfigmolekülen gebildet wird.
In dieser Arbeit wurde eine Reihe neuartiger Bispidin-basierter Kupfer- und Eisennitrenkomplexe synthetisiert, charakterisiert und hinsichtlich ihrer katalytischen Eigenschaften und deren zugrundeliegenden Reaktionsmechanismen untersucht. Die Arbeit wurde dabei in zwei große Abschnitte unterteilt. Im ersten Teil lag der Fokus auf Kupfer-basierten Komplexen und deren Anwendung in der katalytischen Aziridinierung von Styrol. Aufbauend auf der modularen und somit einfach zu verändernden Bispidinsynthese wurde eine Reihe alkylsubstituierter Liganden synthetisiert. Durch die systematische Substitution der Methylgruppe an N7 durch einen Ethyl-, iso-Propyl-, iso-Butyl-, tert-Butyl- bzw. Benzylrest wurde sowohl der elektronische als auch der sterische Einfluss des Substituenten auf die Eigenschaften der Kupferkomplexe sowie deren Katalysefähigkeit untersucht. Zusätzlich wurde der Einfluss von Liganden mit unterschiedlichen Seitengruppen sowie sekundären anstelle der sonst üblichen tertiären Amine analysiert. Hierbei konnte zunächst die aus vorherigen Arbeiten bekannte Abhängigkeit einer gesteigerten katalytischen Reaktivität mit Zunahme des CuI/CuII Redoxpotentials bestätigt werden. Zusätzlich konnte gezeigt werden, dass bereits geringe Änderungen wie die Verseifung oder Reduktion der Seitengruppen ebenfalls zu einer höheren Reaktivität führen. Während die meisten Modifikationen nur eine moderate Steigerung der katalytischen Eigenschaften zur Folge hatten, wurde durch die Substitution der tertiären Amine durch sekundäre eine Reaktivitätssteigerung um das bis zu 1000-fache gegenüber den etablierten Kupfer(I)- und Kupfer(II)komplexen [CuI/IIL1 (MeCN)]+/2+ mit tetradentaten Bispidinliganden L1 (N2py2) beobachtet. Die massive Steigerung der katalytischen Aktivität wurde dabei durch eine reversible Deprotonierung der sekundären Amine im Katalysezyklus erklärt. In der Folge konnte die Plausibilität der Deprotonierung durch die Bestimmung des pKS-Wertes des sekundären Amins demonstriert werden. Zusätzlich wurde durch die Charakterisierung des deprotonierten Kupfer(II)komplexes der Einfluss der Deprotonierung auf die optischen und elektronischen Eigenschaften untersucht. Aufbauend auf diesen Ergebnissen wurde ein um einen reversiblen Deprotonierungsschritt erweiterter Katalysezyklus für die Aziridinierung von Styrol postuliert, der die beobachte Reaktivitätssteigerung erklärt. Im zweiten Teil der Arbeit wurde der Fokus auf Eisen-basierte Nitrenkomplexe gelegt. Dabei wurde erstmals eine Eisennitrenspezies eines Bispidinkomplexes nachgewiesen. Die Untersuchungen wurden anhand von zwei Komplexen mit fünfzähnigen Bispidinliganden und einem Komplex mit vierzähnigem Bispidinligand, mit zwei unterschiedlichen Koliganden, durchgeführt. Während für den Komplex mit vierzähnigem Ligand die Nitrenspezies nur indirekt nachgewiesen werden konnte, gelang der Nachweis für die beiden Komplexe mit fünfzähnigen Liganden sowohl direkt, mittels UV-Vis-NIR Spektroskopie und Massenspektrometrie, als auch indirekt, anhand des Transfers der NTs-Gruppe auf Styrol und Thioanisol. Die erfolgreich nachgewiesenen Nitrenspezies wurden in der Folge mittels Mößbauerspektroskopie hinsichtlich ihrer elektronischen Eigenschaften untersucht. Den reaktiven Eisennitrenspezies beider Komplexe konnte dabei eine Oxidationsstufe von +IV mit einem Spin von S = 1 zugeordnet werden. Zusätzlich wurden die Nitrenspezies durch kinetische Untersuchungen hinsichtlich ihrer Reaktivität in der C-H Aktivierung und des NTs-Gruppentransfers untersucht. Hierbei stellten sich die Bispidinkomplexe gegenüber vergleichbaren Modellkomplexen als besonders reaktiv heraus. Es konnte zudem gezeigt werden, dass die untersuchten Eisenkomplexe vergleichbar hohe Ausbeuten in der katalytischen Aziridinierung von Styrol erreichen wie ihre analogen Kupferkomplexe und dabei hinsichtlich ihrer Reaktivität teilweise überlegen sind. Zuletzt wurden die Abbauspezies der Eisennitrenkomplexe mit tetraund pentadentaten Bispidinliganden untersucht. Diese wurden für alle Komplexe bereits in den ersten Untersuchungen der Nitrenspezies anhand von charakteristischen Absorptionsbanden beobachtet. Hierbei wurden neben den Eigenschaften der Abbauspezies auch deren Bildung und die zugrundeliegenden Mechanismen analysiert, wodurch ein besseres Verständnis der Reaktionswege und Abbaumechanismen der Nitrenspezies erlangt wurde. Abschließend wurde durch den Vergleich der in dieser Arbeit untersuchten Eisennitrenkomplexe mit ihrer nahverwandten Eisenoxidokomplexe große Gemeinsamkeiten der Spezies hinsichtlich ihrer elektronischen und optischen Eigenschaften sowie ihrer Reaktivität identifiziert.
This work aims at a more detailed understanding of non-covalent doping of graphene and Molybdenumdisulfide using aromatic N-heteropolycycles. Therefore a wide variety of molecules is first deposited via wet-deposition onto graphene, to then investigate the induced changes in Fermi energy of graphene with both Raman spectroscopy and Kelvin-Probe-Force Microscopy. The induced shifts in graphene are then correlated with both the molecular geometry and substituents, as well as their electronic properties to derive a structure-effect relation that can be used to guide the fine tuning of graphene’s electronic and surface properties. All methods in this work, form deposition to measurements are done under ambient conditions to mimic the conditions of real live applications and to avoid perfect lab conditions like ultra-high vacuum that are not viable for end-of-the line device production and use. This idea is also applied to the graphene that is used itself, as commercially available graphene was used for all experiments. With this framework in mind the first steps of this project were to establish a suitable sample preparation routine to achieve a reproducible and comparable graphene substrate for the subsequent measurements. Due to CVD-grown and wet-transferred graphene being contaminated with polymer residues and water this was a crucial step for reliable results in the end. Comparing a wide range of different molecules, it was also necessary and important to formulate a deposition procedure that can be applied to all molecules, although probably not optimized for the specific molecule it was optimized for the overall comparison of all molecules on even ground. The first results of the deposition of both TIPS-Tetraazapentacenes and Tetraazaperopyrenes show a strong dependence of the graphene doping on the acceptor strength (=LUMO energy) of the molecules and less on the overall molecular structure (i.e. substituents and substitutional patterns). With those established protocols and findings the relations of charge transfer interaction between molecules and graphene were further refined with additional acceptor molecules (Benzonapthyridines) and also demonstrated for the opposite interaction with donor-type Heterotriangulenes showing trends in-line with the theory. i In case of the Benzonaphthyridines and Heterotriangulenes the graphene modification was carried a step further by utilizing the molecule specific properties of possible protonation with common acids and oxidation via UV irradiation to introduce a second stage of charge transfer after initial deposition. This demonstrated that it is possible to further modify already assembled molecules on graphene (and as a consequence the Fermi level of graphene as well) without major damage to graphene itself, although in our cases the overall changes following the second modification were small, but could easily be increased with specific molecules engineered for those kinds of applications. To delve even further into the non-covalent nanomaterial doping all, the gained insights and experiences from graphene were then taken to Molybdenumdisulfide (MoS2) to see whether the rules of structure-effect-relations derived from graphene can be applied to a different class of nanomaterial and to see specific differences and whether they follow the theoretical expectations. With the self-assembly of molecules being guided by mainly π-π interactions on graphene, MoS2 shows that the acceptor strength is one of the driving factors not only for the electronic modification but also for the deposition itself.
Ozone plays an important role in volcanic plume chemistry, a particular process is its destruction by reactive halogen species, especially BrO. To better understand this chemical system, further measurements of the ozone concentration in volcanic plumes are needed. The usual UV absorption ozone monitors suffer from a severe interference with the high SO2 concentration in volcanic plumes. Therefore, we use the chemiluminescence method, which is based on the detection of photons emitted when ethylene is mixed with ozone containing air. This method has no interference with volcanic plume components, but ist field deployability is so far very limited, because the instruments are typically very heavy and bulky. This thesis reports the construction of a lightweight (< 1.5 kg) chemiluminescence ozone monitor, that can be mounted on a drone to be carried through volcanic plumes. The weight reduction was mainly achieved by using a modern photomultiplier module and omitting its cooling. In addition, the battery and ethylene storage container are easy to exchange between flights. This means that they can be quite small, as they only need to last for one flight. The flow rates and the dimension of the reaction chamber are optimized based on the calculation of the photon rate and a simulation of the photon trajectories.
Volcanic gases are part of the fundamental geochemical cycles on Earth. They provide information on the planet’s interior and influence the climate and the oxidation state of the atmosphere. However, there remain severe inconsistencies between field observations and models within the field of volcanic gas analysis. This cumulative thesis aims to improve the understanding of volcanic degassing processes by combining three different but related approaches: (1) A model for the chemical kinetics within the early turbulent mixing process of hot magmatic gases with atmospheric air is developed. It questions conventional approaches that assume thermodynamic equilibrium during the gas emission phase and, hence, has severe implications for current interpretations of volcanic gas measurements. (2) A high-resolution spectrograph is conceptualised and developed. The resolving power of ca. 100000 exceeds that of conventional field-deployable instruments by more than two orders of magnitude. Its high light throughput and mobility enables a range of new volcanic measurements, such as the quantification of the hydroxyl radical, which is an important intermediate species in hot volcanic gases. (3) A novel imaging technique for volcanic trace gases is developed. It significantly enhances the accuracy of volcanic volatile flux quantification and shows great potential for spatially resolving the still poorly constrained halogen conversion processes within volcanic plumes. Prototypes of both instrument developments demonstrate their anticipated performance in field measurements. The techniques introduced in this thesis also exhibit extensive potential for further atmospheric remote sensing applications including improved measurements of greenhouse gases, air pollutants, atmospheric oxidants, or plant fluorescence.
Two-dimensional materials have gained tremendous interest over the last decade due to their unique properties and their potential to be employed in future electronic or optoelectronic devices. One class of materials that are subject of ongoing research are transition metal dichalcogenides (TMDs) such as MoS2 or WS2. In their 2H-phase, these layered Van der Waals (VdW) crystals are semiconducting and undergo a transition from an indirect to a direct band gap, when the layer number is decreased to the monolayer (ML) limit, giving rise to emerging photoluminescence. One of the research areas where ML TMDs are promising materials due to their high oscillator strength and large exciton binding energies is strong light-matter coupling, where the energy exchange between photons and matter (for example excitons) in optical microcavities results in the formation of hybrid light-matter quasi particles, so-called polaritons. These polaritons exhibit properties of both light and matter, making them interesting for their own sake but also for future polaritonic devices, such as polariton lasers. One of the most commonly applied techniques for the production of two-dimensional nanoobjects is exfoliation of bulk crystals, for example in the liquid phase by sonication assisted liquid phase exfoliation (LPE), where the interlayer binding energies of the bulk crystals are overcome by sonication. However, this process is still not fully understood, and exfoliated nanosheets are relatively small in their lateral dimensions due to scission events within the layers. Additionally, the deposition of the nanosheets from dispersion into homogeneous thin films with preservation of the ML properties remains a major challenge. Therefore, most demonstrations of TMD based applications are designed with single flakes of TMDs, which restricts the scale-up. For example, the formation of polaritons in homogeneous films of TMDs has not been demonstrated yet. The first part of this thesis focuses on the optimization and understanding of the LPE process. It was demonstrated that purity, particle size, and defectiveness do not impact the yield or dimensions of LPE produced nanosheets. However, differences in the PL properties were observed, which might be related to the defectiveness of the starting material. The exfoliation efficiency and the dimensions of the nanosheets can be altered by pretreatment of the starting material, leading to intercalation of the pretreatment agents and reduction of the interlayer binding strength, but the effect is small when high power sonication conditions are chosen. In the next part of the thesis, thin films of TMDs were produced by different strategies, including spin coating of WS2-polymer composite films and deposition of WS2 in Langmuir-type films, that were formed at liquid liquid phase interfaces. The films were characterized and assessed regarding their usability for the implementation in optical microcavities. Here, the Langmuir films were superior to the composite films due to stronger PL, better homogeneity, and lower thickness for a given optical density. The production of high-quality composite films was only possible with low WS2 concentrations, resulting in insufficient optical density or high film thickness. Both composite and Langmuir films were implemented in microcavities, but strong light-matter interaction was only observed in the cavities based on the Langmuir films. While this is the first time that strong coupling is demonstrated based on angle-dependent reflectivity in homogeneous and large-scale thin films of TMDs, it was not possible to measure the PL emission of the cavities, due to low signal intensity. In the last part of this thesis, hydrogen and methyl derivatized germanene (Ge H and Ge Me) were subjected to LPE, since these materials are known for higher PL intensities and are also fluorescent in the bulk structure. The fluorescence properties of Ge-H were not preserved after sonication, but the more stable Ge-Me nanosheet dispersions showed promising properties, including strong PL. However, Ge-Me is susceptible to basal plane degradation under ambient conditions and film preparation was only possible with relatively large nanosheets. In these films, the fluorescence properties were preserved, but no working light-emitting devices could be built, which was attributed to inhomogeneities that are related to the large nanosheets with broad size distribution.
Wnt signaling pathways are a set of signal transduction cascades which are activated through the interaction of Wnt proteins with so-called Frizzled receptors [1-3]. These pathways are critically involved in many biological processes such as embryonic development, regeneration, organogenesis, cell division, cellular and tissue homeostasis, among many others [3, 4]. In addition, alterations of these signaling pathways have been linked to various types of diseases such as cancer [5-7], familial tooth agenesis [8], bipolar disease [9], Alzheimer's disease [10], and cardiac valve formation [11]. Wnt signaling components are accordingly promising drug targets to treat these diseases. Wnt pathways are probably among the best characterized receptor-ligand signaling pathways. Wnt proteins are therefore key players in biological signaling and promising drug targets to treat a plethora of diseases. Although several proteins involved in Wnt trafficking and secretion have been identified over the past years, little is known about the contribution of different lipid species into these processes. The trafficking and secretion of Wnts could be modulated by the type and number of acyl species covalently linked to Wnt proteins. Currently, the best described acyl modification is the palmiteoylation of a serine residue located around amino acids 205-215 mediated by the ER-resident O-acyltransferase Porcupine is responsible for this process. This lipid modification has been described for Wnt3a, Wnt5, xWnt8, and Wnt1, and it has been assumed to also take place in other members of the family of Wnt proteins. Despite the extensive data available, the debate around the lipid-modified amino acids in Wnt proteins has not yet reached a consensus. Recent results from O. Voloshanenko (M. Boutros group, DKFZ, Heidelberg, Germany) suggested that there may be other amino acid residues in Wnts that are lipidated, apart from this canonical serine residue. Furthermore, the specific saturation of the acylated chain that binds to Wnt remains inconclusive.
In this thesis, I aimed to define other putative acylation types and lipid-modified sites in Wnt proteins and to determine the role of these alternative lipidations in Wnt secretion and signaling. Furthermore, I evaluated the impact of Wnt signaling and Wnt secretion on the lipidome of HEK293T and HCT116 cells. To achieve this, I employed a combination of chemical biology tools, mutagenesis experiments, and mass spectrometric measurements. In particular, I focused on Wnt11 as a working model. I studied its acylation using clickable lipids such as palmitic acid alkyne (cC16:0) and palmitoleic acid alkyne (cC16:1n-7). One of the early observations was that palmitoylation and secretion of Wnt11 were not wholly abolished in Porcupine knockout cells or some mutant variants of Wnt11. However, these observations seem to depend on the type of clickable fatty acid used. Our results suggest a lipid modification of Wnt11 at serine 215 via the monounsaturated fatty acid cC16:1n-7, consistent with the previously predicted models. However, lipid modification with the saturated fatty acid cC16:0 showed variations in the experimental replicates, which did not fully resolve whether Wnt11 contains another modification site. Importantly, our experiments stress that unsaturation is a key feature for Wnt acylation. The relevance of covalent lipid binding for the secretion and signaling activity of Wnts has also been assessed. It was demonstrated that lipidation is essential for the signaling activity of Wnt11 but is not strictly necessary for its secretion. In addition, an impact of Wnt protein expression on the overall cellular lipidome of HEK293T and HCT116 cells has been tested, yielding preliminary observations on the crosstalk between the Wnt signaling and the overall cellular lipid homeostasis. This study is expected to contribute to our understanding of how post-translational lipid modifications influence Wnt cellular secretion, signaling and, conversely, how proteins of the Wnt signaling pathway affect the lipid composition of cells.
Redoxaktive Verbindungen zeigen eine starke Änderung ihrer chemischen und physikalischen Eigenschaften in Abhängigkeit ihrer Oxidationsstufen. Im Bereich der Koordinationschemie ist die Verwendung organischer Verbindungen mit leicht veränderbarem Redoxzustand als redoxaktive Liganden ein aktueller Forschungsschwerpunkt. Inspiriert von der katalytischen Aktivität der Redox-Enzyme in der Natur, welche ebenfalls eine Kombination aus redoxaktiven Einheiten und häufig vorkommenden Übergangsmetallen nutzt, entwickeln Chemikerinnen und Chemiker molekulare Komplexe zur Anwendung in der Katalyse und als Komponenten in neuartigen Materialien. In diesem Kontext beschäftigt sich die vorliegende Dissertation mit redoxaktiven Harnstoffazinen, der Untersuchung ihrer Reaktivität in Abhängigkeit ihrer Oxidationsstufen und ihrer Verwendung als Liganden. Harnstoffazine stellen eine Klasse von redoxaktiven Guanidinen, welche sich formal aus der Kondensation von Harnstoffen und Hydrazin bilden. Typisch für die Verbindungsklasse ist ein zweistufiges Redoxverhalten. Innerhalb dieser Arbeit wird erstmals die Synthese von homoleptischen [ML2]-Komplexen mit neu konzipierten partiell-alkylierten Harnstoffazinliganden HL und späten Übergangsmetallen (M = ZnII, CuII & CoII) vorgestellt. Außerdem gelang es Koordinationsverbindungen mit Harnstoffazinliganden in mehreren stabilen Redoxstufen zu isolieren. Die umfassende Untersuchung der [CuL2]-Komplexe zeigt eine niedrige Barriere für intramolekulare Ligand-Metall-Elektronentransferprozesse und daraus resultierend eine Flexibilität der elektronischen Struktur. Diese Flexibilität spiegelt sich auch in der untypisch verzerrten Struktur der Komplexe, zwischen quadratisch-planar und tetraedrisch, wider. Bei der Oxidation der [CuL2]-Komplexe wird ein redoxinduzierter Elektronentransfer (RIET) beobachtet, der zu einer Reduktion des Metalls bei Oxidation der Komplexe führt. Die umfassende Analyse der elektronischen Struktur der oxidierten [CuL2]-Komplexe innerhalb dieser Arbeit zeigt zudem eine starke Abhängigkeit der magnetischen Eigenschaften vom verwendeten Harnstoffazinliganden. Für den Komplex [Cu(L1)2]+ beobachtet man das Vorliegen eines anti-ferromagnetisch gekoppelten Diradikals, während [Cu(L2)2]+ einen ausgeprägten diamagnetischen Charakter besitzt. Daneben wurde die elektronische Struktur von MCl2-Komplexen mit HL-Liganden und den neutralen homoleptischen Zink- und Cobaltkomplexen untersucht. Im Hinblick auf zukünftige redoxkatalytische Anwendungen werden erste Untersuchungen der [CuL2]-Komplexe vorgestellt. Die Komplexe zeigen katalytische Aktivität in der aeroben Oxidation von Alkoholen zu Aldehyden (Imitation der enzymatischen Galactose-Oxidase-Reaktivität). Der modulare Aufbau der Harnstoffazine, die daraus resultierende einfache Variation der elektrosterischen Eigenschaften in Komplexen sowie die besondere Stabilität der Harnstoffazinkomplexe in mehreren Redoxstufen und ihre erweiterte Reaktivität durch N-basische Funktionen im Rückgrat machen Harnstoffazine zu vielseitig einsetzbaren und für spezielle Anwendungen optimierbaren redoxaktiven Liganden. Daneben wurde ein interessantes Verhalten der zweifach oxidierten Form peralkylierter Harnstoffazine identifiziert. Diese zeigen Reaktivität als dikationische Azo-Dienophile in Hetero-Diels-Alder(DA)-Reaktionen mit Dienen (Butadien, Anthracen, Tetracen, Pentacen). Dabei kann das DA-Gleichgewicht durch das vorgelagerte Redoxgleichgewicht beeinflusst werden. Die Untersuchungen zeigen, dass Reduktion zur Retro-DA-Reaktion führt. Daneben wird für Anthracen ein bei Raumtemperatur reversibles dynamisches DA-Gleichgewicht beobachtet. Außerdem ergibt sich aus dem Harnstoffazinstrukturmotiv in den DA-Produkten die besondere Möglichkeit einer baseninduzierten Transformation zu bisguanidinosubstituierten Acenen. Hierbei wird unter anderem die Bildung eines stabilen 6,13-Bisguanidinopentacens gezeigt, welches eines der am stärksten donorsubstituierten Pentacene mit reversiblem Redoxverhalten darstellt.
Redoxaktive Liganden sowie deren Komplexe spielen sowohl in der Natur in Enzymen als auch industriell in der Katalyse eine wichtige Rolle. In der Arbeitsgruppe Himmel wurden in diesem Kontext die guanidinofunktionalisierten Aromaten (GFA) sowie deren Untergruppe die guanidino-funktionalisierten Dioxolene (GFD) entwickelt. Bei GFA-Liganden sind zumeist nur der neutrale und der dikationische Zustand stabil, für flexible Anwendungen sind allerdings zusätzliche stabile Oxidationsstufen von Bedeutung. In dieser Arbeit wird die erstmalige Synthese von GFA auf Dibenzo[1,4]dioxin-Basis vorgestellt. Die neuartigen Verbindungen sind die ersten GFA, die im Cyclovoltammogramm vier Ein-Elektronenoxidationen zeigen, und sich demnach wie Hybride aus den GFA und GFD verhalten. Besonders Kupferkomplexe haben in Kombination mit redoxaktiven Liganden interessante Eigenschaften und Anwendungen gezeigt, weshalb mit den neuen Liganden dinukleare Cu(II)-Komplexe synthetisiert wurden und eine intramolekulare Elektronenübertragung vom Liganden auf die Metallzentren untersucht wurde. Dabei konnte der Einfluss der Donorstärke der Liganden, der Härte der Coliganden, sowie des Lösungsmittelsund der Temperatur gezeigt werden. Zum besseren Verständnis der Cu-Guanidin-Bindung wurden mit zwei GFA eine Reihe an dinuklearen MCl2-Vergleichskomplexen synthetisiert. Neben Verbindungen mit den Übergangsmetallen Co, Ni, Cu und Zn, gelang erstmals die Synthese von GFA-Komplexen mit Mn und Fe. Anhand dieser Reihe wurden die Unterschiede in der Metall-Guanidin-Bindung, basierend auf den Festkörper- sowie den berechneten Strukturen, analysiert und die Sonderrolle der Cu–Guanidin-Bindung in dieser Serie gezeigt. Durch verschiedene strukturelle Besonderheiten wie Koordinationsmodus, Cu-Stickstoff-Bindung sowie Versatz aus der Aromatenebene wird für die Cu-Komplexe ein außergewöhnlich hoher π-Beitrag zur Metall-Guanidin-Bindung möglich. Bei den übrigen Metallen ist der π-Beitrag deutlich geringer ausgeprägt. Als weitere Möglichkeit höheroxidierte Zustände zugänglich zu machen, wurde im letzten Teil der Arbeit die Erweiterung des Ligandensystems durch zusätzliche Guanidinofunktionen in Betracht gezogen. Dazu wurden dendrimerartige Oligoguanidinesynthetisiert, in denen erstmals zwölf Guanidinogruppen–vier direkt und acht in der Peripherie–mit einem aromatischen Kern verknüpft wurden. Die Oligoguanidine sind starke Elektronendonoren mit Redoxpotentialen von bis zu E½ = –0.85 V und bilden sehr stabile dikationische Salze. Die Oxidation nimmt vor allem Einfluss auf den aromatischen Kern sowie die inneren Guanidinogruppen, die Funktionalisierungen in der Peripherie bleiben nahezu unberührt und behalten somit ihren stark Brønsted-basischen Charakter. Sie eignen Oligoguanidine sich daher in ihrer oxidierten Form sowohl als Protonen- als auch Elektronenakzeptoren und sind dementsprechend prädestiniert für protonengekoppelte Elektronentransferreaktionen (PCET), was in dieser Arbeit durch ihre Anwendung als Reagenzienin einer intramolekularen Aryl-Aryl-Kupplungsreaktion gezeigt werde konnte.
Silizium nimmt, als zweithäufigstes Element in unserer Erdkruste, einen wichtigen Platz in der Struktur-, Bio- und Geochemie ein – unter anderem in Form seiner Catecholate. Während hyperkoordinierte Catecholatosilikate gut erforscht sind, ist über die tetravalente Stammverbindung Bis(catecholato)silan 1H (wobei H die Substitution am Catecholat-Rückgrat beschreibt) nur wenig bekannt. Die im Rahmen dieser Arbeit durchgeführte Studie über die Struktur von 1H und seinen Derivaten legte eine niederenergetische Barriere für die Si–O-σ- Bindungsmetathese offen, welche die dynamische Kovalenz dieser Substanzklasse begründet. In der Gasphase nimmt monomeres 1H eine tetraedrische Struktur ein, in der kondensierten Phase sind die Donor-freien Verbindungen unter Standardbedingungen jedoch metastabil und oligomerisieren. Dabei hängt der Grad der Oligomerisierung von der Art des Catechols, der Temperatur sowie der Konzentration ab und die Selbstaggregation führt zur Ausbildung makrozyklischer Gerüste. Einhergehend wurde die Lewis-Säurestärke der Bis(catecholato)silane 1X (X = H, tBu, F, Cl, Br) beleuchtet. Dabei ergab die Analyse mittels effektiver sowie globaler Skalierungsmethoden übereinstimmend eine Lewis-Aziditäts-Steigerung von X = tBu < H ≪ F < Cl < Br. Entgegen der gängigen Annahme, dass der induktive Effekt der Substituenten X ausschlaggebend für hohe Lewis-Azidität ist, zeigte sich, dass diese bei den der Bis(catecholato)silanen eher von der abnehmenden π-Rückbindung in das aromatische Ringsystem der Catecholate herrührt. Dabei erwiesen sich das perchlorierte (1Cl) und perbromierte Derivat (1Br) als Lewis-Supersäuren (FIA(1X) > FIA(SbF5)). Die detaillierte Untersuchung des perchlorierten Derivats lieferte verschiedene Anwendungsmöglichkeiten der Lewis-Supersäure 1Cl. Unter anderem kann 1Cl als Bindungsplattform für anionische, hyperkoordinierte Silikate genutzt werden. Daneben werden stabile Addukte mit neutralen Donoren ausgebildet, die beispielsweise zur (reversiblen) CO2-Fixierung genutzt werden können. Mit bidentaten N,N- oder N,P-heteroleptischen Donoren wurden Addukte erhalten, die eine durch Ringspannung induzierte Frustration aufweisen und für die Bindung von Carbonylen eingesetzt werden können. Dies stellt ein seltenes Beispiel für die Modulation bimolekularer FLPs jenseits sterischen Anspruchs dar. Abschließend wurde die Eignung von 1Cl als Katalysator in verschiedenen Heterodehydrokupplungsreaktionen untersucht. Neben der Kupplung von Amino- und Phosphinoboranen kann 1Cl als erster übergangsmetallfreier Katalysator in der Si−N-Heterodehydrokupplung von Silanen und sekundären Aminen mit geringem sterischem Anspruch verwendet werden.
The field of metabolism research evaluates the molecular basis of many important phenomena in biology and medicine, ranging from cellular function to systemic-level metabolic diseases. Spatial metabolomics investigates these phenomena in situ, by mapping metabolites in their native spatial context. Recent technical advances led to the development of matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) imaging, now established as a key technology for spatial metabolomics. MALDI-MS imaging allows for simultaneous and label-free detection of a wide range of analytes, such as metabolites, lipids, peptides and drugs at single-cell resolution. In this dissertation, I have looked into the capabilities this technology offers for untargeted metabolomics, and applied it to a scientific question that would be difficult to address with other technologies. The first aim of this dissertation was to create a systematic account of metabolite detectability by the common MALDI-MS imaging protocols. Despite the abundance of studies that focus on experimental or theoretical aspects of MALDI-MS, the scope of metabolite detectability by different protocols is not fully established, and choosing a suitable protocol for the detection of metabolites of interest remains a non-trivial task. To address this, I have developed experimental and computational tools for the preparation and analysis of a reference standard sample containing a wide selection of biologically-relevant metabolites. The comparison of 24 MALDI-MS protocols has shown the suitability of MS imaging for untargeted metabolomics and clarified which methods could be applicable for the analysis of individual chemical classes and biochemical pathways. The broad applicability of the obtained results was demonstrated through analyses of standard samples on other MS imaging technologies, as well as in comparison with biological tissue data sets. A community web resource was created to facilitate sharing of results and serve as an aid for the selection of the most suitable protocols for future spatial metabolomics experiments. The second aim of this dissertation was to study the associations between spatial differences in metabolism and composition of microbiota in the murine gut. This topic, important for the understanding of host-microbe interactions and their role in health and disease, remains underexplored in the field of microbiome research. By applying MALDI-MS imaging to this question, I discovered regions with distinct metabolic profiles in the whole faecal-matter filled intestine that previously were undetectable by bulk metabolomics. Next, I examined the contributions of individual metabolites, and found that both host physiology and bacterial metabolism contribute to the formation of the observed regions. Additionally, in a proof-of-principle experiment, I have shown that MALDI-MS imaging can serve as a method for determining bacterial localisation in high spatial resolution. Combining the information on the localisation of metabolites and bacteria is a way forward for obtaining direct functional insights into host-microbe interactions by a single technique, simultaneously, in high spatial resolution. Taken together, the computational developments and experimental results obtained in this dissertation help advance the field of spatially resolved untargeted metabolomics.
Die vorliegende Dissertation befasst sich mit der Synthese und Charakterisierung neuartiger Azaacene und Aza-acenoacene aus Acridonen. Dabei steht der Einfluss der Regioisomerie auf die Kristallpackung und die potentielle Anwendung als Halbleitermaterial in organischen Feldeffekttransistoren im Fokus. Im ersten Kapitel der Arbeit wurden zunächst zwei Typen von Diazapentacen-Regioisomeren 1 und 2 miteinander verglichen (Abbildung 1, links). Die cis-trans-Isomerie verändert die optoelektronischen Eigenschaften, Stabilität und Kristallpackung entscheidend. Die Größe des Silylsubstituenten (triisopropylsilyl TIPS, triethylsilyl TES) beeinflusst die Kristallpackung des cis-Derivats. Ein dargestelltes, zum instabilen trans-Isomer (Abbildung 1, links) verwandtes Tetraazaacen 3 wird durch das Einführen von Stickstoff in den zentralen aromatischen Ring stabilisiert. Eine Verlängerung des aromatischen Systems zum trans-Diazahexacen führte zum Schmetterlings-Dimer 4; das Monomer konnte nicht isoliert werden. Weiterhin wurden Aza-Acenoacene 5 und 6 synthetisiert und die erste Anwendung solcher Moleküle in organischen Dünnfilmtransistoren (OTFT) realisiert (Abbildung 1, Mitte). Schlüssel zum Erhalt einer geeigneten Festkörperpackung war die verringerte Anzahl an TIPS-Ethinylsubstituenten im Vergleich zu ihren verwandten, literaturbekannten Verbindungen. Auch hier konnte eine Abhängigkeit der optoelektronischen Eigenschaften und auch der Performanz in elektrischen Bauteilen von der Regioisomerie festgestellt werden. 6 erreicht maximale Mobilitäten von 2.88·10-2 cm2 (Vs) 1, etwa einem Zehntel der Mobilität, die für das unter gleichen Bedingungen verarbeitete Vergleichsmolekül TIPS-Pentacen gefunden wurde. Im letzten Kapitel wurde die Charakterisierung von organischen Dünnfilmtransistoren der vielversprechenden TIPS-TAP-Derivate Br4TAP und I4TAP untersucht (Abbildung 1, rechts). Mit Cl4TAP wurden von Miao et al. Mobilitäten von bis zu 27.8 cm2 (Vs) 1 gefunden.1 Für die Homologe mit Brom und Iod wurden nach quantenchemischen Rechnungen höhere Mobilitäten erwartet.2 Diese Erwartungen wurden für Br4TAP mit Maximalwerten von 54.4 cm2 (Vs) 1 erfüllt. Für I4TAP konnte aufgrund von Defekten in der Dünnfilmstruktur eine geringere Mobilität von bis zu 9.24 cm2 (Vs) 1 gemessen werden.
Radiomarkierte Fluoreszenzfarbstoffe erfahren aktuell eine stetig wachsende Nachfrage als Medikamente für die multimodale Bildgebung (z.B. PET/OI oder SPECT/OI) und Behandlung von Krebs. Sie versprechen somit ein hohes Potential für klinische Anwendungen. Die radiomarkierten Farbstoffe können zur präoperativen Planung (Prestaging) durch Zuhilfenahme der PET/SPECT-Bildgebung zur präzisen Differenzierung zwischen gesundem Gewebe und Tumorgewebe eingesetzt werden. Die anschließende Fluoreszenz-gestützte intraoperative Chirurgie ist eine äußerst effiziente Methode zur akkuraten R0-Tumorentfernung. In der vorliegenden Arbeit wurden neuartige Nahinfrarot(NIR) absorbierende und emittierende Farbstoffe hergestellt, welche für die bimodale PET/SPECT- und optische Bildgebung geeignet sind. Bisher wurden in der Literatur noch nicht über radiomarkierte Si-Rhodamine berichtet. Die nicht-radioaktiven Farbstoffe, welche zur Familie der Si-Rhodamine gehören, wurden über mehrere organische Syntheseschritte erhalten und anschließend vollständig charakterisiert. Außerdem wurden die photophysikalischen Eigenschaften der Si-Rhodamine in wässriger Lösung mit klinisch zugelassenen Farbstoffen (z.B. Indocyaningrün oder Protoporphyrin IX) verglichen, um die erforderlichen Voraussetzungen für die Fluoreszenz-gestützte Chirurgie zu gewährleisten. Dabei zeigen die nicht-radioaktiven Fluoreszenzfarbstoffe im wässrigen Medium Quantenausbeuten bis zu 10% und hohe Photostabilitäten nach Bestrahlung mit NIR-Licht. In radiochemischen Experimenten wurden die Si-Rhodamine mit den am häufigsten genutzten klinischen Radionukliden Technetium-99m und Iod-123 für die SPECT-Bildgebung und mit Fluor-18 als Positronenemitter für die PET-Bildgebung markiert. So zeigte die Radiomarkierung des Si-Rhodamin-Grundgerüsts mit Technetium-99m eine radiochemische Ausbeute von 59% mit einem Verteilungskoeffizienten von log DpH=7.4=1.11 des isolierten Komplexes 78. Die ausgezeichnete in vitro Stabilität des nicht-radioaktiven Rhenium-Komplexes 77 und des Technetium-Komplexes 78 in Dekomplexierungsexperimenten mit L-Histidin in phosphatgepufferter Salzlösung oder humanem Serum zeigen vielversprechende Resultate der Metallkomplexe für in vivo Experimente. Nach ausführlicher Optimierung der Radiomarkierungsexperimente am Si-Rhodamin mit Fluor-18 wurden radiochemische Ausbeuten von bis zu 54% erhalten. Zusätzlich zeigen die radiofluorierten Si-Rhodamine nach zwei Stunden Stabilitäten über 74% in humanem Serum. Außerdem weisen die kationischen und lipophilen nicht-radioaktiven Si-Rhodamine eine beachtliche Aufnahme in Mitochondrien von PC3-Zellen auf, sodass diese Farbstoffe als Perfusionsmarker für die PET- und optische Bildgebung geeignet wären. Ein wesentlicher Vorteil ist, dass der für die Radiofluorierung genutzte Vorläufer auch für die Radioiodierung mit Iod-123 genutzt werden kann. Somit konnte das radioiodierte Si-Rhodamin mit einer radiochemischen Ausbeute von 54% hergestellt werden und zeigt zudem den höchsten Wert der molaren Aktivität von 7.64 TBq/µmol für NIR-Farbstoffe. Des Weiteren wurde ein für die SPECT-Bildgebung kompatibles Si-Rhodamin exemplarisch an bekannte Tumorvektoren wie z.B. das PSMA-1007-Bindungsmotiv geknüpft. Anschließend wurde in vitro die Affinität des nicht-radioaktiven PSMA-1007-funktionalisierten Si-Rhodamins zu LNCaP-Tumorzellen untersucht. Zusätzlich wurde in vivo die Bioverteilung des Konjugats in Nacktmäusen mit Prostatatumor-Xenograft evaluiert. Die neuentwickelten Si-Rhodamine stellen eine neue Klasse radiomarkierter Fluoreszenzfarbstoffe dar, die vielversprechende Eigenschaften für die multimodale Bildgebung zeigen.
Fluorescence microscopy is a powerful method to examine cellular structures and biological processes with high spatial and temporal resolution. The development of novel microscopy techniques and labeling systems has expanded the limits of cellular imaging. However, this progress also relies on the availability of suitable fluorescent probes, thereby creating a need for new synthetic strategies that enable systematic modification of fluorophores. Rhodamine derivatives are widely used fluorophores, which exist in an equilibrium between a non-fluorescent, cell-permeable spirocyclic form and a fluorescent zwitterion. This spirocyclization equilibrium affects crucial properties of rhodamines regarding their applicability in cellular imaging, including fluorogenicity, cell-permeability and blinking behavior. Strategies that provide control over this equilibrium therefore hold the potential to generate suitable fluorescent probes for different microscopy techniques and labeling systems. This thesis describes the development and application of a synthetic strategy, which allows systematic tuning of the spirocyclization equilibrium of rhodamines. To this end, the ortho-carboxy group of various rhodamine derivatives was transformed into amides with different substituents. Introduction of substituted acyl benzenesulfonamides enables to control the spirocyclization equilibrium with unprecedented precision and to specifically optimize the fluorogenicity for HaloTag and SNAP-tag labeling. The resulting probes show suitable properties for live-cell, no-wash confocal and stimulated emission depletion (STED) microscopy. Replacing the ortho-carboxy group with more electron-rich amides strongly shifts the position of the equilibrium toward the spirocyclic state and results in spontaneous blinking. This led to the development of fluorophores for single molecule localization microscopy (SMLM). The generality of this synthetic strategy allowed conversion of various rhodamine-based scaffolds into highly fluorogenic HaloTag and SNAP-tag probes as well as spontaneously blinking dyes. In addition to HaloTag and SNAP-tag labeling, fluorogenic probes for Escherichia coli dihydrofolate reductase (eDHFR), tubulin and human immunodeficiency virus-1 (HIV-1) protease were generated. The ortho-carboxy group was also used as a handle for further functionalization of rhodamines, thereby introducing a zinc ligand to form a localizable and fluorogenic zinc indicator. Altogether, differently colored fluorescent probes optimized for various microscopy techniques and labeling systems were developed. These results demonstrate the value of systematic modification of rhodamines for expanding the fluorophore palette in cellular imaging.
Diese Arbeit befasst sich mit der Funktionalisierung von Metallsalphenen mit Ni-, Cu-, Zn und Pt-zentren, welche im Zuge dieser Dissertation zur Darstellung poröser polymerer Materialien sowie diskreter Käfigverbindungen verwendet wurden. Zu Beginn wurde der Einfluss elektronenziehender Gruppen auf absorptionsspektroskopische Eigenschaften monometallischer Nickelsalphenkomplexe durch Einführung von Cyano- und Trifluormethylsubstituenten an deren Phenylenbrücken untersucht. Dieses Konzept der Funktionalisierung wurde auf sechsfache Zinksalphenkomplexe mit Triptycengrundkörpern übertragen. Gassorptionsmessungen zeigten, dass die Komplexe mit spezifischen Oberflächen zwischen SABET = 333-509 m2g-1 (N2, 77 K) bis zu 2.1 Gew.-% Methan und 14.5 Gew.-% Kohlenstoffdioxid in Abhängigkeit der funktionellen Gruppen adsorbieren. Palladium-katalysierte Suzuki-Miyaura- Kreuzkupplungsreaktionen zwischen borylierten Metallsalphenen und Hexabromtriptycen führten zur Bildung poröser Ni- und Cu-Polymere. Durch Gassorptionsmessungen konnte für das Nickelpolymer eine spezifische Oberfläche von SABET = 438 m2g-1 (N2, 77 K) ermittelt werden, wohingegen das Kupferderivat „Porosität ohne Poren“ demonstriert, was sich durch selektive Adsorption von Kohlenstoffdioxid verdeutlicht. Zweifach Boronsäure-funktionalisiertes Nickelsalphen wurde in Kondensationsreaktionen zu einem zweidimensionalen gestaffelten Boroxin-Netzwerk mit SABET = 63 m2g-1 (N2, 77 K) umgesetzt. Des Weiteren wurden trinukleare Ni- und Pt-Käfigverbindungen mit kovalent gebundenen Salicylimineinheiten ausgehend von Triptycenkörpern synthetisiert.
In my thesis, I worked on two labeling strategies for cellular DNA in fluorescence microscopy. DNA can be studied by fluorescence microscopy with the aid of stains, that can label the total cellular DNA content in live cells. But for some applications, it is desirable that DNA labeling should only occur in specific regions. To this end, Hoechst33342 was photocaged and its in cell activation with light was investigated in a first project. The activatable DNA stain was successfully applied to label specific regions of DNA in the nucleus of living cells and in clusters of cells in zebrafish larva. Metabolic DNA labeling is frequently applied to label newly synthesized DNA. In metabolic DNA labeling, the cell activates nucleotide precursors and incorporates them into the nascent DNA chain. In a subsequent labeling reaction, the precursors can be marked with a fluorophore. Until now, the visualization of incorporated reporter nucleosides was only amenable in fixed cells. In a second project, different approaches for metabolic DNA labeling were employed and further improved for applications in living cells. Initially, a reported nucleoside building block, 5-vinyl-2’-deoxyuridine (VdU), which is marked in an inverse-electron demand Diels–Alder (iEDDA) reaction was explored. The building block had previously been shown to be effective for labeling of DNA in fixed cells, but not in living cells. I describe the development of a probe for a proximity-enhanced iEDDA labeling of VdU-tagged DNA in living cells. To overcome the slow labeling observed for vinyl-modified DNA, the screening of new metabolic precursors was undertaken, in hope of finding a building block with higher reactivity. Therefore, 7-deaza-2’-deoxyadenosine derivatives were modified with more reactive dienophiles and were investigated. Their incorporation into the DNA was verified by mass spectrometry. In fluorescence imaging, they provided the first signals in the nucleus of proliferating cells. Despite faster labeling kinetics, the overall sample preparation takes long since the reporter is introduced first and visualization with a fluorophore is only possible in the second step. Successful live cell imaging demands labeling methods with high labeling efficiency and speed. Therefore, the use of nucleosides that have the fluorophore already attached was investigated. These new metabolic precursors allowed a signal to be detected immediately after their incorporation into the nascent DNA chain. To enable better incorporation yields, the fluorescent nucleosides were further evolved into pro-nucleotides. Nuclear staining in proliferating living cells could be observed, even though it required incubation times of several hours. In summary, all adenosine derivatives label proliferating cells. Current challenges for more demanding applications are poor spatial and temporal resolution for all metabolic approaches. In addition to low incorporation yields, the labeling is often also accompanied by undesirable cytotoxicity effects. If these drawbacks could be overcome, such could pave the way for observing processes that involve DNA synthesis in living cells. Examples of applications include the study of DNA replication, repair, or retroviral DNA synthesis.
Transition metal dichalcogenides (TMDs) are an intensively investigated class of layered materials and are regarded as promising candidates for various applications based on their exotic, layer-dependent optical and electronic properties. When applications are envisioned for a new material, control over the properties of the material is indispensable for efficient integration. Hence, the functionalization of layered nanomaterials is an ever-growing field with countless possibilities for tailoring these properties. However, literature focuses mostly on novel functionalization approaches and proof-of-principle applications, with fundamental questions of heterogeneous reactions at the nanosheet-solution interface rarely being tackled. In the first part of this thesis, insights into the influence of the surface chemistry on heterogeneous functionalization reactions at surfactant stabilized transition metal dichalcogenide nanosheets will be presented. A significant dependence of the heterogeneous gold nanoparticle functionalization of group VI TMDs, namely WS2 and MoS2, will be presented and a simple model is developed to explain observed regioselectivities based on the choice of surfactant and material. Preferential adsorption of representatives of commonly employed surfactants to distinguishable sites on the nanosheets is demonstrated and linked to the chemical structure of the respective surfactant.
Based on this demonstration, precise surfactant-mediated control of heterogeneous functionalization reactions can be envisioned and a generalization of the model for other material-surfactant systems is plausible.
The layer dependence and sensitivity of optical properties of transition metal dichalocgenides towards their environment is one particularly fascinating characteristic of this class of materials. However, a major drawback of the same characteristic is, that reproducibility and comparability of experimental results cannot be guaranteed where perfect control over the environment is not maintained. Especially for film deposition, where individual nanosheets come in close proximity, film morphology has a severe impact on optical properties and can lead to uncertainties in data interpretation. In the second part of this thesis, a promising method for thin-film production from liquid dispersions of nanosheets is presented, capable of largely alleviating these problems, at least on the laboratory scale. A custom deposition setup was developed to enable reproducible formation and transfer of films after preassembly of the layered materials at the interface between two immiscible solvents. These films are extremely thin and smooth, both on the order of 10^0 to 10^1 nm, and nanosheets are aligned over a sizeable area. A proof-of-principle experiment is presented that demonstrates non-covalent solid-state functionalization of WS2 thin-films with organic dyes and indications for electronic interactions between films and dyes are discussed based on changes in photoluminescence of both dyes and films. This well-defined deposition method is further compared to a complementary deposition approach producing porous films with randomized nanosheet orientation and the influence of morphology on the electrocatalytic activity of WS2 thin-film electrodes towards the hydrogen evolution reaction is discussed.
This deposition method should enable experimental designs previously inaccessible to layered nanomaterials produced from liquid phase exfoliation and improve reliability of both film production and data interpretation.
The members of the cofactor family of nicotinamide adenine dinucleotides are involved in many biological processes. New insights about their role in health and disease have highlighted the need to measure these metabolites in live cells. Fluorescent biosensors have been proven to be valuable tools for metabolite measurements with subcellular resolution. Among them, the NAD(P)‑Snifits have been developed to measure free NAD⁺ levels and NADPH/NADP⁺ ratios, respectively. The applicability of these FRET‑based biosensors in physiological relevant model systems is limited by the permeability of the tetramethylrhodamine (TMR)‑based FRET donor substrate and its SNAP‑tag labelling. In this work, fluorogenic FRET donor substrates were developed by manipulating the spirocyclization equilibrium of TMR. Their permeability and cellular SNAP‑tag labelling outperformed early versions of these substrates, especially when they were derivatized with an optimized SPR inhibitor. Systematic characterization selected two FRET donor substrates that could also label the NAD(P)‑Snifits in cultured primary neurons. Consequently, free subcellular NAD⁺ levels and NADPH/NADP⁺ ratios could be measured for the first time in primary neurons. These improvements allowed the comparison of free subcellular NAD⁺ levels and NADPH/NADP⁺ ratios between U2OS cells and primary neurons by FLIM‑FRET measurements. Significant differences were revealed in free mitochondrial NAD⁺ levels and NADPH/NADP⁺ ratios, which could be the result of differences in oxidative phosphorylation activity and have not been described before. In short, this work provides new tools for the quantification of NAD(P) metabolites in physiological relevant model system and thus help to gain new insights into their metabolism.
This dissertation deals with theoretical methods to simulate the linear and nonlinear absorption of circularly polarized light. Specifically, expressions for the rotatory strength in the intermediate state representation (ISR) of the algebraic-diagrammatic construction (ADC) scheme up to third order are detailed in both the length and velocity gauge, and are used to simulate electronic circular dichroism (ECD) spectra. The well-known origin-dependence inherent to the prediction of magnetic properties within approximate theories is explored related to ECD using the ADC method. The ECD spectra of methyloxirane, methylthiirane and their dimethylated counterparts, H2O2 and H2S2 are calculated at the ADC(2) and ADC(3) levels of theory and compared to the same spectra calculated at CC2, CCSD and CC3 level of theory. The simulated ECD spectra of the bicyclic ketones, camphor, norcamphor and fenchone are analysed at ADC(3) level and compared against experimental gas-phase ECD spectra. Solvent effects are addressed by the use of a polarizable continuum model (PCM) on the simulated ECD spectra of solvated epinephrine. The time-resolved counterpart to ECD, namely excited-state electronic circular dichroism (ESECD) is further derived within the ADC/ISR formalism, replacing the ground state with an excited-state, to obtain excited-state rotatory strengths. The quality of the simulated ESECD spectra of norcamphor at ADC(3) level is compared with those same spectra calculated at time-dependent density functional theory (TDDFT) with several exchange-correlation functionals. Furthermore, the ESECD spectrum of binol in the energetically lowest singlet excited state (S1-ESECD) is computed at the ADC(2) level of theory. The simultaneous absorption of two-photons where at least one of them is circularly polarized, so-called “two-photon circular dichroism” (TPCD), is derived within the ADC/ISR formalism. In this case, three formulations of the TPCD rotatory strength are employed and used to simulate the TPCD spectra of methyloxirane and methylthiirane. The chiroptical properties of a twisted biphenyl molecule is subsequently evaluated in terms of their linear (ECD) and nonlinear (TPCD) spectra. The impact the polarization- propagation of the two light beams have on the simulated TPCD spectra of norcamphor is further demonstrated. Next, expressions for the first-order hyperpolarizability are derived and used to calculate the second harmonic generation (SHG) and hyper-Rayleigh scattering (HRS) within the ADC/ISR formalism. The static first-order hyperpolarizability of several organic and inorganic molecules is then compared at ADC(n) and CC levels of theory. The dynamic, SHG, signal strength of several molecules is subsequently evaluated at ADC(n) levels of theory with respect to experimental measurements. Lastly, the HRS of ammonia is evaluated at ADC(2) and ADC(3) levels of theory.
The major goals of the thesis are design and characterization of functional self-assembled monolayers (SAMs) in context of electrostatic interfacial engineering and molecular electronics as well as a study of their thermal stability. The issue of electrostatic engineering can be addressed using custom-designed SAMs with either terminal dipolar groups or dipolar groups embedded into the molecular backbone. As for the first task, the novel concept of embedded dipole was successfully applied to the oxide substrates, which are highly important for photovoltaic applications. A variation of the work function of indium tin oxide (ITO) by 0.5 eV as compared to the reference non-polar functionalization was achieved at the invariable character of the SAM-ambient interface, allowing, thus, to decouple electrostatic engineering from the interface chemistry. The extremely low work function value for one of the tested monolayers expands a rather limited selection of SAMs capable of significantly lowering the work function of ITO. As a further task, electrostatic effects in charge transport across monomolecular films were studied, which is currently one of the most intensely discussed topics in molecular electronics. The tuning of the electrostatic properties was achieved by the fabrication of binary SAMs of biphenylthiolates (BPT) on Au(111), namely by mixing of BPT with fluorine-substituted-BPT (F-BPT) and 4-methyl-4′-BPT (CH3-BPT) with 4-trifluoromethyl-4′-BPT (CF3-BPT). The charge tunneling rate across the binary SAMs was found to vary progressively with their composition between the values for the single-component monolayers, and could, consequently, be fine-tuned and correlated with the work function. The observed behavior was tentatively explained by the appearance of an internal electrostatic field in the SAMs, leading to a change of the energy-level alignments within the junction upon contact of the SAMs to the top eutectic GaIn electrode. The height of the respective injection barrier is, however, unaffected by such a field, corresponding to the values of the transition voltage, which do not change notably with the SAM composition. Analysis of the presented and literature data suggests that the position of a dipolar group in SAM-forming molecules has significant impact on the charge transport behavior of the respective SAMs in the context of molecular electronics. As the next sub-project in the latter context, custom-designed SAMs of ferrocene/ruthenocene-substituted biphenylthiolates and fluorenethiolates on Au(111) were studied. The novel element of these SAMs was the fully conjugated molecular backbone, in contrast to the previous studies utilizing alkyl linkers as elements of molecular diodes. The designed SAMs exhibited a highly exceptional charge transport behavior showing conductance switching triggered by the applied bias. The extent of this switching, described by a maximum rectification ratio (RR) higher than 1000, was comparable to the best performing molecular diodes but in contrast to these “devices” was maintained at very low bias, close to zero volts. The observed behavior could be tentatively explained by a non-reversible redox process affecting the electronic structure of the molecules and their coupling to the top electrode. The above results are particularly promising to create novel molecular devices for potential applications in electronic circuits, molecular memory, or as an electrochemical sensor. Finally, the issue of thermal stability of functional SAMs on coinage metal and oxide substrates was addressed. This issue is of a crucial importance for applications, defining the temperature range of SAM-based devices and framing the preparation routes involving high temperature steps. Several representative SAMs with thiol anchoring group on Au(111) substrates and phosphonic acid (PA) anchoring group on Al2O3 substrates were studied by high resolution X-ray photoelectron spectroscopy chosen as the most suitable experimental tool. The range of the thermal stability and the degradation pathways were found to depend on the chemical composition of the SAM-forming molecules and the character of the substrates, with such crucial parameters as the strength of substrate-anchoring group bond and the presence of a backbone-specific “weak links”. In general, PA monolayers on oxide substrates were found to have higher robustness and better thermal stability compared to thiolates SAMs on coinage metal substrates. My results show, however, that is always advisable to test thermal stability of a specifically designed functional SAM in context of possible “weak links” as far as this stability is important for a particular application.
This thesis describes in-depth mechanistic investigations of homogeneously catalyzed reactions with industrial relevance. Three different reaction classes were studied with the means of density functional theory: dehydrogenation, carbonylation and vinylation. All projects were carried out in a highly integrated framework with continuous exchange between experimental and computational efforts to achieve a high level of accuracy and efficiency. Firstly, the investigations on the dehydrogenative coupling of alcohols to esters are described. The frequently used Ru-MACHO catalyst was shown to undergo degradation after base- induced activation of the pre-catalyst. Attempts to stabilize the highly active species were successful and were shown to lead to two different structural motifs based on the employed phosphine, both of which are active catalysts in base-free (de-)hydrogenation reactions. Quantum-chemical calculations were employed to gain insights into the phosphine-dependent behavior as well as the reaction mechanism. Secondly, the carbonylation of alcohols to carboxylic acids was explored in two project phases. The initial investigation focused on employing Ni complexes and simple phosphine ligands for the transformation of phenyl ethanol as a model compound for ibuprofen. After the computational studies had provided insights into a combination of two reaction mechanisms, which explain the experimental observations and the crucial role of LiI as an additive, the scope was expanded to tertiary Koch-type carbonylation targets. While the desired conversion for these systems was achieved, the observed selectivities and control experiments clearly indicated that different reaction pathways are responsible for the observed conversion. A second set of quantum-chemical investigations was able to provide relevant information about this adapted reaction mechanism and helped to evaluate the catalytic system. Finally, the vinylation of pyrrolidone to N-vinylpyrrolidone was investigated, which was achieved by phosphine organocatalysis and direct employment of acetylene gas at low pressure. The DFT calculations were used to explain the mechanistic details of the reaction as well as to evaluate several side reactions and degradation pathways. The methods were also able to support a modification of the reaction that employs suitable carbonyl compounds to perform Wittig-type reaction steps after the initial formation of an ylide intermediate.
Single-walled carbon nanotubes (SWCNTs) are a promising material for strongly coupled optoelectronic devices, due to their outstanding electrical properties in combination with their narrowband excitonic absorption and emission in the near-infrared. The rich SWCNT photophysics allow to study the interaction of exciton-polaritons with a range of other quasi-particles, such as phonons and biexcitons, as well as with synthetic, luminescent sp3 defects at room temperature. However, the ultimate goal of polariton condensation has not been achived with SWCNT exciton-polaritons so far, and hence understanding their specific polariton population mechanism with respect to their unique photophysical properties is crucial. Here, time-dependent fluorescence and transmission measurements are used to track the exciton-polariton population in strongly coupled metalclad microcavities, identify the dominant relaxation pathways and transitions, use luminescent sp3 defects to increase the polariton population by radiative pumping, and manipulate the SWCNT absorption edge by strong coupling in hybrid organic photodiodes. By investigating the fluorescence decay of SWCNT exciton-polaritons, it is shown, that the dominant population mechanism in this system is radiative pumping. To overcome the thusly imposed limitation of the polariton population by the low SWCNT photoluminescence quantum yield, the SWCNTs are functionalized with luminescent sp3 defects, leading to a population increase up to 10-fold for highly emissive detunings (photon fractions > 90%). By changing the substituents and the binding pattern, tuning of the defect emission could be further employed to access application-relevant near-infrared wavelengths and improve the conditions for polariton condensation. Furthermore, the SWCNT exciton-polariton dynamics are studied in the ultrafast regime by transient transmission spectroscopy. The results reveal a polariton-mediated biexciton transition, that is threefold more efficient than in weakly coupled SWCNTs. The polariton to biexciton transition under off-resonant polariton excitation also indicates fast population transfer from dark to bright polaritons beyond the exciton and photon dephasing times. The efficient biexciton transition of strongly coupled SWCNTs may enable to study correlated many-body states at room temperature, that are predicted for excitonic molecules in strongly coupled high quality cavities. Lastly, strongly coupled SWCNT hybrid organic photodiodes are presented, demonstrating how exciton-polaritons enable light-detection far beyond the intrinsic SWCNT absorption edge. For equal external quantum efficiency, photocarrier generation was observed 200 nm further into the near-infrared as compared to previously reported strongly coupled photodiodes. Thus, representing the first step towards efficient and tuneable polariton-mediated photocurrent generation by SWCNT hybrid organic photodiodes at application-relevant wavelengths.
Single crystals of organic semiconductors are chemically pristine and exhibit nearly perfect long-range structural order. As such, they provide an ideal platform to investigate intrinsic properties. Vibrational spectroscopy techniques, such as Raman and Fourier-transform infrared spectroscopy (FT-IR), are widely employed techniques for the characterization of organic materials. They are versatile tools that can be used to study molecular packing and polymorphism in crystalline organic semiconductors, albeit with poor spatial resolution. Two fundamentally different scanning probe techniques with infrared spectroscopy and imaging capabilities offer a spatial resolution below 100 nm - atomic force microscopy-infrared spectroscopy (AFM-IR) and scattering-type infrared scanning near-field optical microscopy (IR-SNOM). This thesis compares the AFM-IR and the IR-SNOM with each other and to the conventional FT-IR spectroscopy with regard to their applicability to small-molecule organic semiconductors. To this end, single crystals of TIPS-pentacene, TIPS-tetraazapentacene, rubrene and per uorobutyldicyanoperylene carboxydiimide (PDIF-CN2) are used as the testbed. Significant differences are observed in the spectra of the crystals depending on the technique and polarization of incident light that are associated with the intrinsic molecular structure and packing as well as the different working principles of the applied methods. Furthermore, the imaging mode of the AFM-IR and the IR-SNOM is tested on solution-deposited microcrystals of PDIF-CN2. Micro- and nanostructures of layered organic materials can also be created by liquid-phase exfoliation (LPE), a popular technique used to produce two-dimensional nanosheets from layered inorganic crystals. The orthorhombic and the triclinic polymorphs of rubrene are dispersed in aqueous surfactant solution by ultrasonication. Distinct nanostructures of rubrene, referred to as nanorods and nanobelts, are formed that are isolated via liquid cascade centrifugation. Their crystalline nature is confirmed through electron diffraction measurements and Raman spectroscopy. Absorbance and photoluminescence (PL) of the dispersions are found to be similar to rubrene solutions due to random orientations of the nanostructures, however, their PL lifetimes are comparable to the macroscopic crystals. The likely arrangement of rubrene molecules within the nanorods and the nanobelts is deduced from AFM images, electron diffraction patterns, and IR-SNOM spectra.
The algebraic diagrammatic construction (ADC) method, alongside coupled cluster linear response (CCLR) and equation-of-motion coupled cluster (EOMCC) are among the most accurate and predictive methods currently available for the calculation of excited state properties. However, even the most cost effective variants such as ADC(2) or the CC2 flavors of CCLR and EOMCC, still scale with the fifth power of the system size. In recent years, there has been an increased interest in local excited state methods, which borrow concepts from local correlation methods for computing ground state properties, to lower the scaling of canonical ADC, CCLR and EOMCC. By switching from the delocalized canonical molecular orbital (CMO) basis to a more spatially confined orbital representation, the computational complexity can be significantly lowered. Current implementations of local excited state methods use local molecular orbitals (LMOs), natural orbitals (NOs), or combinations thereof. These methods often have the disadvantage of being state-specific, meaning that the compact orbital representation needs to be recomputed for each individual excited state, which greatly increases the cost prefactor. Moreover, they introduce many parameters for controlling the construction of the orbitals, making the methods less robust. In this thesis, a novel approach to local excited state methods is proposed, where the concept of the atomic orbital formulation of the second-order Møller-Plesset (MP2) energy expression is extended to ADC(2) by virtue of the Laplace transform (LT). The spin-opposite scaled second-order algebraic diagrammatic construction method with Cholesky decomposed densities and density fitting, or CDD-DF-SOS-ADC(2) for short, exploits the sparsity of the two-electron repulsion integrals, the atomic ground state density matrix and the atomic transition density matrix to drastically reduce the computational effort. By using the local density fitting approximation, it is shown that linear scaling can be achieved for linear carboxylic acids. For electron-dense systems, near-quadratic scaling can still be achieved if the transition density is sparse, which is for example the case for hydrated formamide. Furthermore, the memory footprint and accuracy of the CDD-DF-SOS-ADC(2) method are explored in detail. The CDD-DF-SOS-ADC(2) method is implemented in a new quantum chemistry software package called MEGALOchem. It is MPI parallel and supports sparse matrix multiplication and tensor contraction through an interface to the distributed block compressed sparse row (DBCSR) library. The thesis discusses the implementation and structure of MEGALOchem in detail, and summarizes the concepts of parallel computing, as well as the basics of matrix multiplication and storage formats.
Nanomaterials play an important role in the flourishing field of nanoscience. Size reduction of materials results in a broad range of outstanding physical and chemical properties as well as a wealth of potential applications. A particularly interesting class of low-dimensional nanostructures are two-dimensional (2D) materials, i.e. individual layers of so-called van der Waals crystals. The research was triggered in 2014 by Geim and Novoselov through the isolation and characterization of graphene, a single layer of two-dimensionally arranged sp2 hybridised carbon atoms. 2D nanomaterials can be obtained by various methods including bottom-up approaches such as chemical vapour deposition and top-down approaches such as liquid phase exfoliation (LPE) and mechanical exfoliation. In recent years, LPE has gained increasing attention due to the high production rates and broad applicability to a range of structures beyond graphene including transition metal dichalcogenides (TMDs), hexagonal boron nitride, metal phosphorus trisulfides and many more. In LPE, high energy and shear forces (e.g. through sonication) are applied to reduce the dimensions of the crystal and the resulting nanosheets are stabilized in the liquid medium through appropriate solvents and surfactant systems. The resultant nanosheets are extremely polydisperse in lateral size and thickness so that LPE is typically coupled with size selection, for example through centrifugation. Due to this additional processing step, it is difficult to assess the impact of the stabilizer on for example the optical properties of the nanosheets which will be a function of both size and stabilizer. In addition, the number of pure organic solvents suitable to prevent reaggregation is very limited which is a bottleneck for further processing and deposition. The goal of the work conducted within the scope of this thesis is to establish protocols to make high quality 2D nanosheets from LPE accessible in a range of liquid media and to achieve a deeper understanding of the impact of the stabilizer on the optical properties of the nanomaterial. To this end, tungsten disulphide (WS2), a semiconducting transition metal dichalcogenide was chosen as model substance due to unique optical fingerprints of the monolayers (e.g. narrow linewidth photoluminescence from exciton only in WS2 monolayers). Throughout this thesis, monolayer-rich dispersions of WS2 nanosheets were prepared by sonication-assisted LPE in a common detergent solution in combination with liquid cascade centrifugation for size selection. In the first part, a protocol was developed to transfer these nanosheets into a range of additive/solvent systems. The advantage over a direct exfoliation in this systems is that dispersions containing nanosheets of the same size/thickness can be compared. This allowed to assess the impact of various chemical environments on the optical properties and to study effects associated with the dielectric screening of excitons (e.g. changes in exciton energy and width). With this foundation established, the nanosheets were transferred into a range of common pure organic solvents using a modified protocol. This is more challenging due to aggregation taking place. Nonetheless, this broad screening made it possible to relate the changes in exciton response to physical parameters such as refractive index and dielectric constant. Importantly, it was confirmed that monolayers can be stable in solvents that are not suitable for the exfoliation itself greatly expanding the choice of solvent for further processing. The third part focuses on precise deposition of the nanosheets on substrates using spin coating. Experimental difficulties such as aggregation and restacking of nanosheets in solvents are addressed in detail together with solutions to improve the colloidal stability of the nanomaterials. In the optimized samples, monolayer properties, such as exciton photoluminescence, are retained after deposition. At last, a new route for transferring nanosheets from water-based WS2 dispersions into different media is introduced which greatly facilitates deposition. In this approach, water-insoluble polymers are added to the aqueous surfactant solution prior to sonication. Through hydrophpobic interaction, the polymer is driven to the interface between the hydrophobic part of the detergent and the nanomaterial. This polymer coating on the nanomaterial reduces aggregation after transfer to hydrophobic organic solvents, suitable for thin-film processing. Such techniques for nanomaterial processing are highly demanded for the integration of these materials into functional devices.
Semiconducting, single-walled carbon nanotubes (SWCNTs) have mechanical and electronic properties that render them a promising material for solution-processable, stretchable and flexible electronics. However, their strong tendency to form aggregates in dispersion constitutes a large obstacle to realize the film uniformity necessary for the transition of devices from laboratory to commercial scale. The resulting inhomogeneities in film morphology lead to an undesired spread in device performance. Based on the tailored formulation of colloidal inks via suitable solvents and additives the first part of this thesis presents a simple yet effective method to slow down aggregation of polymer-wrapped SWCNTs in organic solvents. This effect on aggregation by 1,10- phenanthroline as a stabilizing additive can be monitored with time-dependent absorption spectroscopy. The improved homogeneity of the SWCNT networks deposited from stabilized dispersions after several days of ink storage lead to higher charge carrier mobilities with strongly reduced device-to-device variations compared to inks without additive. The intrinsic ambipolarity of SWCNTs is a great disadvantage for their use in electronic circuits as it leads to large power dissipation. While pure hole conduction can be achieved relatively easily by doping with, for example, ambient oxygen, facilitating exclusive electron conduction represents a large challenge. A solution-processable n-dopant from the family of guanidino-functionalized aromatics (GFAs) is introduced to overcome this limitation. The resulting SWCNT network field-effect transistors (FETs) exhibit pure electron transport with high mobility while hole transport is fully suppressed, excellent switching behavior and good operational stability. Their application potential (combined with a doped p-type FET) is highlighted by complementary inverters with very low power dissipation. This modification of the charge transport behavior is applied to another promising solution-processable semiconductor, i.e., donor-acceptor-polymers. Doping of these polymers with two GFA compounds under various processing conditions improves electron injection and transport while hole transport is suppressed. Again, these transistors display good environmental stability under operating conditions. The extended applicability of the newly introduced GFA dopants to different semiconductors emphasizes their potential for transistors based on solution-processable semiconductor
Quantum chemical simulations of molecular properties are crucial to obtain in-depth insight into a multitude of chemical and biological phenomena. In particular for investigating light-driven systems, modeling of electronic excitations by computational means is indispensable for supporting, complementing, and extending experimental findings. The complexity in terms of electronic structure, intermolecular interactions, and dynamics of the involved molecular systems, however, pushes the limits of computational feasibility. Hybrid quantum-classical environment schemes tackle this complexity by splitting the system into a quantum region and its environment. Thus, they retain the high-level quantum chemical description for the part of interest without neglecting the pivotal effects of the environment.
In this thesis, I develop methods for modeling molecular properties in complex environments. The first half of the thesis is dedicated to new combined approaches of the polarizable embedding (PE) model and the algebraic-diagrammatic construction (ADC) scheme for the polarization propagator for computational spectroscopy simulations. I derive and implement two PE-ADC coupling schemes: The first scheme – pt-PE-ADC – uses a self-consistent PE reference state with a canonical ADC procedure and is suited for computation of electronic excitation energies including a posteriori perturbative corrections. The second scheme – LR-PE-ADC – includes direct coupling to the polarizable environment in an iterative manner, making it suitable for excited electronic states and higher-order response properties. Furthermore, I derive working equations to evaluate analytic nuclear gradients using PE-ADC. To advance the availability of the PE model in general, I implement a standalone, open-source, and hybrid Python/C++ library, called CPPE, and interface it to several freely available quantum chemical host programs. The PE-ADC schemes are implemented with adcc, a toolkit for development of ADC-based methods and combinable with several Python-driven host programs. The simple and clean design of both libraries allows for extension of existing workflows and rapid prototyping. Moreover, I implement response properties using ADC and the intermediate state representation (ISR) in a new Python library, called respondo. The synergy of all three libraries enables the user to implement new features in a straightforward manner, while maintaining usability and efficiency for practical calculations. I test the individual approaches in several benchmark calculations and case studies. For example, I find that excitation energy errors using pt-PE-ADC for microsolvated p-nitroaniline are much smaller than the intrinsic error of ADC itself. Furthermore, I investigate the charge transfer (CT) state involved in the photoprotection mechanism of the flavoprotein dodecin. In addition, I conduct the first computations of higher-order response properties with ADC and a polarizable model. In these studies, I observe that LR-PE-ADC greatly improves the accuracy of the property compared to simpler coupling schemes. I further show that corrections for electron spill-out artifacts and the physically sound evaluation of PE-ADC intensities are decisive when benchmarking against supersystem calculations. With my theoretical derivations and open-source implementations, I provide, to the best of my knowledge, the most complete and unique feature set of polarizable models combined with ADC to date.
The second half of the thesis first contains a general performance improvement of PE models. I implement a PE scheme where the classical electric fields in the environment are evaluated using the fast multipole method (FMM) instead of direct summation. Consequently, the electric field evaluations as rate-limiting step of the classical part exhibit an asymptotic linear scaling in the PE-FMM scheme, making it suitable for efficient simulations of environments with over a million polarizable sites. Next, I show algorithm details for numerically stable solution of response equations in the ADC/ISR framework, and I analyze convergence behavior of different solver algorithms. These algorithms are beneficial for efficient evaluation of PE-ADC response properties, too. I present derivations and numerical case studies of complex excited state polarizabilities which extend the ADC/ISR framework beyond ground state response properties. Then, I investigate the distortion of molecules under external forces. I develop a new electronic structure method to apply hydrostatic pressure in standard quantum chemical simulations via Gaussian potentials, called GOSTSHYP. This implicit embedding scheme directly exerts pressure on a molecule via compression of the electron density, such that it becomes possible to treat atoms and molecules and to run geometry optimizations and dynamics simulations at a pre-defined pressure. This feature set is not found in any other comparable method. I use steered molecular dynamics (SMD) simulations with quantum chemical strain analysis tools to elucidate the rupture process of rubredoxin. I prove that the extremely low rupture force does not result from hydrogen bond networks to the protein as assumed so far in the literature, but that its origin is likely more intricate. Finally, I present the design of novel photocages based on fluorene derivatives. Using an efficient computational screening protocol, I propose cyclopenta-dithiophene as scaffold, leading to the next generation of fluorene-based photocages with desirable absorption and uncaging properties.
Chemically tailorable styrylbenzene and phenyleneethynylene derivatives (SBs and PEs) are the subject of intense research, and are relevant in the fields of sensory materials and optoelectronic device engineering. To this end, the focus of this thesis is construction of SBs and PEs and investigating their optical properties and sensing applications. In chapter 2, we focus on the styrylbenzene derivatives. On the basis of tristyrylbenzene (TSB), we take the advantage of aggregation-induced emission (AIE) into account, design two isomers and explore the regioisomerism effect on the optical properties (chapter 2.1). Then, using the 1,3,5-tristyrylbenzene as a star-shaped core, we extend the moleculer skeleton and design a series of tristyrylbenzene derivatives to investigate their photophysical properties and optical response to acid and metal ions. The transition metals such as Al3+, Mn2+, Fe3+, Fe2+, Cd2+, Ag+ and Hg2+ can be well discriminated by these SBs (chapter 2.2). Using ionic phenyleneethynylene derivatives as sensors for analytes with similar structure is interesting. In chapter 3, we focus on the phenyleneethynylene derivatives. We first construct a sensor array composed of three anionic poly(p-phenyleneethynylene)s (PPEs), and their electrostatic complexes with metal ions (Fe2+, Cu2+, Co2+). This array discriminates PTH-amino acid residues degraded from an oligopeptide through Edman sequencing (chapter 3.1). Given that synthesis of guanidine-substituted PEs and their characterization remains a challenge, we design a series of PE-trimers bearing N-Boc-protected guanidine side groups, to address the deprotection defects under regular condition (DCM/TFA). Meanwhile, their optical properties are discussed (chapter 3.2). On the basis of above research, we prepare the true guanidinium-PPE (chapter 3.3) and reveal that this material is a precious sensor for nitroaromatics. The guanidinium-PPE could detect picric acid with high selectivity and sensitivity in water. All together, these results contribute to the development of research on hydrocarbon AIEgens and the application of SB/PE-based materials for luminescent chemosensors.
In Chapter 2, a gold-catalyzed direct alkynylation for the synthesis of 1,3-enynes using alkyl 3-aminoacrylates and hypervalent iodine reagents is reported. This reaction, which involves the formation of an alkynyl Au(III) species and a direct C-H activation of alkyl 3-aminoacrylates, reports twenty-six successful conversions in 62-92% yield with excellent functional group tolerance. In addition, only one configuration of 1,3- enynes containing enamines is produced and no further cyclization product is found. In Chapter 3, a gold-catalyzed cascade C(sp3)-H alkynylation/ oxy-alkynylation of β- keto compounds with hypervalent iodine(III) reagents for the synthesis of tetrasubstituted furans is described. The alkynyl Au(III) species plays a crucial role in Au(I)/Au(III) catalytic cycles. The two operating catalytic cycles include an alkynylation of activated C(sp3)-H bond and an oxy-alkynylation of an β-alkynyl ketone. This simple strategy features mild reaction conditions, high functional group tolerance, and a wide substrate scope. Furthermore, the synthetic utility of the method was demonstrated by diverse functionalizations of the final products. Gram-scale synthesis and proposed mechanism are also presented. In Chapter 4, another gold-catalyzed cascade C(sp3)–H alkynylation/Nitrogenalkynylation of 2-pyridine compounds with hypervalent iodine(III) reagents for the synthesis of poly-substituted indolizines is described. The broad substrate scope, good functional group tolerance and good efficiency render this method useful for organic synthesis, especially for the synthesis of nitrogen-containing compounds. Gram-scale synthesis and proposed mechanism are also revealed.
In Chapter 2, a gold-catalyzed domino annulation of diazo-tethered alkynes with nitriles proceeds through a sequential 6-endo-dig cyclization/nitrile insertion/C-H functionalization. This protocol offers a general and modular strategy for the rapid assembly of benzophenanthridine derivatives with a broad functional-group tolerance. Moreover, this methodology, using readily available nitriles as the nitrogen source, represent a versatile platform for the construction of benzophenanthridine frameworks. In Chapter 3, an unprecedented dichotomy in the regioselectivity of carbohydroxylation of diazo-tethered alkynes was observed. The gold-catalyzed 6-endo-dig cyclization leads to the quinoid-carbene species, terminated by direct O-H insertion under additive-free conditions, while the reaction in the presence of Et3N(HF)3 undergoes an O-H ortho-insertion of carbene/rearrangement to give the dihydroxynaphthalene isomers as the major products. In Chapter 4, the gold-catalyzed carbofluorination of diazo-tethered alkynes provides a facile, efficient, and atom-economical route to α-fluoronaphthalene derivatives. An intermediate endocyclic gold carbene, generated by an intramolecular 6-endo-dig cyclization, promotes a carbene H-F insertion to afford the desired products.
The thesis is focused on hydroxylamine-mediated direct arene C-H amination and C-C amination from benzyl alcohols, alkylarenes, styrenes and benzyl ethers/esters, which are used for the anilines synthesis. Additionally, this thesis consists of three parts.
In the first part (Chapter 2), a direct metal-free arene C-H amination mediated by hydroxylamines (TsONHBoc or TsONHR) was discovered, accidentally. Besides one literature reported with only three examples, this is the only report for an aniline synthesis via hydroxylamine derivatives under metal-free conditions. Primary anilines and secondary anilines are afforded under open flask conditions with this protocol, by using TsONHBoc or TsONHR, respectively. In contrast to metal-catalyzed processes, the reaction is triggered by an oxygen-accelerated SET (single electron transfer) from the aromatic systems to the electron-deficient hydroxylamine derivatives. The recombination of an arene radical cation and an aminyl radical, which are in close proximity, then affords the aminated products. The methodology can be applied for the amination of a variety of complex molecules, natural bioactive products and bestselling drugs. The operationally easy, broad functional group tolerance and scalability of this reaction in the absence of any metal make it appealing for both academy and industry.
The second part (Chapter 3) describes an aza-Hock rearrangement of benzyl alcohols by using hydroxylamines (ArSO2ONHR) as reagents under mild conditions, which makes primary anilines accessible from O-(2,4,6- trimethylbenzenesulfonyl)hydroxylamine (MSH) and secondary anilines available from other aminating reagents like TsONHR. Mechanistically we could prove that an aza-Hock rearrangement operates. Other benzyl cation precursors (eg. benzyl ethers/esters/halides and alkylarenes) are also potent substrates for this strategy, expanding the synthetic utility. In addition, chemoselective C-C brominations and oxygenations are possible under similar conditions. Interestingly, despite some early evidence for such a reactivity pattern, until now the synthetic utility of this process is limited and our report might pave the way for further protocols based on such pattern in the future.
A modified aza-Hock rearrangement of benzyl cation precursors – alkylarenes, styrenes and benzyl ethers/esters – mediated by hydroxylamines, was investigated in the third part (Chapter 4). Notably, i-alkylarenes are differentiated by the aminating reagent MSH over n-alkylarenes, and n-alkylarenes are smoothly converted into anilines with TsONHMe. This rare phenomenon points out a way to distinguish different kinds of alkylarenes with such a pattern. Moreover, aminodealkenylation (C-C amination of styrenes) opens a gateway for employing styrenes in a plethora of known benzyl cation transformations, which should serve as a valuable tool for anilines synthesis, adding to the growing catalogue of C-C functionalization.
Although cells represent the smallest building blocks of life, they are already exhibiting a high level of complexity. It is therefore not surprising that researchers tend to utilize simplified systems for investigating, but also reconstituting, cellular processes in artificially constructed cells. The conception of those artificial cells can be done using bottom-up biological approaches. Currently, the reconstitution of cellular process is achieved using natural or nature-derived components like the actomyosin-complex for the reconstitution of cellular motility. Although a reduction of complexity can be accomplished in this way, natural systems still require specialized conditions and sophisticated buffers. Ultimately, the reduction of complexity can only be realized by the reconstitution of cellular processes using completely synthetic materials. In this thesis, a completely artificial cytoskeleton based on thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) to trigger motility of synthetic cells was established. To this end, a PNIPAM-based composite material containing gold nanorods was generated and its physiochemical behavior was characterized. The composite material was introduced and assembled inside water-in-oil emulsion droplets that have been stabilized by either a custom-made PNIPAM-containing surfactant (PNS) or a commercially available fluorosurfactant (CS). Besides the reversibility of the PNIPAM phase transition in bulk and droplet-based synthetic cells, the on-demand inducible deformation of droplets due to this phase transition was shown. Additionally, droplet migration was triggered using asymmetric PNIPAM-containing droplets in combination with fluorophilic-coated surfaces. The production of those cell polarization-mimicking droplets was achieved via targeted fusion of stable and unstable droplets during polymerization. Following the assessment of PNIPAM-mediated droplet motility, for the first time, the artificial cytoskeleton material was combined with the natural cytoskeleton protein actin by a sequential pico-injection approach thus elucidating the biocompatibility of the presented system. Herein, a versatile PNIPAM-based artificial cytoskeleton for synthetic cell applications was designed and implemented. The control over the PNIPAM volume transition processes allowed to achieve the motility of the droplet-based synthetic cells by their dynamic deformation. The biocompatibility of the system by combining natural and synthetic cytoskeleton components could be shown. The tolerance of the PNIPAM system also towards specialized buffer systems, might expand the bandwidth of the bottom-up synthetic biology tool kit, enhancing the assembly of hybrid cellular modules. Therefore, the developed approach represents an important milestone in the development of bottom-up synthetic biology applications.
Diese Arbeit beschäftigt sich mit der Metall-Ligand-Wechselwirkung in Ln(III), An(III) und An(IV)-Komplexverbindungen mit O-, N,O- und N-Donorliganden. Hauptaugenmerk liegt hierbei auf der NMR-Spektroskopie, die durch Methoden wie die Electron Spray Ionization Massenspektrometrie (ESI-MS), die zeitaufgelöste Laserfluoreszenzspektroskopie (TRLFS) und quantenmechanische Modellrechnungen punktuell ergänzt wird. Der erste Teil der Arbeit konzentriert sich auf die NMR-spektroskopische Untersuchung der Komplexierung von Ln(III) und Am(III) mit dem O-Donorliganden N,N,N'N' Tetraethyldigylcolamid (TEDGA). Daraus geht hervor, dass die Ln(III)-O und Am(III)-O Bindung im [M(TEDGA)3]3+ Komplex (M = Ln, Am) ähnliche Bindungseigenschaften besitzen. Die Wechselwirkung zwischen Ligand und Am(III) bzw. Ln(III) ist daher von vergleichbarer elektrostatischer Natur. Im zweiten Teil wird die Komplexierung von Ln(III) und Am(III) mit dem N,O-Donorliganden N,N,N',N'-Tetraethyl-2,6-carboxamidopyridin (Et-Pic) untersucht. Die NMR-Analyse von [M(Et-Pic)3]3+ (M = Ln, Am) legt ähnliche Bindungseigenschaften von Ln(III)-O und Am(III)-O-Bindung nahe. Im Gegensatz dazu zeigen die Ln(III)-N und Am(III)-N-Bindung unterschiedliche Eigenschaften. Der partiell höhere kovalente Bindungsanteil der An(III)-N-Bindung kann mittels TRLFS bestätigt werden, da Cm(III) um eine Größenordnung stabilere 1:3-Komplexe mit Et-Pic bildet als Eu(III). Der dritte Teil der Arbeit beschäftigt sich mit der NMR-spektroskopischen Studie von [Th(nPr-BTP)3]4+ (nPr-BTP = 2,6-Bis(dipropyl-1,2,4-triazin-3-yl)pyridin). Abhängig von der Wahl des Lösungsmittels zeigen sich für [Th(nPr-BTP)3]4+ unterschiedliche Komplexspezies. Eine asymmetrische Spezies wird in polar-protischen Lösungsmitteln gebildet, wohingegen eine symmetrische Spezies in polar-aprotischen Lösungsmitteln auftritt. Die symmetrische Spezies ist dabei isostrukturell zu den bereits untersuchten Komplexen [M(nPr-BTP)3]3+ (M = Ln, Am). Untersuchungen von [Th(nPr-BTP)3]4+ in einer Vielzahl deuterierter Lösungsmittel und binären Lösungsmittelgemischen zeigen, dass die Ligandkonfiguration von der Fähigkeit des Lösungsmittels abhängig ist, aktiv H-Brückenbindungen auszubilden. Ursache hierfür ist eine stärkere Wechselwirkung zwischen dem Komplex und dem Lösungsmittel. Unterstützt werden die experimentellen Befunde durch theoretische Rechnungen, die die Struktur der asymmetrischen Spezies untersuchen.
Die Verbindungsklasse der Boronsäuren zeichnet sich durch ihre vielfältigen Anwendungen aus. Die prominente SUZUKI-MIYAURA-Kreuzkupplung ist heutzutage eine der am häufigsten eingesetzten chemischen Reaktionen. Boronsäuren werden nach wie vor als nützliche synthetische Intermediate zu C–C-Bindungsknüpfungen angesehen, gewinnen jedoch auch zunehmend an Bedeutung in den Materialwissenschaften, der Bioanalytik oder der Strukturbiologie. In der Medizinischen Chemie kennzeichnete die Zulassung des ersten boronsäurehaltigen Arzneistoffs, Bortezomib, durch die FDA im Jahre 2003 einen Meilenstein. Während der synthetische Zugang zu aromatischen Boronsäure-Derivaten gesichert ist, fehlt es an Syntheserouten zur routinemäßigen Darstellung aliphatischer und peptidischer Boronsäuren mit möglichst hoher Diversität. Die häufigsten Probleme bei der Synthese sind dabei der Aufbau der α-Aminoboronsäure-Partialstruktur, die Entschützung der intermediären Boronsäure-Ester sowie die Aufreinigung der finalen Verbindungen.
Im Rahmen der vorliegenden Arbeit wurden verschiedene Routen zur Darstellung von α-Aminoboronsäuren untersucht. Dabei wurde festgestellt, dass sich manche der literaturbekannten Methoden zwar zur Darstellung entsprechender Fragmente eigneten, die anschließenden Fragmentkondensationen in Lösung jedoch nur mit erhöhtem Aufwand realisierbar waren. Daher wurden innovative Ansätze etabliert, die den Aufbau größerer Molekül-Bibliotheken ermöglichen.
Um den Zugang zu komplexen Boronsäuren zu erhalten, wurde eine neuartige Methode zur effizienten und simplen Entschützung von Boronsäure-Estern entwickelt. Die Transesterifizierung mit flüchtiger Methylboronsäure in einphasigen Systemen ermöglichte dabei die quantitative Überführung aromatischer, aliphatischer und peptidischer Ester in die entsprechenden freien Boronsäuren. Die Aufreinigung konnte dabei durch simple Evaporation von Reagenz, Nebenprodukt und Lösungsmittel erfolgen. Auch die Hydrolyse von äußerst stabilen Pinandiolestern erfolgte effizient mithilfe des in dieser Arbeit entwickelten Ansatzes.
Mithilfe der monophasischen Transesterifizierung wurde der Zugang zu einer bisher unbekannten Verbindungsklasse eröffnet, den Fmoc-α-Aminoboronsäuren, welche sich zur routinemäßigen Festphasensynthese an kommerziell erhältlichem 1-Glycerol-Harz eignen. Die hier beschriebenen Synthesemethoden ermöglichen den Zugang zu einer Vielzahl an Boronsäuren nach einem Baukastenprinzip und haben daher das Potenzial, konventionelle Routen zu ergänzen oder sogar zu ersetzen.
Triptycen eignet sich aufgrund seiner inhärenten Rigidität und der vielfältigen Substitutionsmöglichkeiten als Baustein für die Synthese kovalent organischer Käfigverbindungen. Aufgrund des „fused ortho effects“ sind Substitutionen an den ortho-Positionen zu den Brückenköpfen des Triptycens allerdings stark erschwert.
In der vorliegenden Arbeit wurden durch einen mehrstufigen Syntheseweg solche vierfach in ortho-Position formylierten Triptycene synthetisiert. Hierfür erfolgte zuerst der Einbau einer elektronenziehenden Chinoxalineinheit in einen der Triptycenarme, wodurch das benötigte Substitutionsmuster in die zwei restlichen Triptycenarme eingebracht werden konnte.
Während die ursprünglich angestrebte kuboktaedrische [12+24]-Salphen-Käfigverbindung nicht erhalten werden konnte, gelang es im Gegensatz dazu neue Käfigverbindungen zu synthetisieren, die eine strukturelle Ähnlichkeit zu Cucurbiturilen aufweisen; die „Cucurbitimine“. Diese Cucurbitimine konnten in unterschiedlicher Größe hergestellt werden. Somit besteht die Möglichkeit der Synthese von Käfigverbindungen, welche optimal in Größe und Form ihrer Kavität angepasst werden können. Erste Wirt-Gast-Versuche zeigten, dass die Cucurbitimine, ähnlich wie ihre strukturverwandten Cucurbiturile, die Fähigkeit zur Komplexierung unterschiedlicher Substanzen in der Kavität besitzen. Hierbei wurde im Käfig befindliches THF gegen Toluol ausgetauscht. Im Gegensatz zu Cucurbiturilen haben die Cucurbitimine eine ausgezeichnete Löslichkeit in organischen Lösungsmitteln. Zusätzlich besteht die Möglichkeit, chirale Gruppen in die Cucurbitimine einzubringen. Diese Eigenschaften machen die Cucurbitimine zu einer vielversprechenden Klasse an Käfigmolekülen.
In organischen Halbleiterschichten aus Donor- und Akzeptormaterialien besteht einenger Zusammenhang zwischen der Dynamik photoelektrischer Prozesse und den vor-handenen Energiezuständen. Diese werden durch die Eigenschaften der Materialienselbst bestimmt, sind aber auch von der Wechselwirkung der Moleküle miteinanderabhängig und damit von deren relativen Orientierung sowie deren räumlichen Di-stanz. Die Energiezustände sind also direkt von der Morphologie der organischenSchicht mitbestimmt. In dieser Arbeit wird die Morphologie funktioneller Schichtenunter anderem von organischen Solarzellen visualisiert, welche aus einem Polymerund einem Nicht-Fulleren Akzeptor, im Speziellen PBDB -T und ITIC, gemischtwerden. Die Visualisierung der Morphologie erfolgt mittels Hellfeld Transmissions-elektronenmikroskopie (TEM) sowie analytischer TEM und wird mit den jeweili-gen Bauteilparametern korreliert. Durch Kryo-TEM Tomographie wurden kohären-te PBDB -T und ITIC Kristalle am Donor-Akzeptor-Übergang von PBDB -T:ITICMischschichten gefunden. Dabei dominieren ITIC Kristallstrukturen eines spezifi-schen Polymorphs. Mit diesen Resultaten demonstriert die vorliegende Arbeit Mög-lichkeiten zum visuellen Nachweis spezifischer morphologischer Eigenschaften vonorganischen Funktionsmaterialien. Diese Visualisierung ist grundlegend für die Mo-dellierung der genauen Anordnung von PBDB -T und ITIC Molekülen in der Misch-schicht und damit wegweisend für eine Simulation und Optimierung des Modellsys-tems PBDB -T:ITIC und darauf aufbauender Systeme.
Porous organic cages (POC) are an emerging class of functional materials containing cavities large enough to host guest molecules. In recent years, the use of dynamic covalent bond formation has resulted in a vast array of cage compounds with different geometries and sizes. One such commonly used reaction is the imine condensation, which forms cage compounds in excellent yields but has a major disadvantage due its chemically labile nature. This thesis deals with the transformation of imine cages to chemically robust amide cages via the Pinnick oxidation. Historically, amide cages have been synthesized by simply coupling acid chlorides and amines, however, this method is ineffective in accessing larger cage molecules with complex geometries. Using the Pinnick oxidation, a triptycene-based [4+6] salicylbisamide cage was synthesized, which could not be generated via an irreversible amide bond forming reaction. The novel amide cage exhibited excellent chemical and thermal stability, as well as a specific surface area of SA (BET) = 370 m2/g. The versatility of this method to obtain amide cages was established by carrying out a ‘scope and limitation’ study by varying parameters such as electronic effects, solubility, hydrolytic stability of the imine cage, and steric effects. Moreover, it was possible to successfully apply the Pinnick oxidation on imine cages derived from aromatic amines as well as aliphatic amines. Furthermore, the enhanced chemical stability of the amide cages offered a unique opportunity to post-functionalize the cage compounds by well-known reactions such as bromination, nitration, Suzuki coupling, C-H activated borylation, etc. Consequently, functional amide cages could be obtained which have great potential in the encapsulation of small molecules as well as construction of hierarchical structures (such as COFs or polymers).
Singlet fission (SF) is a photophysical reaction where a singlet excited organic molecule shares its energy with a neighbor ground state organic molecule, generating two spin-triplet states. In this work, the role of chemical substitutions and geometrical changes were investigated on SF in thin films, in direct-linked heterodimers, and in bridge-linked heterodimers.
Ozon ist als starkes Oxidationsmittel ein wichtiges Spurengas in der Atmosphäre. In der arktischen Troposphäre liegt die Hintergrundkonzentration von Ozon bei etwa 30-50 nmol/mol. Das Ozon wird hauptsächlich durch photochemische Reaktionen von Stickoxiden und flüchtigen organischen Verbindungen gebildet oder aus niedrigeren Breiten in die Arktis transportiert. Im polaren Frühling werden regelmäßig troposphärische Ozonzerstörungsereignisse (Ozone Depletion Event, kurz ODE) beobachtet. Während eines ODE reduziert sich das Mischungsverhältnis von Ozon in der planetaren Grenzschicht innerhalb von Stunden bis Tagen von der Hintergrundkonzentration auf Werte von nahezu Null. Gleichzeitig werden ansteigende Konzentrationen von gasförmigen Halogenen, insbesondere Brom, beobachtet, welches aus Meersalz im Aerosol, Schnee oder Eis freigesetzt wird. Ein möglicher Emissionsmechanismus ist die autokatalytische "Bromexplosion". Da im Rahmen eines ODE das Oxidationspotential der Atmosphäre und die chemischen Prozesse von Ozon, organischen Gasen und Quecksilber stark verändert werden, besteht Interesse an der Untersuchung von ODEs.
Mit dem eindimensionalen, chemischen Transportmodell KINAL-T wird das Auftreten von oszillierenden ODEs untersucht. Nach dem Abbruch eines ODE ist das Mischungsverhältnis von Ozon auf nahezu Null gesunken, was zu einer Umwandlung von reaktivem Brom zu chemisch trägem Bromid führt. Ozon kann sich dann photochemisch oder durch Transportprozesse erneuern, was zu einer weiteren Bromexplosion und ODE führen kann. Um dies zu modellieren und in einer umfassenden Parameterstudie zu untersuchen, wird das Computermodell optimiert und unter anderem um komplexe Aerosolchemie erweitert. Es werden Oszillationsperioden von mindestens fünf Tagen für photochemisch erneuertes Ozon und von mindestens 30 Tagen für Ozonerneuerung durch vertikalen Transport aus der freien Troposphäre gefunden. Eine wichtige Voraussetzung für oszillierende ODEs ist nach den Ergebnissen dieser Arbeit eine ausreichend starke Inversionsschicht, die den Austausch der Luft zwischen der Grenzschicht und freien Troposphäre minimiert. In einer Parameterstudie wird die Abhängigkeit der Oszillationsperiode von der Stickoxidkonzentration, Stärke der Inversionsschicht, Lufttemperatur, Aerosoldichte und Sonneneinstrahlung untersucht und diskutiert.
Mit dem dreidimensionalen, regionalen Modell WRF-Chem werden Chemie und Transport in einem den Großteil der Arktis umfassenden Gebiet untersucht. Das Ziel ist eine möglichst genaue Vorhersage der Ozon- und Bromchemie im Frühjahr 2009, für das viele Messdaten zum Vergleich vorliegt. Hierzu wird ein bestehender Chemiemechanismus um Halogenchemie und Bromemissionsmechanismen erweitert, außerdem wird die Einspeisung von Daten zur Unterscheidung des Alters des Meereises ermöglicht. In einer Parameterstudie werden verschiedene Emissionsmechanismen getestet und mit GOME-2 Satellitendaten sowie Daten an zwei Messstationen verglichen. Die vom Modell gefundenen Strukturen sind mit den Messdaten konsistent. Eine Erhöhung der Emissionsstärke verbessert die Simulationsergebnisse, zudem verbessert die Annahmen einer Bromfreisetzung durch von Ozon oxidiertes Bromid die Simulation der Auslösung der Bromexplosion. Meterologische Relaxation ist zur korrekten Vorhersage der ODEs über die dreimonatige Simulationszeit nötig. Es stellte sich heraus, dass ohne den Halogenchemiemechanismus keine korrekte Vorhersage der arktischen Chemie im Frühling möglich ist.
Narrowband photoluminescence (PL) in the near-infrared and electrical exciton generation make semiconducting single-walled carbon nanotubes (SWNTs) promising materials for optoelectronic devices. The functionalization of SWNTs with luminescent sp3 defects offers synthetically tunable light emission and enhances their potential for applications such as quantum light sources, bioimaging and sensing. However, the synthetic protocols that are currently used to create these defects are limited to aqueous dispersions of SWNTs, which are compromised by short tube lengths, residual metallic SWNTs and poor solution-processability. Here, the combination of highly selective polymer-sorting and shear force mixing as a mild exfoliation method provides electronically-pure (6,5) SWNTs in toluene with average tube lengths > 1 µm and strategies for their sp3 functionalization are developed based on simple diazonium chemistry. The complexation by an ether crown allows for the solubilization of commercially available aryldiazonium salts in organic solvents and thus enables their reaction with polymer-wrapped SWNTs. The resulting defect-tailored (6,5) SWNTs show a relatively high photoluminescence quantum yield (PLQY) of up to 4 % with 90 % of photons emitted from the sp3 defect. The dependence of the defect-induced PL brightening on the nanotube length indicates that the PLQY of the pristine SWNT may exceed that of the sp3 defect for a sufficiently high nanotube quality. By using custom-synthesized diazonium salts in a modified protocol, stable organic radicals are covalently attached to purified semiconducting SWNTs via luminescent aryl defects. The proximity between the defect-localized exciton and the unpaired electron promotes spin exchange and electron transfer processes, which are identified through time-resolved PL measurements. The results point toward an increased yield of triplet excitons due to radical-enhanced intersystem crossing, which could serve as a general concept to probe triplet states in SWNTs. The dispersion in organic solvents facilitates the integration of defect-tailored, polymer-wrapped SWNTs into optoelectronic devices. A planar dielectric waveguide structure channels the PL emitted from sp3 defects over distances > 1 mm and thus represents a first step toward their interfacing with photonic circuits and photovoltaic devices. Moreover, the demonstration of electroluminescence from sp3 defects in light-emitting field-effect transistors underpins their potential for electrically-driven single-photon sources.
In this work it was investigated to what extent the triptycene unit can be used as a "crystallographic synthon" to induce a tight face-to-face π stacking of aromatic π systems. This arrangement is promising for high carrier mobility in semiconductors. For this purpose, triptycene end-capped Quinoxalinophenanthrophenazine (QPP) derivatives with different substituents at the peripheral phenylene unit were synthesized and their packing behavior was investigated. The influence of crystallization conditions was also tested. From nine QPP derivatives, 19 crystal structures and six donor-acceptor co-crystal structures were obtained. In 24 of these structures characteristic, tightly packed π-dimers were found. This underlines the high robustness of the "triptycene synthon" and shows that it can be used to effectively modify the π stacking behavior towards a high overlap of the π planes. The concept of triptycene end-capping was finally applied to benzothienobenzothiophen (BTBT) to show that this strategy can be used for other π systems as well. This assumption was confirmed with six crystal structures obtained. Additionally, the packing behavior of a series of cyano-substituted pyrene-fused pyrazaacenes (PPAs), which are potential n-type semiconductors due to their electron deficient nature, and Pyrene-substituted QPPs was investigated as well. In all ten crystal structures π-stacking, promising for charge transport, was found. Experimental and theoretical investigations as well as calculated charge transfer integrals indicate that some of the presented materials are promising candidates for semiconductors in organic electronics.
Koordinationsverbindungen sind in der heutigen Chemie omnipräsent und in vielen Bereichen nicht mehr wegzudenken, so zum Beispiel auch in der medizinischen Anwendung in der Diagnose und Therapie. Die sogenannten Bispidine (3,7-Diazabicyclo[3.3.1]nonan-Derivate) sind dafür bekannt Metallionen stabil und selektiv zu binden und werden unter anderem in den Bereichen der Katalyse, der Biomimetik und der Radiopharmazie erforscht. Dabei verbinden diese Bindungsmotive die Vorteile der konventionellen macrozyklischen und azyklischen Liganden. Diese Arbeit beschäftigt sich hauptsächlich mit der Synthese von Bispidin-Liganden für eine Auswahl an Metallionen, welche in der Radiotherapie (Lu(III) und Ac(III)) und der Magnetresonanztomographie (Mn(II)) Anwendung finden. Für das erste Feld wurden nona- und decadentate Liganden synthetisiert (L1-L3) und die radiochemischen Eigenschaften ihrer Komplexe untersucht. Die Liganden L1 (111In, 177Lu, 225Ac) und L2 (177Lu) sind schnell und unter milden Bedingungen quantitativ radioaktiv markierbar (5 min, 40 °C). Weitere Untersuchungen zeigen zusätzlich herausragende Stabilitäten (Resistenz gegen Transmetallierung) des 177LuL1- (87 % nach 7 d) und 225AcL2-Komplexes (85 % nach 10 d) in Humanserum, welche die des 'Gold Standards' DOTA übertreffen. Das Konjugat des Liganden L1 mit dem Octapeptid TATE zeigt ähnlich herausragende Eigenschaften. Die Markierung mit 177Lu geschieht bei milden Konditionen quantitativ (30 min, 40 °C) mit einer für die radiopharmazeutische Anwendung ausreichend hohen spezifischen molaren Aktivität (AM = 125 MBq/nmol). Zudem erweist sich der Radiometallkomplex als stabil in Humanserum (88 % nach 3 d) und soll deshalb zukünftig in in vivo Studien untersucht werden. Aufgrund der in der molekularen Festphasenstruktur gefundenen gesättigten Koordinationssphäre des LuIII-Ions, folgten weitere Betrachtungen verschiedener Lanthanoid-Komplexe bezüglich ihrer photophysikalischen und magnetischen Eigenschaften. Hierbei wurden Komplexe (EuIII, TbIII, YbIII) mit hohen Lumineszenzlebensdauern (τ(EuL1) = 1.51 ms, τ(TbL1) = 1.95 ms, τ(YbL1) = 5.11 µs) und guten Quantenausbeuten (Φ(EuL1) = 35 %, Φ(TbL1) = 70 %) in wässriger Lösung erhalten, welche Derivate dieser Verbindungen als potentielle Kandidaten für Zwei-Photonen-Fluoreszenzmikroskopie auszeichnen. Mit den unsubstituierten Verbindungen liegt die Anregungswellenlänge mit λexc = 310 nm außerhalb des biologischen Fensters, wodurch eine Funktionalisierung mit intra-Ligand-Charge-Transfer Antennen notwendig wird. Zusätzlich legte die gefundene Koordinationsgeometrie, welche oftmals in SMMs gefunden wird, Untersuchungen der magnetischen Eigenschaften einiger Metallkomplexe (Ce(III), Dy(III), Ho(III), Er(III)) nahe. Dabei wurde gezeigt, dass es sich bei DyL1 um einen field-on SMM mit zwei effektiven Barrieren von Ueff;1 = 22.1 cm-1 und Ueff;2 = 46.0 cm-1 handelt. Die Barrieren werden von theoretischen Berechnungen gestützt, die eine ähnlich hohe Relaxationsbarriere voraussagen (Ucalc = 43.5 cm-1), sodass auf dieser Basis effiziente SMMs entwickelt und synthetisiert werden können. Der dritte Teil dieser Arbeit beschäftigt sich mit der Frage nach MnII-selektiven Liganden. Hierbei sollte die in der Irving-Williams-Reihe verankerte Labilität von MnII-Komplexen gegenüber den späteren Übergangsmetallen überwunden werden. Um dies zu bewerkstelligen, wurde der Ligand L4 entwickelt, welcher zur höchsten bisher bekannten MnII Stabilität führt (log K(MnL4) = 22.23), die zudem die des ZnII-Komplexes übersteigt (log K(ZnL4) = 14.30) und somit die Irving-Williams Reihe invertiert. Aufgrund der in der Kristallstuktur gefundenen Koordination eines zusätzlichen Anions, welches in wässriger Lösung mit Wasser austauscht, erweist sich der MnL4-Komplex als ein idealer Kandidat für ein GdIII-freies Kontrastmittel und besitzt trotz einer relativ langsamen Wasseraustauschgeschwindigkeit (kex = 1.2x10^8 s-1) eine für mononukleare MnII-Komplexe unerreicht hohe Relaxationsrate (r1 = 5.04 L/mmol s ). Zusätzlich ergibt sich eine kinetische Stabilität gegenüber Überschüssen an ZnII und CuII. Trotz der vielversprechenden chemischen Eigenschaften wurde in ersten in vivo Studien eine erhöhte Toxizität des MnL4-Komplexes festgestellt, weshalb das Acetyl-Derivat L5 synthetisiert wurde. Seine Ähnlichkeit zum Liganden L4 spiegelt sich vor allem in der berechneten Kavitätsgröße und den erhaltenen Festphasenstrukturen wider. Um die Koordinationssphäre zu sättigen, um damit die Stabilitätskonstante noch weiter zu erhöhen und weitere Anwendungsbereiche von MnII-Komplexen zu erschließen, wurde ein octadentater Ligand L6 synthetisiert. Im Vergleich der Metallkomplexe zeigen sich dabei starke Unterschiede in den Redoxpotentialen, welche eine stark erhöhte Stabilität des MnL6-Komplexes voraussagen. Diese Arbeit zeigt, dass Bispidine ein ideales Werkzeug für die Komplexbildung von Metallionen sind. Die Modularität erlaubt es dabei das Bispidin-Gerüst auf das jeweilige Anwendungsgebiet Maßgenau zuzuschneiden.
This thesis outlines the three-step transformation of imine cages into hydrocarbon cages utilising the Overberger-Lombardino-reaction as the fundamental step, opening a new synthetic pathway towards hydrocarbon cages. This method makes use of the advantages of dynamic covalent chemistry (DCC) like high yields and easy access of imine cages to form the hydrocarbon cage in overall yields up to 24%. The core building block 1,3,5-tri(methylamine)benzene was condensed with derivatives of isopthaldehyde and terephtaldehyde to give a range of [2+3]- and [4+6]-imine cages. After reduction and nitrosylation the Overberger-Lombardino-reaction followed from which the hydrocarbon cages were obtained. By comparison of the hydrocarbon cage yield it is possible to estimate the influence of steric or electronic effects of functional groups from which both the steric and elektronic effect have an influence on the imine cage transformation. Sterically demanding groups lower the yield of the hydrocarbon cage the closer they are set to the reaction site. The highest yields were obtained when the functional groups were pointing inside the cage cavity. An incompletely converted hydrocarbon cage, with one or two N-nitroso groups remaining, was isolated as a side product when no functional group was located in the cage cavity. The electronic properties of the functional groups had no effect on the formation of these side products. From crystal structure analysis and 2D-NMR spectra the orientation of the N-nitroso group could be determined showing the N-nitroso group to be pointing away from the cage center.
Neutrale Silizium(IV)- und monoanionische Aluminium(III)-Verbindungen weisen naturgemäß tetraedrisch umgebene Si- bzw. Al-Atome auf. Das macht sie zu Verbindungen, deren Eigenschaften durch hohe Stabilität und oftmals geringe Reaktivität charakterisiert sind. Einer Verzerrung der Strukturumgebung hin zu ihren planaren Analoga wurde schon vor 40 Jahren von VON SCHLEYER ein stark verändertes Reaktionsverhalten vorausgesagt. Doch blieben die Stabilisierung und Isolation dieser Spezies bis heute unerreicht. Die theoretischen Vorhersagen über eine durch die Planarisierung gesteigerte Lewis-Azidität und eine geringere HOMO-LUMO Lücke konnten daher experimentell nie bestätigt werden.
Die vorliegende Dissertation beschreibt die erstmalige Synthese, Charakterisierung und das Reaktivitätsverhalten von planaren Silizium(IV)- und planaren, anionischen Aluminium(III)-Spezies. Unter Einsatz verschiedener Calix[4]pyrrolato-Liganden konnte die Planarisierung ermöglicht, die freien Formen der Verbindungen isoliert, vollständig charakterisiert und deren Reaktivität gegenüber Substraten studiert werden.
So verifizierte das planare Aluminat durch Bildung der dianionischen Hydrid-, Fluorid- und Chlorid-Addukte, entgegen der Ladungsdiskriminierung, die gesteigerte Lewis-Azidität. Weiterhin wurde eine Aktivierung von Carbonylgruppen (z.B. CO2, Aldehyde, Ketone) oder Nitrogruppen durch ein Element-Ligand-kooperatives Verhalten beobachtet. Der Modus der Aktivierung konnte sowohl thermisch als auch chemisch gesteuert werden. Dieser molekulare Schaltmechanismus ermöglichte Steuerung der Geschwindigkeit von durch das planare Aluminat katalysierten Hydroborierungsreaktionen.
Die stark erhöhte Lewis-Azidität des planaren Silans äußerte sich unter anderem in der Wasserstabilität seines Hydrid-Addukts und der Ausbildung von agostischen Wechselwirkungen – noch nie detektiert für leichte p-Block Elemente in ihren natürlichen Valenzzuständen. Die geringe HOMO-LUMO Lücke führte zur Lichtabsorption im sichtbaren Bereich durch einen Ligand-Element-Charge-Transfer Übergang. Zudem konnte die bereits im Aluminat beobachtete, durch Element-Ligand-Kooperativität vermittelte Aktivierung von Bindungen auf unpolarisierte Substrate wie Alkine und auch auf Nitrile ausgedehnt werden.
Diese Arbeit legt die Grundsteine zur Darstellung und zum tieferen Verständnis von neuen „anti-Van’t Hoff-Le Bel“ Verbindungen und zeigt Anwendungen in Bindungsaktivierungen, der Katalyse und für Materialien auf.
The extraordinary mechanical and charge transport properties of semiconducting single-walled carbon nanotubes (SWNTs) make them a promising material for solution-processable, flexible and stretchable electronics. Many of these remarkable features are even obtained in randomly-oriented SWNT networks that are compatible with established large-scale thin-film processes based on printing techniques or optical lithography. Given the enormous progress in the purification of solely semiconducting nanotubes as well as in the preparation of SWNT networks with a uniform and defined morphology in recent years, their widespread application as active layers in field-effect transistors (FETs) has become feasible. Likewise, this progress raised subsequent questions of what key parameters determine the charge transport processes across these networks and how they can further be optimized.
This thesis investigates charge transport and its limitations in polymer-sorted semiconducting SWNT networks with a focus on the precise nanotube network composition. The employed FET geometry enabled a reproducible and undistorted analysis of composition- and temperature- dependent transport parameters such as the charge carrier mobility. A comparison between nanotube networks with various selected or even precisely defined SWNT species distributions and average tube diameters reveals that additional energy barriers created at the junctions of adjacent nanotubes with different diameters result in inferior transport properties. While the network charge transport was formerly considered to be solely limited by the charge transfer across these inter-nanotube junctions, the results of this work imply that also the transport within each individual SWNT is important. The specific diameter dependence of this intra-nanotube transport can rationalize the substantially higher carrier mobilities observed for large-diameter networks with a certain SWNT bandgap distribution compared to monochiral networks that contain only a single small-diameter nanotube species. These findings suggest that composition optimizations for SWNT network FETs with maximum carrier mobilities should aim at monochiral large-diameter nanotubes.
Aside from insights into the underlying transport mechanisms, this work demonstrates a novel approach to intentionally modify charge transport in semiconducting SWNT network FETs by adding photochromic spiropyran compounds to the dielectric layer. The strong impact of the spiropyran and its photoinduced isomerization to merocyanine on the charge carrier mobilities give these transistors the properties of basic optical memory devices. Upon UV illumination the carrier mobilities are severely reduced until their recovery is induced by annealing or illumination with visible light. This implemented light responsiveness illustrates the fundamental suitability of SWNT network FETs for multifunctional applications beyond integrated circuits.
Die Tröpfchen-basierte Mikrofluidik kombiniert wissenschaftliche Prinzipen mit technologischen Ansätzen und ermöglicht ihrem Nutzer die präzise Verarbeitung und Manipulation von Wasser-in-Öl Tröpfchen. Dabei repräsentiert jedes Tröpfchen einen in sich geschlossenen Mikroreaktor, der zur Beobachtung interner chemischer und biologischer Reaktionen geeignet ist. Des Weiteren erfordert die Technologie nur minimalen Eingriff des Nutzers, ist sparsam im Probenverbrauch und ermöglicht hohe Analysegeschwindigkeiten bei erhöhter Präzision. Diese Vorteile verdeutlichen das enorme Potential dieser Technologie für die Miniaturisierung und Automatisierung biomedizinischer Tests. Trotz der in den letzten Jahren erzielten Fortschritte befindet sich die Tröpfchen-basierte Mikrofluidik immer noch im Entwicklungsstadium. Ziel meiner interdisziplinären Doktorarbeit ist es, die Tröpfchen-basierte Mikrofluidik für automatisierte Anwendungen in der biophysikalischen und biochemischen Grundlagenforschung weiterzuentwickeln. Zu diesem Zweck habe ich während meiner Promotion mehrere Chip-basierte Tröpfchenmanipulationseinheiten entwickelt und optimiert. Insbesondere wandte ich grundlegende physikalische und chemische Prinzipien an, um ihre Leistung zu verbessern. Unter anderem führten meine Entwicklungen zu einer Erhöhung der Tröpfchen-Produktionsrate, indem ich die Geometrie der Tröpfchenmanipulationseinheit modifizierte. Darüber hinaus habe ich die mikrofluidische Tröpfcheninjektionseinheit optimiert, die für die nachträgliche Manipulation des Tröpfcheninhhalts eingesetzt wird. Ich entwickelte ein neuartiges Design zur Destabilisierung der schützenden Tensidschicht ohne Notwendigkeit eines elektrischen Feldes. Die Injektion wird infolge einer schnellen Verformung des Tröpfchens und der damit verbundenen Bildung von Poren in der Tensidschicht ermöglicht. Hervorzuheben ist die Entwicklung einer Einheit zur kontrollierten Freisetzung des Tröpfcheninhalts. Durch das Anlegen eines elektrischen Feldes war es mir möglich, eingekapselte Suspensionszellen in eine kontinuierliche wässrige Phase freizusetzen und somit den Inhalt von der umgebenden Ölschicht zu trennen. Eine Kombination der entwickelten Einheit mit programmierbarer DNA-Funktionalisierung der inneren Tröpfchenfläche ermöglichte die kontrollierbare Filtration des Tröpfcheninhaltes durch kontrollierte Freisetzung der eingekapselten Materialien. Ein weiterer Fokus meiner Arbeit lag in der Entwicklung optischer Verfahren zur Echtzeitüberwachung der Wasser-in-Öl Tröpfchen. Zusammen mit Kollegen habe ich zwei entsprechende Techniken entwickelt. Eine dieser Techniken nutzt eine veränderte Auslesemethode der Fluoreszenzkorrelationsspektroskopie (FCS). Durch Neuinterpretation der Autokorrelationskurve können Aussagen über die Tröpfchenflussrate, deren Homogenität und sogar über den Tröpfcheninhalt getroffen werden. Im zweiten Ansatz wurde eine empfindliche optische Vorrichtung zur markierungsfreien Beobachtung, Charakterisierung und aktiven Manipulation vorbeifließender Tröpfchen entwickelt. Die fortschrittlichen Eigenschaften des entwickelten optischen Geräts wurden durch Messung verschiedener Tröpfchen-Produktionsparameter sowie durch den markierungsfreien Nachweis von eingekapselten Zellen bewiesen. Zusätzlich kann anhand gemessener Parameter eine aktive Manipulation der Tröpfchen durch die Vorrichtung ausgelöst werden. Dies wurde anhand einer markierungsfreien Tröpfchensortierung verdeutlicht. Zusammenfassend konnte ich die Leistung einzelner mikrofluidischer Einheiten verbessern und Anwendungsbereiche aufzeigen. Darüber hinaus verfügt das entwickelte optische Gerät über das Potential zur aktiven Überwachung und Steuerung zusammengeschalteter funktioneller Einheiten, wodurch eine gesamte Prozesskette auf einem einzigen mikrofluidischen Chip durchgeführt werden kann.
Biological cells sense not only biochemical cues but also physical cues from the surrounding microenvironment, and adapt their function and fate. Ample evidence suggests that changes in physical microenvironments of cells play critical roles in development, aging and diseases. However, the understanding of the dynamic response of cells to abrupt changes in physical microenvironments is still incomplete due to a lack of substrates that can provide well defined physical commands. The main thrust of this thesis is the design of two new types of substrates, which dynamically change elasticity or topography in order to unravel dynamic cellular response far out of equilibrium. Chapter 4 presents the design of substrates with periodic wrinkles of adjustable wavelength for the switching of morphology and orientational order of mouse myoblasts. The substrates used in this study were fabricated by the deposition of hard polyimide on soft polydimethylsiloxane under axial strain. In stark contrast to commonly used approaches in topographic control of cells under static conditions (static contact guidance), the wrinkled substrates designed in this study are able to reversibly switch the wrinkle direction by 90° within 60 s simply by axial compression and relaxation. Dynamic contact guidance introduced in this study unraveled the kinetics of shape adaptation and orientational orders of cells as well as the existence of a critical wavelength for rearrangement of the focal adhesions and remodeling of cytoskeletons in response to the abrupt change in wrinkle direction. Chapter 5 deals with the establishment of hydrogel substrates that can reversibly change the bulk elastic modulus for regulation of the morphology, active force generation and the fate decision of human mesenchymal stem cells derived from the bone marrow. The uniqueness of this study is to use hydrogels with reversible host-guest interactions, whose elasticity can be adjusted by the concentration of free host or guest molecules. In contrast to commonly used, chemically crosslinked hydrogel substrates with fixed elastic moduli, this enables to fine-adjust the substrate elasticity as well as to abruptly switch the substrate elasticity at any given time point. The mechanical strength of cell adhesion determined from a self-developed, high-throughput assay utilizing shock waves as well as the total energy dissipation by cellular traction forces indicated the presence of a critical substrate elasticity which triggers the mechanosensory system. Remarkably, an abrupt softening of substrate stiffness across this threshold instantaneously led to a decreasing total strain energy. Furthermore, frequent exchange of the substrate elasticity resulted in decreased proliferation without interfering with the multipotency of stem cells. The dynamic cellular microenvironments established in this study open the new possibility to gain insight into the physical mechanism underpinning the plasticity of life, such as development, aging, and diseases.
Guanidino-funktionalisierte Aromaten (GFA) sind starke Elektronendonoren und besitzen eine hohe Lewis- und Brønsted-Basizität. Sie sind daher als Reagenzien für Protonengekoppelte Elektronentransfer-Reaktionen (PCET-Reaktionen) sowie als redoxaktive Liganden geeignet. Diese Dissertation beschreibt die erstmalige Substitution der aromatischen Protonen eines Tetrakisguanidino-GFA mittels einer C−C-Bindungsknüpfung. Durch Einführung von zwei paraständigen Ethinylgruppen zusätzlich zu vier elektronenschiebenden Guanidinogruppen an den aromatischen Benzolring entsteht ein Ligandensystem mit redoxabhängiger Fluoreszenz. Während die reduzierten Spezies in allen Protonierungsstufen fluoreszieren, führt die zweifache Oxidation des GFA zur Dearomatisierung und einer vollständigen Fluoreszenzlöschung des Systems. Die redoxabhängige Fluoreszenz bildet zusammen mit der Brønsted-Basizität die Grundlage für den Einsatz der vierfach guanidino-funktionalisierten Diethinylbenzole als Fluoreszenzsonden in PCET Reaktionen. Ausgehend von der zweifach oxidierten, fluoreszenzgelöschten Spezies können verschiedene organische Substrate oxidiert werden. Hierbei werden zwei Elektronen und zwei Protonen vom Substrat auf den GFA übertragen, der in die fluoreszenzaktive, reduzierte und zweifach protonierte Form überführt wird. Der Reaktionsfortschritt wird durch die Änderung des Fluoreszenzsignals verfolgt und auf diese Weise kinetische Daten über PCET-Reaktionen erhalten. Durch Verwendung hoher Substratüberschüsse und Anwendung der Isoliermethode werden Rückschlüsse auf die Reaktionsordnung der PCET-Reaktionen gewonnen. Für die betrachteten Reaktionen sprechen die experimentellen Daten für einen konzertierten PCET-Mechanismus. Das entwickelte System ist eines der wenigen Beispiele für den Einsatz einer Fluoreszenzsonde mit redoxabhängiger Fluoreszenz in PCET-Reaktionen. Die vierfach guanidino-funktionalisierten Diethinylbenzole sind zudem in der Lage zweikernige Koordinationsverbindungen mit verschiedenen Cu(I)- und Cu(II)-Salzen zu bilden. Die Komplexierung führt zu einer vollständigen Fluoreszenzlöschung des Systems, was im Einklang mit früheren Ergebnissen mit fluoreszierenden Guanidinliganden steht. In den synthetisierten Komplexen liegt der GFA stets in seiner reduzierten Form vor, da eine Oxidation des Liganden, im Gegensatz zu anderen redoxaktiven GFA, zur Dekomplexierung führt. Die Liganden mit terminalen Alkingruppen bieten zudem die Möglichkeit weiterer Funktionalisierung, durch die sich das GFA-Konzept erweitern lässt. Neben der Möglichkeit von C−C-Kupplungen an den terminalen Alkinen, wofür erste experimentelle Ergebnisse vorgestellt werden, ergibt die Umsetzung mit Lewis-Säuren Moleküle mit ungewöhnlichen Eigenschaften. Die Reaktion mit sterisch anspruchsvollen Lewis-Säuren wie Tris(pentafluorophenyl)boran (BCF) führen zur Bildung zwitterionischer Addukte, bei denen die Lewis-Säure an die terminalen Alkine bindet und die AlkinProtonen auf die basischen Guanidinogruppen übertragen werden. Dies ist ein Spezialfall der Aktivierung eines terminalen Alkins durch ein frustriertes Lewis-Paar, bei dem Alkin und Base im selben Molekül vorliegen. Durch Addition der Lewis-Säuren können die optischen Eigenschaften wie Absorptions- und Emissionsbanden dieser GFA gesteuert werden. Für das Addukt des Tetrakisguanidino-funktionalisierten Diethinylbenzol mit BCF wurde zudem ein deutlicher Anstieg der Elektronendonorstärke erhalten. Die Lewis-Säure Addukte liegen in reduzierter und zweifach protonierter Form neutral vor statt, wie bei GFA üblich, zweifach positiv geladen. Dies resultiert in dem niedrigsten Redoxpotential aller bisher bekannten Tetrakisguanidino-funktionalisierten Aromaten.
Zur Reduktion der Langzeitradiotoxizität und der Wärmeleistung von abgebrannten Kernbrennstoffen wird in einigen Ländern ein Recycling der Actiniden angestrebt. Zur selektiven Abtrennung der Actiniden aus abgebrannten Kernbrennstoffen werden verschiedene flüssig-flüssig- Extraktionsprozesse entwickelt. Durch den EURO-GANEX-Prozess werden nach erfolgter Uranabtrennung die Transuranelemente (TRU) Np, Pu, Am, Cm zusammen von den Lanthaniden (Ln(III)) und den Spaltprodukten abgetrennt. Dies wird durch eine Koextraktion der TRU und Ln(III) mit dem Extraktionsmittel TODGA und einem Modifier gelöst in Kerosin ermöglicht. Der Modifier gewährleistet eine hohe Plutoniumsbeladungskapazität der organischen Phase. Anschließend werden die TRU selektiv mit eine Mischung der Komplexierungsmittel Acetohydroxamsäure (AHA) und dem schwefelhaltigen Bistriazinylpyridin SO3-Ph-BTP in die wässrige Phase rückextrahiert. Ziel dieser Doktorarbeit ist es, die wässrige und organische Phase des EURO-GANEX-Prozesses zu optimieren. Der erste Teil dieser Arbeit befasst sich mit der wässrigen Phase. Ziel ist es, ein schwefelfreies Komplexierungsmittel zu finden, das vergleichbare Komplexierungs- und Extraktionseigenschaften wie SO3-Ph-BTP aufweist. Als mögliche Alternative wurde PTD-OMe untersucht. Mittels zeitaufgelöster Laserfluoreszenzspektroskopie (TRLFS) wird die Speziation von Cm(III) mit PTD-OMe in ein- und zweiphasigen Systemen bestimmt. PTD-OMe zeichnet sich dabei durch sehr gute Komplexierungseigenschaften aus. Aufgrund des erhöhten pKs-Werts von 2.54 ist die Selektivität für An(III) unter Extraktionsbedingungen jedoch geringer. Der zweite Teil der Arbeit beschäftigt sich mit der Optimierung der organischen Phase. Die organische Phase soll dabei nur aus einem Extraktionsmittel in einem Verdünnungsmittel bestehen und trotzdem eine hohe Plutoniumbeladungskapazität aufweisen. Zwei Systeme werden untersucht. Das Extraktionsmittel TODGA in aromatischen Verdünnungsmitteln: Es werden grundlegende Verteilungsverhältnisse bestimmt und die Speziation unter Extraktionsbedingungen – auch bei hohen Beladungen der organischen Phase mit Ln(III) und Sr(II) – ermittelt. Das Extraktionsmittel mTDDGA in Kerosin: mTDDGA existiert in zwei diastereomeren Formen. Mittels TRLFS wird die Speziation von Cm(III) und Eu(III) mit beiden Diastereomeren bestimmt. Zusätzlich kann eine ternären M-L-NO3-Spezies unter Extraktionsbedingungen durch eine Kombination aus TRLFS, vibronischer Seitenbandenspektroskopie (VSBS) und DFT-Rechnungen nachgewiesen und deren Stöchiometrie bestimmt werden. Im Hinblick auf eine Anwendung der beiden Systeme im EURO-GANEX-Prozess, wird deren Pu(IV)-Beladungskapazität bestimmt. Das cis-mTDDGA/Exxsol D80-System kann mit mehr als 48 g/L Pu(IV) beladen werden, wodurch es sich als eine sehr gute Optimierung für den EURO-GANEX-Prozess auszeichnet.
In recent years, hydrogels developed to promising tools for biomedical and industrial applications. For biomedical approaches hydrogels, possess the capacity to immobilize and release cells, they offer the desired 3D environment to induce cell specific behaviour or serves as a drug delivery system. Moreover, they can be used for tissue engineering approaches by mimicking the ECM. In this thesis, a novel hybrid double cross-linked hydrogel is presented and designed based on the bottom-up approach of synthetic biology. It consists of simultaneously formed chemical and physical cross-links and made out of two components: (1) thiol functionalized HA (74 kDa) (HA-DTPH) and (2) ionic crosslinker (Cl+). HA-DTPH provides the chemical cross-link by forming disulphide bonds and the ionic cross-linker forms physical cross-links, such as hydrogen bonds and salt bridges. Three different ionic cross-linker were used: (1) deacetylated disaccharide unit of HA (dHA+) (2) charged glucosamine (GluA+) and (3) ammonium chloride (NH4+). These ionic cross-linker were chosen due to their biocompatibility and ability to form physical cross-links, such as hydrogen bonds and salt bridges. The increasing capacity to form hydrogen bonds from NH4+ to dHA+ enabled us to study the influence of the physical cross-link on the hydrogel properties. I could show that the disulphide bond formation was enhanced, by adding an ionic cross-linker and led to the formation of stable hydrogels. Under the same reaction conditions, HA-DTPH without an ionic cross-linker, needed further oxidation with hydrogen peroxide to result in a stable hydrogel (HA-DTPH-Ox.). By varying the degree of thiolation on HA and additionally by varying the type and concentrations of the used ionic cross-linker, the mechanical stiffness, swelling properties and response to external stimuli were tuneable. Varying the degree of modification and used ionic cross-linker enables a specific adjustment of the hydrogels specifically the hydrogel suitable for cell studies with mechanical range of 0.1 Pa to 8 kPa. Furthermore, swelling ratios of HA-DTPH-Cl+ hydrogels are highly influenced by the ionic strength and pH. Remarkably HA- DTPH- dHA+ hydrogels upon incubation in a solution of pH 7 showed a feedback loop swelling behaviour. At the swollen state of the hydrogel, the ionic cross-linker dHA+, leaked out of the hydrogel network, acidified the solution, which resulted in shrinking of the hydrogel. Biological properties like enzymatic degradability showed that the half-live of HA-DTPH-Cl+ hydrogels are increasing with increasing capacity of the ionic cross-linker to form hydrogen bonds. Moreover, due to the absence of any toxic agent during the hydrogel formation the hydrogel system was used for live cell applications such as cell encapsulation or cell adhesion studies. To conclude, a hybrid double cross-linked hydrogel system could be presented, mimicking the ECM, in a minimal model and a critical influence of physical cross-links is observed from results obtained by characterizing the physical and biochemical properties by investigating the gels’ swelling capability, response to environmental changes and sensitivity to hyaluronidases. Depending on the desired biomedical application, these hydrogel systems can be tuned in regards to their stiffness, swelling behavior and degradability enabling applications in 3D tissue engineering, drug delivery and regenerative medicine.
Diese Arbeit thematisiert die Darstellung und Charakterisierung von Verbindun¬gen, die unter Nutzung des zentralen, starren, D3h-symmetrischen Triptycen-Strukturmotivs in peripher ausge¬dehnten diskre¬ten Molekülen mit intrinsischer Mikroporosität und in porösen Salphen-Netzwerkmaterialien realisiert wurden. Nach sechsfacher Bromierung von Triptycen an dessen 2,3,6,7,12,13-Positionen und C-C-Kreuzkupplungsreaktionen konnten verschiedene Hexaaryltriptycene mit ortho Terphenyl-Substrukturen generiert werden, welche durch Cyclodehydrierungsreaktionen vom Scholl-Typ in hohen Ausbeuten und ohne aufwendige Reinigungsoperationen in ausgedehnte Triphenylen-basierte Triptycene (TBTs) überführt wurden; darunter auch ein intrinsisch mikroporöses Supertriptycenkongener, welches eine spezifische Oberfläche von SABET = 730 m2g-1 zeigte. Zum genaueren Verständnis dieser Reaktion wurden zudem weitere Cyclodehydrierungs-Studien an einfachen ortho-Terphenyl-Derivaten mit variierenden elektronischen Eigenschaften durchgeführt. Ebenfalls unter Verwendung der initialen C-C-Kreuzkupplungsreaktion konnte ein sechsfacher Salicylaldehyd als flexibler Baustein für iminbasierte Salphenmaterialien erhalten werden. In diesem Kontext konnten Reihen isostruktureller Metallsalphenkomplexe sowie Metall-assistierter Salphen-organischer Netzwerke (kurz: MaSOFs; mit M = Zn, Ni, Cu, Pd und Pt) synthetisiert und miteinander verglichen werden. Spezifische Oberflächen von bis zu SABET = 1323 m2g 1, Kapazitäten von 18.6 Gew. % für CO2 und 2.19 Gew. % für CH4 bei 273 K und IAST-Selektivitätswerte von bis zu 〖"S " 〗_(〖"CO" 〗_"2" "/" "N" _"2" )^"IAST" = 56 und 〖"S " 〗_(〖"CO" 〗_"2" "/" 〖"CH" 〗_"4" )^"IAST" = 10 demonstrieren das große Potenzial der MaSOF-Netzwerke. Durch Kombination der Erkenntnisse aus den beiden Themengebieten konnte in einer neun¬stufigen Synthese¬ ein rigider TBT-Salicylaldehyd-Baustein in 13%-iger Gesamtausbeute realisiert werden. Ein daraus resultierender mikroporöser Nickel-Salphenkomplex sowie das korrespondie¬ren¬de Nickel-Salphenpolymer zeigten spezifische Oberflächen, die mit SABET = 473 m2g 1 bzw. 610 m2g 1 quantifiziert werden konnten.
This thesis deals with the synthesis and investigation of larger polycyclic aromatic hydrocarbons (PAHs) obtained via π-extension of 2,10-di-tert-butyldibenzoperylene. Four types of π-extensions based on dibenzoperylene were achieved: 1. Bay region extension (Chapter 3.1): Nine cata-condensed (hetero)annulated coronenes were synthesized by a three-step approach via selective bromination of diarenoperylenes as the key-step. The influence of introducing different heteroatoms (nitrogen and sulfur) on the molecular structures as well as the photophysical and electrochemical properties were investigated. 2. L-region extension (Chapter 3.2.2): Two-fold cyclopentannulation at the L-regions and regioselective triflyloxylations have been achieved in a single step based on a dibenzoperylene. Larger contorted PAHs were obtained based on the bistriflate. The structures of the obtained contorted PAHs were studied by NMR techniques and single crystal X-ray diffraction analyses. 3. Extension at both bay and L-regions (Chapter 3.2.3): Contorted PAHs with two embedded azulene units were synthesized. The influences of the curvature on the aromaticity and the conjugation were investigated by theoretical calculations. 4. Linear extension (Chapter 3.3): Triptycene end-capped perylene oligomers with up to thirteen linearly fused benzene rings were obtained. The influence of the conjugation length on the molecular photophysical properties were studied. Regioselective brominations were achieved on these perylene oligomers and one PAH molecule with two coronene units was obtained.
Infektionen mit dem Hepatitis-B-Virus (HBV) und dem Hepatitis-D-Virus (HDV) stellen eines der größten Gesundheitsrisiken weltweit dar. Als Virusoid produziert HDV keine eigenen Hüllproteine, sondern ist auf HBV als Helfervirus angewiesen. Eine HBV/HDV-Ko-infektion gilt als schwerste Form der Hepatitis und bislang stehen nur stark limitierte Therapieoptionen zur Verfügung. Der first-in-class Eintrittsinhibitor Myrcludex B (Bulevirtide), ein synthetisches 47 Aminosäuren langes Lipo-peptid, das sich von der preS1 Domäne des großen HBV Oberflächenproteins L-HBsAg ableitet, stellt die erste zielgerichtete Therapie gegen eine HDV-Infektion dar. Es besetzt die Bindestelle der Virushülle am Eintrittsrezeptor sodium taurocholate co-transporting polypeptide (NTCP) und verhindert die Aufnahme des Viruspartikels in die Hepatozyte. Myrcludex B wurde in der Forschung vielseitig genutzt z.B. zur Identifizierung von NTCP als viraler Eintrittsrezeptor oder zum spezifischen Transport anderer Moleküle zur Leber. Vor allem die essentielle Sequenz, Aminosäuren 9-15, wurde intensiv untersucht. Da derzeit keine Kristallstruktur von NTCP bekannt ist, ist der exakte Bindemechanismus von Myrcludex B und der Viren schwer zu erfassen.
Ziel des ersten Teils dieser Arbeit war es, Sequenzbereiche innerhalb der akzessorische Domäne (Aminosäuren 22-48) von Myrcludex B zu identifizieren, die entscheidend zur Wirksamkeit beitragen und diese zu charakterisieren. Es wurden verschiedene Peptide mittels Festphasen-peptid¬synthese hergestellt, die durch Deletionen, Alanin-Austausch und Austausch der akzessorischen Domäne gegen wirtsfremde Peptid¬bereiche verändert wurden. Dabei konnte das PDWD-Motiv (Positionen 30-33) identifiziert werden, welches auch in den wirtsfremden Sequenzen vorzufinden war. In Bindungs¬versuchen mit fluoreszenzmarkierten Peptiden und in vitro HBV/HDV-Infektionen konnte gezeigt werden, dass eine intakte akzessorische Domäne für die spezifische Zellbindung sowie die hochpotente Inhibition des Viruseintritts nötig ist. Die Deletion der akzessorischen Domäne resultierte in einem ca. 100-fachen Wirkverlust, ein Alanin-Austausch von 32Trp und 33Asp führte zu einem ca. 20-fach erhöhten IC50-Wert. Die spezifische Leberanreicherung hängt hingegen von der essentiellen Sequenz des Peptids ab, was mittels 125Iod-markierten Peptiden im Mausmodell festgestellt werden konnte. Aufbauend auf diesen Ergebnissen wurde die Hypothese aufgestellt, dass das PDWD-Motiv als Gallensäure-Imitationssequenz mit der Substratbindetasche von NTCP interagiert.
Im zweiten Teil der Arbeit wurde die aufgestellte Hypothese untersucht, indem potentielle duale NTCP-Inhibi¬toren synthetisiert charakterisiert wurden. Dazu wurden Syn¬these¬strategien etabliert, um Arznei¬stoffe, die von NTCP transportiert werden, mit unterschiedlichen Peptiden zu konjugieren, welche keine akzessorische Domäne besitzen. In HBV/HDV-Infektionen in vitro waren deutliche Aktivitätsunterschiede der verschiedenen hybriden Moleküle zu beobachten; variierend einerseits nach Kopplungsposition, andererseits nach Kopplungspartner. Ebenso waren unter-schiedlich starke Einflüsse auf den physiologischen Gallensalztransport festzustellen. Die deutliche, synergistische Wirksteigerung der synthetisierten Substanzen stützt die aufgestellte Hypothese. Um die isolierte inhibitorische Effektivität der verwendeten Arzneistoffe in Infektionen unter-suchen zu können, wurde ein HDV-Infektionsmodell etabliert. Es war möglich, eine hochaktive Leitsubstanz „myr-2-21yK(TRIAC)“ zu synthetisieren und charakterisieren. Das Molekül zeigte keine Zytotoxizität, während im Vergleich zum Vorläufer¬peptid eine verbesserte Wirksamkeit in vitro und eine verlängerte leberspezifische Halbwertszeit in vivo erreicht wurde: myr-2-21yK(TRIAC) inhibierte HBV- bzw. HDV-Infektionen sechs¬fach bzw. 30-fach stärker und reicherte sich im Mausmodell spezifisch in der Leber und der Milz an. Die Leitsubstanz wird schneller von der Milz als von der Leber eliminiert und verbleibt mit einer Halbwertszeit von acht Stunden im Vergleich zum Edukt-Peptid doppelt so lang am Wirkort.
Es wurden dinukleare Kupfer(I)komplexe auf Thiazol-, Xanthin- und 1,2,3-Triazol-Basis synthetisiert und vollständig charakterisiert. Sie wurden auf ihre Eignung als Homogenkatalysatoren in Azid-Alkin-Cycloadditionen getestet und stellten sich als sehr aktiv heraus.
This thesis focuses on the synthesis and characterization of azaacenes and stable azaacene radical cations.
In Chapter 2, the synthesis, properties, and solid state X-ray single crystal structures of two new rubrene derivatives, viz diazarubrene DAR and tetraazarubrene TAR, are reported. Both the azarubrenes are more oxidatively stable than rubrene itself and show similar optical properties but differ in their crystal packing from that of rubrene.
In Chapter 3, the synthesis, property evaluation, and single crystal X-ray structures of 5,7,12,14-tetrafunctionalized diazapentacenes (TDAPs) are presented. Starting from tetrabromo-N,N’-dihydrodiazapentacene, Pd-catalyzed coupling gave the precursors that furnished, after further redox reactions, the diazapentacenes as stable crystalline materials. The performance of the tetraphenylated compound as n-channel semiconductor was evaluated in organic field-effect transistors. In Chapter 4, a series of quinoidal N,N’-diaryl-N,N’-dihydrodiazapentacenes (Quinos) were prepared in a two-step reaction, starting from quinacridone. Oxidation of Quinos furnished stable radical cations, isoelectronic to the radical anions of the azaacenes, whereas the dicationic species are isoelectronic to neutral azapentacenes. The spectroscopic properties of the diaryldiazapentacenes and their oxidized mono- and dications are equivalent to that of the dianion of tetraazapentacene TAP, its radical anion, and the neutral TAP.
In Chapter 5, three stable N,N’-diarylated dihydroazaacene radical cations (DDAs+·) were prepared by oxidation of neutral N,N’-diarylated dihydroazaacenes (DDAs), synthesized through Buchwald-Hartwig aminations of aryl iodides with N,N’-dihydroazaacenes employing a palladium catalyst. The spectroscopic properties, single crystal X-ray structures, and DFT calculations of these neutral compounds and their radical ions were systematically investigated. All the radical cations are stable and their absorption spectra in dichloromethane remained unchanged in ambient conditions for at least 24 hours.
In recent years, fullerenes, as rising stars in carbon clusters, have been widely applied in various fields of science and technology. The high electron affinity of fullerenes, due to unique geometric and electronic structures, leads to wide applications in many fields, e.g., organic solar cells, supercapacitors, catalyzers, and superconductive materials. Due to the difficulty to synthesize of carbon clusters and to determine their structures experimentally, researchers have paid much attention to the theoretical studies of their geometric and electronic structures. It is only recently that it became possible to apply state-of-the-art theoretical methods, e.g., equation of motion coupled cluster singles and doubles method for electron affinities (EA-EOM-CCSD) to these large molecular systems. With such high cost methods, the full picture of electronic states of the first known fullerene C60 has finally been revealed. Study of electronic structures of large molecular systems, such as fullerenes, has become a great challenge for modern theoretical and computational chemistry.
This thesis is devoted to the theoretical study of the electronic states of fullerene anions (e.g., C20–) and fullerene derivatives, utilizing accurate approaches. The latter includes endohedral fullerenes (e.g., Li@C20 and Li@C60) and carbon rings (e.g., C20).
To the best of our knowledge, our work is the first study on bound states of the C20– fullerene anion, employing accurate theoretical approaches. We find that the smallest fullerene anion C20–, can form one superatomic and a manifold of valence bound states. It indicates that possessing superatomic bound states is one of the common properties of fullerenes. We hope that this finding sheds light on the study of fullerenes applications in the future. Our theoretically estimated adiabatic electron affinity of the C20– fullerene, is consistent with the electron affinity obtained in the photoelectron experiment. It verifies the validity of the application of high accurate EA-EOM-CCSD method in studying electronic structures of fullerenes.
The endohedral fullerenes, e.g., Li@C20 and Li@C60, have attracted great attention due to their enhanced properties compared to the parent fullerenes. Our research on Li@C20 shows that the smallest fullerene, i.e., C20, can steal valence electron from the guest Li atom and form a charge separated donor-acceptor system. The Coulomb effect of Li+ is to stabilize the bound states, both valence and superatomic. Noteworthy, due to their different nature, the stabilizing effect on valence states is stronger than on superatomic states. The extra electron density distribution of superatomic states of the charge separated endohedral system is more compact compared to that of the parent fullerene, while the distribution of valence states does not exhibit this behavior.
Based on our calculations on Li@C60, we have found several excited states. Most of the electronic states are charge separated states, the appearance of Li+ stabilized the excited states of Li@C60 compared to those of the parent isolated anion without changing their characters, similarly to our finding for Li@C20. Importantly, for Li@C60 we reported a hitherto unknown non-charge-separated state, which we referred to as the caged-electron state. This state is neither a valence nor a superatomic state, since its extra charge density is mostly distributed at the center of the cage. We demonstrate that the caged-electron state is formed due to the large radius of the C60 cage, which reduces the Coulomb attraction effect between Li+ and the negative carbon cage of the endohedral fullerene. In much larger fullerenes, e.g., Li@C180, this state even becomes the ground state, due to the much weaker Coulomb attraction effect. It is a great example of the impact of the fullerene’s size on its electronic structures. Additionally, we have mentioned several possible applications of this new kind of state.
Last but not least, we turn to the carbon ring as the isomer of fullerenes. Carbon rings are intriguing and elegant species, but determining their geometry is an ongoing challenge. We have performed geometry optimization, vibrational frequency calculations and potential energy surface scans, based on EA-EOM-CCSD. Our work reveals that, similar to its fullerene isomer, the C20– ring can possess several bound states, including one superatomic state. Moreover, our calculation shows a symmetry breaking of the C20– ring anion structure occurring upon attaching an electron to the neutral ring. The discussion of the possible symmetry breaking mechanisms indicates that the shrinking and distortion of the ring upon electron attachment leading to the symmetry breaking, is a result of the interplay between the symmetry breaking and the totally symmetric modes. The discussion enriches the palette of possible symmetry breaking phenomena in carbon clusters.
Nicht-Häm-Eisenenzyme katalysieren eine Vielzahl verschiedener Reaktionen, unter anderem Hydroxylierungen, Halogenierungen und den Sauerstoffatomtransfer auf Heteroatome. Dies macht diese Enzymklasse interessant für biomimetische Ansätze. Die dabei entwickelten Modellkomplexe ermöglichen die einfache Untersuchung der aktiven Spezies und den Reaktionsmechanismen. Das Verständnis über die ablaufenden Prozesse ist essenziell um die Modelle später effizient nutzen zu können. Diese Arbeit befasst sich mit der Synthese von Bispidin-Liganden und spektroskopischer sowie voltammetrischer Untersuchung der daraus gebildeten Eisen(IV)-Oxido-Komplexe, welche als Modellkomplexe der Nicht-Häm-Eisenenzyme fungieren. Im ersten Teil der Arbeit wurde der oxidierte [Fe(N2py2)(Cl)2]-Komplex untersucht. Dabei wurde als erstes die Fähigkeit des Komplexes ein Sauerstoffatom auf Thioanisol zu übertra- gen betrachtet. Anschließend wurden mit HR-ESI-MS-Messungen die Zerfallsprodukte des Komplexes untersucht. Dabei zeigte sich, dass bei niedrigen Konzentrationen des Oxidationsmittels eine µ-Oxido-verbrückte dinukleare Spezies gebildet wird. Durch Erhöhung der Konzentration, wurde ein Zerfallsprodukt des Komplexes beobachtet, welches auf eine intramolekulare H-Atom-Abstraktion zurückgeführt werden konnte. Dies wurde durch den Verlust von Formaldehyd in Tandem-MS-Messungen bestätigt. Durch die beobachteten Zerfallswege wurde eine Eisen(IV)-Oxido-Spezies als aktive Spezies postuliert. Des Weiteren konnte durch Ligandenmodifikation des N2py2-Liganden gezeigt werden, dass die Oxido-Gruppe in diesem Komplex in der äquatorialen Ebene koordiniert und nicht axial. Ebenso konnten die beschriebenen Zerfallswege bei dem [Fe(IV)(O)(N2py2)(MeCN)]2+-Komplex beobachtet werden. Die zuvor erwähnte µ-Oxido-verbrückte dinukleare Spezies konnte nicht isoliert werden. Jedoch konnte durch die Verwendung eines dinuklearen Komplexes, bei welchem die Liganden- Einheiten mittels Ethylenbrücke verknüpft wurden, die Reaktivität hinsichtlich der Sulfoxidierung untersucht werden. Es wurde festgestellt, dass die Ausbeuten bei Verwendung des Komplexes in etwa gleich groß sind wie bei Verwendung des mononuklearen Komplexes. Der zweite Teil der Arbeit befasst sich mit der Synthese neuer Bispidin-Liganden. Dazu wurde je eine Amid-, Amin- bzw. Guanidino-Gruppe am N2py3u-Liganden eingeführt. Anschließend wurden sowohl die Eisen(II)- als auch die nach Oxidation erhaltenen Eisen(IV)-Oxido-Komplexe spektroskopisch untersucht. Des Weiteren sollten die Liganden bei der Bestimmung des absoluten Fe(IV)=O/Fe(III)-O-Redoxpotentials eingesetzt werden. Dieses konnte bis jetzt nicht bestimmt werden. Es wird vermutet, dass die entstehende Eisen(III)-Oxido-Spezies so basisch ist, dass diese sofort weiterreagiert. Durch Einführen der zuvor erwähnten Gruppen, sollte diese stabilisiert werden, um die Bestimmung des absoluten Fe(IV)=O/Fe(III)-O-Redoxpotentials zu ermöglichen. xi Im letzten Teil der Arbeit wurden die Komplexe hinsichtlich des Fe(IV)=O/Fe(III)-O-Potentials voltammetrisch untersucht. Dazu wurden zuerst die Redoxpotentiale durch Redoxtitrationen mit Ferrocen-Derivaten bestimmt. Die dafür erhaltenen Werte lagen zwischen 55mV und −45mV vs fc/fc+. Anschließende cyclovoltammetrische Untersuchungen des [Fe(IV)(O)(TMC)(MeCN)](pftb)- und [Fe(IV)(O)(N2py3u)(MeCN)](pftb)-Komplexes führten zu keinem reversiblen Signal, trotz Variation der Systemparameter. Durch Verwendung der zuvor synthetisierten Komplexe, mit Liganden die die Oxido-Gruppe stabilisieren, konnten für die Komplexe mit N2py3amin -Liganden und N2py3gua-Liganden quasi-reversible Signale bei −209mV und −408mV bestimmt werden, welche wahrscheinlich dem Fe(IV)=O/Fe(III)-O-Potential zuzuordnen sind. Die kathodisch verschobenen Werte wurden durch die Koordination eines formal zweifach negativ geladenen Sauerstoffliganden erklärt. Des Weiteren wurde die Diskrepanz zu den zuvor bestimmten Redoxpotentialen mittels Redoxtitration dadurch erklärt, dass bei den Titrationen nicht Fe(IV)=O/Fe(III)-O-Potentiale bestimmt wurden, sondern hier wahrscheinlich mehrere Prozesse ablaufen.
In dieser Dissertation wird der Einfluss elektronenreicher Guanidin-Liganden auf O‒O und B‒B Bindungsaktivierungsprozesse vorgestellt. Zu Beginn wurde die Aktivierung von molekularem Sauerstoff an Kupfer(I)-Komplexen mit den Liganden 2,6-Bis(tetramethylguanidino-methyl)pyridin (L1) und 2,6-Bis(tetramethyl-guanidino-methyl-ethyl)pyridin (L2) untersucht. Für den dinuklearen Komplex [(L1Cu)2]2+ wurde eine durch Sauerstoff initiierte aliphatische Ligandhydroxylierung beobachtet und mit der Reaktivität des Enzyms Peptidylglycin-α-hydroxylierende Monooxygenase (PHM) verglichen. Experimentelle und theoretische Untersuchungen an dem Modellkomplex lassen einen kooperativen Effekt zwischen den beiden Kupferatomen als Schlüsselschritt für den Hydroxylierungsprozess vermuten. In dem mononuklearen Komplex [L2Cu]+ wurden die zuvor hydroxylierten Stellen des Liganden L1 durch zusätzliche Methylgruppen blockiert. Die Oxygenierung führte dadurch zur Bildung eines Kupfer(II)-Superoxid-Komplexes, welcher mittels in situ UV/Vis- und Raman-Spektroskopie charakterisiert werden konnte. Weiterhin wurden Kupfer(I)-Komplexe mit dem Liganden 1,2-Bis(tetramethylguanidino)-benzol (L3) und dem redoxaktiven Liganden 1,2,4,5-Tetrakis(tetramethylguanidino)benzol (L4) für oxidative C‒C Homo- und Kreuzkupplungsreaktionen von Phenolen mit dem grünen Oxidationsmittel Sauerstoff eingesetzt. Komplexe mit dem elektronenreichen Liganden L4 zeigten hierbei eine signifikant höhere Aktivität und Chemoselektivität der Kreuzkupplungsreaktion. Auf der Grundlage von zahlreichen Testreaktionen wurde ein Reaktions¬mechanismus postuliert. Weiterhin wurden die Synthesen der neuen redoxaktiven Liganden Bis(diisopropylguanidino)dimethylbenzodioxol (L5) und 1,2-Bis(tetramethyl-guanidino)-4,5-bis(dimethylamino)benzol (L6) und ihrer entsprechenden Kupfer(I)-Komplexen entwickelt und erste Untersuchungen einer Sauerstoffaktivierung durchgeführt. Abschließend wurden die Liganden L3, L4 und L6 zur Aktivierung der B‒B Bindung in kationischen Diboranen eingesetzt. Mit den Bisguanidinen L3 und L6 gelang erstmals die Synthese von unsymmetrisch substituierten dikationischen Diboranen mit sp2-sp2-hybridi-sierten Boratomen. Die Verbindungen werden durch eine intramolekulare Umlagerung der initial gebildeten symmetrisch substituierten dikationischen Diborane erhalten. Diese beispiellose, nukleophil katalysierte Isomerisierung wurde im Detail untersucht. Aus der Temperaturabhängigkeit der Reaktionsgeschwindigkeit konnten die Aktivierungsparameter der Reaktion bestimmt werden. Die unterschiedliche Fluorid-Ionen-Affinität der beiden Boratome sowie die Bindungssituation dieser einzigartigen, unsymmetrischen dikationischen Diborane wurde mit Hilfe von computerchemischen Methoden untersucht.
Metal nanoparticles play a significant role in exhaust combustion. They oxidize harmful products like carbon monoxide and hydrocarbons in order to prevent major environmental and health issues. In a converter, platinum nanoparticles (Pt NPs) are impregnated in a thin coating of a porous ceramic oxide. Due to their high surface-to-volume ratio, Pt NPs can provide high catalytic activities; however, elevated temperatures in the exhaust gas flow lead to thermal deactivation of the catalyst via sintering, thereby resulting in large losses in efficiency over the catalyst’s lifetime. In this thesis, the sintering behavior of 5-6 nm sized Pt NPs synthesized via block copolymer micellar nanolithography on various planar oxide-based substrates is investigated. First, their coarsening on both crystalline and amorphous silica (SiO2) and alumina (Al2O3) is evaluated in regard to the mechanisms of Ostwald ripening and particle migration and coalescence. Sinter studies at 750°C in air reveal an enhanced thermal stability on the amorphous alumina-support Al2O3(a). Second, key influencing parameters on the sinter resistivity of the Pt NPs are identified. An increased NP adhesion on the amorphous substrates, a higher roughness and surface potential, as well as a larger contact angle of water on Al2O3(a) are all found to significantly contribute to enhanced sinter stability. Furthermore, the thermal behavior of Pt NPs on dual-structured surfaces is examined at the interface between Al2O3(a) and SiO2 to study the impact of compositional surface heterogeneities. The particles favor the high metal interaction Al2O3(a)-side over the low metal interaction SiO2- side as shown by their diffusion away from the silica. Additionally, structural heterogeneities on sapphire wafers with varying tilt angles, and thus step edges of different height and size, contribute to a smaller increase in Pt NP diameter over time on the more tilted substrates when exposed to 1200°C under vacuum compared to NPs on less tilted substrates. Hereby, larger sintered particles are observed to preferably align along the step edges. This is due to a locally increased surface potential at the edges and because these edges function as Ehrlich-Schwoebel barriers. Thereby they hinder the diffusion of particles on the substrate. Lastly, the sinter stability of Pt NPs is successfully enhanced via the deposition of an isolating silica or alumina layer by solgel techniques. These films are shown not to cover the Pt NPs and also prevent the migration of platinum clusters toward each other during sinter studies at 750°C under atmospheric conditions. Taken together, this data contributes to a better understanding of the thermal stability of Pt NPs catalysts with respect to the underlying support. The information gained from these sinter studies can be harnessed in the design of more thermally stable Pt NP catalysts, which can ultimately contribute to more environmentally sustainable technologies.
Metal microfibers have a wide range of industrial applications, e.g. as filters, fiber-reinforced composites, electrodes, catalysts, sensors, or magnetic shielding materials. In this project, we modified melt-spinning device and its experimental parameters to fabricate metal microfibers. It was shown for the first time that metal microfibers down to 5 μm could be fabricated using a melt spinning device. The size and circularity of formed fibers could be controlled by experimental parameters.e.g. slit distance to the wheel, chamber pressure, slit size, wheel speed. The mechanism of fiber formation relies on two main steps; i)thin film formation on the rotating wheel ii)spontaneous breaking of the film to smaller widths, dewetting the wheel. It was shown that this process is reproducible and could be used for different classes of materials. e.g. intermetallic alloys, conventional alloys, metal elements and amorphous alloys. The modification of the melt spinning device leads to higher quenching rates up to 108!C/s. The high quenching rate made it possible to make fully amorphous stainless steel fibers for the very first time. Heat-treatment of amorphous stainless steel leads to dual-phase microstructure (nanocrystals embedded together with a glassy phase) which was responsible for its ultra-high hardness value, 14GPa. This value is 7 times higher than the original stainless steel hardness. Thus, the technique opens new possibilities for working with conventional and amorphous alloys e.g. mechanically improved conventional alloy microfibers/ribbons, introducing new alloy microstructures.
The transport of charge and energy are two essential processes in optoelectronic devices. In this thesis, using quantum chemical methods, molecular properties, as well as charge and energy transfer performance are studied in novel N-heteropolycycles. N-heteropolycycles are formally N-doped heterocyclic nanographene segments. The position and number of the nitrogen substitution, as well as further modification, can fine-tune their molecular properties such as energy levels, diradical characters, and charge and energy transfer rates. For the investigation of energy transfer, particular interest lies in singlet fission (SF), which has the potential to dramatically increase solar cell efficiency by converting one singlet exciton to two free triplet excitons or a correlated triplet pair. In chapter 3, quantum chemical methods based on DFT and constrained DFT are applied to rationalize how SF is affected by systematic chemical modifications introduced into phenazinothiadiazoles (PTD). The results indicate that unlike unsubstituted tetracene, PTDs fulfill the energetic requirement of SF (E(S_1)≥2×E(T_1)), and the effective coupling can be up to 75.8 meV. Hence, PTDs are promising candidates for SF. In chapter 4, a single-reference DFT-based protocol is proposed to simulate the absorption spectra of excited states involved in SF. The resulting spectra show good agreement with the experiment. This could be helpful for the identification of various species in SF and the understanding of SF dynamics. On the other hand, N-heteroacenes are known as electron-poor counterparts of the acenes, and they are electron transport (n-type) materials. Since the charge transport moiety in bulk films of azaacenes is thought to be the radical anion, in chapter 5, the energetics, electronic structures, and spectroscopic properties of negatively charged N-heteroacenes are investigated. It is found that the anions of the azapentacenes and their derivatives are stable with respect to electron loss and disproportionation into the dianion and the neutral compound. This motivates a further look into their electron transport properties. The results of electron transfer integrals and charge mobilities are demonstrated in chapter 6. Excellent performance of electron transport has been proved for halogenated 6,13-Diethynyl-5,7,12,14-tetraazapentacenes, especially for the bromine and iodine derivatives.
In many parts of physics, chemistry, biology, or material science, excited electronic states, accessible via the interaction of atoms or molecules with electromagnetic radiation, play an essential role. Experimental spectra, however, generally provide only indirect information on molecular structure and dynamics. Thus, a theoretical description of excitation energies and transition strengths is crucial for a comprehensive understanding of light-induced processes. In this dissertation, the theory, implementation, and application of several Hermitian methods to calculate the properties mentioned above are described. If excitation energies are obtained by diagonalization of a non-Hermitian secular matrix, both left and right eigenvectors need to be calculated to obtain spectral intensities and other properties. In this case, the eigenvectors are not orthogonal to each other, and the energy may become complex. Hermiticity is thus a very desirable property since none of the aforementioned problems occurs. Thus, several approaches based on the algebraic-diagrammatic construction (ADC) scheme, as well as the related unitary coupled-cluster (UCC) method, are presented. Within these methods, one-electron properties such as dipole moments are available via the so-called intermediate state representation (ISR) approach, which corresponds to an expectation value of the respective one-electron operator with the wave function. The ISR formalism is also used to derive explicit working equations for the second-order ADC scheme, which is based on a ground state described by Møller–Plesset (MP) perturbation theory. This implies that ADC inherits all weaknesses from the underlying MP model. For the ADC(2) scheme, merely the first-order MP wave function is required, which contains only doubly-excited determinants for a Hartree–Fock reference. Due to the form of the first-order doubles amplitudes, several cancellations occur in the singles block of the ADC(2) matrix. In order to remedy the breakdown of MP2, the first-order doubles amplitudes from MP are replaced by the ones obtained from a coupled-cluster (CC) calculation, which are formally correct through infinite order. The resulting schemes, referred to as CC-ADC(2), are applied to several sets of small to medium-sized molecular systems, where generally minor improvements in excitation energies compared to the standard ADC(2) scheme can be observed. For the ozone molecule, which is known to be a difficult test case for quantum-chemical methods, the experimental first excitation energy is 1.6 eV; standard ADC(2) is far off with 2.14 eV, and CCD-ADC(2) yields 1.59 eV. Excited-state potential energy curves along the dissociation of the nitrogen molecule calculated with ADC(2) break down at around 2 Å due to the failure of MP2. The CCD-ADC(2) curves remain reasonable up to about 3.5 Å. The CC-ADC(2) methods are successively extended to the calculation of static dipole polarizabilities. It is shown that the correlation amplitudes play a more important role in the modified transition moments than in the ADC secular matrix itself, and consistent improvement is obtained for static polarizabilities with the CC-ADC schemes compared to standard ADC, particularly for aromatic systems like benzene or pyridine, which had proven difficult cases for standard ADC. Specifically, the CC-ADC(2) schemes yield significantly better results than the ADC(3/2) scheme, at a computational cost amounting to only 1% of the latter. The ISR derivation can also be carried out with a CC wave function correct through first order instead of the MP one. However, having converged CCD amplitudes instead of the first-order MP ones, the aforementioned cancellations in the second-order singles block do not occur. Hence, the final matrix elements differ between CCD-ADC(2) and this scheme referred to as CCD-ISR(2). As the expansion of the UCC similarity-transformed Hamiltonian does not truncate naturally, it needs to be truncated manually, usually by using arguments from MP perturbation theory. The UCC2 doubles amplitudes correspond to those from LCCD, but the secular matrix elements depend on the treatment of the similarity-transformed Hamiltonian is treated. By employing the Baker–Campbell–Hausdorff expansion, the second-order singles block is equivalent to CCD-ISR(2), but by employing the Bernoulli expansion, the matrix elements are equivalent to CCD-ADC(2), with differences only in the correlation amplitudes. In a strict perturbation-theoretical framework, all methods turn out to be identical. All different Hermitian second-order methods have been implemented and tested on a set of small molecules, where it turned out that the differences in excitation energies between the methods are small whenever the systems are well described by means of perturbation theory. The Bernoulli UCC scheme is further extended to third order, where excitation energies and oscillator strengths on medium-sized organic molecules as well as ground- and excited-state dipole moments are reported for the first time. While vertical excitation energies of the UCC3 scheme are similar to those obtained with ADC(3), significant improvements can be observed for the dipole moments in the ground and excited states. Furthermore, this UCC scheme is applied to the electron propagator, and ionization potentials of the IP-UCC2 and IP-UCC3 schemes of selected amino acids are reported for the first time. Apart from expectation values, molecular properties can be calculated as derivatives of the energy with respect to a perturbation connected to the observable. The two approaches are only equivalent if the Hellmann–Feynman theorem is fulfilled. By using explicit working equations, the relationship between the two approaches is investigated with a focus on orbital relaxation for all standard quantum-chemical methods, in particular MP and ADC. It is shown that for MP2 the expectation value is very close to the orbital-relaxed property. In contrast, for ADC(1) the expectation value includes no orbital relaxation and for ADC(2) only a small fraction. With ADC(3) eigenvectors, on the other hand, the ISR gets closer to the relaxed values, but only for singly-excited states. Numerical investigations underline all the theoretical predictions.
Interactions of atoms or molecules with electromagnetic radiation or free electrons can induce a variety of transformations. Apart from elastic scattering processes, in which the quantum states of the involved particles are preserved, inelastic scattering may occur. The distribution of product states depends on the kind of the interacting particles and the energy transferred in the scattering process.
Among the possible transformations are electronic excitation, photoionization and the formation of electronic resonances, i.e., metastable electronic states which undergo subse quent decay by emission of an electron. The latter states can evolve in electronic excitation processes or as a result of electron attachment. In this dissertation, the implementation and application of quantum chemical propagator methods for the description of the above-mentioned processes are presented.
More specifically, a number of perturbation theoretical methods based on the algebraic diagrammatic construction (ADC) schemes for the electron propagator and the polarization propagator are considered. In the framework of these methods, one-electron properties are available via the intermediate state representation (ISR) approach, which enables the computation of the explicit form of the respective wave functions. The third-order static self-energy Σ(3) appearing in the third-order ADC(3) equations can thereby be replaced by an improved fourth-order quantity resulting from the so-called Σ(4+)-procedure, and this option has been explored in the context of ADC for ionization potentials (IP-ADC), electron affinities (EA-ADC) and, for the first time, excitation energies (PP-ADC).
In the first part of this dissertation, photoionization processes are considered, whose theoretical treatment is possible using IP-ADC(3). In the course of this work, the existing implementation of IP-ADC(3) in the Q-Chem quantum chemical program package has been extended by the possibility to compute photoelectron intensities, and therefore, to simulate photoelectron spectra. Other newly implemented features enable the interpretation of ionization transitions by means of visualization of Dyson orbitals and one-particle density matrix-based quantities as, e.g., detachment and attachment densities, which are available via the second-order ISR(2) approach.
The accuracy of the IP-ADC(3)/ISR(2) methodology with respect to ionization potentials and one-particle properties of electron-detached states has been evaluated in a subsequent benchmark study. Therein, the results obtained for 44 electronic states of small molecules are compared to high-level configuration interaction results. For this set of transitions, ionization potentials exhibit a mean absolute error of |∆| ≈ 0.2 eV. For dipole moments, a relative error of |∆| = 19 % is found. In a second IP-ADC(3) study, the applicability of the newly implemented density matrix-based analyses for the interpretation of photoelectron spectra is demonstrated using the example of the galvinoxyl free radical.
In the second part of this dissertation, electronic resonances are addressed. Due to the unbound nature of the involved electronic states, their theoretical treatment is challenging. Different theoretical approaches for their description within the framework of standard quantum chemical methods have been devised, two of which are considered in this work.
First, the efficient implementation of the Fano-Stieltjes-ADC method in the Q-Chem program is presented. For the first time, the third-order PP-ADC(3) scheme as well as various unrestricted PP-ADC schemes have been combined with the Fano-Stieltjes formalism. The applicability of the implementation for the description of resonances in medium-sized organic molecules is demonstrated in a study of a Feshbach resonance in the naphthalene molecule.
As a second option for the theoretical treatment of electronic resonances, the combination of the subspace-projected complex absorbing potential (CAP) method with PP- ADC(3) and EA-ADC(3) is considered. Results obtained using the novel CAP-EA-ADC and CAP-PP-ADC methods as implemented in the Q-Chem quantum chemical program package show an excellent agreement with theoretical best estimates and experimental data in studies of π* shape resonances in unsaturated molecules. Among the studied resonance states are the ²Πg resonance of the dinitrogen anion as well as the lowest π* resonances of the anions of the non-conjugated organic dienes norbornadiene and 1,4-cyclohexadiene. CAP-EA-ADC(3) calculations are in line with previous findings and show that a strong through-bond interaction mechanism reverses the natural ordering of the π* molecular orbitals in 1,4-cyclohexadiene.
In this thesis, the dielectric behavior including dielectric constants and dielectric characteristics of poly-(p-phenyleneethynylene)s (PPEs) and their influence on organic electronic devices are investigated. In the first part, a method to create gels that compose of PPE and an ionic liquid was invented and named π-ion gels. π-ion gels exhibit a high dielectric constant so that excellent performances are displayed when π-ion gels are applied to the light-emitting electrochemical cells (LECs). The turn-on time, the brightness, the current density of LECs based on π-ion gels are improved by 10 times (0.7~2 s), four times, and 10 times (~20 A/cm2) in comparison to LECs fabricated by a drop- casting method, respectively. Furthermore, π-ion gels are applied to a new type of transistors, π- ion gel transistors (PIGTs). PIGTs display the on/off ratio of ~105, the hole carrier mobility of (0.4 cm2/V s), and the response time of ~20 μs, respectively. Especially, the response time of 20 μs is the fastest among electrochemical based transistors. In the second part, a novel concept for the control of dielectric properties was developed. dipolar units of o-difluorobenzene were incorporated in both poly-(p-phenyleneethynylene)s (PPEs) and liquid-crystalline oligo-(p-phenyleneethynylene)s (PEs). When o-difluorobenzene is introduced in PPEs, ferroelectric behavior is observed as the first example of ferroelectric conjugated polymer based on molecular rotations. Furthermore, a liquid-crystalline PE forms a dipole-aligned crystal via a dual control of the electric field and the temperature (called 2D control). In both cases, the compounds are applied to metal-insulator-metal (MIM) diodes, exhibiting anisotropic currents. Overall, the approaches to control dielectric constants and dielectric characteristics are beneficial for organic electronic devices. The concept is novel and feasible to apply to other materials.
Die vorliegende Dissertation befasst sich mit der experimentellen Untersuchung der elektronischen Struktur und der Reaktivität von Bispidin-Eisen(IV)oxido-Komplexen, welche als Modellkomplexe für Nichthäm-Eisen-Enzyme dienen.
After the discovery of the first exoplanet in 1990’s and a fast growing number of discoveries since then, there have been many attempts to observe and characterize their atmospheres. In particular, water and methane have been the focus of many investigations due to their relevance to the origin of life and habitability, as well as their major roles to shape the structure of planetary atmospheres. Abundances retrieved for these species can be also used as a tracer of carbon-to-oxygen ratio (C/O) and metallicity of these atmospheres; hence potentially linking the formation scenarios with the observations. Water’s spectral signature is everywhere, but despite many efforts, there has been only one robust detection of methane and only recently. The question is, “where is methane?”. By applying a hierarchical modelling approach (utilising more than 177,000 thermochemical equilibrium cloud-free, disequilibrium cloud-free, and thermochemical equilibrium cloudy models) we predict that there are four classes of irradiated gaseous planets; two of them (Class-I and Class-II; Teff<1650 K) likely to show signatures of CH4 in their transmission spectra, if cloudy-free and C/O above a certain threshold (aka the “Methane Valley”). The effect of disequilibrium processes on the classification found to be modest with a more continuous transition between Class-II and III planets. Clouds, however, heat-up the deeper parts of Class-I and Class-II planets; removing CH4 from the photosphere. Simultaneously, clouds obscure any molecular features; hence making the observation of methane even more challenging.
Boron(III) cations are widely used as highly Lewis acidic reagents in synthetic chemistry. By contrast, boron(II) cations are extraordinarily rare and their number is limited to only some few examples with an almost completely unknown reactivity. The compounds are both Lewis acids and electron donors, properties that ensure a rich and diverse chemistry. The use of bridging bicyclic guanidinate substituents in the diborane(4) compound allows the stabilization and investigation of these exceptional boron(II) species. This doctoral thesis deals with the synthesis, characterization and reactivity of base stabilized di-, tri- and tetraborane cations. Starting with the already known diborane(4) compound [HB(hpp)]2 some new potential precursors [XB(hpp)]2 (X = Cl, Me, n-Bu) were obtained. Proceeding from the dichloro-diborane, the chloride abstraction with AlCl3 and GaCl3 was studied. Irrespectively of the salt chosen, the reaction led to formation of a radical tricationic tetraborane [{B(hpp)}4]3+· and permitted some new insights into the reaction mechanism. In the further course of this work a highly electron-deficient sigma-aromatic tetraborane(4) intermediate [{B(hpp)}4]4+ was isolated and fully characterized. This unprecedented compound represents the first cationic structural derivative of [B4H4]4+ and is stabilized by the lattice energy. In addition, the repertoire of electron-deficient cyclic boranes was expanded by a new cationic triborane [{B(hpp)}2(BH2)]+. The second part of this thesis focuses on the double reactivity pattern of boron(II) cations. Starting with the diborane(4) [(TfO)B(hpp)]2 with two easily exchangeable triflate substituents, a facile synthesis of several new boron(II) cations is reported. By systematically increasing the pi-acceptor properties of the sigma-Lewis basic reaction partners, first examples are presented in which the combined Lewis acidity and electron donor properties were used for the reduction of organic substrates. Expanding the organic sigma-donors by redox-active N-heterocyclic linkers resulted in the first members of an unprecedented family of highly charged cationic cyclophanes with integrated diboranyl units. The findings of this thesis provide deeper insight into the structural variety and potential application of borane(II) cations in organic synthesis as well as supramolecular materials.
This thesis describes the investigation of homogeneously catalyzed reactions with quantum chemical methods. Two different reactions were studied in this work: the dehydroperoxidation of alkyl hydroperoxides with both vanadium and chromium catalysts and the direct asymmetric reductive amination of ketones with ruthenium.
In the first part, the dehydroperoxidation of cyclohexyl and 4-heptyl hydroperoxide to the corresponding ketones with a vanadium dipicolinato complex is investigated. It is found that a radical-free mechanism is feasible and that it proceeds through hydrogen abstraction by the vanadium oxo group. The barrier difference for this process for both substrates is in line with higher experimental selectivities for the non-cyclic hydroperoxide. A mechanistic study on the chromium-catalyzed dehydroperoxidation follows, which shows that a similar mechanism is active for Cr. The better selectivity and activity of this catalyst in comparison with the vanadium system is reproduced as the activation energy for dehydroperoxidation is lower with chromium. Finally, we rule out that the reaction proceeds via an intramolecular hydrogen transfer in an alkoxy/alkylperoxo chromium species, which has been suggested in previous research on the topic. The second part of the thesis explores the mechanism of the direct asymmetric reductive amination of ketones with a ruthenium (S,S)-f-binaphane complex. Acetophenone is used as the model ketone for this reaction. The investigations show that the rate-determining step of the reaction is the proton transfer from a σ-dihydrogen complex to liberate the amine. A thorough analysis of possible isomer/conformer combinations turns out to be crucial for a quantitative understanding of the reaction; following such an analysis, the experimental enantioselectivity is accurately reproduced for a series of catalysts with different halide ligands. These results are supplemented by studies on the chemoselectivity of the reaction. The mechanism is then applied to build a simple model for estimating the bite angle dependency of the reaction’s enantioselectivity. It is predicted that larger bite angles should favor higher enantioselectivity. A search in the CCDC database reveals several promising ligand backbone candidates for an optimized binaphane ligand of which a biaryl motif is finally considered as the most promising candidate.
Verbindungen des Phosphors spielen eine Schlüsselrolle als Flammschutzmittel FSM)für Polymere und Coatings, da sie aufgrund der chemischen Vielseitigkeit von Phosphor, aus Gründen der Nachhaltigkeit und nicht zuletzt einer hohen Effektivität auch bei niedrigen Beladungen zunehmend halogenierte FSM substituieren. Das Ziel dieser Dissertation war die Entwicklung neuer phosphorbasierter FSM für Epoxidharze, die über mindestens zwei Phosphoratome mit idealerweise unterschiedlichen Substitutionsmustern verfügen, sodass wichtige Struktur-Eigenschaftsbeziehungen hergestellt werden können. Dazu wurden vor allem Derivate des 9,10-Dihydro-10-oxa-phosphaphenanthren-10-oxids (DOPO), einem wichtigen gasphasenaktiven FSM, dargestellt. Das erste Synthesekonzept beinhaltete zunächst die Darstellung N-phosphorylierter Iminophosphorane mittels Staudinger-Reaktion durch die Umsetzung von Phosphoryla- ziden mit verschiedenen trivalenten Phosphorverbindungen (Phosphine, Phosphonite und Phosphite). Die thermischen Stabilitäten betreffende Untersuchungen bestätigten, dass phosphin-basierte N-phosphorylierte Iminophosphorane wie z.B. DOPO-N=PPh3 thermisch stabiler sind als deren phosphitstämmige Analoga wie z.B. DOPO-N=P(OPh)3. Diese zunehmende thermische Stabilität spiegelt sich in den entsprechenden Winkeln und Abständen der N-phosphorylierten Iminophosphorane wider. Das zweite Synthesekonzept hatte die Erweiterung der Staudinger-Reaktion von DOPO-N3 mit pentavalenten Phosphorverbindungen des Typs RR‘(O)P-H zum Ziel. Mit Hilfe der Röntgenkristallstrukturanalyse wurden den Produkten Imidodiphosphorstrukturen (R2(O)P-NH-P(O)R2) zugewiesen. In einem dritten Synthesekonzept wurden ausgehend vom Vinylphosphonsäuredimethylester (VPADME) und unterschiedlichen P-H-Verbindungen zunächst mittels Phospha-Michael-Addition Phosphonsäureester dargestellt. Diese wurden zu den entsprechenden freien Phosphonsäuren hydrolysiert und anschließend in die korrespondie- renden Melaminsalze überführt. Zur Untersuchung der FSM-Wirkung wurden ausgewählte Verbindungen dieser Stoffklassen in unterschiedliche Epoxidharze eingearbeitet - einem Diglycidylether von Bisphenol A (DGEBA) und einem glycidierten Phenolnovolak (DEN 438) und jeweils mit Dicyandiamid (D) als Härter sowie Fenuron (F) als Beschleuniger ausgehärtet. Dabei wurde die Reaktivität gegenüber der Oxirangruppe eingehend untersucht. Es wurde gezeigt, dass sich alle VPADME-stämmigen ethylenverbrückten Bisphosphorverbindungen, die Iminophosphorane DOPO-N=P(OMe)3 und DOPO-N=P(OPh)3 sowie die Imidodiphosphorverbindung DOPO-NH-DOPO reaktiv in die Epoxidharzmatrix einarbeiten lassen. Alle flammgeschützten Epoxidharze wurden auf ihre Materialeigenschaften und Brennbarkeit untersucht und unter Berücksichtigung der Substitutionsmuster an den Phosphoratomen bewertet. Zusätzlich wurden die Flammschutzmechanismen ausgewählter FSM in DGEBA/D/F und DEN 438/D/F mittels Cone-Kalorimetrie untersucht. Die Flammschutztests ergaben, dass die DOPO-stämmigen N-phosphorylierten Iminophosphorane vor allem in dem Harzsystem DEN 438/D/F einen guten Flammschutz bewirken. Allen voran bewirkte DOPO-N=PPh3 aufgrund seiner primären Gasphasenaktivität in diesem Harzsystem den besten Flammschutz, der sämtliche Referenzverbindungen übertraf. In DGEBA/D/F zeigte der ethylenverbrückte Bisphosphonsäurester (EBBPE) aufgrund seiner primären Aktivität in der kondensierten Phase sehr gute Flammschutzeigenschaften, die denen gängiger Referenzverbindungen entsprechen. Mit dieser Arbeit wurde gezeigt, dass sich phosphororganische Verbindungen, die über mindestens zwei Phosphoratome mit unterschiedlichen Substitutionsmustern verfügen, in einer Eintopfreaktion in guten Ausbeuten herstellbar sind und sehr gute Brandschutzergebnisse in unterschiedlichen Epoxidharzen erzielen.
Despite recent advances leading to unprecedented performance in organic photovoltaic devices, the underlying processes of charge generation in these semiconductors are still unclear. Furthermore, the operational stability of organic solar cells - a key requirement for successful application outside the laboratory - is often neglected. This thesis addresses these urgent and complex challenges by investigating the photophysics and degradation mechanisms of two high-efficiency material systems by employing ultrafast transient spectroscopy. The first part is devoted to the understanding of charge generation in PffBT4T-2OD:PC70BM which acts as a model system for a new class of organic photovoltaic materials. It is unambiguously shown that the separation of electron-hole pairs is field-dependent, with significant implications for the research of novel combinations of materials with low energy offsets. Based on these results, the second part of this thesis focuses on the environmental stability of the aforementioned system which is shown to be exceptionally sensitive to the influence of oxygen. The observed results can be comprehended by oxygen-induced p-doping of the active layer, resulting in rapid deterioration of the device properties. Finally, the photophysics and degradation of solar cells based on the small molecule donor DRCN5T, representative of a new trend in solar cell design, are addressed. These devices display remarkable stability which is accredited to an ultrafast energy transfer from the unstable to the stable components. This insight can potentially influence design rules for future research on organic solar cells. Therefore, this work contributes substantially to the understanding of the photophysics at short timescales and the stability of organic solar cells with high relevance for the field.
Molecular imaging is established as an indispensable tool in various areas of cancer research, ranging from basic cancer biology and preclinical research to clinical trials and medical practice. In particular, the field of fluorescence imaging has experienced exceptional progress during the last three decades with the development of various in vivo technologies. Within this field, fluorescence microscopy is primarily of experimental use since it is especially qualified for addressing the fundamental questions of molecular oncology. As stimulated emission depletion (STED) nanoscopy combines the highest spatial and temporal resolutions with live specimen compatibility, it is best-suited for real-time investigations of the differences in the molecular machineries of malignant and normal cells to eventually translate the acquired knowledge into increased diagnostic and therapeutic efficacy. This thesis presents the application of STED nanoscopy to two acute topics in cancer research of direct or indirect clinical interest. The first project has investigated the structure of telomeres, the ends of the linear eukaryotic chromosomes, in intact human cells at the nanoscale. To protect genome integrity, a telomere can mask the chromosome end by folding back and sequestering its single-stranded 3’-overhang in an upstream part of the double-stranded DNA repeat region. The formed t-loop structure has so far only been visualized by electron microscopy and fluorescence nanoscopy with cross-linked mammalian telomeric DNA after disruption of cell nuclei and spreading. For the first time, this work demonstrates the existence of t-loops within their endogenous nuclear environment in intact human cells. The identification of further telomere conformations has laid the groundwork for distinguishing cancerous cells that use different telomere maintenance mechanisms based on their individual telomere populations by a combined STED nanoscopy and deep learning approach. The population difference was essentially attributed to the promyelocytic leukemia (PML) protein that significantly perturbs the organization of a subpopulation of telomeres towards an open conformation in cancer cells that employ a telomerase-independent, alternative telomere lengthening mechanism. Elucidating the nanoscale topology of telomeres and associated proteins within the nucleus has provided new insight into telomere structure-function relationships relevant for understanding the deregulation of telomere maintenance in cancer cells. After understanding the molecular foundations, this newly gained knowledge can be exploited to develop novel or refined diagnostic and treatment strategies. The second project has characterized the intracellular distribution of recently developed prostate cancer tracers. These novel prostate-specific membrane antigen (PSMA) inhibitors have revolutionized the treatment regimen of prostate cancer by enabling targeted imaging and therapy approaches. However, the exact internalization mechanism and the subcellular fate of these tracers have remained elusive. By combining STED nanoscopy with a newly developed non-standard live cell staining protocol, this work confirmed cell surface clustering of the targeted membrane antigen upon PSMA inhibitor binding, subsequent clathrin-dependent endocytosis and endosomal trafficking of the antigen-inhibitor complex. PSMA inhibitors accumulate in prostate cancer cells at clinically relevant time points, but strikingly and in contrast to the targeted antigen itself, they eventually distribute homogenously in the cytosol. This project has revealed the subcellular fate of PSMA/PSMA inhibitor complexes for the first time and provides crucial knowledge for the future application of these tracers including the development of new strategies in the field of prostate cancer diagnostics and therapeutics. Relying on the photostability and biocompatibility of the applied fluorophores, the performance of live cell STED nanoscopy in the field of cancer research is boosted by the development of improved fluorophores. The third project in this thesis introduces a biocompatible, small molecule near-infrared dye suitable for live cell STED imaging. By the application of a halogen dance rearrangement, a dihalogenated fluorinatable pyridinyl rhodamine could be synthesized at high yield. The option of subsequent radiolabeling combined with excellent optical properties and a non-toxic profile renders this dye an appropriate candidate for medical and bioimaging applications. Providing an intrinsic and highly specific mitochondrial targeting ability, the radiolabeled analogue is suggested as a vehicle for multimodal (positron emission tomography and optical imaging) medical imaging of mitochondria for cancer diagnosis and therapeutic approaches in patients and biopsy tissue. The absence of cytotoxicity is not only a crucial prerequisite for clinically used fluorophores. To guarantee the generation of meaningful data mirroring biological reality, the absence of cytotoxicity is likewise a decisive property of dyes applied in live cell STED nanoscopy. The fourth project in this thesis proposes a universal approach for cytotoxicity testing based on characterizing the influence of the compound of interest on the proliferation behavior of human cell lines using digital holographic cytometry. By applying this approach to recently developed live cell STED compatible dyes, pronounced cytotoxic effects could be excluded. Looking more closely, some of the tested dyes slightly altered cell proliferation, so this project provides guidance on the right choice of dye for the least invasive live cell STED experiments. Ultimately, live cell STED data should be exploited to extract as much biological information as possible. However, some information might be partially hidden by image degradation due the dynamics of living samples and the deliberate choice of rather conservative imaging parameters in order to preserve sample viability. The fifth project in this thesis presents a novel image restoration method in a Bayesian framework that simultaneously performs deconvolution, denoising as well as super-resolution, to restore images suffering from noise with mixed Poisson-Gaussian statistics. Established deconvolution or denoising methods that consider only one type of noise generally do not perform well on images degraded significantly by mixed noise. The newly introduced method was validated with live cell STED telomere data proving that the method can compete with state-of-the-art approaches. Taken together, this thesis demonstrates the value of an integrated approach for STED nanoscopy imaging studies. A coordinated workflow including sample preparation, image acquisition and data analysis provided a reliable platform for deriving meaningful conclusions for current questions in the field of cancer research. Moreover, this thesis emphasizes the strength of iteratively adapting the individual components in the operational chain and it particularly points towards those components that, if further improved, optimize the significance of the final results rendering live cell STED nanoscopy even more powerful.
Borylierungs- und Diborierungsreaktionen sind wichtige Synthesemöglichkeiten in der organischen Chemie. Durch die Bildung von stark polarisierten B-C-Bindungen sind sie elementarer Bestandteil für C-C-Bindungsknüpfungen. Bislang werden fast nur Bor-elektrophile Borane oder Diborane, die in der Regel sp2-hybridisierte Boratome enthalten, eingesetzt. Dies erfordert fast immer die Verwendung von Katalysatoren oder Zusatzreagenzien. Werden bizyklische Guanidinate als verbrückende Substituenten eines sp3-sp3-hybridisierten Diborans(4) verwendet, kann eine außerordentlich hohe Elektronendichte in der B-B-Bindung im Diboran(4) erreicht werden. Durch die daraus resultierende hohe Nukleophilie besitzt das Diboran(4) eine einzigartige Reaktivität. In der vorliegenden Arbeit gelang erstmals eine metallfreie Hydroborierung von CO2 durch ein neutrales, nukleophiles Diboran(4). Dabei konnte bei Raumtemperatur und ohne Zusatzreagenzien durch Wahl eines geeigneten Lösungsmittels entweder das einseitig oder das zweiseitig hydroborierte Diboran(4) erhalten werden. Wird die Nukleophilie der Diborane(4) durch elektronenziehende Substituenten verringert, konnte eine langsamere Reaktionsgeschwindigkeit der Hydroborierung festgestellt werden. Darüber hinaus konnte erstmals eine Diborierung von Nitrilen realisiert werden. Bei der metallfreien Umsetzung des nukleophilen Diborans(4) mit Nitrilen in Anwesenheit von starken Lewis-Säuren wird als Endprodukt ein protoniertes diboryliertes Imin erhalten. Bei diesem liegt ein positiv und negativ polarisiertes Wasserstoffatom benachbart vor, wodurch dieses als Wasserstofftransfer-Reagenz auf ungesättigte organische Verbindungen, wie Imine oder Olefine, eingesetzt werden kann. Wird zum elektronenreichen Diboran(4) ein kationisches Boran [R2B]+ gegeben, bildet sich ein zyklisches kationisches Triboran, dessen Stabilität und Reaktivität je nach Wahl der Substituenten (R) beeinflusst werden kann. Wird ein Substituent ohne freie Elektronenpaare verwendet, konnte eine außerordentliche Stabilität festgestellt werden. Substituenten mit höherem +M-Effekt destabilisieren die zyklischen Triborane. Die gewonnenen Erkenntnisse gewähren ein tieferes Verständnis der Reaktivität von nukleophilen Diboranen. Die erfolgreiche Funktionalisierung von elektronenarmen Substanzen unter milden Reaktionsbedingungen erweitert das Anwendungsgebiet der nukleophilen Diborane in der organischen Synthese durch neue Synthesestrategien.
Charge carrier injection at the metal/organic interface is crucial for the performance of organic semiconductor based (opto)electronic devices. To achieve an efficient charge carrier injection a detailed knowledge of the electronic properties at the metal/organic interface is needed. In this thesis ultraviolet photoemission spectroscopy and (time-resolved, angle-resolved) two-photon photoemission spectroscopy were utilized to reveal occupied as well as unoccupied electronic states including excitonic states and transport levels. On the one hand the electronic structure and excited state dynamics of a pentacene derivative, in particular regarding the singlet fission dynamics with respect to the film thickness on an Au(111) surface, were examined. On the other hand the electronic structure at the interface between several promising Nheteropolycyclic semiconductors, including a porphyrin, a N-heteroacene and different N-heteroperopyrenes, and Au(111) was revealed. The investigations of the N-heteroperopyrenes stand out as the observation of band formation via hybridization between delocalized metal bands and localized molecular orbitals at the metal/organic interface should foster efficient charge injection.
In der vorliegenden Studie wurde überprüft, inwiefern der Fischembryotest (FET) als Werkzeug zur Bestimmung von spezifischer Toxizität in Embryonen des Zebrabärblings (Danio rerio) dienen kann. Als spezifische Endpunkte wurden dioxinähnliche Wirkung mithilfe des modifizierten Live-Imaging-EROD-Assays und Neurotoxizität mittels des Acetylcholinesterase-Assays untersucht. Diese Assays wurden jeweils mit einem Satz ausgewählter Chemikalien geprüft, die aufgrund ihrer Relevanz für die europäische Wasserrahmenrichtlinie ausgewählt wurden: Methylquecksilberchlorid, Chlorpyrifos, Aroclor 1254, 2,3-Benzofuran, Chinolin, Bisphenol A sowie Paraoxon-methyl (für neurotoxikologische Effekte) und eine Reihe von Sedimenten von Standorten mit bekanntem ökotoxikologischen Hintergrund: Altrip und Ehrenbreitstein am Rhein sowie der Veringkanal im Hamburger Hafen. Um die spezifische Toxizität zu untersuchen und schädliche Wirkungen durch akute Toxizität zu vermeiden, wurde zuerst die Effektkonzentration von 10 % (EC10) bestimmt. Hierbei zeigte sich mit fortschreitender Belastungsdauer, dass mit steigendem log Kow die Diffusionsrate ab- und die Akkumulationsrate zunahm. Eine Akkumulation von Substanzen mit einem hohen log Kow war zum einen mit einer verzögerten Toxizität, zum anderen bei verlängerter Exposition durchaus mit gesteigerter Toxizität verbunden. Neben Teratogenität wurde auch die Bioaktivierung über CYP1A mit einer in dieser Arbeit entwickelten Kombinationsexposition untersucht. Eine gleichzeitige Exposition gegenüber Chlorpyrifos + β-Naphthoflavon führten zu einer 40 %igen Steigerung der Toxizität gegenüber Chlorpyrifos als Monosubstanz. Ein Schwerpunkt der vorliegenden Arbeit lag in der Entwicklung und Optimierung eines modifizierten Live-Imaging-EROD-Assays. Die Auswertung des Assays über verschiedene Entwicklungsstufen hinweg (24, 48, 72, 96 und 120 h) zeigte, dass erst Embryonen mit einer funktionsfähigen Leber (≥ 72 h) und nach β-Naphthoflavon-Stimulation ein deutliches Fluoreszenzsignal in der Leber zeigten, dass nach 96 und 120 h dosisabhängig über die Zunahme von Resorufin im Gastrointestinaltrakt abgebildet werden konnte. Nach diesen Ergebnissen sind 96 und 120 h alte Embryonen die geeigneten Entwicklungsstadien, um die EROD-Aktivität in vivo mithilfe des Live-Imaging-EROD-Assays zu ermitteln. Eine Reduktion der Expositionszeit auf 3 h führte zu einem schnellen, effizienten und einfach handzuhabendem Assay. Die Kombinationsexposition mit Induktoren ermöglichte, erstmals in vivo das gleichzeitige Vorkommen von Agonisten und Inhibitoren von CYP1A in komplexen Umweltproben im Embryo darzustellen und ließ somit die Untersuchung der Rolle der CYP1A-Hemmung in Bezug auf die Toxizität zu. Eine geeignete Bildauswertungssoftware erlaubt schließlich eine Quantifizierung und anschließend eine statistische Auswertung der EROD-Induktion, was seinerseits zu einer Vergleichbarkeit sowie einer erhöhten Akzeptanz des modifizierten Live-Imaging-EROD-Assays beiträgt. Der modifizierte Acetylcholinesterase-Assay mit den Embryonen des Zebrabärblings erwies sich als ein geeignetes Werkzeug zum Nachweis der neurotoxischen Wirkungen bestimmter Substanzklassen sowie auch komplexer Umweltproben. Die vorliegende Studie belegt dabei auch, dass PAKs in komplexen Umweltproben zur AChE-Hemmung beitragen können. Embryonen des Zebrabärblings können ein geeignetes Modell zur Untersuchung neurotoxischer Wirkungen darstellen.
Nuclear medicine offers various approaches and methods for using radiation for the diagnosis and therapy of different diseases, e.g. cancer. Imaging techniques such as positron emission tomography (PET) or therapeutic procedures such as radioimmunotherapy (RIT) use so-called tracers in which radio¬nuclides are linked to biomolecules as vector moieties (e.g. peptides or antibodies). These vectors specifically bind to the target tissue and allow imaging of a tumor in the body or inducing death of cancer cells. When using metallic radionuclides, these tracers contain a bifunctional chelator (BFC) which forms a stable complex and connects the metal ion to the desired vector. Due to the versatility of radiometals and their facile insertion into tracers by choosing a suitable BFC, the development and improvement of BFCs has become a constantly growing field of research. High stability of the metal-chelator complex is one of the major criteria for radio¬pharmaceutical application.
The work presented in this thesis is focused on the synthesis and experimental investigation of bispidine ligands, which form stable complexes with metal ions such as CuII, and thus represent suitable BFCs for the use in 64Cu positron emission tomography. Based on bispidine B1, which was already investigated for 64Cu-PET, ligand B2 was developed by substituting one of the pyridines with a pyridazine moiety and consequently reducing intraligand strain caused by pyridine-α-hydrogen atoms upon coordination. This was done in order to optimize the CuII complex geometry and enhance its stability. Coordination of B2 to CuII, NiII and ZnII was investigated, and comparison of CuII-B1 with CuII-B2 by different analytical methods did not show the expected increase in complex stability. The results suggest that the stabilizing effect of the optimized geometry is offset by the lower basicity and inferior donor properties of the modified substituent.
In the second part of this thesis, the promising chelator B4 was further developed into a 64Cu-PET tracer. B4 was functionalized at position C9-OH with a para-isothiocyanatobenzyl group (p-NCS-Bn) and linked to a peptide (TATE). Preliminary radiolabeling experiments of the functionalized ligand show its stability against EDTA as competing ligand, and give reason to expect promising in vitro and in vivo experiments of the ligand-peptide conjugate. The third part covers the investigation of heptadentate bispidine ligands for BiIII, whose isotopes 212Bi und 213Bi are suited for radiotherapy. Initially, DFT geometry optimizations were performed on BiIII complexes of various ligands with pyridyl, picolinate, carboxylate or phosphonate substituents at the tertiary amines of the bispidine platform. Of these, B7-B9 were synthesized and, as well as the literature-known octa¬dentate B3, were reacted with BiIII at room temperature. Single crystals of all complexes were obtained, and the X-ray structural analyses show either dimerization or coordination of a nitrate counter ion, resulting in coordination numbers of eight or nine. These findings suggest that the metal center is not coordinatively saturated with the hepta- and octadentate bispidines, and that therefore nonadentate bispidines could be a suitable choice for BiIII complexation.
The primary aim of this thesis was to quantitatively investigate the physics of complex, biological interfaces in intestines by the combination of well-defined model systems and unique experimental techniques. In Chapter 4, the formation of food colloids, via crosslinking negatively charged polyalginate by Ca2+ ions, was modeled at the o/w interface. The temporal evolution of the polymer chain dynamics during the gelation was detected by means of grazing incidence X-ray photon correlation spectroscopy (GI-XPCS) at the liquid/liquid interface for the first time. In Chapter 5, the significance of interfacial interactions between various lipids and mucin proteins was quantitatively compared by the combination of an in vitro mucus model and label-free microinterferometry. Remarkably, the enrichment of phosphatidylcholine at the mucus/lumen interface cannot be explained by the classical electrostatics. In Chapter 6, the mechanism of the adhesion of probiotic bacteria to the mucins was investigated under hydrodynamic shear mimicking the in vivo intestinal environment. The dynamic adhesion of probiotic bacteria is enhanced at the shear stress of 0.3 Pa, which showed a good agreement with in vivo conditions. The obtained results demonstrated that the combination of in vitro models together with unique experimental techniques yields the structures, dynamics, and interactions occurring at complex, biological interfaces.
The geochemistry of the actinides is of particular interest for the safety case of a nuclear waste repository. The present work focuses on the complexation of pentavalent actinides An(V) with different organic and inorganic ligands in aqueous solution at elevated temperatures. In the first part of the thesis the complexation of NpO2+ with different mono- and dicarboxylic ligands (formate, acetate, oxalate, malonate, succinate) and hydorxyl functionalized carboxylates (lactate, malate, tartrate) is studied. These ligands are either naturally occuring substances in the pore waters of clay rocks or serve as model ligands for macro molecular organic compounds like humic substances or polycarboxylate based cement additives. The speciation of the formed complexes and the thermodynamic functions (log b0i(T), DRH0m,i, DRS0m,i) of the corresponding complexation reactions are determined as a function of temperature and ionic strength using Vis/NIR absorption spectroscopy. Additionaly, the structures of the NpO2+ complexes with oxalate, malonate, succinate and lactate are resolved by EXAFS spectroscopy, ATR-FT infrared spectroscopy and quantum chemical calculations revealing detailed information on the coordination properties of An(V) on a molecular level. In the second part the complexation of NpO2+ with the inorganic anions fluoride, chloride, nitrate and sulfate is studied at various temperatures and ionic strengths revealing the stoichiometry of the formed complexes and the thermodynamic functions of the respective complexation reactions. These inorganic anions are integral parts of natural groundwaters. Additionaly, fluoride and chloride are available in large quantities in salt rock formations which are in discussion as host rocks of nuclear waste repositories. In the third part of this work the NpO2+ complexation up to 200 °C is studied for the first time by absorption spectroscopy. Therefor, a high-temperature spectrophotometric cell is developed at the Institute for Nuclear Waste Disposal (INE) at the Karlsruhe Institute of Technology (KIT). The applicability of this setup for speciation studies up to 200 °C is demonstrated by studies on the complexation of NpO2+ with SO42-. The obtained results contribute to an improved understanding of the (geo)chemical behaviour of pentavalent actinides in aqueous systems and provide detailed information on the complexation properties of An(V) on a molecular level. Furthermore, the implementation of a high-temperature spectrophotometric cell for speciation studies on the complexation of NpO2+ up to 200 °C opens up the possibility for thermodynamic studies at conditions that might occur in the near-field of a nuclear waste repository.
There is an unmet need of fast, reliable and highly sensitive determination of different biomarkers in untreated physiological samples in the Point-of-Care setting. Among many types of biosensors, electrochemical and electronic transducers seem to fulfill many requirements for future diagnostic devices such as label-free and real-time analyte determination, as well as a potential for mass-manufacturability. A recent advancement of nanomaterials, with particular focus on carbon nanomaterials, triggered a foundation of a new branch of biosensors to explore. In this work, two carbon nanomaterials - graphene and carbon nanotubes, were used to construct both electronic and electrochemical biosensors – able to work in physiological environment and with a potential for further development into the Point-of-Care environment. The two types of transduction were assessed - 1) electronic (i.e. field-effect transistor (FET) based), based on analyte determination by its charge, and 2) electrochemical (i.e. amperometric), based on analyte determination by the redox reactions that occur at the electrode. Firstly, for the construction of carbon nanotube network based field-effect transistor biosensor, novel and stable receptor molecules were employed - nanobodies, and studied in a label-free system with green fluorescent protein as a model analyte. The biosensor exhibited a wide dynamic range with low detection limit and triggered the next, more applicable study. Secondly, a graphene-based field-effect transistor (GFET) was employed as a transducer for construction of thyroid-stimulating hormone (TSH) specific biosensor. This solution resulted in coverage (and also going far beyond) of TSH reference values in physiological samples. Finally, for the electrochemical based detection, using the setup from GFET study, graphene was used as a working electrode and in combination with the enzyme - flavin adenine dinucleotide dependent glucose dehydrogenase (FAD-GDH), resulted in an electrochemical glucose biosensor. Direct electron transfer from the enzyme to the graphene electrode was additionally observed. The results of this work shed light and contribute to the development of multimodal detection of analytes in physiological samples for further application in Point-of-Care setting.
Um die Bildgebung von gastrointestinalen Stromatumoren mittels Positronen-Emissions-Tomo¬graphie zu verbessern, wurden in dieser Arbeit neue 18F-markierte PET-Radiotracer entwickelt und evaluiert. Dafür wurde einerseits ein Radiotracer ([18F]Fluor-Norimatinib) entwickelt, der die Sensitivität des Tumors gegenüber Imatinib darstellen sollte und andererseits ein Radiotracer ([18F]Fluor-DOG1), mit dem sich gastrointestinale Stromatumore von anderen Sarkomen ohne invasive Biopsie unterscheiden lassen sollten. Literaturbekannte 18F-markierte Imatinib-Derivate weisen eine hohe Lipophilie und damit eine starke Akkumulation in der Leber auf, die die Bildgebung von gastrointestinalen Stromatumoren erschwert, weshalb in dieser Arbeit der hydrophilere Metabolit Norimatinib als Grundstruktur verwendet wurde. Das Radiolabel wurde am Pyridin-Ring eingeführt, da an dieser Position keine metabolischen Prozesse bekannt waren und [18F]Fluorpyridine über Nitropyridin-Vorläufer einfach zugänglich sind. Die Darstellung des Nitropyridin-Vorläufers und des Fluor-Standards von FNI wurden zunächst in einer 6-stufigen Synthese geplant, die allerdings nur für den Standard Fluor-Norimatinib (FNI) erfolgreich durchgeführt werden konnte, da die harschen Reaktionsbedingungen des letzten Reaktionsschrittes nicht mit dem Nitro-Derivat kompatibel waren. Eine neue 7-stufige Synthese, bei der weitestgehend auf mildere Bedingungen zurückgegriffen wurde, konnte jedoch den Nitropyridin-Vorläufer in guten Ausbeuten liefern. Die zweistufige Radiomarkierung konnte erfolgreich etabliert werden, sodass [18F]FNI nach Radiofluorierung, Entschützung und Aufreinigung in guten Ausbeuten erhalten wurde. Die Eva¬luierung in vitro wies aufgrund der Lipophilie nur eine geringe spezifische Bindung auf, jedoch zeigte FNI ein zu Imatinib analoges Bindungsprofil bezüglich verschiedener KIT-Mutanten. In den in vivo-Studien konnte zwar die renale Ausscheidung des Radiotracers stark erhöht werden, wodurch eine vorteilhafte, geringere Akkumulation in der Leber resultierte, allerdings erfolgte keine hohe Anreicherung in den Tumoren, vermutlich aufgrund deren geringer Vaskula¬risierung. Des Weiteren wurde durch die Metabolisierung des Radiotracers [18F]Fluorid freigesetzt, welches zu erhöhter Knochenanreicherung führte. Dies konnte jedoch durch Administra¬tion kleiner Mengen Ketoconazol reduziert werden, wobei zudem die Anreicherung in den Tumoren leicht stieg. Für die Radiomarkierung von [18F]Fluor-DOG1 wurden zunächst verschiedene Vorläufer mit Nitro-, Triazen- bzw. Borsäureester-Abgangsgruppen erfolgreich synthetisiert. Dabei zeigte sich, dass der Nitro-Vorläufer keine ausreichende Stabilität unter den harschen Markierungsbedingungen besaß, weswegen auf den reaktiveren Triazen-Vorläufer zurückgegriffen wurde. Dessen hohe Reaktivität führte allerdings zu einer Vielzahl an Reaktionsprodukten, die sowohl die Analytik, als auch die Aufreinigung derart erschwerten, dass auch dieser Vorläufer keine sinnvolle Option darstellte. Über die Kupfer-katalysierte Radiofluorierung des Borsäureester-Vorläufers hingegen konnte der gewün¬schte Radiotracer [18F]Fluor-DOG1 in guten Ausbeuten erhalten werden. In ersten in vivo-Studien in Mäusen zeigte der Radiotracer keine zufriedenstellende Pharmakokinetik, da die Anreicherung im Tumor nur unzureichend stattfand, jedoch eine starke Akkumulation in der Leber beobachtbar war. Dies wurde auf die geringe Stabilität von [18F]Fluor-DOG1 in murinem Blutserum zurückgeführt, weswegen eine Optimierung dahingehend vorgenommen werden sollte.
Diborane(4) compounds, exhibiting an electron-precise boron-boron bond, are extremely versatile reagents in organic synthesis, therefore the preparation and reactivity of these compounds is of great interest in modern boron chemistry. The introduction of such boron-boron bonds is limited to very few examples in contrast to the variety of carbon-carbon coupling reactions. Among the established strategies to boron-boron bond formation, dehydrocoupling reactions constitute an elegant, “atom- economic” pathway. However, these reactions are still restricted to a very few selected examples. The aim of this thesis was to establish new strategies to boron-boron bond formation via dehydrocoupling reactions; therefore various bidentate ligands, such as neutral bisphosphanes or anionic amidine or guanidine compounds were introduced. The respective bisphosphane borane adducts were isolated and fully characterized. Furthermore, the reactivity of these diboranes towards carbonyl complexes, hydrid abstraction and potential dehydrocoupling catalysts was investigated. Reaction with iodine selectively replaced one hydride in each borane by iodine, leading to the isolation and characterization of mono iodoboranes, as well as a doubly phosphane stabilized boron dication. However, boron-boron dehydrocoupling could not be achieved from this approach. In contrast, introduction of anionic ligands gave rise to a new route to boron-boron bond formation. The dehydrocoupling strategy developed in this thesis enables access to new nucleophilic diborane(4) compounds. Reaction of the borane adducts (L+H)-BH3 (L+H = 1,2,3,4,4a,5,6,7-octahydro-1,8- naphtyridine) as well as hppH-BH3 (hppH = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-α]pyrimidine) with iodine at room temperature lead to formation of [IB(μ-L)]2 and [IB(μ-hpp)]2. Both diboranes(4) were isolated and fully characterized. Based on a strong set of experimental data and quantum chemical computations, a reaction pathway for this unusual reaction was proposed. In difference to traditional pathways using reducing reagents, the reduction from BIII to BII is paradoxically achieved by the addition of the oxidation reagent iodine. Furthermore, quantum chemical computations were carried out on the diboranes(4) [IB(μ-L)]2 and [IB(μ-hpp)]2, as well as the hydrogen analogues [HB(μ-L)]2 and [HB(μ-hpp)]2, to determine various parameters, such as proton affinity and HOMO energies. All compounds were classified due to their nucleophilicity. The well documented, intensely studied [HB(μ-hpp)]2 constitutes the strongest nucleophilic character among the analysed compounds while the nucleophilicity of [IB(μ- L)]2 is quite low. Overall this thesis established access to an efficient and unprecedented boron-boron dehydrocoupling reaction under mild conditions, applicable to diverse borane adducts.
This thesis evaluates three novel synthesized conjugated polymer series with respect to their sensitivity and selectivity in the detection of nitroaromatic analytes, especially in aqueous environments. Central building blocks of the polymers are functionalized truxene or tetraphenylethene centers, which are polycondensed with different diethinylaromatics by Sonogashira cross- coupling. In a first explorative study, Truxene-based hyper-branched polymers (HCPs) were compared with related linear rod-shaped poly(p-phenylenethynylenes) (PPEs) with respect to their sensor performance of nitroaromatics (Chapter 2). By encapsulation with amphiphilic F-127 in water-soluble micelles, 14 nitroaromatics could be distinguished with 100% accuracy in fluorescence quenching experiments. The HCPs display a better sensor performance than the sensor system for nitroaromatics previously known from PPE (Chapter 2). To increase the sensor performance, tetraphenylethene cores (TPEs) replaced the truxene units in the polymers in a follow-up study (Chapter 3). TPEs use aggregate-induced emission to detect the analytes. A sensor field based on four TPE polymers was able to detect and distinguish nitroaromatics in water with excellent sensitivity (ppm range) compared to HCP or PPE systems (Chapter 3). This improved system is able to detect the regioisomers of nitroaromatics in a specific way. Finally, the performance of the TPE system was improved by varying the TPE moiety with amino or nitro groups for aqueous detection (Chapter 4). The functional TPE polymers (F-TPEPs) also exhibit aggregate-induced emission, with enhanced pH-specific (amino groups) or solvatochrome (nitro groups) sensor sensitivity. The presence of amino groups improves the sensory properties of F-TPEPs in the aqueous nitroaromatic system. The challenge of the detection of nitroaromatics in water could be mastered by the systematic development of F-TPEPs sensor system from the well-known PPE sensor.
The primary aim of this thesis is the creation of new electrochemical biosensor systems on solution-gated GaN/AlGaN/GaN high electron mobility transistors (HEMT) for the transduction of biological functions into electrical readouts. For this purpose, the surface of transistors was functionalized with various biomimetic and bioorganic molecular systems, such as helical peptides, lipid monalayers and membranes. The full characterization of thickness, roughness, and density of such biomimetic molecular assemblies enables to quantitatively translate the change in surface monopoles and dipoles into the carrier mobility. In Chapter 4, monolayers of bio-inspired, non-biological helical peptides were deposited on GaN semiconductor surfaces in order to modulate the electronic band structures of GaN by macromolecular dipole moments. By covalently coupling the peptides via N- or C-terminus to the GaN surfaces, the sign (direction) of exerted dipole moments could precisely be controlled, realizing the modulation of the carrier mobility. Moreover, the chronoamperometry measurements have demonstrated the additional ferrocene terminal group enables the directed electron transfer through peptide chains via an inelastic hopping mechanism. In Chapter 5.3, cell membrane models were deposited on the GaN surfaces pre-coated with hydrophobic, organic silane monolayers. By incorporating lipids with nitrilotriacetic acid (NTA) head groups into lipid membranes, changes in the surface potentials induced by the binding of charged recombinant proteins to the surface lipid membranes could be detected at a high sensitivity. The systematic variation of surface density of NTA lipids and the comparison with impedance spectroscopy data of bulk GaN electrodes, it has been demonstrated that the sensitivity of this system to changes in the surface charge density is as high as ΔQ < 0.1 μC/cm2. In Chapter 5.2, to accommodate the incorporation of transmembrane proteins under nondenaturing conditions, a more realistic cell membrane model, bilayer lipid membranes, was deposited on GaN by using regenerated cellulose films as the polymer support. The current-voltage characteristics clearly indicated the high electric resistance of lipid membranes, which seems promising for the detection of molecular recognition and selective material transport. Last but not least, such molecular constructs were transferred onto the surface of molecularly thin, organic semiconductors that have shown a high charge mobility under dry conditions (Chapter 6). The preliminary attempts already demonstrated the formation of uniform lipid monolayers on organic semiconductor surfaces exposing hydrocarbon chains. Moreover, the reversible binding and unbinding of recombinant proteins has been confirmed. Although further optimization of the device geometry and Ohmic contacts are necessary, the data suggest a large potential of all organic electronic sensors operating under water. The obtained results highlighted the potential of the combination of biomimetic molecular constructs and inorganic and organic semiconductor devices for the highly sensitive and quantitative determination of properties and functions under physiological conditions.
Reactive halogens have a significant impact on atmospheric chemistry in the polar troposphere. Due to a high reactivity, halogen radicals change the oxidative capacity of the atmosphere and alter chemical cycles of other trace gases such as ozone, sulphur species, or gaseous elemental mercury.
This thesis investigates abundances of halogen and other trace gases in the boundary layer of coastal Antarctica and studies release, impact, and fate of chlorine, bromine, and iodine species. For this, an automated Long-Path Differential Optical Absorption Spectroscopy (LPDOAS) instrument was developed and successfully operated on the German Antarctic Station Neumayer III for 32 months from January 2016 until August 2018. This extensive record of trace gas abundances is combined with a comprehensive set of ambient observations from the station.
A frequent presence of bromine monoxide (BrO) was detected with mixing ratios of up to 111.2±0.7 ppt and pronounced daily and annual cycles with activity maxima in spring and autumn, mostly driven by solar radiation and atmospheric dynamics. Chlorine monoxide(ClO) and chlorine dioxide (OClO) were equally detected with mixing ratios up to 105±4 ppt and 7.7±0.8 ppt respectively. Ambient observations indicate a central role of local snow surfaces for the release of both bromine and chlorine species. Iodine monoxide (IO) was rarely present with mixing ratios up to 6.5±1.0 ppt. The influence of cross halogen reactions on ozone mixing ratios was estimated and found in good agreement with observations. An annual cycle of SO2 mixing ratios up to 230±17 ppt was detected and could be attributed to the marine sulphur cycle. A coincidence of natural new particle formation events and elevated BrO mixing ratios was observed.
Intramolekulare Elektronentransferprozesse in Übergangsmetallkomplexen sind nicht nur in der Grundlagenforschung, sondern ebenso für die Forschung in der Katalyse oder den Materialwissenschaften von Interesse. In dieser Dissertation wurden die Möglichkeiten zur Einflussnahme auf die Grenzorbitalenergien von guanidino-funktionalisiertem Phenazin in freier Form sowie in zwei- und vierkernigen Übergangsmetallkomplexen untersucht. Dabei wurden insbesondere die Bedingungen, die zu einem intramolekularen Elektronentransfer führen, betrachtet. Bei der Verbindung 2,3,7,8-Tetrakis(tetramethylguanidino)phenazin (ttmgph) handelt es sich um einen Vertreter der im Arbeitskreis Himmel entwickelten Ligandenklasse der guanidino-funktionalisierten Aromaten (GFA). Im Gegensatz zu den elektronenreichen Vertretern dieser Ligandenklasse mit kleinem aromatischem Grundgerüst, wie z. B. Benzol, führt die Substitution des elektronenarmen heteroaromatischen Phenazins mit elektronenschiebenden Guanidinogruppen nicht zur Bildung eines redoxaktiven Elektronendonors. Das ermöglicht die Weiterentwicklung sowohl zum Elektronendonor- als auch zum Elektronenakzeptor-Liganden. Das ausgeprägte π-System mit kleiner HOMO-LUMO- Lücke erlaubt es außerdem, Änderungen der Grenzorbitalenergien unter anderem anhand von UV/Vis- Absorptions- und Emissionsspektroskopie zu verfolgen. Die Auswirkung von Umgebungseinflüssen auf ttmgph im Festkörper und in Lösung konnte mittels Matrixisolationstechnik untersucht werden. Dadurch wurde gezeigt, dass die Wechselwirkungen in kondensierten Phasen, im Vergleich zum nahezu isoliert vorliegenden Molekül in der Argon-Matrix, eine Verringerung des HOMO-LUMO-Abstands zur Folge hat. Der Stokes-Shift hingegen wird durch das Lösungsmittel nicht beeinflusst, während er im Festkörper eine Zunahme erfährt. Die differenzierte Lewisbasizität der Phenazin- und Guanidin-Iminstickstoffatome ermöglicht die schrittweise Koordination verschiedener Metalle. So konnten zunächst dinukleare Nickel(II)- und Kupfer(II)-Komplexe, durch Koordination der Guanidinogruppen, erhalten werden. In diesen wurden Elektronendonor-Eigenschaften des Liganden in Form von Ligand-Metall-Charge-Transfer-Übergängen (LMCT) beobachtet, welche mit Hilfe von TD-DFT-Rechnungen identifiziert wurden. Die anschließende Koordination der Phenazin-Stickstoffatome an Kupfer(I)-chlorid führt zu gemischtvalenten bzw. hetero-bimetallischen vierkernigen Komplexen, in denen die zuvor beobachteten LMCT-Übergänge bei trigonaler Kupfer(I)-Koordination ausgeschaltet sind, während sie bei linearer Koordination erhalten bleiben. Durch Benzylierung der Guanidinogruppen hingegen konnte deren elektronenschiebende Wirkung kompensiert und somit die Elektronenakzeptor-Eigenschaften des Phenazingerüsts wiedererlangt werden. Dies wurde anhand von Cyclovoltammetrie (CV) sowie, bei anschließender Kupfer(I)- Koordination der Phenazin-Stickstoffatome, in Form von Metall-Ligand-Charge-Transfer-Übergängen (MLCT) beobachtet. MLCT-Übergänge finden, laut Rechnung, auch bei Koordination der Guanidinogruppen an Kupfer(I)-chlorid statt. Anschließende Methylierung der Phenazin- Stickstoffatome senkt die LUMO-Energie des Liganden ab und ein intramolekularer Elektronentransfer vom Metall zum Liganden, der zur Reduktion des Phenazin-Systems führt, wird induziert. So konnten die Grenzorbitalenergien von ttmgph gezielt beeinflusst und somit sowohl Elektronendonor- als auch Elektronenakzeptor-Eigenschaften hervorgerufen werden, wodurch die Ligandenklasse der GFA, die bisher vor allem Elektronendonoren umfasste, um die Elektronenakzeptor-Eigenschaft ergänzt wird.
The adhesion of cells to each other and to a scaffolding matrix is a major feature of multi-cellular organisms. Since misregulation can have fatal consequences, thereto related biological processes, such as wound healing, differentiation and embryogenesis, are tightly regulated in space and time. To get an understanding in these systems it is of big interest to generate dynamically regulated platforms. In order to dynamically and spatiotemporally control integrin-mediated cell adhesion to the extracellular matrix (ECM) several systems have been establish, which can be controlled by an outer stimulus. Nevertheless, these methods are limited by a variety of drawbacks like low resolution, the use of photo-toxic UV-light or tedious synthesis of chemical building blocks. In this thesis, a novel optogenetic tool to control cell-matrix adhesion, combining in a new manner the approaches from material science with optogenetics is presented. By incorporation of naturally occurring ligands for cell-matrix receptors, namely intergrins, like the RGD-sequence or the PHSRN-sequence into optogenetic proteins, they can be applied to mediated cell-surface adhesion. Surfaces coated with the engineered proteins can be switched either once or reversibly, by visible light in their ability to mediate cell adhesion. First, the green light switchable protein CarH from T. thermophilus in order to switch surfaces from an adhesive to a non-adhesive state was employed. The protein monomers form tetramers when the cofactor Cobalamin is incorporated and disassemble into dimers upon green light illumination. By incorporation of the RGD motif into the protein a cell adhesive building block was generated that can be immobilized on surfaces. Upon disassembly of the tetramer, the monomers presenting the RGD motif to the cell are removed and the surface is switched to the non-adhesive state.
In this work, the immobilization of proteins on the surfaces as well as their ability to bind integrin and disassemble under green light in vitro was shown. Further, these results were confirmed in cell adhesion experiments. For the first time, I designed and implemented a green light-switchable system for cell-surface adhesion based on altered ligand presentation. In the second part of my thesis, the blue light-switchable protein domain LOV2 from A. sativa was employed to build a reversible system. This protein domain consists of a small protein core with a long C-terminal Ja-helix, which reversibly unwinds, when illuminated with blue-light. A library of 40 LOV2RGD mutants by insertion of the RGD motif at different positions in the Ja-helix and by combination with further complementing mutations, like the PHSRN motif, was designed. The RGD peptide is caged by the helical conformation in dark and is presented to cells upon unwinding of the Ja-helix under blue light illumination. The library was narrowed to 8 promising mutants through characterization of the ability of the LOV2RGD mutants to bind integrin in dark and under blue light illumination in fluorescence anisotropy measurements. The selected mutants were evaluated for their ability to mediate cell adhesion depending on their switching state, showing significant difference in the spreading area of the cells. Additionally, the reversibility of cell adhesion on such substrates was determined. Finally, the most promising two candidates were evaluated in live cell experiments, showing a significant decrease in the spreading area in dark but not under blue light illumination.
In summary, two protein-based approaches for the dynamic control of cell adhesion using light of two different wavelengths were designed and implemented. The green light-dependent CarH based system can be used to capture and release cells on command, whereas the LOV2 domain-based approach resembles natural timescales for adhesion and can therefore be used in investigations of signaling cascades or other processes involved in cell-matrix adhesion. In conclusion, the herein presented systems can overcome most of the existing drawbacks due to their sensitivity to visible light, their facile way to get produced in high amounts and their high spatial and temporal control.
In dieser Arbeit wurde ein neuartiges duales Kontrastmittel für Computertomographie (CT) und Magnetresonanztomographie (MRT) entwickelt. Das Kontrastmittel lieferte in vitro einen sehr gut sichtbaren Kontrast in CT und MRT Aufnahmen vergleichbar mit dem klinischen Standard. Das CT Kontrastmittel besteht aus Polymernanopartikeln, 2-Methacryloyloxyethyl(2,3,5- triiodbenzoat) (MAOETIB) wurde als Monomer verwendet. Die polyMAOETIB Nanopartikel wurden mit Mikroemulsionspolymerisation synthetisiert. Die Partikelgröße war durch die Variation der Reaktionsparameter in einem Bereich von 30 - 930 nm einstellbar und die Partikel waren in ihrer Größe einheitlich. Die Ergebnisse waren reproduzierbar. Der Polymerisationsprozess wurde unter Variation der Reaktionsparameter evaluiert und der Einfluss der Tensidart, der Tensidmenge, der Initiatormenge, der Durchmischung der Komponenten und der Reaktionstemperatur wurden untersucht. Zur Charakterisierung wurde die Partikelgröße nach der Polymerisation mit dynamischer Lichtstreuung (DLS) bestimmt. Als MRT Kontrastmittel wurden superparamagnetische Eisenoxid (Fe3O4) Nanopartikel (d = 7 nm) zur Verkürzung der T2 Relaxationszeit synthetisiert. Die Eisenoxidnanopartikel wurden über eine basische Fällungsreaktion aus Eisen(II)- und Eisen (III)-Salzen synthetisiert und nach der Reaktion mit Natriumoleat stabilisiert. Der Fällungsprozess wurde durch die Variation der Reaktionsparameter und über die Bestimmung der Partikelgröße nach der Reaktion mit DLS charakterisiert. Durch Variation der Eduktkonzentration, der Stabilisatormenge und der Rührerdrehzahl konnten Fe3O4 Nanopartikel reproduzierbar in einem Größenbereich von 7 - 350 nm hergestellt werden. Um ein duales Kontrastmittel für CT und MRT aus den beiden einzelnen Kontrastmitteln zu erhalten wurden die 7 nm großen Fe3O4 Partikel nach der Herstellung im nächsten Prozessschritt während der Mikroemulsionspolymerisation von polyMAOETIB umschlossen und in die Polymerpartikel einge-kapselt (Fe3O4@MAOETIB). Die Partikelgröße wurde mit DLS bestimmt und war in einem Bereich von 50 - 250 nm durch die Variation der Reaktionsparameter des Polymerisationsprozesses sehr gut einstellbar. Die Ergebnisse waren reproduzierbar. Nach der Herstellung wurden die Komposit Nanopartikel in einem Aufbereitungsprozess gereinigt um ein biokompatibles duales Kontrastmittel für medizinische Zwecke zu erhalten. Zur weiteren Charakterisierung der Partikelgröße, Reinheit und Zusammensetzung der Fe3O4@MAOETIB Nanopartikel wurden die Partikel unter einem Atomic Force Mikroskop und Transmissionselektronenmikroskop bildlich dargestellt. Für die CT und MRT Aufnahmen wurden die Kontrastmittelkonzentration und Zusammensetzung variiert und sowohl der Kontrast für jedes einzelne Bildgebungsverfahren, als auch das CT/MRT-Kontrastverhältnis war in einem großen Bereich einstellbar. Zur Herstellung eines Templates zur Funktionalisierung des dualen Kontrastmittels für eine gezielte biomedizinische Anwendung wurde dem Reaktionsgemisch vor der Polymerisation ein Co-Monomer zugesetzt. Die copolymerisierten Fe3O4@MAOETIB Nanopartikel erlaubten die Funktionalisierung der Partikeloberfläche mit bioaktiven Substanzen. Das Co-Polymer wurde mit Hilfe eines Fluorophors und mit Fluoreszensspektroskopie auf der Partikeloberfläche nachgewiesen. Die Partikel wurden in weiteren Versuchen mit dem Somatostatin Analogon Cystein-Tyr3-Octreotate funktionalisiert und auf eine spezifische Aufnahme durch Somatostatin-Rezeptor positive AR42J Tumor Zellen getestet.
Cell adhesion is essential for the formation and functional integrity of tissues and organs in multicellular organisms. In vertebrates, the epithelium is a specialized tissue that maintains a protective barrier around organs. Epithelial cells are attached to the extracellular matrix and form tight connections with each other via E-cadherin mediated multiprotein complexes called adherens junctions (AJs). In this thesis, I present a method for light-induced dissociation of dimerizer-mediated AJs. This is the first optochemical tool which allows to control the formation and disassembly of adhesion complexes inside living cells with high spatiotemporal precision. The applied dimerizers are bifunctional small molecules that combine ligands of self-labeling protein tags like Halo and SNAP tag, via a photocleavable linker. These synthetic molecules induce dimeric complexes of proteins expressed as fusion constructs with the respective self-labelling tag inside living cells. The complexes are efficiently disassembled by cleaving the dimerizers with light. To utilize photocleavable dimerizers in the context of cell adhesion, I first established a covalent-covalent binding dimerizer to ensure mechanical stability against mechanical forces acting on the induced protein complexes. I showed the potential to control the formation of adhesions complexes via retention, recruitment and complementation approaches for different target proteins. For example, I replaced the catenin binding sites on E-cadherin with a Halo tag and coexpressed them with SNAP-tagged a-catenin that was deficient of the b-catenin binding site. The dimerizer-mediated E-cadherin-a-catenin complexes could restore the epithelial phenotype of human epidermoid carcinoma cells (A431 cells) when induced in a-catenin KOs, but not in E-cadherin deficient A431D cells. I could show that the lack of AJ formation in A431D cells is associated with the failure of recruiting b-catenin. In a-catenin KOs -catenin was indirectly recruited to the dimerizer-mediated E-cadherin-a-catenin complex via lateral clustering with endogenous E-cadherin. This in turn led to the formation of AJ complexes, which are the coupling points for the contractile actomyosin network between epithelial cells. Moreover, the a-catenin KO phenotype could be restored upon light induced dissociation of the dimerizer-mediated AJs via exposure to near UV light. When using a 405 nm laser to cleave the dimerizers, I was able to target the AJs between two adjacent cells with subcellular precision or to create patterns of deactivated cell-cell adhesion in epithelial monolayers. Furthermore, I could prove the mechanical functionality of the reconstituted AJs by performing a correlation analysis of collective monolayer migration and traction force microscopy. Herein, I demonstrated the application of photocleavable dimerizers to study the cellular response to AJ assembly and disassembly at different scales of space and time. Photocleavable dimerizers present several advantages for applications in living cells. Since the proteinprotein interaction depends on external addition of the dimerizers and can be reliably abrogated by breaking the molecule, the setup offers two binary switches for the formation of AJ complexes, virtually without any basal activity. Furthermore, the system is bioorthogonal and light is a trigger that allows to dissociate the protein complexes at subcellular and subsecond resolution. The possibility to combine it with specialized imaging techniques like traction force microscopy renders it a powerful tool to study the mechanobiology of AJs and its contribution to processes in epithelial cell layers like cellular jamming and unjamming, collective migration and stress propagation. This new method will help to gain new insights in the dynamic regulation of cell adhesion in fundamental pathophysiological processes like embryonal development, wound healing or cancer metastasis.
Thanks to their extremely high mobilities, semiconducting carbon nanotubes (CNTs) are a promising material for high speed electronics. Beyond that, CNT networks are inherently flexible and stretchable and can be processed from dispersions resulting in devices with still remarkable electronic properties. They can fulfill many of the various requirements for novel applications including fast switching speeds and high currents at low drive voltages. Depending on the intended use, one or another device property might be more important. CNT networks, processes, and architectures can be tailored to yield devices that can serve the respective purpose. Highly purified semiconducting CNTs are, however, still rather expensive and direct-write techniques are thus preferred to enable variable designs and reduce manufacturing costs. In this work, aerosol-jet printing is investigated as a deposition technique for CNTs that works with small ink volumes but can also be upscaled by parallelization and integrated into high-throughput roll-to-roll printing processes. After the development of printable inks, it is shown that the printing process itself has no influence on the quality of the CNTs although sonication is used to transfer the ink into an aerosol. The electronic properties of CNT networks incorporated in an established transistor structure exhibit reproducibility comparable to other deposition techniques. Moreover, additive manufacturing enables the deposition of several layers on top of each other to increase the overall film thickness up to optically dense films visible to the naked eye. Field-effect mobilities and on-conductances increase and the hysteresis decreases for thicker films compared to dense but thin networks. Based on these findings, CNT films are printed with a thickness of 50–600 nm and vertical charge transport is demonstrated. These films are subsequently sandwiched between electrodes and electrolyte-gating results in doping of CNT films throughout electrode overlap areas of several hundred µm2. The vertical device architecture decouples the printing accuracy from the critical device dimensions while supporting high currents for a small footprint. A comparison of different printed electrode materials reveals the superior properties of printed metals over mixed (metallic and semiconducting) CNTs. Electrodes based on inkjet-printed gold nanoparticles are additionally used on flexible substrates and stable device performance even after several hundred bending cycles is demonstrated for vertical and lateral CNT network transistors. These all-printed devices are promising for further development of electronic circuits that do not require high operating frequencies but rather flexibility, high-currents, and small footprints.
This thesis is focused on the synthesis and modification of [2+3] organic imine cages based on 2,7,14-triaminotriptycene. Many porous cage compounds have been synthesized based on triptycene precursors because of its rigid 3D skeleton and a D3h symmetry. However, modifying the cage compounds with functional groups which may empower the cages is still challenging. In general, post-synthetic modification in pre-synthesized cages and modification of molecular precursors are two main strategies to introduce functional groups into cage compounds. By modifying aldehyde building blocks, ten different side-chains were introduced to the [2+3] terphenyl imine cages. Solubility in organic solvent was improved for all these new cages compared with the unfunctionalized one. Among these cages, the perfluorobutyl chain modified cage exhibits specific surface area up to SABET = 588 m2/g and high Henry selectivity SSF6/N2 = 107 for sulphur hexafluoride over nitrogen, which shows a potential application in the separation of sulphur hexafluoride. Besides the aldehyde building blocks, a new amine building block was constructed by triaminotriptycene and pyridine dicarbonyl dichloride. This new amino building block was used to react with a series of salicylaldehydes with different distance between the aldehyde groups, and the results prove topologies of cage can be affected by the length of the aldehyde precursors. In the third part, through a post-synthetic modification strategy, a carbamate cage was synthesized after two steps based on a [2+3] imine cage (formed by triaminotriptycene and bisphenyl salicylaldehyde). This carbamate cage exhibits high pH stability from pH =-1 to 14 which is proved by NMR spectra, SEM and gas sorption experiments. This is one of the most stable cage compounds reported so far
The photo-induced isomerization of retinal protonated Schiff base (RPSB) inside the protein pocket is one of the fastest (<ps) and most stereo-selective photochemical reactions in nature. The ground state structure of the RPSB and its surrounding protein constructions are thought to be the two most crucial factors to drive this reaction. The investigation of each factor individually was the main goal of this thesis. Anabaena Sensory Rhodopsin (ASR), a recently discovered microbial retinal protein, serves as an ideal system for this study as it binds two structural isomers (all-trans: AT and 13-cis: 13C) of the RPSB within the same protein constructions in its photocycle. In the present work, the photo-induced dynamics of the RPSB in ASR has been explored with the help of time resolved coherent vibrational spectroscopic methods, which monitor the photo-induced sub-ps structural changes of the RPSB. These studies have helped to shed light on the intricate relationship between electronic and vibrational dynamics of the RPSB. In the first half of this thesis, a comparative study showed both electronic and vibrational dynamics are widely distinct for the AT and 13C isomers of the RPSB in ASR. In particular, the 13C isomer exhibited more than five folds faster dynamics than the AT isomer. One possible molecular origin behind this dynamical difference was found by comparing the ground state Raman spectra of the two isomers. It depicted an increase in the amplitude of hydrogen-out-of-plane (HOOP) modes for the 13C isomer, which is usually considered to be an evidence of distortion in the ground state structure for the retinal system. The ground state pre-distortion has been reported as a potential element for the acceleration of the isomerization reaction for the 13C isomer, in analogy with the cis isomers of visual rhodopsin and bacteriorhodopsin. The second half of this work explored the role of the part of protein helix inside the retinal pocket as well as that far away from the pocket. In particular, the replacement of the amino acid residues in vicinity of the RPSB by point mutation caused an acceleration of the reaction rate for the AT isomer, but it had only a minor effect for the 13C isomer of the RPSB. Furthermore, the truncation of the part of the protein, embedded into the cytoplasmic region, affected the formation of the primary photoproduct. All these experimental results lead to two major conclusions of this thesis: (i) the protein constructions govern the retinal isomerization dynamics and (ii) the same protein cage exerts differential interactions on two structural isomers of the RPSB.
Secretion of insulin in response to extracellular stimuli, such as elevated glucose levels and small molecules that act on G-protein coupled receptors (GPCRs), is the hallmark of β-cell physiology. Sufficiently high blood insulin levels are ensured by the coupling of the secretory activity within pancreatic islets. Intercellular and inter-islet coordination are partly mediated by small diffusible ligands of GPCRs within the extracellular space of pancreatic islets. Therefore, insulin release is considered a synchronized multi-cellular process. We show herein that β-cell activity and insulin secretion essentially rely on the presence of extracellular endogenous (autocrine) signaling factors, exemplified by two classes of small cellular metabolites. Trace amines (TAs) are small aromatic metabolites that were identified as low-abundant ligands of the trace amine-associated receptor 1 (TAAR1) in the central nervous system (CNS). In the presented work, we identify TAs as essential autocrine signaling factors that maintain and regulate oscillations of the intracellular Ca2+ concentration ([Ca2+]i oscillations) along with insulin secretion from β-cells via TAAR1. We found that the modulation of endogenous TA levels by the selective inhibition of TA biosynthetic pathways directly translated into changes of [Ca2+]i oscillations and insulin secretion. Application of aromatic amine-withdrawing β-cyclodextrin temporarily reduced [Ca2+]i oscillations. This demonstrates the essential role of TAs for β-cell activity as well as their high metabolic turnover rates. Notably, herein applied inhibitors and synthetic TAAR1 (ant-)agonists are partly approved for the therapeutic modulation of biogenic amine levels within the CNS, and hence for the treatment of common neurological disorders. According to our findings, these drugs even affect β-cell activity and insulin secretion through pancreatic TAAR1. With the discovery of the free fatty acid (FA) receptor GPR40 in β-cells, FAs have come into focus as exogenous insulin secretagogues. However, the role of FAs as endogenous (local) signaling factors of β-cells has not been considered so far. We show herein that lowering endogenous FAlevels in the presence of FA-free bovine serum albumin (FAF-BSA) immediately reduced [Ca2+]i oscillations and insulin secretion. [Ca2+]i oscillations resumed upon exchange of FAF-BSA by buffer or upon restoration of extracellular FA pools. The latter was accomplished by the photolysis of caged FAs on plasma membranes, by the addition of a recombinant lipase or of FA-loaded BSA. Our approach to subordinate β-cell activity and insulin secretion to the presence of autocrine signaling factors of the yet underestimated receptors TAAR1 and GPR40 in the pancreas contributes to a more detailed and complete understanding of the fundamental regulation of β-cell activity and insulin secretion.
Tay-Sachs disease (TSD) is an autosomal-recessive genetic disorder which results in the dysfunction of the metabolic enzyme hexosaminidase A (HexA). It leads to severe lysosomal storage of acidic glycosphingolipid, namely ganglioside GM2, and early fatalities for humans with the infantile on-set form. Despite fifty years of research, to date there is no effective treatment beyond palliative care. It was found that mouse models of HexA deficiency display only moderate GM2 accumulation, which was connected with a late onset neuronal phenotype. Therefore neuraminidases were investigated as possible bypass enzymes for the degradation of GM2 and offer a new opportunity for therapeutic approaches in humans. However, to assess the extent of side effects for such a therapeutic bypass, the substrate specificity and ganglioside (GG) turnover has to be defined in detail. This work presents the development of an HILIC based LC MS2 method as well as mass spectrometry imaging (MSI) using DESI (QqQ)MS2 and MALDI TOF to monitor GG pattern changes in mouse brains. The HILIC MS2 analysis of mouse brain tissue with neuraminidase 3 or 4 deficiency in the background of TSD as well as combined knockouts of GG synthesis enzymes revealed an overlapping but distinct substrate processing for the neuraminidases Neu3 and Neu4. MSI of the same tissue samples displayed similar patterns in spatial neural GM2 accumulation that suggest rather a broad distribution of these sialidases in mouse brain. Proposed neuroinflammation and demyelination in mouse brains of TSD led to a modulated HILIC MS2 method with which hexosylceramide isomer separation of GG precursor β-glucosylceramide (β-GlcCer) and prominent myelin sheath component β-galactosylceramide (β-GalCer) was achieved. Decreased levels of β-GalCer as a marker for demyelination in brains of TSD combined with neuraminidase deficiency could not be observed at the age of 6 month. Furthermore, proof of concept study and screening of various WT mouse tissues revealed the adaptability of this method. Even α-anomeric HexCers could be separated from mammalian β-anomers. In contrast to the mentioned β-HexCers, invariant natural killer T cells are activated most effectively when recognizing galactosylceramide with an α-glycosidic linkage appearing on the cell surface receptor CD1d of antigen presenting cells. One natural bacterial source of this compound in contact with our body is Bacteroides fragilis, a bacterial member of the human gut microbiome. This work highlights the detection and separation of α-GalCer(d17:0;h17:0) in B.fragilis and three other bacteria of the human gut microbiome β-HexCers. Very recent preliminary studies indicate the identification of an α-glycosidic GalCer in the mouse microbiome with the proposed structure of BdS α-GalCer(d18:0;h16:0).
Schnelle und präzise online Messtechnik ist wichtig für die Erforschung von sich schnell verändernden Prozessen, wie beispielsweise der Deaktivierung von Katalysatoren, oder für die Überwachung von chemischen Prozessen für deren effizienten und sicheren Betrieb. Des Weiteren ist die Analyse von Verunreinigungen im Spurenbereich in chemischen Produkten, Nahrungsergänzungsmitteln und Pharmazeutika von größter Bedeutung, um sichere, für den Verzehr geeignete, Produkte zu garantieren. Für solche Anwendungen wird häufig die Selektivität und Empfindlichkeit einer gaschromatographischen (GC) Messung benötigt. Trotzdem bleibt die Charakterisierung von sich schnell verändernden Prozessen mit GC eine analytische Herausforderung, weil GC Methoden oft sehr langsam sind. Darüber hinaus sind GC Detektoren oft nicht empfindlich genug, um die Anforderungen in der Spurenanalytik zu erfüllen. Um diesen Herausforderungen zu begegnen, wurden in dieser Arbeit mehrere GC Verfahren, basierend auf dem Prinzip der Multiplexing Gaschromatographie (mpGC) entwickelt und erforscht. Bei mpGC werden durch die Dosierung aufeinanderfolgender Proben, bevor alle Komponenten von vorherigen Proben die Trennsäule verlassen haben, überlagerte Chromatogramme aufgezeichnet. Wenn die Einzelchromatogramme, die das überlagerte Chromatogramm bilden, sich voneinander unterscheiden ist das berechnete Chromatogramm, das durch Hadamard Transformation erhalten wird, ein gemitteltes Chromatogramm dieser Einzelchromatogramme und enthält so genanntes Korrelationsrauschen. Je mehr sich diese Einzelchromatogramme voneinander unterscheiden, desto höher wird die Intensität des Korrelationsrauschens. Ein Algorithmus für die Unterdrückung von Korrelationsrauschen, verursacht durch die Peaks hochkonzentrierter Komponenten, wurde für die Spurenanalyse in der Prozessanalytik entwickelt. Die Nachweisgrenze für aromatische Verunreinigungen in einem CO2 Strom einer Produktionsanlage wurde im Vergleich zur konventionellen GC Methode von 10 auf 1 ppb verringert. Ein weiterer Algorithmus für die Unterdrückung von Korrelationsrauschen, verursacht durch die systematische nicht-lineare Antwort eines chromatographischen Systems (konstante Unterschiede zwischen den Einzelchromatogrammen unterschiedlicher Dosierungen), wurde entwickelt. Hiermit wurden, im Vergleich zur konventionellen GC Methode, dreimal häufiger berechnete Chromatogramme von Zielkomponenten im Konzentrationsbereich ≤ 1 ppm erhalten. Zusätzlich wurde ein Algorithmus entwickelt, um die Abtastfrequenz des GC Detektors ohne großen Rechenaufwand im berechneten Chromatogramm beizubehalten. Zur vollständigen Vermeidung von Korrelationsrauschen wurde die neue Technik time-division Multiplexing Gaschromatographie (td-mpGC) eingeführt um Hochdurchsatz Messungen durchzuführen, in welchen jedes Einzelchromatogramm von jeder Dosierung reproduziert werden kann. Bei dieser Methode werden verschachtelte Chromatogramme mit basisliniengetrennten Peaks der Zielkomponenten von allen dosierten Proben erzeugt. Diese Technik wurde für die Charakterisierung von verschiedenen katalytischen Reaktionen angewendet, wobei der Probendurchsatz im Vergleich zu konventioneller GC um etwa Faktor 5 erhöht wird. Des Weiteren werden Säulenschaltungen wie Rückspülung und Schnitt, notwendig für die Prozess-GC, erstmals angepasst für die Anwendung in der mpGC.
In chapter 2, the gold-catalyzed C-H annulation of anthranil derivatives with alkynes offers a facile, flexible, and atom-economical one-step route to unprotected 7-acylindoles. An intermediate a-imino gold carbene, generated by an intermolecular reaction, promotes ortho-aryl C-H functionalization to afford the target products. The transformation proceeds with a broad range of substrates under mild conditions. Moreover, the obtained functionalized indole products represent a versatile platform for the construction of diverse indolyl frameworks. In chapter 3, a gold-catalyzed cascade annulation of propargylic silyl ethers with anthranils proceeds through a sequential ring opening/1,2-H-shift/protodeauration/Mukaiyama aldol cyclization. This method offers a regiospecific and modular access to 2-aminoquinolines and other quinoline derivatives under mild conditions and with a broad functional-group tolerance. The conversion is possible on a gram scale, which underlines the synthetic practicability of this methodology. The versatility of the obtained scaffold has been demonstrated by useful postfunctionalization. In chapter 4, gold and platinum-catalyzed counteranion-directed divergent [4+2] annulations have been described, enabling the convergent assembly of densely substituted quinoxaline and quinoxaline N-oxide from benzofurazans and ynamides. A broad scope of functional groups was well tolerated, delivering high regioselectivity. The quinoxaline N-oxides were suitable for the further C-H functionalization. Mechanism studies suggested the counteranion-tuned distinct cyclization pathways toward the corresponding product. In chapter 5, the gold-catalyzed oxidative [2+2+1] annulation of two molecules of ynamide with 2, 3-quinoxaline N-oxide, enables the facile and convergent assembly of fully-substituted symmetric and unsymmetric furan frameworks. A wide range of functional groups is well compatible due to the mild condition. The strategy works also for the intramolecular macrocyclization of di-ynamides for the synthesis of macrocyclic furan derivatives.
Integrin-mediated cell-extracellular matrix (ECM) adhesion and cadherin-mediated cell-cell adhesion are two main interactions that exist in organism. In order to exclude complex interference in living organism to study how these specific interactions affect cell behaviors, integrin ligands or cadherin ligands can be isolated and immobilized on/in biomaterials. In this thesis, integrin ligand RGD peptide and/or E-cadherin ligand HAV peptide were immobilized on 2D surfaces to study the cell adhesion force and the adhesion mechanisms. In part I, cell adhesion force induced by integrin-RGD interaction was studied based on the technology of nitrogen-vacancy (NV) diamond. RGD peptide, which was connected to paramagnetic ion Gd3+, was immobilized onto the NV diamond through PEG chain, generating an NV diamond based force sensor. Spin-spin coupling between Gd3+ and NVs dependent photoluminescence was recorded as a signal when cell traction force exerted. Different immobilization methods were developed, in order to obtain an optimized chemical structure for the force sensor. Cell traction force generated by integrin-induced adhesion was presented as relaxation time T1 map within a cell region. In part II, E-cadherin mimetic HAV peptide was immobilized on continual gold surface or nanopatterned gold surfaces in order to precisely control the immobilized amount. HAV-E-cadherin interaction induced cell adhesion was then studied. The results revealed that the surface immobilized HAV peptide specifically interacted with E-cadherin from cells, inducing the translocation of E-cadherin based adhesion from adherens junction at cell-cell interface to HAV-E-cadherin binding at cell-material interface. This leads to enhanced cell adhesion on the material surfaces and weakened cell-cell contact, which could play important role in wound healing. The HAV-E-cadherin interaction was proved to activate β-catenin signaling pathway, which was the same as E-cadherin based adherens junction at cell-cell interface. These studies according to cell-ligand interactions on specific ligands are helpful to understand the mechanisms of cell adhesion and cell-materials interactions, which also provide new information about cell behavior on biomaterials. These results can be important in the design of new biomaterials. NV diamond based force sensor with respective ligand can be considered as a prospective toolbox to investigate different types of cell adhesions. For example, the HAV peptide in the second section can be included to detect the force of E-cadherin-induced cell-cell adhesion.
Im Rahmen der vorliegenden Dissertation wurden systematische Untersuchungen zur Thermodynamik der Koordinationschemie von Cm(III) in salinaren Systemen bei erhöhten Temperaturen durchgeführt. Fundierte Kenntnisse der aquatischen Chemie der Actiniden bei erhöhten Temperaturen sind wesentlich für den Langzeitsicherheitsnachweis der Endlagerung wärmeentwickelnder Abfälle. Aus diesem Grund wurde im Rahmen dieser Arbeit die Komplexierung von Cm(III) mit anorganischen Liganden im Temperaturbereich von 25 bis 200 °C mittels zeitaufgelöster Laserfluoreszenzspektroskopie (TRLFS) untersucht. Im ersten Teil der Dissertation wurde die Koordinationschemie von Cm(III) mit den schwach wechselwirkenden Liganden Chlorid, der wesentlich für die Endlagerung im Steinsalz ist, Bromid sowie Thiocyanat bis 200 °C untersucht. Für das Cm(III)-Chloridsystem wurden thermodynamische Daten (log β○(T), ΔrH○, ΔrS○) in Abhängigkeit der Temperatur erhalten. Die spektroskopisch auffällige Doppelbandencharakteristik der Cm(III)-Chloridkomplexe wurde auch bei der Koordination von Cm(III) mit Bromid und mit Thiocyanat nachgewiesen und konnte damit eindeutig auf das Hydratationsgleichgewicht von Cm(H2O)9-nXn(3-n)+ und Cm(H2O)8-nXn(3-n)+ zurückgeführt werden. Im zweiten Teil der Dissertation wurde die Hydrolyse von Cm(III) mittels TRLFS untersucht und die Stabilitätskonstanten von Cm(OH)2+ und Cm(OH)2+ erhalten. Untersuchungen zur Temperaturabhängigkeit der Hydrolyse zeigen dabei einen Anstieg der Hydrolysekonstante im Temperaturbereich von 25 bis 80 °C von 1.5 Größenordnungen. Die anhand theoretischer Modelle postulierte Hydrolysespezies Cm(OH)4- konnte auch bei stark erhöhtem pHm und Im spektroskopisch nicht nachgewiesen werden. Zusätzlich hierzu wurde eine Löslichkeitsstudie an Eu(III) als chemischem Analogon durchgeführt, welche die Ergebnisse der Cm(III)-TRLFS untermauert. Der dritte Teil der Dissertation befasst sich mit der Entwicklung einer neuen Hochtemperatur-Spektroskopiezelle, in der nun erstmals spektroskopische Untersuchungen aquatischer Systeme bis 200 °C bei erhöhten pH-Werten (pH > 1) ermöglicht werden. Eine quantitative Studie der Komplexierung von Cm(III) mit Fluorid im Temperaturbereich von 25 bis 200 °C einschließlich der Evaluation von Stabilitätskonstanten für die Spezies CmF2+ und CmF2+ beweist die Anwendbarkeit des neu entwickelten Aufbaus. Die in dieser Arbeit vorgelegten Untersuchungen tragen zu einem verbesserten Verständnis der Koordinationschemie trivalenter Actiniden in natürlichen aquatischen Systemen bei und eröffnen mit der Weiterentwicklung spektroskopischer Messeinrichtungen neue Zugänge zu thermodynamischen Untersuchungen unter Temperaturbedingungen, die im Nahfeld von wärmeentwickelnden Abfällen auftreten können.
The overall topic of this work is the synthesis, experimental and theoretical investigation of various metal bispidine complexes. In the first part of this thesis (chap. 3) the synthesis of several cobalt(II) bispidine complexes and their oxidation with molecular oxygen is described. The formation of a species with a deprotonated nitrogen donor was characterized by X-ray crystallography. Furthermore, magnetic properties of cobalt(II) bispidine complexes were studied. The aerobic methanogenesis of different iron(IV) oxido compounds supported by bispidine ligands is demonstrated in the second part (chap. 4). Moreover, a previously postulated reaction mechanism was substantiated by several techniques. The synthesis and characterization of ruthenium(II) complexes with a range of bispidine ligands is presented in the third part of this thesis (chap. 5). Within this series, one complex was outstanding due to an unexpected color change in solution and was studied in depth. Additionally, a ruthenium(II) half-sandwich complex was used to expand the family of bispidine complexes by introducing an additional coordination sphere. Chapter six focuses on the synthesis of bispidine ligands containing dicarboxylic acids as donor functionalities. The preparation of ligand scaffolds which incorporate malonic acid was examined and this procedure was expanded to the corresponding ligands featuring succinic and glutaric acid. A detailed DFT study investigating the correlation of the pKa values of various donors in the bispidine ligand scaffold and their effect on the spin state of octahedral iron(IV) oxido complexes is described in the fifth and final art of this thesis (chap. 7). Further DFT calculations were conducted to design of a seven-coordinate bispidine ligand system, which is highly promising to promote the formation of low-spin iron(IV) and ruthenium(IV) oxido compounds.
The investigation into how life evolved and cellular complexity developed is an ongoing and highly researched pursuit in science. The central goal of my thesis was to develop a bio-inspired synthetic cell model in order to address this important topic. Towards this end, polymer-stabilized water-in-oil droplets were used as cell-sized compartments for the assembly and testing of specific sets of bioactive components. Moreover, an automated, droplet-based microfluidic technology was implemented for high throughput production of these cell-like compartments and their subsequent manipulation. To resemble the eukaryotic cell architecture, I established a highly-tunable method for the on-demand creation of synthetic cell systems in the form of 3D-supported lipid bilayers, multicompartment systems or free-standing giant unilamellar vesicles (GUVs). To accomplish this, small unilamellar vesicles were encapsulated into polymer-stabilized water-in-oil droplets. By tuning the charge of the inner droplet interface, adsorption of lipids can either be inhibited, leading to multicompartment systems, or induced, leading to the formation of droplet-stabilized giant unilamellar vesicles (dsGUVs) or a combination of multicompartment systems and dsGUVs. Following assembly, the successful release of free-standing GUVs from the polymer shell and the oil phase into physiological conditions was demonstrated. This paves the way towards future applications in which synthetic cell interactions with a physiological environment are crucial. Another significant achievement in this thesis was the assembly of a cellular motility module by the reconstitution of actin cytoskeletal networks and adhesion membrane receptors within droplet-based synthetic cells. These disparate cytoskeletal and adhesive elements were united in the lipid membrane structure of dsGUVs. I showed that this module was able to recapitulate key mechanisms in cell migration – namely cytoskeletal pushing and contractile forces. To date, such synthetic cells containing both cytoskeletal and adhesion-associated functional modules capable of self-propulsion has never been demonstrated. Remarkably, this minimal but functional set of building blocks allowed for the generation of autonomous motion in synthetic cells, and led to the analysis of the mechanism behind this self-propulsion. The powerful microfluidic technology and synthetic cell-like compartments presented in this thesis have the potential for widespread and diverse employment in synthetic biology as they allow for the use of varied sets of both synthetic and natural building blocks. I believe that the scientific achievements presented in this thesis will be of great interest to researchers in fundamental biology, bioengineering and biochemistry.
Self-assembled monolayers (SAMs) are frequently used for interfacial engineering in organic electronics and photovoltaics. The manipulation of injection barriers by introduction of a specific dipole moment at the interfaces between the electrodes and adjacent organic layers (e.g., an organic semiconductor (OSC)) is of a particular interest. This manipulation is usually achieved by selection of a suitable dipolar terminal tail group comprising the SAM-ambient interface, which however has several essential drawbacks. This approach has been recently complemented by embedding dipolar groups into the molecular backbone of the SAMs, with both aliphatic and aromatic SAMs being engineered and mixed aromatic SAMs comprised of the molecules with the oppositely oriented dipolar groups being studied. The major goal of this work is extension and optimization of the embedding dipole approach, along with several other concepts in general context of interfacial dipole engineering. At first, I studied the mixed aliphatic SAMs comprised of molecules which were modified by a dipolar ester group embedded into the alkyl backbone at two different orientations, viz. with the dipole directed upwards and downwards from the substrate. Applying X-ray photoelectron spectroscopy (XPS) as a morphology tool, I could estimate that the mixed SAMs represent homogeneous intermolecular mixtures of both components, down to the molecular level, excluding existence of "hot spots" for charge injection. The composition of the mixed SAMs was found to mimic fully the mixing ratio of both components in solutions from which these SAMs were prepared, which suggests a minor role of the dipole-dipole interaction in the overall balance of the structure-building forces. Varying this composition, work function of the gold substrate could be tuned linearly and in controlled fashion within a ~1.1 eV range, between the ultimate values for the single-component monolayers. As the next task, I studied the applicability of the embedded dipole concept to the different substrates, taking Ag(111) as a representative example. The aromatic SAMs with the embedded pyrimidine group were found to be much more robust in this context as compared to the aliphatic ones (with the embedded ester group), which makes the former systems especially useful in context of the electrostatic interface engineering. In view of these favorable properties, the next task was optimization of the aromatic SAMs with the embedded pyrimidine group. This was achieved by shortening the molecular backbone and excluding aliphatic building blocks. The resulting, optimized monolayers preserved all useful properties of their prototypes in context of dipole engineering but exhibited much better electrical transport properties, which allowed our partners to fabricate organic thin film transistors with high performance and extremely low contact resistance. Another promising tool for tuning the dipole attributes and the respective work function was found to be electron irradiation. This was demonstrated by the example of aromatic SAMs with the embedded pyrimidine group and terminal pyridine group. The observed behavior is presumably related to specific chemical transformations involving the nitrogen atom in these moieties. It leads to several practical implications, including work function lithography, which could be demonstrated by representative patterns. Alternatively, to the embedding of a dipolar group, the selection of a specific anchoring motif was tried in context of interfacial dipole engineering, taking dithiocarbamate-based SAMs as a representative example. The combination of the spectroscopic and work function data with the results of theoretical simulations performed by our partners allowed understanding the structure and electrostatic properties of these monolayers in very detail, paving the way for their applications.
The investigation of electric phenomena occurring in biological cells is the subject of electrophysiological research. The discovery of ionic currents as the origin of membrane resting- and action-potentials led to a comprehensive understanding of various essential biological processes, e.g. trans-membrane transport, signal transduction in the nervous system and muscle contraction. Throughout the 20th century numerous experimental methods for observation of these phenomena have been developed and continuously improved. Precise measurements of intracellular potentials using current- and voltage-clamp based methods have become standard laboratory practice. Despite their huge success, these methods suffer from their invasive nature and inherent workload. Therefore, new methods have been sought, leading to the development of flat microelectrodes, allowing long-term stable electrical measurements with live cells and tissue samples. Arrays of flat electrodes have enabled multi-site and multi-cell measurements, but with the drawback of poor signal amplitude and signal-to-noise ratio. The continuous improvement of nanofabrication methods has enabled the fabrication of vertical nanowires. Such structures have been intensively studied in the past two decades, aiming at the design novel platforms with highly improved electrical properties for intracellular measurements. In this work, fabrication methods for gold nanoelectrode-ensembles are studied in detail. Each step of the manufacturing process for the ensembles is reviewed in detail, resulting in more efficient manufacturing of electrodes with variable diameter and length as well as significantly improving the quality of the obtained samples. The manufactured structures were tested with electrochemical impedance spectroscopy and cyclic voltammetry to evaluate their performance for intracellular recording in in-vitro experiments with live cells.
Metal/organic interfaces as they appear between electrodes and organic semiconductors in organic electronics decisively determine device properties of transistors, light emitting diodes, or photovoltaic cells. The interactions within the organic semiconductor and between organic adsorbate and metallic substrate lead to characteristic properties of the particular interface. These properties, namely the binding strength, the adsorption geometry, and the electronic structure, have been studied with comprehensive surface sensitive experimental methods like high-resolution electron energy-loss spectroscopy (HREELS) and temperature-programmed desorption (TPD). The use of single crystal metal surfaces as substrates and self-assembling small organic molecules as adsorbates lead to insights into structure-property relationships that will contribute to the further development of materials and devices.
The first part of this work investigates the bonding strength between metal substrates and organic adsorbates. With the quantification of binding energies of simple aromatic molecules on coinage metal surfaces by means of TPD, this part enters questions of basic surface science. Besides the delivery of benchmarks of unrivalled accuracy for the further development of computational methods to model binding properties of adsorbate-covered surfaces the focus of this part also lays on the first investigation of the extraordinary coverage dependency of the binding energy of such systems. The second part is about the self-assembly of small-molecule organic semiconductors on metal surfaces, and how this arrangement is influenced by the molecular structure. This part covers the elucidation of adsorption geometries of N-heteropolycyclic aromatic molecules on the Au(111) surface by means of vibrational HREELS. Moreover, electronic HREELS enabled us to get insight into the electronic structure of these interfaces. To maximize the interaction between metal bands and the pi-system of the adsorbate the planar molecules prefer a planar adsorption geometry. This presetting of a flat geometry works subsequently as a template for further layers which leads to a growth mechanism and therefore film structure significantly different from that of the bulk crystal. The last part of this work studies the influence of organic adsorbate films on collective electronic properties of the metal surface with angle-resolved HREELS. Characteristic collective excitations of a two-dimensional electron gas present on the pristine gold surface are strongly influenced in their properties by adsorbate layers, e.g., they show a strongly enhanced intensity and a varied dispersion relation.
Die vorliegende Arbeit befasst sich mit der Synthese und Charakterisierung neuer polycyclischer aromatischer Kohlenwasserstoffe (PAKs). Triptycen als rigide Verbindung wurde als zentraler Baustein für eine lineare Expansion in drei Raumrichtungen zu Azaaceneinheiten verwendet und zudem als endständige Gruppen, um positiv auf die Löslichkeit großer π-Systeme zu wirken. Veratroleinheiten von Hexamethoxytriptycenderivaten konnten selektiv oxidiert werden, sodass resultierende ortho-Chinonfunktionen in Kondensationsreaktionen mit unterschiedlichen aromatischen ortho-Diaminen zu Azaacenen umgesetzt wurden. Neben einer Umlagerungsreaktionen während der ersten Oxidation zu hochfunktionalisierten Fluorenverbindungen, konnte eine Strategie entwickelt werden, die die aromatischen Arme des Triptycens schrittweise und dadurch unterschiedlich erweitert. Die Synthese von 15 unterschiedlichen Derivaten erlaubte eine systematische Studie und zugleich Quantifizierung von intramolekularen Charge-Transfer Übergängen und elektronischen Kopplungen zwischen den Triptycenarmen. Zum ersten Mal konnte ein Hexabenzoovalen (HBO) synthetisiert werden, das aufgrund der sterischen Spannung in seiner Golf-Region eine von der Planarität abweichende, in Lösung stabile Konformation einnimmt. Diese Region erwies sich zudem als reaktiv gegenüber Elektrophilen, sodass sechs unterschiedliche HBOs hergestellt wurden. Neben hohen Quantenausbeuten (Φ bis 58%) konnten trotz der Größe des π-Systems wiesen die Verbindungen gute Löslichkeitseigenschaften auf, die auf die endständigen Triptyceneinheiten zurückzuführen sind. Es wurde zudem der stabilisierende Effekt der Kreuzkonjugation durch peri-Anellierung von Benzolringen in Acen-artige Strukturen untersucht. Durch Pyrenuntereinheiten konnten Phenylen-verbrückte Pyren-Oligomere mit bis zu 20 linear anellierten aromatischen 6-gliedrigen Ringen dargestellt werden. Phenylsubstituenten in sterisch anspruchsvollen Regionen haben zu Verdrillungen geführt, die auch bei höheren Temperaturen in Lösung stabile Konformere bilden. Als weiteres Beispiel wurden 5-gliedrige aromatische Heterocyclen über ihre [c]-Bindung in der KRegion des Pyrens anelliert. Durch die Stabilisierung konnten gewöhnlich instabile Motive wie Isobenzofuran, Isobenzothiophen und Isoindol auf ihre Eigenschaften in Lösung und im Festkörper untersucht werden.
Lignin und Lignocellulose haltige Restbiomassen sind vielversprechende Rohstoffe zur Gewinnung von Treibstoffen und Grundstoffen für die chemische Industrie. Bislang konnte dieses große Potential aufgrund fehlender Verfahren allerdings noch nicht abgerufen werden. Im Rahmen dieser Arbeit gelang es jedoch nach dem Vorbild der direkten Verflüssigung von Braunkohle ein Verfahren zu entwickeln, welches erstmals eine effiziente Umwandlung von Lignin und Restbiomassen zu flüssigen Rohstoffen für die Herstellung von Treibstoffen und aromatischen Grundchemikalien ermöglicht. Zur Realisierung einer Parameterstudie und zur Untersuchung des Prozesses wurden Versuchsanlagen im Labormaßstab, sowie im Technischen Maßstab entwickelt und erprobt. Die Hydrogenolyse von technischen Ligninen konnte damit, sowohl im Labormaßstab, als auch in Technikumsmaßstab erfolgreich realisiert werden. Beim Einsatz von technischen Ligninen aus der Papierindustrie konnten die Ausbeuten an organischem Flüssigprodukt auf über 70 m.% optimiert werden. Den größten Einfluss auf die Umsetzung zeigte die Wahl der Reaktionstemperatur. Es konnte nachgewiesen werden, dass eine gezielte Steuerung der Zusammensetzung des Produktes durch Wahl der Temperatur möglich ist. Das organische Flüssigprodukt besteht zum überwiegenden Teil aus aromatischen Komponenten. Bei Reaktionstemperaturen unter 400 °C erhält man größere Anteile an Methoxy- sowie Hydroxy-substituierte Aromaten, während für Temperaturen über 400 °C der Anteil der sauerstoffhaltigen funktionellen Gruppen sukzessive abnimmt, bis bei 500 °C fast ausschließlich Benzen und dessen Alkylderivate vorliegen. Als wirksame Katalysatoren konnten Eisen- und Molybdänkomponenten identifiziert werden. Besonders Eisen-Schwefelmineralien wie Pyrrhotit sind dabei aufgrund der leichten und günstigen Verfügbarkeit für den Einsatz in einem großtechnischen Prozess geeignet. Da die eigentliche Spaltung der Ligninstruktur vorwiegend thermisch stattfindet, beläuft sich die Wirkung des Katalysators vor allem auf den Transfer von Wasserstoff aus der Gasphase und dessen Bereitstellung in aktivierter Form zur Absättigung der radikalischen, thermochemischen Fraktionierungsprodukte und verhindert so eine Polymerisierung zu koksartigen Feststoffprodukten. Bei der Umsetzung ausgewählter, biogener Reststoffe konnten Flüssigproduktausbeuten von bis zu 65 m.% erreicht werden. Bedingt durch die enthaltenen Polysaccharide entstehen bei der Hydrogenolyse von Biomassen mehr aliphatische Produkte, sowie Kohlenstoffoxide. Basierend auf den experimentellen Ergebnissen konnte eine theoretische Maßstabsvergrößerung durchgeführt werden. Die Auslegung der Anlage erfolgte für eine gemeinsame Verarbeitung von Lignin und erdölstämmigem Vakuumdestillationsrückstand mit einer Kapazität von 500 kt/a. Daraus ergibt sich ein Durchsatz von 65,5 t/h. Das empfohlene Anlagenbudget wurde mit 360 Mio. EUR berechnet. Dabei entfallen die Hauptkosten auf das Reaktionssystem, gefolgt von der Vakuum-Flash-Kolonne und dem Kreislaufgassystem. Die ökologische Bewertung des Verfahrens ergab eine starke Abhängigkeit des Treibhauspotentials und des kumulierten nicht-regenerativen Energieaufwandes von der Art der Wasserstoffquelle. Besonders die Biomassevergasung, als auch die Wasserelektrolyse mit regenerativ gewonnenem Überschussstrom zeigen in Zukunft das Potential die Ökobilanz des Prozesses deutlich zu verbessern, ohne gleichzeitig die Kosten erheblich zu steigern.
Despite its utmost significance in biology, water dynamics has often been the ‘elephant in the room’ in experimental biophysics, owing to the challenges in measuring it. Water dynamics becomes more significant in case of intrinsically disordered proteins (IDPs) as IDPs fall out of the classical ‘structure-function’ paradigm and thus the typical structure-function relationship is modified to a dynamics-function relationship for IDP recognition. No study so far touched the highly important and complex topic on solvation dynamics on protein-protein interactions, let alone IDP recognition. In my PhD thesis my main aim has been to interrogate the interplay between solvation dynamics and binding mechanisms of IDPs involved in the nucleocytoplasmic transport pathway using a combination of steady state and picosecond resolved ensemble fluorescence spectroscopy and single molecule FRET (smFRET). I interrogated surface water dynamics in IDPs and its attenuation upon partner binding using three IDPs from the nucleocytoplasmic transport pathway, Nup153FG, NSP1FG and IBB which share one common binding partner, the nuclear transport receptor (NTR), Importinβ, despite having different binding mechanisms and sites. Nup153FG and NSP1FG belong to the class of IDPs known as FGNups, that constitute the permeability barrier of the nuclear pore complex (NPC). FGNups bind Importinβ through a set of ultrafast transient multivalent interactions retaining its disorder change while IBB forms a helix upon binding Importinβ. Solvent fluctuations in the dynamic Nup153FG-Importinβ complex and NSP1FG-Importinβ complex were unperturbed relative to the unbound state while in the IBB-Importinβ complex substantial relative slowdown of water dynamics was seen. These results directly showed a correlation between interfacial water dynamics and the plasticity of IDP complexes. Based on my results I concluded that solvation retardation poses energy barriers to conformational fluctuations, thus IDPs engage their partners with tunable solvation retardation, which directly correlates to their dynamics in the complex, enabling them to achieve functional diversity. In the context of nucleocytoplasmic transport such differential behavior of these two IDPs can be linked to their functions as well; dynamic FGNup-Importinβ complex likely expedites fast nucleocytoplasmic transport; while stable IBB-Importinβ warrants integrity of the import-complex during a transport event. Additionally I also performed femtosecond resolved fluorescence spectroscopy to explore the dynamics of IBB recognition by Importinβ across timescales spanning over 5 orders of magnitudes from 100fs to ~20ns. Capturing the entire timescale of the dynamics enabled me to look at the nature of these dynamics more closely. Contrary to several hypotheses reporting protein solvation dynamics to be governed by discrete timescales I found that the dynamics could be well explained by a power law type of relaxation suggesting a possible entanglement of the different timescales. This provides new insights into the nature of protein solvation dynamics in general as well in the context of IDP recognition.
Over the past decades, conjugated polymers (CPs) have been applied to electronic and photonic devices, expanding this field in material chemistry. One recent area of interest on CPs comprises their application in the development of chemical sensors. That considered, the focus of this work was on the construction of water-soluble conjugated polymer-based chemical tongues and their application in sensing. Initially, four water-soluble poly(para-phenyleneethynylene)s (PPEs) were prepared, two of which reported for the first time on the basis of this work. The two novel PPEs are negatively charged, posses benzylic side chains, and react sensitively towards 2,4-dinitrotoluene and 2,4,6-trinitrotoluene. Twelve different nitro-aromatics were successfully discriminated by a small sensor array consisting of either the two novel PPEs or additional two neutral PPEs, using linear discriminant analysis to treat the data. A sensor array based on a combination of positively charged water-soluble PPEs, or green fluorescent protein (GFP), and three metal ions (Fe2+, Co2+, and Cu2+) at different pH values was also reported for the first time. The array discriminates all of the 20 natural amino acids in water. The sensitivity of the array was dramatically improved by addition of further sensor elements, and an optimized eight-member sensor array that discriminates all of the 20 amino acids with 100% accuracy was created. The results show great coherence upon grouping the amino acids according to their type: hydrophobic, polar and aromatic. Finally, two types of hypothesis-free sensor arrays, consisting of either three cationic PPEs or the same PPEs complexed with cucurbituril[8] (CB[8]) have been constructed. The PPE-CB[8] array discriminates tea-based amino acids and methylxanthine alkaloids (caffeine, theophylline and theobromine) through a displacement mechanism, while for the PPE-alone array, only caffeine, theobromine and theophylline elicited relevant fluorescence response. Both the PPE and PPE/CB[8] arrays effectivelly generated discriminating patterns for teas on the basis of differential fluorescence quenching, and allowed the differentiation of teas by brand, price, quality grades, and geographic origins. All together, the results herein obtained represent a significant contribution to the development of the field of chemical sensors based on CPs.
In chapter 2, a novel and atom-economical synthesis of fully substituted 4-aminoimidazoles via gold-catalyzed selective [3+2] annulation of 1,2,4-oxadiazoles with ynamides is achieved. This protocol represents a new strategy to access α-imino gold carbenes, which corresponds to an unprecedented intermolecular transfer of N-acylimino nitrenes to ynamides. Moreover, the reaction proceeds with 100% atom economy, exhibits good functional group tolerance, and can be conducted in gram scale.
Chapter 3 describes a novel, short, and flexible approach to diverse N-doped polycyclic aromatic hydrocarbons (PAHs) through gold-catalyzed π-extension of anthranils with o-ethynylbiaryls as reagents. This strategy uses easily accessible starting materials, is simple due to high step and atom economy, and shows good functionalgroup compatibility as well as scale-up potential. Mechanistically, the tandem reaction is proposed to involve a nucleophilic addition/ring opening/regiospecific C–H annulation/protodeauration sequence terminated by a Friedel-Crafts-type cyclization. Photophysical studies of the products indicated violetblue fluorescence emission with quantum yields up to 0.45.
In chapter 4, a facile, site-selective and divergent approach to construct 2-aminopyrroles and quinoline-fused polyazaheterocycles is enabled by a simple gold(III) catalyst from ynamides and anthranils under mild reaction condition. This one-pot strategy uses readily available starting materials, proceeds in a highly stepand atom-economical manner, with broad substrate scope and scale-up potential. Notably, the key element of success in the present tandem reaction is a catalyst-directed preferable quenching of the in-situ generated gold carbene intermediates by a nucleophilic benzyl/2-furanylmethyl moiety on the ynamides as an alternative to the known C–H annulation leading to indoles.
In chapter 5, a gold-catalyzed regioselective cyclocarboamination of ynamides with 1,3,5-triazinanes provides facile and modular access to valuable 5-aminotetrahydropyrimidines in good to excellent yields. It constitutes an unprecedented yet challenging annulation of ynamides with unstrained saturated heterocycles. This new protocol is distinguished by easy operation, readily available starting materials, stable four-atom building units, good functional-group compatibility and scaling-up potential. The preliminary mechanistic studies indicate that the present intermolecular cyclocarboamination arises from a pseudo-threecomponent [2+2+2] cycloaddition.
The aim of this thesis is to combine experimental and computational methods in order to gain a deeper understanding of the ligand field effects of lanthanide(III) ions. Because the magnetic properties of mononuclear lanthanide complexes are determined primarily by the electronic structure of the isolated ion, a thorough understanding of the ligand field effects is essential in order to rationally design new complexes to function as single molecule magnets (SMMs). In this work a variety of experimental techniques are utilised in combination with a detailed theoretical analysis by way of a highly powerful ab initio approach. The approach involves the determination of CASSCF wave functions, from which spin-orbit coupled states are calculated by construction of a state interaction matrix. The magnetic properties are determined by the effective Hamiltonian theory, which yields parameters such as the electron-Zeeman interaction g and also ligand field parameters. Importantly, the validation of the ab initio approach is illustrated not only by comparison with magnetometric results but also by using the highly sensitive optical spectroscopic technique, magnetic circular dichroism. Thorough ligand field analysis of the experimental data was possible utilising the ab initio calculated ligand field parameters, illustrating the accuracy of the computational method.
The first part of this thesis investigates the sensitivity of the electronic structure of terbium(III) and dysprosium(III) to very slight changes of the ligand field. Two different ligands, L1 and L2, were employed that provide coordination spheres comprised of eight homoleptic oxygen donors, meaning the differences in the ligand field of these complexes is purely of geometrical origin. Differences in the magnetic susceptibility of all four complexes revealed different splitting of the ground state J multiplet induced by the two ligand fields. Loose powder magnetisation measurements indicated differences in the ground state g values, which were in qualitative agreement with the calculated values. High frequency electron paramagnetic resonance (HF-EPR) studies of the terbium(III) complexes provided insight into the composition of the ground state MJ levels. Ab initio calculations are utilised to rationalise the experimental results and further illustrate the effect of the structural features on the electronic and magnetic properties of the different complexes. Magnetic circular dichroism (MCD) spectra of the dysprosium(III) complexes illustrate fine details highlighting the differences in the splitting of the J multiplets and allowed for a thorough ligand field analysis. The analysis utilised the ab initio calculated ligand field parameters in order to produce a reasonable fit of the experimental data, illustrating the accuracy of the computational methods. The calculated properties indicated no significant SMM behaviour of the different complexes, leading to the design of a new set of ligands based on L1, which are explored in the second part of this thesis.
The second part of this thesis focuses on the difference in f-electron density of dysprosium(III) and erbium(III), and how more pronounced differences in the ligand field affect the electronic structures of the oblate and prolate ions, respectively. Two ligands were designed that, upon coordination to a lanthanide(III) ion, provide strong electron density in the axial L3 and equatorial regions L4, respectively. The calculated properties indicate that the more strongly axial ligand field promotes strong anisotropy and a large magnetic blocking of dysprosium(III), whereas the strongly equatorial ligand field induces extensive mixing of the MJ states and a large transversal moment. Conversely, the properties of the complexes of erbium(III), having a prolate f electron density, produce the opposite effect. MCD spectra of dysprosium(III) and erbium(III) complexes of ligands L3 and L1 are compared. As in the first part of the thesis, a thorough ligand field analysis was possible utilising the ab initio methods.
Die Chemie des Bors wird fast ausschließlich von seinem elektrophilen Charakter geprägt. Daher lassen sich viele der seit Jahrzehnten etablierten Hydroborierungs- und Borylierungs-Reaktionen lediglich auf ungesättigte organische Substrate anwenden. Eine der größten Herausforderungen der Bor-Chemie ist deshalb die Darstellung von nukleophilen Bor-Reagenzien. Trotz großer Fortschritte der letzten Jahre ist die Anzahl der isolierbaren nukleophilen Bor-Verbindungen überschaubar. Durch die starke Lewis-Basizität bizyklischer Guanidinate wird ein außerordentlich hoher Elektronenreichtum der Diborane erreicht. Zusätzlich wird durch den verbrückenden Bindungsmodus der Schritt der Dehydrokupplung über eine Vororientierung der Boratome begünstigt. Das doppelt guanidinatstabilisierte Diboran(4) verfügt über eine einzigartige Reaktivität, die durch den nukleophilen Charakter der B–B-Bindung bestimmt wird. In der vorliegenden Arbeit gelang durch Einführung neuer Substituenten die Isolierung und Charakterisierung einer Reihe von nukleophilen Diboran(4)-Verbindungen. Bei diesen und bereits literaturbekannten Diboranen wurde der Einfluss der Substituenten auf die Eigenschaften der B–B-Bindung auf Basis experimenteller und theoretischer Methoden systematisch untersucht. Dabei konnte gezeigt werden, dass eine hohe Nukleophilie des Moleküls nicht zwingend eine nukleophile B–B-Bindung zur Folge hat. Die Substituenten der beiden Diborane [HB(μ-hpp)]2 und [nBuB(μ-hpp)]2 verfügen über keinen +M-Effekt und weisen nach eingehender Analyse quantenchemisch berechneter Parameter ausschließlich die B–B-Bindung als nukleophile Position auf. Im Gegensatz dazu wird die Nukleophilie von [(Me2N)B(μ-hpp)]2 primär von den freien Elektronenpaaren der Amin-Gruppen geprägt. Weiterhin wurden mehrere Synthesemöglichkeiten asymmetrischer Diboran(4)-Verbindungen untersucht. Dabei erwies sich die Darstellung von [(PhCC)B(μ-hpp)2BH] über das phosphoniumstabilisierte Diboranyl-Kation [HB(μ-hpp)2B(PCy3)]+ als die beste Methode. Zusätzlich konnte durch die Darstellung von [(PhCC)B(μ-hpp)2B(PCy3)]+ die Bildung des intermediären Diboranyl-Kations [(PhCC)B(μ-hpp)2B]+ bestätigt werden. Oxidationsexperimente an [HB(μ-hpp)]2 führten zum Dimerisierungsprodukt [H4B4(μ-hpp)4]2+. Als Mechanismus zur Bildung wurde eine Einelektronen-Oxidation der B–B-Bindung mit Umlagerung zu einem Bor-zentrierten Radikal-Kation postuliert, welches anschließend über Radikalkupplung dimerisiert. Das intermediär auftretende Radikal-Kation [HB(μ-H)(μ-hpp)2B]•+ konnte mit TEMPO abgefangen werden. Die gewonnen Erkenntnisse gewähren ein grundlegendes Verständnis des nukleophilen Charakters von B–B-Bindungen. Dadurch wird die Basis für weitere Folgeexperimente geschaffen, mit denen der nukleophile Charakter der Diborane(4) weiter ausgebaut und für breitere Anwendungsgebiete geöffnet werden kann.
In this thesis, porous organic polymers were synthesized on the basis of tetrahedral monomers of the group IV. Their optical properties and porosities were investigated and specifically tuned by the choice of monomers, reaction conditions or by postmodification. First, a tetrahedral, silicon-centered monomer with terminal bromides was employed for the Yamamoto homocoupling (Scheme 1, left). The alkyne functionalities at the central atom allow for the cleavage of the silicon-carbon-bond, after which the organic fragments of the insoluble network were identified. The results were compared to a formally structural identical material that was synthesized via an alternative synthesis route. Furthermore, tetrakis(4-ethynylphenyl)stannane was employed in a screening under Sonogashira- Hagihara conditions (Scheme 1, right). Fluorescence and porosity of the formally identical networks were dependent on the chosen reaction conditions. The materials were cleaved at the tin-carbon bonds with chloroacetic acid to analyze the organic linkers and examine the completeness of the polymerization. In addition, networks were screened for the influence of the central atom in the tetrahedral monomer. The elements of group IV (M = C, Si, Ge, Sn) were used as central units. Irrespectively of the applied conditions, the carbon-centered materials revealed the highest BET surface areas whereas the tin-centered ones yielded the lowest. Nevertheless, the absolute dimension of the surface area is related to the chosen synthesis protocol. Moreover, postmodification of porous polymers derived from AA’-polymerization of varying amounts of silicon- and tin-centered monomers was realized. They were selectively cleaved at the tin-carbon bonds to release fractions of the linkers and to tune porosity and emission color. Finally, sulfur containing polymers were synthesized from tetrakis(4-ethynylphenyl)silane for implementation as cathode material in lithium sulfur batteries. The networks showed moderate activities with capacities up to 750 mAh/g.
Die vorliegende Dissertation beschäftigt sich mit der Synthese und Charakterisierung der guanidinofunktionalisierten Naphthyridine 2,7-Bis(tetramethylguanidino)-1,8-naphthyridin (1), 2,7-Bis(N,N‘-dimethylethylenguanidino)-1,8-naphthyridin (2), 2,7-Bis(N,N‘-diisopropylguanidino)-1,8-naphthyridin (3) und 3,6-Dibrom-2,7-bis(tetramethylguanidino)-1,8-naphthyridin (4) und deren Verwendung als Liganden zur Herstellung von mehrkernigen Kupferkomplexen. Die optischen Eigenschaften (Absorptions- und Emissionsspektren sowie Quantenausbeuten) der Liganden wurden untersucht. Durch Reaktion mit [Cu(CH3CN)4]BF4 konnten mit 1, 2 und 4 die Cu4-Komplexe [Cu4(1)2](BF4)4·2 CH3CN, [Cu4(2)2](BF4)4 und [Cu4(4)2(H2O)2(CH3CN)2](BF4)4 dargestellt werden, die kurze Cu···Cu Abstände von 2.42-2.55 Å aufweisen. Die zunehmende Lewis-Acidität der Kupferzentren, welche von [Cu4(2)2](BF4)4 über [Cu4(1)2](BF4)4·2 CH3CN nach [Cu4(4)2(H2O)2(CH3CN)2](BF4)4 größer wird, führt zu einer Koordination von Coliganden, deren Bindungsenergie in gleicher Weise zunimmt. Strukturell ist dies mit einer Änderung von einer linearen Anordnung der Kupferatome hin zu einer Zick-Zack-Kette verbunden. DFT-Rechnungen zeigten für [Cu4(1)2](BF4)4·2 CH3CN, dass HOMO und LUMO an den Liganden zentriert sind. Die energetisch niedrig liegenden Übergänge im UV/Vis-Spektrum konnten den ligandenzentrierten elektronischen Anregungen zugeordnet werden. Die Rechnungen ergaben, dass bei höherer Energie ein Metall-Ligand Charge-Transfer (MLCT) existiert. Während im Festkörper zwei Acetonitrilmoleküle an die Metallkette koordinieren, konnte anhand von NMR-Experimenten gezeigt werden, dass in Lösung eine Dissoziation stattfindet. Ein Austausch der Coliganden gegen neutrale Liganden oder Halogenidanionen konnte nicht beobachtet werden, wohingegen [Cu4(4)2(H2O)2(CH3CN)2](BF4)4 mit Cl--Anionen zu [Cu3(4)2(CuCl2)](BF4)2 reagierte. NMR-Experimente zeigten, dass [Cu4(1)2](BF4)4·2 CH3CN ein geeigneter Katalysator für die Azid-Alkin-Click-Reaktion ist. Die Reaktion von [Cu4(1)2](BF4)4·2 CH3CN mit I2 bzw. CoCp2 führte zur Zersetzung des Komplexes, wobei die Cu3-Komplexe [Cu3(1)2](I5)2(I3) und [Cu3(1)3](BF4)3 als Produkte isoliert werden konnten. Durch Umsetzung von [Cu4(1)2](BF4)4·2 CH3CN mit CuX2 (X = Cl, Br) wurden hexanukleare, diamagnetische Komplexe des Typs [Cu4(1)2(CuX2)2](BF4)2 erhalten, in denen CuX2--Einheiten an die Cu4-Kette koordinieren. Für 4 konnte ein Cu6-Komplex durch Reaktion von [Cu4(4)2(H2O)2(CH3CN)2](BF4)4 mit Iodbenzoldichlorid synthetisiert werden. Die Reaktion mit Kupfer(I)-halogeniden führte bei 1 zur Bildung des Komplexes [Cu3(1)2Br2]Br, während bei 3 der Komplex [(CuCl)23] isoliert wurde. Darüber hinaus konnten mit 3 auch die beiden Zinkkomplexe [(ZnCl2)3] und [(ZnBr2)3] hergestellt werden. Quantenchemische Rechnungen zeigten, dass durch Variation des Metalls in [M4(1)2]4+ (M = Cu, Ag, Au) das HOMO seinen Charakter von einem ligandenzentrierten in [Cu4(1)2]4+ zu einem metallzentrierten Orbital in [Au4(1)2]4+ ändert, was besonders für eine Photoredoxkatalyse interessant ist. Experimentell wurde durch Umsetzung von 1 mit AgPF6 der trinukleare Komplex [Ag3(1)2](PF6)3 erhalten; ein Goldkomplex konnte bisher nicht isoliert werden.
Approaches to novel diphenylacetylene derivatives and related compounds with restricted rotation of the phenyl rings have been developed. Since mutual overlapping of molecular orbitals specifies the electronic communication between aromatic π-systems, regulation of the conformation within a molecule gives control over conductive and photophysical properties of tolane. Amide- and ester bound tethers have been used. The first one resists aggressive factors better, compared with ester. Introduction of amide-functionalized tethers have been demonstrated by synthesis of two bridged tolanes; a novel double-bridged 1,4-bis(phenylethynyl)benzene (I) was prepared.
In addition, synthetic approaches leading to multi-gram amounts of bifunctional tolanophanes are shown, ready for further derivatization. TIPS-acetylene derivatives possessed not only outstanding emissive, but also interest-evoking structural properties, expressed in folded cyclic dimers with electronically interacting chromophore units by means of π-π-stacking. Considering this, series of cyclic oligomers have been synthesized and investigated.
From previous studies it was known, that in the solid state twisted tolanophanes planarize after excitation due to a special arrangement of the electronic states. Introduction of the second tether into the tolanophane molecule gives a more rigid molecule (II) and leads to a better understanding of the emissive properties of tolane chromophores. Compound II showed a twisted conformation in the excited state. Figure I. Selected synthesized and studied molecules.
Further, bifunctional tolanophanes have been used for copolymerization (III). Bridged derivatives of 1,4-diphenyldiacetylene have been investigated, as they are usual defects in poly(para-phenyleneethynylene)s and can significantly affect their properties. Emissive ability of these substances appeared to be not distinct; they showed weak photophysical response on twisting.
Desinfektion ist im Bereich der Schwimmbadwasseraufbereitung obligatorisch, um aus Sicht des Infektionsschutzes die Sicherheit der Badegäste zu gewährleisten. Das am häufigsten eingesetzte Desinfektionsmittel ist freies Chlor (FAC), das aufgrund seiner hohen Reaktivität auch mit Verunreinigungen in verschiedener Form reagieren kann. Dabei entsteht eine Vielzahl an sogenannten Desinfektionsnebenprodukten (DNP). Bisherige Forschungen haben sich mit der Identifizierung der unterschiedlichen DNP, deren Entstehung bei Verwendung verschiedener Aufbereitungstechnologien, den absoluten Konzentrationen im Wasser und in der Luft sowie den Auswirkungen auf den Menschen befasst. Dementgegen gibt es zu der Chemie hinter der Entstehung kaum Untersuchungen. Die vorliegende Arbeit ist die erste umfassende und systematische Studie, die die Entstehung von DNP aus verschiedenen Quellen und darüber hinaus die konkrete Kinetik auf molekularer Ebene untersucht. Zunächst wurde der Eintrag von Verunreinigungen durch Badegäste bestimmt, der im Schnitt 230 mg gelösten organischen Kohlenstoff (DOC), 40 mg partikulären organischen Kohlenstoff (PaOC), 1010 Bakterien (KBE) und 240 mL Urin pro Person beträgt. In weiteren Untersuchungen wurde das Trihalogenmethan-Bildungspotential aus den o. g. Verunreinigungen zu 100 mg Chloroform pro Person bestimmt, das zu 63 % Urin und zu 35 % Verunreinigungen von der Haut zugeordnet werden konnte. Anschließend wurden die Kinetiken von 13 potentiellen Vorläufer-Verbindungen sowie von Gemischen untersucht und Zitronensäure als wichtigster Vorläufer für die Bildung von Chloroform identifiziert. Die Ergebnisse zeigten zudem, dass die Chloroform-Bildung aus Zitronensäure ein verhältnismäßig langsamer Prozess ist (Ausbeute < 60 % nach vier Tagen). Diese Ergebnisse, insbesondere die Kinetiken, wurden im Rahmen des EU-Projekts „Intellipool“ in ein Modell zur Vorhersage von DNP-Konzentrationen in Schwimmbädern implementiert, das bereits zur Optimierung der Technik von Schwimmbadanlagen genutzt wird.
The aim of this thesis was to allow for the processing of large-scale atmospheric 14CO2 samples into graphite targets for high-precision analysis on an accelerator mass spectrometer (AMS) and to further develop the sampling itself, which takes place throughout Europe within the Integrated Carbon Observation System (ICOS) network. For the first part, a largely automated Extraction and Graphitisation Line (EGL) was developed at the ICOS Central Radiocarbon Laboratory(CRL); the construction at the institute workshop was guided and process behaviour and target quality was characterised. Process fractionation in δ13C from the whole-air sample flask to the graphite target cannot be distinguished from zero with (0.04 ± 0.09)‰. The deviation from the absolute canonical Δ14C scale was determined to (0.7 ± 0.5)‰. It was shown that the reproducibility of Δ14C results from processed air samples is at ±1.9‰ or below for the final graphitisation parameters. Compatibility tests provided a deviation of the results of samples processed with EGL and analysed by the AMS at the Curt-Engelhorn-Centre Archaeometry (CEZ) from the results of the CRL Low-Level Counting (LLC) laboratory of (2.2 ± 0.9)‰. The reason for the deviation is currently unknown. For the further development of 14CO2 sampling, a new trajectory-triggered strategy was simulated in an atmospheric forward modelling system. It was shown that weak fossil CO2 signals from emission hotspots at four German ICOS stations can be amplified by a factor of up to 7, while the signal background is estimated with parallely taken samples.
Die vorliegende Arbeit befasst sich mit der Darstellung und Untersuchung poröser Materialien basierend auf unterschiedlich 1,8,13-substituierten Triptycenen. Triptycen erwies sich aufgrund seiner rigiden Struktur und der Möglichkeit zur selektiven Substitution bereits vielfach als geeignetes Strukturelement zur Herstellung von diskreten organischen Käfigverbindungen oder porösen Netzwerkmaterialien. Durch die Optimierung und Aufskalierung der Synthese eines zentralen Triptycen-Trisalicylaldehyds konnte die zehnstufige Synthese im Multigramm-Maßstab durchgeführt werden. Auf Grundlage dessen waren kubische [4+4]-Käfigverbindungen mit spezifischen Oberflächen von bis zu SOBET = 1014 m2/g zugänglich, welche zu den höchsten bislang berichteten Werten für poröse Materialien aus diskreten organischen Molekülen in der amorphen Phase zählt. Mittels Kondensation des Tritpycen-Trissalicylaldehyds mit ortho-Phenylen- oder Triptycendiaminen in Gegenwart eines Metallsalzes wurde eine Serie von isostrukturellen trinuklearen Metallkomplexen mit Zn2+-, Ni2+-, Cu2+-, Pd2+- und Co3+-Zentren hergestellt, deren Festkörperstrukturen Metall-Metall-Abstände um 6.5 Å aufweisen, sodass synergistische Wechselwirkungen mit kleinen Molekülen wie Kohlenstoffdioxid resultieren können. Zur Integration der trinuklearen Anordnungen in porösen Materialen wurden Metall-assistierte Salphen-organische Netzwerke (kurz MaSOFs) hergestellt. Diese zeigten spezifische Oberflächen von bis zu SOBET = 892 m2/g und hohe IAST-Selektivitäten von bis zu "S" _(〖"CO" 〗_"2" "/" 〖"CH" 〗_"4" ) = 13 für Kohlenstoffdioxid über Methan, bzw. "S" _(〖"CO" 〗_"2" "/" "N" _"2" ) = 70 von Kohlenstoffdioxid über Stickstoff, welche die Materialien für Anwendungen in der Separation von Gasgemischen qualifizieren. Des Weiteren konnten erste Schritte zur Stabilisierung von Imin-Käfigverbindungen unternommen werden. Studien entsprechender Modellverbindungen führten zu einer Serie von fluoreszierenden BF2-Komplexen (Φ bis 37%) mit großen Stokes-Verschiebungen und mechanochromem Verhalten. Zudem lieferte die Derivatisierung eines 1,8,13-Trimethoxytriptycens einen molekularem Baustein für eine Serie tetraedrischer Boronsäureester-Käfigverbindungen mit spezifischen Oberflächen von bis zu SOBET = 511 m2/g und unterschiedlichen Substitutionsmustern.
A chromophore is a molecule that appears colorful to the human eye in sunlight. The recognized color is related to the wavelength of light, or in face of particle-wave dualism, to the energy of photons absorbed by the molecule. Light absorption, also called photo-excitation, corresponds to a transition of the molecule from its ground state to an electronically excited state. The energy gained during excitation allows the molecule to undergo manifold chemical and physical processes, giving rise to the presents of a plethora of chromophores in nature and technology. In order to rationalize these light-induced processes, the involved electronic ground and excited states of a molecule can be investigated by means of quantum-chemical methods. These allow to determine the energy and properties of the molecule in its different electronic states. An important step in the interpretation of the results of such calculations is to determine the character of an excited state, which is directly connected with many properties, such as the interaction with an environment, reaction pathways and deexcitation processes. The aim of this work is to develop new tools for the investigation of excited states, their characters, and quantum-chemical methods for their description. The central idea is to rationalize excited states in terms of correlated electron-hole quasiparticles, i.e. excitons, a concept from solid-state physics. The working hypothesis is to identify the one-particle transition density matrix (1TDM) as an effective electron-hole (i.e. exciton) wave function. The character of an excited state can in turn be determined from the calculated exciton properties. These properties are computed by evaluating expectation values of the exciton wave function with respect to operators of interest. In practice, several protocols have been developed, which characterize spatial and statistical properties of the electron-hole quasiparticle. These excited-state descriptors are directly comparable to results from solid-state physics as well as from experiments, emphasizing their physical significance. In contrast to standard approaches, deriving excited-state characters from exciton properties has some immediate advantages. Different types of excited states such as charge-transfer, Rydberg or local, can be directly determined according to a few exciton descriptors. The use of quantitative descriptors is comparably unbiased, since it does not rely on an ambiguous visual interpretation of molecular orbitals (MOs) involved in the electronic transition. Moreover, exciton descriptors allow to investigate excited states that are poorly represented in the MO picture. Since exciton analysis is based on the 1TDM, which is a method-independent quantity, the descriptors allow to investigate quantitative differences between the descriptions of excited states at various levels of theory. The presented approach is particularly relevant for molecules featuring excited states with exciton character. A particularly important substance class are large π-conjugated organic molecules. Here, delocalized π-electrons play a decisive role and require precise description of correlation effects, posing a challenge for quantum-chemical methods. The scientific interest in large π-conjugated organic molecules is triggered by their special electronic properties, which are applied in organic electronics. In the course of this work, a variety of excited states of extended π-conjugated organic molecules is calculated by means of correlated ab initio methods as well as by time-dependent density functional theory (TDDFT) and subjected to exciton analysis. In Chapter 3, exciton sizes are investigated for excited states of poly(para phenylene vinylene) (PPV) oligomers and polyacenes. Excited states are found to differ in exciton sizes depending on irreducible representations and multiplicities. In Chapter 4, PPV is thoroughly investigated as a prototypical organic semiconductor to rationalize its exciton properties from a quantum-chemical perspective. The emergence of excitonic states is examined for a series of PPV oligomers with different chain length. It is found that exciton formation takes place for oligomers with four or more building blocks. To gain insight into the spectroscopic properties of the PPV polymer, the largest still computationally feasible representative, the octamer (PV)7P is studied intensely. A systematic analysis of forty excited states allows to examine their exciton characters in detail. The investigated excitons are found to have well-defined structures that can be rationalized in terms of Frenkel and Wannier exciton models. The results are in good agreement with experimental findings and band-structure calculations of PPV. To investigate the effects of exciton formation for a more chemically diverse set of molecules, a variety of aromats as well as heteroaromats are investigated in Chapter 6. It is found that the first excited state of these π-systems has a uniform exciton character with an exciton size converging towards 7 A very similar to the trends in PPV. The explicit chemical structures and presence of heteroatoms have surprisingly little influence on this character. Shifting the focus to methodological aspects, Chapter 6 reveals the influence of exchange-correlation (xc) functionals on the description of exciton properties in TDDFT. By comparing exciton sizes and electron-hole correlation coefficients, it is found that there are major differences in the excited-state description for the tested xc-functionals. The trends amongst different xc-functionals suggest that these deviations are mostly governed by the amount of nonlocal orbital exchange (NLX) in the xc-functionals. This finding is of great significance showing that a single parameter can induce a complete change in the electron-hole interaction from repelling (anti-correlated) to strongly attractive (correlated). A more general investigation of the same effect is presented for Tozer's benchmark set in Chapter 5. This set is composed of a broad selection of molecules featuring different types of excited states and designed to develop diagnostic tools for TDDFT. It is well-known that excited states which involve nonlocal electron transitions, such as charge-transfer, Rydberg or π → π* states of extended π-systems, show systematic errors in excitation energy for different types of xc-functionals. Here, exciton descriptors reveal that these errors are related to substantial differences in the description of the respective excited states by the xc-functionals. Since exciton descriptors are able to identify all problematic cases, they are suggested as diagnostic tools for TDDFT.
Ultimately, Chapter 7 focuses on the evaluation of excited-state methods. For this purpose, the selection of methods is extended to include also equation-of-motion coupled-cluster singles doubles (EOM-CCSD) and a diverse set of applications is investigated. Exciton properties calculated with correlated ab initio methods (ADC(2), ADC(3) and EOM-CCSD), as well as TDDFT are compared, revealing strengths and weaknesses of the methods in different applications. The most important outcome of investigating exciton properties is that accuracy in terms of excitation energies is not necessary a measure for the quality of description of the underlying wave function and properties of a system. In fact, the best agreement in terms of exciton properties with respect to high level ab initio data is obtained with an xc-functional that is the least accurate in terms of excitation energies for several examples. The presented approach is publically available as open-source code package libwfa and integrated in the Q-Chem program package.
State-of-the-art methods for the calculation of electronic structures of molecules predominantly use Gaussian basis functions. The algorithms employed inside existing code packages are consequently often highly optimised keeping only their numerical requirements in mind. For the investigation of novel approaches, utilising other basis functions, this is an obstacle, since requirements might differ. In contrast, this thesis develops the highly flexible program package molsturm, which is designed in order to facilitate rapid design, implementation and assessment of methods employing different basis function types. A key component of molsturm is a Hartree-Fock (HF) self-consistent field (SCF) scheme, which is suitable to be combined with any basis function type.
First the mathematical background of quantum mechanics as well as some numerical techniques are reviewed. Care is taken to emphasise the often overlooked subtleties when discretising an infinite-dimensional spectral problem in order to obtain a finite-dimensional eigenproblem. Common quantum-chemical methods such as full configuration interaction and HF are discussed providing insight into their mathematical properties. Different formulations of HF are contrasted and appropriate SCF solution schemes formulated.
Next discretisation approaches based on four different types of basis functions are compared both with respect to the computational challenges as well as their ability to describe the physical features of the wave function. Besides (1) Slater-type orbitals and (2) Gaussian-type orbitals, the discussion considers (3) finite elements, which are piecewise polynomials on a grid, as well as (4) Coulomb-Sturmians, which are the analytical solutions to a Schrödinger-like equation. A novel algorithmic approach based on matrix-vector contraction expressions is developed, which is able to adapt to the numerical requirements of all basis functions considered. It is shown that this ansatz not only allows to formulate SCF algorithms in a basis-function independent way, but furthermore improves the theoretically achievable computational scaling for finite-element-based discretisations as well as performance improvements for Coulomb-Sturmian-based discretisations. The adequacy of standard SCF algorithms with respect to a contraction-based setting is investigated and for the example of the optimal damping algorithm an approximate modification to achieve such a setting is presented.
With respect to recent trends in the development of modern computer hardware the potentials and drawbacks of contraction-based approaches are evaluated. One drawback, namely the typically more involved and harder-to-read code, is identified and a data structure named lazy matrix is introduced to overcome this. Lazy matrices are a generalisation of the usual matrix concept, suitable for encapsulating contraction expressions. Such objects still look like matrices from the user perspective, including the possibility to perform operations like matrix sums and products. As a result programming contraction-based algorithms becomes similarly convenient as working with normal matrices. An implementation of lazy matrices in the lazyten linear algebra library is developed in the course of the thesis, followed by an example demonstrating the applicability in the context of the HF problem.
Building on top of the aforementioned concepts the design of molsturm is outlined. It is shown how a combination of lazy matrices and a contraction-based SCF scheme separates the code describing the SCF procedure from the code dealing with the basis function type. It is discussed how this allows to add a new basis function type to molsturm by only making code changes in a single integral interface library. On top of that, we demonstrate by the means of examples how the readily scriptable interface of molsturm can be employed to implement and assess novel quantum-chemical methods or to combine the features of molsturm with existing third-party packages.
Finally, the thesis discusses an application of molsturm towards the investigation of the convergence properties of Coulomb-Sturmian-based quantum-chemical calculations. Results for the convergence of the ground-state energies at HF level are reported for atoms of the second and the third period of the periodic table. Particular emphasis is put on a discussion about the required maximal angular momentum quantum numbers in order to achieve convergence of the discretisation of the angular part of the wave function. Some modifications required for a treatment at correlated level are suggested, followed by a discussion of the effect of the Coulomb-Sturmian exponent. An algorithm for obtaining an optimal exponent is devised and some optimal exponents for the atoms of the second and the third period of the periodic table at HF level are given. Furthermore, the first results of a Coulomb-Sturmian-based excited states calculation based on the algebraic-diagrammatic construction scheme for the polarisation propagator are presented.
Diese Arbeit beschäftigt sich mit der Synthese von löslichen, isomerenreinen und dreidimensionalen Aroylenimidazolen, die an ein zentrales Triptycen geknüpft wurden. Die Anzahl an Aryolenimidazol-Einheiten pro Triptycenkörper wird dabei sukzessive erhöht und ihre Eigenschaften untereinander verglichen. Das Triptycen als Grundkörper unterbricht die Planarität der Aroylenimidazole, was eine verbesserte Phasenseparation in der organischen Photovoltaik bewirken soll. Es führt zudem zu einer bathochromen Verschiebung des längerwelligen Absorptionsmaximums im Vergleich zum unsubstituierten Aroylenimidazol. Mit einer Absorption von 300-600 nm decken die Triptycen-Aroylenimidazole damit nahezu das komplette sichtbare Spektrum des Sonnenlichts ab, wobei sie sich untereinander lediglich durch die Höhe der Extinktionskoeffizienten unterscheiden. Die ermittelten energetischen Lagen des LUMOs von ELUMO = -3.6 bis -3.9 eV machen die hergestellten Aroylenimidazole zu idealen Kandidaten für den Einsatz in der organischen Photovoltaik. Damit sind sie die ersten Aroylenimidazole, die aufgrund ihrer guten Löslichkeit in organischen Solarzellen eingesetzt werden können. Die Morphologie der Systeme wurde durch das Herstellen verschiedener Derivate mit unterschiedlichen Substituenten am Imid-N variiert. In einer Kooperation mit der Arbeitsgruppe von Prof. Dr. Y. Vaynzof (CAM und KIP, Universität Heidelberg) wurden die Aroylenimidazole mit PTB7 als Donor in organischen Solarzellen getestet. Durch das Einführen des Triptycens konnte eine deutliche Steigerung des Wirkungsgrades erzielt werden. Innerhalb der Triptycen-Aroylenimidazole korreliert die Anzahl an Akzeptoreinheiten mit dem Wirkungsgrad, sodass die besten Ergebnisse für das Trisaroylenimidazol erhalten wurden (PCEmax = 2.8%).
In recent years, the rapid development of attosecond pulse techniques opened the door for studying and eventually controlling electronic dynamics. Due to strong coupling between the electronic and nuclear motion, control over the pure electronic step offers the extremely interesting possibility to steer the succeeding chemical reactivity by predetermining the reaction outcome at a very early stage. Using the electron dynamics and quantum coherence to induce a particular chemical process is the new paradigm in the emerging field of "attochemistry".
One example of physical phenomena, where an electronic dynamics significantly affect on reactivity is the process of an ultrafast charge migration. The positive charge created upon ionization of a molecule can migrate throughout the system on a few-femtosecond time scale solely driven by the electron correlation and electron relaxation. Charge migration triggered by ionization appeared to be a general phenomenon taking place both after inner- and outer-valence ionization of molecules.
This thesis is devoted to the theoretical investigation of the fascinating interplay between the faster electron and the slower nuclear dynamics appearing upon ionization of a molecular system in the presence of an external electromagnetic field. The possibilities to manipulate quantum molecular dynamics by applying specifically tailored ultrashort laser pulses are inspected and analyzed. In particular, the focus is made on the role which the coherent electronic dynamics plays and how the control of the electronic movement influences the outcomes of induced processes. We present here both analytical and numerical approaches allowing one to design laser pulses which can force the evolution of a quantum system in a predefined way. We demonstrate by fully ab initio calculations on experimentally interesting molecules that simple pulses can be used to control the charge-migration oscillations. It is further shown how the correlated treatment of electronic and nuclear dynamics affects the coherence of the electronic wave packet. Our full-dimensional calculations on the propiolic acid molecule show that the electronic decoherence time can be long enough to allow one to observe several oscillations of the charge before nuclear dynamics eventually traps it. Utilizing the strong coupling between the electronic and the nuclear motion, we exemplify the key idea of the attosecond control of molecular reactivity. We demonstrate on a simple model of molecular fragmentation that the nuclear rearrangement can be guided by a manipulation of the electronic dynamics only. We argue that this example clearly illustrates the concept of attochemistry and thus can be used as a starting point to deepen our understanding of the possibilities to control chemical reactions.
Photochemical reactions are ubiquitous in nature. Furthermore, they play an important role in organic and inorganic synthesis. In such reactions, light energy is used to induce chemical transformations. Two prime examples of such reactions are photosynthesis – the conversion of light energy to chemical energy, and the cis-trans isomerization reaction in the retina which enables vision. Upon absorption of light, the electrons in a molecule are promoted to higher energy levels; the molecule is elevated from its electronic ground state to an electronically excited state. Once in the excited state, different processes may take place such as the emission of light, interactions with the environment, or chemical reactions. One class of processes often involved in photochemical reactions and of particular importance are charge-transfer processes. A charge transfer can occur intermolecularly i.e., between different molecules or within a molecular complex from a ligand to the center and vice versa. These intermolecular charge- transfer processes, for example, occur in organometal complexes and play a crucial role in numerous catalytic reactions. In intramolecular charge-transfer processes, charge is transferred from one part of a molecule, the donor moiety, to a different part of the molecule, the acceptor moiety. Among those, so-called twisted intramolecular charge-transfer (TICT) processes and the corresponding TICT states are of particular interest. TICT molecules are characterized by the fact that they undergo a rotation about a single bond connecting the donor and acceptor moiety in the excited state. This twisting is accompanied by a charge transfer from the donor to the acceptor, resulting in a highly polar CT state exhibiting a mutually perpendicular orientation of donor and acceptor subsystems. Due to this process, TICT compounds show a very interesting unusual fluorescence behavior, named dual fluorescence, in medium polar and polar solvents. Dual fluorescence means that there are two fluorescence bands observable: one corresponding to the transition from the TICT state and the other from the transition from a planar excited state. In this dissertation, photochemical reactions of different small- and medium-sized organic molecules have been investigated with a particular focus on intramolecular charge-transfer. The well-known and experimentally well-investigated small donor-acceptor TICT compound N- pyrrolobenzonitrile (PBN) and its thiophene derivative 5-(1H-pyrrole-1-yl)thiophenecarbonitrile (TCN) are studied, among others. For this purpose, different quantum chemical electronic structure methods are employed. Especially when used along with spectroscopy, these ab initio methods are powerful tools to study the molecular structure and photochemical reactions. Quantum chemical methods can provide reliable excitation energies, excited state properties, and absorption strengths and allow for the computation of deactivation pathways. In this work, it is shown that the chosen quantum chemical methodology is well suited to describe the photochemical behavior of the considered organic compounds and new insights into the photochemistry of these systems are provided.
Mechanical forces between cells ensure organic development and homeostasis, but they are also associated with diseases such as cancer or viral infections. The absolute forces in nature can be as high as 1.5 kN, which allows the mantis shrimp to smash oysters, down to a few pN transduced by single cellular receptors. However, these small forces are strong enough for cells to probe their local environment. While the mechanism, which enables cells to investigate the stiffness of their surrounding, is already well elucidated, information on how cells sense spatial distribution of ligands is missing. In this thesis I established a method, which allows to measure cellular traction forces on elastic substrates with varying nano-spacing of extracellular ligands. In contrast to previous studies on stiff substrates, adhesion complexes and tractions were larger for longer distances between extracellular adhesion sites. This can be theoretically explained by the force load on individual integrin receptors, which has to exceed a certain threshold value to promote adhesion growth through conformational changes in a protein of the “clutch complex”. In order to experimentally access the force load per integrin heterodimer, I combined molecular tension fluorescence microscopy (MTFM) with traction force microscopy (TFM). For the first time, I could assess a homogeneous distribution of forces > 19pN underneath the adhesion area of cells on soft substrates. Simultaneously, macroscopic tractions up to 2.7 kPa were observed at the cell edges. Applying stronger tension probes and analyzing tractions in the zdirection will help to cross-validate the results obtained from these two state-of-the-art methods in biomechanics as a next step. In the second part I investigated the mechanical parameters of virus particle uptake by cells. Many intracellular pathogens, such as mammalian reoviruses as employed in this thesis, mimic extracellular motives to interact with host cells and initiate their internalization. This leads to the assumption that host cells sense this specific ligand presentation, engage the endocytic machinery and generate forces, which are able to overcome the bending and tension energy of their plasma membrane. I demonstrated that these forces exerted on single reovirus particles on the basolateral side of cells are strong enough to break down the biotin-NeutrAvidin bond used for virus immobilization on stiff and soft substrates. I quantified the forces to exceed 40pN by kinetic analysis of the tearing of viruses from these surfaces and single MTFM with covalently immobilized reoviruses. The herein presented methods are powerful tools to study forces exerted by individual receptors as well as on single particles e.g. during endocytosis. The involvement of the actin cytoskeleton, specific receptors or molecules of the endocytic machinery was examined. Inhibition of the ligand-receptor interactions between reoviruses and cells did not significantly change the rate of virus uptake. Interestingly, bare nanoparticles of comparable diameter lacking specific binding sites were torn off at a similar rate and thus with the same forces as viruses. Hence, specific receptors seem to be dispensable for virus particle uptake.
Guanidinofunktionalisierte Aromaten (GFA) zeichnen sich aufgrund ihrer hohen Elektronendonorstärke sowie ihrer leicht modifizierbaren Redoxeigenschaften als geeignete Liganden für die Entwicklung neuer valenztautomerer Übergangsmetallkomplexe aus. Diese sind für die Verwendung in redoxkatalytischen Prozessen von zunehmendem Interesse. Die vorliegende Dissertation beschäftigt sich mit der Darstellung sowie dem Redoxverhalten neuer molekularer Gallium-, Zink- und Kupfer-Komplexe mit verbrückenden GFA-Liganden. Als redoxaktive Ligandensysteme werden 1,4,5,8-Tetrakis(tetramethylguanidino)naphthalin (ttmgn), 1,2,4,5-Tetrakis(tetramethylguanidino)benzol (ttmgb) sowie 2,3,5,6-Tetrakis(tetramethylguanidino)pyridin (ttmgp) verwendet. Durch die systematische Variation der Coliganden an den Metallzentren wird erstmals gezeigt, dass eine gezielte Steuerung der elektronischen Struktur in zweikernigen Kupfer-GFA-Komplexen möglich ist. Zunächst wird das Reduktionsvermögen von ttmgn gegenüber verschiedenen Oxidationsmitteln untersucht. Die Redoxfähigkeit kann dabei durch Komplexierung stark verringert werden. So stellt die Galliumverbindung [ttmgn(GaCl2)2](GaCl4)2 ein mildes Reduktionsmittel dar, das durch die Umsetzung mit dem Elektronenakzeptor Tetracyanochinodimethan (TCNQ) zur Ausbildung von Donor-Akzeptor-Materialien mit interessanten spektroskopischen und elektrischen Eigenschaften führt. Es erfolgt die partielle Reduktion von TCNQ unter Bildung radikalischer (TCNQ)2•−-Dimere. Diese sind zu Stapeln angeordnet, entlang derer die Ladungsträger im Material frei beweglich sind. Des Weiteren sind in der Arbeit unter Verwendung von ttmgn binukleare Koordinationsverbindungen mit redoxinerten Zink(II)-Salzen sowie redoxaktiven Kupfer(I)-Salzen hergestellt und im Anschluss hinsichtlich ihrer Oxidierbarkeit untersucht worden. Die Synthese des ersten monomeren, binuklearen GFA-Komplexes der elektronischen Struktur [CuI-GFA2+-CuI] gelingt durch die Umsetzung des oxidierten Liganden ttmgn2+ mit Kupfer(I)-Iodid. Eine Addition weiterer Coliganden an das trigonal-planar koordinierte Kupfer(I)-Zentrum dieses Komplexes wird sowohl experimentell als auch quantenchemisch untersucht. Die Koordination von ttmgn mit Kupfer(II)-Salzen führt zu zweikernigen Komplexen der Zusammensetzung [ttmgn(CuX2)2] (mit X = Br, Cl, OAc), die sich je nach Coligand in ihren elektronischen Strukturen voneinander unterscheiden. Harte Donorliganden stabilisieren die elektronische Struktur [CuII-ttmgn0-CuII]. Weiche Coliganden führen im Zuge der Koordination einen intramolekularen Elektronentransfer herbei, sodass der resultierende Komplex mit der elektronischen Struktur [CuI-ttmgn2+-CuI] vorliegt. Beide Formen weisen deutliche Unterschiede hinsichtlich ihrer optischen, strukturellen und magnetischen Eigenschaften auf. Durch Coliganden mittlerer Härte sind Systeme mit energetisch ähnlichen Zuständen zugänglich, deren Besetzung eine starke Umgebungsabhängigkeit aufweist. Unter Verwendung von ttmgb als Brückenligand ist die Synthese dikationischer Komplexe gelungen, an deren Kupferzentren substitutionslabile Neutralliganden koordiniert sind. In Lösung zeigen diese Verbindungen eine temperaturabhängige Valenztautomerie. Durch gezielten Austausch der neutralen Coliganden eröffnet sich ein Syntheseweg zu einer Vielzahl neuer redoxaktiver Koordinationsverbindungen, deren elektronische Strukturen in Abhängigkeit des Coliganden gezielt steuerbar sind.
The hydrated and highly charged extracellular matrix (ECM) plays a vital role in many biological processes. Therefore, mimicking this environment is of great interest in material science as well as biomedical research. In this thesis, an ECM mimetic is presented based on hyaluronic acid also called hyaluronan (HA) as one of the ECM’s abundant negatively charged components. Due to HA’s unique properties, this anionic biopolymer was chosen as biological "module" to design biocompatible charge defined hydrogels in a synthetic biology approach. By varying the degree of chemical modification on the carboxyl groups of the glucuronic acid moiety of HA in addition to differently charged but structurally similar heteroaromatic crosslinkers, the charge density of the hydrogels presented in this thesis can be adjusted. Using thiolation as chemical modification together with two armed crosslinkers carrying unsaturated end groups, the thiol-Michael addition click reaction can be employed for byproduct free crosslinking of HA chains. The composition of the presented hydrogels remains constant and hydrogels with the same degree of thiolation and differently charged heteroaromatic crosslinker cores even result in the same covalent connectivity of the network. I could show that size defined HA with an average molecular weight of 74 kDa is suitable for homogeneous and reproducible hydrogel formation at degrees of thiolation from 18% to 36%. Additionally, the presented hydrogels show a high stability over time, with constant mechanical stiffness over the course of at least four weeks. Using a set of hydrogels synthesized from 74 kDa HA with three different degrees of thiolation in the range of 18% to 33% and one neutral and one structurally similar, positively charged crosslinker, physico-chemical properties were monitored. Two general trends could be observed for mechanical stiffness in the form of Young’s moduli ranging from 0.44 kPa to 6.31 kPa, swelling ratios and mesh sizes between 53.54nm to 183.76nm. (1) With increasing degree of thiolation, mechanical stiffness increases whereas swelling ratios and respective mesh sizes decrease. (2) At each individual degree of thiolation, hydrogels with the charged crosslinker show twice as high Young’s moduli and roughly halved swelling ratios and mesh sizes, compared to the same hydrogels with uncharged crosslinkers. Furthermore, swelling ratios of the presented polyelectrolyte hydrogels are highly influenced by the ionic strength of the swelling solution but independent of the solution’s pH at physiological salt concentration. Biological properties, as for example enzymatic degradability, show the trends described for physico-chemical characterization. (1) Half-lives of hydrogels in hyaluronidase and hyaluronate lyase solutions are increasing with increasing degree of thiolation from 2.5 h to 11.7 h in hyaluronidase with the uncharged crosslinker and (2) for each individual degree of thiolation, half-lives for hydrogels with the charged crosslinkers are always larger than for respective hydrogels with the uncharged crosslinker. Furthermore, cell adhesion of fibroblasts, lymph endothelial cells and breast cancer cells is (1) increasing with increasing degree of thiolation. (2) It could also be observed, that cells adhere better on hydrogels with charged crosslinkers, compared to hydrogels with the same degree of thiolation with uncharged crosslinkers. For all of these trends in physico-chemical as well as biological properties, two influencing factors could clearly be determined in this thesis. Firstly, correlation of all presented properties with the negative network charge of each individual hydrogel could be observed: With decreasing negative network charge, hydrogels are becoming stiffer, show lower swelling capacity and smaller mesh sizes, degradation by hyaluronan degrading enzymes becomes slower, and more cells are able to adhere to their surface. Secondly, the aromatic core of the crosslinker seems to be another important factor for material properties. The naturally occurring pyridinium causes considerably stiffer hydrogels with smaller mesh sizes and lower swelling ratios compared to a structurally similar triazolium based crosslinker. To conclude, a charge defined hydrogel system could be presented, mimicking the hydrated ECM niche, in a minimal model adjusted for studying non-integrin mediated cell attachment. From results obtained by characterizing the material properties, I suggest a strong influence of secondary interactions on physico-chemical and biological properties of the ECM. Both electrostatic interactions, resulting from negative network charge of the hydrogels, as well as aromatic core interactions due to different heteroaromats used in crosslinker design are critically influencing hydrogel properties in a specific way. With the establishment of this defined system further studies on charge dependent ECM characteristics as well as application in three dimensional (3D) tissue engineering, drug delivery or regenerative medicine are possible, given the opportunity to specifically tune material properties by changing the secondary interactions within the network.
In dieser Arbeit werden die chemische Zusammensetzung, die Orientierung und der Ladungstransfer an Grenzflächen mit Hilfe von Infrarotspektroskopie im mittelinfraroten und ferninfraroten Bereich untersucht. An der Anodengrenzfläche wurde der Einfluss der Modifikation von Indiumzinnoxid durch flüssigprozessiertes Nickeloxid (sNiO) und thermisch verdampftes Molybdänoxid (MoO3) auf das Donormaterial, in diesem Fall fluoriertes Zinkphtalocyanin (F4ZnPc), analysiert. Die Messungen wurden in situ während des Aufdampfvorgangs des F4ZnPc durchgeführt. So konnte eine chemische Veränderung des Moleküls an der Grenzfläche zu ITO und sNiO festgestellt werden und ein Ladungstransfer, aber keine chemische Veränderung auf MoO3. Der Ladungstransfer führte zur Bildung des F4ZnPc-Kations, wobei sich eine Raumladungszone mit einer Ausdehnung von 8nm formte. Die Orientierung der Moleküle in der F4ZnPc-Schicht wurde durch die Modifikation für Schichtdicken über 20nm nicht signifikant beeinflusst. Auf der Kathodenseite wurden selbstorganisierende Monolagen (SAMs) aus Dimethylamin- Biphenyl-Phosphonaten dazu verwendet die Austrittsarbeit zu verkleinern, aber nicht den Kontaktwinkel von ITO zu verändern. Die Moleküle der SAM wurden zunächst auf ITO charakterisiert und dabei Neigungswinkel, Austrittsarbeitsänderung und Kontaktwinkel bestimmt. Danach konnte der organische n-Typ Halbleiter N,N’-bis(2- phenylethyl)Perylen-3,4,9,10-bis-(dicarboximid) (BPE-PTCDI) aufgedampft werden und im IR vermessen werden. Eine Korrelation zwischen Orientierung des BPE-PCTDI und der Kontaktwinkeländerung des Substrats konnte gefunden werden. Außerdem wurde die elektronische Wechselwirkung zwischen ITO/ SAM und BPE-PTCDI gemessen, die mit der Austrittsarbeitsänderung durch die SAM einhergeht, und substratabhängig ist.
In this thesis, the redox and coordination chemistry of bisguanidino-functionalized dioxolenes (GFD) is studied. These GFD are "hybrid" compounds consisting of guanidino-functionalized aromatics (GFA) and dioxolenes. In the oxygen-protected GFD form, electrochemical and chemical oxidation experiments show that the 4,5-bisguanidino-benzodioxoles 1Ac (tetramethylguanidino), 2Ac (N,N‘-dimethyl-N,N‘-ethylen-guanidino-) and 5,6-bisguanidino-benzodioxin 2Et (N,N‘-dimethyl-N,N‘-ethylen-guanidino-) can be oxidized reversibly in two 1e- redox processes. In the coordination and redox chemistry of the mononuclear Cu complexes, it is found that the electron donor strength of the protected GFD (L = 1Ac, 2Ac, 2Et) covers precisely the crucial range to study systematically which factors stabilize the electronic structures [L0(CuIIX2)] or [L+•(CuIX2)]. The electronic structure depends on the electron donor strength of the redox active bisguanidine (L = 1Ac, 2Ac, 2Et), the coligand X (X = OAc, Cl, Br), the solvent and the temperature. In the halide complexes [L(CuX2)] with L = 2Ac, 2Et, a temperature- and solvent-dependent equilibrium between the valence tautomers [L0(CuIIX2)] and [L+•(CuIX2)] is found in solution, which affect the redox chemistry of [L(CuX2)]. The influence of the intramolecular electron transfer (valence tautomerism between [(L)2CuII]2+ and [(L+•)CuI(L)]2+) on the intermolecular redox process [(L)2Cu]2+/+ is found in the bis-bidentate guanidine copper complexes and has been studied. Based on the distorted structure (between quadratic-planar and tetrahedral) and low calculated reorganization energy, the prerequisites for efficient intra- and intermolecular electron transfer are given. The coordination and redox chemistry of mononuclear cobalt complexes with the protected GFD reveals that [(L)2Co]2+ and [L(CoX2)] (X = OAc, Cl) are high-spin CoII complexes with one or two neutral ligands. A reversible, ligand-based 1e- redox process is observed in the bis-bidentate CoII complexes [(L)2Co]2+ and the acetato complex [2Et{Co(OAc)2}]. The bisguanidino-functionalized dioxolenes (GFD) with their two different coordination sites can be prepared in their protonated catechol form from the protected acetals 1Ac, 2Ac. The catechol form 12H and 22H can be selectively oxidized by oxygen to the quinones 1, respectively 2. Since the free quinones prone to undergo decomposition, stabilization can be achieved by complexation. In the stable mononuclear complexes [1(MIICl2)] with M = Cu, Pd, the (κ2-N,N’)-isomer is exclusively present according to which the heterobinuclear complex [(κ2-N,N’-PdIICl2)10(κ2-O,O’-CuIICl2)] can be prepared specifically by sequential coordination. The heteronuclear CuIIPdII complex crystallizes as a symmetric dimer with Cu-Cl-Cu bridges and in solution an equilibrium with the heterobinuclear monomer can be found. In the homobinuclear Cu complex [(CuIICl2)1(CuIICl2)], a reversible coordination of a CH3CN molecule on the Cu atom of the dioxolene site of GFD 1 is possible. This reversible coordination to the monocationic complex [(CuIICl2)1+•(CuIICl2)]+ triggers an intramolecular metal-ligand electron transfer leading to the formation of the mixed valence complex [(CuIICl2)1(CuIIICl2(CH3CN))]+.
Understanding the ultrafast excited state dynamics in organic semiconductors after optical excitation is a key requisite on the road towards efficient organic solar cells. Additionally, the creation of functional interfaces built from organic molecular switches and the read-out of the photochromic state are essential for molecular electronics. In this thesis, static second harmonic generation (SHG) measurements were utilized to investigate the photochromism of different indolylfulgimide derivatives immobilized on silicon. During this, the influence of chemical modifications on the switching efficiencies (cross-sections) and the non-linear optical contrast between the switching states were investigated. In the second part of this thesis, femtosecond time-resolved second harmonic generation measurements were used to investigate the ultrafast decay mechanism of optically induced electronically excited states in organic semiconductors and donor/acceptor systems. These led to observations of relaxation into dimer induced states, charge trapping at native silicon oxide and ultrafast vibronic relaxation. For the donor/acceptor configurations, depending on the molecular orientation at the interface and the excitation energy, the creation of charge transfer states were investigated.
The work mainly focuses on amino gallium compounds and their chemistry. First of all, the synthesis and analysis of silylamines and their salts are shown and discussed. Several crystal structures could be obtained.
Lithiated silylamines and their reactions with different gallium sources are the second part of this work. This class of compounds are used as bulky substituents in different disciplines of chemistry. In relation to the current work their reaction with Ga2X4 (X = Cl, I) possibly lead to homoleptic amino digallanes. Novel cage compounds can be obtained by the reaction of these homoleptic digallanes with low valent gallium sources. Their x-ray structures will be discussed as well. Beyond this the focus is on various types of digallanes with a novel heteroleptic digallane and its reactions with carbon dioxide and potassium-tert-butanolate. Crystal structures of Ga(III)-species will be shown afterwards. Those compounds with more than one halide substituent will be treated with reducing agents thus leading to new low valent gallium species.
Amino compounds of Gallium(III) are used in the semiconductor industry which has been developed fast in the last years. It is of great interest to cover the need of high efficient materials through the development of better compounds. As a part of the project ‘development of GaInNAs materials for concentrator solar cells for the photovoltaics’ the goal is to examine new precursor materials for the epitaxy (Chapter 7.5). Based on quantum-chemical calculations a further big goal is the synthesis of the ideal precursor or rather the prediction of possible products of decomposition.
The implementation of actinide recycling processes is considered in several countries, aiming at the reduction of long-term radiotoxicity and heat load of used nuclear fuel. This requires the separation of the actinides from the fission and corrosion products. The separation of the trivalent actinides (An(III)) Am(III) and Cm(III), however, is complicated by the presence of the chemically similar fission lanthanides (Ln(III)). Hydrophilic N-donor ligands are employed as An(III) or Am(III) selective complexing agents in solvent extraction to strip An(III) or Am(III) from an organic phase loaded with An(III) and Ln(III). Though they exhibit excellent selectivity, the complexation chemistry of these ligands and the complexes formed during solvent extraction are not sufficiently characterized. In the present thesis the complexation of An(III) and Ln(III) with hydrophilic N-donor ligands is studied by time resolved laser fluorescence spectroscopy (TRLFS), UV/Vis, vibronic sideband spectroscopy and solvent extraction. TRLFS studies on the complexation of Cm(III) and Eu(III) with the Am(III) selective complexing agent SO3-Ph-BTBP (tetrasodium 3,3’,3’’,3’’’-([2,2’-bipyridine]-6,6’-diylbis(1,2,4-triazine-3,5,6-triyl))tetrabenzenesulfonate) revealed the formation of [M(SO3-Ph-BTBP)n](4n-3)- complexes (M = Cm(III), Eu(III); n = 1, 2). The conditional stability constants were determined in different media yielding two orders of magnitude larger 2-values for the Cm(III) complexes, independently from the applied medium. A strong impact of ionic strength on the stability and stoichiometry of the formed complexes was identified, resulting from the stabilization of the pentaanionic [M(SO3-Ph-BTBP)2]5- complex with increasing ionic strength. Thermodynamic studies of Cm(III)-SO3-Ph-BTBP complexation showed that the proton concentration of the applied medium impacts the hydration, resulting in more negative reaction enthalpies of the complexation in acidic media. Utilizing absorption spectroscopy, the formation of the [Am(SO3-Ph-BTBP)2]5- complex was quantified. The conditional stability constant of this complex is by log2 = 0.2 larger than of the analogous Cm(III) complex. This is in excellent agreement with the separation factor derived from solvent extraction (SFCm(III)/Am(III) = 1.6). Solvent extraction studies were performed in the SO3-Ph-BTBP/TODGA system (N,N,N’,N’-tetraoctyl-diglycolamide) at varied nitric acid concentration, SO3-Ph-BTBP concentration and temperature, demonstrating the separation of Am(III) from Cm(III) and the light Ln(III) with separation factors of SFCm(III)/Am(III) = 2.6-3.0 and SFEu(III)/Am(III) up to 1100. Furthermore, the VII selectivity of the SO3-Ph-BTBP/TODGA system is not affected by Eu(III) concentrations of 2 - 15 mmol/L or by hydrolysis after contact with nitric acid for several weeks. Radiolytic degradation occuring at doses > 10 kGy, however, limits the recycling of SO3-Ph-BTBP. In case of SO3-Ph-BTPhen (tetrasodium 3,3',3'',3'''-((1,10-phenanthroline-2,9-diyl)bis(1,2,4-triazine-3,5,6-triyl))tetrabenzenesulfonate) the coordinating nitrogen atoms of the pyridine moieties of SO3-Ph-BTBP are fixed in cis position by the phenantroline moiety. This results in increased complex stability for lipophilic derivatives. However, TRLFS studies on SO3-Ph-BTPhen and SO3-Ph-BTBP in aqueous solution at pH 3 showed that the preorganization has no significant impact on the stability of the formed complexes. Due to the lower pKa of SO3-Ph-BTPhen the log2 values in acidic media are higher than for SO3-Ph-BTBP. The selectivity of the complexing agent, however, remains unaltered. The Cm(III) and Eu(III) 1:1 complexes formed with the decadentate Am(III) selective complexing agent H4TPAEN (N,N,N’N’-tetrakis[(6-carboxypyridin-2-yl)methyl]ethylenediamine) were investigated using TRLFS. The conditional stability constants of these complexes differ by 1.9 orders of magnitude. This is in excellent agreement with the separation factor derived from solvent extraction (SFEu(III)/Cm(III) ≈ 100). The complexation of M(III) with H4TPAEN is driven by the high positive reaction entropy. PTD (2,6-bis[1-(propan-1-ol)-1,2,3-triazol-4-yl]pyridine) is a charge neutral, CHON compatible complexing agent designed for the selective complexation of An(III). 1:1, 1:2 and 1:3 complexes with Cm(III) and Eu(III) were characterized in aqueous solution at pH 3 and in 0.44 mol/L HNO3. The difference of log3 = 4 for the Cm(III) complexes in the different media is primarily caused by the protonation of PTD. Ionic strength effects and the concurring complexation of Cm(III) by nitrate contribute to a lesser extent. In solvent extraction lower separation factors were observed than calculated from the difference of the log3 values of Cm(III) and Eu(III) (SF(experimental)Eu(III)/Cm(III) ≈ 200 vs. SF(calculated)Eu(III)/Cm(III) ≈ 1000). This was proven to be caused by the presence of lower coordinated species during solvent extraction. The 5D0 → 7F0 transition of more than 20 Eu(III)-BT(B)P/BTPhen complexes was studied. A correlation between the shift of the 7F0 emission band and the number of coordinating N-donors was established, allowing to easily identify the stoichiometry of Eu(III) N-donor complexes. Furthermore, the strong nephelauxetic effect observed is an excellent proof of a covalent share in the Eu(III)-N-donor bond. The results obtained in the present thesis represent a valuable contribution to the fundamental understanding of the complexation of trivalent actinides and lanthanides with hydrophilic N-donor ligands and, thus, to the development of new processes for the recycling of An(III).
The median age of our population causes osteoporosis, bone fractures and disorders, which are also caused by multiple myeloma. In the past 25 years, regenerative medicine had gained in importance, especially for regeneration and renewal of bone tissue, which consists of different cell types composed in a very complex architecture. The growth factor bone morphogenetic protein 6 (BMP-6) belongs to the transforming growth factor β (TGF- β) superfamily and it induces the differentiation of mesenchymal stem cells into mature osteoblasts in bone leading to new bone formation. Besides induction of osteogenic differentiation, BMP-6 is also known to induce cell death in multiple myeloma cells in high concentrations. However, a systemic application is not practicable, since uncontrolled diffusion causes a wide range of side-effects. Immobilization of growth factors allows local treatment of bone fractures and defects, while it prevents uncontrolled release of growth factors. Furthermore, the required amount of growth factors can be reduced tremendously. The objective of this work was the covalent immobilization of BMP-6 co-presented with clicked integrin ligands on a structured gold nanoparticle (AuNP) platform, using blockcopolymer micellar nanolithography (BCMN) developed by Prof. Spatz and co-workers, to study integrin signaling in connection with growth factor responses. BMP-6 was selectively bound to gold nanoparticles organized in a hexagonal structure on the surface allowing to control the amount and density on the surface. I showed that surface co-presentation of BMP-6 and RGD or α5β1 integrin selective ligand promotes SMAD1/5 phosphorylation and osteogenic differentiation of the standard model system C2C12, even at amounts as low as 1 ng, whereas soluble BMP-6 application is significantly less effective. Additionally, BMP-6 was immobilized on gold nanostructured polyethylene glycol diacrylamide (PEG-DA) hydrogels containing different concentrations of cRGD in order to study the influence of the stiffness on the cell signaling. Furthermore, this approach was used to investigate the effect of immobilized BMP-6 in low doses on the multiple myeloma cell line OPM-2 to induce cell death. This approach provides for the first time the successful presentation of BMP-6 in small and defined amounts on surfaces in combination with adhesive ligands. Furthermore, covalent immobilization hinders protein release while maintaining the biological activity of the growth factor.
Im Verlauf dieser Arbeit wurden Harzsysteme für Anwendungen im Automobilbereich entwickelt und untersucht. Im ersten Teil der Arbeit wurden Epoxidharzformulierungen für das Resin Transfer Molding (RTM)-Verfahren entwickelt. Das Ziel bestand darin ein auf dem Diglycidylether von Bisphenol A (DGEBA) basierendes Epoxidharzsystem mit einer Glasübergangstemperatur TG (max. tan δ) von mindestens 190°C und ausreichender Bruchzähigkeit (KIC ≥ 0,7 MPam1/2) zu entwickeln. Diese anspruchsvollen Zielparameter sollten durch die Optimierung des Härtungsprozesses und die Anwendung geeigneter TG- und Zähmodifier erreicht werden. Gemäß der Aufgabenstellung wurden in diesem Versuchskomplex keine Verbundmaterialien sondern nur Reinharzsysteme untersucht. Zunächst wurden die thermischen und mechanischen Eigenschaften von aminisch sowie mittels Homopolymerisation gehärteten DGEBA-Proben untersucht. Als aminische Härter wurden cyclische aliphatische Amine (IPDA, 1,2-DACH und M-DACH), cyclische verbrückte aliphatische Amine (DC und PACM20, DMDC, TMDC) sowie das aromatisches Amin LonzacureTM DETDA 80 verwendet. Die Homopolymerisation des DGEBA erfolgte mit dem Initiator 1-Ethyl-3-methylimidazoliumacetat (EMIM Ac). Bei der Optimierung des Härtungsprozesses wurde festgestellt, dass eine Nachtemperung bei 200°C die Glasübergangstemperatur TG (max. tanδ) deutlich erhöht. Mit aminisch gehärteten, nachgetemperten DGEBA-Proben wurden TG (max. tanδ) Werte von 164-195°C erreicht und KIC-Werte von 0,6-0,76 MPam1/2. Tendenziell zeigten Epoxidharzsysteme mit einer vergleichsweise hohen Glasübergangstemperatur geringere Bruchzähigkeiten. Für das homopolymersierte Harzsystem DGEBA/EMIM Ac wurde im Vergleich zu den aminisch gehärteten Systemen eine wesentlich geringere Bruchzähigkeit bei vergleichsweise niedrigen Glasübergangstemperaturen festgestellt (TG (max. tanδ) = 159°C; KIC = 0,44 MPam1/2). Dann wurde untersucht, welchen Effekt Phosphite (Diethylphosphit (DEP) und 5,5-Dimethyl-1,3,2-dioxaphosphorinan-2-on (DDPO)), die als Nachvernetzer im DGEBA-basiertem Epoxidharzsystem wirken können, auf die Glasübergangstemperatur und die Bruchzähigkeit ausüben. Der größte Einfluss auf die Glasübergangstemperatur wurde für Harzsysteme festgestellt, deren TG ohne Modifier vergleichsweise gering war. Dies ist beim Harzsystem DGEBA/IPDA der Fall, dessen TG (max. tanδ) von 163°C bei Verwendung von DEP (1 w% P) auf 192°C gesteigert werden konnte. Der Einsatz dieser Phosphite bewirkte nicht nur eine Erhöhung der TG, sondern auch eine Erniedrigung der Bruchzähigkeit. Auf diese Weise wurden mit relativ hohen Konzentrationen an Nachvernetzern (1 w% P) zwar hohe Glasübergangtemperaturen erreicht, jedoch erwiesen sich geringe Phosphit-Konzentrationen als die bessere Wahl, da Mengen von 0,1-0,25 w% P (entsprechend 0,44-1,1 w% DEP bzw. 0,48-1,2 w% DDPO) nicht nur die Glasübergangstemperatur, sondern auch die Bruchzähigkeit verbessern. Mit dem Harzsystem DGEBA/DC/DEP (0,5w%P) wurden die Zielvorgaben erreicht (TG (max. tanδ) = 193°C, und KIC = 0,76 MPam1/2). Mit dem Harzsystem DGEBA/DMDC/DEP (0,1 w% P) wurden folgende Parameter erzielt: TG (max. tanδ) = 187°C, und KIC = 0,72 MPam1/2 und somit die Zielparameter beinahe erreicht. Das Harzsystem DGEBA/1,2-DACH erfühlte ohne eine Modifizierung knapp die Vorgaben (TG (max. tanδ) = 187°C, und KIC = 0,70 MPam1/2). Auch das Phosphoramidat DEP(Pip)DEP wurde hinsichtlich seiner nachvernetzenden Eigenschaften untersucht, doch erwies es sich im Vergleich zu DEP und DDPO als weniger effizienter Nachvernetzer. Die Erhöhung der TG beruht auf einer Nachvernetzung durch die Umesterung des Phosphits mit den gebildeten OH-Gruppen der Epoxidmatrix, wobei der entsprechende Alkohol jeweils abgespalten wird. Der Mechanismus der Umesterung wurde mit Hilfe speziell für diesen Zweck synthetisierter Modellsubstanzen untersucht. Mittels NMR- und IR-Spektroskopie wurde gezeigt, dass der erste Schritt der Umesterung bereits bei 80°C stattfindet, der zweite Schritt benötigt eine wesentlich höhere Temperatur bzw. eine längere Reaktionsdauer. Bei Versuchen mit Dimethylphosphit wurde das Freiwerden von Methanol nachgewiesen. Um die Bruchzähigkeit der DGEBA-Harze zu verbessern wurde die zähmodifizierende Wirkung unterschiedlicher, kommerziell verfügbarer Modifier in einem durch Polyaddition härtenden Harzsystem (DGEBA/IPDA) sowie im durch Homopolymerisation härtenden Harzsystem DGEBA/EMIM Ac untersucht. In beiden Harzsystemen wurden folgende Zähmodifier getestet: Nanopox® (Nanosilika-Partikel), Nanostrength® (Blockcopolymere), Nanostrength®+Nanopox®, Albidur® (Kern-Schale-Partikel), Albidur® und Nanopox®, PolyTHF® 650, PolyTHF® 1000, PolyTHF® 2000, (PolyTHF® mit unterschiedlichen Molmassen), Boltorn™ P501, Boltorn™ P1000, Boltorn™ U3000 (dendrische Polymere mit unterschiedlichen Hydroxylzahlen), Genioperl® (funktionelles Silikonpolymer), Virantage® (PESU), Albipox® 1000 (unreaktiver Kautschuk). Zudem wurde ein weiterer Zähmodifier (TEA-Oligomer) synthetisiert und in den Harzen getestet. Die Zähmodifier zeigten teilweise unterschiedliche Wirkungen in beiden Harzsystemen. Als Trend war zu erkennen, dass ein hoher Effekt auf die Bruchzähigkeit mit einer Erniedrigung der Glasübergangstemperatur einherging. Jedoch wurden auch Harzsysteme mit verbesserten mechanischen Eigenschaften und relativ hohen Glasübergangstemperaturen erhalten. Von allen mit den kommerziellen Modifiern modifizierten Harzsystemen lieferte DGEBA/IPDA/Nanopox (5 w%)/Nanostrength(5 w%) die besten Ergebnisse bezüglich der thermischen und mechanischen Eigenschaften (TG (max. tanδ) = 157°C und KIC = 1,15 MPam1/2). Mit Kombinationen aus TG- und Zähmodifiern gelang es eine Verbesserung sowohl der thermischen als auch der mechanischen Eigenschaften der untersuchten Harzsysteme zu erreichen. Ein auf diese Weise verbessertes System ist DGEBA/IPDA/PolyTHF®2000(10 w%)/DEP(0,6 w%) mit folgenden Eigenschaften: (TG (max. tanδ) = 180°C und KIC = 0,86 MPam1/2). Des Weiteren wurden TG- und Zähmodifier chemisch verknüpft und somit eine Anbindung von Zähmodifiern an die Epoxidmatrix geschaffen. Die auf diese Weise erhaltenen Modifier verbesserten zwar die Eigenschaften des Reinharzes, konnten aber mit Harzsystemen, bei denen TG- und Zähmodifier als Einzelkomponenten zugegeben wurden, nicht konkurrieren. Somit gelang es DGEBA-basierte Reinharzsysteme zu erhalten, die sowohl hohe Bruchzähigkeiten als auch hohe Glasübergangstemperaturen TG (max. tanδ) besitzen. Dies wurde durch die Einarbeitung von TG- und Zähmodifiern und die Anwendung eines Nachtemperungsschrittes beim Härtungs¬vorgang erreicht. Die Ergebnisse dieses Untersuchungskomplexes zeigten, dass sich die Bruchzähigkeit der untersuchten Harzsysteme in stärkerem Ausmaß beeinflussen lassen als die Glasübergangs-temperaturen. Im zweiten Teil der Arbeit wurden Furanharz-Preformulierungen, die ebenfalls für Anwendungen in der Automobilindustrie geeignet sein sollten, entwickelt, ihr Härtungsverhalten untersucht und ihre Eignung als Matrix für Naturfaserverbundwerkstoffe getestet. Das Ziel bestand darin ein Furanharzsystem (Prepolymer) zu entwickeln, dessen Gehalt an freiem FA und Formaldehyd 1 % bzw. 0,05 % nicht übersteigt, das kein Phenol enthält und bei 150-200°C ausgehärtet werden kann. Zudem sollte die Viskosität 100 Pa*s aus Gründen der Verarbeitbarkeit nicht übersteigen. Um ein oligomeres Furanharz (Prepolymer) mit den genannten Eigenschaften zu erhalten, wurde Furfurylalkohol (FA) zunächst in Gegenwart des Katalysators Maleinsäureanhydrid (MA) einer Polykondensationsreaktion unterzogen. Dabei wurden unterschiedliche Reaktionsbedingungen angewendet, insbesondere wurde der Einfluss der Reaktionsparameter auf die Viskosität und den Restmonomer-Gehalt untersucht. Mit dem Katalysator MA ließ sich jedoch kein Prepolymer mit den geforderten Eigenschaften erzeugen, da bei noch vorhandenem Restmonomer die Molmasse stark anstieg, was zu einer viel zu hohen Viskosität führte. Dieses Problem ließ sich nicht durch Neutralisation des sauren Katalysators mit anschließendem Abdestillieren des Restmonomers (FA) beheben. Wesentlich erfolgreicher verliefen die Polykondensationsversuche bei Verwendung des Katalysators Itaconsäureanhydrid (IA). Es wurde gezeigt, dass es sich bei IA um einen im Vergleich zu MA viel weniger aktiven Katalysator handelt, der es ermöglicht das Restmonomer durch Destillation unter vermindertem Druck zu entfernen, ohne dass ein starkes Fortschreiten der Polymerisation mit Erhöhung der Viskosität auftritt. Auf diese Weise wurde ein Oligomer-Gemisch mit einem geringen Restmonomer-Gehalt (0,96 w%) und einer geringen Viskosität (80 Pa*s) erhalten. Dies war mit MA nicht möglich. Die somit erhaltenen Prepolymere wurden mit unterschiedlichen analytischen Methoden untersucht, welche bestätigten, dass alle Grenzwerte von toxischen Substanzen wie FA und Formaldehyd eingehalten wurden. Das Härtungsverhalten derartiger mittels IA-katalysierter Polykondensation und destillativer Restmonomer-Abtrennung erzeugter Prepolymere wurde bei Verwendung unterschiedlicher Katalysatoren untersucht. Die mechanischen Eigenschaften der resultierenden Materialien wurden mittels Zugdehnungsversuchs bestimmt und mit denen aus dem Marktprodukt BioRezTM 080101 und BioRezTM 120816 in gleicher Weise hergestellter Proben verglichen. Es wurden nahezu die mechanischen Kenndaten der BioRezTM-Proben erreicht (Bruchspannung von 32-35 MPa und Bruchdehnung von 3%). Zudem wurde das Prepolymer mit den Zähmodifiern PolyTHF® (mit unterschiedlichen Molekularmassen), Boltorn™ mit unterschiedlichen Hydroxylzahlen, PEG 2000, PPG 2000, PE/PEG-Blockcopolymer und Nanostrength® versetzt und getestet, um die mechanischen Eigenschaften des gehärteten Harzes zu optimieren. Die Modifier Boltorn™ U3000, PE/PEG-Blockcopolymer und PolyTHF®2000 haben im Reinharz eine Verbesserung der Eigenschaften hervorgerufen. Dabei wurde mit dem Zähmodifier Boltorn™ U3000 die höchste Verbesserung der Bruchdehnung (6%) und der Bruchspannung (50MPa) erreicht, was auf eine Phasenseparation zurückzuführen ist. Außer gehärteten Reinharzproben wurden auch flachsfaserverstärkte Verbundmaterialien aus den mittels Polykondensation synthetisierten Furanharz-Prepolymeren sowie in gleicher Weise aus dem Marktprodukt BioRezTM hergestellt, und ihre mechanischen Parameter wurden mittels Dreipunktbiegeversuchen ermittelt. Auch hier erzielten aus dem Prepolymer hergestellte Materialien nahezu die gleichen Ergebnisse (Biegemodul Ef = 34 GPa, Biegespannung σfm = 353 MPa) wie mit dem Marktprodukt BioRezTM 120816 (Biegemodul Ef = 37 GPa, Biegespannung σfm = 391 MPa) erzeugte Proben. Des Weiteren wurde die Wirkung von Zähmodifiern in den flachsfaserverstärkten Verbundmaterialien untersucht. Überraschenderweise konnte der bei den Reinharzen erzielte positive Effekt nicht bestätigt werden. REM-Untersuchungen zeigten, dass die bei den Reinharzen beobachtete Phasenseparation in diesem Fall nicht auftritt. Es gelang im Rahmen dieser Arbeit ein neues Furanharzsystem zu entwickeln, dass die vorgebenden Zielgrößen hinsichtlich des maximalen Restmonomer- und Formaldehydgehaltes, der Viskosität sowie der mechanischen Eigenschaften der gehärteten Materialien erfüllt, auf nachwachsenden Rohstoffen basiert und somit wesentliche Eigenschaften für eine kommerzielle Anwendung besitzt.
The probability of being affected by osteoarthritis during lifetime is about 20 % in Germany. The disease originates from a degenerative alteration of joints in which the lipid layers covering the cartilage and the cartilage itself are depleted, and the underlying bone is exposed. The treatment mainly includes pain-relieving therapies and physiotherapy for maintaining mobility. A long-term solution is only an artificial joint replacement (endoprosthesis) which, however, has to be inserted by surgery and must be replaced after about 10 to 15 years.
Since the 90s a new treatment called viscosupplementation exists. This non-surgical procedure promises to preserve one's own natural joint while at the same time recovering its functionality. It is based on studies on diseased joints, which showed that the volume of the synovial fluid increases while the concentration and the molecular weight (MW) of the contained hyaluronic acid (HS) decrease. Further investigations indicate that surfaceactive phospholipids (PLs) play an important role in joint lubrication in addition to the HS. Based on these findings, an intra-articular injection of hyaluronic acid (HS) or mixtures of HS and PL is used during viscosupplementation. However, the effectiveness of the method is discussed controversially.
The aim of this work was, therefore, to investigate the interactions of the main components in a joint by means of a simplified model system, and to examine the impact of HS and polymeric substitutes on PL layers covering the cartilage. Simultaneous in-situ neutron reflection (NR) and infrared (IR) measurements at the instrument BioRef at Helmholtz-Zentrum-Berlin (HZB) should provide insights into the internal structure and phase behavior of the lipid layers. The development of a custom-fit shear cell allows to simulate shear in joints and to gain information on the stability of the systems. Further systematic studies on the nature of interactions between PLs and HS or polymeric substitutes were carried out by means of ellipsometric measurements.
For the investigation of the interaction between PLs and polyelectrolyte (PE) or HS solutions, different parameters of the solutions were deliberately changed in the first experiments. In particular, the charge, the molecular weight and the concentration of the PEs or the HS, the concentration and type of added salts and the pH were varied. For this purpose, silicon substrates coated with lipid oligolayers and exposed to water were first characterized and served as an internal reference. After reaching equilibrium, the system was subjected to the above-mentioned changes, measured again and compared with the reference measurement.
For charged PEs, a strong increase in the lamellar layer thickness of the lipids was found at low concentrations, which decreased with increasing PE concentration. Uncharged polymers induced only low swelling, which increased slightly with increasing PE concentration. This indicated that the strong swelling behavior of the lipid layers is based on electrostatic interactions. It was assumed that the selective adsorption of the PEs on the lipid bilayers electrostatically charges the layers. Experiments on charge shielding byexposure to salt solutions and changes in pH as well as the modeling of NR data further confirmed this assumption.
The exact localization of the PE or HS molecules within the lipid layers should be facilitated by NR measurements. Modeling of the reflectivity curves for polyallylamine hydrochloride (PAH) with an average MW of 58 kDa showed an integration into the chain regions. By means of appropriate contrast variation in the systems utilizing deuterated lipids, a direct, model independent detection of the incorporation of PAH into the layer system was feasible so that possible sources of error during modeling could be excluded. Such incorporation suggests bridging of the lipid layers by HS and PEs, which can lead to the formation of a hydrogel-like structure possibly protecting the cartilage.
In line with the concept of the viscosupplementation, a stabilization of the lipid layers against shear could be determined upon addition of HS or the polymeric substitute PAH. However, the expected MW dependency could not be verified. HS showed a stronger stabilizing effect than the PAH, but only after markedly longer incubation times.
In the present work it was shown that HS and polymeric substitutes show a stabilizing effect on the lipid coating of the joints, which can possibly lead to a reconstitution of lowfriction joint movement. The idea of viscosupplementation appears to be promising, and by taking other components such as proteoglycans or cartilage coatings into consideration, an effective non-operative treatment of osteoarthritis should be possible in the future.
Defeating cancer is one of the major challenges that humankind is facing today. To this end, nuclear medicine offers promising approaches including radiometal-based pharmaceuticals. The work presented in this thesis focused on the development of new ligand systems for application as metal-chelating units in radiopharmaceuticals. These novel ligands were evaluated in various non-radioactive and radioactive metal complexation studies concerning their potential application in nuclear medicine.
This doctoral thesis is divided into four chapters. The main focus of this thesis is on the development of conjugated polymer-based chemical tongues and their sensory applications. In the first chapter, introductions on the synthesis of conjugated polymers and their sensory applications are summarized. In chapters 2-4, several types of polyelectrolyte-based chemical tongues have been constructed and been applied to the discrimination of small molecular analytes, complex mixtures and bioanalytes. In the last chapter, experimental details are provided.
Theoretical chemistry has become an important branch of modern chemistry. Theoretical investigations improve our understanding of chemical problems and can predict properties or reaction pathways. Especially in photochemistry, quantum chemical calculations are used along with spectroscopy to analyze the interactions of molecules with light. In recent years, new methods like time-dependent density functional theory (TD-DFT) and the algebraic diagrammatic construction scheme for the polarization propagator (ADC) have been developed allowing calculations of excited states of molecules of chemical relevant size with an accuracy directly comparable with experimental results. These methods allow not only for the calculation of excitation energies, but also of excited state properties, electron densities, absorption strengths and even photoreaction pathways can be calculated. This paves the way for the theoretical investigation of all photochemical processes. Typically, however, chemical reactions and spectroscopic measurements are performed in solution. Unlike in gas phase, molecules in solution are comparatively close together, leading to an interaction between the solvent and solute molecules. In biochemistry, reactions often take place in the active center of a protein and in technical photochemical applications such as organic light emitting diodes (OLEDs) the chromophore is packed in a matrix. Hence, for comparable quantum mechanical calculations, the influence of the environment has to be considered as well. Since a direct treatment of the full environment is generally not feasible due to the computational demand of quantum chemical methods, an approximative treatment of the interaction using specific environment models is made. In my dissertation, I focused on two main topics involving both the application of existing theoretical methods, and the development of new theoretical methods. In the first part, I investigated the photochemical and electrochemical properties of various phosphorus-tetrathia-[7]heterohelicenes. The ground and several excited states of tetrathia-[7]heterohelicene-dialkylphosphane-borane (TTH-DAPB) and tetrathia-[7]heterohelicene-diphenylphosphane-gold(I)-chloride (TTH-DPP-Au(I)) have been analyzed using DFT, TD-DFT and RI-CC2. These molecules belong to the the class of helicenes, which are characterized by multiple annelated aromatic rings forming a helical structure which induces chirality. The optimized ground state equilibrium structures were compared with experimental structures determined by X-ray crystallography and showed generally good agreement. The eight energetically lowest excited singlet states have been calculated. Employing a constant shift accounting for environment effects and intrinsic errors of the applied method, the calculated spectra almost perfectly resemble the experimental absorption and circular dichroism spectra. In both molecules, both the S1 and S2 state contribute to the first absorption band. Therefore, vibrationally resolved absorption spectra have been calculated for these two states for both molecules. It could be shown that only the first excited state determines the absorption band. The second excited state exhibits a very broad band due to many normal modes contributing to the vibronic excitation. In general, the TTH backbone dominates the photochemical properties and the phosphorus and gold atoms exhibit only minor influences. In addition, electrochemical properties of the phosphine-oxide TTH derivatives TTH-(PO(n-Bu)2)2, TTH-(PO(Ph)2)2 and TTH-PO(Ph)2 as well as of the two phosphine-selenide TTH derivatives TTH-(PSe(Ph)2)2 and TTH-PSe(Ph)2 have been calculated. Ionization energies and electron affinities have been computed both in gas phase and solution. In solution, all first electron detachments and attachments are localized on the TTH moiety with only minor influence of the substituents. Each process is qualitatively determined in all molecules by a single frontier orbital, which has been verified by difference density analysis. For the phosphine-oxide TTH derivatives the gas phase results resemble the results in solution. The phosphine-selenides, however, show a different picture. The lone-pairs are shifted higher in energy without stabilization of the environment, leading to an ionization localized at the selenium atom in the gas phase. The second focus of my dissertation was the development, implementation, and testing of a new method for including environment interaction in the excited state of a central molecule. To this end, I combined frozen density embedding thoery (FDET) with the ADC method to develop the new FDE-ADC method. This method is implemented in the quantum chemical program package Q-Chem as the module fdeman, which manages the FDE-ADC calculation. In FDET, the supersystem is divided in two subsystems: the embedded system (A) and the environment (B). The name „embedded system“ comes from the fact that it is embedded in the electron density of the environment. The inuence of the environment is expressed in an embedding potential, which depends on both electron densities of A and B. In fdeman, the whole FDE-ADC calculation is performed in a four step process: a) generation of the electron density of the embedded system _A(~r), b) generation of the electron density of the environment _B(~r), c) calculation of the embedding potential vlin emb(~r) and _nally d) applying vlin emb(~r) in an FDE-ADC calculation by adding it to the Fock matrix during the SCF The second focus of my dissertation was the development, implementation, and testing of a new method for including environment interaction in the excited state of a central molecule. To this end, I combined frozen density embedding theory (FDET) with the ADC method to develop the new FDE-ADC method. This method is implemented in the quantum chemical program package Q-Chem as the module FDEman, which manages the FDE-ADC calculation. In FDET, the supersystem is divided in two subsystems: the embedded system (A) and the environment (B). The name „embedded system“ comes from the fact that it is embedded in the electron density of the environment. The influence of the environment is expressed in an embedding potential, which depends on both electron densities of A and B. In FDEman, the whole FDE-ADC calculation is performed in a four step process: a) generation of the electron density of the embedded system rho_A, b) generation of the electron density of the environment rho_B, c) calculation of the embedding potential v_emb and finally d) applying v_emb in an FDE-ADC calculation by adding it to the Fock matrix during the SCF followed by an ADC calculation using the orbitals influenced by the environment. While the straight-forward implementation of FDE-ADC uses a supermolecular basis to express both density matrices and the embedding potential, an approximate variant named re-assembling of density matrix (RADM) has been introduced in which the density matrix of A is built together from MP(2) and HF based density matrices like a patchwork. The created embedding potential is subsequently cut to the monomer basis which features an FDE-ADC calculation using only the basis functions of the embedded system. This can be done since in the contraction of the density of A with the embedding potential, only the values of the block in the density matrix representing the embedded system contribute. FDE-ADC has been benchmarked up to third order perturbation theory employing three test systems, designed to exhibit an increasing strength of environment interaction. The test systems are 1) benzene with a hydrogen fluoride molecule in plane with the benzene ring, 2) benzaldehyde with a hydrogen-bonded water dimer and 3) uracil surrounded by five hydrogen-bonded water molecules. In the benchmark, the FDE-ADC results have been compared with supermolecular ADC calculations. The deviation from the reference calculation in excitation energies and oscillator strengths determines the accuracy of FDE-ADC. For SE-FDE-ADC(2) and RADM-FDE-ADC(2), mean absolute errors (MAEs) of 0.025 eV and 0.040 eV in excitation energies have been determined, respectively. For RADM-FDE-ADC(3), an MAE of 0.029 eV has been calculated. These errors are well below the intrinsic error of the underlying ADC methods, thus demonstrating the performance of FDE-ADC. This is furthermore demonstrated in three representative applications. First, the excited states of benzoquinone in 42 methanol molecules have been investigated. Next, the vertical photochemical properties of the photoswitch spiropyran in 100 water molecules have been investigated. In the last application, the core-valence excited states of carbon monoxide inside a C60-cage have been calculated. Using a frozen environment neglects the influence of the embedded system on the environment. This is called environment polarization and can be added following two different approaches. In the first variant referred to as pre-polarization, the ground state influence of the embedded system on the environment is treated by an electrostatic potential which is applied during the calculation of the environment density. This way, rho_B is not calculated in the gas phase but instead in the presence of A. In the second variant, referred to as excitation-induced environment polarization, the influence of an electronic excitation of A on the environment is considered. Therefore, the subsystems are interchanged and alternatingly embedded in each other until self-consistency (freeze and thaw). Here, two approximate variants to include excitation-induced environment polarization are introduced. In the first variant, named state-specific iteration (SSI), the alternate embedding is performed once, which prevents changes in the order of the excited states. In the second variant called difference density polarization potential (DDPP), the environment is embedded consecutively in the ground and excited state density of system A. The electron difference density describing the polarization of the environment is used to create a potential which is employed to calculate an energy correction for the excitation energy of the excited state of A. Both SSI and DDPP as well as the pre-polarization are implemented in the module FDEman in Q-Chem. In tests, both the pre-polarization and SSI could increase the accuracy of FDE-ADC. In the case of SSI, up to 35 % increased accuracy is observed. DDPP currently does not improve the results. In total, the FDE-ADC method is a promising approach for considering environmental effects on electronically excited states. The error of this method is lower than the intrinsic error of the employed ADC method. Using the RADM approximation, explicit treatment of extended environments is directly feasible, making FDE-ADC a „black box“ method for the calculation of excited states in complex environments.
In the scope of this thesis, a systematic study about coherent control with shaped femtosecond pulses in the one-photon regime was performed. This regime is especially important in nature as photochemical and -physical reactions are driven by sun light, i.e. at very low intensities. Apart from the relevance of these conditions in nature, coherent control experiments at low intensity are well suited to gain understanding of the underlying processes as well as to control them by using shaped laser light fields. For the experimental shaping in the visible spectral range, a liquid-crystal spatial light modulator (LCM) was utilized. Here, it was shown for the first time that such an LCM introduces noise on the tailored spectral phase. The detailed characterization of the noise implied that molecular properties like the mobility of the liquid crystals cause the noise. Reliable pulse shapes on a pulse-to-pulse basis were achieved by externally cooling the LCM. Due to appropriate data averaging, coherent control experiments were successfully performed, where even small differences in the shaped pulses are important. These control experiments aimed at the enhancement of electronic population and vibrational coherence in the ground and excited state in dependence on the temporal shape of the excitation pulses for various excitation spectra. The temporal shape of the excitation pulse was tailored to linearly chirp pulses, multipulses, whose interpulse distance matches the period of the dominant molecular mode, and the sum of both as chirped multipulses. While the ideal choice to enhance the population and the vibrational coherence in the ground state is a resonant negatively chirped multipulse, the excited state is enhanced best with a blue-detuned positively chirped multipulse. These transient absorption experiments were performed on a prototype chromophore. However, the results should be applicable to other systems. These kinds of control experiments should be transferred to DNA bases and prototype molecules, which can be easily addressed theoretically. As many organic molecules absorb light in the ultraviolet wavelength regime, an experimental set-up for the shaping of femtosecond pulses in the spectral range between 250 nm and 350 nm was developed and characterized in detail. This setup provides the basis for future experiments with organic samples.
Ab initio quantum chemical methods are useful tools and widely employed for the study of excited states, which are the central quantities in photochemistry. A robust understanding of photochemical processes following electronic excitation of molecules does not only allow for the characterization of the physical and chemical properties, but also offers a solid foundation for the successful design and development of novel light-responsive molecular devices. In light of the importance of excited states in photochemical processes, appropriate quantum chemical methods for a reliable and accurate description of the electronic structure need to be chosen carefully. In practical calculations, density functional theory (DFT) and time-dependent DFT (TDDFT) can provide a good compromise between accuracy and computational effort for the treatment of ground and excited states. The algebraic diagrammatic construction (ADC) scheme for the polarization propagator, which is known to deliver accurate excited states information, is often used to benchmark TDDFT results. The basic background of quantum chemistry and several popular quantum chemical methods for the study of excited states are introduced in chapter 2. To obtain insights into novel multiphotochromic properties and the unique isomerization behavior of multiple azobenzenes, a series of linear- and non-linear multiazobenzenes are investigated with selected quantum chemical methods in chapter 3 and chapter 4. Moreover, an evaluation of the restricted-virtual-space (RVS) approximation within the algebraic diagrammatic construction (ADC) scheme for the polarization propagator for the purpose of speeding up excited state calculations of medium-sized and large molecular systems is presented in chapter 5. In more detail, chapter 3 presents investigations of the absorption spectra and the isomerization mechanism of the parent azobenzene (AB) and linear coupled azobenzenes ((AB-(n)). The relaxed potential energy surfaces along the CNNC rotation, CNN inversion and the concerted-inversion pathways were calculated with TDDFT to explore the isomerization mechanism of linear multiazobenzenes. The results show that the order of electronically excited states changes with increasing chain length because the excitation energies of the low-lying excited states display different levels of decline. A significant dual band appears in the π-π* absorption band of cis-AB-(n)s due to strong excitonic coupling between two connected sub-azo moieties. The S1 potential energy surface of AB and the linear AB-(n)s is essentially barrierless along the rotation pathway and a conical intersection is most likely to appear in all cases of the AB-(n). Thus, it is concluded that the isomerization in the n-π* state favours the rotation mechanism. Although a large barrier was found in the S1 potential surface along the concerted-inversion pathway, the concerted-inversion path is considered to be an energetically favorable mechanism when excitation to the S2 state or even higher excited states occurs. Because the energy gap between the S2 and S1 states becomes quite small, rapid relaxation from higher excited states to the S1 state occurs more easily, which is beneficial to overcome the potential energy barrier on the S1 surface. In the subsequent chapter 4, several non-linear azobenzene systems consisting of two or three azo subunits are studied. The absorption spectra of o-, m- and p-bisazobenzenes were primarily calculated using time-dependent density functional theory together with and without conductor-like polarizable continuum models (C-PCM) modelling solvation. The results show that intramolecular excitonic interaction between the azo subunits occurs in the case of the o-bisazobenzenes, which accounts for the two significant excitonic bands in the absorption spectrum. Strong π-conjugation extending over the two azo subunits was observed for p-bisazobenzene, leading to planarity of the molecule as well as low quantum yield for switching. In contrast, m-bisazobenzene exhibits a very similar spectral feature compared to the monomeric azobenzene and the azo subunits operate nearly independently from each other. The following investigation of meta-tris-azobenzene (MTA) is based on the intriguing meta- connection pattern. TDDFT simulations fully characterize spectral differences in the absorption spectra of MTA and various substituted MTA derivatives. It is found that the distribution of the main π-π* band of MTA is also quite similar to the monomer azobenzene, only differing in intensity, which reveals decoupling of the three sub-azo units. The auxochromic shift in the absorption spectrum can be modulated by a series of introduced functional groups. This study shows that each individual sub-azo unit of substituted MTA can be selectively and reversibly switched by specific wavelengths of light. In addition, the photophysical and photochemical properties of cyclotrisazobenzene (CTA), which shows a high stability due to its constrained ring system, were addressed. The PES along the isomerization pathway of the azobenzene units in CTA show that isomerization is essentially impossible even though the CTA molecule is excited to higher excited states. It indicates that relaxation of excited CTA does not lead to photoisomerization. This study can be extended to relevant CTA derivatives, thereby probably revealing unexpected multiphotochromic behavior. Overall, quantum chemical investigations of coupled multiazobenzenes not only provide deeper insight into multiphotochromic properties and theirs unique isomerization behavior, but also pave the way for the design and development of novel photoresponsive applications, based on azo subunits, with different connection patterns. In Chapter 5, the applicability and limitations of the restricted virtual space (RVS) approximation for use within the algebraic diagrammatic construction (ADC) scheme for the polarization propagator up to third order is evaluated. In RVS-ADC, not only the core but also a substantial amount of energetically high-lying virtual orbitals is disgarded in excitation energy calculations of low-lying excited states. RVS-ADC calculations are performed for octatetraene, indole, and pyridine using different standard basis sets of triple-zeta quality, i.e. 6-311G*, cc-pVTZ and def2-TZVP. The results show that freezing core and less than 30% percent of the high-lying virtual orbitals has a negligible effect on ππ* excited states within RVS-ADC(2). However, for nπ* or πσ* states, the RVS approximation is generally less reliable, whereas its accuracy is greatly improved by using the third-order ADC level. Furthermore, a unified and basis-set independent normalized virtual orbital threshold (NVT) is introduced, making the RVS approximation controllable and applicable.
Die Fluoreszenzmikroskopie hat sich als leistungsstarke Technik in allen Bereichen der Naturwissenschaften zur Untersuchung von Strukturen und dynamischen Prozessen etabliert. Im Laufe der letzten Jahrzehnte wurden Techniken entwickelt, deren Möglichkeiten weit über die herkömmlicher Mikroskopie hinaus reichen und nicht nur das Beobachten kleinster Objekte erlauben, sondern selbst die beugungsbedingte Auflösungsgrenze optischer Systeme überwinden. Mikroskopie im Allgemeinen und hochauflösende Methoden im Speziellen sind jedoch nur so gut wie die eingesetzten Fluoreszenzfarbstoffe. Während modernste Technik in der Lage ist, dreidimensionale Aufnahmen kleinster Strukturen bis hin zu einzelnen Emittern abzubilden, richtet sich nun der Fokus auf die Entwicklung neuer, leistungsfähiger Fluoreszenzsonden, deren Fähigkeit sich nicht alleine auf das Emittieren von Fluoreszenz beschränkt. Durch geschicktes Design können nicht nur elementare Eigenschaften wie molekulare Helligkeit und Photostabilität optimiert werden. Vielmehr kann eine maßgeschneiderte Funktionalisierung völlig neue Anwendungsmöglichkeiten eröffnen. In dieser Arbeit wurden neue Fluoreszenzsonden auf Basis einer unnatürlichen Aminosäure entwickelt, charakterisiert und in unterschiedlichen Methoden eingesetzt. Der modulare Aufbau ermöglicht das einfache Kombinieren unterschiedlicher Fluorophore mit einem Bipyridin-Liganden zu kompakten Fluoreszenzsonden, die aufgrund der Komplexierung von Metallionen zwischen einem hellen, stark fluoreszierenden und einem dunklen Zustand geschaltet werden können und daher den Einsatz lichtgetriebener Prozesse überflüssig machen. Eine Vielzahl an Farbstoffkonjugaten konnte erfolgreich dargestellt werden, die sowohl in Ensemble- als auch in Einzelmolekülmessungen untersucht und anschließend zur Markierung geeigneter Zielstrukturen in fixierten Zellen eingesetzt wurden. Die überzeugendsten Ergebnisse wurden mit dem Atto633-Derivat erzielt, das eine Restfluoreszenz von etwa 11 % zeigt sowie eine Komplexbildungskonstante für Cu(II) von (8.11 ± 0.24) 106 M-1, die aus der Schaltkinetik einzelner Emitter bestimmt wurde. Das Potential der chemischen Schalter wurde durch die Anwendung in der Lokalisationsmikroskopie demonstriert, aus der Halbwertsbreiten der markierten Filamente bestimmt wurden, die mit etwa 70 nm deutlich unterhalb der optischen Auflösungsgrenze liegen. Die Vielseitigkeit wurde durch den Einsatz im chemischen Multiplexing gezeigt, das zudem noch mit der STED-Mikroskopie kombiniert wurde, um hochaufgelöste, mehrfarbige Bilder aus einem einzigen spektralen Kanal zu erzeugen.
In this work, novel materials for organic light-emitting diodes (OLEDs) have been synthesized and characterized. In the first part, the development of new host materials for blue phosphorescent OLEDs is described. These compounds have to fulfill three major requirements: they should possess good charge-transport properties, a stable amorphous phase at operation temperature and, most importantly, their triplet energy E(T1 S0) has to exceed the triplet energy of the emitter. Therefore the conjugated π–system has to be confined. Two different approaches have been pursued: First, the examination of dibenzofurofurans as a novel moiety with a large conjugated π–system, yet high (calculated) triplet energy. Secondly, tetraphenylene was used as a novel molecular design element to connect moieties known for their good charge-transporting properties with little conjugation between these fragments. The properties of all potential target molecules have first been predicted by DFT-calculations. For the most promising candidates, synthetic routes have been developed and executed. In the course of this work, seven novel dibenzofurofuran-based host materials were synthesized, revealing a surprisingly high reactivity of this class of compounds. Furthermore, five new carbazole- and dibenzofuran-annelated tetraphenylenes have been obtained by dimerization of the corresponding biphenylenes. All final products were characterized using UV/Vis-, fluorescence- and phosphorescence spectroscopy, cyclic voltammetry and differential scanning calorimetry. In this way, the most important parameters of a host material, transport levels (ionization potential, electron affinity), triplet energy and glass-transition temperature were determined. Almost all of the obtained compounds show a high glass-transition temperature of Tg > 100°C, transport levels close to those of other common OLED materials and a high triplet energy of E(T1 S0) > 2.7 eV. The most promising candidates were applied in OLED devices, with one of the tetraphenylene derivatives showing an exceptionally high efficency of almost 13%. In the second part of this work, a known emitter was synthetically modified to enable its use in solution-processed OLEDs. Three new, highly soluble emitters have been obtained, showing thermally activated delayed fluorescence (TADF) with high luminescent quantum efficencies (φ > 80%) and short excited-state lifetimes (τ > 4 µs). Moreover, five new host materials for this class of emitters were synthezied and characterized.
Multipulse optical technique is an essential tool on the direct observation of electron-nuclear motions responsible for various molecular properties. For example, light-energy harvesting or anti-oxidation, which flora and fauna have achieved along the course of evolution, are initiated by the molecular dynamics in conjugated hydrocarbons such as conjugated polyenes or porphyrin rings. In the case of the conjugated systems in photosynthetic pigments, a part of the dynamics has been revealed as an electronic-state dynamics. However, it is required to disentangle the remaining part of the molecular dynamics mainly consisting of the vibronic interactions induced by nuclear motions. In the scope of this thesis, the vibronic interactions between the electronic states having Bu or Ag symmetries in conjugated polyenes were detected by use of pump-probe and pump-degenerate four-wave mixing (DFWM) experiments. In addition, as an example of multimodal time-resolved spectroscopies, the combination of the two optical experiments was demonstrated to overcome analytical problems related to precision and accuracy of functional analysis for pump-probe spectra. The significant influences of the vibronic interactions between the electronic states with Ag-Ag or Bu-Bu symmetries were observed by pump-DFWM experiments for a series of the conjugated polyenes having four different conjugated double bond length N = 9, 10, 11 and 13. The frequency shifts of C–C (1100 cm–1) and C=C (1500 cm–1 for Bu state, 1800 cm–1 for Ag states) stretching modes indicated the features and some difference of the two couplings. The coupling between Ag– states appeared for all polyenes under the existence of the excited state with Ag symmetry. On the other hand, the coupling between Bu states only appeared for the polyenes with N = 9 and 10, in which strong degeneracy of two Bu states can exist. In addition, solvent polarizability changed the coupling strength which was examined for lutein (N = 9.5) in three different solvents (hexane, THF and benzene). While the coupling appeared in hexane and in THF, it was absent in benzene since the degeneracy of the ionic Bu+ state and covalent Bu– state were very sensitive to solvent polarizability. The observation could be connected to environmental effects on the photosynthetic polyenes surrounded by proteins and lipids in photosynthetic apparatus. In addition, an example of multimodal approach, which combines two different optical experiments, was demonstrated by the simultaneous analysis of a pair of data sets recorded by pump-probe and pump-DFWM experiments. This approach overcame conventional analytical problems of rotation ambiguity and local minimum in global target fitting. While the characterization of the relaxation model for rhodamine 6G was not uniquely done by global target fitting, the multimodal approach uniquely determined the appropriate kinetic model by the evaluation of four error functions. Moreover, the interpretation of the spectral and temporal elements were based on the response functions of pump-probe and pump-DFWM experiments. The direct detection of vibronic coupling and the methodological development to disentangle the ultrafast molecular dynamics contributes to the investigation of nonadiabatic processes which is crucial to understand molecular properties.
Die vorliegende Arbeit beschäftigt sich im ersten Teil mit der Synthese, Charakterisierung und Anwendung neuartiger TADF-Emittermaterialien zur Optimierung der Quantenausbeute und der Effizienz des Triplett-Singulett-Übergangs. Auf Grundlage von Diphenylsulfonen wurden zunächst durch zeiteffiziente Synthesen zahlreiche Akzeptorstrukturen mit systematischen Variationen hergestellt und mit Carbazol als Donor in Lösung spektroskopisch untersucht. Im zweiten Schritt wurden die Donoren durch bekannte und neu entwickelte ausgetauscht, um die Quantenausbeuten zu erhöhen und die Lebenszeiten angeregter Zustände zu senken sowie eine Prozessierung aus Lösung zu ermöglichen. Dies gelang durch sterische Verdrehung der aromatischen Ringe der Diphenyleinheit. Die hier gezeigten Moleküle wurden in Lösung und im Film detailliert spektroskopisch und energetisch untersucht und in ausreichender Menge hergestellt, sodass sie durch Kooperationspartner als Emitter in OLEDs verwendet wurden. Mit Quantenausbeuten von ungefähr 80 % sowohl in Lösung als auch im Film lagen die entwickelten Materialien unter den besten bekannten blauen TADF-Emittern. Im Rahmen des zweiten Teils der Arbeit wurden Distyrylbenzole entwickelt, die intramolekulare Wechselwirkungen zwischen einer (Diethylamino)methylen-Seitenkette sowie einer Carbonylgruppe aufweisen. Zahlreiche Derivate mit diesem Substitutionsmuster konnten synthetisiert und die Veränderung der Fluoreszenz bei Aufhebung der beschriebenen Wechselwirkung durch Säure gezeigt werden, was eine Verwendung als Sensoren ermöglicht. Mit Nitril- und Sulfonresten konnte das Konzept auf weitere Substituenten mit polarisierten Mehrfachbindungen, jedoch ohne Carbonylgruppen, ausgeweitet werden.
Forschung fasziniert – neue Technik, neue Heilmethoden, oder einfach das Staunen über fremde Planeten und die Wunder der Tiefsee. Was für Köpfe stecken dahinter? Wie kommen WissenschaftlerInnen mit Rückschlägen und Bürokratie klar?
Campus-Reporter Nils Birschmann trifft Prof. Dr. Ed Hurt, der seine Faszination für Forschung zum Beruf gemacht hat.
Der Beitrag erschien in der Sendereihe "Campus-Report" - einer Beitragsreihe, in der über aktuelle Themen aus Forschung und Wissenschaft der Universitäten Heidelberg, Mannheim, Karlsruhe und Freiburg berichtet wird. Zu hören ist "Campus-Report" montags bis freitags jeweils um ca. 19.10h im Programm von Radio Regenbogen (Empfang in Nordbaden: UKW 102,8. In Mittelbaden: 100,4 und in Südbaden: 101,1).
Both, well-defined molecular ordering and the electronic structure at metal/organic interfaces and within thin molecular films are fundamental for charge carrier injection and charge transport in organic electronic devices. This thesis presents a combined study of temperature-programmed desorption, ultraviolet and two-photon photoemission spectroscopy targeting the underlying correlation between charge transfer, hybridization and band formation. Angle-resolved photoemission measurements expose that hybridization at metal/organic interfaces implies a charge carrier density redistribution which in combination with band formation presumably enables improved charge injection. As hybrid bands crossing the Fermi energy additionally determine the transferred amount of charge, charge transfer may serve as sufficient prerequisite for underlying hybridization or band formation at metal/organic interfaces. The observation of an extended space charge region and unoccupied intermolecular hybridization in epitaxial films additionally proves increased charge carrier injection properties in thin molecular films with well-defined molecular ordering and electronic structure.
The antibiotic roseoflavin (RoF) is the only known natural riboflavin (vitamin B2) analogue and is active against gram-positive bacteria. RoF is produced by Streptomyces cinnabarinus (S. cinnabarinus) and Streptomyces davawensis (S. davawensis) and can be considered to be an “antivitamin”. In RoF biosynthesis one of the methyl groups of the predicted precursor riboflavin undergoes a site-specific replacement by a dimethyl amino group whereby 8-demethyl-8-amino-riboflavin (AF) was postulated to be an intermediate. The first discovered enzyme of roseoflavin biosynthesis was the S-adenosyl methionine (SAM) dependent dimethyltransferase RosA which converts AF to RoF. Subsequent systematic gene deletion experiments carried out in the RoF-producer S. davawensis suggested that a single enzyme (RosB) is responsible for the formation of AF. However, when recombinant RosB was tested in an assay mixture containing riboflavin-5’-phosphate (RP) the formation of the predicted final reaction product AF was not observed. Instead the compound 8-demethyl-8-formyl-riboflavin-5’-phosphate (HOC-RP) was detected, probably an intermediate of the RosB reaction. How the formyl-group of HOC-RP was replaced by an amino group to give AF or 8-demethyl-8-amino-riboflavin-5’-phosphate (AFP) remained unclear. The present work was initiated to investigate the predicted oxidation of HOC-RP to 8-demethyl-8-carboxyl-riboflavin-5’-phosphate (HOOC-RP), to identify the amino group donor of the RosB reaction and to shed light on the reaction mechanism of the multi-step enzyme RosB. It was found that RosB accepts only RP as a substrate and not riboflavin (RF). RosB activity depends on the presence of O2, thiamine and the amino group donor glutamate. HOOC-RP was found to be an (additional) intermediate of the RosB reaction. The crystal structure of RosB was solved with bound AFP (1.7 Å) and HOC-RP (2.0 Å). RosB is composed of four flavodoxin-like subunits which have been upgraded with specific extensions and a unique C-terminal arm. Structure-based active site analysis was complemented by mutational and isotope-based mass-spectrometric data to propose an enzymatic mechanism. The present work also shows that the RoF biosynthetic pathway still has not been completely resolved. RosB releases AFP, yet the substrate for the subsequent RosA reaction is AF. Consequently, a phosphatase must be present which has not yet been identified.
Die vorliegende Dissertation beschäftigt sich mit der Untersuchung und Steuerung der Redox-aktivität guanidinofunktionalisierter Aromaten (GFA). Bei diesen in der Arbeitsgruppe Himmel entwickelten redoxaktiven Liganden handelt es sich um starke Elektronendonoren, deren Redoxverhalten unter anderem durch aromatische Substitution oder Komplexierung gesteuert werden kann. Im Rahmen dieser Arbeit wurden die Faktoren, welche für die Reduktionsstärke organischer Elektronendonoren verantwortlich sind, im Detail analysiert. Dabei wurden die intrinsische Reduktionsstärke und die extrinsischen Einflüsse (z. B. durch das Lösungsmittel) getrennt voneinander untersucht. Während die intrinsische Reduktionsstärke durch quanten-chemische Modellierung der Gasphasen-Ionisierungsenergie abgeschätzt werden konnte, beinhalten cyclovoltammetrisch (CV) erhaltene Redoxpotentiale sowohl in- als auch extrinsische Faktoren. Unter anderem durch die Berechnung lösungsmittelabhängiger Ionisierungsenergien konnte gezeigt werden, dass diese Effekte oft in direkter Konkurrenz zueinander stehen. So führt eine Erweiterung des konjugierten π-Systems im Allgemeinen zu einer Zunahme der intrinsischen Reduktionsstärke, aber auch zur Abnahme der Solvatisierungsenergie, welche wiederum einen viel größeren Einfluss auf die Ionisierungsenergie hat als etwa die Generierung von Aromatizität. Zur weiteren Untersuchung der Umgebungseinflüsse wurden Matrixisolationsexperimente, in welchen gasphasenähnliche Bedingungen simuliert werden können, durchgeführt. Hierbei zeigte sich, bei zunehmender Wechselwirkung mit der Umgebung, eine starke Rotverschiebung der elektronischen Übergänge der untersuchten Substanzen. Durch Koordination von Nickel(II)- und Palladium(II)-acetat an den redoxaktiven Zwei-Elektronendonor 1,2,4,5-Tetrakis(tetramethylguanidino)benzol (ttmgb) konnten Komplexe synthetisiert werden, welche in der Lage sind zwei Elektronen in separierten Ein-Elektronen-Schritten abzugeben. In diesen Komplexen scheint der Acetatligand eine entscheidende Rolle bei der Stabilisierung des radikalkationischen Liganden zu spielen. Die starke ferromagnetische Kopplung innerhalb des Monokations [ttmgb{Ni(OAc)2}2]•+ wurde durch SQUID-Messungen im Feststoff, durch paramagnetische NMR-Untersuchungen in Lösung und durch quantenchemische Rechnungen am einzelnen Molekül untersucht. In dieser Arbeit ist mit der Herstellung von Hexakis(N,Nʹ-dimethyl-N,Nʹ-ethylenguanidino)benzol (hdmegb) erstmals die Synthese und Charakterisierung eines stabilen Hexakis(guanidino)benzols gelungen. Trotz seines hohen Stickstoffgehalts, ist hdmegb thermisch stabil und konnte durch Sublimation aufgereingt werden. Durch die maximale Anzahl an Guanidinogruppen, führt der Elektronenreichtum des aromatischen Systems zur Bildung eines starken Elektronendonors mit reversiblem, mehrstufigem Redoxverhalten. Mit einem Redoxpotential von E½ = −0.43 V (gegen Fc/Fc+) für die Abgabe von insgesamt vier Elektronen, ist hdmegb der stärkste bisher bekannte neutrale organische Vier-Elektronendonor. Zudem sollte hdmegb interessante koordinative Eigenschaften besitzen. So sind etwa gemischtvalente Komplexverbindungen des redoxaktiven, potentiell tris-bidentaten Liganden zu erwarten. Aufgrund seiner hohen theoretischen Ladungs-kapazität von 144 Ah·kg−1 ist hdmegb auch als mögliche Alternative zu Li-Ionen-Akkumulatoren interessant. Der Elektronendonor hdmegb ergänzt, durch seinen komplementären Ladungs-bereich, die Reihe etablierter Elektronenakzeptoren als Material zur Ladungsspeicherung.
Der Körper ist eine Hochleistungsmaschine, in jeder einzelnen Sekunde werden in Zellen lebenswichtige Eiweiß-Ketten hergestellt, in mikroskopisch kleinen Fabriken. Wie das funktioniert, wird am Biochemie-Zentrum der Universität Heidelberg erforscht. Campus Reporter Nils Birschmann hat sich dort umgehört und mit Prof. Ed Hurt gesprochen.
Der Beitrag erschien in der Sendereihe "Campus-Report" - einer Beitragsreihe, in der über aktuelle Themen aus Forschung und Wissenschaft der Universitäten Heidelberg, Mannheim, Karlsruhe und Freiburg berichtet wird. Zu hören ist "Campus-Report" montags bis freitags jeweils um ca. 19.10h im Programm von Radio Regenbogen (Empfang in Nordbaden: UKW 102,8. In Mittelbaden: 100,4 und in Südbaden: 101,1).
Die vorliegende Dissertation beschäftigt sich mit der Darstellung, Untersuchung und Optimierung von PPEs im Hinblick auf ihre Anwendung als Halbleitermaterial in organischen Feldeffekttransistoren (OFETs). Speziell die morphologische Untersuchung der Dünnfilme wurde in den Fokus gerückt. Zur Synthese der PPEs wurde die Sonogashira-Kupplung verwendet. Diese erlaubte die Einführung verschiedenster funktioneller Gruppen. Die gezielte Auswahl der Monomere erlaubte die Darstellung halbleitender Polymere mit unterschiedlichen elektronischen Eigenschaften, Löslichkeiten und Schmelzpunkten. Eine anschließende systematische Untersuchung der Halbleitereigenschaften im OFET zeigte, dass ein Zusammenhang zwischen der Polymerstruktur, der Kristallinität im Film und der Transistorleistung bestand. Im Vergleich wiesen PPEs mit linearen gegenüber verzweigten Seitenketten eine höhere Ordnung im Film auf und zeigten die höchsten Ladungsträgerbeweglichkeiten. Es wurden ausführliche Untersuchungen der vielversprechendsten PPEs, bezüglich ihrer Anwendung im Transistor, durchgeführt. Eine wichtige Rolle spielte die Filmmorphologie, welche auf verschiedene Art und Weisen beeinflusst wurde um eine erhöhte Ordnung der Polymerketten zu erzeugen. Dazu wurde die Abhängigkeit von der Temperatur, dem Substrat und dem Elektrodenmaterial im Transistor ausführlich analysiert. Anschließend wurde das Zusammenspiel verschiedener Komponenten im OFET verglichen und ein für PPEs optimierter Aufbau ausgewählt. Die vorliegende Arbeit lieferte auf diesem Weg ein Grundrezept für den Bau von PPE-basierten OFETs. Abschließend sollte überprüft werden, ob für ein ‚perfektes‘, einheitliches PPE eine makroskopische Kristallisation des Filmes erreichbar wäre. Hierfür wurden definierte Oligo(para phenylenethinylen)e (OPEs) dargestellt. Das Hauptaugenmerk wurde dabei auf die Anordnung der OPEs im Festkörper und im Film, also auf die Morphologie, gelegt.
Der Effekt von Elektronenbestrahlung an selbstorganisierende Monolagen (SAMs) von aromatischen Thiolen mit stabförmigen oligophenyl, acene und oligo(phenylen ethinylen) (OPE) Rückgrat, bestehend aus einem bis drei Phenyl Ringen, wurde mit einem besonderen Fokus auf die Entwicklung von strahleninduzierten Prozessen und die Eigenschaften von diesen Filmen als Negativresist in Elektronenlitographie untersucht. Bereits in einem frühen Stadium der Bestrahlung, zeigten alle untersuchten Filme ein ähnliches Verhalten mit einer klaren Dominanz von Quervernetzung. Die Wirkungsquerschnitte für die Modifikation der SAM Matrix und der Beschädigung der SAM-Substrat Grenzfläche wurden mittels einer Primärelektronenenergie von 50 eV bestimmt, welche häufig für die Herstellung von Kohlenstoff-Nanomembranen (KNMs) verwendet wird. Die ermittelten Werte sind ähnlich in innerhalb eines Prozesses und unterscheiden sich nur geringfügig für die verschiedenen Rückgraten. Die zwei-Ring Systeme zeigten mit einer optimalen Dosis von 10-20 mC/cm² bei 0.5-1 keV die beste Eignung als lithographischer Resist. Die Leistung der ein-Ring und drei-Ring Systeme wurde durch die geringere Anzahl an Quervernetzungen und den hohen Widerstand der Ausgangsschichten gegen die Ätzlösungen beeinträchtigt. Ein weiterer Prozess, welcher mit auf die schlechte lithographische Leistung der drei-Ring Systeme zurückgeführt werden kann, aber auch bei den zwei-Ring Systemen bei einer hohen Dosis auftrat, war das spontane Ablösen der quervernetzen SAMs innerhalb der bestrahlten Flächen in Form von KNMs. Aus den lithographischen Daten wurden der Wirkungsquerschnitt und die strahleninduzierte Quervernetzung ermittelt und in Zusammenhang mit Rückstreuung und Sekundärelektronenausbeute diskutiert. Für die drei-Ring Systeme wurde zum ersten Mal die Herstellung von KNMs aus SAMs mit OPE Rückgrat gezeigt. Zusätzlich zu den oben genannten Experimenten wurden die elektrischen Transporteigenschaften von den hergestellten SAMs nach Elektronenbestrahlung (50 eV) untersucht. Die Two-Terminal Junction Methode wurde dafür verwendet. Die erhaltenen Werte für die Stromdichte korrelieren sehr gut mit der molekularen Länge und bestätigen die generelle Formel
The research work presented in this thesis focuses on the synthesis, characterization and preparation of biologically responsive polymers and their nanoparticles containing sulfur in the main chain. Polymerization using click chemistry is relatively new, simple and easy way for the synthesis of linear polymers. Since the discovery of click reactions a decade ago, researchers were much interested in coupling small molecules but eventually more reports have been published in the recent past were polymers and hyper branched structures were prepared by clicking multifunctional groups. Stimuli responsive linear polymers synthesized by click chemistry is one of the less discussed and interesting fields for polymer chemists due its feasibility and unseen potentials. Three different libraries of polymers, polysulfides, poly (β-hydroxy thioethers) and poly(β-thioesters), were synthesized by thiol-yne reactions, thiol-epoxide ring opening polymerization and thiol-ene reactions.
Intensive research is carried out in the area of biologically responsive nanocarries. Many different approaches and methodologies were adapted in the past years for the development of polymer based drug delivery systems. Stimuli based on enzyme response, chemical, pH or temperature changes are already been thoroughly exploited. Response to oxidation is much less investigated, even though there are few literatures based on oxidation sensitive materials there is still a wide area to be explored and understood. Hydrophobic polymer chains of some of the synthesized polysulfides and poly(β-hydroxy thioethers) can be transformed into more hydrophilic ones by oxidation of sulfur to sulfoxides or sulfones using mild oxidizing agents like hydrogen peroxide. A hydrophobic drug/dye encapsulated in the polymer can be thereby released upon an oxidative trigger. Herein polysulfides and poly(β-hydroxy thioethers) polymers were used to prepare nanoparticles by nanoprecipitation, single emulsion and double emulsion techniques. The nanoparticle morphology, size, zeta potential and stability depend on the method of particle preparation which was optimized to meet the final applications. Oxidation responsive drug/dye release was studied under pathological and physiological concentration of hydrogen peroxide. Cellular uptake and cell viability was studied using Hela cells and HUVEC.
Biodegradable polymers are always a good choice for medical applications. In another approach a new library of poly(β-thioesters) was synthesized via base catalyzed thiol-ene polymerization. The presences of β-thioesters bonds make these polymers liable to hydrolysis and hence biodegradable. Synthesized polymers were further used to prepare surfactant stabilized nanoparticles by nanoprecipitation. Nanoparticle size and surface charge was controlled by changing parameters like polymer and surfactant concentrations. Encapsulated drug/dye release kinetics was then studied; an accelerated release of the payload was observed in more acidic condition and lesser in neutral pH.
In conclusion, three different libraries of linear polymers were synthesized using thiol-yne/ene and thiol-epoxide ring opening polymerization. Nanoparticles were then prepared using these polymers and oxidative and pH dependent stimuli response was studied. One of the interesting aspects of this kind of polymerization is its simplicity, mild conditions and less work out procedures. Some of these polymeric nanoparticles efficiently respond to the stimuli applied, release kinetics and nanoparticle degradation were also studied. Cellular uptake and cell viability results confirms good uptake of nanoparticles with minimal toxicity.
Characterization and understanding of electronic properties of nanoscale systems is an important issue in modern nanotechnology including molecular and organic electronics. To advance in this topic, charge transfer (CT) properties of two specific nanoscale systems were analyzed in detail in this work. First, electron transfer (ET) dynamics in supported 2D assembles of molecular wires, self-assembled monolayers (SAMs), were studied by resonant Auger electron spectroscopy (RAES) in a combination with a so-called core hole clock (CHC) approach. A variety of suitable SAMs were custom-designed to address specific questions within the general framework of ET dynamics; most of these SAMs were equipped with nitrile tail groups, serving as a predefined site for the resonant excitation of an electron making the ET. The experiments showed a similar electronic coupling efficiency to coinage metal surfaces for the most frequently used S and Se anchors, solving a long-term controversy. Further, an efficient ET was found in acene-based SAM constituents, manifested by a quite low tunneling decay constant (beta) of 0.25 1/Å, similar to that of oligophenyls. In subsequent experiments on an analogous non-benzenoid system, the same ET properties as for its benzenoid isomer were found. As an ultimate proof of the approach, the nitrile groups were attached directly to the substrate, showing an ET time in the sub-fs region, as has been expected. A well-perceptible contribution of the ET process in the RAES [N1s]pi* spectra of pyridyl-substituted molecules revealed that pyridyl is a suitable resonant group for CHC and can be efficiently used as an alternative to nitrile, while NO2-functionalized SAM constitutents exhibited an inverse ET process. Second, static CT properties of surface-anchored metal-organic frameworks (SURMOFs) were studied, taking the basic and well-known HKUST-1 framework as a most suitable reference system. The measurements were performed with the custom-designed two-terminal junction setup and both pristine and guest-molecule loaded SURMOFs were investigated. The pristine SURMOFs showed CT properties similar to hybrid metal-organic molecular wires, as manifested by avery low beta value of 0.0006 1/Å. The CT experiments performed after the incorporation of the guest molecules, viz. ferrocen, TCNQ and its fluorinated analog F4-TCNQ, into the pores of the framework showed a significant increase in the current density. This increase was especially dramatic in the case of TCNQ, achieving up to 6 orders of magnitude. This finding verified a previously reported and highly announced result for this particular guest molecule, obtaining it, however, for the samples of well-controlled thickness, quality and orientation. At the same time, in contrast to the previous report, loading with F4-TCNQ resulted in a similar increase in the current density as for TCNQ, questioning the proposed CT model. These observations were made for several orientations of the SURMOF and different solvents used for the loading. Based on the experimental data, a novel superexchange mechanism for CT in the redox.-molecule-loades SURMOFs was proposed.
In this thesis, the high degree of control offered by the combination of a broadband femtosecond excitation source and a pulse shaper is exploited to achieve high spectral resolution nonlinear optical microscopy. Especially the coherent anti-Stokes Raman scattering (CARS) process is very important for nonlinear microscopy since it provides label-free three-dimensional contrast based on the vibrational atomic motion. The flexibility of the developed setup not only allows to switch between optimal conditions for the generation of CARS and other nonlinear signals but enables their simultaneous measurement. The complementary contrast of signals like second-harmonic generation (SHG), two-photon fluorescence (TPEF) and the CARS process in a multimodal imaging scheme provides additional information to identify structures and the composition of complex biological samples. It is shown how the individual control over the frequencies taking part in the CARS process can be used to achieve resonant vibrational imaging, overcoming the limitations usually associated with the unspecific excitation of using broadband pulses. Within this tailored spectral focusing approach, CARS signals are enhanced by an order of magnitude and SHG and TPEF intensities are boosted even more, as demonstrated by multimodal imaging of Skin tissue. Furthermore, the method can be directly applied to control the difference frequency generation process occurring when focusing the laser on a nonlinear crystal, to form a tunable broadband infrared (IR) light source. Besides the direct characterization of the IR spectrum by this method, absorption spectroscopy becomes possible in a single-beam approach. A whole new frequency region is hereby unlocked, paving the way for retrieving complementary information from Raman as well as IR interactions in the same setup for the first time.
The blue-green alga Prochloron produces and exports cyclic octapeptides (patellamides) to its obligate host, the ascidian Lissoclinum patella, in large quantities. Since the CuII concentration in the ascidians is a factor of 104 greater when compared to the surrounding sea water, previous studies on model CuII complexes with synthetic cyclic octapeptide derivatives were performed and revealed these complexes to be efficient phosphatase- and carboanhydrase-mimics. Their biological role, however, is so far unknown. With the work presented in this thesis, the dependence of the phosphatase activity of dinuclear patellamide complexes on the side chain configuration as well as on the catalytic metal centre is explored. The results show that the complexes based on ligands with the natural R and S configuration of the patellamide-ligand backbone exhibit 3-5 times higher hydrolysis efficiencies as compared to complexes with ligands that exhibit 4S side chain configuration. Beyond that, the effect on phosphatase efficiency induced by the substitution of the catalytic metal centre CuII for ZnII was investigated. Since only one of the three ZnII patellamide complexes showed catalytic activity, a structural investigation was carried out. In addition to hydrolysis measurements this was accomplished by means of NMR, MS, ITC and a combined MM and QM study. The results indicate a similar binding behaviour of patellamides towards ZnII as shown for CuII, i.e. a coordination site spanned by two nitrogen atoms that are part of a heterocycle and a deprotonated amide nitrogen. Therefore, the lack of phosphatase activity might be caused by the small stability of these complexes under aqueous conditions, as used for the hydrolysis assay. In addition, α- and β-glycosidase- as well as β-lactamase-like activity of the CuII patellamide complexes was examined. It was shown that the imidazole-based complexes act as hydrolases not only for phosphate ester cleavage at pH 7-8 but also for the hydrolysis of glycosidic bonds at alkaline conditions (pH 10). Moreover, β-lactamase-like activity was observed at pH 11.5 for one of the patellamide based complexes. Consequently, these results indicate the ability of the CuII complexes to act as very efficient, pH-dependent catalysts. Recent findings from BEHRENDT et al. pointed to a rapid fluctuation of the pH in close proximity to Prochloron depending on the irradiance. Therefore, the glycosidase and lactamase results could indicate the dinuclear CuII complexes to adopt different functions during day- and night-time, respectively. Abstract X As a contribution towards the elucidation of the metabolic significance of the patellamide complexes, the formation of the complexes was investigated in vitro in buffer at pH 8.2 as well as in vivo. Therefore, a patellamide ligands with an appended reporter groups (RG) were prepared (see Figure 1). The fluorescent tag Atto550 as well as the spin label Proxyl were chosen as the reporter groups. In vitro studies with H4pat-Atto550 indicate the formation of a CuII complex in buffer, however, results from EPR studies with the ligand H4pat-Proxyl and CuII could so far not verify this finding. In addition, a protocol for the uptake of patellamides by Prochloron was developed allowing the introduction of the ligand H4pat-RG into the cells. Results from flow cytometry as well as confocal microscopy support the formation of a CuII patellamide complex in vivo. In addition, preliminary in vivo hydrolysis measurements are presented. In conclusion, the work presented contributes to an improved understanding of the hydrolase-like activities of the patellamide-based copper(II) complexes and gives a first insight on the stabilities of the complexes in Prochloron cells.
Non-local electronic decay mechanisms constitute important pathways for the relaxation of cations produced by the action of ionizing radiation in van-der-Waals or hydrogen bonded chemical environment. Electronically excited cations may undergo the ultrafast Interatomic Coulombic Decay or ICD process, whereby the excess electronic energy is transferred to the environment and used to ionize it. It has been extensively studied by computational and experimental techniques during the last two decades and shown to operate in a variety of systems from rare gas dimers to large biomolecules. In this thesis we investigate using ab initio methods the Electron Transfer Mediated Decay or ETMD process which is responsible for the charge redistribution in environment, whenever atomic cations with a low excess energy and high electron affinity are produced. In ETMD electron transfer to the cation leads to the emission of an electron from the neighboring species. The net result is partial neutralization of the cation and the increase of the charge of the environment by two.
The light rare gas atoms He and Ne have a high ionization potential and, in the presence of a suitable neighbor are likely to undergo ETMD when they are singly ionized, e.g. by photoionization. In particular, we showed that a HeMg cluster efficiently decays by ETMD whenever He is photoionized and a ground state He+ ion is produced. The joint process of photoionization and ETMD corresponds to a one-photon double ionization of Mg. Remarkably, we found that the cross section of this process is three orders of magnitude higher than the cross section of the atomic one-photon double ionization, which demonstrates the prominent role of the neighboring He species in the double ionization. This mechanism of the ETMD driven one-photon double ionization was recently demonstrated experimentally in doped He nanodroplets and is proposed as a method for the experimental production of cold molecular dications.
Multiply charged rare gas cations have higher electron affinities and undergo ETMD with a larger variety of neighboring atoms or molecules. Such cations are naturally produced by the Auger decay following core ionization of rare gases in the X-Ray absorption. The ETMD process reduces their positive charge by one, i.e. leads to their partial neutralization and serves as a purely electronic alternative to neutralization mechanisms driven by the movement of the nuclei. Our calculations show that in small Ne2+Xe and Ne2+Kr2 clusters the ETMD process takes place on a picosecond timescale. The ETMD in these systems is accompanied by nuclear dynamics which in turn enhance the rate of the electronic decay. We show that for such systems ETMD is an important mechanism responsible for the fast redistribution of the localized charge produced in the Auger decay process.
We also demonstrated that multiply charged hydrated metal cations are likely to decay via complicated cascades comprising both ETMD and ICD steps. Our calculations in the Mg2+(H2O)6 microsolvated cluster showed that such a cascade proceeds on a timescale of few hundreds of femtoseconds and leads to a massive degradation of the imetal’s solvation shell through its multiple ionization and emission of slow electrons. Repulsive nuclear dynamics at later stages of the cascade, which were not taken into account explicitly, are expected to considerably reduce its duration. We expect that studying interatomic decay cascades of metal cations is important for understanding mechanisms of the damage caused by X-Rays to metal containing biomolecules such as DNA, metalloproteins etc. For the latter of particular importance is the knowledge of the duration of different interatomic decay steps, since it determines the timescale at which proteins become damaged by X-Rays and beyond which their structure becomes compromised.
These considerations led us to investigate the dependence of ICD lifetimes on atomic charge in excited microhydrated Na2+ and Mg3+ cations. Our ab initio results reproduce within the numerical error the experimental ICD lifetimes of the respective ions in aqueous solutions. We show that the microsolvated Mg3+ cations decay faster than the Na2+ ones, in accordance with experiments on aqueous solutions. The detailed analysis reveals that at characteristic metal-water separations the polarization of the water neighbor enhances ICD the stronger the higher the charge of the metal is. This, together with the shorter Mg-water equilibrium distances, leads to the observed ordering of the ICD rates. We also showed that polarizing the neighbors causes sub-linear growth of ICD rates with the number of water molecules in the first solvation shell. This investigation of ICD in microsolvated metal cations demonstrated the prominent role the cation’s charge and the consequent polarization of the medium have on the decay rate. It also leads to a reasonable expectation that even faster, sub-femtosecond decay lifetimes might be achieved for highly charged solvated metals ions.
Diese Arbeit befasst sich mit der Reaktivität sowie den katalytischen Eigenschaften von Bispidin-Metall Oxo-Komplexen (M = Fe, Ni) bezüglich der Oxidation von Kohlenwasserstoffen. Dabei wird sowohl auf theoretische als auch auf experimentelle Studien zurückgegriffen. Im ersten Kapitel wird eine umfangreiche Dichtefunktionaltheorie-Studie (DFT) über die Reaktivität von Eisen(IV)-Oxo-Komplexen zweier isomerer, pentadentater Bispidin-Liganden beschrieben. Diese unterscheiden sich trotz vergleichbarer Fe(III/IV)=O Redox-Potentiale signifikant in ihrer Reaktivität bezüglich der CH-Aktivierung von Kohlenwasserstoffen und der Sauerstoffübertragungsreaktionen auf Schwefel- bzw. Phosphor-Funktionen. Der Reaktivitätsunterschied wird am Beispiel der CH-Abstraktion von Cyclohexan untersucht und auf die unterschiedlich starke Stabilisierung des elektronischen Grundzustandes der zwei Eisen(IV)-Oxo-Komplexe zurückgeführt. Das zweite Kapitel wendet eine analoge Studie auf die entsprechenden Nickel-Oxo-Komplexe derselben Bispidin-Liganden an. Diese zweite DFT-Studie über die Reaktivität der Komplexe bezüglich der CH-Abstraktion von Cyclohexan wurde in Kombination mit experimentellen Arbeiten aus dem dritten Kapitel angefertigt. Die theoretischen Ergebnisse dieser Untersuchung sollen die experimentellen Ergebnisse prognostizieren bzw. erklären und einen Vergleich mit der Reaktivität der Eisen(IV)-Oxo-Komplexe aus dem ersten Kapitel ermöglichen. Auf Basis dieser DFT-Studie sind im Gegensatz zu den Eisen(IV)-Oxo-Komplexen keine Unterschiede in der Reaktivität bezüglich der CH Abstraktion von Cyclohexan durch die isomeren Bispidin-Nickel-Oxo-Komplexen zu erwarten. Schließlich werden im dritten Kapitel die experimentellen Ergebnisse zur Oxidation von Kohlenwasserstoffen durch Bispidin-Nickel(II)-Komplexe in Anwesenheit eines Oxidationsmittels vorgestellt. Dabei wurden sowohl die beiden isomeren Komplexe, wie sie auch im zweiten Kapitel verwendet wurden, als auch der Nickel(II)-Komplex eines tetradentaten Bispidin-Liganden umfassend charakterisiert und auf ihre katalytischen Eigenschaften bezüglich der Oxidation von Cyclohexan, Adamantan und 9,10-Dihydroanthracen untersucht. Das Reaktionsgemisch bzw. die auftretenden Produkte wurden mit gaschromatographischen Methoden (GC) analysiert und eine mögliche aktive Nickel(III)-Spezies spektroelektrochemisch untersucht. Es konnte gezeigt werden, dass einer der untersuchten Bispidin-Nickel(II)-Komplexe die Oxidation von Kohlenwasserstoffen katalysiert.
Die vorliegende Arbeit liefert neue Erkenntnisse bezüglich der Erhöhung der Porosität für die Synthese von OMIM-Strukturen auf Triptycenbasis. Des Weiteren wird durch die Arbeit klar, dass Triptycenylen-Endgruppen verschiedene Vorteile mit sich bringen. Neben der Löslichkeitserhöhung, was sich auf viele weitere Systeme übertragen lässt, ist es auch möglich die Überlappung der π-Orbitale im Festkörper zu erhöhen. Die Vielzahl an Kristallstrukturen, die während dieser Arbeit erhalten werden konnten, liefern informative Einblicke in das Packungsverhalten der Strukturen. Alle diese Eigenschaften sind interessante Komponenten, die zur Optimierung von organischen Halbleiterstrukturen beitragen können. Erste spektroskopische Untersuchungen zeigten zudem, dass die Kombination aus Porosität und optoelektronische Eigenschaften in den OMIMs grundsätzlich zur Detektion von Analyt-Molekülen geeignet ist.
The primary aim of this thesis is to shed a quantitative light on the mechanics of dynamic biological interfaces with different levels of structural complexities, ranging from lung surfactant models to regenerating tissues. In chapter 3, the correlation between biophysical properties and function of the native extracellular matrix (ECM), mesoglea, of the freshwater polyp Hydra was studied. In the body design of Hydra, mesoglea acts as an interlayer between external (ectodermal) and internal (endodermal) cell layers, sustaining the mechanical integrity of polyps. In this study, nano-focused grazing incidence small angle X-ray scattering on isolated mesoglea revealed that the packing order of Hydra collagen type I was comparable to its vertebrate homologue. The structure was anisotropic with respect to the oral-aboral axis, supporting the extensive extension and contractions of the body along this axis. In the next step, the spatio-temporal evolution of mesoglea mechanics was tracked ex vivo by nano-indentation using an atomic force microscope. The experimental data demonstrated that freshly detached polyps initially had a uniformly soft mesoglea, but mesoglea changed the characteristic "elasticity patterns" during the asexual reproduction. This change could be explained by a quantitative proteome analysis, implying that the mechanical remodeling of Hydra was highly correlated with protease expression activity. When the body column tissue was transformed into head tissue either by a drug or by the over-expression of β-catenin, mesoglea had low elastic moduli over the whole body. This result suggests that the spatio-temporal patterns in mesoglea mechanics is strongly correlated with the stem cell activity. In chapter 4 a highly sensitive two-fingered micro-robotic hand was used to determine the viscoelastic properties of Hydra tissue fragments (regenerates) during early stages of regeneration. Owing to the dexterous grasping motion of microobjects realized by the micro-robot, the bulk elastic modulus of Hydra regenerates could be determined by linearly compressing the tissue by keeping the strain level low. Under a constant strain, the stress relaxation behavior could be interpreted by applying the Maxwell model of viscoelastic materials, yielding the Stokes frictional coefficient and viscous modulus. Furthermore, the forces actively generated by the regenerate were measured and shown to correlate well with shape fluctuations of a freely regenerating sample. In chapter 5, lung surfactant inactivation by serum proteins during the acute respiratory distress syndrome (ARDS) was simulated. As the model of dynamic, oscillating interfaces in lung, the competitive adsorption of dipalmitoylphosphatidylcholine (DPPC) and bovine serum albumin (BSA) to the air/water interface was monitored by periodically changing the surface area. The model was used to investigate the impact of perfluorohexane (PFH) as a potential therapeutics. The lipid-protein composite films at the air/water interface in the presence and absence of PFH gas could be visualized by fluorescence microscopy, indicating an accelerated displacement of a pre-adsorbed BSA by DPPC in saturated PFH atmosphere. The acceleration of BSA-DPPC replacement under PFH atmosphere was accompanied by significant changes in viscoelasticity of the interface, suggesting the incorporation of PFH to the protein layer.
Background: Nucleoside triphosphate (NTP) hydrolysis is a key reaction in biology. It involves breaking two very stable bonds (one P–O bond and one O–H bond of water), in either a concurrent or a sequential way. Here, we systematically examine how protonation of the triphosphate affects the mechanism of hydrolysis. Results: The hydrolysis reaction of methyl triphosphate in vacuum is computed with protons in various numbers and position on the three phosphate groups. Protonation is seen to have a strong catalytic effect, with the reaction mechanism depending highly on the protonation pattern. Conclusion: This dependence is apparently complicated, but is shown to obey a well-defined set of rules: Protonation of the α- and β-phosphate groups favors a sequential hydrolysis mechanism, whereas γ-protonation favors a concurrent mechanism, the two effects competing with each other in cases of simultaneous protonation. The rate-limiting step is always the breakup of the water molecule while it attacks the γ-phosphorus, and its barrier is lowered by γ-protonation. This step has significantly lower barriers in the sequential reactions, because the dissociated γ-metaphosphate intermediate (PγO3 −) is a much better target for water attack than the un-dissociated γ-phosphate (−PγO4 2−). The simple chemical logic behind these rules helps to better understand the catalytic strategy used by NTPase enzymes, as illustrated here for the catalytic pocket of myosin. A set of rules was determined that describes how protonating the phosphate groups affects the hydrolysis mechanism of methyl triphosphate: Protonation of the α- and/or β- phosphate groups promotes a sequential mechanism in which P-O bond breaking precedes the breakup of the attacking water, whereas protonation of the γ-phosphate promotes a concurrent mechanism and lowers the rate-limiting barrier of water breakup. The role played by individual protein residues in the catalytic pocket of triphosphate hydrolysing enzymes can be assigned accordingly.
Die vorliegende Arbeit befasst sich mit der Synthese und Strukturuntersuchung neuartiger Indiumamidinate von der Typ R2InX (R = R”NCR’NR”; R’ = Ph, R” = SiMe3, iPr, dipp; X = Br, Cl) mit der Koordinationsnummer 5 sowie R3In (R = Me3SiNCPhNSiMe3) mit der Koordinationsnummer 6. Durch die bereits verwendeten Synthesemethoden sollen Carbodiimiden mit Organo-Lithium-Verbindungen die entsprechenden Lithiumamidinate erhalten und mittels Transmetallierung mit InBr3 and InCl3 in Indiumamidinate überführt werden. Alle erfassten Strukturen wurden durch Kristallstrukturanalyse, NMR-Spektroskopie, sowie Elementaranalyse geprüft.
Die Fluoreszenzmikroskopie ist ein elementares Werkzeug zur Untersuchung molekularer Vorgange auf der Nanometerskala, das sich in den Lebenswissenschaften breit etabliert hat. Durch spektrale Separation können mehrere mit Fluoreszenzfarbstoffen markierte Proteine verfolgt und ihre Interaktionen untereinander sogar in lebenden Zellen aufgeklärt werden. Limitiert wird dies jedoch durch Beugungseffekte, die die Auflösung optischer Abbildungen auf etwa 200nm begrenzt, sowie durch chromatische Aberrationen, welche eine Korrelation verschiedener Strukturen bei Verwendung mehrerer Farbkanäle erschwert. Mit Hilfe molekularer Fluoreszenzschalter können beide Limitationen zugleich überwunden werden: durch chemisch induziertes Einzelmolekülblinken für die Lokalisationsmikroskopie (Chiron - Chemically Improved Resolution for Optical Nanoscopy) und chemisches Multiplexing (ChemPlexing) zur monochromatischen Abbildung mehrerer Strukturen. Als Vorarbeit wurden modulare chemische Schalter entwickelt, die basierend auf einem DNA-Doppelstrang einen Liganden in räumliche Nahe eines Farbstoffs bringen und durch Cu2+-Koordination reversibel in ihrer Emission geschaltet werden können. Die Fluoreszenzlöschung erfolgt dabei durch einen photoinduzierten Elektronentransfer. Durch Variation von Ligand und Farbstoff wurden neue Verbindungen mit höherer Affinität, geringerer Restfluoreszenz im gelöschten Zustand und einer höheren Photostabilität erhalten. In Lokalisationsexperimenten konnte das chemisch induzierte Blinken einzelner Moleküle ausgenutzt werden, um eine Auflösung von rund 90nm zu erreichen. Zudem wurde das chemische Multiplexing als Methode zur Abbildung mehrerer Strukturen in einem Farbkanal etabliert. Durch Kombination herkömmlicher Immunfluoreszenz mit chemischen Schaltern konnten so bis zu vier Strukturen in einer Probe in zwei spektralen Kanälen sequentiell abgebildet werden. Des Weiteren wurden die Grenzen der Methode ausgetestet und auch ihre Anwendbarkeit in der hochauflösenden STED-Mikroskopie demonstriert. Basierend auf diesen Ergebnissen wurden darüber hinaus neue, auf den Aminosäuren Lysin und 3-Amino-Alanin basierende chemische Schalter mit Dipicolylamin als Ligand entwickelt. Um diese für eine breite Nutzung zugänglich zu machen wurden verschiedene Funktionalitäten (Propargyl-Gruppe, Biotin, (Methyl)-Tetrazin, Halogenalkan, Benzylguanin) verwendet. Am überzeugendsten zeigte sich dabei die Kombination aus Propyl-Atto565 und Biotin-Linker an Dipicolyl-Alanin mit einer Komplexbildungskonstante für Cu2+ von (3.03 +- 0.61) 10^7 L/mol und eine sehr niedrige Restfluoreszenz des gelöschten Zustands von (0.9 +- 0.1) %. In Lokalisationsexperimenten an markierten Mikrotubuli in NIH 3T3 Zellen konnte eine Auflösung von (89 +- 14) nm erreicht werden. Auch beim chemische Multiplexing, sowohl im konfokalen als auch im STED-Mikroskop, konnte eine Auflösung von etwa 90nm in beiden Kanälen demonstriert werden. Das eingeführte Halogenalkan-Derivat als Substrat für das enzymatische Halo-Tag lieferte ebenso gute Ergebnisse wie die Derivate mit Tetrazin- und Methyl-Tetrazin-Funktionalität zur Markierung mittels Kupfer-freier Click-Reaktion. Damit eröffnen sich für die chemischen Schalter vielfältige Methoden zur Markierung, die nun theoretisch auch in lebenden genetisch veränderten Zellen durchführbar sind.
Diese Dissertation beschäftigt sich mit der Entwicklung eines neuartigen Konzepts zur Morphologiekontrolle niedermolekularer organischer Halbleiter. Durch Geometrisierung monomerer, im Feststoff hochkristalliner Acene in rigide, makromolekulare Konstrukte gelang es, spezifische Eigenschaften zu betonen oder abzuschwächen. Die Kontrolle über die Materialmorphologie wurde ohne Einführung zusätzlicher, elektronisch inaktiver Reste erreicht und bedient sich ausschließlich der molekularen Gestalt zur Festlegung der Festkörperinteraktion. Hierbei werden konjugative und absorptive Eigenschaften des Monomers verbessert.
Wegen des heutigen Mangels an morphologisch vielseitigen Elektronenakzeptoren in optoelektronischen Anwendungen wurde sich auf 6,13-Bis(triisopropylsilylethinyl)-5,7,12-14-tetraazapentacen (TIPSTAP) als elektrisch aktive Komponente fokussiert. Aus dem monomeren „nulldimensionalen“ TIPSTAP wurden starre, molekulare Konstrukte verschiedener Dimensionalität geschaffen. Diese sind elektronisch mit C60 vergleichbar, jedoch morphologisch divers, was zur Etablierung von Struktur-Wirkungs-Prinzipien genutzt werden kann. Es konnte gezeigt werden, dass sich das entwickelte Konzept direkt auf das isostrukturelle Pentacen-Derivat übertragen lässt und somit zu generalisieren ist.
In zweidimensionalen und besonders in eindimensionalen Konstrukten wurden Festkörperinteraktionen betont, während sie in dreidimensionalen, expandiert tetraedrischen Konstrukten in etwa denen des Monomers entsprachen. Filmbildungseigenschaften wurden in den dreidimensionalen Tetraedern besonders stark verbessert, sodass dem kristallinen TIPSTAP Material durch Einführung nur eines einzigen zusätzlichen, unkonjugierten Atoms pro vier Monomere jegliche Neigung zur Ausbildung makroskopischer Kristallite genommen werden konnte. Bei den zweidimensionalen Konstrukten kam es zu leichten und bei linearen Konstrukten zu ausgeprägten Aggregationseffekten. Trotz ihrer ausgezeichnet filmbildenden Eigenschaften weisen die TIPSTAP-Konstrukte hohe Ordnung im Festkörper auf, was ein hohes Anwendungspotential der in dieser Arbeit dargestellten Verbindungen für photovoltaische Anwendungen verspricht.
Custom design of organic and biological surfaces and soft matter lithography are important issues of modern nanotechnology and physical chemistry of interfaces. An important tool in this regard is ultraviolet (UV) light which can be used for controlled modification and patterning of organic and biological surfaces. In this context, the effect of UV light on alkanethiolate (AT) self-assembled monolayers (SAMs) on gold substrates was studied, with a particular emphasis on its wavelength dependence. The experiments were first performed for the most basic system of non-substituted AT SAMs which exhibited qualitatively similar photooxidation behavior at UV wavelength variation from 254 to 375 nm but a strong decrease of the photooxidation cross-section with increasing wavelength. Based on these results, the possibility of UV-promoted exchange reaction (UVPER) with non-substituted AT SAMs as the primary matrix and azide-substituted ATs as substituents was tested and successfully realized, resulting in the fabrication of mixed SAMs with variable density of the azide tail groups, capable of the subsequent click reaction with various kinds of molecules and functional moieties with alkynyl group. Such a click reaction with several representative substituents was demonstrated. Further, the above approach was extended to oligo(ethylen glycole) substituted AT SAMs serving as protein repelling primary matrix. Combining UVPER and the subsequent click reaction with a biotin-bearing substituent, biorepulsive templates with controlled density of the docking sites for the specific adsorption of biotin-complementary proteins such as avidin and streptavidin were prepared and successfully tested regarding their non-specific and specific protein affinity. This approach was extended to UV lithography, resulting in preparation of custom-designed, gradient protein-adhesion patterns. Finally, based on the results for the OEG-AT SAMs, the effect of UV light on protein-repelling poly(ethylen glycole) (PEG) nanomembranes was studied. It was demonstrated that UV irradiation induces extensive desorption of the PEG material, without photooxidation or other noticeable changes in the chemical composition, biorepelling behavior and hydrogel properties of the residual membrane. This opens a new way of 3D patterning of all-PEG materials, potentially useful for nanofabrication and biotechnology.
Surface functionalization is important for modern science, technology as well as human¡¯s daily life. To endow different surfaces with various unique properties, lots of effort has been devoted to develop innovative chemical methods utilized for surface functionalization. Due to the controllability both spatially and temporally, photo-based functionalization is one of the most convenient surface modification methods. This doctoral thesis mainly focuses on photo-induced thiol chemistries for surface functionalization.
In Chapter 1, an introduction is given to describe the recent progress in the field of surface patterning technologies as well as newly developed photo chemistries.
In Chapter 2, a fast (<15 s), initiator-free and versatile surface photopatterning method based on UV-induced thiol-yne click chemistry for creating precise superhydrophobic-superhydrophilic micropatterns is introduced. The method is based on the formation and modification of alkyne-functionalized polymer surfaces with porous structure. This alkyne surface can be modified with variety of thiol-containing chemicals under UV irradiation without any photoinitiator, in different solvents and even in water rapidly. Superhydrophobic-superhydrophilic micropatterns with feature resolution down to 10 ¦Ìm could be created facilely on this polymer surface. Applications for the formation of microarrays of droplets as well as high-density microarrays of cells are also shown in the chapter.
In Chapter 3, a simple, rapid and convenient surface functionalization method based on UV-induced thiol-ene click chemistry to create transparent and mechanically robust micropatterns on smooth glass or flexible polymer films is described. These patterns enable the fabrication of high-density arrays of low surface tension liquid microdroplets via discontinuous dewetting. A wide range of organic solvents including ethanol, acetone, DMF, dichloromethane and even hexane (surface tension 18.4 mN/m), could be used to produce such microdroplet arrays with complex shapes. This unique method provides an important solution for ultra high-throughput chemical screening applications. The possibility of parallel addition of different chemicals into the individual organic microdroplets is demonstrated. This approach is also employed to create high-density arrays of polymer microlenses with defined 3D shapes. In addition, this method is uniquely suited to create patterns of hydrophobic nanoparticles that can be only dispersed in organic solvents.
In Chapter 4, a UV-induced 1,3-dipolar nucleophilic addition of tetrazoles to thiols is demonstrated. Under UV irradiation the reaction proceeds rapidly at room temperature, with high yields, without a catalyst, and in both polar protic and aprotic solvents, including water. This UV-induced tetrazole-thiol reaction was successfully applied for the synthesis of small molecules, protein modification, and rapid and facile polymer--polymer conjugation. The reaction has also been demonstrated for the formation of micropatterns by site-selective surface functionalization. Superhydrophobic--hydrophilic micropatterns were successfully created by sequential modifications of a tetrazole-functionalized porous polymer surface with hydrophobic and hydrophilic thiols. In addition, a biotin-functionalized surface could be fabricated in aqueous solutions under long-wavelength UV irradiation.
In the last part of this thesis, a brief summarz and outlook are present.
Die Entwicklung neuer Synthesestrategien zum gezielten Aufbau kettenförmiger Borverbin-dungen mit elektronenpräzisen Bor-Bor-Einfach- und Mehrfachbindungen ist nach wie vor eine große Herausforderung. Die hohe Elektrophilie des Bors, sowie seine starke Präferenz zur Clus-terbildung sind Gründe für die überschaubare Anzahl entsprechender Verbindungen, welche in der Regel eine Stabilisierung durch sterisch anspruchsvolle Substituenten erfordern. Bizyklische Guanidine, wie 1,3,4,6,7,8-Hexahydro-2H-pyrimido[1,2-a]pyrimidin (hppH), 1,5,7-Triaza-bicyclo[4.3.0]non-6-en (Htbn) und 1,4,6-Triazabicyclo[3.3.0]oct-4-en (Htbo) erfüllen diese Voraussetzungen und besitzen zudem den Vorteil gleich zwei Boratome über die Guanidinat-Einheit binden zu können, was eine optimale Präorientierung der beiden Boratome zueinander ermöglicht. Die vorliegende Arbeit knüpft an die außergewöhnliche und vielseitige Chemie dieser guanidinatstabilisierten Diboran-Verbindungen an und beschäftigt sich mit der gezielten Entwicklung neuer Bor-Bor-Kupplungsreaktionen auf Basis der bislang bekannten Diboran(6)- und Diboran(4)-Verbindungen dieser Substanzklasse. Dabei werden vorallem die, durch Hydridabspaltung zugänglichen, kationischen Derivate als potentielle Synthesebausteine untersucht. So konnte [HB(hpp)]2 ausgehend von [H2B(hpp)]2 durch Hydridabspaltung und anschließende Deprotonierung des [H3B2(hpp)2]+-Intermediats erhalten werden. Die Reaktion stellt einen Alternativweg zur katalytischen Dehydrokupplung der Ausgangsverbindung dar. Die Hydridabspaltung an [H2B(E)]2 (E = tbn, tbo) führt hingegen zu den [H2B2(E)3]+-Kationen. Die B−H-Aktivierung an [HB(hpp)]2 führt abhängig von den eingesetzten Lewis-Säuren zu unterschiedlichen kationischen Tetraboranen. So konnte mit B(C6F5)3 das erste stabile dikationische Tetraboran(6) [H2B4(hpp)4]2+ mit rhombischer B4-Einheit und 4-Zentren-4-Elektronenbindung erhalten werden. Die Bildung dieser Verbindung ist einzigartig und entspricht der Kupplung zweier zum Ethylkation isolektronischen [HB(hpp)2B]+-Kationen, die im ersten Reaktionsschritt gebildet werden. Unter Anwesenheit stabilisierender Phosphine konnte dieses Kation in Form der Diboranyl-Phosphonium-Kationen [HB(hpp)2B-PR3]+ abgefangen und ein Beweis für dessen Auftreten im Reaktionsverlauf erbracht werden. Demgegenüber führt die Umsetzung von [HB(hpp)]2 mit der stärkeren Lewis-Säure [Acridin-BCl2][AlCl4] zu dem ersten bekannten radikaltrikationischen Tetraboran(4) [B4(hpp)4]•3+ mit rhombischem B4-Gerüst und 4-Zentren-5-Elektronenbindung. Die gewonnenen Erkenntnisse zeigen die Vielseitigkeit der Lewis-Säure-induzierten Hydridabspaltung und legen den Grundstein für zukünftige Synthesestrategien zum Aufbau oligomerer Borverbindungen.
Die Entwicklung und Untersuchung neuer molekularer Übergangsmetallkomplexe mit redoxaktiven Liganden ist aufgrund ihrer potentiellen Anwendung als Katalysatoren und in den Materialwissenschaften von großem Interesse. Vor allem die Synthese valenztautomerer Komplexe wird durch deren mögliche Verwendung in der Katalyse vorangetrieben. Der erste Teil der Arbeit beschäftigt sich mit der Synthese binuklearer Kupfer(I)- und Kupfer(II)-Komplexe, die über den redoxaktiven GFA-Liganden (Guanidinyl-funktionalisierter Aromat) 2,3,5,6-Tetrakis(tetramethylguanidinyl) pyridin (ttmgp) verbrückt sind, und deren Kontrolle der elektronischen Struktur durch Wahl der Co-Liganden und der chemischen Umgebung. Bisher waren molekulare Kupfer-GFA-Komplexe, die aus zwei Kupfer(I)-Zentren und einem zweifach oxidierten GFA-Liganden ([Cu(I)–GFA(2+)–Cu(I)]) aufgebaut sind, aufgrund ihrer Instabilität nicht zugänglich. Erst die Reaktion von ttmgp mit vier Äquivalenten Kupfer(I)- Halogenid mit anschließender Oxidation führte zu der Bildung tetranuklearer Kupfer(I)-Komplexe mit der elektronischen Struktur [Cu(I)–ttmgp(2+)–Cu(I)], wobei eine Stabilisierung durch die Koordination von zwei [CuI2X3](-)-Einheiten (X=I, Br) erfolgt. Die Komplexe zeigen Thermochromie und besitzen eine starke Charge-Transfer-Bande, die bei Erhöhung der Temperatur durch die reversible Abspaltung von zwei neutralen CuX-Molekülen von beiden [CuI2X3](–)-Einheiten deaktiviert wird, was zur Bildung von [ttmgp(CuIX2)2] mit der identischen elektronischen Struktur führt. Auf Basis dieser Erkenntnisse konnte die erste direkte Synthese eines dinuklearen Kupfer(I)-Komplexes mit der elektronischen Struktur [Cu(I)–ttmgp(2+)–Cu(I)] durch die Reaktion von Kupfer(II)-Bromid mit ttmgp durchgeführt werden. Die tetranuklearen und dinuklearen Cu(I)- Komplexe sind somit die ersten synthetisierten Beispiele für molekulare Komplexe des Typs [Cu(I)–ttmgp(2+)– Cu(I)]. Im Gegensatz dazu führte die Verwendung von Kupfer(II)-Chlorid zu der Synthese des ersten dinuklearen, valenztautomeren Kupferkomplexes, der einen Guanidinliganden enthält. Die elektronische Struktur dieses Komplexes ist stark von Umgebungseffekten abhängig. Im Festkörper und in unpolaren Lösungsmitteln besitzt der Komplex eine elektronische Struktur des Typs [Cu(II)–ttmgp(0)–Cu(II)] beziehungsweise in polaren Lösungsmitteln [Cu(I)–ttmgp(2+)–Cu(I)]. Die Erhöhung der Ionenstärke der Lösung durch Salzzugabe forciert einen intramolekularen Elektronentransfer (IET), der die Überführung des paramagnetischen Cu(II)- in den diamagnetischen Cu(I)-Komplex ermöglicht. Durch die Verwendung von Aceton als Lösungsmittel ist es möglich, auf Grundlage eines reversiblen, temperaturabhängigen Gleichgewichts zwischen beiden Valenztautomeren zu schalten. Im Gegensatz zu den meisten valenztautomeren Komplexen stellt der Kupfer(II)-Komplex mit der größeren Spinmultiplizität den elektronischen Grundzustand dar, was auf die starke Abhängigkeit der Umgebung zurückgeführt werden kann und durch quantenchemische Untersuchungen bestätigt wird. Die Einzigartigkeit von [ttmgp(CuCl2)2] konnte durch die Synthese des analogen CuCl2-Komplexes mit dem benzol-basierten GFA unterstrichen werden. Dessen elektronische Struktur kann zwar durch die Wahl des Lösungsmittels gezielt gesteuert werden, allerdings konnten beide Valenztautomere in Lösung nicht reversibel durch einen IET ineinander überführt werden. Der zweite Teil der Arbeit widmet sich der metallfreien, photoinduzierten C–C-Kupplungsreaktion von Benzylbromiden, die durch ttmgp als Elektronendonor vermittelt wird. Der geschwindigkeitsbestimmende Schritt dabei ist die homolytische N–C-Bindungsspaltung der verwendeten N-benzylierten Pyridiniumsalze von ttmgp. Die kinetischen Untersuchungen der Reaktion wurden für eine Vielzahl an verschieden substituierten Benzylbromiden mittels UV/Vis-Spektroskopie untersucht. Im Vergleich zu Benzylbromid führt die Substituenteneinführung zu einer Beschleunigung der Reaktion. Für einige Derivate konnte die Bildung isomerer Kupplungsprodukte beobachtet werden, die auf einer Isomerisierung der in-situ gebildeten Benzylradikale beruht. Abschließend wurden C–C-Kreuzkupplungen zwischen verschieden substituierten Benzylbromiden durchgeführt, bei denen das Kreuzkupplungsprodukt das Hauptprodukt war. Experimentelle und quantenchemische Untersuchungen deuten darauf hin, dass die Reaktion aus dem ersten angeregten Zustand heraus erfolgt und strukturelle Änderungen des angeregten Zustands zu einer Zunahme der Geschwindigkeitskonstante führen.
Background: Mice with peroxisome deficiency in neural cells (Nestin-Pex5 −/− ) develop a neurodegenerative phenotype leading to motor and cognitive disabilities and early death. Major pathologies at the end stage of disease include severe demyelination, axonal degeneration and neuroinflammation. We now investigated the onset and progression of these pathological processes, and their potential interrelationship. In addition, the putative role of oxidative stress, the impact of plasmalogen depletion on the neurodegenerative phenotype, and the consequences of peroxisome elimination in the postnatal period were studied. Methods: Immunohistochemistry in association with gene expression analysis was performed on Nestin-Pex5 −/− mice to document demyelination, axonal damage and neuroinflammation. Also Gnpat −/− mice, with selective plasmalogen deficiency and CMV-Tx-Pex5 −/− mice, with tamoxifen induced generalized loss of peroxisomes were analysed. Results: Activation of the innate immune system is a very early event in the pathological process in Nestin-Pex5 −/− mice which evolves in chronic neuroinflammation. The complement factor C1q, one of the earliest up regulated transcripts, was expressed on neurons and oligodendrocytes but not on microglia. Transcripts of other pro- and anti-inflammatory genes and markers of phagocytotic activity were already significantly induced before detecting pathologies with immunofluorescent staining. Demyelination, macrophage activity and axonal loss co-occurred throughout the brain. As in patients with mild peroxisome biogenesis disorders who develop regressive changes, demyelination in cerebellum and brain stem preceded major myelin loss in corpus callosum of both Nestin-Pex5 −/− and CMV-Tx-Pex5 −/− mice. These lesions were not accompanied by generalized oxidative stress throughout the brain. Although Gnpat −/− mice displayed dysmyelination and Purkinje cell axon damage in cerebellum, confirming previous observations, no signs of inflammation or demyelination aggravating with age were observed. Conclusions: Peroxisome inactivity triggers a fast neuroinflammatory reaction, which is not solely due to the depletion of plasmalogens. In association with myelin abnormalities this causes axon damage and loss.
Biomimetic systems and interfaces allow to understand and control cellular behavior in a well defined and reproducible manner. In this study three different strategies are developed to prepare such simplified, well-defined biomimetic materials. Firstly, a combination of click chemistry and gold thiol interactions allows the presentation of two distinct signaling molecules at controlled density and arrangement to investigate the cross-talk between two signaling molecules in cell culture. Secondly, the commonly used Ni2+-NTA interaction with His6- tagged proteins is substantially improved in its stability and inertness for protein immobilization on SAMs by replacing the Ni2+ ions with Co3+ in the complex. Thirdly, His6-tagged proteins are stably tethered on TiO2 nanoparticles for targeted delivery. To produce dual functionalized gold nanostructured interfaces, first the presentation of a ligand of interest with azide functionality on glass substrates at controlled density is established. For this pirpose, alkyne terminated poly(ethylene glycol) (PEG) is covalently bound to glass through a silanization reaction and subsequently modified through copper catalyzed azide alkyne cycloaddition (CuAAC). The functionalization density can be statistically tuned through the coimmobilization of a methoxy-terminated PEG. The surface coating and its modification with the CuAAC is analyzed using fluorescence microscopy, XPS, an enzymatic digestion assay for the determination of the ligand density, QCM-D and in cell adhesion studies. This PEG coating is used in combination with the established gold nanostructured surfaces to generate orthogonally dual functionalized biomimetic interfaces where one of the ligands is attached to the PEG coating between the gold nanoparticles using the CuAAC and the second ligand is attached to the gold nanoparticles using the gold thiol interaction. These interfaces, which present two distinct ligands at controlled density and arrangement, are suitable to investigate the mutual influence of two signaling molecules on cell behavior. Exemplarily, the combined effect of the adhesion peptide cRGD and the synergy site PHSRN on REF fibroblast adhesion is investigated. While on neither of the monofunctionalized substrates the cells can attach, the cells adhere on the dual functionalized cRGD and PHSRN presenting interfaces. The second part of this study deals with the stable immobilization of His-tagged proteins on NTA presenting surfaces using the cobalt(III) mediated interaction. The cobalt(III) complex is generated by first preforming the well established cobalt(II) complex between NTA and His6-tagged proteins and the subsequent chemical oxidation of Co2+ to Co3+ with hydrogen peroxide. A comparison of the Ni(II) and Co(III) mediated interaction between NTA moieties and His6-GFP reveals the lability of the Ni(II) and stability of the Co(III) complexes against high concentrations of competing ligands and washing off overtime. Further, also the resistance of the Co(III) mediated interaction against reducing agents is demonstrated. The oxidation step in this immobilization strategy can potentially harm the protein’s activity and this has to be investigated case by case. To illustrate that this method can be used to immobilize functional protein, the His6-tagged protein A is immobilized through the Co(III) mediated interaction and it is shown that the oxidation step dosen’t influence the immunoglobulin binding activity. In the third part the Co(III) mediated stable immobilization of His-tagged proteins is used to biofunctionalize TiO2 nanoparticles. Here, the photocatalytic activity of TiO2 is taken advantage of to perform the oxidation of Co(II) complexes between the chelating TETT surface coating on the TiO2 nanoparticles and a His-tagged protein. The Co2+ ion loading capacity of the nanoparticles and their photocatalytic activity is characterized with a colorimetric assay, fluorescence studies using terephtahlic acid as radical detection reagent, absorbance measurements, DLS and zeta potential measurements proving the photo-mediated oxidation of coordinated Co2+ ions to Co3+. Exemplarily, the stable immobilization of the model protein His6-GFP and of the glycoprotein transferrin-His6 is studied.
In der vorliegenden Arbeit wird die Herstellung von mikro- und makroskaligen Kristallen der polyanionischen LiMPO4 und Li2MSiO4 M = (Mn, Fe, Co) Verbindungen mittels der mikrowellengestützten Hydrothermalsynthese und des optischen Zonenschmelzverfahrens dargestellt. Die hergestellten Materialien wurden strukturell mittels Einkristall- oder Pulverröntgendiffraktometrie sowie metallurgisch, chemisch und ihre Morphologie betreffend mittels Mikroskopie und Röntgenspektroskopie charakterisiert und weiterführend durch elektrochemische Zyklierung, Impedanzspekroskopie, Magnetometrie und Myonen-Spin-Rotations-/Relaxationsmessungen untersucht. An hydrothermal additivgestützt hergestelltem LiCoPO4 wurde ein deutlicher Einfluss der Partikelmorphologie auf die elektrochemischen Eigenschaften und die Einsetzbarkeit als Lithium-Ionen Batteriematerial festgestellt. Darüber hinaus wurden zwei polymorphe LiCoPO4 Modifikation mit Zn und Fe dotiert und die Auswirkungen der Übergangsmetallsubstitution auf die magnetischen und elektrochemischen Eigenschaften untersucht. Die Spin-Dynamik der tetraedrischen Modifikation wurde anhand von kernmagnetischer Resonanz und μSR untersucht. Dabei wurden magnetische Flukutationen bis zu hohen Temperaturen beobachtet. Makroskopische Einkristalle der Verbindungen LiMn1−xFexPO4 (x = 0, 0.1, 0.2, 0.3, 0.5, 1) und Li2FeSiO4 wurden im Zonenschmelzverfahren bei erhöhtem Druck hergestellt und deren genaue Züchtungsparameter bestimmt. Die Untersuchungen der magnetischen Eigenschaften und Leitfähigkeit von LiMn1−xFexPO4 zeigen eine deutliche Dotierungsabhängigkeit des magnetischen Grundzustandes und der magnetischen Anisotropie sowie der anisotropen Hochtemperaturmobilität der Lithium-Ionen. Die Einkristallstruktur der erzeugten Li2FeSiO4 Modifikation wurde zum ersten Mal bestimmt und deren magnetische Eigenschaften untersucht.
Linear acenes are a widely studied class of materials in the field of Organic Electronics. Their aromatic system and the strong interaction of the π-electrons of neighbouring molecules in the solid state allow an efficient charge transport in these materials. The defined molecular structure of these small molecules and the possibility to tune their optical and electronic properties as well as the solid state packing through careful chemical design and synthesis have resulted in numerous applications of acenes in organic transistors and optoelectronic devices. This work focuses on the application of N-Heteroacenes and non-conjugated pentacene-based polymers as semiconductors in solution-processed organic field-effect transistors. These devices are used to evaluate the charge transport properties of the materials and derive structure-function relationships for the various compounds. To draw structure-function relationships from the studies described in this thesis, a myriad of characterisation techniques was employed to obtain an insight into the optical, electronic, electrical and morphological properties of each material. The effects of order, energetics and processing of the semiconductor on the transistor performance are all investigated. While non-conjugated pentacene-based polymers offer an ease of processability, their amorphous nature inhibits efficient hole transport, resulting in a relatively poor transistor performance. The fashion in which the pentacene systems are connected to the polymer backbone changes their flexibility and therefore affecting the injection behaviour and charge transport properties. The nitrogen substitution in N-Heteroacenes results in an energetic stabilisation of the frontier molecular orbitals, allowing for an enhanced electron injection into these materials. For the symmetrical tetraazapentacene and two halogenated phenazine derivatives relatively high electron mobilities were achieved demonstrating their potential for future application as n-type semiconductors in organic field-effect transistors. The use of N-heteroacenes is not limited to electron transport only. Their N,N’-dihydro forms are electron rich compounds that exhibit good hole transport. This is demonstrated for differently substituted tetraazapentacenes as well as for a N,N’-dihydro diazahexacene and -heptacene. For these materials it is shown that the processing conditions not only affect the macroscopic transistor performance, but also influence the formation of polymorphs in thin films. The solid state packing of functionalised acenes is typically determined by their solubilising side chains. A norbornadienyl substitution at the side chain of the well-known 6,13-bis(triisopropylsiliylethynyl)pentacene and its tetraaza derivative was shown to result in an enhancement of the charge transport properties for the p-type derivatives and deterioration of the performance of the n-type transistors. These observations are related to changes in the charge transfer integrals, the film microstructure and the solid state packing. In conclusion, this work contributes to the development of guidelines for the design and synthesis of next generation N-heteroacenes to be applied in the future in state of the art organic electronic devices.
Glaucoma is a very prevalent eye disease with more than 60 million people affected worldwide. The only form of therapy is the artificial lowering of the intraocular pressure of the aqueous humor, which is the main cause for the disease. This can be achieved for example by the application of an intraocular implant to drain excess liquid. Due to a nonoptimal biocompatibility these intraocular stents often induce inflammation and fibrosis of their surrounding tissue. This subsequently blocks the outflow of liquid through the implant and results in long-term failure of the therapy. The goal of this thesis was the development of a new type of glaucoma implant made from titanium enhanced by hyaluronan hydrogels. The basic concept was the coating of the outer surfaces of a small tube with hydrogels made from hyaluronic acid to enhance cell adhesion for a better biocompatibility and a lower occurrence of inflammation and fibrosis. Simultaneously the interior was to be filled with hyaluronan hydrogels with slightly different properties to block a clogging of the drainage path by cell growth and act as a valve to regulate the intraocular pressure. In addition the economical and work safety aspects for an industrial mass production and biomedical application of these implants were considered. In order to achieve this goal, a number of methods to fabricate, and tools to analyze, hydrogel-enhanced glaucoma implants have been investigated in this thesis. Reaction sequences were developed to simultaneously crosslink and immobilize hyaluronan hydrogels on glass and titanium surfaces by a combination of several established methods. In addition, fluoresceinamine was integrated into the process to generate fluorescently labeled hydrogels, which was an effective tool for further analysis. Also, a number of methods were designed to observe the behavior of the hydrogel-modified implants when exposed to external pressures. It was possible, by using these methods, to verify the stability of the immobilization, with hydrogels within the tubes being able to withstand the pressures encountered in the glaucomatous eye without breaking apart. Furthermore it was shown that a regulation of external liquid pressures by these hydrogel-filled tubes was possible which illustrated these implants’ potential to drain excess intraocular fluid from the glaucomatous eye without causing hypotony. The mechanism of the pressure regulation was further explored and related to the presence of channels within the hydrogels that enabled liquid flow at certain pressure levels. Since the natural occurrence of these channels during the production process of the implants was initially random, two methods were developed to allow their artificial and reproducible creation. This was achieved either by the use of a laser to burn channels into the hydrogels or by the implementation of small glass fibers prior to the gel formation within the tubes. The methods established and the results gained in this thesis provide the means to generate hydrogel-enhanced implants and illustrate their general usability in glaucoma therapy by reducing intraocular pressure. In addition the process for the implant creation was successfully streamlined to allow for a cost effective, low-hazard production on an industrial scale. Future research based on the established concept will comprise the optimization of the hydrogels’ capabilities to either improve or resist cell adhesion as necessary. Also setups will have to be designed for a miniaturization and industrial mass fabrication of the implants.
The development of quantum chemical methods for the study of excited states had to major advancements in the ability to investigate the photochemistry of medium-sized to large organic molecules. In particular, tools for transition and difference density matrix analysis, allowing for the visualization of detachment/attachment, and difference density plots, along with natural transition orbitals, serve as compact descriptions of the excited state. Throughout this work, time-dependent density functional theory (TD-DFT) and the algebraic diagrammatic construction (ADC) scheme for the polarization propagator were used as the primary methods of investigation. An overview of the available quantum chemical methods for the study of excited states is given in Chapter 2. Several different molecular systems were studied, each presenting their own unique challenges, but unified under the theme of excited state proton transfer processes.
Pigment Yellow 101 (PY101), a commercially available and highly photostable fluorescent yellow pigment, is the first system studied. Relaxed scans of the potential energy surfaces connecting the most stable conformers of the pigment were computed using TD-DFT. It was found that PY101 undergoes excited state intramolecular proton transfer (ESIPT) and trans-cis isomerization after photoexcitation to the bright first singlet electronically excited state (S 1 ). A simple kinetic rate model is presented for gaining a first look at the dynamics of the system, and information obtained from the potential surface scans and geometry optimizations of PY101 is used as input. Time-dependent quantum dynamics simulations are not yet feasible for systems larger than PY101, and therefore the development of such models is important. The results from the kinetic model agree well with those from time-resolved experiments, indicating that such models are promising new tools. The results of the PY101 project are presented in Chapter 3.
The fluorescence quenching behavior of benzaldehyde in water is the primary subject of Chapter 4. TD-DFT calculations along the coordinate of proton transfer from an explicit water molecule to benzaldehyde show that photoexcitation is followed by ultra-fast decay from the bright S 3 (ππ ∗ ) state to the S 1 (nπ ∗ ) state, where the system then evolves. Along this coordinate, benzaldehyde is found to act not as a photobase but rather abstracts a hydrogen atom from the water, forming as a result a pair of radicals. Subsequent electron transfer to the hydroxyl radical, forming a hydroxide anion, is followed by proton back transfer and restoration of the initial scenario. For the elucidation of the fluorescence quenching mechanism of benzaldehyde in water, tools for detachment/attachment densities and Mulliken population analyses, as implemented for ADC, were employed. This study was then extended to chemical relatives of benzaldehyde, for example by increasing the number of aromatic rings.
In Chapter 5, the photoacidic properties of a series of pyranine-based photoacids were studied using TD-DFT and a series of excited state descriptors based on the exciton wave function. Stronger photoacids exhibit higher lying states of charge transfer character from the substituents to the core, while these states are lower lying by about 1 eV in the weaker photoacids of the series. The stronger photoacids are characterized by more strongly electron-withdrawing substituents. In addition, single point calculations along the dissociation coordinate of neutral derivatives of pyranine reveals a second type of charge transfer state, going from the oxygen of the photoacid to the solvent molecule moeity, which crosses down over the course of the acid dissociation coordinate. It is suspected that this state may interfere with the excited state intermolecular (ESPT) process, as it does not cross down as rapidly in the case of a photoacid with more strongly deactivating substituents. More extensive study is necessary to fully describe the roles of these charge transfer states on the pyranine-based photoacids, and suggestions in this regard are made in detail at the end of Chapter 5.
On the whole, the breadth of quantum chemical methods used to study ESPT processes in a range of organic systems were highly effective in this regard. This speaks not only to the effectiveness of currently available methods for the study of excited states, but also has allowed for the obtainment of detailed insights into these complex systems of industrial and biological relevance.
In this thesis artificial nanostructured surfaces inspired by the moth eye were developed on both inorganic and organic substrates. Two properties, i.e. anti-reflective (AR) and anti-bacterial (AB) were studied in detail. On inorganic fused silica (Suprasil®) substrates, nanopillar arrays were fabricated by combining block copolymer micellar lithography (BCML) and reactive ion etching (RIE) techniques. The nanopillar arrays were fabricated on a large area and the parameters of the pillars were controlled. The substrates were used as molds to create nanostructures in organic substrates using two methods: replica molding and nanoimprinting. The first method transferred the pillar structure into a polyurethane substrate creating nanoholes. However, it was shown that this method was limited due to the low aspect ratio and difficulties in mold removal. Using nanoimprinting methods instead solved these problems. Both nanohole and nanopillar structures were homogeneously imprinted in a large area of the intermediate polymer stamp (IPS®) and polymethylmethacrylate (PMMA) materials. The AR properties of both organic and inorganic substrates were characterized using optical spectrometry. On Suprasil® surfaces, the transmittance was increased over a wide wavelength range of 200-1000 nm, with a maximum of 99.5% transmission per interface. Nanoimprinted IPS® and PMMA also depicted highly improved transmittance, with an increase from 91.5% to 95% with a single-sided nanohole array on IPS® and from 91.5% to 97.5% with a double-sided nanopillar array on PMMA. Excellent AR performance was achieved to a high incident angle of 60°, which significantly outperformed traditional thin-film AR coatings. A theoretical model was also set up matching the experimental results very well. The AB properties of the moth eye inspired structures were investigated on the nanostructured Suprasil®. The surface coverage of Staphylococcus sciuri (S. sciuri) bacteria was statistically analyzed by optical microscopy and the attachment sites between the bacteria and the nanostructures were observed by scanning electron microscopy (SEM). Although the surface coverage showed no significant difference between the nanostructured and planar surfaces, SEM images clearly revealed a different interaction of the bacteria and the nanostructures compared to plain surfaces. Nanofibers most likely fimbriae connecting the bacteria and the nanopillar tips were observed. Therefore, it was shown that the bacterium is able to sense the nano-scale features and respond with cell morphological alterations.
Nowadays, X-ray absorption spectroscopy (XAS) techniques are important tools to investigate the electronic structure of molecules. Mostly, these methods are applied in the field of organic electronics to study unoccupied molecular levels, which provide information about charge generation and transport properties. With the help of modern synchrotron soft beam sources, molecules can absorb high-energy X-ray photons, thereby promoting an electron from the core level, e.g. K-shell 1s orbitals, to the unoccupied molecular level. As a result, meta-stable bound core-excited states are generated. Since core orbitals are energetically well-separated from the remaining occupied and virtual orbital space, they are strongly contracted and the corresponding core-excited states are very localized. As a consequence, the generated core-hole interaction induces a rearrangement of the valence electrons, because the effective shielding of the nucleus is reduced. This effect leads to a lowering of the core-excitation energy of the final state. This rearrangement of the electrons can be understood as an orbital relaxation effect. To fully understand and interpret experimental spectra, an accurate knowledge about core-excitation energies, transition moments, the character of the core-excited states as well as their corresponding properties is necessary. Such information can be obtained with quantum chemical (QC) methods. They help to analyze and interpret experimental spectra, thereby providing a deep insight into the nature of core-excited states. Generally, a plethora of methods is available to calculate excited states and simulate absorption spectra. The larger the system, the more expensive are the computations. Hence, certain levels of approximation have to be introduced to lower the computational cost. This leads to a loss of reliability and accuracy of the results. The time-dependent density functional theory (TD-DFT), for example, currently is the prevalently used excited-state method for the calculation of large molecules up to 300 atoms. However, TD-DFT has several disadvantages like the self-interaction error (SIE), which leads to wrong descriptions of certain kinds of excited states, e.g. charge-transfer states or core-excited states. The excitation energies of these types of states are strongly underestimated, but if these issues are kept in mind, TD-DFT is a useful tool, providing proper spectral features. The algebraic diagrammatic construction scheme (ADC) is a prominent QC method for the calculation of excited states, which is known to provide accurate valence-excited states of small- and medium-sized molecules in an adequate computational time. The ADC approach is based on a Green’s function formalism in combination with partitioning the Hamiltonian using perturbation theory. Due to its size-consistency and Hermitian ADC secular matrix structure, the level of approximation can be improved systematically and properties can be computed straightforwardly. It is possible to calculate one-particle state properties in combination with the intermediate state representation (ISR) approach, e.g. static dipole moments and state densities, which altogether provide enhanced information about absorption spectra. A further advantage of ADC is the indirect inclusion of orbital relaxation effects via couplings to higher-excited configurations, which are important to describe core-excited states properly. However, the calculation of core excitations is tedious using the unmodified ADC approach, because, in order to solve the ADC eigenvalue problem, numerical iterative eigenvalue solvers are employed usually only providing the energetically lowest eigenstates. Core-excited states, however, are located in the high energy X-ray region of the optical spectrum and in order to calculate them directly, one has to compute all energetically underlying valence excitations as well. This is computationally very expensive and not feasible for medium-sized systems. The direct calculation of the core excitations is prevented by couplings between the valence and core-excited states. A solution to this issue is the application of the core-valence separation (CVS) approximation to the ADC approach, which results in the CVS-ADC method. This approximation is based on the fact that core orbitals are energetically well-separated from the remaining orbital spaces and as a consequence, the couplings between core- and valence-excited states are small and can be neglected. In other words, the CVS approximation decouples the core and valence excitation spaces from each other and allows for a direct computation of core-excited states. In former work, it was proven that a very good agreement with experiments can be obtained at the extended second order level CVS-ADC(2)-x.
My PhD project mainly consists of two important parts. One was to enhance and develop variants of the CVS-ADC method and implement all approaches efficiently in the adcman program, which is part of the Q-chem program package. Secondly, I benchmarked these implementations and simulated X-ray absorption spectra of small- and medium-sized molecules from different fields. In this thesis, I present my implementations, as well as the results and applications obtained with the CVS-ADC methods and give a general introduction into quantum chemical methods. At first, I implemented the CVS-ADC approach up to the extended second in an efficient way. The program is able to deal with systems up to 500 basis functions in an adequate computational time, which allows for accurate calculations of medium-sized closed-shell molecules, e.g. acenaphthenequinone (ANQ). Afterwards, the CVS-ADC implementation was extended for the first time to deal with open-shell systems, i.e. ions and radicals, which implies a treatment of unrestricted wave functions and spin-orbitals. The resulting method is denoted as CVS-UADC(2)-x. For the first time, I applied the CVS approximation to the the third order ADC scheme, derived the working equations, and implemented the CVS-ADC(3) method in adcman. As the last step, I applied the CVS formalism for the first time to the ISR approach to enable calculations of core-excited state properties and densities. This provides the basis for subsequent evaluations of transition- and density matrices, which give access to exciton sizes, e.g. hole sizes or distances between hole and electron densities. All implementations are presented and discussed in the scope of my thesis.
To benchmark all restricted and unrestricted CVS-ADC/CVS-ISR methods up to third order in perturbation theory, I chose a set of small molecules, e.g. carbon monoxide (CO). The calculated values of core-excitation energies, transition moments and static dipole moments are compared with experimental data or other approaches, thereby estimating complete basis set (CBS) limits. Furthermore, a comprehensive study of different basis sets is performed. As it turns out, the CVS-ADC(2)-x method provides the best agreement with experiments, while CVS-ADC(3) overestimates the core excitation energies. In combination with the CBS limit of the aug-cc-series, a mean error of -0.23%±0.12% for core-excitation energies can be identified at the CVS-ADC(2)-x level for carbon, nitrogen and oxygen K-edge excitations, whereas CVS-ADC(3) exhibits errors of 0.61%±0.32%. This is due to fortuitous error compensation of basis set truncation, electron correlation, orbital relaxation and neglect of relativistic effects at the CVS-ADC(2)-x level. I show that this error compensation is broken at the third order level, because the ratio between terms describing relaxation and polarization effects is shifted in a way that the excitation energy increases. However, transition moments and spectral features, as well as static dipole moments, are excellently described with both CVS-ADC(2)-x and CVS-ADC(3). Overall, considering the detailed investigation of the basis set influence on the results, I conclude that the use of restricted or unrestricted CVS-ADC(2)-x in combination with a diffuse triple-ζ basis set in its Cartesian version can be seen as a black-box method for the calculation of core-excited states of organic molecules. Especially the 6-311++G** basis set provides an excellent ratio of accuracy to computational time. Another important topic is the description of orbital relaxation effects. In the scope of this thesis, I show, how these effects are included indirectly within the CVS-ADC approaches. For this purpose, two different descriptors are used, i.e. electron promotion numbers and the amount of doubly excited amplitudes. Furthermore, with the help of detachment/attachment (D/A) densities, which can be constructed via the CVS-ISR approach, relaxation effects can be visualized. For this purpose, the (D/A) densities are compared with hole/electron (h/e) densities based on the transition density matrix. With this knowledge, the X-ray absorption spectra of medium-sized molecules and radicals from the fields of organic electronics and biology are investigated and analyzed. On the basis of these studies, the restricted and unrestricted versions of CVS-ADC(2)-x in combination with the 6-311++G** basis set exhibit mean errors of core-excitation energies around 0.1%, compared to experimental values. Additionally, core-excited state characters are analyzed with the help of state densities obtained via the CVS-ISR approach or the transition density matrix. To demonstrate that the CVS-ADC(2)-x approach can be employed as a benchmark black-box method, TD-DFT results are compared directly with the ones at the CVSADC(2)-x level. As expected, TD-DFT underestimates core-excitation energies up to 4% due to the SIE, which is about 10 eV in the case of carbon 1s excitations. Since the CVS approximation leads to both a simplification of the ADC working equations, as well as a restriction of the excitation space to correspond only to core excitations, the computational cost is reduced compared to the general ADC approach. To demonstrate the computational savings as a function of the size of the core space, several systems are investigated. CVS-ADC(3) calculations take about 8 – 10 times longer than CVS-ADC(2)-x calculations and since the results are generally more accurate with the latter method, the use of CVS ADC(3) is not justified. Compared to general ADC(2)-x, the speed-up at the CVS-ADC(2)-x level is about a factor of 4.0, but this factor strongly depends on the size of the system and the size of the core space. Next, I present applications from the field of organic electronics. The remarkable agreement with experimental data at the CVS-ADC(2)-x level justifies the prediction of yet non-recorded experimental X-ray absorption spectra. Therefore, I chose the anthracene cation, which can be seen as a model system of pentacene and its derivatives, which are commonly used as hole conductors (p-type). X-ray absorption spectra of the pentacene cation could provide deeper insight into its charge carrier properties, but measurements of experimental spectra of ionized species are usually very challenging. With the help of CVS-UADC(2)-x calculations, I show that the anthracene cation exhibits additional peaks due to the half-filled single-occupied molecular orbital. They are located approximately 3.5 eV – 1.5 eV below the first peak of neutral anthracene, which may help to distinguish a cation from the neutral species. Furthermore, the cationic spectrum exhibits peak broadening, compared to the two first peaks of neutral anthracene. Other applications concentrate on the trends of core-excited state properties along important potential energy surfaces (PES) of ANQ, phenol and bithiophene. Therefore, static dipole moments, energies, and exciton sizes are analyzed as a function of the C–O distances of ANQ and phenol, as well as the torsion around the central dihedral angle of bithiophene. Finally, another aspect of the CVS-ISR method is the accessibility of transition moments between two states, which can be used to calculate oscillator strengths for core-excited state absorption (CESA) spectra. To the best of my knowledge, no experimental data of CESA processes between two core-excited states have been recorded yet. However, such spectroscopic data could exhibit new insights and the calculation of CESA transition moments using the CVS-ADC/CVS-ISR approach is straightforward. Hence, first results of CESA processes were calculated and are presented in this thesis. In the case of ANQ, particularly bright transitions can be identified from the lowest oxygen 1s excited-state to higher ones.
The principle of chiral recognition is of central significance in enantioselective catalysis. Therefore, high efficiency in terms of synthesis, separation and analysis of chiral compounds plays an important role. In the first chapter, novel chiral stationary phases for enantioselective separation by gas chromatography will be presented. The chromatographic data provided information on enantiospecific interactions between chiral selectors and selectands. NMR experiments with these selectors in presence of corresponding products of enantioselective catalysis allowed transferring the results from the gas to the liquid phase. This shows that enantioselective gas chromatography can be used as a tool for the screening of selector-selectand interactions. The information obtained was directly applied for the design of a new ligand that can be used in rhodium catalyzed enantioselective hydrogenation. The effect of chiral selectors on dynamic systems was investigated in a double aldol reaction. Therefore, a stereochemical bias was applied onto a dynamic catalyst by addition of an external selector. The induced orientation of the catalyst is reflected the enantiomeric ratio of the chiral product. The excellent separation performance and enantiospecific interactions between the valine based selector with many derivatized amino acids included this structural element covalently bound on a stereodynamic biaryl ligand to give a specifically designed ligandfor asymmetric hydrogenation. This system enables the product of the reaction to transfer chiral information to the coordination complex of catalyst and substrate by interaction with the selectors. In this manner, the chiral information of the product can be transferred on the prochiral substrate. In the second chapter, an accessible chiral derivative of 2,4-disubstitued adamantine diamine was synthesized and separated into its four stereoisomers by reversible derivatization. Combination of unique symmetry and stability make adamantane an interesting structural element in drugs. The isolated and fully characterized stereoisomers of adamantan-2,4-diamine are currently used in medical studies in collaboration as DNA-binder trough influence on the melting temperature of the DNA double helix.
The primary aim of this thesis is to clarify how the structures and functions of biological membranes are influenced by the oxidative damage mediated by free radicals. As a precisely defined model systems, artificially reconstituted lipid membranes (Langmuir monolayers, vesicles, supported membranes, multilamellar membranes) incorporating two oxidized phospholipids bearing aldehyde or carboxyl groups at the end of truncated sn-2 acyl chains were fabricated. By the combination of various experimental methods, the generic impact of chain oxidization on physical characteristics of membranes (e.g. lateral cooperativity, fine-structures perpendicular to membrane planes, electrostatics) and the specific interactions of oxidized phospholipids with EO6 peptides and acute immune response proteins was investigated. In the first step, the influence of oxidized phospholipids (OxPL) on the thermodynamics and electrostatics were investigated using Langmuir film balance at the air-water interface. The pressure-area (π-A) isotherms and surface potential (Δψ-A) measurements implied that both OxPLs lead to a decrease in the isothermal compression modulus. In fact, surface potential measurements suggest changes in the orientation of oxidized moieties that decrease the lateral cooperativity. Further increase in the fraction of oxidized lipids resulted in the loss of molecules into bulk water, which seems consistent with the destabilization of cell membranes under oxidative stresses. In the second step, the impact of lipid oxidization on the electrostatics of membranes was examined by the combination of high-energy specular X-ray reflectivity (XRR) and grazing-incidence X-ray fluorescence (GIXF). The scattering length density profiles reconstructed from XRR results suggested that both OxPL leads to membrane thinning, which seems plausible from the decrease in the lateral cooperativity suggested by Langmuir isotherms. GIXF offers an unique possibility to localize specific target elements within Å accuracy, suggesting that the binding affinity (Ca2+ > Cs+ > K+) could be interpreted in terms of the solvation entropy (Hofmeister series). Further, the impact of oxidization on the vertical structural ordering of vertically stacked membrane models was investigated by off-specular neutron scattering. A decreased lamellar periodicity d indicated that incorporation of OxPL into the membrane displace water molecules from the inter-membrane region due to the reorientation of oxidized moieties. In the third step, the combination of experimental techniques was utilized to shed light on specific interactions of OxPLs with peptides and proteins; C-reactive protein that is characteristic for the acute immune responses and monoclonal antibody EO6 to oxidized lipids. Following the fundamental characterization of membrane-protein interactions using isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) of vesicle suspensions, in addition to XRR, GIXF, off-specular neutron scattering, dual waveguide polarization interferometry (DPI) was used to monitor the changes in thickness, refractive index, and the optical anisotropy (birefringence) of lipid membranes simultaneously. Furthermore, the specific binding of EO6 was verified from the fluorescence imaging of glioblastoma multiforme cells undergoing apoptosis, where a clear accumulation of OxPLs could be identified in apoptotic blebs. The obtained results demonstrated that the combination of well defined membrane models and unique physical techniques is a powerful tool to shed a new quantitative light on the generic and specific impacts of lipid oxidization on the lateral cooperativity, vertical fine-structures, electrostatics, and specific interactions in inflammation and apoptosis.
Reactive halogen species (RHS) have a significant impact on the chemical composition of the atmosphere. With its high halite abundance and unique topography the Dead Sea Valley (DSV) is predestined for the investigation of RHS. In the frame work of this thesis, two extensive measurement campaigns were carried out at the DSV in May 2012 and November 2014. The comparison of MAX-DOAS and LP-DOAS data with meteorological measurements indicates strong impact of transport process on the observed trace gas dynamics. The strong depletion of NO2 mixing ratios during daytime coincides with increased RHS abundance and suggests the formation of halogenated nitrate compounds. These are assumed to enhance the release of RHS from aerosol surfaces by heterogeneous processes. Elevated, confined layers of BrO of up to 50 pptv suggest the release of reactive bromine compounds from aerosol surfaces. The correlation of IO with surface waves indicates abiotic iodine release as a result of increased gas exchange at the water surface. For the first time, gaseous molecular iodine (up to 70 pptv) was detected at the DSV serving as a precursor for reactive iodine. Further, first direct evidence for reactive chlorine chemistry at the DSV was found by the detection of OClO at mixing ratios of up to 6 pptv.
In the human organism more than 500 proteases have been described so far. Many of them are essential in the regulation of physiological processes, as inflammation, immune response, coagulation or growth. A dysregulation in protease activity corresponds to severe malfunctions and causes numerous pathophysiological diseases, as neurodegenerative disorders, cardiovascular diseases and cancer. When it comes to cancer, proteases play an important role in progression and metastasis. Some are secreted from the tumor and can be found in the extracellular matrix of the tumor microenvironment and also in the bloodstream. Functional protease profiling aims at discovering tumor associated protease activity in clinical specimens (serum, plasma and tissue), which could be used for diagnostic and prognostic purposes. Therefore, it is necessary to find substrates, which are specifically cleaved by cancer-associated proteases. Various approaches using antibody based antigen detection or MS-based techniques, are limited in the number of samples, which can be screened in parallel. To overcome these problems, peptide microarrays were used. Compared to Ronald Frank´s SPOT-synthesis, micro-particle solid phase peptide synthesis (mpSPPS) allows much higher peptide densities with up to 1000 different peptides per cm2, dependent on the layout. This PhD thesis dealt with the development of a high-throughput screening assay platform based on in-situ synthesized peptide microarrays. As first step a model system, using known proteases (trypsin, thrombin, proteinase k etc.), was developed. To check for general applicability of the PEGMA/MMA surface, on which the peptide synthesis takes place, the manufactured peptide microarrays, containing N-terminal antibody recognition sequences (FLAG- & HA-tags), were used without further chemical modification. After proteases incubation, the respective fluorescently labeled anti-FLAG- & anti-HA antibodies will only bind to peptides, bearing the intact tag-sequence, leading to a decrease in fluorescence intensity, where the enzymes were active. After demonstrating on-chip proteolysis, using indirect antibody labeling, the biotin-streptavidin system was introduced to minimize the peptide label to a smaller tag. This allowed greater sequence variability and avoided false positive cleavage, as when using a proteinogenic tag sequence. Together with the PEPperPRINT Company, a biotin toner was developed, to integrate this labeling reagent into the in-situ synthesis process, which turned out to be advantageous compared to in-solution modification of the peptide content. To further overcome limitations on the part of the solid support, the polymer film was optimized, by introducing a new dextran surface. Preliminary experiments in lab-scale showed good proteolytic cleavages with model proteases and spotted peptides. The transfer to production scale however, showed the requirement of optimization, regarding polymer composition and peptide density, which is an ongoing process.
Die vorliegende Arbeit ist ein Beitrag zur Aufklärung der auf molekularer Ebene bisher unverstandenen Selektivität von N-Donorliganden wie 2,6-Bis(5,6-dipropyl-1,2,4-triazin-3-yl)pyridin (nPrBTP) und 2,6-Bis(5-2,2-dimethylpropyl)1H-pyrazol)-3-yl-pyridin (C5-BPP) für die Komplexierung von dreiwertigen Actinidenionen gegenüber Lanthanidenionen, die für eine selektive Abtrennung der dreiwertigen Actiniden von den Spaltlanthaniden im Rahmen des P&T-Konzepts diskutiert werden. Ein wesentlicher Erklärungsansatz für die Selektivität der untersuchten Liganden ist, dass die Metall-Ligand-Bindung in den Actinidenkomplexen eine höhere Kovalenz aufweisen sollte als in den Lanthanidenkomplexen. In der NMR-Spektroskopie an paramagnetischen Komplexen bietet sich der durch die Delokalisierung von Elektronenspindichte mittels kovalenter Bindungen übertragene Fermi-Kontaktshift als Kriterium zum Nachweis der Kovalenz an. Verschiedene Ansätze, die diesen Anteil vom Pseudo-Kontaktshift (dipolare Kopplung des magnetischen Moments der ungepaarten Elektronen und dem Kernspin) abtrennen können, wurden angewendet und verglichen. Hierzu wurden die Ln(III)-Komplexe mit Ausnahme von Gd(III) und Pm(III) sowie der Am(III)-Komplexmit nPrBTP und C5-BPP synthetisiert und NMR-spektroskopisch untersucht. Es wurden vollständige Datensätze von 1H, 13C und 15N-Spektren erhalten. Durch die Anreicherungmit dem NMR-aktiven Isotop 15N an den Positionen 8 und 9 konnten die Resonanzsignale dieser Stickstoffatome in allen Lanthanidenkomplexen detektiert werden. Eine Methode zur Trennung von FCS und PCS ist die Bleaney-Methode, die auf einer unterschiedlichen Temperaturabhängigkeit von FCS (T^(−1)) und PCS (T^(−2)) bei der Entwicklung der chemischen Verschiebung in eine Reihe temperaturabhängiger Glieder beruht. Sie wurde für beide Liganden auf alle Kerne der Lanthanidenkomplexe angewandt. Für alle Kerne, insbesondere jedoch die Protonen, wurden, verglichen mit Erwartungen aus der Theorie, unrealistisch hohe Werte für den FCS berechnet. In einigen Fällen zeigte die Bleaney-Methode das vorliegen von Spinpolarisation als Wechselwirkungsmechanismus zwischen Metallion und Ligand an. Zur weiteren Untersuchung wurden polynomiale Anpassungen an eine erweiterte Temperaturreihenentwicklung, bei der das temperaturunabhängige Glied a_0 nicht vernachlässigt wird, durchgeführt. Der physikalisch nicht erklärbare temperaturunabhängige Shift TIS (entspricht a_0) ist in allen Fällen nicht vernachlässigbar klein, sondern macht bis zu 50% der beobachteten chemischen Verschiebung aus. Der errechnete PCS ist dagegen in der Regel klein, was insbesondere bei den schweren Lanthaniden nicht der gängigen Theorie entspricht. Die mit der Bleaney-Methode erkannten Trends, wie beispielsweise Spinpolarisation, konnten mit der erweiterten Temperaturreihenentwicklung nicht bestätigt werden. Beide temperaturabhängige Methoden zeigen ein deutliches Überwiegen des FCS gegenüber dem PCS an. Dieses Ergebnis ist ein Widerspruch zum physikalisch-chemischen Verhalten der Lanthanidenionen, bei denen die Delokalisation von Elektronenspindichte durch kovalente Bindungen gegenüber dem dipolaren PCS eine untergeordnete Rolle spielen sollte. Eine theoretisch gut fundierte, temperaturunabhängige Methode ist die Reilley-Methode. Hierwerden zwei theoretisch bestimmte Werte, der Bleaney-Parameter C_Ln und der Spinerwartungswert der Lanthanidenionen in z-Richtung, <S_z>_Ln, zur Berechnung von FCS und PCS verwendet. Für diese Methode existieren zwei Datensätze und zwei Auftragungsvarianten. Die Reilley-Methode liefert plausible Werte für FCS und PCS und bildet darüber hinaus auch die magnetische Anisotropie der Komplexe richtig ab. Es zeigt sich, dass auch die Metall-Stickstoff-Bindung der Lanthanidenkomplexe einen erheblichen kovalenten Anteil besitzt, für die Protonen jedoch der PCS den maßgeblichen Wechselwirkungsmechanismus darstellt. Die Heteroatome zeigen deutliche Einflüsse des PCS und das Auftreten von Spinpolarisation wird bestätigt. Im Rahmen der Reilley-Methode tritt eine Unterteilung der Lanthanidenserie in schwere und leichte Elemente bei Gd(III) auf. Um zu untersuchen, ob dies auf einer strukturellen oder einer elektronischen Veränderung der Komplexe beruht, wurde die Zweikernmethode nach Spiliadis und Pinkerton angewendet. Die Auswertung für die Protonen beider Komplexe ergibt, dass Isostrukturalität für alle Lanthanidenkomplexe vorliegt. Die Ergebnisse der Kohlenstoffkerne bei beiden Liganden und der Stickstoffatome bei nPrBTP deuten jedoch auf Abweichungen von der Isostrukturalität hin. Dieser scheinbare Widerspruch wird auf das Auftreten von ligandenzentriertem Pseudo-Kontaktshift in beiden Komplexsystemen zurückgeführt. Damit ist die Hypothese einer konstanten Hyperfeinkopplungskonstante für die gesamte Lanthanidenreihe zumindest für Heterokerne in den nPrBTP-Komplexen widerlegt. Bei den Komplexen des C5-BPP-Liganden gilt dies nur für die Kohlenstoffkerne. Dies ist ein Hinweis auf unterschiedliche Bindungseigenschaften in nPrBTP- und C5-BPP-Komplexen. Da für Am(III), wie für alle Actiniden, keine Spinerwartungswerte und Bleaney-Parameter vorliegen, wurden auch für diese Komplexe die temperaturabhängigen Methoden angewendet. Obwohl sich nach der Bleaney-Methode hervorragende lineare Anpassungen ergeben, sind die Werte für FCS und PCS sehr kritisch zu betrachten: Die paramagnetische chemische Verschiebung ist nahezu temperaturindifferent und es ergibt sich für alle Kerne ein annähernd konstantes Verhältnis (70:30) von FCS zu PCS. Die erweiterte Temperaturreihenentwicklung liefert wie bei den Ln(III)-Komplexen große Werte für a_0, die oft über 50% der paramagnetischen Verschiebung ausmachen. Die Ergebnisse zeigen eindeutig, dass die temperaturabhängigen Methoden nur mit großen Einschränkungen zur Trennung von FCS und PCS in den Actinidenkomplexen angewendet werden können. Ohne eine zuverlässige Methode zur Bestimmung des FCS an den Ligandenkernen des Komplexes ist eine Quantifizierung der Kovalenz in der Metall-Ligand-Bindung in den Am(III)-Komplexen nicht möglich. Qualitativ kann jedoch ein erheblicher Einfluss durch Kovalenz übertragener Effekte in den Am(III)-Komplexen konstatiert werden. An den koordinierenden Stickstoffen tritt eine weitgehend lokalisierte, große Verschiebung der Resonanzsignale von über 250 ppm relativ zu den Lanthanidenkomplexen auf. Die Ursache hierfür ist die bei den Actiniden deutlich stärkere Spin-Bahn-Wechselwirkung, die auf den Stickstoffkern übertragen wird. Wie der FCS beruht auch dieser Mechanismus auf dem Vorhandensein einer signifikanten Kovalenz in der Metall-Ligand-Bindung. Damit ist dies der erstmalige NMR-spektroskopische Nachweis von Kovalenz in einer Actinid-Ligand-Bindung. Mit der Analyse der 15N-Verschiebungen in den Lanthaniden- und Americiumkomplexen konnten neue Daten für die Verschiebungen von direkt an das Metallion bindenden Heterokernen in organischen Liganden gewonnen werden. Diese erlauben eine Überprüfung der Theorie der paramagnetischen NMR-Spektroskopie und können als Benchmark für quantenchemische Rechnungen dienen. Darüber hinaus tragen die Ergebnisse dazu bei, ein tiefgehendes Verständnis für die Bindungs- und Extraktionseigenschaften von Liganden auf molekularer Ebene zu erreichen. Dieses ist unverzichtbar für das zielgerichtete Design verbesserter Extraktionsmittel für die Trennung von Lanthaniden und Actiniden sowie für die Optimierung von Extraktionsprozessen.
Reactive iodine species impact atmospheric chemistry in several ways. They play an important role in the process of ozone destruction at mid-latitudes and possibly in polar regions. Reactive iodine compounds (besides bromine) also affect the atmospheric cleaning mechanisms by changing its oxidation capacity. Recent field studies indicate that reactive iodine may impact the local climate in coastal areas by playing a key role in the formation of new particles which could influence cloud micro physical properties. Particularly high concentrations of the reactive iodine are found at mid-latitude coastal sites, which are most likely emitted by seaweed exposed to oxidative stress during low tide. However, there is still very limited knowledge on the involved seaweed species and their contribution to local, regional and global iodine emissions and also the potential iodine mediated particle formation.
In the frame of this work a new mobile Open Path CE-DOAS instrument was developed for direct measurements of IO, one of the most important reactive iodine species. It was applied successfully in two field campaigns on the Irish west coast for measurements in the inter-tidal zone, directly above air-exposed seaweed patches. These measurements for the first time identify exposed seaweeds as IO "hot-spots" with very high IO mixing ratios often exceeding 50 ppt. This shows that local IO concentrations are sufficiently high to initiate the strong particle nucleation events previously observed at the Irish West Coast.
Furthermore, during the field campaigns on the Irish west coast, combined LP-DOAS and CE-DOAS measurements were applied, which extended previous observations of reactive iodine at Mace Head and the close by MRI to further locations. These observations now cover ten shores. This study showed that the major sources of reactive iodine at the Irish West coast are wave sheltered shores and not, as previously believed, wave exposed shores, like Mace Head. Since seaweed beds at wave sheltered shores cove larger areas and are longer exposed to air, this shows that Irish, and most likely also global, iodine emissions from coastal areas should be much higher compared to previous estimates based on wave exposed shores. From this finding a yearly emission of 2*10^8 gI/yr to 3*10^9 gI/yr is estimated for global coastal areas.
In a third field study on the east coast of the New Zealand south island, for the first time high IO mixing ratios of up to 68 ppt were observed on a southern hemispheric coast. Four, previously uninvestigated, seaweed species were identified as emitters of reactive iodine species and emission rates were estimated. The observations in New Zealand showed also distinct differences in the seaweed distribution to northern hemispheric locations which need to be considered in global estimates of coastal iodine emissions.
Die vorliegende Arbeit beschäftigt sich mit monodentaten Phosphinliganden, bei denen drei Imidazolreste durch Kondensation von Boranen verbrückt sind. Es resultieren kegel- bzw. schalenförmige Moleküle, die sich durch Winkel von annähernd 90° zwischen den P-C-Bindungen auszeichnen. Die Substituenten der verbrückenden BR2-Einheiten können über einen weiten Bereich variiert werden, wodurch sowohl der sterische Anspruch als auch die Symmetrie der Liganden kontrolliert werden können. Durch Verbrückung mit drei C2 symmetrischen R,R 2,5-Dimethylborolan-1-yl-Einheiten wurde ein enantiomerenreines, C3 symmetrisches Phosphin erhalten. Mit diesem konnte der erste, C3-symmetrische Monophosphin-Gold-Komplex hergestellt werden. Mit einem achiralen Phosphin-Derivat konnte noch ein weiterer Gold(I)-Komplex sowie vier Nickel(0)-Komplexe hergestellt werden. Die Metall-Phosphor-Bindungsabstände in allen Komplexen sind sehr kurz. Diese kurzen Abstände, IR-Messungen, DFT-Rechnungen und Substitutionsexperimente deuten darauf hin, dass die neue Phosphinklasse im Vergleich zu Triphenylphosphin über schwache σ Donor- und starke π Akzeptoreigenschaften verfügt.
Quantitative information is key to unravel molecular processes in all fields of research. Counting by Photon Statistics (CoPS) is a single molecule technique that provides such quantification for fluorescent species. CoPS exploits the photon antibunching effect to infer the number of independent emitters and their molecular brightness from multiple photon detection events. I laid the foundation for high quality results by improving the microscope detection efficiency more than threefold compared to earlier measurements. Using both simulations and experiments with defined, DNA-based probes, I investigated the critical interplay of fluorophore properties and analysis parameters. I discovered that measurements at high molecular brightness can be ten times faster than previously established which opens new possibilities for time resolved quantification. The findings stress that the choice of analysis parameters is vital and provide an objective measure of fluorophore eligibility for CoPS. I characterized sixteen organic dyes across the visible spectrum based on their molecular brightness and photostability. This study accomplished the transition of CoPS from a proof of concept technique to a widely applicable quantification method. Experiments demonstrated that CoPS can reveal the label number distribution of fluorescent markers, a prerequisite for quantitative investigations in biology. Moreover, I showed that CoPS offers new perspectives for characterization of photophysical processes in photoluminescent materials.
Background: Cancer-associated pain is a major cause of poor quality of life in cancer patients and is frequently resistant to conventional therapy. Recent studies indicate that some hematopoietic growth factors, namely granulocyte macrophage colony stimulating factor (GMCSF) and granulocyte colony stimulating factor (GCSF), are abundantly released in the tumor microenvironment and play a key role in regulating tumor-nerve interactions and tumor-associated pain by activating receptors on dorsal root ganglion (DRG) neurons. Moreover, these hematopoietic factors have been highly implicated in postsurgical pain, inflammatory pain and osteoarthritic pain. However, the molecular mechanisms via which G-/GMCSF bring about nociceptive sensitization and elicit pain are not known. Results: In order to elucidate G-/GMCSF mediated transcriptional changes in the sensory neurons, we performed a comprehensive, genome-wide analysis of changes in the transcriptome of DRG neurons brought about by exposure to GMCSF or GCSF. We present complete information on regulated genes and validated profiling analyses and report novel regulatory networks and interaction maps revealed by detailed bioinformatics analyses. Amongst these, we validate calpain 2, matrix metalloproteinase 9 (MMP9) and a RhoGTPase Rac1 as well as Tumor necrosis factor alpha (TNFα) as transcriptional targets of G-/GMCSF and demonstrate the importance of MMP9 and Rac1 in GMCSF-induced nociceptor sensitization. Conclusion: With integrative approach of bioinformatics, in vivo pharmacology and behavioral analyses, our results not only indicate that transcriptional control by G-/GMCSF signaling regulates a variety of established pain modulators, but also uncover a large number of novel targets, paving the way for translational analyses in the context of pain disorders.
Background: Circadian clocks control rhythmic expression of a large number of genes in coordination with the 24 hour day-night cycle. The mechanisms generating circadian rhythms, their amplitude and circadian phase are dependent on a transcriptional network of immense complexity. Moreover, the contribution of post-transcriptional mechanisms in generating rhythms in RNA abundance is not known. Results: Here, we analyzed the clock-controlled transcriptome of Neurospora crassa together with temporal profiles of elongating RNA polymerase II. Our data indicate that transcription contributes to the rhythmic expression of the vast majority of clock-controlled genes (ccgs) in Neurospora. The ccgs accumulate in two main clusters with peak transcription and expression levels either at dawn or dusk. Dawn-phased genes are predominantly involved in catabolic and dusk-phased genes in anabolic processes, indicating a clock-controlled temporal separation of the physiology of Neurospora. Genes whose expression is strongly dependent on the core circadian activator WCC fall mainly into the dawn-phased cluster while rhythmic genes regulated by the glucose-dependent repressor CSP1 fall predominantly into the dusk-phased cluster. Surprisingly, the number of rhythmic transcripts increases about twofold in the absence of CSP1, indicating that rhythmic expression of many genes is attenuated by the activity of CSP1. Conclusions: The data indicate that the vast majority of transcript rhythms in Neurospora are generated by dawn and dusk specific transcription. Our observations suggest a substantial plasticity of the circadian transcriptome with respect to the number of rhythmic genes as well as amplitude and phase of the expression rhythms and emphasize a major role of the circadian clock in the temporal organization of metabolism and physiology.
The rational design of organic semiconductors for optoelectronic devices relies on a detailed understanding of how their molecular and morphological structure condition the energetics and dynamics of charged and excitonic states. Investigating the role of molecular architecture, conformation, orientation and packing, this work reveals mechanisms that shape the spatially resolved densities of states in organic, small-molecular and polymeric heterostructures and mesophases. The underlying computational framework combines multiscale simulations of the material morphology at atomistic and coarse-grained resolution with a long-range-polarized embedding technique to resolve the electronic structure of the molecular solid. We show that long-range electrostatic interactions tie the energetics of microscopic states to the mesoscopic structure, with a qualitative and quantitative impact on charge-carrier level profiles across organic interfaces. The computational approach provides quantitative access to the charge-density-dependent open-circuit voltage of planar heterojunctions. The derived and experimentally verified relationships between molecular orientation, architecture, level profiles and open-circuit voltage rationalize the acceptor-donor-acceptor pattern for donor materials in high-performing solar cells. Proposing a pathway for barrier-less dissociation of charge transfer states, we highlight how mesoscale fields generate charge splitting and detrapping forces in systems with finite interface roughness. The associated design rules reflect the dominant role played by lowest-energy configurations at the interface.
Microfluidics combines principles of science and technology, and enables the user to handle, process and manipulate fluids of very small volumes. This technology permits the integration of multiple laboratory applications into one single microfabricated chip, requires minimal manual user intervention and sample consumption, and allows enhanced data analysis speed and precision. Due to these numerous advantages, the potential for this technology to be applied in fundamental biophysical and biomedical research is vast. The major aim of this thesis was to explore the capacities of microfluidics, particularly droplet-based microfluidic technology in the following topics: 1) Mimicry of the immune system cellular environment, with the ultimate goal of programing T cells for adoptive T cell therapy; 2) Bottom-up assembly of minimal synthetic cells. Towards this end, a novel approach to form gold-nanostructured and specifically biofunctionalized water-in-oil droplets was developed. This thesis highlights the advanced properties of nanostructured droplets to serve as 3D antigen presenting cell (APC) surrogates for T-cell stimulation. The combination of flexible biofunctionalization and pliable physical droplet properties work in tandem, providing a flexible and modular system that closely models in situ APC-T cell interactions. The research within this thesis focused also on the dissection of complex cellular sensory machinery implementing an automated droplet-based microfluidic approach. Towards this goal, nanostructured droplets as cell-sized compartments and droplet-based pico-injection technology were used to achieve the bottom-up assembly of the minimal number of proteins required for a “simple synthetic cell.” While the applied methodology has a potential for assembly of a wide range of subcellular functional units, the focus in this thesis was on the reconstitution of the actomyosin cortex. Successful optimization of the biochemical and biophysical conditions within the droplets allowed to achieve precise control over the actin polymerization and actomyosin network organization by their linkage to the droplets periphery. These experimental steps were also necessary to generate signaling events including myosin-driven droplet migration and self-propulsion with reduced molecular complexity compared to living cells.
Calculation of electronic and magnetic properties of mixed transition-metal/lanthanide complexes with ab initio methods.
Due to the growing concern on the issues of global warming, climate change, and energy shortage, more rigorous requirements are imposed on the energy conversion process of combustion. Due to the relative safety and convenience in transportation and storage, liquid fuels are commonly used in many practical combustion systems such as diesel engines, gas turbines and industrial furnaces. In these combustion devices, turbulent spray flows are involved. The character of spray dispersion, evaporation, mixing and combustion of fuel droplets strongly determines the performance of these systems with respect to the combustion efficiency, stability, and emissions. Therefore, an improved understanding of turbulent spray combustion and the development of predictive models are needed for a better design of more efficient combustion systems.
The present work focuses on the development of a computational methodology based on the transported joint probability density function (PDF) method for the modeling and simulation of two-phase turbulent spray flows without and with chemical reactions. In the non-reacting situation, the dependent variables of the joint PDF include the gas velocity and the mixture fraction. For the simulation of reacting spray flows, a three-variate joint PDF transport equation is derived and modeled in order to account for the pre-vaporization effects and partially premixed regime in turbulent spray flames. The dependent variables include the gas phase mixture fraction, the reaction progress variable and gas enthalpy. Detailed combustion chemistry is considered through an extended spray flamelet model by including a reaction progress variable in addition to the classical formulation.
The dilute spray is simulated using a Lagrangian discrete parcel method for the description of droplet motion, heating and evaporation. The infinite conductivity model with consideration of non-equilibrium effects based on the Langmuir-Knudsen law is considered. The spray evolution and flame structures in the frame of the polydisperse reacting spray flows are investigated. Numerical results are compared with experimental data provided by Prof. Masri at the University of Sydney, Australia, and the test cases include three different turbulent non-reacting acetone spray flows in air and turbulent spray flames with the liquid fuel ethanol.
For the acetone spray flows, computational results generally show good agreement with experimental data in terms of the droplet size and mean velocity distribution, as well as the liquid volume flux. The results show that the inflow liquid mass loading hardly affects the droplet diameter distribution, whereas the inlet turbulence level has a pronounced effect. The tendency of droplet accumulation near the jet centerline is found with a somewhat overprediction of liquid volume flux at downstream locations. A more sophisticated turbulence model is expected to eliminate this discrepancy. Moreover, the local joint PDF of the gas velocity and the mixture fraction is analyzed. A linear correlation of the gas velocity and the mixture fraction exists close to the nozzle exit outside the main spray jet, and no regions are found where statistical independence prevails.
For the simulation of spray flames, computations with the newly developed spray flamelet/progress variable approach and with the previous standard spray flamelet formulation are carried out and compared with the experiments by Prof. Masri at the University of Sydney. A good agreement between the computations with the new formulation and the experiments for gas temperature and droplet size and velocity is achieved. The major spray and combustion properties are correctly captured using this new formulation, which is compared with an unphysically attached flame near the nozzle exit predicted by the previous model.
A partially premixed combustion prevails in this piloted turbulent spray flame. Due to the prevaporization of the ethanol droplets near the nozzle exit, a lean premixed gas mixture is found at the inner side of spray jet. Moving downstream, the lean-sided diffusion flame is promoted towards the inner fuel-rich side by heating up the inner premixed core that is controlled by the droplet evaporation. Additionally, it is observed that in the far-field region, the diffusion flame becomes the dominant combustion mode.
In summary, an efficient computational model based on the transported joint PDF method is developed to two-phase turbulent spray flows. The combined transported joint PDF and a newly proposed spray flamelet/progress variable approach shows an improved performance in the prediction of complex turbulent spray flames, and new insights on the local flame structure influenced by evaporating sprays are obtained.
The interaction of light and matter is central in some of the most fundamental processes in nature. The theoretical description of these processes is essential for numerous applications in all fields of science. To gain an understanding of light-induced reactions at a microscopic scale, it is necessary to study quantum mechanical phenomena, for which quantum chemical methods are required. Quantum chemical methods offer access to excitation energies, potential energy surfaces and excited-state properties, which are key for the description of photo-chemical reactions. A variety of well-established quantum chemical methods is available, but however, many of these methods have limited applicability due to their exceedingly large computational demands. In general a numerically exact description is only possible for molecules with few atoms. Yet, biologically or technically relevant systems comprise hundreds or thousands of atoms. Examples are protein-chromophore complexes, which take part in photosynthesis or the reception of light in the eyes of humans and animals. An important part in the field of quantum chemistry is the development of suitable methods, which offer both, a sufficiently accurate description of the involved physical effects, and feasible computational requirements. Of the available methods, which fulfil the above-stated requirements, many suffer from severe drawbacks. The central information obtained from quantum chemical calculations is the energy of electronic states. However, for many interesting questions, further properties of the electronic states are required. Hence, an important part of the development of quantum chemical methods is the derivation and implementation of methodologies for the description of excited state properties. A key property is the gradient of the energy. It is required to efficiently explore potential energy surfaces and for the theoretical modeling of experimental findings. Other important quantities are absorption cross-sections, which correspond to absorption coefficients in spectroscopical experiments. In this thesis, the so-called algebraic diagrammatic construction (ADC) scheme for the polarization propagator is considered for the description of electronically excited states. It is a quantum chemical method, which has gained more attention over the last decade. It could be shown that ADC offers for many relevant systems a well-balanced mix of both accuracy and computational demand. In particular, in this thesis the derivation and implementation of excited state energy gradients is presented. Furthermore an approach to obtain optical properties using the so-called intermediate state representation (ISR) is discussed. The ISR/ADC approach for the computation of two-photon absorption cross-sections and its implementation are presented. Both implementations are numerically tested and applied to two model systems, all-trans-octatetraene and trans-bithiophene. The results for trans-bithiophene are very promising, however, in the case of all-trans-octatetraene limitations for the description of the excited state geometry by the presented derivative approach are encountered.
Naturally occuring cyclic peptides exist in the ascidians Lissoclinum Patella of the Pacific and Indian Oceans. The biological role of these structural interesting marine secondary metabolites is still unclear. The patellamides are able to bind a variety of transition metal ions. Some of the copper(II) complexes of cyclic pseudo-peptides are known to form carbonato-bridged complexes when exposed to CO2. Thus, in previous studies a library of patellamide derivatives has been designed and prepared. The copper(II) coordination properties of these patellamide derivatives is widely understood. Interestingly, the corresponding dinuclear copper(II) complexes are able to efficiently, catalytically hydrolyze phosphoesters and hydrate CO2. The natural peptides are produced by the cyanobacteria prochloron didemnid, a photosynthetic symbiont of L.Patella. Since the patellamides are extracted from hydrophyllic cytoplasmic environment, together with notably high concentrations of some transition metal ions like copper(II) and zinc(II). It is likely that a natural function of probably existing transition metal complexes in this environment is hydrolase activity. The biologic background as well as the state of art regarding the copper(II) coordination chemistry is summarized in Chapter 1. The synthesis of the patellamide derivatives is shortly discussed. In Chapter 3, the electrochemistry of the copper(II) complexes is discussed. Cyclic voltammetry and square wave voltammetry were used to study the existence of a complexation equilibrium between various species in solution. From the obtained results, it is concluded that the copper(I/II) redox chemistry is propably not a biologic relevant biologic function at neutral pH. Under basic conditions, it is possible that stable copper(I) species exist. It can be proposed that these are carbonate or bicarbonate bridged. Moreover, under basic conditions an oxygenation test reaction was performed, and it was shown that a dinuclear copper(II) complex of an patellamide derivative is involved in an oxygenation reaction under these rather unphysiological conditions. A tentative mechanistic proposal is discussed, which is based on the observation of a radical coupling product and insights obtained from a low temperature NMR experiment. In addition the proposed copper(II) complexation equilibria of the ligand H4pat4 is discussed, and the respective EPR spectra with their simulations are in the focus of the last section of Chapter 3. Especially while regarding the formation of heterodinuclear copper(II)/ zinc(II) complexes with H4pat4 in Chapter 5this equilibrium is requested. Since biological relevant hydrolysis chemistry is often based on zinc(II) enzymes, zinc(II) complexes of the macrocyclic peptides were studied. Chapter 4 presents the formation of zinc(II) complexes, which are explored using isothermal calorimetric titrations in combination with NMR spectroscopy and mass spectrometry. After an overview of the biological relevance of zinc(II) based hydrolases, Chapter 4 presents a proposed zinc(II) complexation equilibrium. In Chapter 5, the formation of heterodinuclear copper(II)/ zinc(II) complexes is described based on spectroscopic results. EPR spectroscopy, paramagnetic NMR and UV/vis spectroscopy in combination with mass spectrometry are used to describe two different heterodinuclear complexes. Furthermore, Chapter 5 describes the formation of a copper(II)/ zinc(II) complex due to a distinct cooperative effect, with a ligand that does not form stable spectroscopically characterizable homodinuclear zinc(II) complex. Phosphoester hydrolysis reactions with a model substrate of all complexes, described in Chapters 3,4 and 5 have been investigated in a kinetic assay. The pH dependent results are discussed in Chapter 6. Furthermore the substrate dependency of the initial rate was tested. All complexes discussed exhibit catalytic activity in a pH range close to neutral. Comparison of all data obtained shows that the zinc(II) complexes are slightly more active than the corresponding homodinuclear copper(II) complexes.
Background: Neuromyelitis optica (NMO, Devic syndrome) is associated with antibodies to aquaporin-4 (NMO-IgG/AQP4-Ab) in the majority of cases. NMO-IgG/AQP4-Ab seropositivity in patients with NMO and its spectrum disorders has important differential diagnostic, prognostic and therapeutic implications. So-called cell-based assays (CBA) are thought to provide the best AQP4-Ab detection rates. Objective: To compare directly the AQP4-IgG detection rates of the currently most widely used commercial CBA, which employs cells transfected with a full-length (M1)-human AQP4 DNA in a fashion that allows leaky scanning (LS) and thus expression of M23-AQP4 in addition to M1-AQP, to that of a newly developed CBA from the same manufacturer employing cells transfected with human M23-AQP4-DNA. Methods: Results from 368 serum samples that had been referred for routine AQP4-IgG determination and had been tested in parallel in the two assays were compared. Results: Seventy-seven out of 368 samples (20.9%) were positive for NMO-IgG/AQP4-Ab in at least one assay. Of these, 73 (94.8%) were positive in both assays. A single sample (1.3%) was exclusively positive in the novel assay; three samples (3.9%) were unequivocally positive only in the ‘classic’ assay due to high background intensity in the novel assay. Both median fluorescence intensity and background intensity were higher in the new assay. Conclusions: This large study did not reveal significant differences in AQP4-IgG detection rates between the ‘classic’ CBA and a new M23-DNA-based CBA. Importantly, our results largely re-affirm the validity of previous studies that had used the ‘classic’ AQP4-CBA to establish NMO-IgG/AQP4-Ab seropositivity rates in NMO and in a variety of NMO spectrum disorders.
Although several lipids have been shown to participate in intracellular signal transduction events and to influence central cellular processes, the bioactive actions of most lipids remain unexplored. This lack of knowledge is mainly due to a shortage of tools to manipulate lipid levels within living cells in a non-invasive way and to identify new protein interactors of single lipid species. This work presents the development of two methods to overcome these drawbacks applied to sphingosine (Sph). The origin of calcium signaling properties of Sph and its involvement in the pathophysiological development of the lysosomal storage disease Niemann-Pick type C (NPC) are reported. First, ‘caged’ variants of sphingosine were synthesized which enable the precise elevation of Sph levels in single living cells within seconds using light. This acute increase in Sph concentration led to an immediate release of lysosomal calcium through the actions of the two-pore channel 1 (TPC1). In cells derived from NPC patients, an accumulation of Sph in the endolysosomal compartments was visualized for the first time. Additionally, NPC cells exhibited reduced calcium signals upon Sph uncaging, indicating that Sph accumulation is upstream of a calcium defect in this disease. Sph-induced calcium release also initiated the nuclear translocation of transcription factor EB, which positively regulates the expression of autophagic and lysosomal biogenesis genes, further underlining the importance of lysosomal calcium release in direct lysosome-to-nucleus signaling pathways. In order to capture Sph-interacting proteins, a trifunctional Sph (TFS) was developed. TFS facilitates the release and immediate crosslinking of Sph to its interacting partners within the living cell. Mass-spectrometric analyses identified known Sph-binding proteins such as the ceramide synthase, as well as novel putative Sph-interactors. The general applicability of this method was proven by using trifunctional diacylglycerol as well as a trifunctional fatty acid. TFS was further employed in investigations of the subcellular localization and transport of Sph through the cell. NPC patient fibroblasts showed a striking accumulation of Sph in late endosomes and lysosomes. Sph transport out of these vesicles was severely hindered in the NPC condition. The kinetics of Sph efflux correlated with the severity of symptoms in different NPC patients, so this assay could potentially be used for monitoring and prognosis of NPC disease severity.
Die hier vorliegende Arbeit beschäftigt sich mit der Synthese und Charakterisierung kleiner, aromatischer, dipolarer, zu SAM–Bildung fähiger Moleküle zur Modifizierung von Austrittsarbeiten von Elektroden–Material bei gleichzeitiger Kontrolle der Benetzungseigenschaften der Oberfläche.
The control over the work function of surfaces and interfaces is one of the most important issues of modern surface science and nanotechnology, e.g. in context of organic electronics and photovoltaics. The goal of this work was to look for new ways to control the work function of metal substrates by using molecular self-assembly. Two different strategies were used. The first strategy was to use aliphatic and aromatic molecules which contain an embedded dipolar group (midchain functionalization). Such self-assembled monolayers (SAMs) allow for tuning the substrate work function in a controlled manner, independent of the docking chemistry and, most importantly, without modifying the SAM-ambient interface. In the case of aliphatic films, we used alkanethiols functionalized with an embedded ester dipole, with the length of both top and bottom segments as well as the direction of the embedded dipole being varied. In the case of aromatic systems, we used terphenyl based thiols functionalized with an embedded pyrimidine dipolar group, with the direction of the dipole being varied. The electronic and structural properties of these embedded-dipole SAMs were thoroughly analyzed using a number of complementary characterization techniques combined with quantummechanical modeling. It is shown that such mid-chain-substituted monolayers are highly interesting from both fundamental and application viewpoints, as the dipolar groups are found to induce a potential discontinuity inside the monolayer, electrostatically shifting the core-level energies in the regions above and below the dipoles relative to one another. Particularly imptortant, in context of the present work, is the fact that the mid-chain functionalized films are indeed well suited to adjust the work function of metal substrates. This could be e.g. done by varying the orientation of the dipolar group but also by mixing the molecules with differently oriented dipoles as was demonstrated in the present work. Within the second strategy, we used photoresponsive systems, viz. azobenzene substituted alkanethiols, having a specially designed architecture to control the packing density and carrying an additional dipolar tail group. These novel SAMs were studied in detail by using spectroscopic and microscopic techniques. Performing photoisomerization experiments we obtained a reproducible, stimuli-responsive change in the work function which was, however, limited to some extent due to the strong steric hindrance effects. In order to reduce these effects, we diluted the azobenzene molecules with short spacer molecules, which resulted in an improvement in the photoswitching behavior.
Since both healthy human hematopoietic stem and progenitor cells (HSPC) and leukemia initiating cells (LIC) are sustained in a dormant state in bone marrow niche, they are protected against cytotoxic effects of chemotherapy. Thus, quantitative identification of differential adhesion of HSPC vs. LIC to bone marrow niche would help for the development of an effective clinical therapy of leukemia. The main aim of the present thesis was the fabrication and application of self-assembled, planar phospholipid membranes on solid support as in vitro model of bone marrow niche. A special focus was put on the influences of relevant ligand-receptor pairs and acute myeloid leukemia (AML) on the adhesion and morphological dynamics of HSPC. As the model of bone marrow niche, supported lipid membranes functionalized with N-cadherin and SDF1alpha were utilized to study their relative significance. In Chapter 2, the deposition of supported membranes and their quantitative functionalization with N-cadherin and SDF1alpha were confirmed by high energy specular X-ray reflectivity (XRR) and quartz crystal microbalance with dissipation monitoring (QCM-D). The fine structures perpendicular to the membrane surface and the lateral density of membrane-anchored proteins were determined by XRR with sub-Ångström resolution. Real-time monitoring by QCM-D of membrane deposition and functionalization demonstrated the quantitative variability of the average intermolecular distance <d> of proteins and elucidated their viscoelastic properties such as the shear elastic modulus and shear viscosity. In Chapter 3, the strength of HSPC adhesion was quantitatively evaluated by the determination of (a) the fraction of adherent cells, (b) the area of tight adhesion and (c) the critical force of cell detachment as a function of the average intermolecular distance <d> of N-cadherin nd SDF1alpha. The results clearly demonstrated that the binding of HSPC to the in vitro niche model was a positively cooperative process, and the adhesion mediated by the SDF1alpha/CXCR4 axis was stronger compared to adhesion mediated by the homophilic N-cadherin axis. The statistical image analysis of stochastic morphological dynamics unraveled that HSPC on in vitro niche models displaying SDF1a dissipated energy by undergoing oscillatory deformation, whereas cell locomotion mediated by the homophilic binding of N-cadherin was hardly impaired with morphological deformations. In order to verify the clinical relevance, the adhesion of leukemic blasts (LB) from AML patients was investigated in a systematic manner. In comparison to HSPC, LB exhibited a significantly higher affinity to the in vitro niche model reflecting the partial ineffectiveness of chemotherapy and the difficulties of replacing them by allogenic transplanted HSPC. The obtained results demonstrated that the combination of precisely defined cell surface models, a novel non-invasive assay for evaluating the cell adhesion strength, and statistical analysis of live cell images in Fourier space is a powerful tool to quantitatively analyze different functions of ligand-receptor pairs in bone marrow niche, which cannot be assessed by phenomenological observation.
This thesis deals with the study of the properties of bispidine iron(IV)-oxo complexes. These are biomimetic model compounds for non-heme iron enzymes. The first part describes the thermal spin crossover behavior of the tetradentate bispidine ligands’ iron(II) complexes. These compounds were precisely characterized using UV-vis-NIR and Mößbauer spectroscopy as well as Evans NMR spectroscopy and SQUID measurements. The tetradentate bispidine ligands’ iron(IV)-oxo complexes were characterized using UV-vis-NIR and Mößbauer spectroscopy. They were also analyzed computationally with DFT calculations. In addition, it was possible to characterize a high spin iron(IV)-oxo species by Mößbauer spectroscopy. This species’ electron transfer properties were analyzed. The second part of this study is about the photocatalytic generation of an iron(IV) oxo species with water as oxygen source. [RuII(bpy)3] 2+ was used as a photosensitizer. After irradiating it with visible light it was oxidized with [CoIII(NH3)5(MeCN)] 3+ to [RuIII(bpy)3] 3+, which catalytically generates in situ an iron(IV)-oxo species with water as source of oxygen. This reaction is also interesting with regard to environmental issues as it seems promising to use solar energy to produce highly energetic species. The third part of this study covers the redox properties of the pentadentate bispidine ligands’ ferryl complexes when the redox inactive metal ion Sc3+ is present. The presence of Sc3+ shifts the redox potential of the ferryl complex to higher potentials. This effect can be used to manipulate the electron transfer properties of the ferryl compound. This FeIV(O)- Sc3+ complex can serve as a model compound for the Mn4CaO5 cluster in the photosystem II. The last part of this study is about the non heme iron-oxo-catalyzed methanogenesis. The ferryl complexes of the tetra- and pentadentate bispidine ligands produce methane from methionine and other thioethers. In the first step of the process, methionine is oxidized to methionine sulfoxide. A bifurcation of the reaction pathway to a sulfone or methyl radical production marks the second step of the process. The generation of methyl radicals was confirmed by spin trapping experiments. By way of detailed DFT calculations it was possible to shed light on the mechanism of methane formation in a highly oxidative environment.
Die weltweit steigende Zahl der Infektionen durch multiresistente Krankheitserreger ist eine bedeutende Herausforderung für unser modernes Gesundheitssystem. Zu ihrer effektiven Bekämpfung werden Antibiotika mit neuen Wirkmechanismen benötigt. Im Entwicklungsprozess eines neuen Antibiotikums können zwar viele antimikrobielle Substanzen erzeugt werden, die Identifikation neuer Wirkmotive stellt jedoch eine zeit- und kostenintensive Hürde dar. In dieser Arbeit wird die Anwendung von Röntgenkleinwinkelstreuung (SAXS) mit Synchrotronstrahlung als Hochdurchsatzverfahren zur Klassifizierung antibiotischer Wirkmechanismen präsentiert. Hierzu wurden Escherichia coli mit einem Satz klinisch relevanter Antibiotika und mit einem kurzen kationischen Peptid mit unbekanntem Wirkmechanismus behandelt, und mit SAXS untersucht. Mithilfe einer Hauptkomponentenanalyse konnten die Antibiotika anhand ihrer morphologischen Änderungen klassifiziert werden. Die hierfür relevanten Zellstrukturen konnten durch Korrelation mit Transmissionselektronenmikroskopie und zonenplattenbasierter Röntgenmikroskopie (TXM) identifiziert werden. Ein einfaches Modell erlaubte es, aus Kleinwinkelstreukurven ganzer E. coli den Volumenanteil und die Anzahl wichtiger Zellkomponenten (DNS und Ribosomen) zu extrahieren. In der Röntgenstreukammer HORST wurde kryo-SAXS im weichen Röntgenbereich etabliert, um kryogene biologische Proben, zusammen mit der existierenden kryo-TXM Einheit, korrelativ in Real- und Fourierraum zu untersuchen.
Mehr als 2.500 Physiker aus dem In- und Ausland waren bei der Frühjahrstagung der Deutschen Physikalischen Gesellschaft an der Universität Heidelberg zu Gast. Es ging um Fragestellungen aus dem Bereich der Atom- und Molekülphysik, der Quantenoptik und der Physik der Hadronen und Kerne. Einen thematischen Bezugspunkt bildet dabei das von der UNESCO ausgerufene „Internationale Jahr des Lichts“, dem zahlreiche Veranstaltungen gewidmet waren. Neben dem wissenschaftlichen Programm gab es drei öffentliche Vorträge. Im Mittelpunkt des Interesses stand dabei der Chemie-Nobelpreisträger Professor Stefan Hell, der sowohl am Max-Planck Institut in Göttingen, am Deutschen Krebsforschungszentrum wie auch an der Universität Heidelberg forscht.
Oxymethylene dimethyl ethers (CH3O(CH2O)nCH3) bearing 3 to 5 CH2O-units (OMDME 3-5) are promising diesel additives, as they are able to reduce soot and NOx emissions. However, due to economic restrictions, an industrial synthesis process for these compounds has not been realized yet. As presented in this thesis, it was possible to synthesize oligomeric OMDME from dimethoxymethane (DMM) and trioxane (TRI), catalyzed by solid acids, in a more efficient and economical way as described in the literature. For the first time, it was possible to carry out the synthesis of OMDME at atmospheric pressure and mild reaction temperatures below 40 °C, maintaining high reactivity. Besides optimizing process parameters and testing of catalysts, reaction kinetics were also evaluated and determined. Furthermore, the synthesis of oxymethylene diethyl ethers (OMDEE) and oxymethylene diacetate (OMDAc) was investigated and compared with each other. The oligomerization of OMDME is a typical equilibrium reaction. In addition to DMM and TRI as starting materials, a series of oligomeric OMDME are also present in the equilibrium. All tests showed that the OMDME product mixture follows the Schulz-Flory distribution, even with varying DMM/TRI ratios. Solid acids, such as cation exchanger resins and zeolites, served as catalysts. Out of all tested resins and zeolites, Amberlyst36 among resins and BEA25 among zeolites exhibited the strongest catalytic activity. The chemical equilibrium was reached within a few minutes at room temperature. However, this high reactivity was only possible, when the synthesis of OMDME was performed in the absence of water, as minor traces of water already caused a significant loss of catalyst activity. For the first time, it was further possible to verify that during the oligomerization the direct insertion of TRI into DMM takes place. This was observed due to an increased OMDME 4 concentration at the beginning of the reaction. Because of these and other results, a detailed reaction mechanism was postulated, which implies the insertion of TRI into the catalytically activated DMM. The proven high rate of transacetalization in the OMDME reaction led to the Schulz-Flory distribution even before chemical equilibrium was reached.
Nanoparticles (NPs) can be utilized in a wide variety of industrial, environmental and medical applications. Most important to the work presented here is the excellent ability of NPs to serve as catalysts for various reactions. In this study, the influence of metal type, temperature, atmospheric conditions, and substrate on catalytic performance were examined in both mono- and bimetallic NPs. Sintering, phase segregation and NP/support interaction could be observed under specific experimental conditions, and are described here. Au, Pt and Pd monometallic and AuxPt1
Higher members of the acene molecule class, like the benchmark compound pentacene, are known to undergo singlet fission (SF). This extraordinary process is attractive regarding its ability of boosting quantum effciencies in photovoltaic cells and overcoming the Shockley-Queisser limit of single junction devices. There is consensus that in pentacene SF proceeds on an ultrafast timescale (<100 fs), but the details of the process are still subject of debate. Within this work, pump-probe as well as pump-depletion-probe techniques were used in combination with rate model simulations to disentangle the initial steps of SF. In particular, the effect of nitrogen atoms, which were incorporated into the pentacene backbone, on the photoinduced dynamics of TIPS-pentacene was studied. These solution-processable azaderivatives, called Diaza-TIPS- pentacene and Tetraaza-TIPS-pentacene, are great building blocks for the design of new architectures with optimized electronic properties and represent promising candidates for their use in photovoltaic devices. Measurements in the visible as well as in the near-infrared spectral region were performed in order to get a complete picture of the triplet manifold. This required the design and implementation of a new experimental setup. By applying global target analyses and numerical simulations, a detailed kinetic model of the excited state dynamics of all investigated materials could be established. The experimental observations indicate a participation of the intermediate coupled triplet pair state 1TT, which has become a hot topic regarding its role in mediating SF. The nitrogen substitution in the heteroacenes not only accelerates the formation of the 1TT state compared to TIPS-pentacene, but also the population of the final triplet state T1 via the 1TT state, implying higher quantum efficiencies. The absorption of all relevant exited states were successfully assigned with regard to their spectral occurence.
Im Rahmen dieser Arbeit wurden neuartige Distyrylbenzol-Derivate (DSB-Derivate) für den Aufbau nicht-spezifischer Sensorfelder zur Detektion von Aminen und Proteinen synthetisiert und charakterisiert. Die Generierung analytspezifischer Fluoreszenzantworten basiert auf der Adduktbildung der aldehydfunktionalisierten DSBs mit Aminen und funktionellen Seiten¬ketten von Proteinen, die eine hypsochrome Verschiebung der Emission und eine deutliche Erhöhung der Fluoreszenzintensität hevorruft. Zur Synthese wurden Heck- und Horner-Routen verwendet, welche die modulare Eincodierung unterschiedlicher elektronischer Eigenschaften und die Einführung löslichkeitssteigernder Oligoethylenglykol-Seitenketten (Swallowtails, Sw) in Aldehyd-DSBs erlauben. Somit wurde die Optimierung der Sensitivität der Sensoren und deren Anwendung in wässrigem Medium ermöglicht. Die Optimierung hinsichtlich der Sensitivität erfolgte durch Einführung und unterschiedliche Positionierung elektronenziehender Substituenten, Erweiterung des Fluorophors, sowie Post¬funktionalisierung der Aldehyde via Knoevenagel-Kondensation. Bei der Konstruktion von Sensorfeldern zur Unterscheidung der Analyten in wässrigem Medium wurde die Abhängigkeit der Fluoreszenzantworten vom pH-Wert als zusätzlicher diskrimi¬nierender Faktor integriert. Um eine lösungsmittelfreie Detektion von Amindämpfen zu ermöglichen, wurde ein einfaches und effizientes Verfahren zur Immobilisierung der Fluorophore auf festen Trägermaterialien entwickelt. Die Leistungsfähigkeit von Sensorfeldern auf Aluminium¬oxid (Alox), Silicagel und Umkehrphasen-Silicagel wurde verglichen, wobei Silicagel als tauglichste Festphase identifiziert wurde. Die Auswertung der erhaltenen Fluoreszenzantworten erfolgte mittels Digitalphotographie und Fluoreszenzspektroskopie. Falls eine Unterscheidung der Analyten aufgrund des visuellen Eindrucks nicht zweifellos möglich war, wurden die photographischen oder spektroskopischen Daten unter Verwendung statistischer Hilfsmittel analysiert und konnten dadurch objektiver differenziert werden. Mit diesen Konzepten konnten leistungsfähige nicht-spezifische Sensorfelder aufgebaut werden, die eine einwandfreie Unterscheidung von Aminen und Proteinen sowohl in Lösung als auch in der Dampfphase ermöglichen. Sie stellen eine praktikable und kostengünstige Alternative zu etablierten Detektionsverfahren dar.
Die vorliegende Arbeit befasst sich mit der Untersuchung hochvalenter Metalloxo-Komplexe. Insbesondere werden die Reaktivitäten und der Einfluss elektronischer Eigenschaften auf diese untersucht. Dabei liegt das Hauptaugenmerk darauf, eine Korrelation zwischen diesen beiden Eigenschaften zu ermitteln, damit umgekehrt Rückschlüsse auf die Reaktivität von Verbindungen mit bekannten elektronischen Eigenschaften gezogen werden können. Des Weiteren werden die Komplexe von Ligandensystemen mit identischem Rückgrat und unterschiedlichen elektronischen Eigenschaften des Donorsets miteinander verglichen, um den Einfluss unterschiedlicher Substitutionsmuster am Liganden auf die Reaktivität zu erkennen. Der erste Teil dieser Arbeit geht auf die Kinetiken der Oxidationsreaktionen mit Bispidineisen(IV)oxo-Komplexen ein. Hierbei wird auf die drei verschiedenen Reaktionstypen, CH-Aktivierung von Alkanen, Epoxidierung von Alkenen und Sauerstoff-Übertragung eingegangen. Ebenso wird die Abhängigkeit der Reaktionsgeschwindigkeit von der Protonenkonzentration untersucht. Im zweiten Teil dieser Arbeit werden die Redoxpotentiale behandelt. Für die Metalloxo-Komplexe wird der reine, nicht-Protonengekoppelte Elektronenübergang spektro-photometrisch untersucht und somit das M(n/n-1)+-Reduktionspotential bestimmt. Auch hier wird der Einfluss bei Zugabe von Protonen auf die Oxidation von Ferrocen gezeigt. Der dritte und letzte Teil dieser Arbeit befasst sich mit der Bestimmung der Reorganisationsenergie des Elektronentransfers von Eisen(IV) zu Eisen(III) in den Bispidinkomplexen und erörtert den Einfluss dieser Größe auf die Reaktions-geschwindigkeits¬konstanten der Oxidations- und Oxygenierungsreaktionen.
Bedingt durch die potentiellen Anwendungsmöglichkeiten basenstabilisierter Borverbindungen als Wasserstoffspeicher- und Transferreagenzien hat das Interesse an diesen Verbindungen in jüngerer Vergangenheit deutlich zugenommen. Zusätzlich wird dieses durch die isoelektronische Beziehung zwischen basenstabilisierten Boranen und Alkanen verstärkt, welche erlaubt diese Verbindungen als Modellsysteme für C–H-Aktivierungsprozesse heranzuziehen. Die vorliegende Arbeit beschäftigt sich mit der Synthese, Charakterisierung und Koordinationschemie basenstabilisierter Diboran(4)-Verbindungen, wobei als stabilisierende Lewisbasen hauptsächlich bizyklische Guanidine verwendet werden. Ausgehend von kommerziell erhältlichen Boranverbindungen wurden zunächst experimentelle und quantenchemische Studien zur Synthese basenstabilisierter Borane und Monochlorborane durchgeführt. Die erhaltenen Reaktionsprodukte wurden anschließend in weiteren Versuchen auf ihre Eignung als Vorläuferverbindungen für die Darstellung neuer und bekannter basenstabilisierter Diborane hin untersucht. Bei Verwendung des bizyklischen Guanidins hppH als Lewisbase lässt sich durch eine Reaktionssequenz aus einer thermischen N–B- und übergangsmetallkatalysierten B–B-Dehydrokupplungsreaktion die Verbindung [HB(hpp)]2 herstellen. Auf Basis von Vergiftungs- und Mikrofiltrationsexperimenten konnten neue Erkenntnisse über den Reaktionsmechanismus der bislang nahezu einmaligen B–B-Homokupplung gewonnen und neue aktive Präkatalysatoren für diese Reaktion gefunden werden. Ausgehend von [HB(hpp)]2 war es möglich durch dessen Umsetzung mit verschiedenen Übergangsmetallverbindungen des frühen und späten d-Blocks eine Vielzahl neuer Koordinationsverbindungen darzustellen und zu charakterisieren. Hierbei zeigen sich im Zuge der Komplexbildung je nach Metallfragment deutlich verschiedene spektroskopische und strukturelle Parameter für den koordinierten Diboranliganden. Diese Beobachtungen konnten durch einen kombinierten experimentellen und quantenchemischen Ansatz erklärt werden und als deren Ursache die unterschiedlichen Beiträge der B–B- bzw. der B–H-Bindungen an der Ligand-Metall-Wechselwirkung identifiziert werden, welche je nach koordiniertem Metallfragment unterschiedlich groß sind. Diese Arbeit liefert somit neue detaillierte Einblicke in die Wechselwirkungen zwischen Übergangsmetallen und der Verbindungsklasse der basenstabilisierten Diborane, welche zur Entwicklung neuer selektiver Folgereaktionen genutzt werden können.
Ziel dieser Arbeit war die Synthese mehrkerniger Metallkomplexe in denen 4f-Elemen-te koordiniert sind. Hierzu wurden Liganden synthetisiert die, durch Ausnutzung der Oxophilie, gezielt 4f-Elemente koordinieren. Zudem wurden Liganden dargestellt, die zusätzlich präorganisierte Bindungstaschen für 3d-Elemente aufweisen. Der erste Teil dieser Arbeit befasst sich mit homodinuklearen Verbindungen der dreiwertigen 4f-Elemente (Kapitel 3.2). Eine Serie der zweikernigen Ln(III)2 (Ln = Y, Nd, Gd, Tb, Dy, Ho, Er, Lu) konnte synthetisiert und charakterisiert werden. Mit Ausnahme des Nd(III)-Derivats wurden Kristalle erhalten und Strukturen gelöst, die unterschiedliche Koordinationszahlen an beiden Zentren aufzeigen. Die magnetischen Messungen sind in guter Übereinstimmung mit den erwarteten Werten und zeigen einen antiferromagnetischen Kurvenverlauf auf. In den dynamischen ac-SQUID-Messungen zeigen sich für Dy(III)2 ein schwaches SMM-Verhalten. Unter Verwendung von CASSCF(9,7)-Rechnungen konnten die magnetischen Daten eindeutig interpretiert werden. Anhand von MCD-Spektroskopie konnte das unterschiedliche Ligandenfeld beider Zentren nachgewiesen werden. Unter Verwendung von high-field-ESR-Spektroskopie wurde eine intramolekulare dipolare Wechselwirkung gefunden und quantifiziert. Im zweiten Teil (Kapitel 3.3) wird die Synthese und Analyse heterodinuklearer Verbindungen besprochen. Es war möglich zwei Derivate Ni(II)-Dy(III) und Co(II)-Dy(III) zu synthetisieren und zu charakterisieren. Die magnetischen Messungen zeigen eine ferromagnetische Wechselwirkung für Ni(II)-Dy(III) und eine antiferromagnetische für Co(II)-Dy(III). Ac-SQUID-Messungen zeigten ein SMM Verhalten für Ni(II)-Dy(III) und keines für Co(II)-Dy(III). Durch Berechnung der Anisotropieachsen der Dy(III)-Zentren beider Moleküle wurde eine Ausrichtung der Achse in Ni(II)-Dy(III) entlang der Kernverbindungsachse und in Co(II)-Dy(III) senkrecht dazu gefunden. In Ni(II)-Dy(III) kann daher von einer additiven Wechselwirkung beider Einzelionenanisotropien ausgegangen werden. Als Ursache konnten die Co-Liganden an Dy(III) (Pivalat) ausgemacht werden, da diese, wie in den Kristallstrukturen beider Moleküle ersichtlich, unterschiedlich und entlang der Dy(III)-Anisotropieachse orientiert sind. In Kapitel 4.2 wird die Synthese von homotrinuklearen Ln(III)3-Verbindungen (Ln(III) = Y, Gd, Tb, Dy) beschrieben und auf ihre magnetischen Eigenschaften analysiert. In den Kristallstrukturen ist eine gewinkelte symmetrische Anordnung der drei Zentren zu sehen. Zudem wurden für das zentrale und die äußeren Ionen unterschiedliche Koordinationszahlen gefunden. Die magnetischen Messungen zeigen eine gute Übereinstimmung mit den erwarteten Werten und folgen antiferromagnetischen Kurvenverläufen. In den ac-SQUID-Messungen ergab nur Dy(III)3 Signale und diese sind nicht quantifizierbar. Durch eine diamagnetische Verdünnung von Dy(III)3 in Y(III)3 wurden bessere Signale erhalten, die allerdings auch nicht auswertbar waren. Dies veranschaulicht, dass durch die Entfernung der Ionen voneinander die Relaxation der Magnetisierung teilweise unterdrückt werden kann. Durch die Berechnung der Orientierung der Anisotropieachsen wurde deutlich, dass keine der lokalen Achsen der drei magnetischen Zentren in Dy(III)3 gleichgerichtet sind. Für Gd(III)3 wurde anhand der magnetischen Messungen eine sehr kleine Wechselwirkung zwischen den Zentren bestimmt. Eine Serie von Ni(II)2Ln(III) Komplexen (Ln(III) = Y, La, Ce, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Lu) wurde synthetisiert und charakterisiert (Kapitel 4.3.1). Bei den Kristallstrukturen der Moleküle waren, außer bei Ni(II)2Sm(III), Ni(II)2Eu(III) und Ni(II)2Tb(III), eine lineare Anordnung der drei Zentren und eine pseudo-C3-Achse entlang der Metallverbindungsachse feststellbar. In Ni(II)2Sm(III), Ni(II)2Eu(III) und Ni(II)2Tb(III) sind zusätzlich Aqua-Liganden am Lanthanid koordiniert, wodurch eine gewinkelte Struktur erreicht wird. Die magnetischen Messungen zeigen wie erwartet einen antiferromagnetischen Kurvenverlauf. Die dreikernige Ni(II)2Ln(III)-Verbin-dungen, Ni(II)2Y(III), Ni(II)2La(III) und Ni(II)2Lu(III), konnten als dinukleare Ni(II)-Verbindungen analysiert werden und ergaben elektronische Parameter für die Ni(II)-Ionen. Durch Subtraktion der Suszeptibilitäten dieser Verbindungen wurden schwache ferromagnetische Kurvenverläufe bei den Sm(III)-, Eu(III)-, Ho(III)-, Er(III)- und Dy(III)-Derivaten aufgezeigt. Paramagnetische NMR-Messungen von Ni(II)2Dy(III), Ni(II)2Tb(III), Ni(II)2Er(III) und Ni(II)2Y(III) stimmen mit CASSCF-Rechnungen dahingehend überein, dass eine lineare Anordnung der Einzelionenanisotropien der drei Zentren vorliegt. Trotzdem wurde in den ac-SQUID-Messungen kein SMM-Verhalten detektiert. Die CASSCF-Rechnungen identifizierten das Ligandenfeld am Lanthanid als Ursache hierfür. Abschließend (Kapitel 4.3.2) wird eine Serie von Co(III)2Ln(III)-Komplexen (Ln(III) = Y, Gd, Dy) vorgestellt. In der Kristallstruktur von Co(III)2Gd(III) waren an das Gd(III) drei zusätzliche Aqua-Liganden koordiniert. UV-Vis-NIR-Spektroskopie bestätigte die Oxi-dationsstufe von Kobalt als +3. Die magnetischen Messungen zeigten einen ferromagnetischen Kurvenverlauf. Der untypische Kurvenverlauf lässt auf ein mögliches Vorhandensein von Radikalen schließen. Die Verbindung Co(III)2Dy(III) wurde durch ac-SQUID-Messungen als SMM charakterisiert.
Spray combustion under turbulent conditions occurs in many technical devices. Therefore, the proper prediction of the characteristics of turbulent spray flames is of vital importance for the design of new combustion technologies in view of efficiency and pollutant reduction, where the latter requires consideration of detailed chemical reaction mechanisms. Unfortunately, a direct inclusion of detailed chemical reactions dramatically increases the computational cost of the numerical simulations of technical combustion processes, and it is prohibitive in practical situations.
Models based on the assumption that turbulent ames can be seen as an ensemble of laminar stretched flame structures, the so-called flamelet models, represent a very promising approach for the cost effective inclusion of detailed chemical reaction mechanisms in the simulation of turbulent spray flames.
Several flamelet models are currently available in the literature for the simulation of pure non-premixed and pure premixed gas flames. Additionally, some two-regime flamelet formulations have been proposed in the last years for situations where nonpremixed and premixed gas combustion coexist and interact. These models, however, are not adequate for the simulation of turbulent spray combustion, since they do not take into account spray evaporation, which strongly affects the flame structure. Although a spray flamelet model has been proposed for the simulation of flames where non-premixed and evaporation-dominated combustion regimes coexist, most studies of turbulent spray flames use gas flamelet models, neglecting the effects of evaporation on the flame structure. In the present thesis, a common framework is developed in which the several single and two-regime flamelet models existing in the literature can be described and combined in order to advance the development of a comprehensive multi-regime spray flamelet model for turbulent spray flames. For this purpose, a set of multi-regime spray flamelet equations in terms of the mixture fraction and a reaction progress variable is derived, which describes all combustion regimes appearing in spray flames. The flamelet equations available in the literature for single and two-regime flames are retrieved from these multi-regime spray flamelet equations as special cases. Additionally, exact transport equations of the mixture fraction and its scalar dissipation rate are derived, which are then used to evaluate the validity of several assumptions commonly made in the literature during their derivation, such as the use of unity Lewis number and the negligence of spatial variations of the mean molecular weight of the mixture. These assumptions had not yet been tested for the calculation of the scalar dissipation rate of the mixture fraction in spray flames, and their validation is of vital importance for the formulation of any spray flamelet model.
Numerical simulations of axi-symmetric laminar mono-disperse ethanol/air counterflow spray flames are carried out to analyze the influence of spray evaporation on the flame structure. Parametric studies of the influence of the initial droplet radius and strain rate are presented, which clearly illustrate the major importance of evaporation in the determination of the flame structure. Additionally, the relative importance of non-premixed and premixed combustion regimes in the previously analyzed counterflow spray flames is studied by means of the derived multi-regime spray flamelet equations. The results show that premixed effects can be neglected in this kind of flame with all fuel injected in liquid phase. Moreover, the derived transport equations of mixture fraction and its scalar dissipation rate are solved for the counterflow spray flames considered in this work considering and without considering the assumptions of unity Lewis number and spatially uniform mean molecular weight of the mixture. The results are compared, and it is found that the assumption of unity Lewis number may lead to non-physical values of the scalar dissipation rate of the mixture fraction, whereas the use of a mass-averaged diffusion coefficient of the mixture is an acceptable approximation. Effects associated with the spatial variation of the mean molecular weight of the mixture are found to be small at low strain rate and negligible at high strain rates. These results confirm the validity of the use of Fick's diffusion law in highly strained flames. Finally, a set of non-premixed spray amelet equation is obtained by neglecting premixed effects in the previously derived multi-regime spray flamelet equations. This set of equations, which is valid in situations where non-premixed and evaporation-dominated combustion regime coexist, is similar to the classical non-premixed gas flamelet equations, but it contains two additional terms for the description of evaporation effects. These equations are then used to evaluate the relative importance of the effects attributable to evaporation. The results show that they are always relevant and they should be always considered.
Surface functionalization methods are very important for modern science and technology in order to endow surfaces with various novel and unique properties. Examples include slippery property, antibacterial and antifouling properties, superhydrophobicity and superhydrophilicity, biocompativity and conductivity. As an important branch of surface functionalization, surface patterning has attracted a lot of attention. Patterned surfaces can find a wide range of applications in various fields such as microfluids, printing devices, sensors and diagnose devices to name a few. Photo-based surface functionalization is one of the most powerful surface modification and patterning methods due to its controllability both spatially and temporally. Different goals could be achieved by surface modification, for example, addition or remove of functionalities and formation of 3D morphologies. This thesis contains three parts, which deal with different topics related to surface functionalization. Part I demonstrates the method of UV control of dopamine (DA) polymerization and polydopamine (PD) deposition. PD coating is a recent surface modification strategy inspired by the adhesive performance of mussels. DA is able to self-polymerize in aqueous solutions under basic conditions. The adhesive nature of the resulting PD, allows it to attach to any immersed substrates forming a PD layer. Further functionality can be introduced using the reactivity of PD layer towards thiols, amines and metal ions. The simplicity, generality, and the possibility of versatile secondary modifications have promoted the PD coating method to be a promising coating strategy in many fields. Since the first report in 2007, PD coatings have been widely applied in different fields. Currently, the main drawback of the PD coating method is the lack of spatial and temporal control during the polymerization process, limiting its applications and making the mechanism investigations difficult. On the other hand, photo-assisted methods have been widely investigated and are known to be highly controllable. The idea of introducing the control offered by photo-assisted reactions into DA polymerization might result in a more controllable PD coating strategy. In this thesis, it was shown that reactive oxygen species (ROS), formed upon UV irradiation of oxygen-containing solutions, could serve as oxidants for DA. Therefore, UV light could be used to achieve a better control over the DA polymerization. I investigated the effects of UV irradiation on DA solutions. It was found that DA polymerization was accelerated by UV irradiation, and that under neutral conditions a well-controlled DA polymerization could be achieved. By cooperation with an antioxidant, sodium ascorbic acid (SA), DA polymerization in basic solutions can also be well-controlled. UV-triggered DA polymerization could be used toreflective absorption specotroscopy (IRRAS), time-of-flight secondary ion mass spectroscopy (ToF-SIMS), X-ray reflectivity (XRR) and scanning electron microscopy (SEM). In the part II, a photo based reversible surface modification strategy is demonstrated. Reversible surface modification represents a new generation of surface modification strategies because they are capable of producing reversible surfaces with reversible properties. Reversible surface exhibits significant advantages compared to normal functional surface, for example, the capability of “write and erase” process, possibility to renew and reuse the surface, formation of complex, multi-component and gradient patterns, capture-and-release properties, and the possibility of in-situ manipulation of local environments. However, currently most reported reversible surface functionalization strategies suffer from time-cost reversible cycle and non-controllable processes, which greatly limit potential applications of the method. In order to develop a smart reversible photopatterning strategy, I introduced a photodynamic disulfide exchange reaction as a method for surface modification. Surface photo-disulfide exchange was applied and characterized on a porous HEMA-EDMA surface. The results showed that reversible photopatterning could easily be achieved and that the kinetics of the exchange is extremely fast. A reversible photo functionalization/patterning strategy could also be obtained. The disulfide exchange reaction was investigated and analyzed by water contact angle (WCA) measurement, SEM, ToF-SIMS and microscopy. The part III describes a facile method to create a superhydrophobic surface on different substrates. Superhydrophobic surfaces hold great promise in a variety of applications where extreme water repellency can lead to novel properties and functionalities. Most of the existing techniques, however, require multi-step and laborious procedures as well as only applicable to certain substrates. In the last part of the thesis, I present a facile one-step (“paint-like”) method for creating superhydrophobic porous polymer coatings. The approach is based on the anionic polymerization of 2-octyl cyanoacrylate in the presence of aqueous ethanol. This leads to the formation of a highly porous superhydrophobic polymer film. The morphology of the porous structure could be controlled by varying the ethanol/water ratio. The method is fast, convenient, does not require any special equipment, and can be performed in the presence of oxygen. It was shown that the technique could be used to coat variety of materials, is applicable to three-dimensional substrates and leads to the formation of stable and strongly adherent superhydrophobic coatings. The surface was characterized by WCA measurement,and SEM.
Polyfluorenes or copolymers based on fluorene as a building block are important materials for organic electronics and sensorics. In this work novel polymeric materials based on fluorene as a building block for organic light emitting diodes (OLED), highly efficient electron-injecting materials, polymeric sensors and for organic field-effect transistors (OFET) have been synthesized, characterized and proven. In the first part of this work (chapter 3.1), the synthesis of photochemically cleavable groups for switching the solubility of π-conjugated polymers at a certain wavelength is described. The photochemically removable groups are linked via alkyl chains to the polymer backbone. By fabrication of functional devices, it was possible to proof the concept. In the second part (chapter 3.2), the synthesis and the use of ionic functionalized polyfluorenes and polyfluorenes with polar groups as electron-injection materials in OLEDs, or as an ionic conducting and emitting material in a light-emitting electrochemical cell (LEC) are described. The synthesis and the investigation of a powerful biphasic mercury ion sensor in a microfluidic setup are reported in chapter 3.3. In the last part of this work (chapter 3.4), the synthesis and characterization of non-fluorescent polyfluorenes with exocyclic double bonds as materials for OFETs are shown.
The focus of the presented work lies on the introduction of novel structural motifs into the solid state structure of functionalized N-heteroacenes by synthesis and quantum chemistry. Additionally literature known (aza-)acenes were studied in terms of transfer integrals and it was tried to optimize the crystal packing of tetraazapentacene derivatives regarding their transfer integrals. Di-iso-propylethylsilyl- and cyclopropyldi-iso-propylsilyl groups were introduced as slightly smaller and larger silyl groups respectively than TIPS. Transfer integrals showed a concentration on one of the two overlap regions instead of balanced values for both. A series of diazadioxaacenes, which are analogous to the N,N‘-dihydroazaacenes, were synthesized and their optical, electronic and morphologic properties were examined. Doing attempts for incorporating seven-membered rings into the acene backbone, acetyl quinoxaline derivatives and quinoxalotropones were obtained as products of oxidation reactions. Ethynylated benzoquinoxalotropone shows a low LUMO energy, a highly symmetric crystal packing, and thus interesting properties for application in organic thin-film transistors. Since large azaacenes tend to stabilize via dimerization or reduction, a conjugative link between smaller acene units can help with the building of large structures. Therefore the incorporation of cyclobutadiene rings into the acene backbone was computationally studied for symmetrical and non-symmetrical biphenylene derivatives. The symmetrical compound and its hydrogenation products show interesting structural and electronic properties. The question concerning aromaticity was discussed. The non-symmetrical azaacenes were examined for the electronics and compared to the corresponding pure azaacenes.
The enzyme Purple Acid Phosphatase (PAP) is an important target for the development of new anti-osteoporotic drug leads. The major goal of this thesis is to better emulate the synergy that occurs between the primary and secondary coordination sphere within the active site of phosphatase enzymes, such as PAP. This was perceived by development of synthetic methods for new biomimetics, i.e. low-molecular weight metal complexes. Therefore, asymmetric dinucleating ligands which mimic the peptide backbone of the active site of PAP including the ability to form hydrogen bonds with a phosphoester substrate or a nucleophile were designed and synthesized. Using these ligands, more accurate model systems for the enzyme active site were achievable as they combine the two essential structural features known to influence the catalytic activity towards the hydrolysis of phosphoesters, i.e. the asymmetry of the dinuclear active site and the capacity for hydrogen bond formation. The latter was verified by the observation of hydrogen bonds in the X-ray structures of dizinc(II) and diiron(II) complexes. Moreover, two asymmetric dizinc(II) complexes were formed with two different Zn(II) sites and an unusual hydroxido co-ligand, representing two important features in the active site of PAP, the difference of the metal sites and the nucleophile needed for the phosphoester hydrolysis. In addition, hydrogen bond formation detected in these X-ray structures was accounted for the stabilization of the hydroxido co-ligand. In this work, a new synthetic approach towards more sophisticated model systems for the active form of mammalian PAP was developed. Chemical oxidation of the diiron(II) complex of an asymmetric ligand results in the generation of the Fe(III)Fe(II) complex that has been specifically designed to both satisfy the requirement of a heterovalent diiron core and to mimic the second coordination sphere of the active site of PAP. Similarly, more accurate model systems for the active site of plant PAPs have been generated in the form of heterovalent heterodinuclear complexes of asymmetric ligands bearing, adjacent to the Ga(III)Zn(II) core, functionalities capable of forming hydrogen bonds. Analysis of the complexation behavior of the respective ligands revealed the selective formation of the Ga(III)Zn(II) complexes in solution. The model complexes described above imitate successfully the extensive hydrogen bond network that is formed by the second coordination sphere within the active site of PAP as well as in a structural and functional similar phosphatase, Alkaline Phosphatase. Thus, those complexes allow to study the impact of hydrogen bonds on the reaction mechanism. The main impact of the secondary interactions in the dizinc(II) complexes was found to be the increased substrate affinity. This catalytic parameter was shown to be dependent on both the hydrogen bonding sites and the type of the hydrogen bonding groups. Although the substrate affinity of the Ga(III)Zn(II) complex was revealed to be lower compared to the dizinc(II) complex, a 50-fold faster hydrolysis rate and a 6-fold increased efficiency was detected for the heterodinuclear complex. Moreover, the mechanism previously proposed, in which the phosphoester is activated by the Zn(II) center and the Ga(III) being accountable for providing the hydroxide nucleophile at near physiological condition, was supported in this study and an accelerating effect by the interplay of the two metal ions was detected. However, the inhibition was found to be favored in the Ga(III)Zn(II) complex compared to the respective monogallium(III) complex, most likely due to bridging coordination of the hydrolysis product, additionally stabilized by coordination of the adjacent pivaloyl-amide residue. The proposed arrangement in the catalyst-hydrolysis product adduct derives from a structure of a stable phosphoester-bridged dizinc(II) complex bearing the same ligand backbone. However, the Ga(III)Zn(II) complex is the first heterodinuclear model complex that mimics the essential function of PAPs, the ability to cleave phosphomonoesters and therefore supports the crucial impact of the second coordination sphere in the active site of PAP.
Die vorliegende Dissertation beschreibt die Komplexierung von Cm(III), Eu(III) und Am(III) mit humanem Serumtransferrin. Dieses ist eines der wichtigsten Blutserumproteine,das für den Eisentransport und die Abgabe des Eisens an Zellen verantwortlich ist. Transferrin hat eine komplexe, hochdefinierte dreidimensionale Struktur und ist unterteilt in zwei Lobes, die jeweils eine Bindungsstelle für dreiwertiges Eisen aufweisen. Ziel der Arbeit ist es, die in Lösung vorliegenden An(III)- und Ln(III)-Transferrin-Komplexspezies zu identifizieren und spektroskopisch und thermodynamisch zu charakterisieren sowie die Struktur der entsprechenden Spezies zu analysieren. Von besonderem Interesse sind hierbei Untersuchungen bei physiologisch relevanten Bedingungen (pH 7,4, T = 310 K, c(Carbonat)tot = 25 mM,c(NaCl) = 150 mM). Die Ergebnisse sollen Informationen über den Einfluss von Transferrin auf die Biochemie inkorporierter trivalenter Actiniden in einem Organismus liefern. Neben der zeitaufgelösten Laserfluoreszenzspektroskopie (TRLFS) und der Lumineszenzspektroskopie wurde hierfür die EXAFS-Spektroskopie(Extended X-Ray Absorption Fine Structure) eingesetzt. Mittels TRLFS konnte erstmals die Bildung zweier Cm(III)-Transferrin-Spezies in Abhängigkeit des pH-Werts nachgewiesen werden. Bei der Cm(III)-Transferrin- Spezies I, die im pH-Bereich von 3,5 bis 9,7 gebildet wird, handelt es sich um eine nichtspezifische Komplexspezies, bei der das Metallion an Aminosäurereste auf der Proteinoberfläche bindet. Im Falle der Cm(III)-Transferrin-Spezies II (pH ≥ 7,0) komplexiert Cm(III) an der Fe(III)-Bindungsstelle, wobei die erste Koordinationssphäre durch zwei Wassermoleküle, vier Aminosäurereste des Proteins (His, Asp, 2 x Tyr) sowie drei weitere Liganden (vorzugsweise OH- oder CO32-) gebildet wird. Aufgrund der unterschiedlichen Bindungseigenschaften des C- und N-Lobes erfolgt die Komplexierung von Cm(III) unter den experimentellen Bedingungen dabei ausschließlich an der C-terminalen Bindungsstelle. In Ergänzung zu den Komplexierungsuntersuchungen mit Transferrin wurde die Wechselwirkung von Cm(III) mit dem rekombinanten N-Lobe des humanen Serumtransferrins (hTf/2N), das als Modell für den N-Lobe des Transferrins dient, untersucht. Im Gegensatz zu Transferrin wird mit hTf/2N keine unspezifische Komplexspezies gebildet. Die Cm(III)-hTf/2N-Spezies hingegen steht in exzellenter Übereinstimmung mit der Cm(III)-Transferrin-Spezies II, wodurch die Ähnlichkeit der Koordinationsumgebung an den Bindungsstellen des C- und N-Lobes des Transferrins bestätigt wird. Sowohl die Komplexierung von Cm(III) mit hTf/2N als auch an der C-terminalen Bindungsstelle des Transferrins wird durch eine Temperaturerhöhung von Raumtemperatur (T = 22,0°C) auf physiologische Temperatur (T = 37,5°C) deutlich begünstigt. Die Komplexierungsreaktion ist für beide Proteine endotherm und wird durch einen großen Entropiegewinn getrieben, was auf den ausgeprägten Chelateffekt des Proteins bei einer Komplexierung des Metallions an der Fe(III)-Bindungsstelle zurückgeführt werden kann. Die Cm(III)- Komplexe mit Transferrin und hTf/2N unterscheiden sich jedoch deutlich in ihren Stabilitäten. Dies spiegelt sich auch in den Stabilitätskonstanten der Cm(III)- Transferrin-Spezies II und der Cm(III)-hTf/2N-Spezies wider, die sich um ca. zwei Größenordnungen unterscheiden. Aufgrund der Tatsache, dass Carbonat bei der Komplexierung von Fe(III) mit Transferrin als synergistisches Anion wirkt, sollte untersucht werden, ob Carbonat auch einen Einfluss auf die Komplexierung von Cm(III) mit Transferrin hat. Untersuchungen bei verschiedenen Carbonatkonzentrationen (c(Carbonat)tot = 0 mM, 0,23 mM und 25 mM (physiologische Carbonatkonzentration)) haben dabei gezeigt, dass eine Erhöhung der Carbonatkonzentration die Bildung der Cm(III)-Transferrin- Spezies II bei deutlich kleineren pH-Werten begünstigt. Folglich hat Carbonat auch einen synergistischen Effekt für die Komplexierung von Cm(III) an der C-terminalen Bindungsstelle. Allerdings ist die Carbonatkomplexierung auch eine wichtige Konkurrenzreaktion. Die Bildung der nichtspezifischen Cm(III)-Transferrin-Spezies I wird bei physiologischer Carbonatkonzentration (c(Carbonat)tot = 25 mM) vollständig unterdrückt und auch die Anteile der Cm(III)-Transferrin-Spezies II sind deutlich kleiner als bei Abwesenheit von Carbonat. Im Gegensatz zu Transferrin konnte kein synergistischer Effekt von Carbonat auf die Komplexierung von Cm(III) mit hTf/2N nachgewiesen werden. Stattdessen wird die Bildung der Cm(III)-hTf/2N-Spezies aufgrund der konkurrierenden Carbonatkomplexierung sehr stark zurückgedrängt. In Ergänzung zu den Komplexierungsuntersuchungen von Cm(III) mit Transferrin wurde die Wechselwirkung von Eu(III) mit Transferrin mittels Tieftemperatur-TRLFS untersucht. Während bei pH ≤ 6,0 eine unspezifische Eu(III)-Transferrin-Spezies gebildet wird, die der Cm(III)-Transferrin-Spezies I entspricht, erfolgt bei pH ≥ 7,4 die Komplexierung von Eu(III) analog zur Komplexierung mit Cm(III) an der Fe(III)-Bindungsstelle des Transferrin. Die spektroskopischen Charakteristika zeigen dabei eine identische Zusammensetzung der Koordinationssphären in beiden Komplexen. Neben der Identifizierung und Charakterisierung der verschiedenen Cm(III)- und Eu(III)-Transferrin-Spezies war die Strukturaufklärung ein wichtiges Thema. Zu diesem Zweck wurden EXAFS-Untersuchungen mit Eu(III)- und Am(III)-Transferrin durchgeführt. Die Analyse des Am(III)-Transferrin-Spektrums bei pH 8,5 zeigt das Vorliegen von neun Nachbaratomen im mittleren Abstand von 2,38 Å. Dies entspricht den Abständen, die beim Einbau von Am(III) in Mineralstrukturen auftreten und bestätigt eine starke, multidentate Koordination von Am(III) an der Fe(III)- Bindungsstelle des Transferrinmoleküls. Der Nachweis der unspezifisch gebundenen Transferrinspezies erfolgte anhand von Eu(III)-Transferrin bei pH 7,2, wobei diese Spezies einen wesentlich größeren mittleren Bindungsabstand von 2,41 Å aufweist. Um Aussagen über den potentiellen Transport von Actinidionen im menschlichen Körper treffen zu können, sind die Ergebnisse der Komplexierungsuntersuchungen bei physiologischen Bedingungen (pH 7,4, T = 310 K, c(Carbonat)tot = 25 mM, c(NaCl) = 150 mM) von besonderer Bedeutung. Die vorliegende Arbeit zeigt, dass unter diesen Bedingungen die Bildung der Cm(III)-hTf/2N-Spezies aufgrund der konkurrierenden Carbonatkomplexierung vollständig unterdrückt wird. Unter der Voraussetzung, dass hTf/2N ein geeignetes Modell für den N-Lobe des Transferrins darstellt, ist die Komplexierung von Cm(III) an der N-terminalen Bindungsstelle somit nicht relevant für den Transport von Actinidionen im Körper. Im Gegensatz hierzu werden unter physiologischen Bedingungen mit Transferrin ca. 15% der Cm(III)-Transferrin-Spezies II gebildet. Dies ist eine wesentliche Voraussetzung für die potentielle Bindung an den Rezeptor sowie die Endocytose in die Zelle. Die vorliegende Arbeit liefert wichtige Informationen über Bindungsmechanismen, Struktur und thermodynamische Daten der Komplexierung trivalenter Actinidionen mit Transferrin. Diese Ergebnisse tragen zu einem besseren Verständnis der relevanten biochemischen Reaktionen trivalenter Actinidionen bei und stellen eine wichtige Grundlage für die Entwicklung potentieller Dekontaminationsstrategien dar.
Ziel der vorliegenden Arbeit war die Entwicklung der Synthese und die Charakterisierung neuer Derivate von [2.2.2]Parayclophan-1,9,17-trien mit unterschiedlichem Substitutionsgrad des bekannten Rückgrats. Durch ringöffnende Metathese-Polymerisation (ROMP) wurden aus den Monomeren Poly(para-phenylen)vinylen-Derivate (PPVs) hergestellt, deren Topologie mit der Substitution des Monomers variierte. Die neu entwickelte Syntheseroute der Paracyclophantriene verläuft über den Aufbau eines Phenylen-Ethinylen-Rückgrats, welches durch ein Grignard-Reagenz zur Phenylen-Vinylen-Einheit reduziert wird. Der Ring wird anschließend mittels McMurry-Reaktion geschlossen. Die Flexibilität der Synthesestrategie gewährt durch die Kombination der Molekülbausteine einen Zugang zu einer Vielfalt an Derivaten in guten Ausbeuten. In der ROMP wurden zweifach, vierfach und sechsfach homo-substituierte Derivate als Monomere eingesetzt und sowohl die Polymerisation, als auch die Polymere selbst untersucht. Die Polymerisation von zweifach und vierfach substituierten Monomeren wurde erfolgreich optimiert und hohe Molekulargewichte erzielt. Die Polydispersitäten waren etwas höher als nach lebender Polymerisation zu erwarten. Das Hauptaugenmerk lag auf dem Einfluss des jeweiligen Restes und dessen Fähigkeit die Löslichkeit im Polymer zu beeinflussen. Bei zweifach substituierten PPV-Derivaten wurde ein Zusammenhang zwischen der Art der Substitution und dem erreichbaren Molekulargewicht des Polymers gefunden. Ebenfalls wurde ein Zusammenhang zwischen dem Molekulargewicht und der Absorption in Lösung, sowie der Lage der Energieniveaus im Festkörper festgestellt. Die PPV-Derivate aus vierfach substituierten Paracyclophantrienen zeigten aufgrund der zusätzlichen Substitution keine Beschränkung des Molekulargewichts durch die Löslichkeit. Die Absorption und Emission verschieben sich bathochrom in Abhängigkeit des Substitutionsgrades. In dünnen Filmen vergrößert sich die optische Bandlücke (hypsochrome Verschiebung) und die Energie des emittierenden Zustands wird herab gesetzt (bathochrome Verschiebung). Dies ist Änderungen der Konformation beim Übergang von Lösung zum festen Zustand zuzuschreiben.
Mechanical signaling plays a crucial role in cell communication. Translating mechanical force into biochemical reactions is vital for virtually all cellular processes such as cell proliferation and differentiation. Mechanosensors, which can respond to an external force in form of controllable conformational changes, are key regulators in the mechanical signal transduction processes. In this work, we present results from Molecular Dynamics (MD) and biochemical network simulations that suggest Focal Adhesion Kinase (FAK) as a mechanosensing enzyme in the signaling pathway. FAK is a non-receptor tyrosine kinase, located at the cytoplasmic site of the cell membrane. During the last decade, a growing body of evidence shows that tensile stress acting on cells leads to increased FAK activity. However, the mechanism of FAK mechanical activation has not been resolved. The auto-inhibitory conformation of the FAK FERMkinase fragment suggests that the major mechanism of the regulation of FAK activity is the release of Tyr576/577 on the activation loop from the N-terminal FERM domain. We first addressed the allosteric regulation of the FAK by PIP2 binding (Chapter 3), a recently recognized stimulus for FAK activation, by performing all-atom MD simulations of FAK FERM-kinase fragment and comparing the dynamics in absence and presence of ATP and PIP2. A closing-opening motion between the kinase and FERM domain upon ATP and additional PIP2 binding was observed in close agreement with corresponding changes in fluorescence resonance energy transfer experiments. As an underlying allosteric mechanism, using Force Distribution Analysis (FDA), a signal network spanning from the PIP2 and ATP binding site to the distant interface between the FERM and kinase domains could be identified. However, our results also demonstrated that the ligand induced conformational changes are insufficient for FAK catalytic turnover, which requires full exposure of Tyr576/577. This suggests that an additional biochemical or mechanical stimulus is required for FAK activation. Following the study of FAK allosteric regulation, we suggest a mechanical model of FAK activation in which tensile forces, propagating from the membrane through the PIP2 binding site of the FERM domain and from the cytoskeleton-anchored FAT domain, activate FAK by relieving the occlusion of the central phosphorylation site of FAK (Tyr576/577). To test the hypothesis of FAK as a force-sensor, extensive Force Probe Molecular Dynamics (FPMD) simulations, with varying loading rates, pulling directions and membrane PIP2 concentrations, were carried out. They directly supported the notion of a specific force-induced opening and activation of FAK. This is remarkable given that force-induced unfolding of the primarily α-helical FERM and kinase domains are competitive processes but were observed to be less favored over domain-domain dissociation. To assess downstream consequences of FAK mechano-sensing, force-dependent FAK kinetics based on extrapolated MD data were implemented as parameters to establish a mechano-biochemical network model, which connects force-dependent FAK activation to the downstream exchange rate of GTP/GDP in Ras. Our computational study provides direct evidence for FAK-mediated mechanical signaling through Ras to the nucleus, with predictions directly testable by cell stretching experiments and single molecule force spectroscopy.
Nuclear forensic science or nuclear forensics, is a relatively young discipline which evolved due to the need of analysing interdicted nuclear or radioactive material, necessary for determining its origin. Fundamentally, nuclear forensic science makes use of measurable material properties, referred to as "signatures", which provide hints on the history of the material. As part of the advancement in this multi-faceted field, new signatures are constantly sought after and as well as analytical techniques to efficiently and accurately determine the signatures. The work carried out in this study is part of this fulfilment to investigate new structural and morphological parameters as possible new nuclear forensic signatures for selected uranium compounds. The scientific goals have been oriented into three parts for investigations in this study. Firstly, five different compositions of uranium ore concentrates (UOCs) were prepared in the laboratory under well-defined conditions. These materials were subsequently characterized by several techniques such as X-ray diffraction, thermogravimetry/differential thermal analysis, Infrared and Raman spectroscopy, mass spectrometry, scanning electron microscopy etc. Such materials were pivotal for comparison with the industrial samples. Secondly, several uranium compounds, mainly UOCs were measured using Raman spectroscopy. At least three different Raman spectrometers were used and a comparison made in their performance and suitability for nuclear forensics. Raman spectra of industrial uranium materials were interpreted with regard to compound identification and to determination of (anionic) impurities. Anionic impurities that were present were identified and they could provide clues to the processing history of the samples. Statistical techniques such as principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) were applied to several Raman spectra. The analysis showed that different compositions of uranium compounds could be discerned based on their spectra. Apart from bulk analysis of the samples, Raman was also used to measure single particles. Results showed that although particle analysis could be slightly less precise in terms of the peak positions, it could still distinguish the different form of ore concentrates. Raman spectroscopy is therefore, a useful technique for probing the molecular structure of different uranium compounds. It can be used not just for forensic purposes, but for nuclear safeguards as well. Last but not the least, microstructural fingerprints were investigated as part of the search for ways to differentiate different forms of UOCs. Currently, forensic investigations involve studying the morphology of interdicted samples using scanning electron microscope (SEM). This approach has remained qualitative and more quantitative ways are needed to study the variety of samples available. In this study, the concept of morphological fingerprint was explored by studying the sizes and shapes of dispersed particles. Although this method can be tedious, it can be applied to small number of samples. Two samples were shown to have different sizes but similar shapes and therefore they could be distinguished. A different property of the sample, known as image texture was studied for the first time, using Angle Measure Technique algorithm. SEM images were taken and transformed into numeric data using the algorithm. The data processed by PCA and PLS-DA indicated that image texture could differentiate the samples. Both structural (Raman spectroscopy) and morphological (using SEM) aspects of UOCs have been studied at great lengths, demonstrating that these signatures may provide useful hints on the history of the material. The data provided in this thesis can serve as a good reference for future nuclear forensic investigations.
Ziel der vorliegenden Arbeit war es, Galliumheterocyclen darzustellen und ihre chemischen und physikalischen Eigenschaften zu untersuchen. Es konnten, ausgehend von Biphenyl, einige neue Vertreter der Substanzklasse der Gallafluorene dargestellt und charakterisiert werden. Um Zugang zu neuen Ausgangsverbindungen für Gallafluorene zu erhalten, wurde mit Silicium- und Zinkverbindungen experimentiert, was zu der Synthese und erstmaligen Charakterisierung von Zinkafluoren führte. Die heterocyclische Verbindung eröffnete den Weg zu neuen Gallafluorenen. Daneben konnten weitere Typen heterocyclischer Galliumverbindungen hergestellt und charakterisiert werden. Unter anderem auch eine kationische Galliumspezies, die erfolgreich auf ihre katalytischen Eigenschaften bei der Polymerisierung von Cyclohexenoxid untersucht wurde. Weiterhin wurden Experimente mit N-heterocyclischen Carbenen durchgeführt, welche zu einem neuen monokationischen Trigallan führten.
The interaction of complex molecular systems with light has great relevance in nature as well as for many of the latest technological developments. The process of photosynthesis converts light into chemical energy, thereby providing the primary energy source for life on Earth. Photovoltaic devices, as the technological implementation of this principle, constitute one of the most promising sources of electrical energy for the 21st century, whose application has increased tremendously in the past decade. The reverse process, the controlled emission of light from electronically activated (excited) molecules, is central to many modern technologies, the most prominent of which are presumably the ever smaller yet higher resolving display screens of hand-held computers.
For all these applications, a fundamental understanding of the processes taking place at the atomistic scale is of key relevance to allow for a rational design and improvement of new technologies. However, due to the ultra-short time-scales on which the elementary steps of most light-induced phenomena occur and their inherent complexity, an exclusively experimental investigation is often tedious, in particular concerning the interpretation of the results. Here, the combination of experimental techniques and theoretical models can help to gain insights into the involved processes. For this purpose, the electronic structure of ground and light-activated (excited) states of the involved molecules as well as the interaction with their environment has to be approximated, which is the central topic of this work.
In the first part, namely chapters 2-4, I present applications of the quantum-mechanical methodology introduced in chapter 1 to study light-induced processes in molecular systems. The so-called caged compounds studied in chapters 2 and 3 constitute an attempt to employ the remarkable spatio-temporal light control of modern lasers to control chemical reactions. For this purpose, the investigated, prototypical molecules nitro-phenylacetate (NPA) and ortho-nitrobenzylacetate (oNBA) serve as precursors for the active compounds CO2 and acetate, respectively. Upon irradiation with UV light, the active compound is released within nano- to microseconds, and may e.g. trigger subsequent reactions. In the above-mentioned sense, my theoretical investigation accompanied and guided an experimental study, which allowed to shed light on the molecular processes and to resolve the detail of the mechanism responsible for the light-induced reactivity.
The common structural motif of NPA, oNBA and many other photo-active systems is the nitroaromatic moiety in the form of its smallest representative nitrobenzene (NB). Due to this prototypical character, the photochemistry of NB is relevant for many photochemical applications. In chapter 4, I report an extensive theoretical investigation of ground and excited states as well as the non-radiative decay of NB, which due to its small size and high symmetry allows for an application of a hierarchy of state-of-the-art quantum-chemical methods. Surprisingly, I found this small molecule to pose a serious challenge to electronic structure theory and consequently, some rather sophisticated ab initio methods fail to afford an accurate description, e.g. with respect to the photochemically very important ordering of the lowest triplet states. Nevertheless, I determined the mechanism of non-radiative decay in good agreement with experimental findings and, moreover, suggested an experiment to test my hypothesis.
Although there exist a number of accurate and reliable quantum chemical methods that allow for an investigation of the ground and excited states of isolated systems with the molecular size of NPA, oNBA and NB, the environment often plays a crucial role and may decisively influence the light-induced processes, as e.g. in NPA. Hence, the approximate modeling of molecular environments for quantum-chemical problems in condensed phase is a very active field of research, which culminated in the 2013 Nobel Price for Chemistry, which was awarded to Karplus, Levitt and Warshel for their pioneering developments in the field of multiscale models for complex chemical systems. To enable a quantum-chemical description of photo-chemical excitation processes in condensed phase, I extended and implemented a quantum-classical polarizable-continuum model (PCM) for calculation of vertical excitation energies, which is described in chapter \ref{part:pcm}. In general, PCMs allow for an efficient computation of the often dominating electrostatic portion of the solute-solvent interaction by means of the macroscopic descriptors epsilon (dielectric constant) and epsilon_opt = n^2 (optical dielectric or squared refractive index, respectively). The implementation of the method was realized in such a way that its application to any quantum-chemical model that affords electron densities for ground- and excited-states is straightforward. For the systematic evaluation of the method, I composed the first set of experimental Benchmark Data for Solvatochromism in Molecules (xBDSM), and part of the data points were measured by myself. Comparing calculated gas phase to solvent shifts to the xBDSM set, I was able to demonstrate the convincing accuracy of my approach in combination with various levels of electronic structure theory and could shed light on the relation of different flavors of excited state PCMs. Moreover, a close examination of the contributions to the calculated shifts revealed general patterns, which are essential regarding any evaluation of calculated solvent shifts by comparison to the experiment. The implemented methodology will be released with one of the next versions of the Q-Chem quantum-chemical software package.
Schon Jules Verne hatte die Vision, aus Wasser und Sonnenenergie Wasserstoff als den nachhaltigsten und umweltfreundlichsten Energieträger zu erzeugen. Erst in jüngster Zeit ist es durch wichtige Entdeckungen in der chemischen und biologischen Katalyse gelungen, die Solarenergie-basierte Zerlegung von Wasser in Wasserstoff und Sauerstoff tatsächlich zu realisieren. Der Vortrag stellt die kürzlich erzielten Meilensteine von der Idee bis zur Realisierung der künstlichen Photosynthese heraus und möchte aufzeigen, warum diese grundlegenden Erkenntnisse für eine zukünftige Energieversorgung ohne fossile Brennstoffe unverzichtbar sind.
Prof. Dr. Matthias Drieß studierte Chemie und Philosophie in Heidelberg. Er lehrt Anorganische Chemie an der Technischen Universität Berlin und ist seit 2007 Sprecher des Exzellenzclusters Unicat.
Der Vortrag "Die künstliche Photosynthese: Von der Vision zur Realisierung" wurde am 19. Januar 2015 im Rahmen der Veranstaltungsreihe Studium Generale der Universität Heidelberg gehalten. Die Veranstaltungsreihe richtet sich an alle Mitglieder der Universität und an die interessierte Öffentlichkeit. Die Vorträge eines Semesters stehen unter einem gemeinsamen Rahmenthema, das von Wissenschaftlern verschiedener Fachrichtungen aus der Sicht ihrer Disziplin behandelt wird. Im Wintersemester 2014/2015 widmet sich das Studium Generale dem Thema „Licht“. Die Reihe mit sechs weiteren Veranstaltungen endet am 26. Januar 2015.
Die vielversprechenden Ergebnisse von Alphastrahlern in der gezielten Alphatherapie (TAT) zur Behandlung von Krebs bereiten ein enormes Interesse für Fortschritte in der Forschung der Radionuklid-Produktion und in der Herstellung und Untersuchung von Radioimmunokonjugaten. Zum einen soll der hohe Bedarf therapiegeeigneter Radionuklide gedeckt sein, zum anderen ist es unabdingbar die Eigenschaften der Radioimmunokonjugate zu kennen, um ihr Verhalten in vivo einschätzen zu können. Ziel der vorgelegten Doktorarbeit war die Untersuchung von 2,9-Dicarboxy-1,10- phenanthrolin (DCP) bzw. seiner Derivate 4,7-Bisphenyl-2,9-dicarboxy-1,10-phenanthrolin (DPDCP) und 4,7-Bis(chlorosulfophenyl)-2,9-dicarboxy-1,10-phenanthrolin (BCPDA) hinsichtlich ihrer Komplexierungseigenschaften mit dem Uranyl-Kation.U-230 ist aufgrund seiner optimalen Zerfallseigenschaften im Blickpunkt des Interesses. Mit einer Halbwertszeit von 20.2 Tagen zerfällt es in einer Kaskade und generiert dabei fünf Alpha-Teilchen, die mit einer kumulativen Energie von 34.2 MeV eine hohe zytotoxische Wirkung verursachen können. Der Komplex UO2-DCP bzw. UO2-BCPDA sollte bezüglich seiner Eignung für den Einsatz in der TAT untersucht werden. Blickpunkt waren zunächst die thermodynamischen Eigenschaften des Komplexes, sowie seine analytische Charakterisierung und anschließend die Entwicklung eines effizienten und reproduzierbaren Protokolls für die Kopplung des monoklonalen Antikörpers MabThera® mit dem Liganden DCP, bzw. seiner Derivate BCPDA und 5-Isothiocyanato-2,9-dicarboxy-1,10-phenanthrolin (DCP-NCS) mit anschließender Evaluierung der Uran markierten Konjugate in vitro. Dabei wurde vor allem die zeitabhängige Stabilität unter dem Einfluss verschiedener potenzieller konkurrierender Liganden und im Blutserum untersucht. Außerdem wurde die Bindungsaffinität des schon etablierteren Komplexsystems Ac-225-DOTA-MabThera® an Zellen untersucht. Zunächst wurden die Protonierungskonstanten des Liganden BCPDA mittels der pH-abhängigen Änderung der Absorption mit der UV-Spektroskopie bestimmt. Die ermittelten pKs-Werte von 4.71 und 2.68 in 0.1 M NaClO4 stimmen mit den literaturbekannten Werten des unsubstituierten Liganden DCP überein, welche von Dean et al. untersucht worden waren. Dieses Ergebnis zeigt, dass die Derivatisierung des DCP mit Chlorosulfophenylgruppen keinen Einfluss auf die komplexierenden Eigenschaften der Carboxylgruppen ausübt. Um eine quantitative Aussage über die Stabilität des Liganden mit dem Uranyl-Kation machen zu können, ist die Kenntnis der Stabilitätskonstante eine wichtige Voraussetzung. Diese wurde durch Verwendung der beiden Urantracer U-230 und U-237 und den unterschiedlichen analytischen Methoden Instant Thin Layer Chromatography (ITLC) und dem Kationenaustauscherharz AG MP-50 auf log K 7.4 ± 0.2 in 0.1 M NaClO4 bestimmt. Eine Ionenstärkekorrektur mit der Davies-Gleichung ergab log K 8.2 ± 0.2 bei der Ionenstärke 0. Um die thermodynamischen und kinetischen Eigenschaften des Komplexes beurteilen zu können, wurde der Komplex unter dem Einfluss verschiedener potenzieller konkurrierender Liganden untersucht. Hierfür wurde die Bildung der ternären Komplexe UO2-BCPDA-OH− und UO2-BCPDA-CO2−3 in Abhängigkeit vom pH Wert mit UV-Spektroskopie untersucht. Für die Bildung des ternären Komplexes UO2-BCPDA-OH− konnte in Abhängigkeit vom pH-Wert eine Änderung der Absorption beobachtet werden. Durch Auswertung mit Hilfe einer Steigungsanalyse wurde mit steigendem pH-Wert die Anlagerung einer Hydroxogruppe an den binären UO2-BCPDA Komplex beobachtet. Es konnte unter Vorbehalt eine Bruttokomplexbildungskonstante von log K = 13.2 ± 0.2 in 0.1 M NaClO4 geschätzt werden. Die Bildung des ternären Carbonatokomplexes wurde mit einem erhöhten Partialdruck von CO2 und der damit verbundenen Gleichgewichtskonzentration in Lösung in Abhängigkeit vom pH-Wert untersucht. Hier kam es zunächst zur Bildung des ternären Komplexes. Bei höheren pH-Werten wurde die Dissoziation des UO2-BCPDA Komplexes zugunsten der Bildung des UO2(CO3)34−-Komplexes beobachtet. Zum besseren Verständnis der Komplexierungseigenschaften von UO2-DCP und UO2-DPDCP wurden unterschiedliche Addukte synthetisiert und mit Kristallstrukturanalyse, NMR, IR- und UV-Spektroskopie charakterisiert. Zunächst ist es gelungen das Polymer [UO2-DCP]n mit Hilfe einer einfachen Extraktion zu synthetisieren. Auf analoge Weise wurde mit dem Liganden DPDCP das Tetramer [UO2-DPDCP]4 hergestellt. Die Herstellung und Charakterisierung dieser und weiterer ternärer Kristalle gab ein tieferes Verständnis für das Verhalten des Komplexes unter dem Einfluss verschiedener Liganden, auch in Lösung, und dessen bemerkenswerte kinetische Stabilität. Die Komplexe UO2-DCP, UO2-DPDCP, UO2-BCPDA und die entsprechenden Konjugate UO2-DCP-MabThera® und UO2-BCPDA-MabThera® wurden in vitro untersucht. UO2-DCP und UO2-DPDCP zeigen im Blutserum keine Dissoziation. Eine suggerierte Dissoziation von UO2-BCPDA, UO2-DCP-MabThera® und UO2-BCPDA-MabThera® kann mit Schwierigkeiten der analytischen Methode und der dichten Matrix des Blutserums erklärt werden. Das durchgeführte Zellbindungsexperiment von Ac-225-DOTA-MabThera® an den Lymphomzellen K422 zeigte eine Bindungsaffinität im nanomolaren Bereich an die Zellen. Dieses Radioimmunokonjugat mit dem Antikörper MabThera®, welcher auch für das neue System UO2-DCP untersucht wird, hat somit eine starke Affinität zu den Zellen. Die Untersuchungen und durchgeführten Experimente zeigen, dass das untersuchte System UO2-DCP durchaus Potenzial für den Einsatz in der TAT besitzt, da der Komplex sich durch eine bemerkenswerte kinetische Stabilität auszeichnet. Es sollten jedoch noch weitere Experimente durchgeführt werden, um die Stabilität der Radioimmunokonjugate im Blutserum zu untermauern. Letztendlich muss auch die Immunoreaktivität der hergestellten Radioimmunokonjugate, die Affinität an Zellen, sowie die Zytotoxizität von U-230-DCP-MabThera® bzw. U-230-BCPDA-MabThera® untersucht werden.
Im Rahmen der vorliegenden Doktorarbeit wurden verschiedene mono- und polymere Akzeptor- und Donor-Akzeptormaterialien synthetisiert und erfolgreich in organischen Leuchtdioden (OLEDs) als Matrixmaterialien eingesetzt. Zum einen gelang die Synthese verschiedener bisher unbekannter 2,6-Bis(thiophen-2-yl)-1,5-naphthyridine über Stille- und Kumada-Kreuzkupplungsreaktionen. Verfahren zur rationaleren Synthese dieser Verbindungen über direkte Arylierungsreaktionen im Sinne eines rationaleren Materialzugangs wurden untersucht. Des Weiteren konnte die Synthese von an den äußeren Pyridinringen unsubstituierten 1,5 Anthrazolinderivaten über Doebner-Miller-Reaktion realisiert werden, was bis dato als nicht möglich galt. Dadurch ergab sich ein Zugang zu verschiedenen ausschließlich 9,10-disubstituierten Anthrazolinen, von denen die vielversprechendsten Kandidaten ebenfalls als Matrixmaterialien in OLEDs eingesetzt wurden. Alle in organisch-elektronischen Bauteilen verarbeiteten Materialen sind gut prozessierbar. Sie weisen eine hohe Stabilität auf, so dass sie einerseits bei Raumtemperatur und ohne Schutzgasatmosphäre über längere Zeit lagerbar sind, andererseits per Sublimation zu dünnen Schichten für Bauelemente abgeschieden werden können. Daneben sind sie aufgrund ihrer guten Löslichkeit in verschiedenen halogenierten und nichthalogenierten Lösungsmitteln flüssigprozessierbar, beispielsweise per Spincoating. Die untersuchten Naphthyridin- und Anthrazolinderivate bilden eine neue Substanzklasse, die ein großes Potential in der Anwendung in organisch-elektronischen Bauteilen besitzt.
Acene sind in der organischen Elektronik weit verbreitet, da sie die erforderlichen molekularen elektronischen Eigenschaften mit einer bevorzugten Festkörperstruktur verbinden. Das Ziel der vorliegenden Arbeit war es Pentacen- und Tetracenderivate in Polymere aus der ringöffnenden Metathesepolymerisation (ROMP) zu integrieren, um so neue n-halbleitende Materialien für flüssigprozessierte Dünnschichttransistoren zu erhalten. Es wurden pentacenhaltige Polymere mit verschiedenen Verknüpfungen zwischen Polymer-rückgrat und Acenen hergestellt und ihre Eigenschaften u.a. durch die Verwendung in elektronischen Bauteilen untersucht. Alle pentacenbasierten Polymere bilden nach der Rotationsbeschichtung amorphe Filme, die in Dünnschichttransistoren für amorphe Materialien typische Lochmobilitäten von 10^-6–10^-5 cm^2/Vs aufwiesen. Durch die Variation der Verknüpfung von Polymerrückgrat und Pentacen konnte innerhalb dieser Serie die Mobilität mehr als vervierfacht werden. Die pentacenhaltigen Monomere wurden hinsichtlich ihrer Festkörperstruktur untersucht. Für TIPS-Pentacen führt die Susbtitution eines Isopropylrestes der Triisopropylsilylgruppe durch Norbornadien zu einem verbesserten Kristallwachstum, wohingegen diese Substition für TIPS-Tetraazapentacen negative Folgen hat. Dünnschichttransistoren mit der Pentacenverbindung zeigten hohe Lochmobilitäten bis zu 1 cm2/Vs. Aufgrund der kleinen kristallinen Domänen wurden jedoch für das Tetraazapentacenderivat nur geringe Elektronenmobilitäten bis zu 10^-3 cm^2/Vs gemessen. Ein tetracenbasiertes Polymer konnte in eine organsiche Leuchtdiode (OLED) integriert werden und zeigte eine höhere Lichtausbeute von L = 0.06 cd/A (7 V), verglichen mit L = 0.01 cd/A (12 V) für eine ähnliche OLED mit Triisopropylsilylethinyl-(TIPS)-tetracen. Diese Verbesserung wird durch die amorphe Struktur des emittierenden Polymerfilms verursacht. Unterschiedlich substituierte Teracene und Diazatetracene der Monomersynthesen wurden genutzt um Effekte auf die Festkörperstruktur und die optischen Eigenschaften zu untersuchen. Für TIPS-Dibrom- und TIPS-Diioddiazatetracen wurden in ihren Kristallen schwache Halogen-Stickstoff-Bindungen gefunden, die das Packungsmotiv beeinflussen. Im Gegensatz zu dem für TIPS-Diazatetracene typischen Ziegelmauermotiv, wurden für die Dihalodiazatetracene Fischgrätenmuster gefunden. Mit dieser Arbeit wurde gezeigt, dass Acene in ROMP-Polymere für organische elektronische Bauteile integriert werden können. Durch die Variation der Verbindung zwischen Acen und Polymer und/oder durch Variation der Acene wurden vielversprechende Materialien zugänglich. Zudem konnten die Vorläufermoleküle der Monomere genutzt werden um gewünschte Festkörperstrukturen von Pentacen- und Tetracenderivaten zu erzeugen
High mass stars (stars with mass M > 8 Msolar) are one of the most fundamental building blocks in the Universe. Deeply embedded in the dense clouds at further distances than their low mass counterparts, the forming processes of these fast evolving objects are still unclear. In the earliest phases of the high mass star forming regions (HMSFRs), many complicated astrophysical processes, such as fragmentation, accretion, inflows and outflows are coexistent that dynamic studies are not enough to understand all the mysteries. Therefore, chemistry has developed into a powerful tool in probing the nature of them. With the aim of understanding the chemical and physical processes in the very beginning of high mass star formation, I selected a series of HMSFRs at different evolutionary stages, and studied their chemical-physical properties via high spatial resolution observations at (sub)mm wavelengths. The results can be summarised shortly as follows: 1. At a spatial resolution of < 1500 AU, fragmentation process is observed in the continuum maps of all the resolved sources. Above all, the fragments in 4 starless clumps are on average more massive (with M > 10 Msolar) than the Jeans mass of the large-scale clump, indicating that thermal motions is not the dominant support to against collapse, and high mass stars may form in a “scaled up” version similar to the low mass stars. 2. Observations at a spatial resolution of 1 000 AU resolve NGC 7538 S into at least 3 fragments, having comparable sizes and masses derived from continuum emissions. However, these fragments exhibit distinguishing spectral line emissions at 1.3 mm wavelength, revealing different evolutionary stages. Combing with a 1-D gas-grain model fitting, for the first time, this project suggests that these fragments may result from different warm-up paces after synchronised fragmentation, and that the warm-up processes from one stage to another is rapid. 3. Chemical variations at small scales may be caused by the evolutionary stage diversity of fragments, but may also come from chemical difference of molecular species. With the first complimentary data obtained from both interferometric and single-dish telescopes at 1.3 mm, I analysed the continuum and spectral line features at a spatial resolution of 1 200 AU in Orion-KL. From the central warmer condensations to the cooler outflow regions, gas temperatures and densities differ, leading to spatial distribution inhomogeneity and abundance diversity of nitrogen (N-) bearing, sulfur (S-) bearing and oxygen (O-) bearing molecules. 4. Even at a spatial resolution of 1 000 AU, NGC 7538 IRS1 remains unresolved. At 1.3 mm, this core has a unique spectrum at the continuum peak: a majority of the lines exhibit absorption feature, while at least 3 lines from CH3OH and HCOOCH3 exhibit strong, pure emission. I proposed several hypotheses, attempting to interpret this by source geometry and/or line excitation states. 5. Complex organic molecules (COMs) are ubiquitously detected in the hot molecular cores (HMCs). Thanks to the high sensitivity observations, I identified several low abundant COMs demonstrating complicated chemistry in my sources. 6. In addition to the fragmentation process, the high mass starless cores are not completely chemically quiescent. None line detection in 4 infrared dark clouds at 1.1 mm may indicate these regions are in the early, cold evolutionary stage. However, detection of several dense gas tracers (> 5rms) especially at 3 mm, implies the presence of active gas phase chemistry. From our study, chemistry is an efficient tool in diagnosing evolutionary events coexistent at the small scales of HMSFRs.
Laser-Induced Fluorescence (LIF) techniques are applied to visualize air-water gas exchange across the aqueous mass boundary layer in wind/wave facilities. Dissolved oxygen is made visible by quenching of the fluorescence of an organic ruthenium complex (tris(4,7-diphenyl-1,10-phenanthroline disulfonic acid) ruthenium(II) dichloride, Ru(dpp ds)3), and acid or alkaline volatile species such as CO2, HCl or diethylamine by the fluorescent pH indicator 1-hydroxy pyrene-3,6,8-trisulfonic acid (HPTS). Fluorescence of both dyes can be stimulated by a 473 nm DPSS laser. The spectral peaks of the fluorescence emission (510 nm for HPTS and 610 nm for Ru(dpp ds)3) are different enough, so that the concentration fields of both dyes can be measured simultaneously using two cameras with different bandpass filters. The paper details the properties of the two dyes and demonstrates their usage with some preliminary visualization experiments.
Der Bewuchs künstlicher Oberflächen im Kontakt mit Meerwasser, das marine Biofouling, stellt aufgrund seiner ökonomischen und ökologischen Folgen seit jeher ein Problem für die Marineindustrie dar. Aufgrund des Verbotes ehemals erfolgreicher aber hochtoxischer Biozide und einem zunehmenden Umweltbewusstsein ist die Entwicklung umweltverträglicher Beschichtungen, die die initiale Anlagerung der entsprechenden Organismen beeinflussen, in den Fokus der Forschung gerückt. Da die Adhäsionsprozesse der so genannten Fouler von einer großen Bandbreite an Oberflächen¬eigenschaften beeinflusst werden, macht man sich in diesem Zusammenhang Modellsysteme mit reduzierter Komplexität zunutze, um selektiv einzelne Variablen untersuchen zu können. Gegenstand dieser Arbeit war die Präparation und Charakterisierung stark hydratisierter Modelloberflächen und die biologische Evaluierung ihrer Fouling-Resistenz. Als biologische Modellsysteme wiederum dienten stellvertretende Spezies aus allen Stadien des komplexen Biofouling-Prozesses: Cobetia marina für marine, biofilm-bildende Bakterien; Diatomeen für die schleimbildenden Mikrofouler; Zoosporen der Grünalge Ulva linza für weiche Makrofouler und Cyprislarven der Seepocke Balanus amphitrite für die harten Makrofouler. Da im realen marinen Umfeld eine Vielzahl von Faktoren ineinander greifen, wurden außerdem Feldstudien durchgeführt, um einen Überblick über diese zu gewinnen. Zwitterionische Substanzen werden aufgrund von elektrostatischen Wechselwirkungen der vorhandenen entgegengesetzten Ladungen hydratisiert. Um den Einfluss verschiedener Ladungen und ihrer Kombination auf die biologischen Modelsysteme näher zu analysieren, wurden selbst-assemblierende Monolagen (SAMs) aus Mischungen von Alkanthiolen mit unterschiedlichen geladenen Gruppen auf Gold präpariert. Die Adsorption von Testproteinen und die Anzahl adhärenter Organismen im Feldexperiment wurden durch die gleichzeitige Präsenz der entgegengesetzten Ladungsträger an unterschiedlichen Molekülen reduziert; die Ablösbarkeit der Kieselalgen erhöht. Zoosporen der Grünalge Ulva linza wiesen dagegen komplexere Adhäsionspräferenzen auf, die von der exakten Terminierung der Oberflächen abhingen. Polysaccharide sind hydrophile Biopolymere, deren Hydratation über Wasserstoffbrückenbindungen zustande kommt. Drei strukturell leicht variierende Vertreter dieser Klasse, Alginsäure (AA), Hyaluronsäure (HA) und Chondroitinsulfat (CS), wurden kovalent auf Oberflächen immobilisiert und anschließend an ihren Säuregruppen mit einem fluorierten Amin modifiziert. Dadurch wurden einerseits freie Carboxylgruppen für die Wechselwirkung mit zweiwertigen Kationen blockiert und andererseits amphiphile Eigenschaften in den hydrophilen Polymernetzwerken etabliert. Die zugrundeliegende Hypothese, dass die verminderte Fähigkeit zur Komplexierung von Ca(II)-Ionen die inerten Eigenschaften der Polysaccharidfilme im marinen Medium verbessert, konnte für AA und HA für die Adhäsion von C. marina, das Besiedlungsverhalten von U. linza und B. amphitrite und im Feldversuch bestätigt werden. Entgegengesetzt dazu verfügte das sulfatierte Polysaccharid CS im unmodifizierten Zustand über bessere antiadhäsive Eigenschaften. Als dritte Materialklasse wurden Poly(Hydroxyethylmethacrylat)-Filme, die ebenfalls durch ihr chemisches Grundgerüst eine wasserstoffbrückenbasierte Hydratation aufweisen, charakterisiert und bezüglich ihrer Proteinresistenz getestet. Für die durch oberflächeninitiierte RAFT-Polymerisation hergestellten Substrate wurde eine Schichtdickenabhängigkeit der Resistenzeigenschaften demonstriert.
ABSTRACT The aim of this study is to generate nanopatterned surfaces with feature sizes between 10 and 100 nm on large lateral scale in order to investigate confinement effects on the activity of adsorbed enzymes. To achieve this purpose, novel patterning techniques based on colloidal lithography were developed to generate five different types of nanopatterned surfaces: i) metal-semiconductor nanopatterns, ii) charge heterogeneous 2D and 3D nanopatterned polyelectrolyte multilayers (PEMs), iii) gold nanoparticle arrays on charge heterogeneous nanopatterned PEMs, iv) metal-dielectric hybrid nanopatterns, and v) nanopatterned oligo(ethylene)glycol silane self-assembled monolayers (SAMs). All of the fabricated nanopatterned surfaces were characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), scanning electron microscopy (SEM), ellipsometry and UV-visible spectroscopy. Metal-semiconductor nanopatterns and charge heterogeneous 2D and 3D nanopatterned PEMs were chosen for protein adsorption investigations based on their excellent reproducibility and the capability to produce uniform and high density nanopatterns. Specifically, porous metal-semiconductor nanopatterns with 25 nm (type A25) and 60 nm (type A60) adsorption site diameter and honeycomb-like dielectric nanopatterns with 60 nm (type B60) and 100 nm (type B100) adsorption site diameter were fabricated to evaluate the specific enzymatic activity of surface-bound glucose oxidase (GOx). The amount of GOx adsorbed onto these nanopatterned surfaces was quantified by enzyme linked immunosorbent assays (ELISA). The specific activity of GOx on the nanopatterned surfaces was compared to the specific activity of GOx on poly(allyamine hydrochloride) coated non-patterned surfaces and in solution phase. It was found that the confinement of GOx into nano-domains of patterned substrates has a significant effect on protecting the enzymatic activity of GOx. When the adsorption site diameter was selected similar to enzyme size, the activity of the protein was well preserved and only a small loss of activity was observed. This is in line with the observation that proteins tend to unfold and lose their activity upon contact with surfaces which offer sufficient free surface area. We may therefore conclude from the study that geometrical confinement is a promising strategy to overcome this problem and stabilize surface-bound enzymes.
Superhydrophobic surfaces have numerous important practical applications in research and industry. These materials have been widely used for production of self-cleaning, anti-icing, anti-corrosive, non-adhesive, anti-biofouling coatings and surfaces. The phase separation method of producing porous polymer films is a simple and cheap approach that allows producing materials with desired physical and chemical properties, such as polymer globule size, porosity, hydrophobicity or hydrophilicity and surface functional groups. Additionally, the surface can be also later functionalized using available surface modification techniques. However, so far, due to the not optimal surface topography the produced surfaces have exhibited large contact angle hysteresis which limits their practical applications. The goals of this PhD thesis were to: (1) develop a method for the preparation of superhydrophobic polymer surfaces with high water contact angles and low contact angle hysteresis; (2) to characterize the produced surfaces; (3) to investigate the effect of the surface topography and hierarchy on the surface wettability; (4) and to explore their properties in microfluidic and biological applications.
The task to design surfaces with outstanding surface characteristics requires understanding of the influence of the surface topography on the wettability. Due to the ease of production, porous poly(2-hydroxyethylmethacrylate-co-ethylene dimethacrylate) (polyHEMA) and poly(butyl methacrylate-co-ethylene dimethacrylate) (polyBMA) surfaces with different surfaces topographies prepared for these studies. The polymer surfaces with protruded and grooved surface topography were prepared simultaneously by photopolymerization in a mold consisting of two glass slides. However, due to the breakage of the polymer film during separation, surfaces with characteristic protruded and grooved topography were made. Photografting of the polyHEMA surfaces with 2,2,3,3,3-pentafluoropropyl methacrylate (PFPMA) resulted in the formation of a complex hierarchical structure. The surface functional groups of polyHEMA could be modified through consecutive esterification and thiol-yne reaction. Influence of the surface topography, hierarchy and chemistry on the surface wettability were investigated by Scanning Electron Microscopy (SEM), confocal optical profiler and water contact angle measurements.
Recently, microfluidic devices attracted a lot of attention as they allow handling of small liquid volumes and miniaturization of the measurement systems. In this thesis, open microfluidic channels based on the Laplace micro-pump were prepared by photografting PFPMA on the grooved polyHEMA surface creating superhydrophilic micro-channel surrounded by superhydrophobic borders. The working principle of the passive Laplace micro-pump in the produced micro-channel was investigated. The formation of a laminar flow in the absence of an external force was studied. Additionally, the kinetics of the flow in the micro-channels with different dimension was examined.
The ability to control stem cell differentiation shows great promise for numerous applications such as stem cell therapy, treatment of diabetes, Parkinson and Alzheimer diseases and many other. However, it is a complex process that depends on both the physical and chemical cues. In this thesis, polyHEMA surfaces with different roughness and surface chemistry were used to investigate the influence of the surface properties on the stem cell differentiation. Retardation of stem cell differentiation for over three weeks of culture on the micro-rough surfaces was shown.
In der vorliegenden Arbeit wurden zwei unterschiedliche Ligandensysteme und deren Metallkomplexe als potentielle, homogene Katalysatoren für die Kupplung von Epoxiden mit Kohlenstoffdioxid (CO2) zu den entsprechenden organischen Carbonaten getestet. Dabei stand die selektive Umsetzung zu cyclischen Carbonaten oder zu aliphatischen Polycarbonaten im Fokus. Das große Interesse für diese Kupplungsreaktion beruht auf der Möglichkeit CO2 als Synthesebaustein zu benutzen und eine zukünftige kommerzielle Nutzung dieser Kupplungsprodukte voranzutreiben. Als Ausgangspunkt der Synthese des ersten Komplexsystems fungierten Variationen des N,N-Bis(2-pyridincarboxamid)-1,2-benzen-Liganden (N4-bpb-Ligand). Durch Umsetzung dieser N4-Liganden mit einerseits Übergangsmetallacetat- bzw. Übergangsmetallhalogenid-Precursoren und den entsprechenden Tetraalkylammonium-Salzen und andererseits mit Diethylaluminiumchlorid, sowie Diethylzink, gelang es 21 ionische, oktaedrische Cobalt-, Eisen-, Chrom(bpb)-Komplexe und acht neutrale Aluminium- bzw. Zink(bpb)-Komplexe zu synthetisieren und teilweise ihre Struktur mittels Röntgenstrukturanalyse genau zu beschreiben. Das zweite Komplexsystem besteht aus der basischen Variante der Metallacetate von Chrom, Eisen und Mangan, welche eine außergewöhnliche, dreikernige, 3 oxo verbrückte, ionische Struktur besitzt, sowie dem zweikernigen Dichrom tetraacetat-dihydrat-Komplex. Diese Verbindungen konnten erfolgreich durch Umsetzung geeigneter Metallprecursoren mit Eisessig bzw. Natriumacetat synthetisiert werden. Zur Überprüfung ihres Katalysatorpotentials für die Kupplungsreaktion erfolgten systematische Katalysetests beider Komplexsysteme mit den Standardtestsubstraten Propylen- und Cyclohexenoxid. Des Weiteren wurde für einige aktive Katalysatoren ein breiteres Screening mit anderen, kommerziell erhältlichen Epoxiden durchgeführt. Ihre Testung zeigte, dass sich durch die Wahl des Katalysators selektiv aliphatische Polycarbonate oder cyclische Carbonate darstellen lassen. Die Cobalt(bpb)bromid- und Eisen(bpb)chlorid-Komplexe eignen sich ohne Zusatz eines Cokatalysators zur quantitativen Synthese von Propylencarbonat. Im Gegensatz dazu benötigen die Zink- bzw. Aluminium(bpb)-Komplexe den Zusatz eines ionischen Cokatalysators wie Tetrabutylammoniumiodid um eine quantitative Umsetzung zu erreichen. Hervorzuheben sind die Zink(bpb)-Komplexe, die auch unter milden Reaktionsbedingungen (60°C, 2 bar CO2-Druck) Propylencarbonat bilden. Zur Gewinnung von reinem Polycyclohexencarbonat sind die Cobalt(bpb)acetat- und Cobalt(bpb)chlorid-Komplexe zu bevorzugen. Aliphatische Poly-ether-carbonate aus Propylenoxid konnten stattdessen nur mit den basischen Metallacetaten hergestellt werden. Eine weitere wichtige Erkenntnis ist, dass zum Beispiel im Falle der Cobalt(bpb)chlorid-Komplexe eine Modifikation des N4-Liganden-Gerüstes mit einem elektronenziehenden Substituenten am ortho Phenylen-Linker (Einbau einer Nitro-gruppe) zu einer deutlichen Steigerung der Ausbeute an Propylencarbonat von 42 auf 86 % führt. Weiterhin gelang es aus den Erkenntnissen der Katalysatortestung, teilweise unterstützt durch kinetische Messungen mittels in situ FT-IR-Spektroskopie, für die verschiedenen neuen Katalysatortypen in dieser Arbeit jeweils Postulate über den Reaktionsmechanismus aufzustellen.
Die vorliegende Arbeit befasst sich mit der Synthese, Charakterisierung, Redoxaktivität und Koordinationschemie der neuen Tetraguanidinyl-funktionalisierten Benzochinone 2,3,5,6-Tetrakis(tetramethylguanidinyl)-p-benzochinon (ttmgbc, 1), 2,3,5,6-Tetrakis(di-methylethylenguanidinyl)-p-benzochinon (tdmegbc, 2), und der ersten in unserer Arbeits-gruppe synthetisierten Hexaguanidinyl-funktionalisierten Aromaten (GFA-6) 2,3,6,7,10,11-Hexakis(tetramethylguanidinyl)triphenylen (htmgt, 3) und 2,3,6,7,10,11-Hexakis(dimethyl¬ethylenguanidinyl)triphenylen (hdmegt, 4). Sie stellen zum einen starke Stickstoffbasen dar, deren pKBH+-Werte in Acetonitril mit Hilfe quantenchemischer Rechnungen bestimmt wurden. Zum anderen sind sie starke Elektronendonoren, deren Redoxaktivität durch Zyklovoltammetrieexperimente nachgewiesen werden konnte. Diese zeigten, dass sich 1 und 2 in einem ersten Zweielektronenschritt mit zwei anschließenden Einelektronen¬schritten, 3 und 4 in drei Zweielektronenübergängen reversibel oxidieren lassen. Durch ihre elektronenziehenden CO-Gruppen wird zudem die HOMO-Energie der Benzochinon¬liganden herabgesenkt, was zu kleinen HOMO-LUMO-Lücken und damit veränderten optischen Eigenschaften führt. Daneben wurde eine Reihe dinuklearer (1, 2) und trinuklearer (3) Komplexe dargestellt, wobei ein besonderer Fokus auf die Koordinationschemie von 3 gelegt wurde. So wurden Cu(I)- und Cu(II)-Komplexe erhalten, deren elektronische Eigenschaften detailliert diskutiert werden. Die Koordinationsgeometrie der Cu(II)-Komplexe mit KZ 4 liegt zwischen tetraedrisch und quadratisch planar. Zudem konnten niedrigenergetische elektronische Übergänge einem LMCT zugeschrieben werden. Eine Oxidation des Kupfer(I)-iodid-komplexes führte, im Gegensatz zu schon bekannten redoxaktiven GFA-Liganden, zu einer Oxidation des Kupfers anstelle des Liganden. Die durch den Triphenylenliganden vermittelte magnetische Kopplung der paramagnetischen Cu(II)- und Co(II)-Komplexe wurde mit Hilfe von SQUID-Messungen untersucht, welche sehr schwache ferromagnetische Wechelwirkungen erkennen ließen. Weiterhin wurde gezeigt, dass mit 3 ein- und zweidimensional verknüpfte Koordinationspolymere und poröse Materialien durch Reaktion mit Silberhalogeniden zugänglich sind. Darüber hinaus wurde 3 in einer Kooperation auf seine Eignung als organisches Halb-leitermaterial getestet und sein Verhalten auf einer Au(111)-Oberfläche mittels IR-Spektroskopie untersucht.
Die vorliegende Dissertation befasst sich mit der Synthese und Charakterisierung der neuen Guanidinyl-funktionalisierten Aromaten (GFA-4) 2,3,7,8-Tetrakis(N,N,N´‚N´-tetramethyl-guanidinyl)phenazin (ttmgph) 1 und 2,3,6,7-Tetrakis(N,N,N´,N´-tetramethylguanidinyl)fluoren (ttmgf) 2 sowie deren Koordinationschemie. Beide Liganden sind starke Stickstoffbasen, deren pK(BH+)-Werte (21.8 für 1 und 23.7 für 2 in CH3CN) mit Hilfe quantenchemischer Rechnungen bestimmt wurden. Das Redoxverhalten wurde mittels Zyklovoltammetrie untersucht. Die erste Oxidation bezogen auf das Redoxpaar Fc/Fc+ liegt bei -0.14 V für 1 und bei -0.46 V für 2. Die meisten Übergänge sind dabei irreversibler Natur. Beide Liganden zeigen Fluoreszenz, dabei wurde die Quantenausbeute des Liganden 1 in Diethylether (0.39) und Wasser (0.02) bestimmt. Die Umsetzung der beiden Liganden mit Cu(I)-Salzen führte zur Bildung zweikerniger Koordinationsverbindungen, welche vollständig charakterisiert werden konnten und hinsichtlich ihres Redoxverhaltens untersucht wurden. Außerdem wurde der Ligand 1 mit Silbercyanid umgesetzt. Die Untersuchung optischer Eigenschaften zeigt, dass durch Kupfer(I) im Gegensatz zu Silber(I) die Fluoreszenz dieser Verbindungen gelöscht wird. Der Ligand 1 wurde außerdem mit Zn(II)-Salzen, die starke Lewis-Säuren sind, umgesetzt. Wird ZnCl2 eingesetzt, so ist die Wahl des Lösungsmittels für das entstehende Produkt entscheidend. In Acetonitril wird vergleichbar den Umsetzungen mit Cu(I)- bzw Ag(I)-Salzen ein zweikerniger Komplex [1(ZnCl2)2] erhalten. In Dichlormethan wird eine zusätzliche Koordination einer weiteren ZnCl2-Einheit am Stickstoffatom des Phenazinsystems und damit eine Verbrückung des zweikernigen Komplexes zu [12(ZnCl2)5] beobachtet. Wird dieser verbrückte Komplex in Acetonitril gelöst, einem im Gegensatz zu Dichlormethan koordinierenden Lösungsmittel, so verdrängen die Lösungsmittelmoleküle die zusätzliche ZnCl2-Einheit und mit der Zeit liegt in Lösung der zweikernige Komplex [1(ZnCl2)2] vor. Zinkbromid zeigt ein ähnliches Verhalten, während die deutlich schwächere Lewis-Säure Dimethylzink auch in Dichlormethan nicht fähig ist, an den Phenazinring zu koordinieren. Außerdem konnte die Umsetzung des zweikernigen Komplexes durch Zusatz von Zinkchlorid in Schritten von 0.2 Äquivalenten zum verbrückten Komplex mittels UV-Vis-Spektroskopie beobachtet werden. Diese Spektren enthielten den ersten Hinweis auf das Vorliegen eines Gleichgewichtes mehrerer Spezies in Lösung, wobei eine weitere Verknüpfung zu oligomeren Ketten durch Überschuss an ZnCl2 denkbar wäre. Das Fluoreszenzverhalten von Zn(II)-Komplexen wurde ebenfalls untersucht. So emittiert [1(ZnCl2)2] bei 506 nm in Dichlormethan, dem verbrückten Komplex [12(ZnCl2)5] könnte die zusätzliche Emission bei 602 nm zugeordnet werden. Es wird vermutet, dass in Dichlormethan neben [1(ZnCl2)2] und [12(ZnCl2)5] noch längere über Zinkchlorid verbrückte Ketten vorliegen.
Acute myeloid leukaemia is a malicious disease. Although the initial chemotherapeutic treatment often leads to a complete remission (a disappearance of all manifestations of disease), the effective survival rate is only (30-40) % over 4 years due to a high relapse rate. This relapse is attributed to leukaemic stem cells residing in the protective environment of the bone marrow niche. There are two major approaches aiming at achieving better long-term therapeutic results. The first is to make the leukaemic stem cells more susceptible to chemotherapeutic agents and the second is to increase the efficiency of haematopoietic stem cell transplants, which are used to regenerate the haematopoietic system after failure due to chemotherapy. When searching for a receptor-ligand pair suitable as target for therapeutic agents, the prerequisite is that it must exhibit differences between the interaction it mediates in healthy and leukaemic cells. A detailed understanding of the mediated interaction and the differences would then allow exploitation of these to selectively mobilise the leukaemic stem cells increasing their susceptibility for chemotherapeutic drugs. In this work the flow-induced rolling interaction of leukaemic cells with hyaluronic acid was studied in detail using a suspension and an epithelial model cell line. It could be demonstrated, that the flow induced rolling interaction on hyaluronic acid observed for these cells was solely mediated by the cell surface receptor CD44 and that it was independent of the cell type tested. Next to a detailed validation and characterisation of this dependency and the properties of the interaction, the relevance of this interaction for the haematopoietic system and for leukaemic cells was evaluated. Therefore, the CD44 mediated interaction with hyaluronic acid of healthy haematopoietic progenitor cells from umbilical cord blood, mobilised peripheral blood and the bone marrow with that of leukaemic blasts was compared. Throughout the cell types tested two forms of interaction with hyaluronic acid were observed; a flow induced rolling and an immobile adhesion. It could be shown that while the rolling interaction was comparable for all cell types tested, the immobile adhesion to hyaluronic acid and its susceptibility to a monoclonal CD44 antibody (clone BU52) were not. The immobile adhesion was found predominantly in leukaemic cells, only playing a subordinate role in the interaction of healthy cells with hyaluronic acid. It could be demonstrated that a vicinity of the cells to the bone marrow upon isolation was directly correlated to an incomplete suppression of the immobile adhesion by BU52. Furthermore, this incomplete suppression could be linked to a non-response to induction chemotherapy and subsequently to a poor therapeutic outcome. Besides investigating the interaction with surfaces artificially coated with hyaluronic acid, the possibility of using surfaces covered with mesenchymal stromal cells isolated from the bone marrow as more realistic binding partners was explored. Furthermore, the effect of a routinely used mobilisation reagent, namely Plerixafor®, on the migration and cell-surface interaction under flow was investigated. It is not only of great interest to understand the mechanisms of retention in the niche, but also to develop more sophisticated methods of in vitro stem cell expansion. In this context the slow and continuous release of e.g. cytokines or growth factors is of great interest. The cavities in porous materials present the unique opportunity of achieving just that by being pre-loaded with such agents. These can then under the right conditions be released to the cells. Amongst the porous materials the metal-organic frameworks protrude due to their high structural and chemical flexibility. In this work a novel 2-D metal-organic framework structure, namely SURMOF 2, was tested towards its biocompatibility and smart-release properties. It could be shown that SURMOF 2 was highly stable in protein free aqueous media and that its building units did not impair the growth of rat embryonic fibroblasts. Although the stability in cell culture medium is still limited, the water stability and the biocompatibility of the components are the starting point for future SURMOF 2 cell culture applications. A first application of SURMOF 2 as a smart-release matrix was achieved with the marine bacterium Cobetia marina under salt water conditions. The results demonstrated the general applicability of SURMOF 2 as bioactive substrates with responsive properties. For the future, fine-tuning of the stability of SURMOFs will allow to tailor drug release systems for cytokine or growth factor delivery in in vitro stem cell cultures.
In this work, single-molecule super-resolution microscopy with photoswitchable fluorophores was integrated into a multi-component microscopy platform. This platform enabled combined high-throughput widefield/confocal microscopy, in order to first validate relevant target cells, and subsequent sub-diffractional imaging of selected cells via direct stochastic optical reconstruction microscopy (dSTORM). In a first project, a single-molecule sensitive fluorescence microscope was set up, and equipped for single-molecule localization microscopy. As suitable photoswitchable fluorophores for dual-colour imaging, Alexa Fluor 647/ Cy5 and Alexa Fluor 532 were identified. Software solutions were developed to analyze the raw data of a localization-based experiment and to reconstruct super-resolution images. Strategies to correct for chromatic aberration between two spectrally separate channels were developed by using fiducial markers and a registration software. The achieved localization precision was determined to be sigma(SMLM) = 12.5 nm in the image plane. The chromatic aberration could be corrected with a precision of 10 nm. In order to integrate the super-resolution imaging into the microscopy platform, a work-flow was developed that allowed transferring the sample between different microscope setups and relocating identified targets into the field of view. This procedure is based either on external reference markers on the respective cellarray/coverslip, or builds on using a stitched overview image with low resolution. Individual cells were relocated into the field of view with a precision of less than 4 µm. For validation, widefield low-resolution images of a cis- and a trans-Golgi marker (GalT and Gm130) in cells were recorded and served to select individual cells for further analysis by confocal and super-resolution imaging. Images of representative control cells as well as cells treated with nocodazol (depolymerizes tubul network) and brefeldin A (relocates Golgi into the endosplasmic reticulum (ER)) were analyzed for colocalization using intensity-based colocalization analysis (ICA). The results indicated that nocodazol treatment fragmentizes the Golgi complex by the depolymerization of the tubul network. Contrarily, brefeldin A leads to a relocalization of the Golgi into the ER. The colocalization of GalT and GM130, calculated from confocal images, decreased from 9.6% (control cells) over 7.7% (nocodazol treatment) to 5.5% (brefeldin A treatment). This observation is in accordance with reports in the literature. The same decrease of colocalization was calculated from the super-resolution images (5.5%, 4.2% and 1.6% respectively). Next to conventional colocalization analysis, single-molecule localization microscopy data can directly be analyzed using the coordinates of individual fluorophores (coordinate-based colocalization (CBC)). This analysis showed that after treatment with nocodazole, the colocalization of GalT and GM130 was not affected compared to the control cell. The Golgi complex disassembled into smaller structures, but the internal membrane structure remained intact. The treatment with brefeldin A degraded the whole Golgi and membrane assembly and therefore changed the colocalization pattern of the cis- and trans-Golgi marker. In a second project, newly developed and sequence-specific oligonucleotide probes for messenger ribonulceic acid (mRNA) detection (synthesized in the group of professor Mokhir, Erlangen) were evaluated at the single-molecule level. This mRNA probe is synthesized to be intrinsically photoactivatable and specific due to a dual-strand design. The probe consists of a first oligonucleotide strand, which is conjugated to a fluorophore and linked to a quencher by a cleavable linker (-CHS=SHC-). The second oligonucleotide strand is conjugated to a photosensitizer, which upon irradiation with light catalytically produces singlet oxygen. Singlet oxygen cleaves the linker between the quencher and the fluorophore, releases the quencher and restores the fluorescence signal. Single-molecule experiments were performed to validate the functioning of a probe that was designed to specifically bind actin-mRNA. Here, the fluorophore was conjugated to the first oligonucleotide strand by the cleavable linker. Illumination with light leads to the production of singlet oxygen, subsequent cleavage of the linker and release of the fluorophore. The experiments showed that the cleavage reaction is highly specific and is not triggered if no activation light is applied, nor the strand of the photosensitizer includes a mismatching sequence to the target sequence. If the fluorophore was conjugated to the first oligonucleotide strand without a cleavable linker, the singlet oxygen for cleavage did not induce a release of the fluorophore.
Die als Biofouling bezeichnete Besiedelung fester, von Wasser bedeckter, Oberflächen stellt in vielerlei Hinsicht ein großes Problem dar. Eine Möglichkeit, wirksame und dennoch umweltverträgliche Gegenstrategien zu entwickeln, besteht darin, die Funktionsweise der biologischen Klebstoffe zu verstehen, mithilfe derer die Foulingorganismen auf ihren Substraten adhärieren. Im Idealfall könnten ungiftige Substanzen mit der Adhäsion bzw. Kohäsion der Klebstoffe interferieren und so die Anhaftung verhindern. Seepocken sind bedeutsame Foulingorganismen, welche mit verschiedenen Arten weltweit in allen Küstenbereichen zu finden sind. Ein entscheidender Schritt ihres Lebenszyklus stellt die permanente Adhäsion der motilen Cyprislarve dar, bevor diese die Metamorphose zur sessilen adulten Form durchläuft. Die Larve sekretiert dazu einen als Cypriszement bezeichnete Klebstoff. Die Analytik dieser Substanz wird unter anderem durch die geringe Materialmenge in Nanogrammbereich erschwert, welche von den Larven einmalig sekretiert wird. Aus diesem Grund ist über die Zusammensetzung des Cypriszements im Gegensatz zum Zement der adulten Seepocken bisher wenig bekannt. In dieser Arbeit wurde erstmals synchrotronbasierte μ-Röntgenfluoreszenzanalyse (μ-RFA) verwendet, um die Elementverteilungen in den Seepockenarten Elminius modestus, Balanus amphitrite und Balanus improvisus sowie deren Cyprislarven in vivo zu untersuchen. Die an der Synchrotronstrahlungsquelle ANKA durchgeführten Experimente lieferten erste Hinweise auf erhöhte Konzentrationen einiger Elemente im Cypriszement, allen voran Brom, deren Vorkommen bisher noch nicht beschrieben worden war. Um die Hinweise zu überprüfen, wurden anschließend mit der gleichen Methode Proben der von B. amphitrite und B. improvisus auf einem Kaptonsubstrat hinterlassenen Adhäsive in situ untersucht. Neben Brom wurden dabei auch noch weitere Elemente gefunden, deren Vorkommen in dieser Substanz bisher nicht bekannt war. Motiviert durch diese Erfolge wurde die Anwendung der μ-RFA auf weitere Foulingorganismen getestet. Erste In-vivo-Messungen bei ANKA am Kalkröhrenwurm Ficopomatus enigmaticus verliefen erfolgreich. Auch die vergleichsweise kleine marine Kieselalge Navicula perminuta konnte an der Synchrotronstrahlungsquelle PETRAIII untersucht werden. Bislang war es jedoch noch nicht möglich, Fluoreszenzsignale der adhäsiven Sekretspuren zu detektieren, die die motile Alge auf Substraten hinterlässt. Dies ist höchstwahrscheinlich auf die schwache Wechselwirkung der verwendeten harten Röntgenstrahlung mit dem sub-μm-dicken Probenmaterial zurückzuführen. Weiche Röntgenstrahlung zeigt eine deutlich stärkere Wechselwirkung. Um die Möglichkeiten zu untersuchen, die Photonen dieses Energiebereichs für eine Untersuchung mikroskopischer biologischer Proben bieten, wurde ptychographische Röntgenmikroskopie an der Synchrotronstrahlungsquelle BESSY II verwendet, um den Phasen- und Absorptionskontrast verschiedener Probentypen zu charakterisieren. Als Alternative zum Elementkontrast der RFA wurde dabei an einer Testprobe aus Mikrokugeln sowohl ptychographisch als auch mittels Vollfeldmikroskopie das Potential des NEXAFS-Kontrasts demonstriert, welcher in der Lage ist, chemische Bindungszustände zu differenzieren und somit prinzipiell geeignet erscheint, Einblicke in die Zusammensetzung biologischer Klebstoffe zu erhalten.
Among the different biofouling species, barnacles resemble a specific threat as they are difficult to remove, able to damage fouling release coatings and increase the drag force of ships. Additionally, barnacles are a good model system for research on permanent underwater adhesion strategies. This study aims to understand and compare the spatial organization and the chemistry of the adhesive secreted by two different species (Balanus amphitrite and Balanus improvisus) of cyprid larvae and juvenile barnacles for settlement. Raman spectromicroscopy and synchrotron based X-ray microprobe fluorescence analysis have been applied for the in-situ and ex-situ investigation of juvenile barnacle cement chemistry. Confocal Raman spectromicroscopy revealed the chemical heterogeneity of the barnacle baseplate and allowed to distinguish three regions of various chemical compositions. The adhesive of cyprids was different from the one of larvae and analyzed in detail from the metamorphosis to the age of fourteen days. The results of these studies provided information on the chemical composition and morphological structure of both barnacle species at different life stages.
Im Rahmen dieser Arbeit wurden neuartige, überbrückte Phenylacetylen-Derivate hergestellt, bei denen sich durch die Wahl des Linkers gezielt bestimmte Torsionswinkel der Phenylringe zueinander einstellen lassen. Eine effektive Syntheseroute erlaubte den Einbau verschiedener Linker über Disäurechloride. Die Kristallstrukturen der erhaltenen Tolanophane wiesen sowohl planare als auch verdrillte Konformationen auf. Durch den Einbau eines Malonyl-Linkers wurden erstmals nahezu orthogonale Grundzustandsgeometrien erreicht, wodurch der Einfluss auf die photophysikalischen Eigenschaften maximiert wurde. Dies ist in der daraus resultierenden vergrößerten HOMO-LUMO Bandlücke begründet und spiegelt sich in einer starken hypsochromen Verschiebung im Absorptionsspektrum wieder. Die Fluoreszenzbanden planarer und verdrillter Tolanophane sind jedoch fast identisch, da in Lösung eine Planarisierung des angeregten Zustands stattfindet und die Emission aus den gleichen angeregten Zuständen erfolgt. Durch das Einbetten in eine kryogene Matrix bei 77 K wurden die Grundkonformationen "eingefroren" und die erwartete Blauverschiebung der Fluoreszenz konnte beobachtet werden. Während die planaren Spezies ausschließlich fluoreszierten, wurde für die verdrillten Tolane außergewöhnlich starke Phosphoreszenz detektiert. Die gemessene lange Lebenszeit für diese Substanzklasse von ca. einer Sekunde war für diese Triplett-Emission bisher unbekannt. Das Konzept wurde auf die erweiterten pi-Systeme Dibrom- und Dipropinyl-Diphenylacetylene sowie 1,4-Bis(phenylethinyl)benzole übertragen, wobei auch für diese dieselben luminophoren Eigenschaften nachgewiesen wurden. Durch diese Erkenntnisse ist es möglich, die Konformationen von Phenylacetylen-Derivaten gezielt zu verändern und somit weitere, bisher unbekannte Materialeigenschaften zu erforschen.
Zum markierungsfreien in situ Nachweis biospezifischer Bindungsereignisse in hoch-dichten Pep-tidarrays wurde die Ausbildung optischer Extinktionen in Kern-Schale-Nanopartikelfilmen mit me-tallisierten hexagonal dicht angeordneten dielektrischen Partikeln eingehend untersucht und die Nanostrukturen für den Einsatz in der Biosensorik optimiert. Die Extinktionsspektren im sichtba-ren Spektralbereich wiesen scharfe Peaks auf, deren spektrale Lage sensitiv auf Änderungen des Brechungsindexes in der Sensorumgebung reagiert. Die Signalentstehung wurde experimentell charakterisiert, mit elektronenstrahllithographisch hergestellten Nanostrukturen moduliert und die Spektren mit rigoroser Beugungsanalyse im Fourier-Raum berechnet. Es konnte gezeigt werden, dass die Signale durch eine Kombination aus Interferenzen und plasmonischen Anregungen her-vorgerufen werden. Zur in situ Detektion von Bindungsereignissen ist es von zentraler Bedeutung, den Einfluss von Moleküladsorbaten und Brechungsindexänderungen der Volumenphase auf das Sensorsignal zu trennen. Es wurden Lichteinfallswinkel gefunden, unter denen der Einfluss des Brechungsindexes der Flüssigkeit auf die Peakposition im Extinktionsspektrum vernachlässigbar war. Unter diesen Winkeln wurde die Adsorption von Biomolekülen in situ und zeitaufgelöst detektiert. Durch geziel-te Beschichtungen mit Metall-organischen Gerüstverbindungen konnte die Nachweisempfindlich-keit gegenüber Diffusionsprozessen aus der Gasphase gesteigert werden. Im Hinblick auf diag-nostische Anwendungen wurde unter Verwendung hochauflösender Lokalisationsmikroskopie die laterale Position einzelner Peptidmoleküle auf hexagonal angeordneten Goldnanopartikeln nach einer kovalenten Anbindung von Farbstoffmolekülen nachgewiesen.
„Clara Immerwahr – Fritz Haber. Was können wir aus der Geschichte lernen?“ – Diese Frage stand im Mittelpunkt des Vortrags im Studium Generale der Universität Heidelberg, der am 2. Juni 2014 in der Aula der Neuen Universität stattfand. Prof. Dr. Gudrun Kammasch von der Beuth Hochschule für Technik in Berlin ging darin am Beispiel des Konflikts zwischen den Eheleuten Clara Immerwahr und Fritz Haber auf die ethischen Dimensionen von Wissenschaft und Forschung ein.
Während der Chemiker und spätere Nobelpreisträger Fritz Haber im Ersten Weltkrieg über Giftgas forschte und Kampfgaseinsätze leitete, stand seine Frau Clara Immerwahr, ebenfalls Chemikerin, seinem Tun sehr kritisch gegenüber. Der Konflikt zwischen den beiden Wissenschaftlern und Ehepartnern endete mit dem Suizid Immerwahrs: Sie erschoss sich 1915 in der gemeinsamen Berliner Villa, nachdem der erste deutsche Giftgaseinsatz in Flandern tausende Opfer gefordert hatte. Was Fritz Haber davon abhielt, auf die Warnungen seiner Frau vor den Folgen der Gaseinsätze zu hören, und was wir heute aus der Auseinandersetzung mit diesem Aspekt von Habers Forschung lernen können, erläuterte Frau Prof. Kammasch in ihrem Vortrag.
Das Studium Generale ist eine Veranstaltungsreihe der Universität Heidelberg, die sich an alle Mitglieder der Universität und die interessierte Öffentlichkeit wendet. Die Vorträge eines Semesters stehen unter einem gemeinsamen Rahmenthema, das von Wissenschaftlern verschiedener Fachrichtungen aus der Sicht ihrer Disziplin behandelt wird. Im Sommersemester 2014 widmet sich das Studium Generale dem Thema „Der Erste Weltkrieg und die Folgen“.
The Interatomic/ Intermolecular Coulombic Decay (ICD) as well as the Electron Transfer Mediated Decay (ETMD) are electronic decay processes, which occur in a multidude of systems ranging from noble gas dimers to biological systems. If heavy atoms are involved in these processes, relativistic effects cannot be neglected. However, their influence has so far not been investigated thoroughly. In this thesis, the influence of the spin-orbit coupling as well as scalar-relativistic effects on openings and closings of decay channels as well as on the corresponding decay widths are studied. For this purpose, asymptotic expressions for the decay widths of both ICD and ETMD are derived. They allow for analytic studies of basic properties and estimations of the decay widths based on properties of the constituting atoms or molecules of the total system. A more precise description of the decay widths required the transfer of the non-relativistically known FanoADC-Stieltjes method to the relativistic regime and its implementation into the relativistic quantum chemical program package Dirac. Using this method, small noble gas systems are investigated. Experimentally, these decay processes are usually studied in noble gas clusters consisting of 100 – 2000 atoms. These clusters are too large to be treated with ab initio methods. In order to allow for a comparison of theoretical and experimental results, the influence of the cluster environment on the secondary electron spectra are investigated. These findings are used for the development of a method for the decay width estimation of clusters based on the asymptotic expressions or calculated decay widths for a multitude of geometries. This method was implemented as the program HARDRoC and is used for the investigation of the two competing processes ICD and ETMD in ArXe clusters. Additionally, it is the foundation of a new structure determination method of heteronuclear noble gas clusters, which is exemplarily explained for NeAr clusters.
Die vorliegende Arbeit befasst sich mit der Synthese und Charakterisierung neuer zweikerniger Kupfer- und Silber-Komplexe sowie Silber-Koordinationspolymeren mit guanidinofunktionialisierten Aromaten (GFAs). Hierbei werden die Synthesen der erhaltenen Komplexe und Koordinationspolymere sowie die mit Hilfe der Einkristallstrukturananalyse erhaltenen Molekülstrukturen in der kristallinen Phase vorgestellt. Dabei werden die charakteristischen strukturellen und elektronischen Besonderheiten der Verbindungen unter Einbeziehung der Ergebnisse quantenchemischer Rechnung erörtert. Zur Synthese der in dieser Arbeit vorgestellten Verbindungen standen die Tetrakisguanidinverbindungen 1,2,4,5- Tetrakis(N,N,N’,N’-tetramethylguanidino)benzol (LI) und 1,2,4,5-Tetrakis(N,N’-dimethyl- N,N’-ethylenguanidino)benzol (LII), sowie das am aromatischen Rückgrat funktionalisierten Derivat 1,2,4,5- Tetrakis(N,N,N’,N’-tetramethylguanidino)-3,6-diiodbenzol (LIa) zur Verfügung. Bei den verwendeten GFA-Verbindungen handelt es sich um starke Elektronendonoren und redoxaktive Liganden mit einer großen Affinität zu späten Übergangsmetallen wie Kupfer und Silber. Dadurch ergibt sich die Möglichkeit durch den Einsatz von Kupfer(II)-Salzen Elektronentransferserien aufzustellen und zu charakterisieren. Dabei wurden in dieser Arbeit Komplexe mit der allgemeinen Grundform [CuII | (GFA) |CuII] und [CuII | (GFA)·+ | CuII], [CuII | (GFA)2+ | CuII] hergestellt. Besonders interessant ist hierbei der Komplex [(LI)(Cu(OAc)2)2], der durch geeignete Wahl des Oxidationsmittels gezielt in Komplexverbindungen in denen LI als Radikalkation bzw. als Dikation vorliegt, umgesetzt werden kann. Die magnetische Suszeptiblität der erhaltenen dinuklearen Kupfer(II)-Komplexe wurde mit Hilfe eine SQUID-Magnetometers ausführlich untersucht und dabei in allen Komplexen eine schwache antiferromagnetische Kopplung zwischen den beiden Kupfer(II)- Zentren festgestellt. Bei Komplexen vom Typ [CuII | (GFA)·+ |CuII] wurde zusätzlich eine starke ferromagnetische Kopplung zwischen dem Kupferzentrum und dem GFA-Liganden festgestellt. Durch den Einsatz von Silber(I)-Salzen können Komplexe mit der allgemeinen Grundform [AgI | (GFA) |AgI] und [AgI | (GFA)2+ |AgI] erhalten werden. Dabei zeigen die Komplexe mit einem ungeladenen GFA-Liganden eine trigonal-planare Koordinationsgeometrie, während Komplexe vom Typ [AgI | (GFA)2+ |AgI] eine tetraedrische Koordinationsgeometrie aufweisen. Eine Ausnahme bildet hierbei der bei der Reaktion von LI mit Ag(tfa) (tfa = Trifluoracetat, CF3COO) entstandene Komplex [(LI)(Ag(tfa)3Ag(CH3CN))2] in dem jeweils zwei Silberatome über tfa– verbrückend koordiniert werden. Somit stellt diese Verbindung eine mögliche Vorstufe für die Ausbildung eines 1-D Koordinationspolymers dar. Der Einsatz von Silber(I)-Salzen mit den schwachkoordinierenden Anionen BF–4 und PF–6 führt zur Ausbildung von linearen Ketten vom allgemeinen Typ [AgI | (GFA)2+]n, in denen die GFA-Einheiten als LI2+ direkt über die Silber(I)-Atome miteinander verknüpft sind. Eine Untersuchung der Leitungseigenschaften des Koordinationspolymers {[(LI)Ag](PF6)3}n zeigte, dass es sich bei Verbindungen diesen Typs um einen klassischen Halbleiter handelt, wobei die Bandlücke des Koordinationspolymers auf etwa 3 eV abgeschätzt werden kann. Ebenso konnten mit den Silber(I)-Salzen Ag(ECO) (ECO = Ethyl-cyanoglyoxalat-2- oxim, C5H6N2O3) und AgNO3 weitere ein- bzw. zweidimensionale Koordinationspolymere erhalten werden.
The synthesis of commercially relevant organic carbonates from CO2 can contribute to a sustainable utilization of this greenhouse gas. The catalytically controlled reaction with epoxides leads to the production of cyclic carbonates and aliphatic polycarbonates. In this work, we succeeded in finding innovative homogeneous catalysts for this task. The foundation was a very variable ligand system closely related to the salen compounds with an N2O2 framework, that was converted with the metals iron, zinc and aluminum to the corresponding metal complexes. The various combinations of ligand and metal yielded 66 different potential catalysts, of which some structures were investigated via x-ray structure analysis. High-pressure experiments were carried out to test the catalysts’ performance, allowing some insights in the relationship between structure and catalytic activity. The conversions were documented by means of the test substrates propylene oxide and cyclohexene oxide. Additionally a wider range of epoxides has been tested in some promising cases.
One result is, that the control of the product spectrum via selection of the optimal epoxide-catalyst-combination is possible. The most active iron(III) catalyst was able to produce quantitative yields of propylene carbonate from propylene oxide without the addition of a cocatalyst. With the zinc catalysts the same result was possible, also under mild reaction conditions (40 ◦C, 2 bar CO2, cocatalyst Bu4NI). However, the aluminum catalysts were suitable for the quantitative conversion of cyclohexene oxide to fully alternating polycarbonates.
Another important finding is, that the contributing nucleophiles in the reaction have a decisive influence on the formation of the product, regardless if they came from the catalyst itself or from a cocatalyst. While the more nucleophile and according to the HSAB-concept softer iodide anion ismore suitable for the synthesis of cyclic carbonates, the anions bromide and chloride are rather successful in the synthesis of polycarbonates.
By the analysis of the many catalytic test results and additional kinetic measurements via in situ FT-IR spectroscopy, it was possible to postulate mechanisms for the different new catalysts of this work.
Surface patterning is important in a wide spectrum of applications ranging from microelectronics, sensors design and material science to high throughput screening, tissue engineering and cell biology. A number of methods for specific patterning applications, such as photolithography, soft lithography, or electron beam and dip-pen nanolithography, have been developed. However, there is still a clear need for the development of novel methods permitting patterning of different cell types, nano- and microparticles as well as hydrogels incorporating cells. These novel patterning methods are vital for the advancement of such research fields as tissue engineering, biomaterials and for fundamental investigation of cell-cell communication, tissue and organ development. The aims of this PhD thesis were: a) develop a technique for creating droplets of liquid with defined geometries that can be used for patterning water soluble components; b) optimize the conditions for the fabrication of porous polymer surfaces for the liquid patterning; c) characterize the produced patterned polymer surfaces; d) further develop the technique for maskless generation of liquid patterns with arbitrary geometry; e) optimize the method for the patterning of different materials (chemicals, hydrogels, microparticles); f) show an application of the method for patterning of living cells and characterize their behavior on the composite surface during cultivation; g) show an application of the technology to mimic natural cell-cell communication in vitro via signaling protein propagation between patterned cell populations in co-culture. The first part of the work was devoted to the development of porous polymer layers with precise micropatterns of hydrophilic and hydrophobic areas. In order to fabricate these patterns, UV-initiated photografting of 2,2,3,3,3-pentafluoropropyl methacrylate (PFPMA) on porous poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) (HEMA-EDMA) was optimized. Before and after photografting, both polymer substrates were thoroughly characterized using water contact angle measurement, UV-Vis spectroscopy, scanning electron microscopy (SEM) and time of flight secondary ion mass spectrometry (ToF-SIMS). Porous properties were characterized by UV-Vis spectroscopy, SEM and dynamic light scattering techniques (DLS). Due to the high difference in wettability of the hydrophilic HEMA-EDMA polymer film and hydrophobic regions coated with PFPMA polymer brushes, aqueous solutions can be trapped in the hydrophilic areas, taking the shape of these areas. The transparency of the HEMA-EDMA monolith originated from porous properties of the polymer makes it suitable for microscopic monitoring of liquid patterns during experiments. The method was for the first time applied for the simultaneous micropatterning of multiple cell types. More than ten different cell populations separated by hydrophobic borders could be cultured in microreservoirs. After adhesion, the cells could be placed in the mutual culture medium, allowing cell-cell communication among populations. During 3 days co-culture in the mutual medium, cross-contamination was shown to be less than 1,5%, although the cells were pre-patterned in the hydrophilic areas separated by hydrophobic borders of only two to three cell diameters. The capability of cell patterning and long term cultivation opens the way for many interesting bio-applications, such as in vitro mimicking important biological processes that involve and depend on the organization of multiple cell types into complex micropatterns in vivo. As a case study, I together with Dr. Steffen Scholpp and Dipl. Eliana Stanganello (ITG, KIT) used the developed technique to visualize spreading of signaling molecules (Wnt protein) from one micropatterned population of fibroblast cells to another fibroblast population by activation of the reporter system. Thus, we were able to simulate paracrine signaling system in vitro. In addition, I further developed our technique into a new type of mask-less liquid patterning or digital liquid patterning (DLP) method. The idea of this method is similar to the working principle of a digital score board. A digital score board consists of many small bulbs, which generate light symbols on it. In the case of DLP, instead of the bulbs, small liquid droplets (digits) form a more complex liquid pattern on a substrate. The substrate for DLP is a composite surface, consisting of a grid of hydrophilic HEMA-EDMA spots divided by hydrophobic PFPMA barriers. The method allows on-demand fabrication of liquid patterns without the need to change the substrate and use an additional photomask. Patterns with customized geometries can be prepared manually by simply pipetting liquid inside the spots and successively coalescing the generated droplets to form a liquid micropattern. The DLP does not require clean room or high-precision microfabrication and allows the manual positioning of microdroplets in the range of micrometer scale. It was also shown that using superhydrophilic/superhydrophobic patterned surfaces leads to spontaneous dewetting of the coalesced microdroplets on the interface of the superhydrophobic border and the superhydrophilic spot. Hence, the usage of hydrophilic/hydrophobic patterned surface ensures the stability of liquid patterns during manipulations. Furthermore, the developed technique enables patterning of not only solutions, e.g. different chemicals, but also suspensions of living cells and microparticles, hydrogels, or formation of liquid multi-component gradients with complex geometries. Thus, this method will be especially useful for biological studies, which require the generation of complex patterns of different or the same cell types, or bioactive materials and cellular gradients without the need for sophisticated microfluidic and printing equipment, or for designing additional masks
Die vorliegende Dissertation befasst sich mit der Synthese und Charakterisierung des neuen Guanidinyl-funktionalisierten Aromaten (GFA-4) 2,3,5,6-Tetrakis(N,N,N´,N´-tetramethylguanidinyl)pyridin (ttmgp) sowie dessen Koordinationschemie, die Funktionalisierung am Pyridinstickstoffatom und die daraus resultierende Photochemie. Bei ttmgp handelt es sich um eine starke Stickstoffbase, deren pK(BH+)-Wert (24.6 in CH3CN) mit Hilfe quantenchemischer Rechnungen bestimmt werden konnte. Die Untersuchung des Redoxverhaltens erfolgte sowohl durch Cyclovoltammetrie als auch mit chemischen Oxidationsmitteln. Das Halbstufenpotential des reversiblen Zweielektronenübergangs bezogen auf das Redoxpaar Fc/Fc+ liegt bei -0.75 V, und ein weiterer reversibler Einelektronenübergang tritt bei +0.86 V auf. Infolge der chemischen Oxidation mit Iod oder Brom trat eine Substitution des aromatischen Protons auf und die Aromatizität des Pyridinrückgrats wurde aufgehoben. Die erhaltenen Produkte können am besten als zwei Bisguanidinylallyl-Einheiten beschrieben werden, welche durch zwei C-C-Einfachbindungen verknüpft sind. Die Umsetzung mit Cu(I)- und Ag(I)-Salzen führte zur Bildung zweikerniger Koordinationsverbindungen, welche vollständig charakterisiert werden konnten und hinsichtlich ihres Redoxverhaltens untersucht wurden. Mit Hilfe mehrerer Alkylhalogenide und -triflate wurde ttmgp zu den entsprechenden N-Alkylpyridiniumsalzen umgesetzt, was eine deutliche Verringerung des HOMO-LUMO-Abstandes von 4.3 eV (ttmgp) zu 3.4 eV (ttmgpMe+), 3.5 eV (ttmgpBn+) (Bn = CH2Ph) und 3.4 eV (ttmgpAllyl+) zur Folge hat. Die Bestrahlung einer intensiv gelben Lösung von (ttmgpBn)Br mit einer Quecksilberdampflampe führte zu einem raschen Farbumschlag nach rot, wobei mittels GC/MS-Untersuchungen 1,2 Diphenylethan als C-C-Kupplungsprodukt nachgewiesen werden konnte. Quantenchemische Rechnungen zeigten, dass die Guanidinylsubstituenten das Pyridinrückgrat zu einem starken Elektronendonor machen, was zu einer deutlichen Schwächung der N-C-Bindung im Vergleich zu freiem Pyridin führt. Die Reaktion verläuft über radikalische Zwischenstufen, wobei der homolytische N-C-Bindungsbruch den geschwindigkeitsbestimmenden Schritt (k = 0.23 +- 0.03 s-1) darstellt. Während die analoge Bestrahlung einer Lösung von (ttmgpAllyl)Br zu einer raschen Bildung des Kupplungsprodukts 1,5 Hexadien führt, läuft die Reaktion mit (ttmgpMe)I deutlich langsamer ab. Wird der Reaktionslösung ein weiteres Äquivalent Alkylhalogenid zugesetzt, so lässt sich eine Ausbeute des Photo-Kupplungsprodukts von bis zu 60 % erreichen.
Noble gas isotope composition (especially helium) in thermal waters from different areas along the Dead Sea Transform in Israel reveals local intrusions of volatile gases and heat flux from the mantle into the crust. The distinct 3He/4He ratios in the atmosphere, crust and mantle enable one to separate the total helium concentration into mantle, crustal and atmospheric components. Helium isotope ratios of all sampled waters exceed the typical crustal ratio, indicating contributions of mantle derived helium to the total helium concentration. A clear trend can be observed in 3He/4He ratios from different areas. Northern samples show higher 3He/4He ratios than southern ones. Noble gas temperatures (NGTs) were used to determine the atmospheric helium component. Most of the samples contain less than 3% atmospheric helium, whereas the mantle derived helium component ranges from 2% to 38%. In addition to helium, the origin of CO2 in the water is examined. Measurements of 13C indicate no mantle derived CO2. Furthermore, stable isotopes data (18O and 2H) show no evidence of mantle derived water or water from reservoirs exceeding 100°C.
Um Verbrennungsmotoren emissionsreduziert zu betreiben, eird eine umfangreiche Abgassensorik benötigt, mit der neben Sauerstoff und Kohlenwasserstoffen auch Stickoxide erfasst werden können. Ein vergleichsweise neuer Ansatz ist hierbei der Einsatz von chemisch funktionalisierten Feldeffekttransitoren (kurz ChemFETs) im heißen Abgas. Bei diesen sind für die Messung von wasserstoffhaltigen Gasen die grundlegenden Mechanismen hinlänglich verstanden. Mittlerweile ist es gelungen, auch NOx-sensitive Feldeffekttransitoren herzustellen, allerdings existiert bislang noch kein belastbares Modell dafür, wodurch hierbei das elektrische ChemFET-Signal hervorgebracht wird. Im Zuge der vorliegenden Arbeit wurden mögliche signalgebende Mechanismen für die Verwendung eines ChemFETs als Stickoxidsensor untersucht. Die Ergebnisse dienen der Entwicklung eines umfassenden Modells für den Signalbildungsmechanismus. So sollte ein tieferes Verständnis für die auf der nanoporösen, katalytischen Gateelektrode ablaufenden Oberflächenprozesse erlangt und die für die Signalgebung besonders ausschlaggebenden Bereiche identifiziert werden. Zu diesem Zweck wurden neben mit einer Finite-Elemente-Methode durchgeführten Simulationen umfangreiche spektroskopische in situ-Oberflächenanalysen durchgeführt. Als Hauptmethode diente die polarisationsmodulierte Infrarot-Reflektions-Absorptions-Spektroskopie (PM-IRRAS). Hierfür wurden ein spezieller Messaufbau konzipiert und geeignete Proben hergestellt, die mit zusätzlichen Methoden wie Rasterelektronenmikroskopie(REM) und Röntgen-Photoelektronen-Spektroskopie (XPS) analysiert wurden. Mittels PM-IRRAS ließen sich einzelne Adsorbatzustände von CO und NO auf verschiedenen Platin- und Rhodium-haltigen Oberflächen identifizieren und deren zeitliche Entwicklung beobachten. Die Analyse der Adsorbatzustände und der gasförmigen Reaktionsprodukte zwischen Raumtemperatur und 350°C lieferten Einblicke in die von der Gasumgebung abhängig wechselnden Oberflächenregime. Zudem wurde der nichtresonante Schwingungsuntergrund ausgewertet. Es wurde dabei gezeigt, dass dieser Rückschlüsse auf den Oxidationsgrad einer Probenoberfläche ermöglicht. Diese hier phänomenologisch als PM-IRRAS-Offset bezeichnete Messgröße zeigte eine starke Korrelation mit der Gatespannung von zeitgleich in derselben Messapparatur gemessenen, identisch beschichteten ChemFETs. Aus den gewonnenen Erkenntnissen wurde das Schema eines Signalbildungsmodells abgeleitet, das neben atomarem Wasserstoff auch atomaren Sauerstoff als signalgebende Spezies beinhaltet. Die wesentliche Signalbildung findet durch Anlagerung dieser Spezies an bzw. in der Oberfläche des Gatedielektrikums und besonders im Bereich der Dreiphasengrenzen zwischen Dielektrikum, Katalysator und Gasphase statt. Stickoxide wirken hierbei im Wesentlichen auf dem indirekten Weg der Bereitstellung bzw. des Verbrauchs von atomarem Sauerstoff bzw. Wasserstoff. Somit konnte gezeigt werden, dass die NOx-Sensitivität der betrachteten ChemFETs ein mehrstufiger Prozess mit atomarem Sauerstoff als Signalgeber ist.
Bei der Entwicklung innovativer Brennstoffkreisläufe spielt die Trennung von Actiniden und Lanthaniden eine wichtige Rolle. Diese Trennung ist aufgrund der großen Ähnlichkeit der chemischen Eigenschaften und der Ionenradien von trivalenten Actiniden und Lanthaniden sehr anspruchsvoll, kann aber beispielsweise durch Flüssig-Flüssig-Extraktion mit hoch-selektiven Extraktionsmitteln erreicht werden. Es hat sich gezeigt, dass eine ausreichende Selektivität nur mit Stickstoff- oder Schwefeldonor-Liganden möglich ist. In der vorliegenden Dissertation wurde die Komplexierung von Cm(III) und Eu(III) mit verschiedenen partitioning-relevanten N-Donor-Liganden mittels zeitaufgelöster Laser¬fluoreszenzspektroskopie (TRLFS) untersucht. Ziel dieser Arbeiten ist ein besseres Verständnis für die molekularen Ursachen der Selektivität dieser Liganden. In diesem Zusammenhang werden in zahlreichen nationalen und internationalen Projekten zum einen detaillierte Untersuchungen von BTP- und BTBP-Liganden, welche zu den erfolgreichsten N-Donor-Liganden für die selektive Extraktion trivalenter Actinide zählen, durchgeführt und zum anderen werden Moleküle, die strukturell von diesen Liganden abgeleitet sind, auf ihre Extraktions- und Komplexierungseigenschaften hin untersucht. So wurden beispielsweise bei dem in dieser Arbeit untersuchten C5-BPP-Liganden (2,6-Bis(5-(2,2-dimethylpropyl)-1H-pyrazol-3-yl)pyridin) die Triazinringe des BTP-Grundgerüsts durch Pyrazolylringe ersetzt. Bei der Untersuchung der Komplexierung von Cm(III) mit C5 BPP wurde die Bildung von drei (Cm(C5-BPP)n)3+-Komplexen (n = 1 ‒ 3) beobachtet. Die aus den spektroskopischen Daten bestimmte Stabilitätskonstante des 1:3 Komplexes beträgt log β3 = 14.8 ± 0.4. Aus Extraktionsexperimenten mit C5-BPP ist bekannt, dass dieser Ligand für die selektive Extraktion von trivalenten Actiniden aus salpetersauren Lösungen ein zusätzliches lipophiles Anion benötigt. Eine mögliche Erklärung für die Notwendigkeit dieses lipophilen Anions liefert der Vergleich der Stabilitätskonstanten des (Cm(C5-BPP)3)3+-Komplexes mit der Stabilitäts¬konstanten des (Cm(nPr-BTP)3)3+-Komplexes. Wie im Rahmen dieser Arbeit gezeigt werden konnte, liegt die Stabilitätskonstante des 1:3-Komplexes mit nPr-BTP bei vergleichbaren Bedingungen mehr als 3.5 Größenordnungen über der des 1:3-Komplexes mit C5-BPP. Die deutlich schwächeren Komplexierungseigenschaften sind offenbar die Ursache, warum C5 BPP, im Gegensatz zu nPr-BTP, nicht in der Lage ist trivalente Actinide als Nitrate aus salpetersaurer Lösung zu extrahieren. Um ein besseres Verständnis der Funktion des lipophilen Anions zu erlangen, wurden auch Komplexierungsstudien in Anwesenheit von 2 Bromhexansäure durchgeführt. Der Vergleich der Fluoreszenzspektren der Komplexspezies, die dabei mit steigender C5-BPP-Konzentration auftraten, mit jenen, die in Abwesenheit des lipophilen Anions beobachtet wurden, zeigt, dass 2 Bromhexanoationen an das Cm(III)-Ion koordinieren, diese aber bei höheren C5-BPP-Konzentrationen durch den N Donor-Liganden verdrängt werden. Infolge der Konkurrenz des lipophilen Anions als Liganden für das Metallion ist die Stabilitäts¬konstante des (Cm(C5-BPP)3)3+-Komplexes mit log β3 = 13.3 ± 0.4 in Anwesenheit der 2 Bromhexansäure etwas niedriger als im System ohne zusätzliches lipophiles Anion. Basierend auf den Ergebnissen der einphasigen Experimente konnte die Zusammensetzung der Komplexspezies, die nach einer Extraktion in der organischen Phase vorliegt, bestimmt werden. Die laserfluoreszenz¬spektroskopische Untersuchung der organischen Phase eines Cm(III)-Extraktionsexperiments hat gezeigt, dass auch in diesem Komplex drei C5-BPP-Moleküle an das Metallion koordiniert sind und sich die für die Ladungsneutralität benötigten 2-Bromcarbonsäureanionen in einer äußeren Koordinations¬sphäre befinden. Da die Zusammensetzung der Koordinationssphäre des Metallions aufgrund assoziativer Wechselwirkungen der Ligandmoleküle in der organischen Phase nicht durch eine Steigungsanalyse der Daten aus Extraktionsexperimenten bestimmt werden konnte, leisten die TRLFS-Untersuchungen einen wichtigen Beitrag zum Verständnis der Funktion des zusätzlichen lipophilen Anions. Zwei weitere Liganden, die im Rahmen der vorliegenden Arbeit untersucht wurden, sind der CyMe4 BTBP-Ligand (6,6‘-Bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-benzo-1,2,4-triazin-3-yl)-2,2‘-bipyridin), welcher das derzeitige europäische Referenzmolekül für die selektive Extraktion trivalenter Actiniden darstellt, sowie der CyMe4 BTPhen-Ligand (2,9 Bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-benzo-1,2,4-triazin-3-yl)-1,10-phenanthrolin), der eine Weiter¬entwicklung des CyMe4 BTBP-Liganden darstellt. Dabei wurde die Bipyridineinheit durch eine Phenanthrolin¬einheit ersetzt, so dass die für die tetradentate Koordination an ein Metallion notwendige cis-Konformation durch die Molekülstruktur vorgegeben ist. Es konnte gezeigt werden, dass diese Präorganisation des Liganden einen positiven Einfluss auf das Komplexierungsverhalten hat. Die Stabilitätskonstanten der Cm(III)- und Eu(III)-CyMe4-BTPhen 1:2-Komplexe sind größer als die der jeweiligen CyMe4-BTBP-Komplexe [Cm(III)-CyMe4-BTPhen: log β2 = 13.8 ± 0.2; Eu(III)-CyMe4-BTPhen: log β2 = 11.6 ± 0.2; Cm(III)-CyMe4-BTBP: log β2 = 12.4 ± 0.2; Eu(III)-CyMe4-BTBP: log β2 = 11.3 ± 0.2]. In Überein-stimmung mit literaturbekannten Extraktionsdaten ist die Differenz zwischen den für Cm(III) und Eu(III) bestimmten Werten für den CyMe4-BTPhen-Liganden größer als für den CyMe4-BTBP Liganden. Somit konnte gezeigt werden, dass die Präorganisation des Liganden neben den Komplexierungseigenschaften auch die Selektivität verbessert und somit ein wichtiger Faktor ist, der im Hinblick auf die Weiterentwicklung der Extraktionsliganden berücksichtigt werden muss. Obwohl bekannt ist, dass die Speziation von An(III)- und Ln(III)-BTP-Komplexen vom verwendeten Lösungsmittel abhängt, gab es bisher keine systematischen Studien zu diesen Lösungsmitteleffekten. Da die Untersuchungen der Komplexierungseigenschaften von N-Donor-Liganden häufig in verschiedenen Lösungsmitteln durchgeführt werden, ist eine genaue Kenntnis dieser Abhängigkeit jedoch unumgänglich, um die Komplexierungseigenschaften der Liganden vergleichen zu können. Daher wurden in dieser Arbeit der Einfluss des Wassergehalts in Alkohol/Wasser-Gemischen sowie der Einfluss des verwendeten Alkohols auf die Komplexierung von Cm(III) und Eu(III) mit nPr-BTP (2,6-Bis(5,6-dipropyl-1,2,4-triazin-3-yl)pyridin) untersucht. Dabei hat sich gezeigt, dass der Einfluss des Wassergehalts enorm ist. Im Methanol/Wasser-System nimmt die Stabilitätskonstante des (Cm(nPr-BTP)3)3+-Komplexes beim Übergang von einem Gemisch mit 50 Vol.-% Wasser zu einem Gemisch mit 5 Vol.-% Wasser um 3.5 Größenordnungen zu. Die gleiche Abhängigkeit wurde auch für die Stabilitätskonstante des (Eu(nPr-BTP)3)3+-Komplexes beobachtet. Die Stabilitätskonstanten steigen dabei mit abnehmendem Wassergehalt erst geringfügig und bei geringem Wasseranteil (< 20 %) sehr stark an. Die Zunahme an sich ist mit der schwächeren Koordination von Methanolmolekülen an die Metallionen im Vergleich zu Wassermolekülen zu erklären. Der Verlauf ergibt sich durch die Vorzugssolvatation der Metallionen durch Wasser, das heißt durch die abweichende Zusammensetzung der Solvathülle im Vergleich zu der Zusammensetzung im Lösungsmittelreservoir. Bei der Untersuchung der Komplexierung von Cm(III) mit nPr-BTP in 2-Propanol/Wasser-Gemischen hat sich gezeigt, dass die Stabilitätskonstanten bei der Reduzierung des Wasser-gehalts im Lösungsmittelgemisch von 50 Vol.-% auf 5 Vol.-% sogar um 5 Größenordnungen zunimmt. Der Vergleich beider Alkohol/Wasser-Systeme ergab, dass sich der unterschiedliche Verlauf durch die Überlagerung verschiedener Effekte ergibt. Neben der unter¬schiedlich stark ausgeprägten Vorzugssolvatation der Metallionen durch Wasser in verschiedenen Alkohol/Wasser-Gemischen und der unterschiedlichen Koordinationsstärke der Alkohole spielt auch ein Wechsel in der Triebkraft der Komplexierung (enthalpie- zu entropiegetrieben) eine wichtige Rolle. Aufgrund dieses komplexen Zusammenwirkens verschiedener Faktoren und des in dieser Arbeit nachgewiesenen sehr starken Einflusses des Lösungsmittels ist die Verwendung des gleichen Lösungsmittelgemisches bei den Untersuchungen von zu vergleichenden Liganden unbedingt empfehlenswert. Ist dies beispielsweise aus Gründen der Löslichkeit nicht möglich, können die in dieser Arbeit durchgeführten systematischen Untersuchungen als Grundlage für eine Abschätzung von Daten für eine Gegenüberstellung der Komplexierungseigenschaften von verschiedenen N-Donor-Liganden bei vergleichbaren Bedingungen dienen.
Die vorliegende Arbeit untersucht die Möglichkeiten gaschromatographischer Anreicherung von Tritium zur Messung von Low-Level-Proben. Es konnte ein trägergasfreies Verfahren entwickelt werden, das aus einer Kombination von Frontalanalyse und Verdrängungsentwicklung besteht. Es ist einfach zu handhaben, aber genauso effektiv wie kompliziertere bisherige Verfahren mit Trägergas (Kapitel 2). Verbesserungen im Kolonnenbau machen größere Anreicherungsfaktoren möglich. Durch eine optimalere Wahl der Adsorber und den Übergang zu tieferen Temperaturen (63,2°K, Sieden von flüssigem Stickstoff unter vermindertem Druck) läßt sich die vierfache Menge an Wasserstoff im gleichen Volumen anreichern wie mit den bisherigen gaschromatographischenVerfahren. Das gaschromatographische Verfahren ist gegenüber dem Trennrohr schneller und platzsparender: eine 20 Nl Wasserstoffprobe läßt sich in weniger als 2 Stunden in einer 0,3 1 Kolonne bei 63,2°K auf 1,3 Nl mit mehr als 99,0% Tritiumausbeute einengen. Auch größere Mengen H2 lassen sich verarbeiten, sodaß der bisherige Anreicherungsweg für Low-Level-Tritiumproben weiter vereinfacht werden kann (Kapitel 7). Breiten Raum nehmen grundlegende Untersuchungen ein, die erst eine optimale Parameterwahl ermöglicht haben. Im Kapitel 4 werden Grundlagen der Adsorption beschrieben und die Adsorber auf ihre Adsorptionskapazitäten verglichen, die Theorie der Adsorption selbst findet sich in Anhang A2, die Meßverfahren in Anhang A1. Die Untersuchung der Trennfaktoren der Adsorption ist Gegenstand von Kapitel 5. Da für HT geeignete Trennfaktoren in der Literatur fehlen, wurden sowohl eigene Messungen unternommen, als auch versucht mit 3 Adsorptionsmodellen die Beziehung der Trennfaktoren untereinander (logarithmische Verhältnisse, Bigeleisenfaktoren) theoretisch zu berechnen (Kapitel 5, Anhang A3). Dabei ergab sich, daß Isotopentrennfaktoren einschließlich der Ortho-Para-Trennung (Kapitel 3) ein geeignetes Mittel sind, zwischen verschiedenen Vorstellungen über die Adsorption zu unterscheiden, was mit Isothermenmessungen nur schwer möglich ist (Anhang A2). Das Modell einer mobilen Adsorption der H -Moleküle mit einer weitgehenden Störung der Rotation in einer Ebene senkrecht zur Oberfläche entspricht den Messergebnissen am besten.
In the present work the complexation of Cm(III) and Eu(III) with a hydrophilic 2,6-bis-(1,2,4-triazinyl)-pyridine (aq-BTP) is studied. Aq-BTP complexes actinides(III) selectively over lanthanides(III) in nitric acid solution. The object of this work is the identification and the spectroscopic and thermodynamic characterization of the Cm(III) and Eu(III) complex species present in solution. The results should contribute to a better fundamental understanding of the driving force behind BTPs selectivity towards trivalent actinides on a molecular level. Time-resolved laser fluorescence spectroscopy (TRLFS), luminescence and UV/Vis spectroscopy are applied. Information on the structure of M(III)-aq-BTP complex species is obtained from density functional theory. Three different M(III) complex species containing one, two or three aq-BTP ligands are identified in H2O at pH 3.0. Relative fluorescence intensity factors are determined for each of the [M(aq-BTP)n] complexes (M = Cm(III)/Eu(III), n = 1 – 3). These factors are required to quantify the complexes. The stability constant logβ3 of the [Cm(aq-BTP)3] complex (which is the one relevant to extraction processes) is two orders of magnitude higher than that of the corresponding Eu(III) complex. This difference is in agreement with the separation factor (SF Am(III)/Eu(III) = 150) determined experimentally by liquid-liquid extraction. The difference in the stability constants originates from the different reaction enthalpies for the formation of the [M(aq-BTP)3] complexes. These results represent the thermodynamic driving force for the aq-BTPs selectivity towards trivalent actinides over lanthanides. Comparing the stability constants of the [M(aq-BTP)n] species (M = Cm(III)/Eu(III), n = 1 – 3) shows an increasing selectivity with increasing number of coordinated aq-BTP ligands. Hence, high selectivity is achieved if the f-element ions are fully coordinated by nine N-donor atoms (three aq-BTP ligands). A less polar solvent (i-PrOH:H2O 1:1) results in a destabilization of the highly charged [M(aq-BTP)3] complexes (z = −9), while a more polar solvent (0.1 M NaClO4, pH 3.0) stabilizes these species. However, the solvent does not change the selectivity (∆logβ3 = 2.1, 0.1 M NaClO4, pH 3.0). In the separation process the trivalent lanthanides are extracted from the trivalent actinides from aqueous solution with 0.5 M nitric acid. Hence, the complexation of Cm(III) and Eu(III) with aq-BTP was studied in HNO3. In contrast to the complexation in H2O at pH 3.0, the [M(aq-BTP)3] complex is directly formed under acidic conditions; the M(III) complexes with one and two aq-BTP ligands are suppressed. The selectivity (∆logβ3 = 2.1) is almost identical to the values found in H2O (pH 3.0), in 0.1 M NaClO4 (pH 3.0) and in extraction studies. As already shown in H2O at pH 3.0, this difference is attributed to a difference in the reaction enthalpy of the complex formation. Comparing stability constants determined in 0.5 M HClO4 and in 0.5 M HNO3 shows no influence of the counter ion (ClO−4 , NO−3 ) on aq-BTPs selectivity. However, a significant influence on the spectroscopic properties of the [M(aq-BTP)3] complexes is found; e.g., the fluorescence intensity of the [Eu(aq-BTP)3] complex is by a factor of four higher in 0.5 M HClO4 as compared to 0.5 M HNO3. This originates from different interactions between the anions in the outer coordination sphere and the coordinated aq-BTP ligands. Thereby, it is shown that the difference in the fluorescence intensity correlates with the experimentally determined quantum yield of [Eu(aq-BTP)3] . Another important aim of the work is the investigation of the [M(aq-BTP)n ] (M = Cm(III)/Eu(III), n = 1 – 3) complex structure and bonding. The [Eu(aq-BTP)n] complexes 5D0→7F0 emission band position and the corresponding structural composition of the first Eu(III) coordination sphere are correlated. According to this correlation, the solution coordination structure of Eu(III) complexes coordinated with varying N-heteroaromatic ligands can easily be predicted. The nephelauxetic parameters which were determined in this context indicate a higher covalent degree in the Eu(III)-N(triazine)-bonds in comparison to the Eu(III)-N(pyridine)-bond. Furthermore, the bond lengths between f-element ion and donor nitrogen atoms were calculated by density functional theory and compared to the literature values of hydrophobic [M(n-Pr-BTP)3]3+and [M(H-BTP)3]3+ complexes. The calculated bond lengths between the f-ion and the pyridine nitrogens are in agreement with the literature. However, the distance between the f-ion and the triazine nitrogen is 5 pm longer than the M(III)-N(triazine) distance of [M(H-BTP)3]3+. This is a consequence of the sterically demanding sulfophenyl substituent of aq-BTP and/or the electrostatic repulsion of the negatively charged -SO−3 group. The comprehensive thermodynamic and spectroscopic investigations of the present work contribute to a better molecular understanding of the coordination chemistry of trivalent 4f- and 5f-element ions and hydrophilic bis-triazinylpyridine ligands under conditions relevant to a process. The determined thermodynamic and spectroscopic data are of major importance for the future intelligent design of improved extraction systems and for process optimization.
Phosphorescent OLEDs (PHOLEDs) based on organic small molecules offer a great potential for a variety of future applications. In terms of efficiency PHOLEDs can already compete with conventional light sources. However, PHOLEDs typically suffer from a steady decrease in efficiency at high current densities, known as efficiency roll-off. One of the reasons for this is the high probability for triplet-triplet quenching processes. On the one hand these processes happen due to the long lifetime of the triplet phosphors and on the other hand due to the high triplet density in the rather narrow recombination zone in common OLED heterostructures. One approach to minimize this roll-off is to introduce a mixed host structure in the light emitting layer. This is done by mixing one mostly hole-transporting material and one mostly electron-transporting material with each other.
In the first part of this thesis, the characteristics of PHOLEDs with a conventional heterostructure, a uniformly mixed host structure and a graded mixed host structure were studied in detail. PHOLEDs with a graded mixed structure showed an increased quantum efficiency, a reduced efficiency roll-off and a longer lifetime compared to them with conventional heterostructure. These effects are attributed to the broadening of the recombination zone and a better charge balance inside the light emitting layer.
Existing techniques for the detection of intermixing are very expensive and time consuming. In the second part of this thesis, it was tested whether impedance spectroscopy can be used as a suitable and cheap tool to measure the degree of intermixing between two layers. Measurements of the single materials were made to extract their characteristic parameters. Two fit functions were formulated and applied to measurements of devices with different degrees of intermixing. One of the fit functions was able to identify intermixing for all tested devices very well.
Processes initiated by photoexcitation play an important role in many biological systems as well as in technical applications. A whole variety of quantum chemical methods for the treatment of such excited states has been developed over the past years. However, many are either restricted to small or medium-sized systems or only applicable to certain types of electronic excitations. Therefore, the development of efficient quantum chemical excited states methods is one of the central aspects of modern theoretical chemistry.
In this work, different excited state approaches within the algebraic diagrammatic construction (ADC) family of methods were derived and implemented. First, the scaled-opposite spin approximation was used to develop a variant of the extended ADC(2) methods that allows for an improved treatment of doubly excited states at reduced computational cost. Additionally, the generation of spin-orbit coupling elements based on an atomic mean-field approach was implemented for the whole hierarchy of ADC methods up to third order. Test calculations and comparison with existing methods revealed very good results. Last but not least, a scaling approach for the identification of plasmons in molecules previously introduced for TDDFT has been adopted to the ADC methods. Such plasmons are of great importance in the field of organic electronics. Here, the scaling approach was shown to work efficiently for a series of linear polyenes. All three theoretical methods were implemented in a development version of the adcman module of the Q-Chem program package. Thereby, the functionality of this module has been further extended making it applicable to a wider range of molecular systems and photochemical problems. Finally, ADC methods were used in combination with experimental results to successfully unravel the photochemical relaxation network of coumarin derivatives which turned out to incorporate two parallel radiationless relaxation pathways.
Marine biofouling, associated with the accumulation of marine colonizers on submerged surfaces, has been a longstanding problem. Among different surface properties, cell substrate interaction is strongly influenced by surface topographies. Therefore, in this work responses of representative marine fouling species were investigated in relation to different topographies. The settlement of zoospores of Ulva linza was explored on a hot-embossed honeycomb gradient. The highest settlement was found on microstructures with a similar or larger size than spores. Spore settlement density correlated with the Wenzel roughness of the topographies and ‘kink sites’ resembled preferred attachment positions. Following the gradient study, different settlements of cells of Navicula incerta, Ulva zoospores, and cyprids of B. improvisus were observed on soft-casted discrete honeycombs with the feature size as the only variable. The correlation between the ‘attachment point theory’ and the diatom attachment was in line with the literature. Settlement of spores deviated from the guideline of Wenzel roughness mainly due to the gregarious settlement on PDMS substrates, while the settlement of cyprids could be correlated with both Wenzel roughness and the interaction between sensory structures and comparably sized microtopographies. Furthermore, tapered microstructures with different feature spacings and aspect ratios were prepared via hot embossing and hot pulling to avoid unfavorable corners and to minimize the surface contact area. Topographic preferences of Navicula diatoms and Ulva spores during settlement were proven to be dominated by the ‘attachment point theory’ and Wenzel roughness, respectively. Topographic cues guiding the settlement turned out to be complicated as they were related to both, topographies and fouling species. As effective antifouling strategies, the combined effect of a variety of surface properties seems appropriate. Along these lines, the concept of slippery liquid-infused porous surfaces (SLIPS), which combined both surface lubricity and topographies, were tested against fouling under both laboratory and field conditions. Immersion tests suggested a correlation between the stability of slippery coatings in seawater and fouling resistance efficacy. On stable slippery surfaces, settlement of Ulva spores and Balanus amphitrite cyprids was remarkably reduced. Although both marginal fouling-release and poor field performance indicated the requirement of significant improvement of such coatings for practical applications, the fouling resistant potential of the SLIPS concept was demonstrated.
Porous polymethacrylates have numerous important applications in different research and industrial fields. These materials have been used as stationary phases for separation and catalysis, as substrates for thin layer chromatography, as materials for solid-phase extraction or filtration, or for making valves in microfluidic devices. The main advantage of porous polymethacrylates is that their physical and chemical properties, such as porosity, pore and polymer globule size, stiffness, hydrophobicity or hydrophilicity, as well as surface functional groups can be conveniently controlled by adjusting the composition of the polymerization mixtures. Porous polymethacrylate can be also functionalized using available surface modification strategies. This unique ability to control properties of porous polymethacrylates makes them suitable for the design and synthesis of novel functional materials. Surprisingly, most of the applications of porous polymethacrylates have been limited to their use inside columns, capillaries or microfluidic channels and their applications as open surfaces remained to a great extent unexplored. The goals of my PhD thesis were to: (1) develop methods for the preparation of (bio)functional porous polymethacrylate surfaces with well-defined surface properties; (2) characterize produced surfaces; (3) explore their unique properties in different biological applications. Surfaces with gradient properties have been widely used in many cell-surface interaction studies because these gradient surfaces offer the possibility to avoid the difficulties associated with the one-sample-for-one-measurement approach as well as the problems with sample variations. However, up to now, there are only a few methods for the preparation of surfaces with gradient properties. Taking advantage of the tunable porous properties of polymethacrylates, porous poly(butyl methacrylate-co-ethylene dimethacrylate) (BMA-EDMA) surfaces with gradient surface morphologies were prepared using a PDMS microfluidic chip designed and produced for this study. The produced BMA-EDMA surface possessed a gradient polymer globule size ranging from ~ 0.1 µm to ~ 0.5 µm. The surface with the globule size gradient in this range is useful for cell studies such as investigation of the effect of surface morphology on cell behavior. Porous polymethacrylate surfaces with a gradient in density of functional groups were also prepared via photografting by gradually varying the UV dosage along one direction on the surface during surface modification. The formation of the gradient was confirmed with X-ray photoelectron spectroscopy and water contact angle measurements. To show the potential of using the surface with a gradient density of functional groups, the behavior of human fibrosarcoma HT-1080 cells was studied on the surface. Recently, bio-inspired slippery liquid infused porous surfaces have attracted much attention due to their unique liquid repellent and self-cleaning properties. In this thesis, stable slippery surfaces were prepared by infusing the porous BMA-EDMA surface with water immiscible hydrophobic poly(hexafluoropropylene oxide) or perfluorotripentylamine. The antibacterial and anti-marine fouling properties of the slippery BMA-EDMA surfaces were carefully investigated. Our results demonstrated that the slippery BMA-EDMA surfaces had good antibacterial and anti-marine fouling properties. However, the results also revealed that the antibacterial property of the slippery BMA-EDMA surface was bacterial strain dependent. In addition, Ulva sporelings (young plants) were able to firmly attach to the slippery surface although the surface is able to resist Ulva spore adhesion. The ability to transform a superhydrophobic surface to a superhydrophilic one is essential for many applications such as creating superhydrophobic-superhydrophilic micropatterns or microarrays. Most of the existing methods for this transformation are time consuming or require harsh conditions. In this thesis, a new facile method to transform the superhydrophobic BMA-EDMA surface to a superhydrophilic one was developed. This method is based on the physisorption of an amphiphilic phospholipid on the hydrophobic surface of porous BMA-EDMA through hydrophobic-hydrophobic interactions. Using this method, superhydrophobic-superhydrophilic micropatterns could be fabricated simply by printing the phospholipid “ink” on the superhydrophobic BMA-EDMA surface with a contact printer.
Within this work various catalysts for the direct synthesis of dimethyl ether from CO-rich synthesis gas have been investigated and tested in a continuously operating laboratory plant. The employed catalyst systems have been either bifunctional catalysts, which combine active sites for the methanol synthesis and its dehydration, or admixed catalysts consisting of a conventional methanol catalyst and different acid solids. The catalysts have been prepared by wet-chemical methods, the sol-gel-process, hydrothermal reaction, deposition of complexes and colloids on an acid solid and by flame-spray pyrolysis. The latter method proved to be very efficient for the preparation of highly active methanol- and dimethyl ether-catalysts. The flame-made methanol catalyst showed high synthesis gas conversion and in combination with γ-Al2O3 a very good dimethyl ether selectivity that were as high as in the case of a commercially available methanol catalyst. Various admixed catalyst systems have been tested focusing on their long-term stability. A system that contained the zeolite H-MFI 400 as dehydration component showed the highest CO-conversion. However, this system was not stable and its activity decreased after a catalyst passivation and -regeneration process. A catalyst system containing a SiO2-doped alumina was the most stable in the passivation and regeneration process, because the high metal dispersion in the catalyst did not change during the procedure. The obtained data show that the synergy between the active sites for methanol synthesis and the active sites for methanol dehydration plays an important role for catalyst activity. Therefore, an overlapping of the active sites needs to be prevented for the preparation of highly active bifunctional catalysts.
Motivation für diese Arbeit was die Entwicklung einer neuen Präparationsmethode, um eine Einzelstrang-DNA (engl.: single stranded DNA, ssDNA ) innerhalb eines biokompatiblen Templats zu immobilisieren und zudem ssDNA-Muster beliebiger Form und Größe herzustellen. Als Ansatz wurde eine strahlungsinduzierte Austauschreaktion (engl.: irradiation promoted exchange reaction, IPER) im Rahmen des konzepts der Chemischen Lithographie verwendet. IPER ermöglicht es mittels Elektronenbestrahlung, das Ausmaß der Austauschreaktion zwischen einer primären, das Substrat bedeckenden selbstorganisierten Monoschicht (engl.: self-assembled monolayer, SAM ) und einem molekularen Substituent je nach Dosis zu steuern. Physikalisch bedeutet IPER die Erzeugung von chemischen und strukturellen Defekten in dem primären SAM, die die Austauschreaktion fördern. Im dieser Arbeit wurde der IPER Ansatz auf eine kontrollierte und ortsspezifische Immobilisierung von ssDNA auf Au(111)-Substraten erweitert. Um eine unspezifische Adsorption außerhalb der ssDNA bedeckten Bereiche zu verhindern, wurde als Ausgangsmatrix eine biokompatible Oligoethylenglykol-substituierte Alkanthiol (OEG-AT) Monolage verwendet. Im ersten Abschnitt wurden thiol-terminierte ssDNA als Substituenten eingesetzt. IPER mit diesen Substituenten und einem OEG-AT-SAM als Vorlage führten zu homogen gemischten ssDNA/OEG-AT Filmen der gewünschten Zusammensetzung, die anhand der eingestellten Dosis angepasst werden konnte. Basierend auf diesen Ergebnissen wurde IPER mit Elektronenstrahllithographie (EBL) verwendet, was die Herstellung komplexer ssDNA-Muster mit der gewünschten Form und Nanometergröße (bis zu 25-50 nm) innerhalb der biokompatiblen Matrix erlaubte. Diese Muster wurden dann als Vorlagen für die oberflächeninitiierte, enzymatische Polymerisation (SIEP) eingesetzt, was die Präparation von komplexen, räumlichen ssDNA Bürsten erlaubte. Ausgehend von den genannten Ergebnissen wurde die Möglichkeit überprüft, IPER mit kommerziell verfügbaren ssDNA-Disulfid Substituenten durchzuführen. Zunächst wurde eine Studie unter Verwendung eines Referenzfilms aus einem nicht-substituierten AT auf Gold und einem symmetrischen COOH-substituierten Dialkyldisulfid als Substituent durchgeführt. Dabei wurde festgestellt, dass IPER mit Disulfid-Substituenten in der gleichen Weise wie mit Thiolen durchgeführt werden kann. Es konnte gezeigt werden, dass die Kinetik der Austauschreaktion in beiden Fällen ähnlich ist, wenn auch das Ausmaß der Reaktion bei den Disulfiden geringer war. Dennoch konnten gemischten SAMs mit einer Konzentration der substituenten Spezies von bis zu 60% hergestellt werden. Basierend auf diesen Ergebnissen wurde die Möglichkeit verschiedener symmetrischer wie asymmetrischer ssDNA-Disulfide als Substituenten für IPER untersucht, wobei beide Systeme sich als geeignet für die IPER erwiesen. Die asymmetrischen Disulfide zeigten ähnlich hohe Wirkungsgrade, während die Effizienz der symmetrischen Disulfide insbesondere bei niedrigen Bestrahlungsdosen (< 0,6 mC/cm² ) deutlich niedriger war. Die Verwendung von IPER erfordert Hochvakuum und im Fall komplexer Strukturierung aufwändige Versuchsaufbauten wie Rasterelektronenmikroskop. Daher wurde in einem weiteren Abschnitt UV-Licht als Initiator für die Austauschreaktion zwischen der primären OEG-AT Matrix und den ssDNA Substituenten eingesetzt. UV-Licht wurde zur homogenen und lithographischen Strukturierung, zur Herstellung gemischter ssDNA/OEG-AT Filme und ssDNA Muster eingebetten in eine biokompatible OEG-AT Matrix verwendet. Auch hierbei konnte die Zusammensetzung der gemischten Filme durch die Wahl der Dosis eingestellt werden. Es wurde auch gezeigt, dass das UV-Licht unterschiedlicher Wellenlängen (254 oder 365 nm) neue Möglichkeiten für die Lithographie eröffnet. Zuletzt wurde eines der Systeme, ssDNA Polymerbürsten gekoppelt an ein monomolekulares ssDNA Templat, im Rahmen dieser Arbeit detailliert untersucht. Eine Kombination von mehreren komplementären spektroskopische Techniken wurde verwendet, um die chemische Integrität, Reinheit und molekulare Ausrichtung dieser mittels SIEP hergestellten Objekte zu untersuchen. Die Spektren der Polymerbürsten waren nahezu identisch mit denen der monomolekularen ssDNA Vorläufer und wiesen keine Spuren von Verunreinigungen auf. Neben der wohldefinierten chemischen Integrität und dem kontaminationsfreien Charakter, zeigten die Bürsten eine vergleichsweise hohe Orientierungsordnung, mit vorzugsweise aufrechter Ausrichtung der einzelnen Stränge. Die entwickelten Herstellungsmethoden beiten die Möglichkeit, ssDNA/OEG–AT Filme und Muster für die Bindung und den Nachweis der komplementär ssDNA Stränge sowie für die Erkennung von DNA-bindenden Proteinen zu präparieren, was unter anderem eine Grundlage für Sensorfabrikation bildet. Ferner dienen sie als vielseitige Plattform für Nanofabrikation, wie anhand der komplexen ssDNA Bürste in dieser Arbeit demonstriert wurde.
Die vorliegende Arbeit beschreibt den Einsatz gezielt geformter Femtosekundenlaserimpulse zur Erlangung chemischer Selektivität mit dem Ziel einer mikroskopischen Bildgebung. Die Methode der kohärenten anti-Stokes-Ramanstreuung in einer Einzelstrahlvariante mit breitbandigen Laserimpulsen (Single-Beam-CARS) steht dabei im Mittelpunkt. Die beiden Ansätze der Kontrolle der Anregung und des Multiplexing werden dabei in Theorie, Simulation und Experiment untersucht, jeweils im Hinblick auf die Erlangung spektroskopischer Information und die Möglichkeit einer Bildgebung. Die Kontrolle der Anregung zielt darauf ab bestimmte Schwingungsübergänge in Molekülen zu bevorzugen. Nur diese bestimmte Spezies liefert dann einen Signalbeitrag und kann so identifiziert werden. Der Vorteil dabei ist, dass eine Einkanaldetektion verwendet werden kann, was schnelle Messwertaufnahmen ermöglicht. Der Ansatz des Multiplexing liefert hingegen Schwingungsspektren oder Ausschnitte daraus. Dafür ist jedoch eine spektral aufgelöste Messung notwendig. Zur Erlangung spektraler Information ist Multiplexing daher sehr geeignet. Für schnelle Bildgebung hingegen weniger, es sei denn die Information ist über das Spektrum verteilt und kann nicht einzelnen Banden zugeordnet werden. Dann ist es möglich mit einer anschließenden Datenanalyse einzelne Komponenten zu identifizieren. Bemerkenswert ist, dass alle Methoden mit demselben experimentellen Aufbau realisiert werden können. Darüber hinaus wurde in dieser Arbeit auch gezeigt, dass es möglich ist unerwünschte Signalbeiträge zu kontrollieren. In diesem Fall wurden Beiträge von Zweiphotonenfluoreszenz in Single-Beam-CARS-Messungen unterdrückt.
Membrane trafficking is an abstraction describing material transport within different organelles of the cell. It is one of the areas of interest in molecular and cell biology. The practical interest for the investigation of membrane trafficking is lying in its relation to an increasing list of diseases, such as cancer. Identification of genes involved in membrane trafficking and their regulation within the cell are in particular focus of interest. Microscopy based observation of membrane trafficking events in the native or close to native context is the method of choice. It allows relating different stages of the whole process to specific cellular organelles with spatial and temporal resolution. It also has the advantage of better statistics over other population mean based methods, as results are concluded from the observation of a high number of individual cells. Despite the versatility of fluorescence microscopy, the application of any particular technique for cell biology requires more application layers such as fluorophores and labelling strategies, data acquisition and storage, digital image analysis, data interpretation in a biological context, and last but not least – the biological process of interest itself. Improvements of those application layers or even synergy of different microscopy techniques increases information content what can be extracted from a single experiment. Currently we call this approach as high-content microscopy. During the time of my studies I was working on improving some of application layers as well as creating stronger link between them. This thesis describes my experimental and data analysis work which was done to address some of the specific membrane trafficking related cases in context of high-content microscopy: a) The organization kinetics of the Golgi complex, which is the major membrane trafficking organelle, and the influence of over-expressed membrane proteins on it. Live cell fluorescence screening microscopy was employed to address this question. b) Statistical data analysis of a cargo protein secretion screen. Influence of specific RAB GTPases over-expression on collagen-I secretion was evaluated. c) The development of a comprehensive fluorescence microscopy based platform to investigate messenger RNA (mRNA) and micro RNA (miRNA) interactions in live cells.
Die unerwünschte Besiedlung von künstlichen Oberflächen mit Mikroorganismen, das sogenannte Biofouling, stellt sowohl in der Biomedizin als auch in der marinen Industrie ein großes Problem mit gesundheitlichen und finanziellen Folgen dar. Daher besteht ein großes Interesse den Bewuchs von Oberflächen zu verhindern. Da viele der Organismen, auch als Biofouler bezeichnet, motil sind, d.h. in der Lage sind sich aktiv fortzubewegen, leisten Studien hinsichtlich ihrer Motilität einen wichtigen Beitrag zum Verständnis des Besiedlungs-verhaltens und damit zur Entwicklung von Strategien zur Biofouling Bekämpfung. Im Rahmen dieser Arbeit wurde das Schwimm- und Besiedlungsverhalten von zwei verschiedenen flagellierten Modellorganismen, nämlich des pathogenen Bakteriums Pseudomonas aeruginosa und der Sporen der Grünalge Ulva linza, mittels digitaler in-line Holographie analysiert. Dabei konnten für die planktonische Schwimmbewegung von P. aeruginosa verschiedene Schwimmmuster klassifiziert werden, was nach unserem Wissen zum ersten Mal überhaupt zum experimentellen Nachweis helikalen Schwimmverhaltens für ein kleines Bakterium wie P. aeruginosa führte. Des Weiteren konnte gezeigt werden, dass P. aeruginosa Übergänge zwischen den verschiedenen Schwimmmustern aufweist. Bei den Sporen der Grünalge Ulva linza wurde neben dem Schwimmverhalten auch das Besiedlungsverhalten auf positiv geladenen Arginin und Tyrosin enthaltenden Oligopeptid Oberflächen untersucht. Es hat sich gezeigt, dass die Besiedlung dieser Oberflächen sehr hoch ist und die Anlagerung der Sporen äußerst schnell, innerhalb von wenigen Sekunden stattfindet. Durch das 3-dimensionale Tracken der Sporen konnte gezeigt werden, dass diese in Anwesenheit der ArgininTyrosin (ArgTyr) Oberflächen das sogenannte „Hit and stick“ Schwimmmuster aufweisen, bei dem sie direkt beim ersten Kontakt an der Oberfläche kleben bleiben, wonach einige der Sporen sporadische Zappelbewegungen auf der Oberfläche zeigten. Kontrolluntersuchungen mit einer reinen Glycin (Gly) Oligopeptid Oberfläche zeigten hingegen ein komplett anderes Schwimmverhalten der Sporen. Neben den Laborexperimenten mit den Modelorganismen P. aeruginosa und Ulva linza wurden im Rahmen dieser Arbeit auch Feldexperimente mit Organismen in ihrer natürlichen Umgebung durchgeführt. Diese Untersuchungen führten zur erstmaligen Beschreibung und Klassifizierung des planktonischen Schwimmverhaltens motiler mariner Mikroorganismen.
Das Halbleitermaterial Titandioxid (TiO2) baut unter UV-Bestrahlung adsorbierte organische Substanzen ab und wird u.a. für die Beseitigung von organischen Umweltgiften intensiv erforscht. Am Beispiel des Malonsäureabbaus wurde versucht, die Zwischenschritte des komplexen Prozesses durch infrarotspektroskopische Oberflächenuntersuchungen im Subsekundenbereich zu erklären, um effizientere Systeme zu ermöglichen. Hierfür ist es notwendig, das Verhalten UV-Photonen-angeregter Elektronen mit Zwischenprodukten zu vermessen, um Zusammenhänge zu den kurzlebigen Spezies zu erklären. Ein multimodularer Aufbau bestehend aus einem Infrarotspektrometer mit Reflexionseinsatz, einem Messsystem zur Bestimmung der elektrischen Leitfähigkeit und der Temperatur wurde konzipiert, um an einer mit Drähten verpressten TiO2-Oberfläche zeit- und ortsgleiche Messungen durchzuführen. Nach Charakterisierung des Aufbaus liegen temperaturbereinigte Daten vor, die den Einfluss von sichtbaren- und UV-Licht auf das elektronische Verhalten der Probe erklären und einen Vergleich zu den IR-Spektren ermöglicht. Das Anlegen eines externen elektrischen Feldes führte nachweislich zu einer Minimierung der Rekombination von UV-angeregten Elektronen und Löchern und beeinflusste oberflächengebundene Ladungsträger.
Ziel der vorliegenden Arbeit war die Synthese und Charakterisierung großer, linear anellierter N-Heteroacene. Durch gezielte Derivatisierung sollten ihre Material-eigenschaften auf Basis literaturbekannter Kriterien für einen effektiven Elektronentransport optimiert werden. So konnten N-Heteroacene bis hin zu Azahexacenen über unterschiedliche Kupplungsmethoden dargestellt werden. Dabei wurde der Pd-katalysierten Aminierung eine erhöhte Beachtung geschenkt, da durch diese gleichsam junge und effektive Methode elegante Synthesewege möglich sind. Aber auch klassische Methoden fanden Einsatz, sodass eine Vielzahl neuer Verbindungen dargestellt werden konnte. Ansätze, die Klasse der Azaacene durch Azaheptacene zu erweitern, blieben dagegen bis zuletzt ohne Erfolg. Darüber hinaus wurde der Einfluss des Heteroatoms in einer Serie von Acenothiadiazolen und Acenoselenadiazolen untersucht. Dabei zeigte der Austausch des Schwefelatoms gegen das elektropositivere und voluminösere Selenatom bemerkenswerte Veränderungen in optischen und elektronischen Eigenschaften, sowie in der Festkörpermorphologie der Heteroacene. Mit dem Ziel, potente Elektronenhalbleiter darzustellen, wurden die einzelnen Fragmente der N-Heteroacene systematisch variiert und optimiert, woraus ein besseres Verständnis dieser Verbindungsklasse resultierte. Durch gezielte Modifikationen der Struktur konnten dabei Morphologie, Löslichkeit, elektronische Struktur und Stabilität angepasst werden, woraus etliche potentielle Ladungstransport¬materialien resultieren.
Die Arbeit untersucht die Synthese und die physikalischen und elektrochemischen Eigenschaften von nano- und mikroskalierten Materialien für Lithium-Ionen-Batterien, wobei neben den elektrochemischen Eigenschaften auch grundlegende physikalische Fragestellungen im Vordergrund standen. Zur Herstellung der Materialien wurden dabei sowohl die konventionelle als auch die mikrowellenunterstützte Hydrothermalsynthese benutzt. Die physikalische Charakterisierung der Materialien erfolgte vor allem mittels Röntgendiffraktion, Magnetisierungsmessungen und Elektronenmikroskopie, darüber hinaus wurden als elektrochemische Methoden zyklische Voltammetrie und galvanostatische Zyklierung eingesetzt. Als relevante Batteriematerialien wurden sowohl Oxide (TiO2, LiCoO2) als auch Phosphate (LiMPO4 mit M=Mn, Fe, Co, Ni) untersucht. LiCoO2 dient dabei als Modellsystem für die mikrowellenunterstützte Synthese, welches durch die Niedertemperatursynthese in nanoskalierter Modifikation hergestellt und mit konventionell synthetisiertem Material verglichen wurde. Des Weiteren wurden TiO2-Nanoröhren und -Nanopartikel untersucht, die beide deutlich verbesserte elektrochemische Eigenschaften als die entsprechenden Bulk-Materialien zeigen. Für die Herstellung von LiMPO4 (M=Mn, Fe, Co, Ni) wurde eine Vielzahl verschiedener Syntheseparameter untersucht, mit deren Hilfe die Morphologie und das Agglomerationsverhalten phasenreiner nano- bzw. mikroskalierter Materialien gezielt manipuliert und studiert werden konnten. Ein wichtiges weiteres Ergebnis ist die erstmalige Darstellung und Untersuchung eines neuen LiCoPO4-Polymorphs (Raumgruppe Pn21a). Für LiFePO4 und LiMnPO4 konnte ein deutlicher Einfluss der Größenreduktion bzw. Form auf die elektrochemischen Eigenschaften gezeigt werden. Zusammen mit der Anwendung eines Oberflächenbeschichtungsverfahrens können so die elektrochemischen Eigenschaften deutlich verbessert werden.
Spray drying is one of the most widely used drying techniques to convert liquid feed into a dry powder. The modeling of spray flows and spray drying has been studied for many years now, to determine the characteristics of the end products, e.g. particle size, shape, density or porosity. So far, the simulation of polymer or sugar solution spray drying has not been studied because drying behavior as well as properties are unknown. Previous studies concentrated on the systems of milk, salt solution, colloids or other materials for which the thermal and physical properties are well tabulated.
The present study deals with the modeling and simulation of polyvinylpyrrolidone (PVP)/water and mannitol/water spray flows. PVP is a polymer, widely used as a pharmaceutical excipient, and mainly manufactured by BASF under several patented names, whereas mannitol is a sugar, which is used in dry powder inhalers and tablets. Experimental studies have shown that the powder properties of PVP and mannitol are significantly influenced by the drying conditions. The growing importance of PVP or mannitol powders and the inability of existing studies to predict the effect of drying conditions on the properties of the end product have prompted the development of a new reliable model and numerical techniques.
Evaporating sprays have a continuous phase (gas) and a dispersed phase, which consists of droplets of various sizes that may evaporate, coalesce, or breakup, as well as have their own inertia and size-conditioned dynamics. A modeling approach which is more commonly used is the Lagrangian description of the dispersed liquid phase. This approach gives detailed information on the micro-level, but inclusion of droplet coalescence and breakup increase computational complexity. Moreover, the Lagrangian description coupled with the Eulerian equations for the gas phase, assuming a point-source approximation of the spray, is computationally expensive. As an alternative to Lagrangian simulations, several Eulerian methods have been developed based on the Williams’ spray equation. The Euler – Euler methods are computationally efficient and independent of liquid mass loading in describing dense turbulent spray flows.
The objective of this thesis is the modeling and simulation of spray flows and spray drying up to the onset of solid layer formation in an Euler – Euler framework. The behavior of droplet distribution under various drying conditions in bi-component evaporating spray flows is examined using, for the first time, direct quadrature method of moments (DQMOM) in two dimensions. In DQMOM, the droplet size and velocity distribution of the spray is modeled by approximating the number density function in terms of joint radius and velocity. Transport equations of DQMOM account for droplet evaporation, heating, drag, and droplet–droplet interactions.
At first, an evaporating water spray in nitrogen is modeled in one dimension (axial direction). Earlier studies in spray flows neglected evaporation or considered it through a simplified model, which is addressed by implementing an advanced droplet evaporation model of Abramzon and Sirignano, whereas droplet motion and droplet coalescence are estimated through appropriate sub-models. The assumption of evaporative flux to be zero or computing it with weight ratio constraints was found to be unphysical, which is improved by estimating it using the maximum entropy formulation. The gas phase is not yet fully coupled to the DQMOM but its inlet properties are taken to compute forces acting on droplets and evaporation. The simulation results are compared with quadrature method of moments (QMOM) and with experiment at various cross sections. DQMOM shows better results than QMOM, and remarkable agreement with experiment.
Next, water spray in air in two-dimensional, axisymmetric configuration is modeled by extending the one-dimensional DQMOM. The DQMOM results are compared with those of the discrete droplet model (DDM), which is an Euler – Lagrangian approach. Droplet coalescence is considered in DQMOM but neglected in DDM. The simulation results are validated with new experimental data. Overall, DQMOM shows a much better performance with respect to computational effort, even with the inclusion of droplet coalescence.
Before extending DQMOM to model PVP/water spray flows, a single droplet evaporation and drying model is developed, because most of the evaporation models available in the literature are valid for salts, colloids or milk powder. The negligence of solid layer formation effects on the droplet heating and evaporation is addressed, and treatment of the liquid mixture as the ideal solution is improved by including the non-ideality effect. The PVP or mannitol in water droplet evaporation and solid layer formation are simulated, and the results are compared with new experimental data, which shows that the present model effectively captures the first three stages of evaporation and drying of a bi-component droplet.
Finally, PVP/water spray flows in air are simulated using DQMOM including the developed bi-component evaporation model. Simulation results are compared with new experimental data at various cross sections and very good agreement is observed.
In conclusion, water and PVP/water evaporating spray flows, and preliminary stages of PVP/water and mannitol/water spray drying, i.e., until solid layer formation, are successfully modeled and simulated, and show good agreement with experiment.
The major aim of this thesis is to create a novel in vitro model substrate for the controlled cell differentiation in pluripotent tissue sheets by fine-tuning the balance between cell-cell (in plane) and cell-matrix (out of plane) interactions. As the model substrate to culture tissue explants, planar lipid membranes deposited on solid substrates (supported membranes) were functionalized with the extracellular domain of Xenopus cadherin-11 (Xcad-11), expressed in embryos during the neural crest cell (NCC) differentiation. In Chapter 4, the quantitative functionalization of supported membranes with Xcad-11 was confirmed by the combination of specular X-ray reflectivity (XRR), grazing incidence X-ray fluorescence (GIXF), and quartz crystal microbalance with dissipation (QCM-D). In Chapter 5, "animal cap" tissue sheets isolated from blastula stage embryos of Xenopus laevis were placed on membranes functionalized with Xcad-11.Interactions of the isolated tissue with membranes sheets displaying Xcad-11 were investigated by the combination of reflection interference contrast microscopy (RICM) and fluorescence microscopy. The capability of such a model system to induce the NCC differentiation was demonstrated by the activation of NCC marker gene marker slug by enhanced green fluorescent signal of the fusion protein. In Chapter 6, the two opposite concentration gradients of two recombinant proteins was established by means of "membrane electrophoresis", utilizing the fluidic nature of supported membranes. This allows for the creation of one-dimensional gradients of morphogens (e.g. Wnt and BMP) on supported membranes, which can guide the development of three-dimensional tissues in vitro.
Der Fungus Neurospora crassa ist ein etablierter Modellorganismus zur Untersuchung des molekular-genetischen Netzwerks um das tagesrhythmisch schwingende Gen frequency (frq). Dieses Netzwerk besitzt als sensorisches Bindeglied zu den umgebenden Temperatur- und Lichtbedingungen eine regulierende Signalwirkung für zahlreiche tagesabhängige zellphysiologische Prozesse wie zum Beispiel die Sporenbildung. Dabei ist in den letzten Jahren der Mechanismus der Temperaturwirkung mit wachsendem Interesse untersucht worden und es konnte unter anderem gezeigt werden, dass das Splicing der frq-mRNA eine hohe Temperaturabhängigkeit besitzt, wodurch eine Regulierung der Periodenlänge und der Phase der Schwingung durch Änderungen in der Umgebungstemperatur und damit vermutlich auch die Temperaturkompensation, also die Eigenschaft einer konstanten Periodenlänge bei unterschiedlichen Temperaturen, ermöglicht wird. In theoretischen Studien wurde jedoch auch gezeigt, dass für die Temperaturkompensation mehr als eine biochemische Reaktion für Temperaturänderungen sensitiv sein müssen. Eine wesentliche Frage liegt demnach darin, welche biochemischen Reaktionen eine besonders hohe Empfindlichkeit gegenüber der Temperatur besitzen.
In dieser Arbeit wird über eine biochemisch-quantitative Analyse der Verlauf der frq-Transkript- sowie der FRQ-Proteinmenge bei einem Temperaturanstieg von 18 auf 28°C gemessen und mit dem ebenfalls gemessenen Verlauf bei konstanter Temperatur von 25°C verglichen. Durch die Verwendung von bis zu zwölf technischen Replikaten können die Daten der frq-mRNA-Messung dabei in Anbetracht der t-Statistik mit einer um bis zu fünf Mal höheren Auflösung im Vergleich zu einer Einzelmessung ausgewertet werden und auf diese Weise bereits entsprechend kleinere Änderungen in der mRNA-Menge registriert werden. Desweiteren wird die biologisch-intrinsische Standardabweichung der frq-mRNA-Menge gemessen und in der Analyse mit berücksichtigt.
Die Messungen der frq-mRNA- und der FRQ-Proteinmengen zeigen in beiden Fällen einen unmittelbaren Anstieg nach der Temperaturerhöhung, so dass nicht unmittelbar ersichtlich ist, ob die Temperatur auf die Transkription, die Translation oder beide Prozesse wirkt. Zur numerischen Analyse wird die frq-Genexpression auf der Basis eines gewöhnlichen Differentialgleichungssystems zunächst als dreistufige Rückkoppelungsschleife modelliert. Dabei wird auf den Transkriptionsfaktor White-Collar-Complex (WCC) Bezug genommen, dessen aktivierende Wirkung auf die frq-Genexpression durch steigende Mengen phosphorylierten FRQ-Proteins gehemmt wird. Mit diesem in der Literatur bereits erprobten Goodwin-Modell ist es nach einer numerischen Parameterschätzung möglich, die Messdaten der frq-mRNA- und FRQ-Proteinmengen bei konstanter Temperatur im Rahmen der Standardabweichung zu simulieren. Eine Simulation der Messdaten mit Temperaturanstieg kann mit diesem Modell jedoch selbst mit Temperatursensitivität in allen Reaktionsraten nicht erreicht werden, dies wird erst durch die Einführung einer zusätzlichen Variablen zwischen der Transkription und der Translation möglich. Mit Hilfe dieses vierstufigen Modells wird schließlich eine Sensitivitätsanalyse der einzelnen biochemischen Reaktionen hinsichtlich der Temperatur durchgeführt. Das Ergebnis bestätigt die primäre Wirkung über einen post-transkriptionalen Mechanismus und es zeigt, dass der Anstieg in der Transkriptmenge nach dem Temperaturanstieg auf die Rückkoppelungswirkung über WCC zurückzuführen ist. Die Ergebnisse zeigen jedoch auch, dass zusätzlich eine Temperatursensitivität im Transkriptionsmechanismus vorliegt.
The major goal of this thesis is to gain a better understanding of the molecular self-assembly on GaAs, which can be useful for design of functional self-assembled monolayers (SAMs) on this technologically important semiconductor substrate. For this purpose, high quality SAMs of non-substituted alkanethiols and some specially designed molecules, including 4,4´-terphenyl-substituted alkanethiols, -(4´-methyl-biphenyl-4-yl)-alkanethiols, partially fluorinated alkanethiols (PFAT), and dihexadecyl diselenide have been prepared on GaAs (001) through the optimization and careful control of the rigorous experimental conditions. These SAMs were investigated in detail by a combination of advanced surface characterization techniques, providing a deep insight into the molecular organization and properties of these films. In the first place, pronounced chain length effect for all studied SAM systems on GaAs was elucidated, viz. deterioration of the film quality occurs with decreasing length of the molecular chain, accompanied by a partial oxidation of the GaAs substrate, due to the less effective protection property. In the second place, by using the series of the 4,4´-terphenyl-substituted alkanethiols and -(4´-methyl-biphenyl-4-yl)-alkanethiols, the existence of so called bending potential at the headgroup-substrate interface in the SAM/GaAs(001) system with a preferable GaAs-S-C angle of ~104° was demonstrated. For the above SAMs, this potential plays the dominant role in the balance of the structure-building forces, mediating the odd-even behavior in the molecular orientation and packing density. This result suggests that the bending potential should always be taken into account at the design of functional molecular films on GaAs substrate. The influence of the above factors, viz. the chain length effect and the bending potential, were additionally studied by the example of PFAT SAMs with variable length of the fluorocarbon chain, viz. CF3(CF2)n-1(CH2)11SH (denoted as FnH11SH, n = 6, 8, and 10). To better understand the structure and organization of these films, the corresponding study of the reference PFAT/Au system was performed first, resulting in a variety of valuable general findings regarding the balance of the structure-building interactions in complex monomolecular films. As for the PFAT/GaAs system, the respective SAMs were found to be highly ordered and densely packed, and consequently able to protect the GaAs surface from the oxidation. This protection depended on the chain length and was less effective for the films with shorter fluorocarbon chain due to their lower quality. Indeed, with decreasing length of the fluorocarbon segment, progressive deterioration of the orientation order accompanied by a slight decrease in the packing density was observed in the fluorocarbon part. In contrast, the hydrocarbon segments in FnH11SH/GaAs exhibited similar orientation, with the average tilt angles close to the optimum one determined by the bending potential. This underlines once more the important role of bending potential in the balance of structure-building interactions in aliphatic SAMs on GaAs.
Bedingt durch unsere Lebensweise und die Umwelteinflüsse denen wir in den Industrienationen ausgesetzt sind, stellen Krebserkrankungen heutzutage ein immer ernster zu nehmendes Problem dar. Dank der stetigen Forschung der letzten Dekaden war ein besseres Verständnis der Krankheit möglich, das es uns erlaubt durch weiterentwickelte gezielte Diagnoseverfahren den Ausbruch von Krebserkrankungen in immer früheren Stadien zu bemerken. Durch eine frühzeitige Erkennung von krankhaften Gewebsveränderungen ist es möglich, eine adäquate Therapie zu entwickeln, um dem Patienten die größtmöglichen Chancen auf eine Heilung zu ermöglichen. Diagnostische Bildgebungsverfahren wie z.B. Magnet-Resonanz-Tomographie (MRT) und Computer-Tomographie (CT) sowie nuklearmedizinisch unterstützte Diagnoseverfahren wie z.B. Positronen-Emissions-Tomographie (PET) und Szintigraphie, um nur einige zu nennen, stellen in der Früherkennung wichtige klinische Werkzeuge dar, die aus der onkologischen Diagnostik nicht mehr wegzudenken sind. Durch die Kombination der Vorteile der verschiedenen Diagnosemethoden, kann eine effizientere Früherkennung der Tumore und somit eine schnellere und besser angepasste Therapie realisiert werden. Zu diesem Zweck stehen multimodale Kontrastmittel für klinische Bildgebungsverfahren im derzeitigen Fokus der Forschung. Diese Arbeit befasst sich mit der Synthese neuartiger bispidinbasierter Liganden und ihren Übergangsmetallkomplexen als potentielle mono- oder bimodale Kontrastmittel für eine radiopharmazeutische Anwendung mittels des Radioisotops 64Cu in der Positronen-Emissions-Tomographie (PET). Die zwei synthetisierten Liganden L und LOH offerieren die Möglichkeit der Ausbildung eines Ruthenium(II)polypyridinkomplexes mittels eines Donorsets des Liganden, der als Fluoreszenzmarker fungieren kann und nachfolgend kann die Komplexierung von 64Cu(II) durch die noch vakante Kavität des Liganden erfolgen um eine Verbindung zwischen den bildgebenden Verfahren der Positronen-Emissions-Tomographie (PET) und der optischen Methoden (OI) zu schaffen. Der (bpy)2Ru(II)-Komplex des Liganden L zeigt zwei unterschiedliche Fluoreszenz-aktive Banden mit unterschiedlichen Lebensdauern von denen lediglich eine durch die weitere Koordination von Cu(II) gelöscht wird. Des Weiteren zeigen die Liganden L und LOH eine approximierte Cu(II)-Stabilitätskonstante, die mit der des isomeren Liganden N2py4, der bereits als 64Cu-Radiopharmakon evaluiert wurde, vergleichbar ist. Weitere Übergangsmetallkomplexe Fe(II), Fe(III) und Mn(II) zeigen interessante strukturelle Eigenschaften auf wie z.B. die Ausbildung pentagonal-bipyramidaler Koordinationspolyeder. Zur Ausbildung stabiler und ungeladener 64Cu(II)-Komplexe für die Positronen-Emissions-Tomographie wurden drei zyklische Bispidinliganden mit Amiddonoren entwickelt. Diese Bispidindioxotetraazamakrozyklen stellen durch die Fusion des äußerst rigiden Bispidinrückgrats mit dem Motiv eines makrozyklischen Diamids eine neue Klasse an hochgradig präorganisierten Bispidinliganden dar. Durch zwei deprotonierbare amidische Donoren bilden sie quadratisch-planare bzw. quadratisch-pyramidale hoch stabile, ungeladene Cu(II)-Komplexe aus, die auch die Stabilisierung von Kupfer in der Oxidationsstufe +III zeigen. In der Evaluation für eine radiopharmazeutische Anwendung als Tracer für die Positronen-Emissions-Tomographie mit dem Radioisotop 64Cu(II), zeigen die Bispidindioxotetraazamakrozyklen eine schnelle und effiziente Radiomarkierung >95% nach maximal 60 Minuten und eine ausgeprägte spezifische Aktivität von bis zu 26 GBq/µmol. Insbesondere ein Ligand (H2BBDT) weist in Radio-Challenge-Experimenten gegen EDTA und in humanem Blutplasma eine hohe Stabilität auf, mit einer Transchelatisierung von maximal 8% gegen einen 20-fachen Überschuss an EDTA und keiner verzeichneten Dekomplexierung in humanem Blutplasma nach jeweils 48 h. Aus Bioverteilungsstudien in Kyoto-Wistar-Ratten geht eine nahezu vollständige Ausschleusung des leicht lipophilen Komplexes [64Cu]Cu-BBDT aus dem Organismus nach einer Stunde nach erfolgter Injektion hervor. Der Cu(II)-Komplex des Propionsäuremethylester-funktionalisierten Zyklus H2BBDTA-Me ermöglicht die Kupplung an ein Zielvektormolekül, Nanopartikel oder ein Fluoreszenzlabel zur Darstellung multimodaler Kontrastmittel.
Forces play a crucial role in the regulation and function of biological processes. One of the most commonly used tools for measuring forces are elastic micropillars made of poly(dimethylsiloxane). By using poly(ethylene glycol) (PEG) micropillars, several new ex- perimental approaches could be developed. The aim of this thesis was the enhancement and the experimental application of these PEG micropillars. Not only the achievable geometries, but also the functionalization potential was significantly enhanced. For this, the PEG micropillar fabrication was combined with the transfer of hexagonal gold nanoparticle structures to PEG hydrogels. As a result, PEG micropillars exhibiting gold nanoparticle structures on their tops were obtained. These gold nanoparticles can serve as anchor points for a variety of proteins or other biologically active compounds. To study integrin dependent cell adhesion they were func- tionalized with αvβ3- or α5β1-integrin selective peptidomimetics. Cell experiments showed that fibroblasts exerted higher maximum forces on the α5β1-integrin selective ligand than cells on the αvβ3-integrin ligand. These observations were supported by higher local zyxin densities in adhesion clusters and the analysis of further proteins involved in the adhesion process. Further- more, the achievable PEG pillar force resolution of 9 ± 2 pN was demonstrated by investigating the contractile forces of in vitro actin networks bundled by magnesium ions.
This thesis deals with the synthesis and analysis of bispidine-iron(II)-complexes which act as model systems for nonheme iron enzymes. These enzymes participate in a wide range of natural oxidation reactions. The first part of the thesis describes the synthesis of bispidine ligands with para-substituted pyridine donors as well as their iron complexes. For this purpose the literature known ligands L and LO were used and altered at their pyridine donors. The influence of these substituents on the reactivity of the corresponding iron complexes was analyzed in CH-activation reactions, sulfoxidations and in the oxidation of water. The second part gives detailed information about the redox behavior of bispidine-iron-complexes in water and acetonitrile. Moreover, in case of bispidine-iron-complexes with pentadentate ligand systems, the influence of the coligand in sixth position was carefully investigated. In water, it was shown that the complexes of the pentadentate ligands LO, LU and their substituted analogues exist in an equilibrium of aqua- and hydroxido compounds. It was further demonstrated, that in acetonitrile Cl- shifts the FeII/III redox potential due to coordination to more negative values, whereas in water the only species detected are the aqua- and hydroxido species without Cl- having any influence on the redox potential. In addition, it was revealed that the FeIII/IV Redox potential of FeIV=O compounds is not accessible by the method of cyclic voltammetry. In the third part, the newly synthesized as well as the already known complexes were reacted with iodosylbenzene to form reactive FeIV=O species, which then were exposed to organic substrates. In these reactions, rate constants for CH-activation reactions and sulfoxidation were determined. Since trends in FeIII/IV redox potentials are expected to be closely related to the corresponding trends in FeII/III redox potentials, FeII/III potentials were correlated with rate constants. These correlations do not reveal a clear trend, which would allow a prediction of the reactivity of FeIV=O species in oxidation reactions, based on the FeII/III redox potentials. The forth part of the thesis deals with the oxidation of CH-bonds with bispidine iron(II) complexes and dioxygen as the only oxidant. The reaction shows typical features of dioxygen activation but a thorough analysis indicates that this reactivity is not based on oxygen activation. Experiments with radical starters and radical scavengers, followed by a detailed spectroscopic analysis substantiate the assumption that the observed autocatalytic reaction is started by an autoxidation of the substrate. These findings lead to a proposed mechanism for the oxidation of organic substrates with the participation of iron(II) and dioxygen, which is based on autoxidative radical chemistry. The fifth and last part of this thesis treats with the oxidative cleavage of water into dioxygen and protons. For this part the iron complexes with tetradentate bispidine ligands were used exclusively. Only iron complexes with tetradentate bispidine ligand systems show reactivity in the dioxygen generation when exposed to the oxidants cerium ammonium nitrate and sodium periodate. The redox potentials found in part two of this thesis were taken into consideration to conclude an influence of the potential on water oxidation. Here, it was found, that a high FeII/III potential is not beneficial for high yields of dioxygen.
This thesis deals with the remote sensing and the flux calculation of atmospheric trace gases, using Differential Optical Absorption Spectroscopy (DOAS). Since 2010, within the CARIBIC project (Civil Aircraft for the Regular Investigation of the atmosphere Based on an Instrument Container), a new DOAS instrument is installed in the cargo compartment of a passenger aircraft once per month as part of a fully automated measurement container. With this instrument, nitrogen dioxide (NO2), sulfphur dioxide (SO2), bromine oxide (BrO), nitrous acid (HONO), formaldehyde (HCHO) and ozone (O3) are measured. The results of these measurements are presented with focus on SO2 and NO2, which were observed in the downwind plumes of large industrial plants and cities. Using flux calculations, the emission of SO2 from a nickel smelter in Norilsk (Siberia) and the NO2 emission of the city of Paris are estimated. Thereby, the uncertainty factors are discussed and comparison with satellite data are performed. The question is dealt with, whether such calculations can be used to quantify further emission sources using similar instruments onboard additional passenger aircraft.
Die heterogene Katalyse von chemischen Reaktionen ist von großer Bedeutung sowohl in Forschung als auch in der chemischen Industrie. Durch Weiterentwicklung bestehender Katalysatorsysteme können hierbei die Effizienz und die Selektivität für spezifische Produkte verbessert werden. In der hier vorliegenden Arbeit wurde die Umsetzung von Dimethylether zu Olefinen (Dimethylether-to-Olefin Prozess, DTO), im Besonderen zu Ethen und Propen, an zeolithischen Katalysatoren untersucht. Hierzu wurde in einem ersten Teil der Arbeit eine kontinuierlich betriebene Laboranlage erfolgreich in Betrieb genommen. Diese Laboranlage wurde speziell auf den Einsatz des Edukt¬gases Dimethylether und die entsprechenden Reaktionsbedingungen zugeschnitten sowie eine Onlineanalytik installiert. Parallel hierzu wurden sowohl mittelporige (ZSM-5) als auch kleinporige (ZSM-34 und SSZ-13) Katalysatoren mit unterschiedlichen Silizium- und Aluminiumgehalten hergestellt. In weiteren Versuchen wurden diese mit verschiedenen Metallen (Co, Mn, La und Ir) in unterschiedlichen Konzentrationen dotiert. Alle Katalysatoren wurden mittels BET-Analyse, Energie Dispersiver X-Ray Analyse (EDX), Induktiv-gekoppelter Plasmaanalyse mit Atomemissionsspektroskopie (ICP-OES), Temperatur¬pro¬gramm¬ierter Desorption (TPD) und Pulver¬diffrakto¬metrie (XRD) charakterisiert. Die Testung der hergestellten Katalysatoren in der kontinuierlich betriebenen Laboranlage zeigte, dass Katalysatoren vom Typ ZSM-34 mit Cobalt- und Mangan-Dotierung die Ethenselektivität erhöhten. Im Gegensatz dazu verbesserten Lanthan-dotierte ZSM-34 Katalysatoren die Propenselektivität. Die kataly¬tischen Umsätze und die Standzeit der jeweiligen Katalysatoren wurden jedoch durch die Dotierungen leicht reduziert. Dahingegen führten Cobalt-, Mangan-, Lanthan- und Iridium-Dotierungen an Katalysatoren des SSZ-13 Typs zu einer Erhöhung der Standzeit der Katalysatoren. Als effizientes Katalysatorsystem wurde im Rahmen dieser Dissertation ein mit Mangan-dotierter SSZ-13 Katalysator hergestellt. Mit diesem konnte erfolgreich sowohl der Umsatz gesteigert als auch die Laufzeit sowie die Ethen- und Propenselektivität erhöht werden.
Neue mehrfunktionelle phosphorhaltige Flammschutzmittel wurden nach drei unter-schiedlichen Konzepten erschlossen und in verschiedenen Epoxidharzsystemen untersucht. Gegenstand des ersten Konzeptes ist die Generierung drei- und vierfunktioneller Additive von sternförmiger Geometrie, welche sich als vorteilhaft für die Glasübergangstemperatur der zu beladenden Polymere erwiesen hat. Aus 1,3,5-Tris(2-hydroxyethyl)isocyanurat (THIC) und Pentaerythritol wurden nach verschiedenen Synthesemethoden mehrfunktionelle Derivate des 6H-Dibenzo[c,e][1,2]oxaphosphinin-6-oxids (DOPO), Diphenylphosphinoxids (DPhPO) und 5,5-Dimethyl-1,3,2-dioxaphosphinan-2-oxids (DDPO) synthetisiert. Aufbauend auf vorangehenden Arbeiten der Gruppe Döring wurde ein breites Portfolio phosphorhaltiger Additive mit unterschiedlicher chemischer Umgebung am P-Atom dargestellt und in drei verschiedenen Epoxidharzsystemen (RTM6, DGEBA/DMDC und DEN438/DICY/Fenuron) eingearbeitet. Die resultierenden Materialien wurden einer Flammschutzprüfung nach der UL 94-V Methode (Underwriter Laboratories 94-Vertikal Brenntest) sowie DSC- und TGA-Untersuchung unterzogen. Zum Zweiten wurden verschiedenartige phosphorhaltige Additive entwickelt, die selbst Oligomere bzw. Polymere darstellen. Auf Grundlage von DOPO und THIC wurden lineare, verzweigte und vernetzte P-haltige Polyether hergestellt und deren Synthese im vergrößerten Maßstab optimiert. Phosphorhaltige Duromere wurden aus verschiedenen mehrfunktionellen Acrylaten und [P]-H-Verbindungen erschlossen und des Weiteren mit DOPO funktionalisierte Phenol-Novolake nach verschiedenen Methoden synthetisiert. Alle Typen der polymeren Additive wurden in den oben genannten Epoxidharzsystemen untersucht. Das dritte Konzept beinhaltet die Synthese von phosphorhaltigen Diolen als Comonomere für inhärent flammgeschützte Epoxidharze und andere Polymere. Neben phosporhaltig disubstituiertem Pentaerythritol wurde eine neue Methode zur Synthese von di-, tri- und tetra-phosphorylierten p-Hydrochinonderivaten entwickelt, die im Gegensatz zu den bisher bekannten Methoden nicht auf identische Phosphorgruppen beschränkt ist. Darauf basierend wurde eine breite Auswahl an neuen Chinonverbindungen erschlossen und charakterisiert.
Nonlinear optical microscopy is ideally suited for in vivo imaging: it provides label-free contrast revealing intrinsic structural and chemical properties of the sample in a non-invasive way. Successful nonlinear microscopy relies on the use of pulsed lasers to obtain high signal levels at moderate average laser power. In particular, broadband excitation increases the nonlinear generation efficiency as well as the spectral coverage. However, lower photodamage thresholds and less straightforward signal interpretation have prevented its application to sensitive samples. In this thesis, a pulse shaper is used to tailor ultrashort pulses for optimal imaging. This work concentrates on Coherent Anti-Stokes Raman Scattering (CARS) because it provides an access to highly specific vibrational spectra. The main concept is to encode molecule-specific information directly in the excitation. This is realized either by direct tailoring in a shaperassisted variant of a Multiplex CARS setup or by phase shaping of a single ultrashort pulse (<10fs). The photon load reduction and the optimization of the pulse profile achieved by shaping are demonstrated with the imaging of polymer samples and sensitive biological tissue. The flexibility of the setup allows switching between spectrally resolved acquisition for precise chemical mapping and single channel detection for rapid imaging. Further nonlinear effects can likewise be controlled by pulse shaping. In this work, the systematic modification of the relative intensities of Second Harmonic Generation (SHG), Two-Photon Excited Fluorescence (TPEF) and CARS is investigated as well as selective excitation of fluorophores and molecular vibrations. Multimodal imaging with shaped ultrashort pulses proves to be particularly efficient for biological samples as illustrated by the imaging of plant cells and skin biopsies.
The successful application of alpha-emitters in targeted alpha therapy (TAT) goes together with developments in radionuclide production and labelling chemistry. Especially profound understanding of the coordination chemistry of the respective metal ion-ligand system is of major importance to develop protocols for the synthesis of radioimmunoconjugates and to predict the fate of radionuclides in vivo.
Radioconjugates of the therapeutic alpha-emitter Ac-225 with polyamino-polycarboxyl ligands as chelating agents are being actively studied [1, 2, 3, 4]. In particular the macrocyclic ligand 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) has shown promise due to the high kinetic- and thermodynamic stability (log K > 20) of its complexes with trivalent metal cations [5]. The scope of the presented work was the experimental characterisation and evaluation of DOTA as a suitable chelator for trivalent actinides (An(III)), particularly in terms of stable binding of the long-lived alpha-emitting radionuclide Ac-225 to biomolecules for safe application in radioimmunotherapy (RIT). The project included not only basic studies to contribute to a better understanding of the complexation mechanisms and kinetics, but, based on these findings, was aimed at the development of a robust labelling protocol for facile and effective synthesis of an Ac-225-DOTA-MabThera® conjugate. In the course of the investigations, focus was set on in vitro testing of the obtained radioimmunoconjugate, in particular the evaluation of the kinetic stability in presence of competing agents as well as in human blood serum. Assessment of the antigen binding affinity of the antibody conjugate completed the work.
The protocol for the design and synthesis of Ac-225 radiopharmaceuticals of McDevitt et al. provided the starting point for this study [6]. This research group developed a synthetic scheme to radiolabel DOTA-proteins with Ac-225. Later, the protocol was applied to antibodies in form of a two-step synthesis, with the first step being the Ac-225 DOTA-Bn-NCS complexation, followed by the coupling of the Ac-225-DOTA-Bn-NCS to the mAb. The idea behind this two-step approach was that, when the complexation of Ac(III) with DOTA is conducted at elevated temperatures and basic pH (first step), presumably a more stable complex is formed. However, since higher temperature / pH are known to have a negative effect on the antibody efficiency, the conjugation to the biomolecule can hence only be conducted at lower temperatures in a second step. This two-step synthesis though suffers from yields below 10 %, which is assumed to be due to the competing hydrolysis reaction of the isothiocyanate moiety occurring at the pH used during the complexation step. This makes the labelling protocol an interesting subject for further studies on how this synthesis can be improved.
From the findings of McDevitt et al it was apparent that a number of variables needed to be investigated in order to improve on the low efficiency of the protocol. These studies were conducted previously and are summarised in the Diploma Thesis, S. Kannengieÿer, 2009 [7]. A one-step synthesis protocol was tested and the labelling yields for Ac-225 were found to be dependent on temperature and especially on the pH of the reaction mixture. Eventually, an optimised protocol for radiolabelling of DOTA-peptides and MabThera® with Ac-225 activities up to 2 µCi (= 74 kBq) per 100 µg mAb was established, offering labelling yields > 95 %. The present work now aimed on translation of the developed synthesis protocol to higher specific activities of clinical relevance (>10 µCi (>370 kBq) per 100 µg mAb).
To gain profound knowledge about the complexation reaction mechanism and the thermodynamic and kinetic properties of the An(III)-DOTA system, the coordination chemistry was initially studied by means of time resolved laser fluorescence spectroscopy (TRLFS). Since Ac(III) has no suitable spectroscopic properties, the metal ion complexation by DOTA was investigated with Cm(III) as substitute for the trivalent actinides. A comparable study on [Eu(III)DOTA]- has been reported before [8, 9, 10]. Besides determination of the kinetic rate constants and thermodynamic parameters (log K, deltaG, deltaH, deltaS) at labelling-relevant temperatures up to 90 °C, attention was also paid to the detection of possible intermediate species which are frequently discussed in the literature [11].
TRLFS is a powerful speciation method which makes use of the excellent fluorescence properties of Eu(III) and Cm(III), both regarded as good representatives for trivalent lanthanides and actinides. With TRLFS it is possible to detect and characterise complex species in sub-micromolar concentrations without influencing the chemical equilibrium of the system. An experimental setup was chosen which allows for adjusting the concentration of the reactive DOTA species by variation of the pH of the reaction. Due to the slow kinetics of the complexation reaction at room temperature, experiments at 45 to 90 °C were conducted to identify the complex species and quantify their relative ratios by means of peak deconvolution. Based on the potentiometrically determined pKa,n values of HxDOTA(4-x)- for the respective conditions, from these ratios the conditional complex stability constants log K of [Cm(III)DOTA]- were calculated (I = 0.1, 45 to 90 °C). Application of the van't Hoff law allowed for extrapolation of the log K at 25 °C to be 22.0±0.4. The parameters deltaG, deltaH and deltaS obtained from the Gibbs Helmholtz relation indicate that the reaction is exergonic, endothermic and driven by the change of entropy.
Identification and further characterisation of the involved complex species was done by comparison of the fluorescence lifetimes, which give information about the first coordination sphere of the metal cation. Furthermore, additional investigations with NMR were executed to identify and understand the mechanism related to the complex formation with DOTA-Bn-NCS. Based on the results of the NMR study, the complexation kinetics of DOTA and DOTA-Bn-NCS were further investigated and compared to gain insight into the involved reaction mechanisms.
Proper understanding and interpretation of the thermodynamic behaviour of the Cm(III)-DOTA complex formation allowed for facile translation of the experimental settings to the Ac(III)-DOTA system. Since no spectroscopic methods are available for this system, Chelex cation exchange resin as well as Instant Thin Layer Chromatography (ITLC) were chosen as radiochemical speciation methods and were evaluated for their feasability. Determination and refinement of the stability constant log K of Ac(III)DOTA]- for the temperature range of 25 to 90 °C was done in analogy to the Cm(III)-DOTA system, resulting in a log K25°C = 19.5±0.4. To obtain reliable results, the protocol for the radiochemical separation of Ac-225 from Ra-225 required optimisation to ensure highest purity and quality of the radionuclide.
Based on these findings, the studies on the Ac-225-labelling of DOTA-Bn-NCSMabThera® for targeted alpha therapy of Non-Hodgkins-Lymphoma were subsequently continued. The previously established protocol was modified and further optimised in order to be applicable for facile clinical synthesis of radioimmunoconjugates with higher specific activities (SA) within 20 min. In this regard, the antibody labelling kinetics were reviewed respective reaction temperature and ideal pH of the high-yield radiolabelling, which permitted further improvement of the labelling effectiveness (pH 9, 37 - 42 °C, 5 - 15 min; ave. yields 94 - 96 %, > 98 % RCP after purification). The protocol was successfully evaluated for reliability with SA up to 50 µCi (= 1.85 MBq) per 100 µg mAb. The obtained radioconjugates were assessed for their kinetic stability in different buffers as well as under physiolocigal conditions in human blood serum and proved to be satisfyingly stable over up to 30 days ( > 85 % Ac-225 still bound).
Finally, a preliminary radiobiological study with cancer cells (K422 cell line, B-cell lymphoma) was conducted to determine the antigen binding afinity of the radiolabelled CD20-antibody (SA = 1 µCi (= 37 kBq)/100 µg mAb, Bmax= 8.88 nM, Kd = 52.55 nM). The results give rise to further preclinical in vitro studies. In summary, it was demonstrated that rapid, high-yield radiolabelling of DOTAchelated mAbs is possible under alkaline conditions at rather low temperatures. Under these conditions a thermodynamically and kinetically stable radioimmunoconjugates with specific activities suitable for application in clinical TAT studies is formed while the integrity of the antibody is preserved.
Seit der Isolierung des ersten stabilen freien N-heterocyclischen Carbens von Arduengo et al. im Jahre 1991 hat diese Substanzklasse eine breite Anwendung in der Katalyse und als Liganden von Metallkomplexen gefunden. Dabei zeichnen sie sich vor allem durch ihre, im Vergleich zu Phosphanen, erhöhte σ-Donorfähigkeit aus und können so oftmals zu einer besseren Stabilisierung von Intermediaten führen. Neben ihren elektronischen Eigenschaften besitzen N-heterocyclische Carbene häufig einen größeren sterischen Anspruch als Phosphanliganden, was ebenfalls einen Einfluss auf die Stabilität von Metallkomplexen haben kann. In dieser Arbeit wurde das sterisch anspruchsvolle N-heterocyclische Carben IPr** untersucht. Ausgehend vom Imidazoliumsalz bzw. Silberkomplex von IPr** konnten zahlreiche Komplexe mit folgenden Übergangsmetallen erhalten werden: Platin, Kupfer, Palladium und Gold. Die Goldkomplexe IPr**AuCl (11) und IPr**AuNTf2 (12) wurden eingehender untersucht. So führte die Chloridabstraktion von IPr**AuCl (11) mit einem Silbersalz zur Bildung eines kationischen Toluol-stabilisierten Goldkomplexes. Bei der Reaktion in Dichlormethan gelang die Isolierung eines Intermediates dieser Reaktion, bei dem man die Abstraktion des Chlorids vom Goldatom durch das Silberkation beobachten kann. Wird anstelle von AgSbF6 das Natriumsalz des schwach koordinierenden BArF24-Anions als Chloridabstraktionsmittel verwendet, so konnte der entsprechende, bisher einzige nicht durch koordiniertes Lösungsmittel stabilisierte kationische 12-Valenzelektronen-Goldkomplex erhalten werden. Mit der Zeit kam es zur C-B-Bindungsspaltung des BArF24-Anions durch den kationischen Goldkomplex und zur Bildung eines Goldaryl-Komplexes. Somit ist es erstmals gelungen mit Hilfe eines Metallkomplexes der Oxidationsstufe (I) die C-B-Bindung im BArF24-Anion zu aktivieren. Ein weiteres Ziel war die Isolierung eines Gold-Carben-Komplexes durch Umsetzung des in situ darstellbaren, kationischen Goldkomplexes mit Carbenvorläufern. In dieser Arbeit konnte gezeigt werden, dass eine Gold-Kohlenstoff-Doppelbindung auf diese Art nicht erhalten werden kann. Neben der Eignung des IPr**Au-Systems, Intermediate zu stabilisieren, sind auch dessen katalytische Fähigkeiten von Interesse. Hierbei konnte IPr**AuNTf2 (12) eine bisher unerreichte Kombination von katalytischer Aktivität, Stabilität und Selektivität als Katalysator in der Hashmi-Phenolsynthese sowie der goldkatalysierten Hydratisierung von Alkinen erzielen. Die Entstehung eines isomeren Nebenproduktes in der Hashmi Phenolsynthese wurde mit Hilfe eines methylsubstituierten Furanderivats untersucht. Vermutlich beruht dessen Bildung auf einer Wagner-Meerwein-artigen-Methylgruppenverschiebung. Substituenteneffekte, relative Reaktionsgeschwindigkeiten und Konkurrenzexperimente in der goldkatalysierten Hydratisierung von Alkinen belegten, dass die Protonierung des Vinylintermediates der geschwindigkeitsbestimmende Schritt dieser Reaktion ist. Der erhaltene Palladium-PEPPSI-Komplex von IPr** wurde auf seine katalytische Aktivität in der Suzuki-Miyaura-Kreuzkupplung, der Sonogashira-Reaktion und der Buchwald-Hartwig-Aminierung getestet. Die besten Ergebnisse konnten in der Buchwald-Hartwig-Aminierung erzielt werden, welche auch in Bezug auf Katalysatorbeladung und Substratvielfalt eingehend untersucht wurde.
The copper-catalyzed azide-alkyne cycloaddition for the synthesis of 1,4-disubstituted 1,2,3-triazoles (CuAAC) is a variant of Huisgen’s 1,3-dipolar cycloaddition which disburdens the thermal reaction from its major drawbacks such as poor regioselectivity, long reaction times and harsh conditions. In contrast to the widely used “black box” reagent mixtures, a molecularly defined, highly active catalyst system for homogeneous CuAAC reactions has been developed in this PhD project. In dependence on the postulated stepwise mechanism, its most important structural feature is the presence of two copper(I) ions irreversibly bound in the same catalyst molecule. A highly modular and profitable synthesis for bistriazolium hexafluorophosphate salts as precursors for the ancillary ligand system was devised. In analogy to the CuAAC catalyst systems of general formula [(NHC)2Cu]PF6 described in literature, novel dinuclear copper(I) complexes with a bistriazolylidene ligand backbone and 1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene (IPr) as sacrificial ligand were prepared. However, these complexes did not show the expected high catalytic activity, most probably due to the strong coordination of the IPr ligands. In consequence, another family of dinuclear copper(I) complexes with µ-coordinated acetate as labile ligand was synthesized by reaction of the bistriazolium hexafluorophosphate ligand precursors with copper(I) acetate in the presence of a base. The broad applicability and high catalytic activity of one of these bistriazolylidene dicopper acetate complexes was confirmed by a series of gaschromatographically monitored CuAAC reactions in different solvents and with various substrates. The order of reaction with respect to the initial concentration of the precatalyst was investigated by determination of the half value periods of reactions with different concentrations of the dinuclear copper acetate complex. The results of these kinetic experiments with phenylacetylene and ethyl propiolate were rationalized by postulating different catalyst resting states and rate-determining steps in dependence on the properties of the alkyne substrate. Direct evidence of a dinuclear copper acetylide intermediate in the CuAAC reaction’s mechanism was gained by NMR spectroscopy and mass spectrometry.
In this work thermodynamic properties of molten fluoride salts and salt mixtures are investigated. Fluoride salts have advantageous properties to be used in energy producing systems based on the conversion from heat to energy like i.e in Molten Salt Reactors. For this purpose it is very important to have detailed information about the heat capacity of the pure salts and salt mixtures. To get a better understanding about the heat capacity in mixtures drop calorimetry measurements of mixtures of LiF with other alkali fluorides were conducted and compared. The investigation of fluoride salts at elevated temperatures is complicated by the fact that fluoride vapour is aggressive to many materials. In order to protect our sensitive measurement equipment the salt samples were encapsulated in nickel crucibles using a laser welding technique and afterwards the whole nickel capsule was measured. This method was veried by the measurement of unmixed CsF and KF where in both examples an excellent agreement with literature data was obtained. Afterwards various intermediate compositions of the systems LiF-KF, LiF-CsF and LiF-RbF were investigated and a general trend according to the difference in cation radii could be established. In combination with literature data for the LiF-NaF system the heat capacity of the liquid state follows the order LiF-NaF <LiF-KF <LiF-RbF <LiF-CsF. An other very effective source of information about materials is their phase diagram. From such diagrams multiple data about phase transition temperatures, vapour pressures, enthalpy of fusion, enthalpy of mixing or solubilities can be deduced. Based on own measured phase diagram data using differential-scanning calorimetry (DSC) with a special encapsulation technique and on available literature data a complete description of the LiF-NaF-CaF2-LaF3 phase diagram was obtained. With the help of mathematical models the phase diagrams can be calculated and also higher order systems can be predicted. The LiF-NaF-CaF2-LaF3 system was calculated with the classical polynomial model and the quasi-chemical model in parallel in order to evaluate which of the two models provide a better extrapolation to higher order systems (ternary or quaternary) based on the related binary systems. The two models behaved very similar at the investigated system and the quasi-chemical model was chosen for further assessments of phase diagrams. This model was selected, since it considers the chemical nature of the investigated system and to simplify the integration of the obtained data in an already existing database of fluoride salt phase diagrams at the Institute for Transuranium Elements in Karlsruhe, Germany. In the Molten salt reactor technology UF3 has a big influence on the corrosion properties of the used salt mixture. But only limited phase diagram data exist regarding this compound. Therefore, the LiF-UF3 and NaF-UF3 system was measured with the DSC method and the LiF-NaF-UF3-UF4 quaternary system was mathematically assessed. The assessment was complicated by a disproportionation of UF3 during the measurements which is faster in the NaF-UF3 system due to the fluoroacidity difference of LiF and NaF. A key system for various designs of the Molten Salt Reactor is LiF-ThF4 binary system. The phase diagram of that system was reassessed based on various newly measured data in this study. In this context also a modication to the used DSC measurement technique was done in order to be able to measure enthalpies of mixing of the two components LiF and ThF4. This method was developed during this work and was veried by the measurement of the LiF-KF system where experimental data exist. A very good agreement between the measured data and the literature was obtained. Also an intermediate solid compound of the LiF-ThF4 system, namely Li3ThF7, was synthesized and the enthalpy of fusion was determined. All new experimental results were considered in the reassessment of the phase diagram. As consequence the assumption of the liquid heat capacity of ThF4 was corrected from 133.9 J ·K^-1 · mol^-1 to 170 J ·K^-1 · mol^-1. With the obtained results and several new phase diagram descriptions it was investigated, if CaF2 is a beneficial component to be used in the salt mixture of two different molten salt reactor designs. It is concluded that CaF2 has no profitable influence on the LiF-NaF-BeF2-PuF3 salt mixture in a specific transuranium burner design (MOSART concept). But it has advantageous influence on the LiF-ThF4 mixture of a thorium breeder design (MSFR) and should be subject to further investigations. During the experimental work of this thesis several scientific articles were published. Major parts of this work can be found in:
O. Benes, M. Beilmann, R. J. M. Konings, "Thermodynamic assessment of the LiF-NaF-ThF4-UF4 system", J. Nucl. Mat 405 (2010) 186-198.
M. Beilmann, O. Benes, R. J. M. Konings, Th. Fanghänel, "Thermodynamic investigation of the (LiF + NaF + CaF2 + LaF3) system", J. Chem. Thermodyn., 43 (2011) 1515-1524.
M. Beilmann, O. Benes, R. J. M. Konings, Th. Fanghänel, "Thermodynamic assessment of the (LiF + UF3) and (NaF + UF3) systems", J. Chem. Thermodyn., 57 (2013) 22-31.
O. Benes, R. J. M. Konings, D. Sedmidubský, M. Beilmann, O. S. Valu, E. Capelli, M. Salanne, S. Nichenko, "A comprehensive study of the heat capacity of CsF from T = 5 K to T = 1400 K", J. Chem. Thermodyn., 57 (2013) 92-100.
E. Capelli, O. Benes, M. Beilmann, R. J. M. Konings, "Thermodynamic investigation of the LiF-ThF4 system", J. Chem. Thermodyn., 58 (2013) 110-116.
M. Beilmann, O. Benes, E. Capelli, R. J. M. Konings, Th. Fanghänel, "Excess heat capacity in liquid binary alkali fluoride mixtures", Inorg. Chem., http://dx.doi.org/10.1021/ic302168g.
Biofouling, the undesired colonization of surfaces, is a major problem for marine-related industries. To prevent unwanted effects caused by biofouling, suitable non-toxic coatings for the marine environment are required. Conditioning, i.e. the adsorption of proteins and macromolecules influences, as surface chemistry and morphology do, the settlement of fouling oragnisms. Investigating the temporal dynamics of conditioning film formation on functionalized self assembled monolayers (SAMs), it was shown that the obtained film thickness of about 10Å to 20Å is independent of the surface chemistry but differences occur concerning the composition of these films. While on hydrophilic surfaces more proteinaceous compounds are detectable, the hydrophobic surfaces show a lower intensity of proteins. Furthermore, is was shown that in standard Ulva linza spore settlement assays the influence of a molecular conditioning layer is likely to be small, but by increasing pre-conditioning time this influence gains importance and should be considered in long term experiments. Preconditioning also resulted in detectable surface differences in field studies. It was found that preconditioned samples which contain more proteinaceous compounds seem to be more attractive for settlement. Experiments with matured laboratory biofilms formed by Pseudomonas aeruginosa demonstrated that using a protein-rich medium results in conditioning film formation. Conversely, surface conditioning is reduced when a media containing a smaller amount of proteins is utilized. Furthermore, it was observed that surface chemistry has no remarkable effect on the fraction of inoculated bacteria that adhere to a surface. Finally, inspired by the nanostructured skin of dolphins, electron-beam lithography was utilized to create a honeycomb topography made of poly(N-isopropylacrylamide) (PNIPAM). The evaluation showed that structures from 0.75 μm to 2.5 μm in diameter reduce Ulva settlement in comparison to a smooth PNIPAM surface. It should be noted, that wet polymer structure heights in the range of only 0.01 μm do have an effect on spores with a body size of around 5 μm.
Marine biofouling, the colonization of submerged surfaces by unwanted organisms, has an important economic and environmental impact. This PhD thesis focuses on the smaller organisms involved in the biofouling process such as bacteria, diatoms and protozoa also called microfoulers. As bacteria are usually among the first organisms to settle on submerged surfaces, the characterization of their adhesion to these surfaces is essential for the development of strategies for antifouling, and in particular fouling release coatings. To this end, the adhesion of the bacterium Cobetia marina on various model systems for anti fouling coatings was investigated using a microfluidic shear stress assay which applies shear stresses covering a range of nearly six orders of magnitude from 0.01 to 5,500 dyn/cm2. For this assay, the experimental parameters such as medium, incubation time and increase of the applied volumetric flow were optimized.
In this work various surface properties relevant for bioadhesion were investigated, namely wettability, chemistry, hydration, transition from monolayers to polymeric coatings, and the controlled release properties of metal organic frameworks as a smart release coating. The surfaces used for this study were self-assembled monolayers (SAMs) with different chemical end groups and hydration levels, polysaccharide coatings with and without capping of their carboxylic groups, poly[oligo(ethylene glycol)methacrylate] (POEGMA) brushes and copper based metal organic frameworks (Cu SURMOF 2). The results showed that in general the hydration of the surface is more important for the resistance against bioadhesion than the wettability. It was demonstrated that the critical shear stress needed for removal of bacteria from a SAM system based on ethylene glycols (EGs) decreased with an increasing number of EG units which is directly related to an increment of hydration. Furthermore, good fouling release properties of polysaccharide coatings were demonstrated, especially if the free carboxyl groups of alginic acid (AA) and hyaluronic acid (HA) were capped with a hydrophobic amine. Cu SURMOFs 2 were investigated as an example of smart release coatings. When bacteria interacted with these surfaces they induced a loss of crystallinity and a harmful effect on themselves. These findings, together with the observed stability of the coatings in artificial seawater (ASW) and the integrity of the coating in areas without bacteria demonstrated a stimulus response of these surfaces upon presence of bacteria. In order to compare the performance in the field of the surfaces investigated in the laboratory assays, a set of well characterized samples were immersed into the ocean at the Sebastian test site of the Florida Institute of Technology. The aim of these field tests was to compare the results of the laboratory experiments, which solely investigated a single species under controlled conditions, with field experiments which employed a mixed species marine environment under natural conditions. The results showed that air and water temperature seemed to be an important factor for the abundance of species and composition of the fouling community. Furthermore, the level of hydration of the surfaces was found to be more important for their colonization than their wettability. Some trends that have also been observed in previous laboratory assays such as the good performance of the polysaccharide coatings and the EG SAMs, compared to other SAMs, could be confirmed in the field. Hence, the inert properties of hydrophilic hydrogels could be demonstrated in both laboratory assays and in the natural marine environment.
Seit Jahrzehnten stellt filamentöses Aktin aufgrund seiner bedeutenden Rolle in Hinblick auf Zellmobilität, -integrität und Kraftgenerierung einen wichtigen Gegenstand zellulärer Untersuchungen dar. Als Resultat seiner semiflexiblen Natur zeigen Aktinnetzwerke sowohl viskoses als auch elastisches Verhalten. In vitro Untersuchungen der mechanischen Eigenschaften von Aktin sind aber zumeist auf 3-dimensionale Gele oder Einzelmolekülexperimente beschränkt, obwohl es sich bei den bedeutendsten zellulären Aktintrukturen um 1-dimensionale Bündel, die sogenannten Stressfasern, und um ein 2-dimensionales Netzwerk, den Aktinkortex, handelt. Aus diesem Grund war es Ziel der Arbeit, neuartige Aktin und Aktin-Membran Strukturen innerhalb mikrofluidischer Umgebungen zu erzeugen und ihre viskoelastischen Eigenschaften mittels passiver Einzelpartikel-Mikrorheologie zu untersuchen. Im Vergleich mit 3- und 2-dimensionalen Netzwerken zeigte sich, dass gerichtete Strukturen ein zwischen transversaler und longitudinaler Richtung divergierendes viskoelastisches Verhalten aufweisen, welches sich bei Bündelung mittels Mg2+ Ionen angleicht. Zeitabhängige Untersuchungen des Bündelungsprozesses im Konzentrationsbereich von 5 - 12mM deuten darauf hin, dass die Bündelung auch bei geringeren Mg2+ Konzentrationen auftritt als bislang aus 3-dimensionalen Gelen bekannt ist. Außerdem zeigen sie eine Langzeitstabilität, selbst nach Mg2+ Entfernung aus der Lösung. Darüber hinaus wurde als Modellsystem ein freistehender Aktin-Membran Komplex auf funktionalisierten Lochstrukturen entwickelt, ähnlich dem Aktin-Membran Kortex in Zellen. Mit multiplen Vorteilen gegenüber existierenden Modellsystemen ausgestattet ermöglicht es zukünftige Studien der physikalisch-chemischen Eigenschaften von plasmalemmaverknüpften Aktinnetzwerken.
In the event of exposure of spent nuclear fuel to groundwater in a final repository, the preferential dissolution of grain boundaries rather than matrix dissolution would cause a rapid increase of the surface area exposed to groundwater, with effects on the mobilisation of radionuclides and on the overall mechanical stability of the spent fuel pellet. In this respect, a research project has been launched at the Institute for Transuranium Elements (ITU, Karlsruhe, Germany), with the goal of gaining understanding of the mechanisms of the penetration of water into polycrystalline UO2 under conditions relevant for final disposal in a geological repository. As a first approach to this issue, the study has been initially focused on natural UO2 with well defined grain size and morphology. The experiments have then been extended to SIMFUEL, an inactive analogue of UO2 fuel containing elements simulating a spent fuel, to assess potential effects associated to the presence of fission products. The experiments consisted of static leaching tests on UO2 fuel pellets using 18O-labelled water. Unlike most of the diffusion studies on UO2, the experiments in this study were conducted at low temperature (≈ 25°C and 60°C), in order to reproduce the temperature range expected in the geological disposal scenario temperatures. To ensure sufficient contact time between the solid phase and the solution for penetration to be detectable experiments lasted 3-9 months. Experiments were carried out initially in oxidising conditions (in air or in N2 glovebox) and thereafter under 10 bar H2 atmosphere, in order to approach conditions more similar to the anoxic and reducing environment expected in the final repository. Pre- and post-corrosion surface characterisation was performed by means of scanning electron microscopy (SEM), atomic force microscopy (AFM) and X-ray photoelectron spectrometry (XPS), while solution analysis was performed by inductively coupled plasma mass spectrometry (ICP-MS). The penetration of water was assessed by depth profiling of the tracer 18O using Secondary Ion Mass Spectrometry (SIMS) microscopy. Well-known analytical models were used to fit of the profiles and determine the relevant diffusion coefficients. For the first time in this study, the chemical diffusion coefficient of oxygen in different UO2+x phases was experimentally determined at temperatures below 100°C. The good agreement with extrapolated literature data obtained from high-temperature diffusion experiments verifies the viability of the SIMS depth profiling method for the determination of diffusion coefficients, even with a diffusion length of tens of nm. The study has also reported for the first time evidence of the presence of oxygen/water grain-boundary diffusivity in polycrystalline UO2 and an estimate of the diffusion coefficient at 25°C is here presented. The study has also shown that the possibility to observe grain boundary diffusion by SIMS depth profiling might depend to a large degree on the grade of surface oxidation of UO2. In general, all these experimental findings have given an important starting point for the study of water penetration in the spent fuel. Zusammenfassung ii Charakterisierung der Penetration von Wassermolekülen in polykristallines UO2 Stichwörter: Urandioxid; SIMFUEL; Sekundärionen-Massenspektrometrie; Tiefenprofil; Korrosion; Auslaugen; chemische Diffusion; Korngrenzendiffusion; Kristallgitter Diffusion; Sauerstoff-Diffusion; Endlagerung; abgebrannte Brennelemente
Main aspect of this work is the investigation of the ultrafast relaxation dynamics following photoexcitation in carotenoids using time-resolved nonlinear spectroscopy. Special attention is paid to the early dynamics of less than 100 fs after excitation. The chosen spectroscopic method is pump-degenerate four wave mixing (pump-DFWM), a two-dimensional technique which allows for the simultaneous observation of population and vibrational dynamics. Numerical model simulations of the signal are implemented in order to provide unambiguous interpretation of the complicated pump-DFWM signal. This permits analysis of the general characteristics of the pump-DFWM signal of complex molecules as well as the influence of experimental parameters such as pulse length and chirp. Carotenoids are natural pigments which play a crucial role in photosynthesis. The relaxation pathway after excitation with visible light of these molecules, however, is still not clear. The properties of the excited states of carotenoids depend strongly on the conjugation length N. This work starts with the investigation of lycopene (N = 11) as a typical member of the carotenoid family. It is shown that a long-living pump-DFWM signal at early delays is key to the answer of the question whether additional dark states play any role in the relaxation. This signal is assigned to a stimulated emission from the excited state to a vibrationally hot ground state (hot-S0). No hints for a participation of additional states are found for lycopene. Comparison of several carotenoids with different conjugation lengths from N = 9 to 13 as well as measurements of the closed-chain carotenoids -carotene and lutein in different solvents, however, reveal unusual characteristics in the signal around N = 10. The appearance of an additional absorption signal, a delay of the stimulated emission as well as interferences in the vibrational spectra of spheroidene and lutein point to a mixing of the initially excited state with an additional dark state. Hence, participation of a dark state in the relaxation pathway for N = 10 is shown while no hints are found for additional dark states in all other carotenoids.
In this work reactions of guanidinyl-functionalised aromatic compounds 1,2,4,5-tetrakis-(N,N,N´,N´,-N´´,N´´,N´´´,N´´´-tetramethylguanidino)-benzene (1), 1,2,4,5-tetrakis-(N,N‘-dimethyl-N,N‘-ethyleneguanidino)–benzene (3) and 1,2-bis-(N,N,N´,N´-tetramethylguanidino)-benzene (2) with Cu(I), Ag(I) and Au(I) salts are explored. 1 and 2 are able to transfer two electrons to an acceptor and act as ligand by coordination with imine nitrogen atoms to metal centers, wich results in formation of binuclear complexes. Reaction of 1 with CuCl and CuCN leads to trigonal-planar coordination compounds 1(CuCl)2 and 1(CuCN)2. Oxidation of 1(CuI)2 with I2 leads to formation of semiconductive coordination polymer {[1(CuI)2][2I3]}n with band gap of 1.05 eV. Decomposition of this polymer is achieved with 1,10-phenanthroline with simultaneous oxidation of copper(I)-centers to Cu(II). A radical cationic complex [1(Cu2Cl2I2)][I3] is obtained by analogous reaction of 1(CuCl)2 with I2. DF-calculations show two Cu(II)-centers and one free electron located within the C6-backbone of the ligand. The strong oxidation agent Br2 allows the synthesis of [2Br1(CuBr2)2][CuBr4] by four electron oxidation of 1(CuBr)2, wich goes along with bromination of 1. The choice of electron acceptors determines the number of transferred electrons from the coordination compounds 1(CuBr)2 and 1(CuI)2. Formation of trigonal-planar complexes 2(CuX) (X = I, CN) is observed in case of using 2 as ligand. First coordination compounds of ligand 1 with AgX (X = Cl, Br, I) are obtained. Polarity of the solvent influences the progress of reaction. Using unpolar solvent toluene prefers coordination of Ag(I)-centers and formation monomer 1(AgCl)2, while in more polar acetonitrile coordination, oxidation and formation of polymeric structures is observed and product mixture of 1(AgCl)2, {[1][Ag4Cl6]}n and [1][2Cl] is obtained. Polymer compounds [1(AgBr)2]n and [1(AgI)2]n are synthesised by reaction of 1 with AgBr and AgI in acetonitrile. Pyrolysis leads to formation of graphite-like carbonitride phase with semiconducting properties. In methanol electrondonor nature of ligand 1 dominates over coordination character and oxidation of 1 in presence of AgCl and AgBr to dication 12+ is observed, while in presence of AgI oxidation is associated by coordination and dicationic units of 12+ are connected by silverhalogenide-cluster. The different properties of ligand 1 within the 1/AgX-system (X = Cl, Br, I) can be influenced by the selection of the solvent and/or halogenides, which offers an access to different products involving the guanidinyl-functionalised ligand 1. 1D-Chains of [1(AgBr)2]n and [1(AgI)2]n show different behaviour towards the oxidizing agents I2, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), 2,3,5,6-tetrachlorobenzoquinone (TCQ) and tetracyanoquinodimethane (TCNQ). Polymer structures such as {[1][Ag5Br4I3]}n as well as donor-acceptor couple such as [1][2DDQ] are obtained. The formation of this compounds coincides with change of coordination geometry respectively dissociation of Ag(I)-centers from ligand. 1 acts as two-electron donor towards the oxidizing agent. First Au(I)-cyanomethylcomplex 3/[PPh3AuCH2CN]2 is obtained by reaction of 3 with AuPPh3Cl in acetonitrile. Coordination of Au(I) to guanidine-groups is not observed. The interplay of basic properties and steric feature of guanidine-groups allows 3 the deprotonation of the C-H-acidic compound acetonitril. The presence of 3 and AuPPh3Cl allows also deprotonation of phenylacetylene, 3-ethynylpyridine, 4-ethynylpyridine, 1,4-diethylylbenzene and 4-ethinyl-1,1´-biphenyle. Two reaction channels are observed. Redox-channel leads to formation of [3][2Au(RX)2] whereas the deprotonation channel results in formation of neutral Au(I)-complexes PPh3Au(RX). Favored linear geometry in all Au(I)-complexes is realized.
Das Zusammenspiel der verschiedenen Organe in einem komplexen System wie dem menschlichen Körper erfordert fein aufeinander abgestimmte Steuer- und Kontrollmechanismen. Der JAK/STAT Signalweg ist einer der direktesten Informations-Übertragungswege von extrazellulären Botenstoffen, die das Signal über die Zellmembran in das Zytosol bis in den Zellkern zu den jeweiligen Zielgenen weiterleiten. Der Wachstumsfaktor Epo spielt unter anderem in der Erythropoese in Zusammenhang mit dem EpoR und dem Signalprotein STAT5b eine wesentliche Rolle. In dieser Arbeit wird das STAT5b-Protein in lebenden NIH3T3 Maus Fibroblasten hinsichtlich seiner Diffusion im Zytosol und im Zellkern und bezüglich der Bindungseigenschaften an seinen aktivierenden Rezeptor (EpoR) untersucht. Die Experimente werden mit den Einzelmolekül-spektroskopischen Methoden FCS und „VA-TIRF“ durchgeführt. Hierfür muss zunächst eine geeignete Farbstoffmarkierung des STAT5b gefunden werden. Die Verwendung eines Fusionsproteins aus STAT5b und fluoreszierendem mCherry bietet eine spezifische und stöchiometrische Markierung. Allerdings zeigt mCherry in den Versuchen eine ausgeprägte Fluktuation in seiner Emission, das so genannte „Blinken“, und eine geringe Photostabilität. Damit ist das Fluoreszenzprotein für FCS-Messungen nur bedingt geeignet. Für DIFIM, eine Methode die durch punktweise FCS-Analysen ein Raster von relativen Diffusionszeiten eines Ausschnitts einer Zelle anfertigt, ist STAT5b-mCherry ungeeignet. Um die Untersuchungen der Diffusion und Bindung des STAT5b dennoch erfolgreich durchzuführen wird es mit dem SNAP-Tag-Protein fusioniert, welches dann mit dem organischen Farbstoff TMR-Star stöchiometrisch markiert wird. In dieser Arbeit konnte ein Markierungsprotokoll etabliert werden, welches sicherstellt, dass die Markierung spezifisch und das Signalübertragungsprotein funktional ist. Die FCS-Messungen im Zytosol und Zellkern ergeben für unterschiedlich behandelte Zellen verschiedene Diffusionskoeffizienten (D). Für unbehandelte und gehungerte Zellen sind die mittleren D im Zytosol schneller als im Zellkern. Nach der Aktivierung des Signalwegs mit Epo kehrt sich das Verhältnis um und der mittlere D im Zellkern nimmt zu. Wahrscheinlich führt die Dimerisierung des aktivierten Proteins zu einer Verringerung, während die Bindung des aktivierten STAT5b-Dimers an die DNA im Zellkern vermutlich zu der Erhöhung des D führt. Die Messungen mit „VA-TIRF“ zeigen für die Bindung des Proteins an der Zellmembran keine einheitliche Bindungszeit und auch keinen Unterschied hinsichtlich Epo-stimulierten und -unstimulierten Zellen. Daher kann davon ausgegangen werden, dass unspezifische Wechselwirkungen des STAT5b mit der Zellmembran und anderen Rezeptoren in der Zellmembran der Bindung mit dem EpoR überlagert sind. Bei der Analyse der gesamten Aktivität des Proteins an der Zellmembran zu verschiedenen Zeitpunkten nach Epo-Stimulierung ergibt sich ein Aktivitätsmaximum bei 7,5 min. In den Bindungs-An-Zeiten des STAT5b ist hingegen kein Unterschied zu erkennen. Die gesteigerte STAT5b-Aktivität ließe sich durch verkürzte Bindungs-Aus-Zeiten des Proteins zum EpoR oder durch eine erhöhte Anzahl der Rezeptoren in der Zellmembran infolge der Epo-Stimulierung erklären. In Übereinstimmung zeigen Untersuchungen der Phosphorylierung von STAT5b durch V. Becker et. al. die maximale Phosphorylierung bei 7.5 min durch eine erhöhte Rekrutierung von EpoR aus dem zytosolischen Pool an die Zellmembran. Videoaufnahmen mittels „Variable-Angle-TIRF“ mit Belichtungszeiten von nur 5 ms pro Einzelbild zeigten, dass es möglich ist über ImTIR-FCS-Analysen Diffusionskoeffizienten des STAT5b zu erhalten. Die Wechselwirkung mit der Zellmembran wird durch die langsame Diffusion des Proteins widergespiegelt, die mit 1,4 – 2,4 µm2/s zwischen der von zytosolischen und Transmembran -Proteinen liegt. Die ermittelten Diffusionskoeffizienten und der Verlauf der STAT5b-Aktivität können im Weiteren in Modelle für den JAK/STAT Signalweg eingefügt werden und so den Ablauf der Aktivierung in diesem System verdeutlichen. Diese Arbeit leistet somit einen Beitrag zum tieferen Einblick in die Signalweiterleitung.
Die vorliegende Dissertation befasst sich mit der Synthese und Analyse von Bisguanidinen mit flexiblem Biaryl-Rückgrat und deren Umsetzung zu Bisguanidinkomplexen der Gruppe-10-Übergangsmetalle. Darüber hinaus wurden potentielle Anwendungen der hergestellten Komplexverbindungen in der Katalysechemie untersucht. Bei den eingesetzten Bisguanidinen 2,2’-Bis(N,N,N’,N’-tetramethylguanidino)-1,1’-biphenyl (LI), 2,2’-Bis(N,N’-dimethyl-N,N’-ethylenguanidino)-1,1’-biphenyl (LII), (R)-2,2’-Bis(N,N,N’,N’-tetramethylguanidino)-1,1’-binaphthalin (LIII), (R)-2,2’-Bis(N,N’-dimethyl-N,N’-ethylenguanidino)-1,1’-binaphthalin (LIV), 3,3’-Bis(N,N,N’,N’-tetramethylguanidino)-2,2’-bipyridin (LV) und 3,3’-Bis(N,N’-dimethyl-N,N’-ethylenguanidino)-2,2’-bipyridin (LVI) handelt es sich um starke Stickstoffbasen. Anhand von Protonierungsexperimenten wurde gezeigt, dass die vorgestellten Bisguanidine der Klasse der Protonenschwammverbindungen angehören. Diese experimentellen Ergebnisse wurden durch quantenchemische Rechnungen gestützt. Es wurden Bisguanidinkomplexe unterschiedlicher Nuklearität, Koordinationsmodi und -geometrie erhalten. Die strukturelle und elektronische Vielfalt der Bisguanidine zeigte sich im Besonderen beim Wechsel vom homoaromatischen (LI–LIV) zum heteroaromatischen Rückgrat (LV und LVI). Im Falle der mit LI–LIV erhaltenen Koordinationsverbindungen agierten die Imin-Stickstoffatome als Lewis-Basen. Dadurch wurden κ2-koordinierte, tetraedrische Nickel(II)-Dihalogenidokomplexe (16–19) und κ1-koordinierte, quadratisch-planare Platin(II)-Olefinkomplexe (28 und 29) synthetisiert. Es erfolgte eine vollständige Charakterisierung der Koordinationsverbindungen, die im Falle der paramagnetischen Nickel(II)-Komplexe zusätzlich durch magnetische Messungen und detaillierte NMR-Untersuchungen sowie quantenchemische Rechnungen zur Bestimmung der Spindichteverteilung ergänzt wurde. In ersten Versuchen zur katalytischen Hydrosilylierung von Olefinen zeigten die Platin(II)-Komplexe 28 und 29 eine hohe katalytische Aktivität. Hingegen war die Selektivität bei der Oligomerisation von Ethen, welche durch die Nickel(II)-Komplexe 16–19 katalysiert wurde, nicht zufriedenstellend. In den Übergangsmetallkomplexen der Bisguanidine LV und LVI erfolgte die Koordination ausschließlich über die Pyridin-Sticktoffatome an das Metallzentrum. Das Bipyridin agiert in den Platin(II)- (31 und 32) und Nickel(II)-Komplexen (20 und 21) als Chelatligand und es werden einkernige Metallkomplexe erhalten. Dabei konnte gezeigt werden, dass das kleinere Nickel(II)-Ion unter vollständiger Ligandensubstitution bevorzugt mit drei Molekülen der Bisguanidinobipyridine zu den dikationischen, oktaedrischen Nickel(II)-Komplexen 20 und 21 reagiert. Des Weiteren gelang die Synthese und vollständige Charakterisierung der binuklearen Palladium(II)-Allylkomplexe 22 und 23 unter der in der Literatur bisher nicht beschriebenen κ1-Koordination der Liganden. Als Katalysatoren der Heck-Reaktion zeigten die Verbindungen 22 und 23 in ersten Versuchen eine hohe Aktivität.
The hope of a successful treatment of genetically based diseases like cancer increased with the development of gene therapy in the early 1990’s. The major challenge thereof is the safe and efficient transfer of nucleic acids into eukaryotic cells. As viral vectors (genetically modified viruses) are toxic and immunogenic, non-viral gene delivery systems (synthetic polymers) lacking these disadvantages continue to gain a high profile. To achieve an efficient and safe delivery of nucleic acids into living cells, low generation asymmetric peptide dendrimers comprised of the basic amino acids lysine and arginine were synthesized using the well established solid phase peptide synthesis approach. The mechanisms of peptide dendrimer/DNA complex(dendriplex) formation as well as the complex stoichiometry were inspected by electrophoretic mobility shift assay and a PicoGreen exclusion assay. The dendriplex formation is of electrostatic nature and strongly depends on the charge ratio as well as on the number of dendrimer head group charges. The peptide dendrimers are able to form stable complexes with DNA of various sizes at a charge ratio of two and higher. For effective tracing of the pathway through the cell membrane and quantitative evaluation of cellular uptake the peptide dendrimer was site-specifically labelled with a fluorophore. The optimal transfection charge ratio and the capacity of the peptide dendrimers as a DNA delivery system were examined in two different cell lines (NIH3T3 EpoR and HeLa) by confocal laser scanning microscopy. Efficient transfection of plasmid DNA as well as of single and double stranded oligonucleotides of various lengths with minimal cell toxicity was achieved for both cell lines at a charge ratio of five. The intracellular distribution of the dendriplexes was limited to the cell cytoplasm. The cellular internalization of dendriplexes was found to occur by energy dependent endocytosis including both clathrin-dependent and clathrin-independent uptake pathways. Furthermore, the actin cytoskeleton and the lipid rafts/caveolae are not involved in the dendriplexe uptake mechanism. Due to their low pH (between 5.5-6.5), fluorescent dendriplexes are mainly directed to lysosomes and partially to mitochondria. These studies has demonstrated that low fluorescent labelled generation asymmetric peptide based dendrimers can transfect different mammalian cells in vitro. To possess a potential as a non-viral gene delivery vectors for gene therapy a significant improvement of their transfection efficiency is needed.
The lack of reliable quantitative methods in fluorescence microscopy prevents the detailed investigation of basic molecular processes. Single-molecule fluorescence spectroscopy offers several techniques to determine the stoichiometry of fluorescent probes. Among them, an approach using the single-photon emission of an individual quantum system, also known as photon antibunching, yields access to both the emitter number and their molecular brightness. Previous work demonstrated the feasibility of the method to estimate up to five dyes without further physical characterization. In this work, I investigated and improved the reliability and robustness of this method. I developed different fluorescent probes with a defined label stoichiometry to explore the performance of our approach in experiments. I could demonstrate, in combination with simulations, that it can provide reliable estimates of up to 18 fluorescent emitters at a time resolution of approximately 200 ms. Furthermore, I inspected the dependency of the estimation bias and precision on the laser intensity, the analysis time and the number of expected molecules in detail. My results designate the scope for future stoichiometry determinations. In initial experiments, I analyzed the labeling distributions of different fluorescent probes. In addition, I could combine our counting approach with super-resolution STED-microscopy and identify critical parameters for possible applications
Mechanical force alters a protein's stability not only due to its ability to unfold the biomolecule. As soon as a disulfide bond cross-linking the protein is exposed to force, its reduction rate is altered. Our first aim was quantifying the direct effect of force onto the chemical reactivity of sulphur-sulphur bonds in contrast to indirect, e.g. steric or mechanistic, influences. To this end, we evaluated the dependency of a disulfide bond's redox potential on a pulling force applied along the system. Our hybrid quantum and molecular mechanics simulations of cystine as a model system take conformational dynamics and explicit solvation into account and show that redox potentials increase over the whole range of forces probed here (30 - 3320 pN), and thus even in the absence of a significant disulfide bond elongation(<500 pN). Instead, at low forces, dihedrals and angles as the softer degrees of freedom are stretched and contribute to the destabilization of the oxidized state. We find physiological forces to be likely to tune the disulfide's redox potentials to an extent similar to the tuning within proteins by point mutations. Next, we asked how internal strain resulting from the protein structure tunes redox potentials using free energy calculations, more precisely nonequilibrium Molecular Mechanics transformations and the Crooks Gaussian Intersection method. We added a residue to the Charmm force field that models a disulfide bond in the reference state and that can be transformed into a thiol in the product state. To our knowledge, this is the first approach to open a covalent bond by means of free energy transformation. We tested our method on E. coli and S. aureus thioredoxin, and could partly reproduce relative redox potentials of the wild-type and some mutants. We discuss promising routes to improve the accuracy of these challenging calculations. Finally, we investigated the impact on force-induced unfolding by a special type of disulfide bond, a vicinal disulfide that links two adjacent cysteines. Our model system here is the von Willebrand factor (vWF) A2 domain. We observe similar stabilities in equilibrium for both the native system and its analogue with the disulfide bond broken and also similar collective motions. Application of an external force, however, induces a difference: Unfolding of the vWF A2 domain with the vicinal disulfide bond present leads to higher rupture forces than when it is missing. This indicates that the vicinal disulfide bond prevents the domain from unintentional unfolding.
In der hier vorliegenden Arbeit wird die Synthese von 1,4-disubstituierten 1,2,3-Tri-azo¬len und ihre Anwendung als Liganden für Übergangsmetalle vorgestellt. Diese Sub¬¬strate bieten verschiedene Koordinationsmöglichkeiten, sie können koordinative Bin¬¬dun¬gen über die Stickstoffatome des Heterocyclus ausbilden, der C5-Kohlenstoff im 1,2,3-Triazol kann deprotoniert werden und als anionischer Ligand fungieren oder es können Donorfunktionen in den Substituenten in 1-und 4-Stellung des 1,2,3-Tri¬azols eingebaut werden. Zum einen wurden in einer linearen Synthese beginnend mit einer Kupfer(I)-¬kata¬ly-sier¬ten Azid-Alkin Cycloaddition zwei 1,2,3-Triazole herge¬stellt, die einerseits eine Amin¬funktion und andererseits eine Carboxylat- bzw. Sul¬fo¬natgruppe an den Substi¬tuenten aufweisen. Diese Moleküle wurden mit einem Ru¬the¬nium¬vor-läuferkomplex um¬¬ge¬setzt und es wurden Hinweise auf die Bildung zweier Komplexe erhalten, in de¬nen das Ruthenium an den C5-Kohlenstoff, die Amin- und die Säurefunktion gebun¬den ist und die synthetisierten Triazole so als tri¬den-tate Liganden agieren. Des Wei¬te¬ren wurde als Referenz¬system zur Untersuchung der eben genannten Substrate ein 1,2,3-Triazol syntheti¬siert, das lediglich am N1-Stickstoff mit einer Aminfunktion versehen ist, in 4-Stellung jedoch keinen Substituen¬ten mit Donorfunktion trägt. Mit die¬sem Liganden wurden nach Umsetzung mit Ruthenium und Palla¬dium Komplexe er¬hal¬ten, in denen die Metalle durch den Stick¬stoff der Aminfunktion und den N2 Stick¬stoff des Heterocyclus koordiniert werden. Zum anderen wurden zwei 1,2,3-Triazole synthetisiert, die aufgrund ihrer Substi-tuenten einen großen räumlichen Anspruch besitzen. Eines konnte in C5-Stellung depro¬toniert werden. Auf diese Weise wurden das Iod- und das Trimethylsilylderivat erhal¬ten. Ersteres konnte in eine Grignardverbindung überführt werden; diese re-agiert mit Kupfer- und Goldsalzen zu ein- und dreiwertigen Münzmetallkomplexen.
Diese Arbeit untersucht den resonanten Augerprozeß in gasförmigem Wasser. In diesem Prozeß entsteht ein hochangeregter, kurzlebiger Zustand des Wassermoleküls, indem durch elektromagnetische Strahlung unterhalb der Rumpfionisationsschwelle von 540 eV ein Elektron aus dem Rumpforbital in ein unbesetztes Valenzorbital gehoben wird. Durch Autoionisation wird innerhalb einiger Femtosekunden das Rumpforbital wieder aufgefüllt und ein Augerelektron aus einem der drei äußeren Valenzorbitale ausgesendet. Aufgrund der elektronischen Übergänge entfaltet sich auch eine komplexe Kerndynamik auf einer vergleichbaren Zeitskala. Daher liegt der methodische Schwerpunkt dieser Arbeit in der Simulation der Kerndynamik im resonanten Augerprozeß. Das Hauptergebnis, das ausführlich präsentiert wird, ist das Spektrum der Augerelektronen, berechnet bei verschiedenen Anregungsbedingungen. Die Bestimmung aller relevanten elektronischen Zustände und die quantenchemische Berechnung ihrer adiabatischen Potentialflächen für die Kernbewegung wurde im wesentlichen von Prof. Martin Jungen (Basel) durchgeführt, seine Vorgehensweise und die Ergebnisse werden in dieser Arbeit zusammengefaßt. Da die valenzionisierten Zustände vibronisch koppeln, wurden ihre Potentialflächen in gekoppelte diabatische Potentialflächen transformiert. Dies wird ausführlich dargestellt. Anhand simulierter Photoelektronenspektren wird die gute Qualität der berechneten kationischen Flächen und der Diabatisierung gezeigt. Um mögliche Interferenzeffekte der Kerndynamik zu berücksichtigen, wurden Bewegungsgleichungen für die Kerne verwendet, die auf der zeitabhängigen Schrödingergleichung des Systems aus Wassermolekül und Strahlungsfeld beruhen. Diese Methodik kam bereits in vorangegangen Arbeiten bei zweiatomigen Molekülen erfolgreich zum Einsatz, in dieser Arbeit wurde zum ersten Mal der resonante Augerprozeß in einem Molekül mit drei Freiheitsgraden der Kernbewegung simuliert. Die Lösung der Kernbewegungsgleichungen erfolgte mit der MCTDH-Methode (multiconfiguration time-dependent Hartree), deren Grundzüge in dieser Arbeit auch vorgestellt werden. In der Diskussion der berechneten resonanten Augerspektren wird der Einfluß der Kerndynamik im rumpfangeregten Zustand auf die Schwingungsanregung im Kation aufgezeigt und auf die Möglichkeit zur Fragmentbildung im Molekül eingegangen. Bei genügender spektraler Auflösung können auch Effekte der vibronischen Kopplung im Spektrum identifiziert werden, wozu z.B. die Aufspaltung von spektralen Linien gezählt wird. Die Übereinstimmung der Ergebnisse mit experimentellen Spektren ist v.a. bei Verwendung der diabatischen Potentialflächen sehr gut.
N-heterozyklische Carbene (NHC) können in vielfältiger Weise modifiziert werden, indem zusätzliche Funktionalitäten über die Stickstoffatome des heterozyklischen Rings eingeführt werden. Viele verschiedene donorfunktionalisierte NHC, ihre Übergangsmetall-Komplexe und ihre Verwendung in der homogenen Katalyse wurden bisher untersucht. Während Stickstoff-, Sauerstoff- oder Phosphordonoren häufig auftreten, sind NHC mit einer Schwefelfunktionalität relativ selten. Beispiele schwefelfunktionalisierter NHC enthalten meist eine Thioethergruppe und nur selten das reaktivere freie Thiol. In dieser Arbeit wurden die Synthese von 1,2,4-Triazoliumsalzen mit einem Thiophenolsubstituenten und deren Anwendung als NHC-Thiolato-Liganden erarbeitet. Durch eine modulare Synthesestrategie konnten neben thiolsubstituierten Mono- und symmetrischen Bistriazoliumsalzen auch unsymmetrische Bistriazoliumsalze erhalten werden, in denen eine thiolsubstituierte Triazolium-Einheit mit einer zweiten, nicht weiter funktionalisierten Triazolium-Einheit verbunden ist. Die Freisetzung des Thiols durch Abspaltung der Schutzgruppe bildete in der Syntheseroute jeweils den letzten Schritt. Bei der Oxidiation der so erhaltenen Ligandenvorläufer mit Dimethylsulfoxid wurde beobachtet, dass nicht die zu erwartenden Disulfide entstehen, sondern das Triazoliumsalz unter Ringschluss zum Benzothiazol oxidiert wird. Nach Deprotonierung konnte das thiolsubstituierte Triazoliumsalz als C,S-Chelatligand an verschiedene Übergangsmetalle koordiniert werden. Die resultierenden Palladium- und Nickel-Komplexe wurden erfolgreich als Katalysatoren in Kreuzkupplungsreaktionen eingesetzt. Im Falle der unsymmetrischen Bistriazoliumsalze konnte das thiolfunktionalisierte Triazolium-Fragment mit einer milden Base deprotoniert werden, während die andere Triazolium-Einheit unter diesen Bedingungen unberührt blieb. Durch eine solche selektive Deprotonierung des Bis(NHC)-Liganden ist es gelungen, stufenweise zunächst Palladium und danach Kupfer bzw. Gold unter Bildung von heterobimetallischen Komplexen einzuführen.
Novel fluorophores were synthesized, characterized, and examined with respect to their metal-binding properties. These compounds (Figure 1) consist of a heteroaromatic core substituted with two triazole rings, synthesized via copper-catalyzed azide-alkyne cycloaddition. Binding of a metal ion is achieved through coordination between two nitrogens (one in the triazole ring, and one in the heteroaromatic core). For practical purposes, these sensors must be soluble in water. This is accomplished through the use of a water-soluble side chain; in this case, one with a branched oligoethylene glycol substituent. This bulky side-chain decreases fluorescence quenching from intermolecular aggregation, resulting in metal ion sensors that are brightly fluorescent, even in water. Figure 1 Metal ion sensors. R represents tri(ethylene glycol) monomethyl ether, X represents H, F, or Cl, and Y represents O, S, or Se. These molecules are designed so that they serve as the binding receptor and the sensing element. We are then able to tune the structure of the core molecule, thereby adjusting the metal-binding activity, as well as the optical properties. In Figure 1, the series of molecules on the left is tunable through halogen substitution of the phenazine core. On the right, variation of the chalcogen heteroatom serves the same purpose. Increasing understanding of this kind of structure-property relationship is vital for the future construction of highly sensitive and selective fluorescent sensors. The results show that of the phenazine-containing compounds, those that are more electron-poor (halogen-substituted) are not able to efficiently bind metal ions in aqueous solution. A similar effect is seen with the benzochalcogendiazole compounds, with binding affinity increasing moving down the group, parallel to the decreasing electronegativity of the chalcogen atom. The heteroaromatic core also plays a significant role in the selectivity; the phenazine compound functions as a selective silver sensor, while the benzochalcogendiazole compounds respond to copper, silver, and nickel. The response to each metal is unique, and statistical analysis of the resulting data enables differentiation of these three metals with a single molecule.
Motivation dieser Arbeit ist die Präparation ultradünner Nanomembranen (< 10 nm), die außerdem biokompatibel bzw. proteinresistent sind, um als Trägerfilm biologischer Proben für die hochauflösende Transmissionselektronenmikroskopie (HRTEM) Verwendung finden zu können. Als Basis werden selbstaggregierende Monolagen (SAMs) aus 4‘-Nitrobiphenyl-4-thiol (NBPT) auf einem Au(111)-Substrat eingesetzt, die durch Bestrahlung mit niederenergetischen Elektronen lateral quervernetzt und deren terminale Nitrogruppen zu oberflächengebundenen Aminogruppen reduziert werden (iNBPT). An diese lassen sich Epoxid-terminierte Polyethylenglykole (PEG) derart koppeln, dass die resultierende PEG-iNBPT Doppelschicht bei einer Gesamtdicke von nur 5 nm biokompatibel wird und der Adsorption von Fibrinogen als Testprotein widersteht. Ferner wird ellipsometrisch und röntgenspektroskopisch (X-ray photoelectron spectroscopy, XPS) untersucht, welchen Einfluss Schichtdicke und Packungsdichte des PEG-Films auf die proteinabweisenden Eigenschaften des PEG-iNBPT-Films ausüben und die Resultate mit denen eines etablierten, biokompatiblen SAMs aus Oligoethylenglykol-terminiertem Undecanthiol verglichen. Zuletzt muss der PEG-iNBPT Film vom Substrat abgelöst und als Membran über ein TEM-Grid mit freistehenden Bereichen von mindestens 10 x 10 µm² gespannt werden können, ohne dass die Folie dabei ihre Biokompatibilität verliert. Ihre Eignung als HRTEM-Trägerfilm wird anhand von Gold-Nanopartikeln und dem Eisenspeicherprotein Ferritin demonstriert. Wegen der vielseitigen Anwendungsmöglichkeiten von NBPT-SAMs wäre es interessant, ein alternatives SAM-bildendes System mit ähnlichen Merkmalen zu besitzen. In einer führen Arbeit wurde bereits aufgeführt, dass 4‘-Cyanobiphenyl-4-thiol (CBPT) Monolagen ebenfalls durch Elektronenbestrahlung quervernetzt und die terminale Nitrilgruppe zu einer Aminogruppe reduziert wird. Darauf aufbauend wird in dieser Arbeit gezeigt, dass sich CBPT-SAMs als negatives Resist-Material in Elektronenstrahllithographie, sowie als Templat in der chemischen Elektronenstrahllithographie (EBCL) eignen. In diesem Zusammenhang wird der Einfluss der Elektronenenergie im Bereich von 0.5 10 keV auf den Grad der Quervernetzung aromatischer SAMs sowie auf die Effektivität der Reduktion terminaler Gruppen beleuchtet, um so Aufschlüsse über zugrundeliegende Prozesse bei der Elektronenbestrahlung selbstaggregierender Monolagen zu gewinnen. Außerdem wir der Frage nachgegangen, ob alle durch elektronenstrahlinduzierte Reduktion entstandenen, oberflächengebundenen Aminogruppen gleichermaßen in der Lage sind, als Anker zur Kopplung weiterer Moleküle zu dienen. Die SAM-basierenden, PEGylierten Nanomembranen sind mit 5 nm zwar außerordentlich dünn, aber nur einseitig biokompatibel. Es wird in dieser Arbeit eine zweite Präparationsmethode vorgestellt, die es ermöglicht, direkt und ohne den Umweg über quervernetzte SAMs, doppelseitig biokompatible Nanomembranen variabler Dicke herzustellen, die ab 20 nm ausreichend mechanische Stabilität aufweisen, um freistehend existieren können. Als Vorstufe dient ein aus Epoxid- und Amino-terminierten, multifunktionellen Polyethylenglykolen bestehender Zweikomponentenfilm, der per Rotationsbeschichtung auf ein flaches Substrat aufgebracht und thermisch quervernetzt wird. Die 6 - 300 nm dicken PEG-Filme werden ellipsometrisch sowie XPS- und infrarotspektroskopisch charakterisiert und auf ihre filmdickenanhängige Proteinresistenz untersucht. Durch die Quervernetzung zeigt das polymere Netzwerk ein Hydrogel-typisches, reversibles Quellverhalten beim Kontakt mit Wasser, welches eingehend ellipsometrisch analysiert wird. Zudem können Gold-Nanopartikel (AuNPs) irreversibel und in hohen Dichten in der Matrix des PEG-Films immobilisiert werden und so das Quellverhalten in eine optische Antwort des Systems umwandeln. Ein zweiter Aspekt bezüglich der PEG-Filme betrifft ihre Reaktion auf die Bestrahlung mit Elektronen. Das Verhalten von Polyethylenglykolen wird diesbezüglich erstmals systematisch mit Hilfe der PEG-Filme XPS- und infrarotspektroskopisch sowie mit Röntgen-Nahkanten-Absorptions-Spektroskopie (NEXAFS) untersucht. Ferner wird rasterkraftmikroskopisch (AFM) und fluoreszenzmikroskopisch ermittelt, wie sich die dosisabhängige Elektronenbestrahlung auf die PEG-Filme in Bezug auf Quellverhalten, Topographie, Benetzbarkeit und Biokompatibilität auswirken. Zuletzt werden die PEG-Filme von ihrem Substrat abgehoben, freistehend über eine Gitterstruktur gespannt und die mechanischen Eigenschaften wie Elastizitätsmodul und Eigenspannung der Membranen bestimmt. Auch in diese können Gold-Nanopartikel eingebettet werden und somit eine Verbundmembran mit erweiterten optischen Eigenschaften hergestellt werden. Sie zeigt zudem ebenfalls ein ausgeprägtes Quellverhalten, welches zu veränderten Eigenschaften in Abhängigkeit von äußern Parametern wie Temperatur oder Luftfeuchtigkeit führt.
This work focuses on the synthesis and characterization of the new guanidinyl-functionalized aromatic compounds (GFA-4) 1,4,5,8-tetrakis(N,N,N',N' - tetramethylguanidinyl)naphthalene (ttmgn) and 1,4,5,8-tetrakis(N,N,N',N'-dimethylethylenguanidinyl)naphthalene (tdmegn) as well as on the coordination chemistry of these ligands and the use of the new coordination compounds to stabilize monoanionic polyhalides. ttmgn and tdmegn represent strong electron-donors and redox-active ligands. Investigation of the redox behavior using cyclic voltammetry showed the existence of two reversible oxidation processes (oxida-tion to two and fourfold oxidized species) respectively, where tdmegn is a slightly better electron donor in CH3CN than ttmgn. Two and fourfold oxidized ligands were obtained fully characterized. Study of the basic properties showed ttmgn to be a double proton sponge. The protonation experiments on these "superbases" were supported by quantum chemical calculations. A general feature of the characterized coordination compounds was the displacement of the metals from the aromatic plane. The copper(I) complexes [ttmgn(CuI)2] and [ttmgn(CuBr)2] were synthesized and their redox chemistry analyzed. Magnetic superexchange through the ligand unit is studied for the binuclear Co(II) complexes trans-[ttmgn(CoCl2)2] and cis-[tdmegn(CoCl2)2]. SQUID measurements show an extremely weak antiferromagnetic coupling. The dynamic behavior of the metal centers was studied on the example of the Al(III) complex [ttmgn(AlMe2)2][BPh4]2 using NMR experiments. Furthermore, a number of new mono- and binuclear cationic boron complexes was prepared with the ligands ttmgn and btmgn (1,8-Bis(N,N,N',N'-tetramethylguanidinyl)naphthalene). The exchange process between the BF2 groups and BF4 anions in the salt [ttmgn(BF2)2][BF4]2 measured with 19F EXSY NMR spectroscopy points to a complexation equilibrium. It could be shown that the guanidine-boron bond is sufficiently weak to allow the presence of a small quantity of the redox-active ttmgn in solution. Finally, a strategy for the synthesis of polyhalide monoanions was introduced, in which the reducing agent ttmgn is in the cationic complex [ttmgn(BF2)2][BF4]2 "wrapped". Wrapped up in the cationic complex, the reduction power is evidently greatly reduced. Moreover, the relatively large size of the cationic complexes conduces to stabilize monoanionic polyhalides. So reaction of [ttmgn(BF2)2][BF4]2 with I2 and Br2 led respectively to the formation of [I7]‒ and [Br5]‒. This work provides the first complete characterization of the [Br5]‒ monoanion including X-Ray crystal structure.
Das Ziel dieser Arbeit ist die Entwicklung dinuklearer Galliumhydridverbindungen, in denen sich die Galliumatome in einer Entfernung zueinander befinden, die bindende Wechselwirkungen zwischen ihnen erlaubt. Diese Verbindungen sollen auf ihre Eignung als Substrate einer reversiblen Dehydrokupplung unter Bildung einer direkten Gallium-Gallium-Bindung untersucht werden.
In der vorliegenden Arbeit wurden überwiegend Verbindungen untersucht, die sich von Trimethylamingallan (H3Ga·NMe3) und bizyklischen Guanidinen (hppH, Htbn und Htbo) ableiten. Diese Liganden eignen sich als elektronenreiche Systeme mit einer Neigung zu verbrückender Koordination ausgezeichnet zur Synthese dimerer Verbindungen, in denen die koordinierten Atome eine relative Flexibilität an ihren Koordinationsstellen besitzen. Auf diese Weise gelang die Darstellung des Dimers [H2Ga(μ-tbo)]2.
Die zum Vergleich synthetisierten dimeren Verbindungen aus subvalentem Galliumiodid und azyklischen Guanidinaten weisen hingegen eine terminale Substitution der Liganden auf, was sie für die Zielsetzung dieser Arbeit weniger geeignet macht. Aus den Umsetzungen mit hppH und Htbn konnten zunächst nur sauerstoffhaltige Zyklen der Art [Ga3H5(μ3-O)(μ-Guan)2] (Guan = hpp−, tbn−) erhalten werden. Diese entstehen durch gezielte Zugabe von Wasser zur Reaktionsmischung und bergen die Möglichkeit der Substitution von zwei weiteren Hydridatomen durch einen dritten bizyklischen Liganden, was an zwei Beispielen gezeigt werden konnte. Durch den katalytischen Einsatz der Iridiumverbindung [(p-HPCP)IrH2] konnten das Dimer [H2Ga(μ-hpp)]2 und das guanidinstabilisierte Galliumguanidinat [H2(tbn)·Htbn] erhalten werden. Es gelang somit durch Katalyse die Spezifität der Reaktionen bei tiefen Temperaturen zu erhöhen.
Während die Dehydrierung von [H2Ga(μ-tbo)]2 weder auf thermischen Weg noch durch Katalyse zum gewünschten Ergebnis führte, scheint der Einsatz des frustrierten Lewispaares PtBu3/B(C6F5)3 möglicherweise zum Ziel geführt zu haben. Die analytischen Daten enthalten Hinweise auf die Bildung zweier Dehydrierungsprodukte, möglicherweise [HGa(μ-tbo)]2 und [H2Ga(μ-tbo)HGa(PtBu3)(μ-tbo)]+[HB(C6F5)3]−.
In der vorliegenden Arbeit werden vornehmlich niedervalente Galliumverbindungen behandelt. Es konnten einige neue Vertreter dieser Verbindungsklasse synthetisiert und durch Kristallstrukturanalyse charakterisiert werden. Anhand der Verbindungen [{K([18]Krone-6)(thf)2}2{K([18]Krone-6)I (Ga2I6)], [{Ga(Tol)}2{Ga(OTf)3}2], BrI[Ga{(N(ipp)CMe)2CH}]2, [IGa{(N(Mes)CMe)2CH}]2 und [Ga2I4(Pyrazin)2] konnte das Dimerisierungsverhalten von zweiwertigen Galliumverbindungen untersucht und diskutiert werden, eine Verifizierung der einzelnen Strukturen erfolgte mittels DFTRechnungen. Die Verbindungen [{Ga([18]Krone-6)}2(Ga2I5O)2], [{Ga([18]Krone-6)(thf)2}{Ga(OTf)4(thf)2}], [{Ga([18]Krone-6)(thf)2}GaI4] und [{Ga([18]Krone-6)}GaI4] beinhalten exemplarisch ein Galliumatom in der Oxidationsstufe +I in der Lücke eines [18]Krone-6-Ethers. Sowohl die Art der koordinativen Sättigung am subvalenten Galliumatom, als auch die Natur der jeweiligen Gegenionen wurden ausführlich besprochen und anhand von quantenmechanischen Rechnungen verifiziert bzw. eingehender untersucht. Die Verbindung [{Ga(Tol)}2{Ga(OTf)3}2] gibt dabei einen Ausblick auf weiterführende Experimente, da sie sich als ausgezeichneter Präkursor auf dem Gebiet der Gallium-Clusterchemie erweisen könnte.
The steadily increasing demand for energy worldwide has resulted in the depletion of the existing fossil energy resources and the pollution of the atmosphere by greenhouse gases such as CO2, which are responsible for global warming. To curb these problems, research activities aiming at CO2 conversion into value-added products, e.g. fuels like methanol, using sunlight have intensified over the last few years. In this work, TiO2 nanoparticles functionalized with perylene-based dyes containing either a carboxylic acid or anhydride group as molecular anchor to the TiO2 surface were studied as potential photocatalyst for solar light-driven CO2 reduction. The dye binding geometry is of particular importance since it influences the electron transfer from the dye to TiO2 and hence the photocurrent output of any given dye/TiO2 system. Two dyes, ID1157 and ID1152, structurally identical apart from their anchor group, were selected to allow direct comparison. In addition, a simple model substance bearing an anhydride group was investigated to facilitate the interpretation of the lesser known anhydride binding mode. Surprisingly, despite their structural similarity, the observed photocurrent amplitude of the ID1157/TiO2 system containing a carboxylic acid anchor was much higher than for the ID1152/TiO2 system containing an anhydride anchor. With the help of ultraviolet/visible (UV/Vis) absorption, infrared (IR), Raman and vibrational sum-frequency generation (VSFG) spectroscopy it was sought to determine whether the photocurrent signals were correlated to the dissimilar anchor groups and their binding modes. From the UV/Vis spectra it was found that the anhydride group opened upon binding. As for the IR and Raman studies it could be concluded that the carboxylic acid anchor of ID1157 and both carboxylate groups of the opened anhydride of ID1152 bound via a bidentate bridging pattern. Furthermore, it was shown from the background-suppressed VSFG spectra of the bound dyes in air and water that these adsorbed in an orderly fashion, ID1157 more so than ID1152, but with both only slightly disturbed in the presence of water. In addition, it was found that all molecules in the ID1157 dye layer were adsorbed on the TiO2 surface via chemisorption. By contrast, the ID1152 dye layer was composed of chemisorbed as well as physisorbed dyes, the latter being coordinated via a closed anhydride group. Also, ID1157 displayed a higher surface density of adsorbed molecules compared to ID1152. From a preliminary polarization analysis, it was suggested that the dyes with carboxylic acid anchor adopted a tilted binding geometry. In view of the results obtained on the binding geometry of the dyes ID1157 and ID1152 it was possible to identify some criteria important for the generation of a high photocurrent: 1) binding of the dye via chemisorption with 2) a high surface density and possibly through 3) a tilted geometry. These findings have important implications for the understanding of the mechanism of dye functionalization. Finally, methanol and CO2 adsorption on TiO2 films was investigated by VSFG spectroscopy. Only molecularly adsorbed methanol was observed which was easily displaced by water or methanol/water mixtures. However, CO2 adsorption could not be detected in the spectral range which was investigated.
The impact of the nuclear dynamics during an electronic decay process followed by fragmentation in a diatomic system is investigated for three different examples, by using a time-dependent approach.
The first example is the prediction of the interatomic Coulombic decay (ICD) process in NeAr, following the Ne 1s Auger decay. It is a two-step (cascade) decay process where the first step is a fast Auger decay and the second step is the ICD of interest. A full cascade calculation has been performed to provide the (time-resolved) Auger electron and (time-resolved) ICD electron spectra. Our results show that the line width of the Auger electron spectrum contains also the information on the total ICD width at the equilibrium internuclear distance of NeAr. In addition, simulations show that the nuclear motion during the first Auger step has no impact on the following ICD process. This ICD process has been verified by experiment, and if a simple modification of the ab initio ICD transition rate is adopted, our simulated ICD spectrum agrees well with the experimental result.
For an electronic decay process followed by fragmentation, the energy spectrum of the emitted electron and the kinetic energy release (KER) spectrum of the ionic fragments are usually considered to be mirror images of each other. This is termed "mirror image principle" and is often applied in experiments. It is usually valid for the ICD electron spectrum and its corresponding KER spectrum. However, the principle is merely an empirical rule and can break down even in a diatomic system. The molecular Auger process in CO is chosen as the second example, as it exhibits such a break down of the mirror image principle. Calculated KER and electron spectra for this process also agree well with experiment.
The resonant Auger process of HCl is chosen as the last example to demonstrate that the interaction between a molecule and an intense laser pulse (as are available today in free electron lasers) can lead to a strong light-induced non-adiabatic effect. It is a general effect that can be found in molecules interacting with an intense laser pulse, which gives rise to strong molecular overall rotation.
Besides the above applications, a new elegant and numerically efficient formulation for evaluating the (time-resolved) KER spectrum in an electronic decay process followed by fragmentation is derived in this work. The KER spectrum now has a simple physical interpretation: it is the accumulated (over time) generalized Franck-Condon factor between the nuclear wave packet on the intermediate decaying state and the discrete continuum eigenfunctions of the dissociative final state. This new representation allows one to analyze the KER and the electron spectra, and it provides the conditions for the mirror image principle to hold.
Die vorliegende Arbeit beschäftigt sich mit der Synthese und Charakterisierung neuer Alkylzinkverbindungen mit stark nukleophilen Stickstoffliganden sowie der Untersuchung der chemischen Eigenschaften und der Reaktivität dieser Verbindungen. Alkylzinkkomplexe mit basischen Amidliganden eignen sich zur Fixierung von CO2, wobei es durch Insertion eines CO2-Moleküls in die Zn-N-Bindung zur Bildung von Zinkcarbamaten kommt. Durch Umsetzung dieser tetrameren Carbamatkomplexe mit N,N’–chelatisierenden Bisguanidinen konnten monomere Alkylzinkkomplexe synthetisiert werden, deren Carbamatliganden in dem seltenen μ1, η1 -Bindungsmodus vorliegen. In anschließenden Experimenten wurde die Umsetzung der monomeren Komplexe zu kationischen Zinkverbindungen durch Alkylabstraktion untersucht. Des Weiteren wurden mehrere trisubstituierte Guanidinliganden synthetisiert. Diese können zu anionischen Guanidinaten deprotoniert werden, die in Komplexen Metallamidbindungen ausbilden. Die Ligandsynthesen gelangen durch katalytische Guanylierung der jeweiligen Amine. Die fluoreszierenden Guanidin-Pyridin-Hybridliganden 2-(N,N’-Diisopropylguanidino)pyridin (L1H2) und 2-(N,N’-Diisopropylguanidino)chinolin (L2H2) konnten mit Hilfe von ZnMe2 in die entsprechenden Zinkguanidinate überführt werden. Es konnte dabei gezeigt werden, dass bei Raumtemperatur monoanionische Zinkguanidinate zugänglich sind, während eine Erhöhung der Reaktionstemperatur zu einer vollständigen Deprotonierung des Liganden L1H2 und zur Bildung eines dianionischen Zinkguanidinats führt. Dieses enthält neben zwei Zinkatomen mit der bevorzugten Koordinationszahl vier auch zwei Zinkatome, die lediglich dreifach koordiniert sind. Niedrig koordinierte Metallzentren zeigen Eigenschaften, die beispielsweise für Anwendungen in der Katalyse interessant sind. Die Reaktivität der synthetisierten dimeren Zinkguanidinate wurde sowohl gegenüber koordinierenden Verbindungen wie CH3CN oder Pyridin, als auch gegenüber CO2 untersucht. Es wurden außerdem neue Guanidinliganden mit mehreren Guanidineinheiten dargestellt, so unter anderem das Tetrakisguanidin 1,2,4,5-Tetrakis(N,N’-diisopropylguanidino)benzol (L4H8). L4H8 gehört der Verbindungsklasse der Guanidin-funktionalisierten Aromaten (GFAs) an und zeigt die hierfür typischen Eigenschaften wie Redoxaktivität und hohe Basizität, die durch Umsetzung mit Oxidationsmitteln und Komplexierung des Liganden belegt werden konnten. Im Gegensatz zu bereits bekannten GFAs stellt L4H8 nicht nur einen Elektronendonator, sondern auch einen Protonendonator dar, was durch Isolierung des neutralen Produkts L4H6 bestätigt werden konnte und die neue Verbindung interessant für den Einsatz in Oxidationsreaktionen macht.
Zwei neue redoxaktive Stickstoffbasen 1,2,4,5-Tetrakis(tetramethylguanidino)benzol (1a) und 1,2,4,5-Tetrakis(N,Nˈ-dimethylethyleneguanidino)benzol (2a) wurden im Rahmen dieser Doktorarbeit hergestellt. Durch Substitution der beiden verbliebenen aromatischen Protonen der Verbindungen 1a und 2a durch Iod bzw. Nitrogruppen wurden vier weitere Verbindungen 1b und 2b bzw. 1c und 2c erhalten. Quantenchemische Rechnungen und experimentelle Untersuchungen zeigen auf wie sich die Substitution auf die Redoxeigenschaften und die Basizität der sechs Guanidinverbindungen auswirkt. Die berechneten Säurekonstanten erstrecken sich in einem pK(BH+)-Wertebereich von 19.6 bis 25.5. Die strukturelle Untersuchung der protonierten Verbindungen zeigt im Wesentlichen eine Änderung der Bindungslängen der Guanidingruppen. Die Energie des am tiefsten unbesetzten Orbitals wird durch die Substitution erheblich abgesenkt, so dass die HOMO-LUMO-Aufspaltung sinkt. Das macht sich unmittelbar an der roten Farbe der nitrierten Verbindungen 1c und 2c bemerkbar. Das Halbstufenpotential des Zweielektronenübergangs der sechs Guanidinbasen bezogen auf Fc/Fc+ liegt zwischen –0.76 und –0.41 V. Ein weiterer reversibler Einelektronenübergang ist bei 0.68-0.79 V zu erkennen. Die nach einer chemischen Oxidation strukturell untersuchten Produkte lassen sich als zwei Bisguanidinoallyl-Einheiten, welche durch eine C-C-Einfachbindung zusammengehalten werden, beschreiben. Erste dinukleare Pt(II)-Komplexe mit den Guanidinen 1a, 2a und 1c wurden hergestellt. Die Reaktion zwischen 1a bzw. 2a mit cis-[Pt(DMSO)2Cl2] führt zu den dikationischen Komplexen [(1a)Pt2(DMSO)2Cl2]2+ bzw. [(2a)Pt2(DMSO)2Cl2]2+. Die Liganden 1a, 2a und 1c reagieren mit Zeise-Dimer (Pt2(C2H4)2Cl4) zu den entsprechenden Komplexen [(1a)Pt2(C2H4)2Cl2]2+, [(2a)Pt2(C2H4)2Cl2]2+ und [(1c)Pt2(C2H4)2Cl2]2+. Abhängig vom verwendeten Lösungsmittel entstehen Cl‒ oder [Pt(L)Cl3]‒ (mit L = DMSO oder C2H4) als Anionen in den erhaltenen Verbindungen. In allen Fällen koordinieren beide Iminstickstoffatome der benachbarten Guanidineinheiten an das Platinatom. Die kationischen Komplexe liegen in Lösung, je nach Stellung der Chlorid- und DMSO/C2H4-Liganden, in einem Gleichgewicht zwischen zwei isomeren Formen cis und trans vor. Es wurden ausschließlich Komplexe des trans-Typ Isomers auskristallisiert. Abschließend wurde der Komplex [1c(CuI)2] hergestellt und seine Reaktivität in Bezug auf verschiedene Oxidationsmittel untersucht. Die hier vorgestellten Ergebnisse zeigen deutlich, dass sowohl basische Eigenschaften als auch das Redoxverhalten der Guanidinbasen durch die Substitution der aromatischen Protonen in einem weiten Bereich verändert werden können.
Die nichtlineare Multiplex Coherent Anti Stokes Raman Scattering- (MCARS)-Mikroskopie bietet auch ohne den Einsatz von Kontrastmitteln eine schnelle Möglichkeit zur Charakterisierung von Materialien und biologischen Proben. Dennoch bestanden im Verglich zur spontanen Ramanmikroskopie methodische Schwierigkeiten wie z.B. das Rekonstruieren der Raman-Information aus den bei CARS durch Interferenzeffekte verfälschten Spektren und das effiziente Analysieren von Daten für die chemisch-selektive Bildgebung1. Um diese Einschränkungen zu umgehen, wird in dieser Arbeit eine Vergleichsstudie zwischen zwei in der Fachliteratur für die Phasenrekonstruktion vorgeschlagenen Algorithmen durchgeführt. Zusätzlich werden neue Methoden zur Datenauswertung präsentiert, die das gesamte Schwingungsspektrum nutzen, um auch schwache Beiträge unterschiedlicher Probenbestandteile für die chemisch-selektive Bildgebung zu nutzen. Deren Anwendung auf Hirngewebe von Mäusen erlaubt die Unterscheidung zwischen biologischen Komponenten analog zu den Informationen, die von HE-gefärbten Referenzpräparaten geliefert wurden. Der direkte Vergleich mit der spontanen Ramanmikroskopie zeigt, dass MCARS in der Lage ist, mit einem relevanten Geschwindigkeitsvorteil Raman-äquivalente Informationen über die Probe zu liefern.
Das Ziel dieser Arbeit war die Entwicklung von halogenfreien Flammschutzmittelmischungen für den Einsatz in Polystyrolschäumen. Der Hintergrund für diese Forschung war die Aufnahme des derzeit verwendeten Flammschutzmittels Hexabromcyclododekan in die SVHC-Liste. Als Ersatz für diese Substanz wurden primär phosphorbasierte Verbindungen als Flammschutzmittel für Polystyrol untersucht. Um niedrige Beladungen zu erreichen, wurde weiterhin nach geeigneten Synergisten gesucht, welche zusammen mit den Phosphorverbindungen zu effizienten Flammschutzmittelmischungen führen. Basierend auf dem schon bekannten Synergismus zwischen phosphororganischen Verbindungen und elementarem Schwefel, wurden in dieser Arbeit thermisch stabile organische Disulfide als Flammschutzmittelkomponente eingeführt und deren synergistische Wirkung mit diversen Phosphorverbindungen untersucht. Im weiteren Verlauf der Arbeit kamen zusätzlich auch Carbonate, Ester, Diazoverbindungen und Peroxide zum Einsatz. Die Vorgehensweise wurde in drei Teile gegliedert: Zunächst wurden ausgewählte phosphororganische Flammschutzmittel und sulfidische Synergisten synthetisiert. In einem einfachen Screening in Block-Polystyrol wurden die Flammschutzmittel bzw. Mischungen dieser getestet. Bei erfolgreichen Ergebnissen der Brandtests wurden Polystyrolschaumkörper mit entsprechenden Verbindungen beladen. Zu diesem Zweck wurde ein Laborextruder in Betrieb genommen und durch gezielte Umbauten so modifiziert, dass Additive in EPS eingearbeitet werden konnten, ohne dass es zu einem Entweichen des Treibmittels Pentan kam. Aus dem so erhaltenen Material wurden mit einem speziellen Verfahren die Schäume hergestellt. Letztere wurden anschließend einer genormten Brandprüfung unterzogen. Der finale Schritt bestand in der Syntheseoptimierung einiger geeigneter Verbindungen. Bei allen durchgeführten Versuchen stand besonders die mögliche Anwendbarkeit in einem industriellen Maßstab im Vordergrund. Naturgemäß war die Flammschutzeffizienz einer Verbindung bzw. Additivkombination das wichtigste Kriterium, daneben wurden aber folgende Anforderungen an sämtliche Substanzen gestellt: •Preisgünstig zugänglich •Nicht-toxisch •Geruchsfrei, auch und besonders nach Einarbeitung in die Schaumkörper •Geringe Auswirkungen auf die Materialeigenschaften der Schäume •Speziell XPS: Thermisch stabil bis mindestens 200 °C •Speziell EPS aus Suspensionspolymerisation: Schwefelfrei Additive welche eine oder mehrere dieser Bedingungen nicht erfüllten, wurden als ungeeignet bewertet. Teilweise wurden diese Verbindungen aber weiter untersucht um theoretische Erkenntnisse zu erlangen. Es hat sich gezeigt, dass viele organische Disulfide hervorragende Synergisten für bestimmte Phosphorverbindungen darstellen. Peroxide erwiesen sich als gute Synergisten in festem Polystyrol, nicht jedoch in Schaumkörpern. Für die anderen getesteten Substanzklassen wurden keine positiven Ergebnisse erhalten. Auf diese Weise wurden letztlich fünf Verbindungen identifiziert, welche potentiell als Flammschutzmittel bzw. Synergisten in XPS eingesetzt werden können. Besonders die Verbindung 10 zeigte eine ausgezeichnete Flammschutzeffizienz, ohne dass ein zusätzlicher Synergist benötigt wurde. Die beiden benötigten Komponenten liegen hier im selben Molekül vor. Allerdings wurde zur Herstellung von 10 eine Vorstufe benötigt, deren literaturbekannte Synthese sich als ungeeignet für eine Übertragung in den großtechnischen Maßstab erwies. Es wurde daher eine neue Möglichkeit der Darstellung von 8 entwickelt, wobei günstigere Edukte verwendet wurden, die Aufarbeitung deutlich vereinfacht wurde und die Ausbeuten signifikant gesteigert werden konnten. Die kommerziell erhältlichen Verbindungen 46 und 50 stellen hervorragende Synergisten dar. Durch die polymere Struktur haben sie im Vergleich zu anderen Disulfiden zudem kaum Weichmachereffekte. Letztere Eigenschaft prädestiniert sie für den Einsatz in Schaumkörpern. Als nachteilig wurde die Entwicklung eines unangenehmen Geruchs bei der Extrusion bei hohen Temperaturen erkannt. Untersuchungen haben gezeigt, dass die Verbindungen 46 und 50 tatsächlich Substanzgemische darstellen. Durch verbesserte Synthesen gelang es die Entstehung von Nebenprodukten einzuschränken, die thermische Stabilität zu steigern und so letztendlich geruchsfreie Produkte zu erhalten. Ein weiteres Ziel der vorliegenden Arbeit war die Untersuchung von mechanistischen Aspekten des Synergismus zwischen Phosphorverbindungen und Schwefel bzw. Disulfiden. Zu diesem Zweck wurden mittels TD-MS-Messungen die bei der Zersetzung der Additive und Polystyrolmatrix entstehenden Fragmente untersucht. Durch Korrelation dieser Ergebnisse mit den Flammschutztests und der TGA- und DSC-Analytik wurden die essentiellen Komponenten für effektiven, halogenfreien Flammschutz in Polystyrol identifiziert.
Das Einatmen von Partikeln in den menschlichen Körper hat zwei verschiedene Aspekte im Hinblick auf die Gesundheit des Menschen. Einerseits existieren schädliche Partikel wie beispielsweise Feinstaub in der Umwelt, der nach Eintreten in den menschlichen Körper Krankheiten wie Herzerkrankungen und Erkrankungen der Atemwege auslösen kann, und der sogar zum Tod führen kann. Hier sind insbesondere Partikel, die kleiner als 2,5 µm sind, relevant. Andererseits ist es in der medizinischen Therapie einiger Atemwegerkrankungen wünschenswert, gezielt Partikel den Atemwegen zuzuführen. Die medikamentöse Aerosol-Therapie, bei der das Medikament durch den nasalen oder oralen Atemweg in die Lunge oder einen anderen Ort des Atemtrakts gebracht wird, wird gern verwendet, um Krankheiten wie z.B. Asthma oder chronisch obstruktive Lungenerkrankungen zu behandeln. Diese Therapie hat den Vorteil der kleinen Dosierung, der minimalen systemischen Nebenwirkungen und der schnellen Wirkung. Das Medikament soll hier tief in die Lunge, in der die Krankheit auftritt, eindringen. Die typische Größe dieser Partikel liegt im Bereich von 1 bis 5 µm. Fokus ist die gezielte Steuerung des Medikaments in spezielle Regionen wie beispielsweise zu einer Tumorposition, sodass Nebenwirkungen durch Ablagerung in anderen Regionen vermieden werden. Ein verbessertes Verständnis des Gesamtprozesses beinhaltet die Kenntnis der charakteristischen Luftströmung und des Partikeltransports sowie deren gegenseitige Beeinflussung. In der vorliegenden Arbeit, in der die Luftströmung sowie die Partikelverteilung und -ablagerung in den menschlichen oberen Atemwegen untersucht werden, werden vier verschiedene Geometrien verwendet: die verengte Luftröhre, das auf einem Gussstück basierende Mund-Rachen-Modell, das auf Computertomographie (CT) basierende Mund-Rachen-Modell und das auf CT-Skans basierende Nasenhöhlen-Modell. Die Software NeuRa2 wird zur Generierung des numerischen Oberflächengitters verwendet und ANSYS ICEM CFD-11.0, um Volumengitter zu erzeugen. Ein-Weg- und Zwei-Wege-Kopplung zwischen der Gasphase und den Partikeln werden in der Arbeit in Abhängigkeit verschiedener Partikelvolumenanteile angewendet. Dreidimensionale inkompressible Navier-Stokes (N-S) Gleichungen werden zur Beschreibung der Luftströmung verwendet. Large Eddy Simulation (LES) wird zur Modellierung der turbulenten Strömung herangezogen, und das Smagorinsky Feinskalen-Modell sowie das dynamische Smagorinsky Modell dienen der Beschreibung der kleinen turbulenten Skalen. Unter der Annahme eines großen Partikel-Luft Dichteverhältnisses, der Vernachlässigbarkeit der Partikelrotation und der Kollision zwischen den Partikeln sowie der Annahme, dass die Trägheitskraft die Partikelbewegung dominiert, werde Lagrange-Gleichungen herangezogen, um die Bewegung der Partikel zu modellieren. Im Falle von Partikeln, die kleiner als ein Mikrometer sind, wird die Brownsche Kraft zusätzlich berücksichtigt. Zur Lösung der Gleichungen wird die Software-Plattform OpenFOAM 1.5 benutzt, für die neue Solver entwickelt werden, die die Luftströmung mit LES und die Teilchenbewegung mit Hilfe einer Lagrange-Formulierung lösen können. Abhängig von der Partikelbeladung wird Ein-Weg- oder Zwei-Wege-Kopplung mit oder ohne Berücksichtigung des Einflusses des Partikelimpulses auf die Gasphase verwendet. Zunächst wird die Luftgeschwindigkeit an der Mittellinie und in unterschiedlichen Querschnitten stromabwärts der Glottis in der verengten Luftröhre mit numerischen Ergebnissen und experimentellen Daten aus der Literatur verglichen, hier wird ein Modell der Reynolds-gemittelten Navier-Stokes-Gleichungen (RANS) bei niedriger Reynolds-Zahl, das k-omega; Modell, verwendet. Die hier verwendete Methode verbessert die vorliegenden Literaturergebnisse, sodass sie die Basis für weitere Berechnungen in den verbleibenden Geometrien bildet. Die Luftströmung wird im Gussstück-basierten Mund-Rachen-Modell für drei verschiedene Inhalationsgeschwindigkeiten simuliert. Die numerischen Ergebnisse zeigen, dass das Geschwindigkeitsfeld der instationären Luftströmung sehr stark vom mittleren Geschwindigkeitsfeld abweicht, dies gilt insbesondere für das Auftreten von Wirbeln. Die numerische Simulation zeigt, dass die Partikelablagerung von der Partikelgröße, ihrer Ausgangsposition, der Inhalationsgeschwindigkeit sowie von der Geometrie abhängt. Turbulenz und Existenz von Rezirkulationszonen haben ebenfalls großen Einfluss auf den Partikeltransport. Eine polydisperse Partikelverteilung, die aus Messungen an einem Trockenpulver-Inhalator zur Verfügung steht, wird ebenfalls zur Simulation herangezogen. In diesem Fall wird Zwei-Wege-Kopplung verwendet. Polydisperse Partikelablagerung zeigt im Vergleich zur monodispersen Partikelablagerung stark unterschiedliche Charakteristika. Deshalb ist es notwendig, polydisperse Partikelverteilung und Zwei-Wege-Kopplung zu verwenden, wenn die reale medikamentöse Dosis eines Hubs berücksichtigt wird, die bei der klinischen Behandlung Anwendung findet. Um das Strömungsfeld bei einer realistischeren zeitabhängigen Inhalation zu untersuchen, wird eine numerische Simulation für das Gussstück-basierte Mund-Rachen-Modell unter den gleichen Bedingungen durchgeführt. Die Untersuchung zeigt, dass das Strömungsfeld signifikant verschieden ist in der beschleunigenden und der verlangsamenden Phase der Inhalation: In der Beschleunigungsphase ist die Luftströmung laminar während sie in der verlangsamenden Phase eher turbulent ist. Zur Untersuchung des Einflusses geometrischer Eigenschaften auf die Partikelablagerung werden numerische Simulationen für das CT-basierte Mund-Rachen-Modell durchgeführt. Im Ergebnis ist das Strömungsfeld im CT-basierten Mund-Rachen-Modell sehr verschieden von dem im Gussstück-basierten Mund-Rachen-Modell. Obwohl das Geschwindigkeitsfeld sowohl im mittleren als auch im zeitabhängigen Fall ähnlich ist, hat das Strömungsfeld ein sehr kompliziertes Wirbelfeld mit hoher räumlicher und zeitlicher Dynamik. Partikel der Größe 2 µm können den Pharynx passieren, sich in der Luftröhre ablagern oder weiter in die Lungenregion vordringen. Um die Eigenschaften des Geschwindigkeitsfelds in der Nasenhöhle zu untersuchen, wurde ein geometrisches Modell der Nasenhöhle aus CT-Skans konstruiert. Die numerischen Ergebnisse zeigen, dass die Luft durch die Hauptluft-Passage der Nasenhöhle fließt und nur wenig Luft die Spitzen der Nasengänge und der olfaktorischen Region erreicht.
Die Beschreibung und das Verständnis einzelner Prozess-Schritte bei der Herstellung einer farbstoffsensibilisierten Solarzelle ist ein entscheidender Vorgang zur systematischen Weiterentwicklung derselben. Für eine erfolgreiche industrielle Anwendung sind einerseits die systematische Steigerung des Wirkungsgrades und die zuverlässige Kontrolle der einzelnen Prozessschritte notwendig, andererseits ist die Erhöhung der Lebensdauer von einigen Tagen bis Monaten auf mehrere Jahre unabdingbar. Um dies zu ermöglichen, wird im Rahmen dieser Arbeit zunächst eine analytische Methode entwickelt, um die Herstellung der farbstoffsensibilisierten Solarzelle konsequent zu beleuchten. Es muss realisierbar sein, die molekularen Zusammenhänge zu beschreiben und gleichzeitig Rückschlüsse auf die Zellfunktion zu ermöglichen. Aus diesem Grund wird aus der Prozess-Kette der farbstoffsensibilisierten Solarzelle der wichtige Schritt der Infiltration des Farbstoffs in das poröse System genau untersucht. Die Anbindung des Farbstoffs an poröses Titandioxid ist ausschlaggebend für die Übertragung von Elektronen. Um diesen Herstellungsschritt zu untersuchen wurde überwiegend die Methode der ATR-IR-Spektroskopie eingesetzt. Eine optimierte ATR-IR-Durchflusszelle ermöglicht dabei zeitaufgelöste Untersuchungen der Anbindungsreaktion in einem Vakuum-Spektrometer. Mit Hilfe der Transmissions-Spektroskopie auf Silizium-Wafern können Charakteristika des porösen Titandioxids exakt aufgelöst und die Art der Anbindung von Farbstoffen auf Titandioxid analysiert werden. Die experimentell ermittelten Daten wurden durch eine theoretische Beschreibung und eine Simulation der IR-Absorption in Abhängigkeit der Zeit gestützt. Ein weiterer Schritt ist die Korrelation aller spektroskopisch ermittelten Daten mit elektrischen Daten der entsprechenden Solarzelle. Durch die gezielte Auswahl strukturähnlicher Farbstoffe wurde sowohl der Einfluss der Anker- und Seitengruppe als auch der des Grundgerüstes untersucht. So ist sowohl eine frühe Prozesskontrolle als auch eine systematische Weiterentwicklung der farbstoffsensibilisierten Solarzelle.
Molybdenum and tungsten active site model complexes, derived from the protein X-ray crystal structure of the first W-containing nitrate reductase isolated from Pyrobaculum aerophilum, were computed for nitrate reduction at the COSMOB3LYP/SDDp//B3LYP/Lanl2DZ(p) level of density functional theory (DFT). The molybdenum containing active site model complex has a considerably larger activation energy (34.4 kcal/mol) for the oxygen atom transfer from the nitrate to the metal center as compared to the tungsten containing active site model complex (12.0 kcal/mol). Oxidation of the educt complex is close to thermoneutral (-1.9 kcal/mol) for the Mo active site model complex but strongly exothermic (-34.7 kcal/mol) for the W containing active site model complex. The low relative energy for the oxidized W metal complex makes the regeneration of the +IV oxidation state much more difficult as compared to the Mo metal complex. The MVI to MIV reduction requires much more reductive power (more negative redox potential)when the metal center M is a tungsten rather than a molybdenum atom. So, although the reduction of nitrate is stimulated when W replaces Mo in the active site of Nar the catalytic cycle breaks after the reduction of nitrate to nitrite when the biochemical reducer is not strong enough to reduce the metal center. Ethylbenzene dehydrogenase (EBDH) is an enzyme that catalyzes the oxygen-independent, stereospecific hydroxylation of ethylbenzene to (S)-1-phenylethanol. EBDH active site models, derived from protein X-ray crystal structure, were computed at the COSMOB3LYP/SDDp//B3LYP/Lanl2DZ(p) energy level of DFT in order to investigate most probable mechanism, ionic or radical pathway. In addition, different protonation states and participation of amino acid residues near to the Mo center were considered. Models with protonation of His192, Lys450, Asp223 and model without protonation were investigated for comparison. Computed relative energies indicate that the overall lowest energy barrier pathway results when ionic and radical pathways are mixed. This mechanism of ethylbenzene hydroxylation starts with a homolytic C1-Hs bond cleavage (TS1’) resulting in the formation of a radical type intermediate (I’) and then in order to continue the reaction by the easier O1Hs anion transfer, an electron needs to be transferred from the substrate to the Mo-OH moiety to transform the di-radical to the zwitter ionic intermediate. Then the transfer of O1Hs anion from the Mo to the cationic substrate (TS2) results in the formation of product bound complex (P). Among those the protonated Lys site corresponds to the energetically best pathway for the hydroxylation of ethylbenzene by EBDH. Acetylene hydratase (AH) of Pelobacter acetylenicus is a tungsten (W) containing iron-sulfur enzyme that catalyzes the transformation of acetylene to acetaldehyde. DFT studies were performed on the model complexes derived from the native protein X-ray crystal structure of AH. Based on the computational results we proposed the most likely nucleophilic mechanism for the hydration of acetylene by the acetylene hydratase (AH) enzyme. In this mechanism, the water (Wat1424) molecule is coordinated to the W center and Asp13 is assumed to be in anionic form. The Wat1424 molecule is activated by W and then donates one of its proton to the anionic Asp13 forming the W-bound hydroxide and protonated Asp13. The W-bound hydroxide then attacks the C1 atom of acetylene together with the transfer of proton from the Asp13 to its C2 atom, resulting in the formation of a vinyl alcohol intermediate complex. The energy barrier associated with this step is 14.4 kcal/mol. The final, rate limiting, step corresponds to the tautomerization of the vinyl alcohol intermediate to acetaldehyde via intermolecular assistance of two water molecules, associated with the energy barrier of 18.9 kcal/mol. An alternative, electrophilc pathway, was also considered but the energy barriers are found to be higher than for the nucleophilic pathway described here. Sulfite oxidase (SO), selenate reductase (SeR) and nitrate reductases (NRs) are among the mononuclear molybdenum enzymes involved in the catalysis of metabolic redox reactions.The active site composition of SO has one molybdopterin (MPT) ligand and it oxidizes the sulfite to sulfate, SeR has two MPT ligands and it reduces the selenate to selenite, while NRs reduces nitrate to nitrite by either one or with two MPT’s at the active site. Is the active site itself special in some way for the oxidation/reduction of one or the other substrate? Or do the different active sites behave essentially the same way and it is the role of the protein to make it specific. To clarify these, DFT studies were performed on the computational model complex, [MoVIO2(S2C2Me2)SMe]- (A, derived from the X-ray crystal structure of native SO),and on the experimental model complex [MoVIO2(mnt)2]2- (B, coordination mode similar to the active site of SeR) for the oxidation of selenite and sulfite. For the oxidation of sulfite model A which resembles the SO active site is clearly the best choice (lowest barrier, minor exothermicity). For the reduction of selenate a smaller activation is computed for model A, but the reaction is less exothermic with model B, which resembles the SeR active site. DFT computations were also carried out on simple active site model complexes of SeR to investigate different ways of binding the substrate and the OAT reaction. Unfortunately, the results are little conclusive. Larger models might be needed to obtain more meaningful computational results.
Compared to the human genome, which is formed by approximately 25,000 genes, the human proteome comprises over a million functional proteins and thus represents a much higher diversity. Although genetic research provides valuable information on the proteins which can be translated, a great task in the future will be the exploration of the entire protein interaction network. Understanding protein interactions will greatly help scientists to identify the mechanisms behind fatal diseases such as cancer, AIDS, and tuberculosis and, hopefully, provide new cures. Hence, micro arrays containing proteins or small protein fragments in the form of peptides have become of great interest in proteomic research. Using these microarrays a large number of potential target molecules can be screened for interaction with a probe in a short time frame. However, protein and peptide micro arrays are still lagging behind oligonucleotide arrays in terms of density, quality and manufacturing costs. A new approach developed at the German Cancer Research Center (DKFZ) has improved the synthesis of high density peptide arrays. The current technology is capable of producing arrays with up to 40,000 different peptides per cm² by means of a micro particle-based solid phase peptide synthesis (mpSPPS). Similar to Ronald FRANK’s SPOT synthesis, the peptides are combinatorially synthesized directly on a solid support, whereby the exact location of each peptide is known. However, the in situ synthesis bears a conceptual disadvantage: The quality of the peptides is dependent on the efficiency of the synthesis. Inefficient coupling produces peptide fragments which are present in the resulting array among the desired full length peptides. Thus, this PhD thesis dealt with the improvement of the peptide quality of in situ synthesized micro arrays. The central achievement is a new method allowing for the fast one-step purification of entire peptide arrays without loss of resolution or spatial information. The key principle is the transfer of an in situ synthesized array to a gold-coated polyvinylidenefluoride (PVDF) membrane, onto which only full-length peptides are allowed to rebind via an N-terminal cysteine. Peptides are synthesized on a solid support by means of mpSPPS using the acid-labile RINK amide (RAM) linker as an anchor group which allows for cleavage and removal of side chain protecting groups in one-step. After the synthesis, the array is brought into direct contact with the gold coated PVDF membrane. The membrane is soaked in trifluoroaceticacid (TFA) transfer medium which immediately initiates the peptide release and at the same time catalyzes a thiol-gold bond formation. Specific transfer could be verified down to a resolution of 10,000 spots per cm². Only cysteine terminated peptides which represent the full-length array members were transferred, whereas other peptides and synthesis fragments were excluded. The fluorescence signals on the target membrane appeared to be strong and almost background-free. Furthermore, no lateral diffusion was observed, which provides access to high complexity and high-quality peptide arrays in an easy manner.
Im Rahmen der vorliegenden Arbeit wurde eine kontinuierlich betriebene Laboranlage zur Umsetzung von CO-reichem Synthesegas, wie es beispielsweise durch Vergasung biologischer Reststoffe entsteht, mit dem Fokus auf der Herstellung von Ethanol und höheren Alkoholen aufgebaut und in Betrieb genommen. Der Schwerpunkt der Arbeit lag in der Herstellung neuartiger heterogener Katalysatoren auf der Basis von mit Cobalt und Kupfer bzw. Eisen und Kupfer dotierten Silicium- und Aluminiumoxiden. Zur Synthese der kalzinierten Vorstufen kamen verschiedene Methoden zum Einsatz: Imprägniertechniken, Fällungstitration, Sol-Gel-Verfahren und Hydrothermalsynthese. Zudem wurden unterschiedliche Ausgangsmaterialien gewählt: Metallnitrate, Cobalt-Nanopartikel, Kupfer/Cobalt-Partikel und der Komplex [Cu(Salen)CoCl2]. Das Produktspektrum der mit Cobalt und Kupfer dotierten Systeme bestand zu einem Großteil aus Methan (42 bis 65%) und höheren Alkanen (10 bis 42%). Alkoholselektivitäten wurden bis zu 13% erreicht, darin waren höhere Alkohole von bis zu 76% enthalten. Mit diesen Systemen wurden bei einem einmaligen Durchgang durch den Reaktor CO-Umsätze von bis zu 42% erreicht. Bei der Variation verschiedener Parameter an den Katalysatorsystemen wurde deutlich, dass die Metallanteile, die Herstellungsmethoden und die Reihenfolge des Einbringens der Metalle zum Teil signifikante Änderungen der Reduktionseigenschaften und der Aktivität in der Umsetzung von Synthesegas mit sich brachten. Dabei wurde ein synergistischer Effekt zwischen CuO und Co3O4 gefunden, der es erlaubte, dass sich diese Metalloxide bei Temperaturen unterhalb von 300 ˚C vollständig reduzieren ließen. Das Ziel die zwischenmetallische Wechselwirkung zu erhöhen, wurde versucht durch eine räumliche Annäherung der Metalle in Kupfer/Cobalt-Partikeln bzw. dem Komplex [Cu(Salen)CoCl2] als Edukte zur Katalysatorherstellung, zu erreichen. Der Komplex [Cu(Salen)CoCl2] wurde erfolgreich synthetisiert und durch Anpassung einer Hydrothermalsynthese ohne dessen Zersetzung in ein Siliciumoxidgitter eingebracht. Die Anwesenheit einer CuCo2O4-Spezies nach der Kalzinierung des Systems belegte die verbesserte Wechselwirkung der Metalle. Weitere Variationen der entwickelten Synthesemethode führten zu einem Katalysatorsystem, welches im Vergleich zu den anderen Systemen einen stabileren CO-Umsatz zeigte und zu einem Anteil von 98% an Alkoholen in den flüssigen kohlenstoffhaltigen Katalyseprodukten führte, welcher zu 37% aus Methanol und zu 63% aus höheren Alkoholen bestand.
This work concerns the use of optimization methods to systematically improve the agreement of chemical kinetic combustion models with available experimental pro les. Under many circumstances, chemical kinetic parameters can neither be evaluated analytically from experiments nor accurately calculated through quantum chemistry methods. Thus, optimization methods relying on the numerical solution of the underlying di erential equations (accounting for the experiments) are needed [14]. The program package Kine t has been developed in C++. Based on the software Homrea, for the simulation of gas phase homogeneous systems, it allows the optimization/estimation of parameters against experimental data. It uses four optimization methods, namely an adaptive Random Search (RS), a Genetic Algorithm (GA) and CONDOR and BOBYQA, two optimization programs based on trust regions. Since in many cases several sub-optimal local minima exist, the three local optimization methods (RS, BOBYQA and CONDOR) were globalized through the introduction of random restarts in the parameter space. The classical analysis methods for reaction mechanisms (sensitivity analyses and reaction flow analysis) have proven to be insufficient for identifying the influential parameters suitable for the optimization. Thus, a new method, called "reaction signi cance analysis" has been developed. It shows the in uence of all parameters on the global distance between model prediction and experimental values. Only the parameters having a signi cant influence are candidates for the optimization. Box constraints on each parameter are often not sufficient if several parameters of the same reaction are optimized simultaneously. Consequently, penalty terms were implemented to put constraints on the whole reaction rate coefficient. Numerical tests were created to validate the optimization methods. They use the H2-O2 sub-mechanism of the GRI-mechanism [54]. Arti cial experimental pro les were generared using all initial values of the parameters. The most influential parameters were then identi ed and modi ed in such a way to introduce great discrepancies with the "experimental" pro les. One cause of the oscillations of the distance as a function of separately varied parameters was identi ed: it is related to the exponential decrease of concentrations due to self-ignition. Optimization problems based on six experiments with respectively three pro les were constructed. The optimization methods were rst validated for problems without self ignition. It was shown that they can reliably identify optimal parameter sets for problems involving respectively 6 pre-exponential factors, six pre-exponential factors located on bounds while using the penalty terms and 6 pre-exponential factors, temperature coeffi- cients and activation energies. The optimization methods were then validated for problems where a signi cant amount of oscillations occur. All methods were able to solve a problem involving seven parameters, all methods except one could solve a problem with 7 temperature coefficients and activation energies. All optimization methods failed for a complex problem involving seven pre-exponential factors, temperature coefficients and activation energies. The program package Kine t was then used to evaluate whether or not the GRI-mechanism is refuted by real experiments involving the pyrolysis of CH3 and C2H6 [47]. With the initial parameter values, considerable discrepancies exist whereas after the optimization good agreements were achieved. Mechanism reduction methods are often utilized for chemical kinetic optimization and can be relevant for problems pertaining to soot formation, always characterized by very large reaction mechanisms. As a consequence a C++ reduction program was developed during this work. The reliability of reduction approaches in the contex of parameter optimization was evaluated on an example involving the experiments of CH3 and C2H6 pyrolysis to which the GRI-mechanism was optimized [47]. The results indicate that reduction methods are only reliable for optimization problems where parameters are varied within narrow ranges. Finally, the program package Kine t was employed for an optimization problem involving a semi-detailed reaction mechanism accounting for the pyrolyses of the propargyl radical and 1,5-hexadyine [59]. Propargyl is a vital species for accurate simulations of PAH (PolyAromatic Hydrocarbons) and soot formation since it plays a crucial role for the formation of the fi rst aromatic ring.
This thesis is intended to further extend the scope of camphor and camphor-derived building blocks in the synthesis of chiral ligands, catalysts and selectors, their successful application in catalysis and in enantioseparation sciences. The thesis is divided into four independent chapters each focusing on the development of novel camphor-based compounds and their application as catalysts or metal-selectors. A short introduction is given for each chapter dealing with recent progress in the field of interest as well as providing essential basics of the affected chemistry, like Pd-catalysis, polymer and separation science. In chapter 1, after an introduction about general aspects of chiral stationary phases (CSPs) and their application in complexation gas chromatography (CGC) the total synthesis of novel, extended CSPs derived from 1S-(+)-camphorsulfonic acid is presented. The developed Chirasil-Metal-OC3 phases are synthesized with overall high yield in six steps. Overall seven different Chirasil-Metal polymers with different separation capabilities are reported by metal-incorporation of nickel(II), oxovanadium(IV), europium(III), lanthanum(III) and variation of the amount of ligand content on the polymer. Their performance in enantioselective complexation gas chromatography (CGC) is studied in terms of selector-type, selector-concentration, polymer film thickness, polymer composition and column length. Superior activity and separation of 29 small-sized compounds, encompassing inter alia epoxides, derivatized alkenes and alkynes as well as alcohols and amides, is presented with throughout high separation factors. The thermal stability and the broad applicability, synthetic versatility and effectiveness of the newly derived Chirasil-Metal-OC3 phase is reported. The 2nd chapter of deals with the synthesis of a novel bidentate N,N-heterocyclic ligand motif derived from d-(+)-camphor. After a short introduction into isomerization reactions and the Wacker-oxidation of olefins, the synthesis and structural analysis of overall 11 new ligands is reported and the coordination to palladium, copper and cobalt is investigated. The 3rd Chapter of this thesis aims at the synthesis of a chiral NHC-pincer ligand derived from camphoric acid as the chiral building block. Preparation is presented in overall five steps in moderate to good overall yield. The molecular structures of the NHC- and triazole pincer ligand is presented and the structural characteristics are discussed in detail. The results are supported by X-ray chrystallographic measurements and an explaination for the observed coordination properties is given. The 4th chapter of this thesis focuses on the structure-reactivity relationship in the asymmetric intramolecular oxindole synthesis using Pd-NHC isonitrile catalysts featuring a successively increasing steric demand while maintaining the same chiral substitution pattern (camphor). After a short introduction into chiral NHCs used for this transformation, three six-membered hexahydropyrimidine core based, camphor-derived (bornylamine) NHC-Pdisonitrile complexes are presented and their application in the enantioselective alpha-amide arylation to form 3,3-disubstituted oxindoles is described. The results are discussed taking steric effects at the catalyst metal-center and steric demand of the substrates into account.
Die hämatopoietischen Stammzellen (HSC) zeigen beispielsweise nach einer Stammzelltransplantation eine chemokingesteuerte Wanderung aus dem Blutkreislauf heraus hin zu ihrem Anknüpfungspunkt im Knochenmark, der hämatopoietischen Stammzellnische. Dieses Verhalten von Zellen, einem Konzentrationsgradienten aktiv nachzufolgen, wird allgemein als Chemotaxis und speziell im Falle der Stammzellwanderung als „homing“ bezeichnet. Neben der Suche nach relevanten Botenstoffsystemen und Einflussfaktoren auf die gerichtete Wanderung der HSC, besteht vor allem bei der Quantifizierung des Migrationsverhaltens und der Sensitivität der HSC noch großer Forschungsbedarf. Selbst für das bereits seit längerem bekannte Botenstoffsystem bestehend aus dem Chemokin Stromal cell-derived factor-1 (SDF-1) und dessen zugehörigen Rezeptor CXCR4 sind der Einfluss von Absolutkonzentration, Gradientensteilheit und Konzentrationsschwellwerten, sowie die Wirkungsweise des CXCR4-Inhibitors AMD3100 noch weitgehend ungeklärt. Das Migrationsverhalten von humanen hämatopoietischen Stammzellen im Bezug auf das SDF-1/CXCR4-Botenstoffsystem wurde daher im Rahmen dieser Arbeit anhand von in vitro-Experimenten näher untersucht. Zur Quantifizierung der HSC-Wanderung wurden zunehmend komplexere Chemotaxis¬experimente angewandt, Microwell-Experimente, ein Transwell-Assay und ein in dieser Arbeit neu entwickelter Mikrofluidikaufbau. Die diffusive Ausbildung der Botenstoffgradienten in diesen Mikrostrukturen wurde mittels Farbstoff- und Partikelexperimenten überprüft und zusätzlich durch numerische Simulationsrechnungen verifiziert. Neutrophile Granulozyten, die den Leukozyten und dem Immunsystem des Körpers zugeordnet werden, sind eine bereits gut erforschte und ebenfalls chemotaktisch migrierende Blutzellspezies. Sie wurden als Modellsystem anstelle der raren und aufwändig zu isolierenden HSC zum Test der Chemotaxisexperimente und vor allem des neuen Mikrostruktursystems eingesetzt. Dabei wurden Möglichkeiten zur Bestimmung der einzelnen Wanderungsparameter ermittelt und die Neutrophilmigration anhand der Mikrofluidikexperimente detailliert untersucht. Für die Untersuchung der Stammzellchemotaxis wurden vorrangig primäre Knochenmarkzellen, die mesenchymalen Stromazellen (MSC), als Modell für die Stammzellnische und als Botenstoffdonoren verwendet. Die Ausschüttung des Chemokins SDF-1 sowie der Einfluss von AMD3100 auf die SDF-1-Sekretion der MSC wurden in dieser Arbeit anhand von ELISA-Tests und Immunofluoreszenzfärbungen ausführlich erforscht. Dadurch wurden eine genaue Definition der diffusionsbasierten Chemokin-gradienten und eine absolute Berechnung der Mindest¬konzentration für die HSC-Migration möglich. Schließlich konnte für die Chemotaxis¬experimente in den Mikrostrukturen ein Zusammenhang zwischen der Entwicklung des Botenstoffgradienten und der HSC-Wanderung gefunden werden, der zu einer Bestimmung des Schwellwertes für die Sensitivität der HSC gegenüber einem SDF-1-Gradienten führte. Anhand der Korrelation des Wanderungsverhaltens der Neutrophile und HSC mit den durch die Mikrostrukturen definierten Botenstoffgradienten konnte die chemotaktische Zellmigration quantifiziert werden. Die Ergebnisse dieser Arbeit zeigen insgesamt, dass durch die Anwendung des entwickelten Mikrofluidikexperimentes neue Erkenntnisse über die Chemotaxis von Blutzellen gewonnen werden können.
Ziel dieser Arbeit ist es, neue Magnesiumverbindungen zu entwickeln, die die Fähigkeit besitzen, das Treibhausgas CO2 zu binden und in Verbindungen mit h¨oherem Nutzen umzuwandeln. Der erste Schritt der Transformation ist die Koordination des zu bindenden Moleküls am Magnesiumzentrum. Dieser Prozess wird in Anwesenheit von elektronenreichen Stickstoffatomen erleichtert. Im nächsten Schritt wird die eigentliche Umwandlung des CO2-Moleküls in neue Produkte vollzogen. Das Metallatom dient hierbei als Katalysatorzentrum und ermöglicht eine effizientere Umwandlung. Solche CO2-Fixierungen funktionieren gut mit Magnesiumamidverbindungen, insbesondere mit monomeren Vertretern dieser Spezies. Da die Klasse der Magnesiumamidverbindungen zur Dimerisierung bzw. Oligomerisierung neigt, müssen durch geschickte Wahl des Ligandgerüstes diese ungewollten Reaktionen unterbunden werden. Ein weiteres wichtiges Kriterium ist, dass das fixierte CO2-Molekül keine Insertionsreaktion in die Magnesium- Stickstoff-Bindung eingehen darf, wie es oft in Magnesiumamidsystemen beobachtet wird. Dadurch wird das CO2-Molekül in die Struktur des Magnesiumkomplexes unumkehrbar eingebaut und ist für spätere Transformationen nicht mehr verfügbar. Als elektronenreiche Stickstoffsysteme gelten Guanidine wie hppH (1,3,4,6,7,8-Hexahydro-2H-pyrimido[1,2-a]pyrimidin). Durch Umsetzung mit einer Grignardverbindung wird das entsprechende Magnesiumhalogenidguanidinat erhalten, welches für eine potentielle CO2-Fixierung eingesetzt werden soll. Da es sich laut Kristallstrukturanalyse aber nicht um eine monomere, sondern um eine tetramere Spezies handelt, ist dieses Molekül für solche Prozesse ungeeignet. Dem gegenüber steht ein vielversprechender Ansatz, der vom sterisch anspruchsvollen primären Amin Ph3SiNH2 ausgeht. Durch dessen voluminösen Rest soll eine Dimerisierung verhindert werden. Mit Dialkylmagnesiumverbindungen reagiert es jedoch zu einer tetrameren Magnesiumimidspezies. Dieses unerwartete Produkt wird quantenchemisch untersucht, wobei die Aufklärung des Bildungsmechanismus von besonderem Interesse ist. Um das Ziel der Synthese einer monomeren Magnesiumamidspezies zu erreichen, wird nach den obigen Erkenntnissen ein System mit einem nahezu eingeschlossenem Magnesiumatom benötigt. Hier bieten sich Kryptanden an, die den Magnesiumkomplex durch ihre Ligandenhülle vor Dimerisierung schützen. Mit Hilfe von quantenchemischen Rechnungen wird ein geeignetes Käfigsystem bestimmt. Nach erfolgreicher Synthese des Kryptanden muss dieser zu einem Magnesiumbisamid funktionalisiert werden. Dazu werden auf drei unterschiedlichen Wegen Experimente mit verschiedenen Magnesiumverbindungen durchgeführt. Eine Synthesevorschrift für die Darstellung des Magnesiumbisamids kann allerdings nicht präsentiert werden. Die Experimente bestätigen aber, dass Magnesiumionen und Metallionen mit ähnlich großem Ionenradius, wie z.B. Lithium- und Zinkionen komplexiert werden.
Ziel dieser Arbeit ist es ein grundlegendes und detailliertes Verständnis der strukturellen Eigenschaften neuer ein- und mehrkerniger Zinkkomplexe mit (aromatischen) Bis- und Tetrakis-guanidin- sowie bizyklischen Guanidin- und Guanidinatliganden zu erlangen und deren Verhalten in Lösung zu untersuchen. Das Zinkguanidinsystem wurde ausgewählt, da Zink(II) mit den stark Lewis-basischen Guanidinen stabile Komplexe bildet, prinzipiell als redoxinaktiv gilt und im Gegensatz zu einigen anderen Übergangsmetallen diamagnetisch ist. Während bizyklische Guanidin- und azyklische Bisguanidinliganden zu einkernigen Zinkkomplexen führen, konnten mit Tetrakisguanidinen zweikernige Komplexe erhalten werden. Mit bizyklischen Guanidinatliganden konnten sogar drei- und vierkernige Zinkguanidinatkomplexe mit unterschiedlichen Koordinationsmodi synthetisiert werden. Desweiteren wurde eine Reihe von Zinkkomplexen mit Bis- und Tetrakisguanidin-liganden mit unterschiedlichen aromatischen Spacereinheiten synthetisiert. Erste Versuche in unserer Arbeitsgruppe zeigten, dass aromatische Bisguanidine als Liganden in katalytischen Reaktionen eingesetzt werden können. Die synthetisierten Zinkkomplexe wurden strukturell mit der Röntgenstrukturanalyse, sowie die dynamischen Prozesse in Lösung in Kooperation mit Prof. Dr. Enders anhand von VT-NMR-Experimenten untersucht. Dabei konnte ein Durchschwing-mechanismus des Zinks und der Guanidineinheiten durch die aromatische Ebene beschrieben werden. Dieser Mechanismus ist für alle bisher bekannten (verzerrt) tetraedrisch koordinierten Komplexe mit Bis- und Tetrakisguanidinliganden mit starrem aromatischem Gerüst gültig. Neben den Iminstickstoffatomen sind prinzipiell auch die Aminstickstoffatome der Guanidineinheiten in der Lage an das Metallzentrum zu koordinieren. Eine hemilabile Metall-Amin-Bindung kann für katalytische Reaktionen interessant sein, bei denen, ohne die Koordination eines Substrates zu behindern, eine freie Koordinationsstelle am Zentralatom stabilisiert werden muss. Bisher konnte weder bei den Bisguanidin- noch bei den Tetrakisguanidinkomplexen eine direkte Metall-Amin-Bindung nachgewiesen werden. Beim Verzicht auf ein aromatisches oder aliphatisches Rückgrat, einhergehend mit der direkten Verknüpfung der beiden Guanidineinheiten wie in den beiden neuen Bisguanidinen tmua (Tetramethylurea-azin) und bdmeu (N,N’-Dimethylethylenurea-azin), ist es allerdings gelungen eine Metall-Amin-Bindung zu bilden. In Kooperation mit der Arbeitsgruppe von Prof. Dr. Herres-Pawlis konnte gezeigt werden, dass der [ZnCl2(tmua)]-Komplex in der Tat katalytische Aktivität in der Ringöffnungs-polymerisation von Lactid besitzt.
In dieser Arbeit werden die Synthese, Charakterisierung und die Anwendung von verschiedenen lipophilen Anionen vorgestellt. Der Begriff „lipophiles Anion“ erscheint auf den ersten Blick als paradox, da die Ladungstrennung in Salzen in Anion und Kation am besten durch die Solvatisierung polarer Lösungsmittel stabilisiert wird. Lipophile Anionen besitzen meist eine negative Ladung. Zusätzlich wird durch eine sehr lipophile Oberfläche der Anionen eine hohe Löslichkeit der entsprechenden Salze in unpolaren Lösungsmitteln erzielt. Verwandte Systeme, welche zu der Kategorie der schwach koordinierenden Anionen gehören, weisen meistens eine Vielzahl von Fluorsubstituenten auf, welche eine Ladungsverteilung über das gesamte Anion bewirken und dadurch dessen Nukleophilie herabsetzen. Durch zusätzliche sterische Abschirmung der reaktiven Zentren wird ein inertes fluorophiles Anion erreicht. Ein Problem besteht in der aufwändigen Synthese dieser Systeme, welche häufig unter Einsatz von kostspieligen Substraten verläuft. Die in dieser Arbeit verfolgte Strategie basiert auf preiswerten Ausgangsverbindungen, welche in wenigen Stufen in hohen Ausbeuten in das gewünschte Anion überführt werden können. Hier sind neben Boratester-Anionen auf Tartratdiamidbasis Anionen hervorzuheben, welche ausgehend von zwei 3,3´,5,5´-Tetra-tert-butylbiphenyl-2,2´-diolen dargestellt werden konnten.Hierbei handelt es sich um das sogenannte Bortebat 2- und das sogenannte Altebat 1-. Aufgrund der acht tert-Butyl-Gruppen wird eine außerordentliche Löslichkeit in polaren Lösungsmitteln erreicht [Li(thf)4-Altebat 74: 7 g/L, Li(thf)4-Bortebat 129: 40 g/L]. Zu diesen bis 200 °C temperaturstabilen Salzen des Altebats 1- und Bortebats 2- werden effiziente und preiswerte Synthesen [z.B.: Li(thf)4- Altebat 74 < 0.1 €/g] im großen Maßstab vorgestellt. Ferner wird die Hydrolysestabilität und die Leitfähigkeit ausgewählter Verbindungen diskutiert. Zusätzlich zu den experimentellen Daten wurde die Strukturaufklärung durch quantenchemische Methoden vertieft. Kraftfelduntersuchungenstellten dabei ein Reißbrett für weitere Anionen mit verbesserten Eigenschaften dar, welche als Agenda für zukünftige Arbeiten dienen können. Ein weiterer Meilenstein war die Erarbeitung von synthetisch praktikablen Umsalzungsreaktionen mit deren Hilfe die genannten lipophilen Anionen mit einer Vielzahl verschiedener Kationen kombiniert werden können. Hier hat sich ein Natriumsalz des Altebats 1- oder des Bortebats 2- mit einem möglichst geringen Anteil an Tetrahydrofuran-Liganden (Verbindungen 117 und 131) als besonders geeignet erwiesen. Im Zuge dieser Arbeit wurde eine Reihe von Salzmetathesen durchgeführt,welche nahe legen, dass sich das Anion in fast alle Systeme einführen lässt, sofern diese ein Anion besitzen, welches in Dichlormethan oder Aceton ein schwer lösliches Natriumsalz bildet.Es war sogar möglich, von einem NHC-Silberchlorid-Komplex ein Chlorid durch eine Salzeliminierungsreaktion mit Natriumaltebat 117 zu eliminieren. Im Rahmen dieser Arbeiten zeigte sichdie besonders hohe Tendenz des Altebat-Anions 1-, mit Kationen rautenförmige Einkristalle zu bilden. So konnte in zahlreichen Einkristall-Röntgenstrukturanalysen (siehe Kapitel 14.4), die geringe Koordinationstendenz der hergestellten Anionen an die jeweiligen Kationen belegt werden.Superabsorbierende Polymere für wässrige Lösungen sind seit über 30 Jahren bekannt und heute allgegenwärtig. Superabsorber für unpolare Lösungsmittel sind jedoch erst 2007 von Sada et al. vorgestellt worden. Der für den superabsorbierenden Effekt nötige osmotische Druck zwischen der Innen- und Außenseite des polymeren Materials wird durch die in dem jeweiligen Lösungsmittel solvatisierbaren lipophilen Salzen erzeugt. Dies stellt eine Paradeanwendung für lipophile Anionen dar, da diese auf die Löslichkeit in unpolaren Lösungsmitteln hin optimiert sind. Durch den Einsatz von Altebat 1- als Anion konnten preiswert herzustellende Polymere im Gramm-Maßstab synthetisiert werden, welche hohe Quellwerte für unpolare Lösungsmittel aufweisen. So kann zum Beispiel über das 200-fache der eigenen Masse an Dichlormethan absorbiert werden. Eine praktische Anwendung der Superabsorber zeichnet sich dadurch ab, dass auch Dieselkraftstoffe (“Shell FuelSave Diesel”) mit Quellfaktoren von 33 absorbiert werden konnten.Zusätzlich wurden die Einflüsse der Polymerisationsmethoden, der Vernetzerkonzentrationen, der copolymerisierten Salze sowie der unterschiedlichen Monomerkonzentrationen untersucht und auf einen maximalen Quellfaktor bei gleichzeitiger mechanischer Stabilität des Polymers hin optimiert. Eine genaue Untersuchung der Quelleigenschaften lieferte neben einer Möglichkeit, die Quellge-schwindigkeit deutlich zu erhöhen, auch Daten zur Temperaturabhängigkeit der Quellge-schwindigkeiten bei verschiedenen Polymeren.
Biologische Membranen sind ein Hauptbestandteil von lebenden Organismen. Sie trennen das Zellinnere von dessen Umgebung und wirken als selektiv permeable Barrieren. Solche Membranen können durch Selbstaggregation von Lipiden gebildet werden. Modell-Membranen dieses Typs können verwendet werden um grundlegende strukturelle Prinzipien im Nahbereich von Phasenübergängen zu verstehen und um biologische Phänomene wie die Gelenkschmierung zu untersuchen. Zu diesem Zweck wurden Lipidbeschichtungen an der Fest-Flüssig-Grenzfläche präpariert und vermessen. Dabei wurden die Reaktionen der Membranen auf unterschiedliche äußere Parameter und die Wechselwirkung mit organischen Molekülen in den Mittelpunkt der Untersuchungen gestellt. Die Rotationsbeschichtung (spin-coating) und die Luftdruckbeschichtung (air-brush) wurden als einfache und zuverlässige Herstellungsverfahren für Modellmembranen eingesetzt. Die Struktur der hergestellten Membranen wurde in Röntgen- (XR) und Neutronenreflektometrie (NR) Experimenten verifiziert. Die Fourier-Transformations-Infrarotspektroskopie (FTIR) wurde in der oberflächenempfindlichen, abgeschwächten Totalreflexions (ATR) Geometrie eingesetzt, um die Schwingungsmodi der untersuchten Systeme in Kontakt mit Flüssigkeiten zu charakterisieren. Die uneingeschränkte Vergleichbarkeit zwischen ATR-FTIR- und NR-Ergebnissen wurde durch gleichzeitige Messungen an derselben Probe gewährleistet. Dies erforderte die Konstruktion einer externen ATR-FTIR Strahlführung, welche am BioRef-Neutronenreflektometer der BER II Neutronenquelle am Helmholtz-Zentrum Berlin realisiert wurde. Die dynamische Differenzkalorimetrie (DSC) wurde als eine ergänzende Methode angewandt, um das Verhalten von Membranen in Lösung am Phasenübergang zu untersuchen. Neben vielfältigen Umgebungsbedingungen wie Temperatur- und Druckänderungen, wurden die Beschichtungen in unterschiedlichen Lösungen inkubiert. Darüber hinaus wurde der Einfluss von äußerer Scherung auf die Modellmembranen getestet. Die Stabilität der präparierten DMPC-Lipidbeschichtungen wurde zuerst in reinem Wasser (D2O) verifiziert: Die Beschichtungen sind stabil in der Rippel-Phase der Lipiddoppelschichten. Dies konnte für verschiedene Druck- und Temperaturbedingungen bis hin zu physiologisch relevanten Temperaturen und etwa 100 MPa gezeigt werden. Zudem reagierten die Beschichtungen stabil auf äußere Scherkräfte und hafteten sowohl auf reinen Silizium-Oberflächen als auch auf Oberflächen mit Titanbeschichtung. In der flüssigen Phase der Lipide hingegen lösten sich die oligolamellaren Beschichtungen irreversibel vom Substrat. Der Einfluss des Hauptphasenübergangs auf die Struktur der Beschichtungen wurde mittels einer multilamellaren Lipidbeschichtung gemessen. In der Rippel-Phase sind die Lipidketten in all-trans Konformation, was zu einer erhöhten Schichtdicke der Lipidmembranen beiträgt. Im Vergleich dazu wurde in der flüssigen Phase mit geschmolzenen Lipidketten eine verminderte Schichtdicke gemessen. Darüber hinaus wurden strukturelle Veränderungen der Beschichtung mittels NR beobachtet, die nicht auf das Schmelzen der Lipidketten (gemessen durch ATR-FTIR) zurückgeführt werden können: ein anormales Quellverhalten der Lipiddoppelschichten bei Annäherung an den Hauptphasenübergang. Neben den Messungen in reinem Wasser wurden Lipidbeschichtungen auch in Lösungen aus Hyaluronsäure (HA) in Wasser (D2O) untersucht. Dieses System wurde als ein Modell für Säugetiergelenke verwendet. Es wurde festgestellt, dass HA tiefgreifende Veränderungen der Lipidmembranen verursacht: Bei Raumtemperatur und Umgebungsdruck entstand eine neue lamellare Phase, in der die Lipiddoppelschichten drastisch an Dicke zugenommen haben. Eine detaillierte Analyse der Streukurven ergab, dass sich HA-Moleküle außerhalb der einzelnen Lipidlamellen in der Nähe der Kopfgruppen anlagern. Das Überschreiten des Hauptphasenübergangs von der Ripple-Phase in die flüssige Phase der Lipidmoleküle führte nicht zum Ablösen der Lipidbeschichtung. Darüber hinaus wurde nachgewiesen, dass die Lipiddoppelschichten mit Lipidketten in geschmolzenem Zustand (gemessen mit ATR-FTIR) an Dicke zunehmen (gemessen mit NR). Es konnte gezeigt werden, dass das Quellen der Lipidbeschichtung durch Zugabe von 1 M Kochsalz in die HA-Wasser-Lösung unterdrückt werden kann. Hiermit verbunden ist die Abschirmung der elektrostatischen Wechselwirkungen im System. Der Einfluss von HA auf die Lipidmembranen wurde qualitativ auf der Basis der DLVO-Theorie unter Berücksichtigung zusätzlicher sterischer Wechselwirkungen diskutiert.
Die vorliegende Arbeit beschäftigt sich mit der Wechselwirkung von dreiwertigen Lanthaniden und Actiniden (Eu(III), Gd(III) und Cm(III)) mit den Aluminiumoxid/-hydroxidphasen Korund/Saphir (alpha-Al2O3), Gibbsit (alpha-Al(OH)3) und Bayerit (beta-Al(OH)3) sowie den Al-Polyoxokationen „Al13“ (Al13O4(OH)24(H2O)127+) und „GaAl12“ (GaO4Al12(OH)24(H2O)127+). Die Ergebnisse sollen zu einem besseren Verständnis der Wechselwirkungen von Radionukliden an der Wasser-Mineralphasen-Grenzfläche im Nah- und Fernfeld eines nuklearen Endlagers in tiefen geologischen Formationen beitragen, wobei die Retention insbesondere durch Sorptions- und Einbaureaktionen an/in Mineralphasen beeinflusst wird. Batch-Untersuchungen zur Wechselwirkung von Eu(III) mit den Mineralphasen Korund (alpha-Al2O3) und Bayerit (beta-Al(OH)3) zeigen im Bereich niedriger Metallkonzentrationen ([M(III)] ~ 1E-7 M) ähnliche oberflächennormierte logKd-Werte, was auf die Existenz sehr ähnlicher Oberflächengruppen und damit auf die Bildung von hydroxidischen Strukturen auf der Aluminiumoxidoberfläche zurückgeführt werden kann. Ähnliche logKd-Werte wurden in früheren Untersuchungen auch für die Sorption von Eu(III) an gamma-Al2O3 beschrieben. TRLFS-(time resolved laser fluorescence spectroscopy)-Untersuchungen zur Sorption von Cm(III) an Korund und Bayerit zeigen eine ähnliche Cm(III)-Speziation, wobei im pH-Bereich 3 < pH < 13 drei sorbierte Cm(III)-Spezies voneinander unterschieden werden können ([Oberfläche-Cm(OH)x(H2O)5-x]3-x mit x = 0, 1, 2). Vergleichbare Cm(III)-Spezies werden anhand von spektroskopischen Befunden auch auf den Oberflächen der Saphir (001)-Einkristalle sowie den Al(III)-Clustern „Al13“ und „GaAl12“ angenommen. Im Fall von Gibbsit führt der hohe isoelektrische Punkt zu einer erst bei pH 5.5 beginnenden M(III)-Sorption, wobei eine Cm(III)-Spezies der Art Gibbsit-Cm(H2O)5 übersprungen wird und sich wahrscheinlich direkt der erste Cm(III)-Hydrolysekomplex ausbildet. Weiter kann eine in kleinen Konzentrationen vorliegende, eingebaute Cm(III)-Spezies nachgewiesen werden, deren Bildung durch Al(OH)3-Ausfällung als Folge einer - bezüglich der Löslichkeit von kristallinem Gibbsit - übersättigten Suspension ermöglicht wird. Mit Ausnahme der Saphir (110)-Oberfläche weisen die TRLFS-Ergebnisse damit auf eine ähnliche Koordination des Metallkations an den Oberflächen der Aluminium(hydr)oxide hin. In Übereinstimmung dazu können anhand von Gd(III)-EXAFS-Untersuchungen ähnliche M(III)-Bindungsplätze auf Oberflächen von Gibbsit, Bayerit und Korund bestimmt werden. Im Fall von Gibbsit und Bayerit ist eine M(III)-Sorption sowohl an die Basal-, wie auch an die Kantenflächen möglich, wobei das Metallkation über zwei oder drei Aluminolgruppen an die Oberflächen gebunden wird (bi- bzw. tridentate Koordination). Eine entsprechende Zuordnung ist für Korund aufgrund der sphärischen Morphologie der Aluminiumoxidpartikel ohne die Ausbildung definierter Kristallflächen nicht möglich. Die Ergebnisse der EXAFS-Untersuchungen zeigen weiter, dass die Metallionen offensichtlich an unterschiedliche Oberflächenplätze gebunden werden können, so dass von mehreren nebeneinander vorliegenden M(III)-Oberflächenspezies ausgegangen werden kann. Zusammenfassend zeigen die im Rahmen dieser Arbeit erhaltenen Ergebnisse, dass eine Kombination verschiedener Untersuchungsmethoden die Aufklärung der Prozesse, die (dreiwertige) Kationen an der Wasser-Aluminium(hydr)oxid-Grenzfläche eingehen können, erleichtert. So können mit Hilfe der Cm(III)-TRLFS unterschiedliche M(III)-Oberflächenspezies an den verschiedenen Aluminium(hydr)oxid-Phasen bestimmt werden, während die EXAFS-Untersuchungen den Metallkationen definierte Bindungsplätze zuordnen. Jedoch weisen die Ergebnisse darauf hin, dass die Existenz verschiedener, in unterschiedlicher Koordination vorliegender M(III)-Oberflächenspezies wahrscheinlich ist. Weiter können neben Sorptionsreaktionen auch Einbaureaktionen in (amorphe) Al(OH)3-Festphasen nachgewiesen werden.
Cell migration is an essential characteristic of both physiological and pathological processes within the human body. In order to study the complex process of cell migration different in vitro model systems have been developed in the past. The challenge for all these assays is to provide the cells a substrate that mimics particular properties of the extracellular matrix (ECM) while a high control over experimental parameters and monitoring is desired. However, migration assays commonly used in cell biology and medical research are rather limited in the control over the architecture of the provided matrix on or through which the cells move or by the lack of adequate imaging devices to monitor cell dynamics. To overcome some limitations of conventional migration assays, it was the aim of this work to develop two different methods and employ them in order to quantify migrative behavior of cells under precisely controlled in vitro conditions. The first assay consists of microfabricated three dimensional (3D) scaffolds, which allow to study cell migration dynamics through confined environments via live-cell imaging. Channel structures of precisely defined dimensions were utilized to quantify the invasiveness of single cancer cells with respect to modifications of their cytoskeleton organization. In addition, dynamical migration patterns of the cells inside these confined 3D environments were analyzed and found to be significantly changed from their counterparts on flat, two dimensional (2D), surfaces. Furthermore, it was shown that such microfabricated structures could be functionalized in the nanometer range with patterns of gold nanoparticles. Thus, the selective binding of ECM-derived ligand motifs, to the gold particles allows for mimicking specific features of the ECM in 3D.
Aus molekulardynamischen und quantenchemischen Rechnungen an wässrigen Actinidkomplexen werden strukturelle, spektroskopische und thermodynamische Daten errechnet. Diese zeigen eine sehr gute Übereinstimmung mit aktuellen experimentell gewonnenen Daten und können daher in weiteren Studien zur Vorhersage oder Erklärung von Messwerten genutzt werden. Die gewonnen Ergebnisse gehen unter anderem als Parameter in Langzeitstudien zur Endlagersicherheit ein.
Die vorliegende Arbeit behandelt die Synthese und Charakterisierung neuartiger cyclometallierter Poly(pyridyl)iridium(III)-Komplexe und deren Anwendung als Lumineszenzsonden für die Detektion hoch negativ geladener Glykosaminoglykane und sulfatierter Polysaccharide. Es konnte gezeigt werden, dass die Bindung der neuen Farbstoffe an die Analyten primär auf elektrostatischen Wechselwirkungen beruht. Die gewonnenen Erkenntnisse wurden genutzt, um selektive und sensitive Nachweisverfahren für diverse Glykosaminoglykane in unterschiedlichen Medien zu entwickeln. Besonders interessant im Hinblick auf die klinische Diagnostik ist der Nachweis des Antikoagulationsmittels Heparin in Proben, die Blutserum oder -plasma enthalten. Im Rahmen der vorliegenden Arbeit ist es gelungen, auf Basis der neuen Poly(pyridyl)iridium(III)-Komplexe Heparin in serum-, plasma- oder urinhaltigen Proben quantitativ nachzuweisen. Der Quantifizierungsbereich korreliert gut mit dem klinisch relevanten Konzentrationsbereich. Weiterhin konnten bereits geringe Verunreinigungen durch das stark sulfatierte, semisynthetische, schwere Nebenwirkungen hervorrufende Glykosaminoglykan OSCS in Heparinproben detektiert werden. Zusätzlich konnte gezeigt werden, dass vor allem Iridium(III)-Komplexe mit einer hohen positiven Gesamtladung in der Lage sind, als Heparinantagonisten die antikoagulatorische Aktivität von sowohl unfraktioniertem als auch niedermolekularem Heparin zu neutralisieren. Die Verbindungen weisen eine vergleichbar starke Bindung an Heparin auf wie das standardmäßig eingesetzte Heparinantidot Protamin.
Periodische Lochgitter in Metallfilmen zeigen überraschende optische Eigenschaften, welche auf die resonante Anregung von Oberflächenplasmonen (OP) zurückzuführen sind. So kann eine verstärkte Transmission bei Resonanzwellenlängen der OP beobachtet werden, welche unter anderem vom Brechungsindex der Umgebung des Metallfilms abhängt. In einer Reihe von Anwendungsfeldern wird der Einsatz von Lochgittern gegenwärtig untersucht, darunter die Verwendung in chemischen oder biologischen Sensoren. Trotz des Anwendungspotentials dieser Strukturen erfordert die Herstellung mit gegenwärtigen Methoden den Einsatz kostspieliger Verfahren oder ist nur mit geringem Durchsatz möglich. In dieser Arbeit wurde daher ein neuartiges, lithographisches Verfahren entwickelt, mit dem sich Lochgitter in Metallfilmen mit rein chemischen Methoden herstellen lassen. Hierzu wurde zunächst ein simples Verfahren entwickelt, um zweidimensionale Kolloidkristalle herzustellen. Dabei wurden Hydrogel-Mikrosphären aus Poly-(N-isopropylacrylamid) (PolyNIPAM) eingesetzt, da diese eine Reihe bemerkenswerte Eigenschaften aufweisen. Insbesondere führt der reversible Volumenphasenübergang der Mikrosphären zur Bildung nicht-dichtest-gepackter Kristalle, welche direkt als lithographische Maske in den nachfolgenden Prozessschritten eingesetzt werden können. Daneben kann die induzierte Oberflächenaktivität ausgenutzt werden, um durch mechanisches Tempern die Anzahl der Kristallgrenzen drastisch zu reduzieren. Dabei konnten Einkristalle erhalten werden, dessen Ausdehnung in der Größenordnung von mm^2 liegt. Der kolloidale Kristall fungiert im folgenden Prozessschritt als lithographische Maske bei der Erzeugung eines Lochgitters in einem Goldfilm. Dieser Schritt basiert auf der gerichteten Bindung von Goldnanopartikeln an das Glassubstrat und deren Vergrößerung durch chemische Goldabscheidung. Hierbei wurde unter anderem untersucht, wie sich die strukturellen Eigenschaften, wie Gitterkonstante, Oberflächenrauheit und Filmdicke, präzise einstellen lassen. So kann etwa durch den Einsatz von Mikrosphären variablen Durchmessers die Gitterkonstanten zwischen ~ 300 - 1200 nm eingestellt werden. Dies ermöglicht die präzise Kontrolle der Position der Transmissions-Maxima im Spektrum. Die Transmission der erzeugten Lochgitter wurde im dritten Teil der Arbeit eingehend untersucht und wird erwartungsgemäß vor allem durch die Gitterkonstante bestimmt. Insbesondere wurde der Einfluss der Struktur, wie etwa die Ordnung des Lochgitters, auf die optischen Eigenschaften untersucht. Daneben wurde die Sensitivität der Resonanzen auf Änderungen des Brechungsindex bestimmt. Je nach betrachteter spektraler Signatur und Gitterkonstante ergab sich dabei die Sensitivität zu 300 - 800 nm/RIU. Sie ist damit vergleichbar mit Lochgittern, welche mit aufwendigeren Verfahren hergestellt wurden. Das letzte Kapitel beschäftigt sich mit der Entwicklung eines Modellsystems, das künftig bei der Untersuchung des invasiven Potentials von Tumorzellen eingesetzt werden könnte. Das System basiert auf einem Lochgitter, welches mit einem Gelatinefilm definierter Dicke beschichtet wird. Durch die Aktivität von Kollagenasen, welche typischerweise von invasiven Tumorzellen sezerniert werden, kann die Gelatine abgebaut werden. In ersten Experimenten konnte gezeigt werden, dass der enzymatische Abbau im Transmissionsspektrum der Lochgitter verfolgt werden kann. Dies belegt die praktische Relevanz der untersuchten Lochgitter.
Leopold Gmelin (1788 - 1853) gilt als einer der führenden Naturwissenschaftler des 19. Jahrhunderts. Insbesondere auf dem Gebiet der Chemie erlangte er durch sein bis heute fortgeführtes, außergewöhnlich umfangreiches und vollständiges "Handbuch der Chemie" große Berühmtheit. Seine Versuche über die Verdauungsvorgänge und die dadurch erlangten Erkenntnisse über die Magensäure, die Gallenflüssigkeit und die Resorption der Nährstoffe aus dem Magen-Darm-Trakt machten ihn zum Mitbegründer der modernen Physiologie. Die vorliegende Studie stellt ein umfassendes Gesamtbild vom Leben und Wirken dieses Heidelberger Chemikers dar. Sie gibt nicht nur Aufschluss über seine zahlreichen Forschungsarbeiten, Entdeckungen und Veröffentlichungen, sondern beleuchtet auch das wissenschaftliche und private Umfeld, und vermittelt einen Eindruck von den Umständen, unter denen Leopold Gmelin arbeitete und lebte. Auf Basis von alten Schriftstücken, Akten und Briefen wird Gmelins Beziehung zu seiner Familie, seinen Verwandten und Freunden beschrieben. Dabei zeigt sich, dass er nicht nur ein Forscher, sondern auch ein romantischer Dichter war. Die Transkription und Auswertung des bisher größtenteils unveröffentlichten Briefwechsels von Gmelin liefert neue Erkenntnisse sowohl über die Privatperson als auch über den Wissenschaftler. Es tritt die Wahrheit über ein verbotenes Duell im Jahr 1811 ans Licht, das bislang in der Literatur anders dargestellt wurde. Außerdem geben die Schriftstücke Kenntnis von Gmelins Situation an der Universität Heidelberg, über seine Bemühungen um das chemische Laboratorium, sein privates und kollegiales Verhältnis zu anderen Wissenschaftlern und zu seinen Schülern. Neben seiner Forschungs- und Lehrtätigkeit half Gmelin bei der Überführung eines Mörders, erkannte und warnte als Erster vor der Giftigkeit arsenhaltiger Wand- und Tapetenfarbe, besaß eine eigene Papiermühle und setzte sich unermüdlich für den Bau eines Aussichtsturmes auf dem Heidelberger Königstuhl ein. Mit dieser Studie wird der Lebensweg von Leopold Gmelin aufgezeigt, dessen Forschungsarbeiten und literarische Werke Spuren bis in die heutige Zeit hinterlassen haben.
Adherent cells are sensitive to physical and chemical cues in their environment and can adapt their response accordingly. Receptors in cells membrane are crucial elements in the recognition of such signals by binding external ligands (key-and-lock principle). Thereby these receptors and associated proteins transduce external cues in internal signals. Chemical nature of the ligands and their spatial arrangement can provide important information to the cells. In particular, spatial clustering of the ligands at the nanometer scale is considered to be a general principle by which the signal transduction of many biological processes gets modulated. Examples are the formation of focal adhesions (FAs) or of the immunological synapse. To investigate such clustering effects at the molecular scale, there is an immanent need for the precise chemical modification of surfaces. Therefore, the aim of this work was to (i) develop a substrate on which the spatial arrangement of bound particles could be precisely controlled and varied at the nanometer scale, and (ii) to demonstrate the utility of such substrates in cell adhesion studies. During this work an elastic poly(ethyleneglycol)-diacrylate (PEG-DA) hydrogel (HG) was used as carrier substrate on which an array of gold nano-particles (AuNPs) with well defined inter-particle distances (Delta L) was immobilized. Delta L could be successfully varied at the nanometer scale by mechanical stretching of the carrier substrate. For cell adhesion studies the AuNPs were functionalized with a c(RGDfK) peptide so that integrin binding was preferentially invoked. Due to the protein repellent properties of PEG, the AuNPs constituted the only anchor points on which cells could adhere. Thereby nanometer precision on the spatial arrangement of the ligands was achieved. To show the versatility of PEG-DA HGs as bio-mimetic substrates, the surfaces of a series of HGs were homogeneously functionalized with Fibronectin (FN). Strain applied to the HGs was successfully transmitted to cells and FAs and their reaction to the strain and to the change in inter-ligand distances was monitored and analyzed. The anisotropy generated in the ligand array by the uni-axial stretching influenced cell adhesion. FAs reaction was more prominent when stretched on HGs + FN than on HGs + AuNPs + RGD. In summary, fabrication of a material system for the dynamic variation of Delta L in the tens of nanometers was accomplished in this work. By rendering these substrates bio-mimetic, cell adhesion studies with dynamic variation of inter-ligand distances could be performed.
Der Fokus dieser Arbeit liegt im Design und der Herstellung von Eisenoxyd- Nanopartikeln zur Verwendung als Kontrastmittel für die Magnetresonanztomographie MRT) sowie die optische Bildgebung (OI). Eisenoxyd Kerne der Größe 5-6 nm, mit niedrigem Polydispersitäts-Index wurden durch Kopräzipitations-Strategien unter wässrigen Reaktionsbedingungen hergestellt. Zunächst wurden lanthanid-dotierte Nanopartikel (Ln-USPIO) getestet, welche scheinbar aufgrund von zu geringen Mengen von, in das Eisenkristallgitter inkorporierten, Lanthaniden nicht fluoreszent waren. Dies lässt sich durch die größenbasierenden Unterschiede zwischen Lanthaniden und Eisenkationen erklären, welche die Dotierungseffizienz entscheidend verringern. Als zweites haben wir eine Fluoreszenzummantelung der Nanopartikel durch Naphthalin-Sulfonsäure und deren modifizierter Analoge verwendet, was allerdings (trotz vorhandener Stabilität) ebenfalls erfolglos blieb, da die Partikel nicht fluoreszent waren. Grund war das Quenchings der Fluoreszenz aufgrund von Elektronenübertragung zwischen den aromatischen Naphthalin-Sulfatringen und den Eisenoxyd-Partikeln. Danach erforschten wir adsoptive Coatingsubstanzen, welche nicht quenchen und relativ stabil sind. Erfolgversprechend erwiesen sich Flavinanaloga (Flavinmononukleotid (FMN) und Flavin Adenin Dinukleotid (FAD)). Dies sind relativ simpel strukturierte, endogene Moleküle, die von Krebs- oder metabolisch aktiven Zellen, über den Flavin Rezeptor (RCP) internalisiert werden. Biokompatible, fluoreszierende und nicht-polymere FMN-und FAD-beschichtete USPIO (FLUSPIO und FAD USPIO) konnten als vielseitiges MR-Kontrastmittel entwickelt.Herstellung stabiler flavin adsorbierter Nanopartikel durch Beschallung der USPIO mit FMN/FAD mit anschließender GMP-Beschichtung unter wässrigen Bedingungen. Der Kerndurchmesser, die Oberflächenmorphologie und die Oberflächenbedeckung der FMN- und FAD-ummantelten USPIO (FLUSPIO; FAD USPIO) wurden mittels TEM,DLS, SEM, AFM, Power XRD, EDX und TGA ermittelt. Die magnetischen Eigenschaften der FLUSPIO und FAD USPIO wurden mit Hilfe von MRT und SQUID untersucht. Die Analyse der Fluoreszenzeigenschaften von FLUSPIO and FAD USPIO erfolgte durch Fluoreszenz -Spektroskopie, Mikroskopie und Bildgebung. Zellvitalität und Biokompatibilität der FLUSPIO und FAD-USPIO wurden durch Trypanblau-, 7-AAD- und TUNEL-Färbung ermittelt. Die in vitro-Evaluierung der Labelingeffizienz sowie der Spezifität bezüglich RCP wurde mittels MRT und Fluoreszenzmikroskopie untersucht. Das pharmakokinetische Verhalten von FAD USPIO wurde in CD1 Nacktmäusen nach intravenöser Injektion durch Fluoreszenzspektroskopie gezeigt. Die in vivo Aufnahme der FAD USPIO Nanopartikel wurde in männlichen, subkutane Prostatakarzinome tragenden CD1 Nacktmäusen ermittelt. Die Aufnahme wurde mit der des klinisch verwendeten SPIO Kontrastmittels Resovist verglichen und weiterhin getestet durch Berliner Blau- sowie immunhistologische Färbungen an Tumorschnitten. Die hohe Relaxivität (r2 und r1), sowie das superparamagnetische Verhalten der FLUSPIO / FAD USPIO wurden mittels MRT und SQUID validiert. Die Biokompatibilität der FLUSPIO und FAD USPIO wurde durch verschiedene Zellvitalitätsassays und Färbungen nachgewiesen. Die hohe Effizienz der FLUSPIO / FAD USPIO in Bezug auf die Markierung von Krebszellen (PC-3, DU-145, LnCaP) sowie aktivierter Endothelzellen (HUVEC) und ihre Spezifität für RCP wurde durch MRT, ICP-MS und Fluoreszenzmikroskopie bestätigt. Die in vivo-Aufnahme der FAD USPIO durch experimentell erzeugte Prostatakarzinome war signifikant höher als die Aufnahme des kommerziellen SPIO-Kontrastmittels Resovist. Zusammenfassend lässt sich sagen, dass sich in unseren Ansätzen magnetischfluoreszente Eisenoxyd-Nanopartikel mit FAD/FMN Beschichtung als am aussichtsreichsten erwiesen. Diese Partikel zeigten eine starke RCP-vermittelte Aufnahme durch Krebs – und aktivierte Endothel-Zellen sowie eine starke Akkumulation innerhalb der Tumoren, nach intravenöser Injektion. Die Möglichkeit des RCP-Targeting könnte demnach ein neuer vielversprechender Weg sein, um Nanopartikel und Arzneimittel in metabolisch aktive Krebszellen einzuschleusen.
The present work contains the results of our theoretical studies of Intermolecular Coulombic decay (ICD) following ionization of noble gas dimers and of biochemically relevant hydrogen bonded systems. We have investigated the ICD following Auger decay of the weakly bound Ne2, Ar2, and NeAr. It was shown that despite their seeming simplicity the noble gas clusters are lavish in interesting physical phenomena and provide the opportunity for studying various kinds of ultrafast and fast interatomic processes, such as: direct ICD, exchange ICD, electron transfer mediated decay (ETMD), processes of photon emission, and relaxation by coupling to the nuclear motion. Our results have largely expanded the qualitative and quantitative understanding of this type of cascade decay processes. A better interpretation of experimentally observed phenomena was achieved with our numerical data which were also used to computed ICD electron spectra within the framework of the time-dependent theory of wave packet propagation. The ICD following inner-valence ionization was studied for the hydrogen bonded H2O· · ·H2O, H2O· · ·HCHO, H2O· · ·H2CNH, H2O· · ·NH3, NH3 · · ·H2O, H2O· · ·H2S, and H2S· · ·H2O (p-donor · · · p-acceptor). This set of small hydrogen bonded systems contains seven types of hydrogen bonding which are typical for biochemistry and thus its investigation provides insight into the processes that can take place in living tissues. In particular, an estimate of the ICD in biosystems interacting with water (their usual medium) is made. This decay mode is expected to be a source of low-energy electrons proven to be of extreme genotoxic nature. The study of H2O· · ·H2O also includes the first quantitative description of the ICD of doubly ionized states created via Auger decay. For the purpose of our study we have used high-precision ab initio methods in optimizing the geometries and computing the ground state energies, as well as the single-, double-, and triple-ionization spectra of the studied species. The energy range of the emitted ICD electrons, as well as the kinetic energy of the dissociating ions produced by ICD is also reported. Potential energy curves of the different electronic states involved in the investigated processes were computed and analyzed where it was needed.
In der vorliegenden Arbeit wurde die Motilität des Blutparasiten Trypanosoma brucei brucei untersucht. Dieser vor allem in Subsahara-Afrika verbreitete Organismus wird von der Tsetse-Fliege auf Menschen und Tiere übertragen und löst die unbehandelt tödlich verlaufende Afrikanische Schlafkrankheit aus. Nur wenige Medikamente sind bekannt, diese zeichnen sich jedoch meistens durch das Auftreten schwerer Nebenwirkungen aus. Der Organismus ist lange bekannt und seine Eigenmotilität wird seit langem mit seiner Pathogenität in Verbindung gebracht, trotzdem fehlen bislang weitgehend quantitative Untersuchungen zur Fortbewegung, vor allem der im infizierten Organismus vorkommenden Blutstromformen. Eine Strategie des Parasiten um die Immunantwort des Wirtes zu umgehen ist das „Abwaschen“ an der Zelloberfläche gebundener Antikörper durch gerichtetes Schwimmen. Desweiteren ist die Eigenbewegung von großer Bedeutung für die Zellteilung und damit erfolgreiche Vermehrung des Organismus sowie für die Verteilung im Wirt, da im Endstadium der Krankheit durch den Parasiten aktiv die Blut-Hirn-Schranke passiert wird. Die Kenntnis des zugrundeliegenden Fortbewegungsmechanismus ist also von grundlegender Bedeutung zum Verständnis der Pathogenese und damit zur Entwicklung von Strategien zur medikamentösen Bekämpfung des Erregers im infizierten Wirt. Im Rahmen dieser Arbeit wurde das Motilitätsverhalten von Trypanosomen unterschiedlicher Lebenszyklusstadien bei verschiedenen Temperaturen mikroskopisch untersucht. Dazu wurde ein portables, holographisches Mikroskop entwickelt, dass die Vermessung von Trypanosomen bei physiologischen Temperaturen mit hoher Auflösung und Stabilität erlaubt. Die erhaltenen 3D-Daten erlauben erstmals eine quantitative Analyse frei schwimmender Trypanosomen über große Volumina und Zeiträume. Aus den Daten wurden zwei deutlich unterscheidbare Schwimmzustände abgeleitet, für die charakteristische Schwimmparameter, wie mittlere Schwimmgeschwindigkeiten und –winkel sowie typische Ausbreitungsverhalten abgeleitet werden konnten. Die Schwimmzustände konnten durch Referenzmessungen mit Motilitätsmutanten und unter Verwendung spezieller Probenkammern erfolgreich zwei unterschiedlichen Bewegungsmodi der die Trypanosomen antreibenden Struktur, dem Flagellum, zugeordnet werden. Die erhaltenen Daten zeigen deutlich die Adaption der Lebenszyklusstadien an ihre jeweils physiologische Temperatur und stützen eines der postulierten Modelle für die Trypanosomenbewegung, das run-and-tumble-Modell. Sie stellen somit einen wichtigen Beitrag zur Diskussion des Fortbewegungsmechanismus von Trypanosomen dar.
The molecular-level understanding of biological molecules on solid surfaces is critical in areas including medicine, biologically-based industry, and the development of biotechnologies. In order to gain further knowledge of the orientation and organization of biological molecules adsorbed on surfaces, we used the label-free, interface-specific technique of sum-frequency generation (SFG) spectroscopy. This technique has the distinct advantage of being able to be operated in situ as well as ex situ, allowing for direct comparison of changes in biological molecules between these two states. Films of surface-bound single-stranded DNA (ssDNA) on gold were chosen as model biological systems due to their numerous applications in genetic profiling, nano-assembly, and bio-computing, as well as their relative simplicity as biomolecular layers. Sensitivity and proof-of-principle tests on simple surface-bound, short alkane chains demonstrated the ability of SFG spectroscopy to detect molecular concentrations low enough to be useful in the investigation of biological molecules and to accurately detect the interactions of water with model hydrophobic and hydrophilic self-assembled monolayers. Investigations of multilayers of thymine, adenine, and cytosine nucleobases alone revealed a high degree of order in the thymine layers, with the signals from the methyl group unique to this base clearly visible. Films of both thiolated and non-thiolated surface-bound DNA in air showed little and moderate orientation, respectively, with the methylene stretches of the sugar-phosphate backbone dominating the spectra. Comparison of the changes in signal intensity among thymine, adenine, and cytosine ssDNA films in air and in H2O revealed differences in their solubility, which agreed with current ex situ knowledge of the manner in which these differing DNA types adsorb on gold surfaces. These experiments also revealed the appearance of nucleobase-specific spectra upon exposure to water, which was tied to the higher mobility of the sugar-phosphate backbone under these conditions. Investigations of hybridized ssDNA films in air using SFG spectroscopy indicated that the hybridization process in surface-bound DNA molecules does not necessarily correspond with an increase in molecular order, as is known to happen with DNA molecules in solution, and furthermore that even gentle processing of such hybridized samples for ex situ analysis can significantly disrupt the hybrid structure. These results were confirmed using near-edge absorbtion fine structure spectroscopy. Finally, the results obtained from the model DNA films were applied to a more complex biomolecule, fibronectin, on gold surfaces. Experiments showed that SFG spectroscopy could detect a fibronectin film even under a layer of fixed cells. Further tests on living cells over alkanethiol self-assembled monolayers confirmed this observation. These results give new information on the orientation and organization of DNA films on solid surfaces both in and ex situ, and show how this knowledge can be applied to more complex biological systems. Furthermore, this work contributes to a knowledge base for the application of SFG spectroscopy to future questions in which the label-free, in situ knowledge of surface-bound biological molecules is of critical importance.
6. Marsilius-Vorlesung am 30.06.2011 in der Alten Aula der Universität
Um die Begriffe "Internationalität" und "Interdisziplinarität" geht es in der Veranstaltung der Alexander von Humboldt-Stiftung (Bonn) und des Marsilius-Kollegs der Universität Heidelberg, die am 30. Juni 2011 an der Ruperto Carola stattfindet. Professor Dr. T. Douglas Price von der University of Wisconsin-Madison, USA, spricht über die Altersbestimmung von archäologischen Funden mit naturwissenschaftlichen Methoden. Die Veranstaltung ist Teil der Jubiläumsfestwoche der Ruperto Carola, dem festlichen Höhepunkt der Feierlichkeiten zum 625-jährigen Bestehen der Universität Heidelberg.
Teil 1: Begrüßung durch Prof. Dr. Bernhard Eitel
Teil 2: Einführung durch Dr. Ulrike Albrecht
Teil 3: Marsilius-Vorlesung Prof. Dr. T. Douglas Price
New, efficient and reproducible methods for the fabrication of Metal-Insulator-Metal (MIM) junctions for applications in spintronic devices have been developed. The junctions consisted of a gold substrate as bottom contact, p-terphenyl-based self-assembled monolayers (SAMs) as insulator layer, and thin ferromagnetic metal films (nickel) as top contact. Both pristine and electron irradiated (denoted by the prefix CL-) SAMs of [1,1’:4’,1”-terphenyl]-4,4”-dimethanethiol (TPDMT), (4’-(pyridin-4-yl)biphenyl-4-yl)alkanethiol (PPPn, n = 1,3) and perfluoroterphenyl-substituted alkanethiols (FTPn, n = 2,3) on Au(111) were used as test systems. All molecules were found to form well-ordered, high quality SAMs, a prerequisite for the fabrication of SAM-based MIM devices. In addition, the influence of the SAMs’ molecular architecture on its transport properties has been investigated. In particular, we have studied the effect of the small alkane linker (between the head group and the p-terphenyl backbone) found in all the molecules used in this work. The alkane linker was found act as an insulator, allowing us to decouple of the aromatic core’s electronic system from the substrate. We then studied the effects of electron irradiation on PPPn/Au and FTPn/Au SAMs. Both SAMs were modified with electrons. In particular, the charge transport properties of the FTPn/Au surface could be fine-tuned simply by controlling the irradiation dose. Finally, nickel was deposited on all SAMs to test their usefulness as dielectric layers in MIM devices. Whereas nickel was found, by XPS and NEXAFS spectroscopy, to penetrate into and through the SAMs of TPDMT, CL-TPDMT, PPP1 and CL-PPP1 on Au(111), a single layer of palladium chloride, deposited from solution on either TPDMT/Au or CL-PPPn/Au, promoted the nucleation and growth of nickel thin films on top of the respective SAMs via alloying of nickel with palladium. Furthermore, reaction of nickel with the perfluorinated FTPn SAMs yielded a new class of organometallic thin films in which nickel was found to reside mainly at the top. Irradiation of the FTPn monolayers with electrons gave us precise control over the work function of the CL-FPTn/Au surfaces (a crucial parameter for the fabrication of nanoelectronic devices) while favouring the nucleation and growth of top ferromagnetic contacts. The penetration of nickel into and through CL-FTPn/Au SAMs was found to decrease by as much as 30 % at high irradiation doses (> 30 mC/cm2) making FTPn systems attractive as dielectric layers for nano junctions.
Adhesion strength is a measure to determine the interaction between cells and their environment. Numerous types of devices and coatings are developed in order to meet medical and non medical issues and surface properties can be tuned in order to evoke specific cell response. In this work various properties of solid surfaces were investigated towards their impact on adhesion process and adhesion strength of mammalian cells, which both give information on the cell interaction with the substrate. Therefore a sophisticated assay to observe cell adhesion and measure cell adhesion strength on artificial surfaces was developed. Its capability to measure cell adhesion strength in the order of five magnitudes with a high reliability and quantitative output was applied to synthetic surfaces with different degree of hydration, anisotropic topography, bioactivity and different polarizations. Investigation of fibroblast adhesion on ethylene glycol self assembled monolayers showed that cell adhesion strength is reduced by increasing degree of hydration. At the same time it was found that cell adhesion strength was independent of cell spreading area, in particular when a certain spreading size was reached. This finding may strengthen the zipper detachment mechanism by which the cell detachment occurs after distinct bonds are broken. Another study on hydrogel like polysaccharides confirmed the inability of fibroblasts to attach to hydrated surfaces. At the same time it was found that hematopoietic progenitor cells expressing CD44 receptors overcome the inertness and attach to the coating by shear force induction through a hydrodynamic flow. This finding may explain the fact that the presence of hyaluronan is a prerequisite in the stem cell homing and engraftment process into the bone marrow. Besides receptor ligand interactions more basic surface polarity effects were studied, which have been reported to have a minor impact towards cell adhesion. Here it was shown by investigation of fibroblast adhesion on periodically poled ferroelectric lithium tantalite crystals, that the gradient between two opposite polarities can be sensed by cells but not the polarity itself. The cells do not distinguish the overall polarity of a surface, but avoid placing the nucleus in proximity to the sharp borders in between to inverse polarities as the cells start to spread. Even though this astonishing reaction is unexpected it is not contradictive to the absence of polarity sensing because sensing of a polarity gradient is different from a distinct polarization spread over a large area. Instead of a gradient, anisotropic surface properties can be achieved by directional surface texture. Anisotropically textured poly(p-xylylene) surfaces, which consist of dense packed tilted nanorods, revealed a force directional dependence of fibroblast cell adhesion strength. The hydrodynamic shear force applied with the direction of nanorod tilting revealed a reduced cell adhesion strength compared to force application perpendicular and against the tilting. This finding could be explained by a model which accounts for cell filopodia attaching between nanorods of the surface. In order to prove the filopodia attachment theory more sophisticated imaging, which reveals ultrastructural components, was needed. Therefore, cell preparation protocols were established with special attention to preserve cellular structure to image via X-ray holography under ultrahigh vacuum conditions. The imaging project was conducted in a consortium of researchers and first successful imaging was demonstrated.
In the course of this doctoral work, a series of organophosphorus derivatives were synthesised in order to deepen our understanding of the influence of the environment around the phosphorus on the flame retardant mechanism. The Friedel-Crafts reaction of PCl3 with 2-hydroxybiphenyl, 2,2-dimethylpropane-1,3-diol and 2-aminobiphenyl yielded the phosphorus chloride precursor of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO), 5,5-dimethyl-[1,3,2]-dioxaphosphorinane-2-oxide (DDPO) and 9,10-dihydro-9-aza-10-phosphaphenanthrene 10-oxide(DAPO) respectively. The phosphorus chloride derivatives were then either hydrolised, oxidised, or thionised to yield a series of molecules where the environment around the phosphorus atom varied. The synthesized molecules were chemically incorporated(preformulation) in phenol epoxy novolac (DEN 438) with different phosphorus concentrations. According to standard EE processes, the modified resins were then cured using DICY as hardener and Fenuron as accelerator. The influence of the chemical modification of the epoxy phenol novolac resin, on the glass transition temperature (Tg) of the cured material, was investigated using DSC. As a result of the decreasing number of epoxy functional group available for cross-linking, the Tg decreased with increasing phosphorus loading. This effect was enhanced when sulphur containing molecules were used. However, chemical modification with DAPO only resulted in a negligible impact on Tg as the amine functionality could contribute to the cross-linking. The flame retardant efficiency of the modified resin with different phosphorus loading was evualted using the UL-94 test, in accordance with the DIN IEC 60695-11-10. All phosphorus derivatives improved the flame retardancy of phenol epoxy novolac resin with comparable phosphorus loading to DOPO. However, 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-sulfide (DOPS) imparted UL-94 V0 rating with only 1.0 % phosphorus loading. In order to further understand the role of the PO and PS radicals in the mode of flame retardancy of DOPS, Limiting Oxygen Test (LOI) and thermal desorption mass spectrometry (TD-MS) were carried out. TD-MS experiments revealed that PS and PO radicals are released sequentially in the gas which can rationalise the better efficiency of DOPS in comparison to DOPO. LOI experiments showed that the intumescent mechanism of DDPO was reduced when sulphur replaced oxygen in 5,5-dimethyl-[1,3,2]-dioxaphosphorinane-2-sulfide (DDPS). Finally, a part of a cooperation with Prof. G. Camino (Politecnico di Torino, Italy), a DOPO modified resin was cured in the presence of an organically modified montmorrillonite nanoclay (Cloisite 30B), in an effort to understand the interactions between DOPO and nanoclays and their impact on the flame retardancy of epoxy phenol novolac. The flammability of cured materials was tested using UL-94 test, LOI and cone calorimetry. The cone calorimeter enables to measure the heat released by the polymeric material under controlled conditions, as well as the gases evolving from the combustion process.
Im Rahmen dieser Arbeit wird das Fibronektin (Fn) Dimer (welches im Blut vorkommt und zur Fibrillenbildung fähig ist) oder Monomer (welches nach der Reduktion von Dimeren erhalten wird) an unterschiedlich dicht verteilte und circa 7 nm große Gold-Nanopartikel auf Oberflächen gebunden. Die Herstellung dieser Oberflächen erfolgt mittels Diblockcopolymer-Mizellen-Nanolithographie (engl.: block copolymer micelle lithography (BCML)). Eine Herausforderung ist hierbei die effiziente und reproduzierbare Anbindung einzelner, unmodifizierter Fn Dimere oder Monomere an einzelne Gold-Nanopartikel auf Oberflächen sowie deren Charakterisierung. Hierfür wird die Effizienz a) einer direkten Anbindungsstrategie, bei der das Molekül statistisch orientiert an Gold-Nanopartikel gebunden wird, und b) einer indirekten Anbindungsstrategie, bei der das Molekül gerichtet orientiert über einen Linker an Gold-Nanopartikel gebunden wird, mittels der Schwingquarzmikrowaage mit Bestimmung des Dissipationsfaktors (engl. quartz crystal microbalance with dissipation (QCM-D)), einer Kombination von QCM-D und Reflektometrie, Fluoreszenzmikroskopie, Rasterelektronenmikroskopie (REM), Transmissions-elektronenmikroskopie (TEM) und Rasterkraftmikroskopie (engl. atomic force microscope (AFM)) untersucht. Ein Vergleich der Hydrophilie von Oberflächen untereinander geschieht hier mit Hilfe der statischen Kontaktwinkelmessung.
Oberflächenladung und ionenspezifische Effekte, die an der Metalloxid/Wassergrenzfläche auftreten, spielen eine entscheidende Rolle in verschiedenen biologischen, ökologischen, geophysikalischen und industriellen Prozessen. Trotz ihrer Bedeutung ist der Einfluss dieser Effekte auf die Anordnung der Wassermoleküle an der Grenzfläche zu geladenen Oxidoberflächen noch nicht völlig verstanden. In dieser Arbeit wurden Oberflächenladung und ionenspezifische Effekte an der ITO/Wassergrenzfläche mit Hilfe von in situ Schwingungs-Summenfrequenzgenerations (SFG)-Spektroskopie zusammen mit Voltammetrie untersucht. Der n-Typ ITO-Halbleiter mit großer Bandlücke wurde als Versuchsmaterial wegen seiner guten chemischen Stabilität, hohen optischen Transparenz und seines geringen elektrischen Widerstandes gewählt. Diese Eigenschaften ermöglichen simultane spektroskopische und kontrollierte voltammetrische Messungen in wässeriger Umgebung. Um diese Messungen an dieser Grenzfläche und anderer geladener fest/flüssig Grenzflächen durchzuführen, wurde der vorherige SFG-Spektrometeraufbau substantiell verändert. Im Besonderen wurde ein Fabry-Perot Etalon für die zeitliche Pulsmodifizierung und unabhängige Phasenmessungen hinzugefügt, ebenso wurde der Probenbereich für eine einfache Bedienung und schnelle Wechsel der Messzelle neu gestaltet. Zusätzlich wurde eine Referenzlinie für Messungen absoluter Intensitäten installiert. Außerdem wurde eine neuartige Drei-Elektroden spektroelektro-chemische Zelle mit einem ITO-beschichteten und IR-transparenten Prisma als Arbeitselektrode konzipiert und angefertigt. Die dünne aufgedampfte und temperierte ITO-Schicht wurde zunächst bezüglich ihrer strukturellen, elektrischen und optischen Eigenschaften mit Hilfe von Röntgenbeugung, Rasterelektronenmikroskopie, Vierpunktmessungen und optischen Spektroskopien charakterisiert. Eine homogene, polykristallin strukturierte Oberfläche mit geringer Schichtresistivität (ca. 10^-2 Ohm cm) und hoher Transmission (ca. 80–90%) im sichtbaren Bereich wurde gefunden. Der isoelektrische Punkt (pHiep = 3) von ITO wurde durch Messungen des Strömungspotentials inWasser und wässerigen Salzlösungen bestimmt. Der Einfluss des angelegten Potentials auf die Anordnung der Wassermoleküle und auf die Ionenaffinität wurde mit SFG-Messungen an zwei Positionen in der Region für gebundenes OH (ca. 3150 cm^-1 und ca. 3400 cm^-1) mit Schwerwasser, Wasser und zwei Reihen anionischer und kationischer Salzlösungen untersucht. Die Experimente mit Wasser zeigten das Vorhandensein eines starken nichtresonanten Beitrages der ITO-Schicht, der möglicherweise alle resonanten Beiträge dominieren könnte, außer vielleicht bei hohem positiven Potential. Für die anionischen und kationischen Salzlösungen konnte kein ionenspezifischer Effekt entdeckt werden. Einige weiche Ionen zeigten jedoch eine bestimmte Affinität für die ITO-Oberfläche. Zusätzlich wurde die Oberflächenstromdichte in beiden spektralen Bereichen und die Anwesenheit von Korrosionseffekten auf ITO gemessen, welche besonders auffällig für Halogensalze waren.
The demand of compact and energy saving procedures for the synthesis of H2, synthesis gas and olefins from hydrocarbon fuel is expanding very rapidly as these are essentially needed in fuel cells, additive for fuel and for the cleaning and purification of flue gas. The concern is in particular to more efficient and environmentally more compatible concepts of the energy supply and reduction of pollutant emissions in mobile and stationary applications. Aliphatic hydrocarbons can be reformed efficiently through catalyst aided partial oxidation over noble metals such as rhodium and the hydrocarbons can also be converted into basic chemical substances. Due to the complex interaction between homogenous and heterogeneous reaction as well as transport processes, many experimental findings could not be interpreted till now. Only with models which are based on molecular processes, it will be possible to understand the catalysis and surface science chemistry better. Computational studies can be very useful in understanding the interaction of adsorbates with metal surfaces. These studies allow obtaining information that is difficult to measure experimentally such as adsorption energies, geometries of adsorbed molecules and activation energy of surface reactions in particular. The aim of the present work is to study the reactions relevant to partial oxidation of C1, C2 and C3 hydrocarbons in catalytic surface of rhodium by first principles calculations. DFT simulation of individual elementary step reactions is carried out. The kinetic parameters and derivative of thermodynamic data is obtained by means of the program CASTEP and VASP, which are based on periodic boundary conditions. The detailed comprehension of the surface processes enables to improve understanding of the partial oxidation catalysis occurring at Rh surface.
The aim of this PhD project was to develop a fast and reliable method for the calculation of exchange coupling constants which are used in the description of the coupling of unpaired electrons in di-, tri- and oligonuclear transition metal complexes. In order to achieve both accurate results and low computational costs, a combination of quantum chemistry (QC) and molecular mechanics (MM) calculations has been employed.
In der vorliegenden Arbeit wurden mono- und bimetallische geträgerte Nanopartikel für Untersuchungen zur katalytischen Ruß- und Propanoxidation hergestellt. Dabei wurden sowohl konventionelle Platingruppenmetalle, wie Platin und Palladium, als auch geeignete Nichtedelmetalle wie Mangan, Eisen, oder Cobalt untersucht. Für die Herstellung der metallischen Nanopartikel in einem Partikelgrößenbereich von 2-20 nm wurde das Verfahren der gepulsten Laserdeposition eingesetzt. Dabei wurden die metallischen Nanopartikel auf nanoskaligen, oxidischen Trägermaterialien aufgebracht. Zur physikalisch-chemischen Charakterisierung der hergestellten Katalysatoren wurden die Rastertunnelmikroskopie zur Bestimmung der mittleren Partikelgrößen und die Röntgenphotoelektronenspektroskopie zur Analyse der Oxidationszustände der metallischen Nanopartikel eingesetzt. Thermogravimetrischen Messungen zur katalytischen Rußoxidation in einem dieselähnlichen Modellabgas haben gezeigt, dass die zum Rußabbrand mit Sauerstoff notwendigen Temperaturen von etwa 600°C durch den Einsatz der hergestellten Katalysatoren um mehr als 100°C abgesenkt werden können. Untersuchungen zur katalytischen Propanoxidation zeigten unterschiedliche Sensitivitäten der katalytischen Systeme bezüglich der Partikelgröße der eingesetzten Metalle. Unter den Nichtedelmetallen konnte in der Propanoxidation Cobalt geträgert auf Cerdioxid als sehr aktiv identifiziert werden.
The aim of the present thesis is to close some gaps in our understanding of the factors that govern the rates of mobilization of antimony from its natural sources, viz. from its most abundant minerals, namely stibnite, the most abundant antimony mineral, and its principal weathering products in the supergene zone, namely senarmontite, valentinite and stibiconite. Antimony may also become enriched in soils and sediments, as a result of anthropogenic or natural contamination, and be mobilized thence; therefore, the specific mobilization of antimony in the form of Sb(V) from sediment was also considered. The first (introductory) Chapter is meant to give a comprehensive summary of the known geochemistry of antimony along with an outline of the theoretical basis of most of the material presented in the main chapters. In the second Chapter, we study the rate of oxidative dissolution of stibnite in acidic solution and derive a rate law in terms of hydrogen ion concentration and dissolved oxygen, and the activation energy of the process is measured. The effect of Fe3+ and other trivalent cations on the rate, and the formation of elemental sulfur at the dissolving mineral surface are also examined. In Chapter III, essentially the same study is repeated in basic solution and the observed dissolution rate in a natural system, specifically, the antimony mineralization near Goesdorf (L), is explained on the basis of our findings. Activation energies indicate that the dissolution processes are diffusion controlled in acidic, and surface controlled in basic solution. Another important (new) finding is the promotive effect exerted by metal cations, both in acidic and in basic solution. These are, to our knowledge, the first reported instances of metal-promoted dissolution in the case of a sulfide mineral. In Chapter IV, we investigate and rationalize the effects of organic ligands which commonly occur in the soil solution on the rate of dissolution of stibnite. Both the type of ligand and the contact time of the solution with the mineral determine whether an enhancement of the Sb mobilization is to be expected. In Chapter V, we turn to the oxide minerals of antimony; we derive rate laws for their proton-promoted dissolution over the environmentally relevant pH range (2 to 11) and measure the activation energies of these processes. These energies are in the range of surface controlled mechanisms, except for valentinite in basic solution, which appears to be transport-controlled, and stibiconite, which dissolves with a negative activation energy in acidic solution. Negative activation energies for mineral dissolution are exceedingly rare though their existence was predicted on theoretical grounds. Stibiconite represents the first reported oxide mineral with a negative dissolution activation energy. The results from this Chapter permit to derive the following sequence of dissolution rates, valid over most of the pH range 2-11: valentinite>senarmontite>stibiconite>stibnite. Geochemical implications of this order of reactivities are discussed. In Chapter VI, the mobilizing effect of common inorganic anionic aquatic species on antimony bearing sediment, and on pure phases representative of those present in sediments, is examined. The main objective consists in verifying whether carbonate and phosphate, known to mobilize As from sediments and soils, mobilize Sb as well. Phosphate at environmental concentrations has little impact, while that of carbonate, at environmentally relevant concentrations, is very slight, although significant. The Appendices contain, among others, detailed experimental results that are merely mentioned in the main text, or that are only presented there in graphical form, as well as the development of a UV-photometric method for the determination of elemental sulfur on mineral surfaces. The method is applied to weathered stibnite in Chapters II and III; it is more sensitive, more economic, more environmentally friendly, and easier to carry out than the literature method.
In the combustion processes, spontaneous emission of chemiluminescence species responsible for ultra-violet and visible light is in abundance. Due to its natural occurrence, it offers an inexpensive diagnostic tool for flames and other combustion processes. It is non-intrusive in nature and gives the facility to avoid expensive laser instrumentation. In hydrocarbon oxidation most common electronically excited species are OH*, CH*, C2*, and CO2*, where * represents the electronically excited state of a given radical or molecule. In the early 1970s chemiluminescence has been identified as a marker for heat release, reaction zone, and equivalence ratio, thereby providing a relatively easy diagnostics alternative for online measurement of these features in practical combustion applications. However, the quantitative relationship between chemiluminescence, heat release, and equivalence ratio is mostly unknown except for a few correlations available in literature over small range of conditions. Therefore a reaction kinetic model predicting these species is necessary for the fundamental understanding of the chemiluminescence. This mechanism then can be provided for predicting excited species in simulations of various combustion devices. A detailed reaction mechanism of chemiluminescence is not well studied. Therefore, the objective of this work is to develop a reaction mechanism of chemiluminescent species which can predict their concentrations in shock-tube and one-dimensional laminar flame experiments. The mechanism developed in this thesis is validated against various experimental conditions in shock-tube experiments where it reproduces the ignition delay time very well. In addition, the species profiles which provide a more stringent test on the mechanism validation are calculated to reproduce the measured excited species concentrations in laminar premixed and non-premixed flames. The comparison proves accuracy of the mechanism. The mechanism presented provides therefore a first step to quantitative understanding of the excited species and can be further used in the simulation of practical combustion systems.
Die vorliegende Arbeit beschäftigt sich mit Synthese, Struktur und Reaktionen von neuartigen, amidinatstabilisierten Oligogallanen des Typs Ga{n}Am{n}I{2} mit n = 1, 2, 3, 4. Die Kettenlänge wird hierbei durch den Substituenten gesteuert. Die Verwendung von Amidinaten als Substituenten ermöglicht eine Absättigung des Elektronenmangels des Galliums. Das führt dazu, dass die Galliumeinheiten zu n-alkanähnlichen Ketten aggregieren. Alle Verbindungen sind röntgenographisch charakterisiert. Jeder Strukturbeschreibung der Galliumamidinate geht eine Darstellung des HOMOs des entsprechenden Substituentanions voran, welches für die Bindung an das Galliumatom verantwortlich ist. Für jedes der Galliumamidinate wurden quantenchemische Rechnungen angestellt, um Struktur, Ladungsverteilung und Bindungsverhältnisse besser erklären zu können. Diese folgen im Aufbau nach der Diskussion der jeweiligen Kristallstrukturanalyse. Die Synthese der Tri- und Tetragallane erfolgt durch Reaktion von "GaI" mit passenden Lithiumamidinaten, die Synthese der Digallane erfolgt einerseits analog, andererseits durch Reduktion eines Amidinatodiiodmonogallans mit Kalium. Die Monogallane werden einerseits durch Salzmetathese von Gallium(III)iodid mit einem Lithiumamidinat, andererseits durch Oxidation oder Disproportionierung höherer Oligogallane hergestellt. Durch die Reaktion von Natriumsuperhydrid mit einem der Trigallane entstand durch Substitution das erste Gallium(II)hydrid. Bei einigen der Verbindungen konnte der Einfluss des Lösungsmittels auf die Konformation der Verbindung im Kristall dokumentiert und diskutiert werden. Diese neu charakterisierten Oligogallane bieten durch die endständigen Iodatome weitläufige Möglichkeiten zur Synthese von weiteren Ketten-, Ring- und Käfigverbindungen, die Gallium-Gallium-Bindungen beinhalten.
DNA ist der Speicher der genetischen Information. In Eukaryoten ist die DNA in Nukleosomen organisiert, d.h. kurze DNA-Abschnitte sind zweimal um einen Kern aus Histonproteinen gewunden. Die Nukleosomen beeinflussen die zelluläre Maschinerie, die die genetischen Informationen abliest. Dass zu jeder Zeit die passende Information auf der DNA zugänglich ist, wird unter anderem durch die Dissoziation und die Assemblierung von Nukleosomen reguliert. In dieser Arbeit wurde eine Methode entwickelt, um diese Prozesse in vitro zu analysieren. Dazu wurden Nukleosomen sowohl an verschiedenen Histonen als auch an der DNA mit Fluorophoren markiert und mit Fluoreszenzkorrelationsspektroskopie (FCS) und Einzelmolekül-Förster-Resonanzenergietransfer (spFRET) in einem konfokalen Mikroskop untersucht. Durch Variation der Ionenstärke wurde dabei die Dissoziation und die Assemblierung der Nukleosomen induziert. Mittels FCS wurde aus Fluktuationen der Fluoreszenzintensität der Diffusionskoeffizient von Nukleosomen ermittelt. Da der Diffusionskoeffizient ein Maß für die Größe und Form eines Moleküls ist, konnte durch dessen Änderung die Dissoziation von Nukleosomen verfolgt werden. So wurde gezeigt, dass der Proteinkern schrittweise von der DNA abdissoziiert und substöchiometrische DNA-Histon-Komplexe als Zwischenprodukte auftreten, in denen die DNA für die zelluläre Maschinerie leichter zugänglich ist. FRET ist ein Prozess, bei dem Energie strahlungslos zwischen zwei Fluorophoren übertragen wird. Aus der Emission der Fluorophore lassen sich deren Abstände in Molekülen untersuchen. In dieser Arbeit wurde Energietransfer in einzelnen durch das Fokusvolumen diffundierenden Nukleosomen gemessen. Im Vergleich zu Messungen an Molekülensembles, bei denen der Interfluorophorabstand über alle Nukleosomen gemittelt wird, konnten so verschiedene Zustände identifiziert werden, die sich im Interfluorophorabstand unterscheiden. Auf diese Art konnte eine bislang unbekannte Nukleosomkonformation nachgewiesen werden, die vor der Dissoziation der Histone von der DNA auftritt, und in der die Histone und die DNA leichter für externe Faktoren zugänglich sind. Auch konnte gezeigt werden, dass bei der Assemblierung von Nukleosomen die gleichen Zwischenprodukte in umgekehrter Reihenfolge durchlaufen werden, und der Prozess vollständig reversibel ist. In vivo wird die Stabilität der Nukleosomen unter anderem durch den Austausch von Histonen durch Histonvarianten reguliert. In dieser Arbeit wurde mit spFRET der Einfluss einer Histonvariante (H2A.Z) untersucht und es wurde gezeigt, dass bei der Dissoziation von Nukleosomen, die diese Histonvariante enthalten, andere Zwischenprodukte auftreten. Die Histonvariante kann daher signifikante Auswirkungen auf die Zugänglichkeit der DNA haben.
Der Schwerpunkt der Arbeit liegt auf der Untersuchung der Aktivität und Sekundärstruktur von adsorbierter Glucose Oxidase (GOx). Das Enzym wird zum einen auf planare Gold- und Siliciumoberflächen abgeschieden, die zuvor mit verschiedenen Thiolaten bzw. Polyelektrolyten chemisch modifiziert wurden. Im Vergleich zum nativen Enzym in Lösung bleibt die enzymatische Aktivität der adsorbierten GOx auf positiv geladenen Oberflächen zu bis zu 80 % erhalten und sinkt auf aromatischen Oberflächen auf nur noch ca. 8 % des Referenzwertes. Die gemessenen spezifischen Aktivitäten der GOx sind umso niedriger, je niedriger der infrarotspektroskopisch quantifizierte Sekundärstrukturanteil an alpha-helicalen Elementen ist und je höher der Anteil an beta-Faltblattstrukturen im Vergleich zur nativen Struktur ist. Die GOx wird weiterhin auf Submonolgen von Goldnanopartikeln (AuNP) mit Durchmessern von 11 - 40 nm adsorbiert. Die AuNP werden mit den gleichen Thiolaten wie die planaren Goldoberflächen beschichtet und in eine proteinresistente Matrix eingebettet um eine Adsorption der GOx zwischen den AuNP zu verhindern. Die Aktivität der GOx ist auf allen AuNP-Filmen erheblich geringer als die des nativen Enzyms in Lösung sowie - unabhängig von der chemischen Natur der AuNP-Oberlfäche - auch geringer als die der GOx-Adsorbate auf den homogen beschichteten Substraten. Ursächlich hierfür ist hauptsächlich eine starke Denaturierung der adsorbierten GOx auf den AuNP, die mit einem hohen Anteil an beta-Faltblättern einhergeht. Zur großflächigen, nanoskaligen Strukturierung von Oberflächen wird auch die kolloidale Lithographie herangezogen. Mittels Gasphasenabscheidung eines oligo(ehtylenglykol)-terminierten Silans durch Monolagen aus Silica-Nanopartikeln auf Siliciumsubstraten können Ringstrukturen mit Durchmessern von 50 bzw. 100 nm präpariert werden, auf denen selektiv die Proteine BSA und Lysozym adsorbiert werden können. Begleitend zu den experimentellen Arbeiten werden das Adsorptionsverhalten von Polystyrol- und Silica-Nanopartikeln auf Gold- und Siliciumoberflächen auch theoretisch untersucht. Durch Zugabe von NaCl zur Partikelsuspension kann das repulsive Potential zwischen den Partikeln und den Substraten so weit abgeschirmt werden, dass die Partikel als statistisch dicht gepackte Monolage auf ein planares Substrat adsorbieren. Die Menge an NaCl, die hierfür benötigt wird, ist dabei abhängig vom Partikelradius sowie den Oberflächenladungen und Hamaker-Konstanten der verwendeten Materialien. Es werden die Wechselwirkungspotentiale bestehend aus einem attraktiven van-der-Waals-Term, einem repulsiven Coulomb-Term sowie einem repulsiven Born-Term für verschiedene Partikel-Substrat-Kombinationen berechnet. Die Übereinstimmungen mit den experimentellen Ergebnissen sind sehr gut.
Motorproteine sind komplexe Nanomaschinen, die chemische Energie aus der Hydrolyse von Adenosintriphosphat (ATP) in mechanische Energie umwandeln und so gerichtete Bewegung mit extrem hoher Spezifität und Effizienz ausführen. Sie sind essentiell für die Funktion lebender Organismen, da sie maßgeblich an überlebenswichtigen Prozessen wie der Zellteilung beteiligt sind. Das Verständnis ihrer Funktion ist die Basis um das Potential dieser Enzyme in der Nanotechnologie zu nutzen sowie Krankheiten zu verstehen, die auf defekten Motorproteinen beruhen, und Therapien zu ihrer Heilung zu entwickeln. Trotz reger Aktivität auf dem Gebiet liegen für viele Motorproteine nur wenige Informationen bezüglich der Wechselwirkung mit anderen Proteinen und des Verhaltens bei Einwirkung chemischer Substanzen vor. Eine der Standardmethoden zur Untersuchung molekularer Motoren in vitro sind so genannte Gleitexperimente, in denen Motorproteine auf Oberflächen angebunden werden und fluoreszenzmarkierte Filamente über die Oberfläche transportieren. Im Rahmen dieser Arbeit wurde eine Methode zur Durchführung dieser Gleitexperimente auf Oberflächen, die mit hexagonal angeordneten Goldnanopartikeln dekoriert sind, entwickelt. Die molekularen Motoren werden hierzu über Chelatisierung einer rekombinant eingeführten Histidinfunktionalisierung durch Übergangsmetallchelatoren gerichtet auf den Goldnanostrukturen immobilisiert. Die Nanopartikel dienen somit als Ankerpunkte. Das System weist den Vorteil auf, dass ein Motorprotein pro Partikel immobilisiert werden kann. Zusätzlich kann ihre Dichte über den Abstand der Partikel kontrolliert werden. Das entwickelte Substrat erlaubt die Untersuchung aller mit einer Histidinsequenz funktionalsierten Motorproteine. Seine Eignung zur Untersuchung von Motorproteinen in Gleitexperimenten wurde mittels der Untersuchung eines gut erforschten Kinesin-1 Konstrukts demonstriert. Dieses zeigte literaturbekanntes Verhalten. Zusätzlich zum Gleitexperiment wurde ein Funktionalitätsnachweis entwickelt, der die Aktivität der orientiert auf den Goldnanopartikeln angebundenen Motorproteine unter den im Gleitexperiment gewählten Bedingungen überprüft. Dieser Nachweis stellt eine wichtige Ergänzung des Gleitexperiments zur Überprüfung der Aktivität der Motorproteine auf molekularer Ebene dar. Die Kombination der beiden Methoden ermöglicht die zuverlässige in vitro Untersuchung des Verhaltens von Motorproteinen unter Sicherstellung des Erhalts ihrer Aktivität und erlaubt es so Informationen zum Verständnis molekularer Motoren zu erlangen. Molekulare Motoren zählen in vivo zu den Hauptbestandteilen gerichteter molekularer Transportsysteme. Dies prädestiniert sie für eine Verwendung zum Aufbau effizienter in vitro-Nanotransportsysteme. Das Ziel dieser Arbeit war daher neben der Entwicklung der oben genannten Methoden die Entwicklung von Templaten zur Erzeugung so genannter molekularer Fließbänder. Als molekulare Fließbänder werden unter Kontrolle der Polarität auf strukturierten Oberflächen angebundene Mikrotubuli bezeichnet, auf denen sich Motorproteine gerichtet bewegen. Im Rahmen der Arbeit wurden mikronanostrukturierte Oberflächen hergestellt, die der polaritätsorientierten Anbindung und gerichteten Polymerisation von Mikrotubuli dienen. Hierbei handelt es sich um Oberflächen auf denen nanostrukturierte Bereiche in der Dimension einiger Mikrometer bis einiger hundert Nanometer von unstrukturierten Bereichen umgeben sind. Die erfolgreiche Funktionalisierung der Goldnanopartikel mit Übergangsmetallchelatoren oder Streptavidin, die eine Anbindung von Mikrotubuli ermöglichen, wurde durchgeführt. Somit wurden erfolgreich Template zur Erzeugung molekularer Fließbänder hergestellt.
Die vorliegende Arbeit behandelt die Synthese von unterschiedlich funktionalisierten Poly(pyridyl)ruthenium(II)-Komplexen und deren biologischen Anwendung. Durch Kopplung eines Anthrachinonderivats an Poly(pyridyl)ruthenium(II)-Komplexe konnte die Wechselwirkung dieser Komplexe mit Polynukleotiden sowie die Zellgängigkeit verbessert werden. Es zeigte sich weiterhin, dass Substituenten an den Bipyridin-Liganden die Wechselwirkung der Komplexe mit Polynukleotiden modulieren. Kleine, wasserstoffbrücken-bildende bzw. positiv geladene Substituenten förderten die Bindung an Polynukleotide. Dahingegen verhinderten große bzw. negativ geladene Substituenten die Wechselwirkung dieser Rutheniumkomplexe mit Polynukleotiden. Aufnahmegeschwindigkeit, -mechanismus und Verteilung der synthetisierten Poly(pyridyl)ruthenium(II)-Komplexe wurde an drei adhärenten Krebszelllinien sowie an einer Krebssuspensionszelllinie untersucht. Die adhärenten Zelllinien zeigten ein anderes Aufnahmeverhalten als die Suspensionszelllinien. Während die adhärenten Zellen die Rutheniumkomplexe hauptsächlich durch energieabhängigen Transport akkumulierten, wurden die unpolarsten Komplexe der getesteten Reihe von den Suspensionszellen über energieunabhängige Transportwege aufgenommen. Alle Zelllinien zeigten nach 4 h Inkubationszeit mit den Rutheniumkomplexen die für Poly(pyridyl)ruthenium(II)-Komplexe typische punkförmige Verteilung im Zytoplasma mit Aussparung des Zellkerns. Weiterhin wurden [Ru(HDPA)2dppz]2+ (HDPA = Di-2-pyridylamin, dppz = Dipyrido-[3,2-a:2‘,3‘-c]phenazin) und dessen Derivate hergestellt und hinsichtlich ihrer Fluoreszenz-eigenschaften, Erkennung von DNA-Defektstrukturen und zellulären Verteilung untersucht. Von strukturell ähnlichen Komplexen ist in der Literatur bekannt, dass diese nur bei tiefen Temperaturen Fluoreszenz aufweisen. Durch Alkylierung des HPDA-Liganden konnte in aprotischen Lösungsmitteln Fluoreszenz bei Raumtemperatur erreicht werden. Es zeigte sich, dass die alkylierten Komplexe als Fluoreszenzsensoren für die Erkennung von Basenfehl-paarungen in DNA geeignet sind. Zudem wurden alle dppz-Rutheniumkomplexe von HeLa-Zellen akkumuliert und wiesen wiederum die für Poly(pyridyl)ruthenium(II)-Komplexe typische punktförmige Verteilung im Zytoplasma ohne Anfärbung des Nukleus auf.
Peptide or protein chips which can track hundreds or thousands of distinct proteins from a blood or urine sample at a single step are highly desired. It will allow the diagnosis of diseases in their formative, treatable stages just by detecting proteins that are markers for these specific diseases. To simultaneously and efficiently detect where blood´s proteins bind on the grid, label-free detection methods are favorable in order to reduce time and cost demands and facilitate the detection of low-affinity binding events. In this work, a label-free biosensor based on localized surface plasmon resonance (LSPR) was developed and specifically optimized regarding its application as a solid substrate in the synthesis of high-density peptide arrays, and in the detection of molecular interactions occurring on the sensor surface. Three main issues which are crucial in achieving this goal have been covered in this work: (i) development and optimization of the LSPR biosensor, (ii) Synthesis of a protein resistant layer on the LSPR biosensor, (iii) Label-free detection of biomolecular interactions on the polymer coated LSPR biosensors. For this purpose, a LSPR-based biosensor was first constructed. It consists of two gold layers and an intermediate dielectric layer in-between. The LSPR biosensor shows several pronounced resonance peaks in the UV-visible region of the electromagnetic spectrum, which are highly sensitive to changes in the refractive index of the surrounding medium. The LSPR biosensor was optimized in terms of plasmon resonance line shape, optical homogeneity, and sensitivity to facilitate its application in the label-free detection of biomolecular interactions in array format. In a second step, a poly(ethylene glycol) based polymer was synthesized on the sensor surface at mild reaction conditions by using Atom Transfer Radical Polymerization (ATRP). The sensor was first coated with a silica gel to stabilize the sensor and provide a sufficiently high number of functional groups. ATRP initiators were immobilized on the silica gel surface in 2 steps by silanization and esterification to enhance the coupling efficiency. Subsequently, polymerization was carried out with oligo(ethylene glycol) methacrylate (OEGMA) as the monomer resulting in a poly(ethylene glycol) methacrylate (PEGMA) polymer film. In the second approach, a graft copolymer film was synthesized on the sensor surface with methyl methacrylate (MMA) as the diluting monomer in order to reduce the protein-resistance of the sensor coating and further enhance the sensor stability. Graft copolymer films with 10% PEGMA/ 90% MMA and a thickness of 50-60 nm were successfully synthesized by setting the polymerization time between 9.5 and 10.5 hours. This thickness regime is required to ensure a high-loading of amino functional groups, which serve as the starting point for the subsequent peptide array synthesis. At the same time, this film thickness does not exceed the surface sensitivity regime of the LSPR biosensor. To test the performance of the LSPR biosensor, an array of fluorescent-labeled antibodies was formed on its surface by a spotting robot. The LSPR image displays an array of spots which corresponds to the fluorescence image. Moreover, the quantity of antibody bound to the sensor surface was correctly predicted based on the measured wavelength shifts in the quadrupole regime and a mass sensitivity factor known from literature. This shows that the LSPR biosensor described in this thesis has the potential to allow the detection of molecular interactions in a miniaturized array format in a quantitative manner. In the final part of this thesis, the polymer-coated LSPR biosensor was successfully utilized as the solid substrate in the synthesis of a peptide array via a novel laser printing technique developed at the Cancer Research Center Heidelberg (DKFZ). An array with 9x20 variants of hemagglutinin/HA (YPYDVPDYA) epitope was synthesized on a polymer-coated LSPR biosensor and incubated with IR-dye conjugated specific antibody. The LSPR image was generated by evaluating the wavelength shift in the octapole resonance peak and has successfully displayed the entire peptide array formed on the sensor surface. In a separate study, the potential of single, small particles for biosensing applications in miniaturized format was investigated. Whispering gallery modes (WGM) of fluorescence-doped sulfonated polystyrene (PS) particles with a diameter of 2 µm were studied with respect to their resonance shift after adsorption of polyelectrolyte multilayers. The resonance shifts were plotted as a function of the film thickness and a slope of 0.038 nm/ Å was obtained from a linear fit to the experimental data. This sensitivity factor can be translated into a detection limit of 3 fg by assuming a spectral resolution of 0.1 nm and a polyelectrolyte mass density17 of 0.81 g/cm3.
The use of biomass as a CO2-neutral renewable fuel and the only carbon containing renewable energy source is becoming more important due to the decreasing resources of fossil fuels and their effect on global warming. The projections made for the Renewable Energy Road Map [1] suggested that in the EU, the use of biomass can be expected to double, to contribute around half of the total effort for reaching the 20 % renewable energy target in 2020 [2]. To achieve this goal, efficient processes to convert biomass are required. At the Karlsruhe Institute of Technology (KIT), Germany, a two-stage process called bioliq [3], for the conversion of biomass into synthetic fuel, is being developed. In this process, straw or other abundant lignocellulosic agricultural by-products are converted to syngas through fast pyrolysis and subsequent entrained flow gasification. After gas cleaning and conditioning, the syngas is converted into different chemicals via known processes such as direct methanol synthesis or Fischer-Tropsch synthesis. The prime goal of this thesis was the modeling and simulation of the gasification of biomass-based pyrolysis oil-char slurries in an entrained flow gasifier, which is an important step of the bioliq process. Computational Fluid Dynamics (CFD), as a powerful tool for modeling and simulation of fluid flow processes, was utilized in this thesis. A lab scale entrained flow gasifier, located at KIT, was simulated using the CFD code ANSYS FLUENT 12.0. Due to the turbulent nature of the flow, the realizable k-epsilon model was used to model the turbulence. The discrete phase model (DPM) was employed to describe the fluid phase, consisting of char particles suspended in ethylene glycol. Ethylene glycol served as non-toxic model fuel for pyrolysis oil, mainly because of its similar C/H/O-ratio and its similar physical properties to biomass derived liquid pyrolysis products. A detailed reaction mechanism for high temperature oxidation of ethylene glycol was implemented in the CFD code. The mechanism comprised of 43 chemical species and 629 elementary reactions. The use of detailed chemistry enables one to have a deeper insight into the gasification process. Turbulence-chemistry interactions were modeled with the eddy dissipation concept (EDC). The in-situ adaptive tabulation (ISAT) procedure was employed to dynamically tabulate the chemistry mappings and reduce computer time for the simulation. The effect of the thermal radiation was taken into account by using the discrete ordinates model (DOM). The radiative properties of the gas were described with the weighted sum of gray gases model (WSGGM). The simulation results were compared with the experimental measurements wherever possible, with good agreement. The simulations depicted the importance of the recirculation zone in entrained flow gasification. Furthermore, the main reaction path of ethylene glycol gasification could be observed and analyzed. In order to study the effect of boundary conditions on the gasification process, a series of simulations were done to perform sensitivity analysis. Four parameters were varied, namely: oxidizer and fuel inlet temperatures, the oxidizer composition, the air-fuel ratio and the operating pressure of the gasifier. Effects of the parameter variations on the gasification efficiency and the composition of the product gas were studied. Three different chemistry models (i.e. equilibrium chemistry, flamelet model and EDC) were studied in this thesis. Their relative advantages and disadvantages for the simulation of gasification processes were examined. The EDC model proved to be the better choice for entrained flow gasifiers with recirculation zones. The slurry gasification simulations were performed to study the effects of the mass fractions of the char particles on the process. With the aid of the detailed chemistry model, sub-processes could be analyzed and suggestions for the improvement could be made. The simulations performed in this work help to better understand the gasification process inside entrained flow gasifiers and considerably reduce the number of experiments needed to characterize the system. The simulations produced spatial and temporal profiles of different system variables that are sometimes impossible to measure or are accessible only by expensive experiments. However, more experimental measurements help to validate and optimize the CFD model. The sensitivity analyses performed in this study are considered as a basis to find optimized operating conditions and assist the successful scale-up of entrained flow gasifiers.
Der Fokus dieser Arbeit ist auf die Entwicklung eines künstlichen Modellsystems der extrazellulären Matrix (EZM) gerichtet, um die Reaktion diverser Zellphänotypen auf unterschiedliche Umweltbedingungen zu erfassen. Die Imitation der verschiedenen biochemischen sowie biomechanischen Eigenschaften von Gewebe durch das hier definierte System, diente dabei zur Untersuchung des Adhäsions- und Bewegungsverhaltens von Malaria Parasiten, speziell des Plasmodium Sporozoiten Stadiums, da diese nach Injektion durch die Anopheles Mücke zunächst Gewebe passieren müssen bevor sie in die Blutbahn gelangen. Die Basis des Modellsystems stellt ein proteinabweisendes Polyethylenglykol-Diacrylat (PEG-DA) Hydrogel dar, dessen Elastizität in einem Bereich von 0,6 kPa bis 6 MPa einstellbar ist. Die Hydrogeloberfläche wurde durch einen Transferprozess mit Goldnanopartikeln dekoriert, welche zuvor mittels Block-Copolymer-Nanolithographie in einer quasi-hexagonalen Ordnung mit gezielt justierbaren Partikelabständen von 40 nm bis 270 nm auf Glas generiert wurden. Diese Goldpartikel wurden über Thiolbindungen mit verschiedenen bioaktiven Molekülen funktionalisiert und fungierten hier als Adhäsionsanker, welche in definierten Abständen und somit unterschiedlicher Dichte angeboten werden können. Eine weitere Modifikation der Hydrogeloberfläche wurde durch Carbonsäure-Funktionen erzielt. Diese konnten in bestimmten Bereichen der Geloberfläche, beispielsweise in Form einer Mikrostruktur, erzeugt werden und anschließend über Peptidbindungen mit entsprechenden Molekülen weiter umgesetzt werden. Erstmals wurde eine Anbindung der unterschiedlich elastischen und funktionalisierten Hydrogele in Form dünner Schichten auf dünne Glassubstrate ermöglicht. Hierdurch konnten verschiedene Parameter, wie Elastizität, Abstände der Adhäsionsanker und Funktionalisierungen unabhängig voneinander in zahlreichen Kombinations-möglichkeiten auf einem Glassubstrat variiert werden. Diese Methode erbrachte große Vorteile für die Mikroskopie und Substrathandhabung. Die Untersuchung der Plasmodium Sporozoiten auf diesen Substraten zeigte die höchste Motilität dieser Parasiten auf Oberflächen mit Adhäsionsabständen von 55-100 nm und einer Elastizität entsprechend derer von Zellkulturplastik. Durch Zugabe eines Aktin-polymerisationsfördernden Wirkstoffes konnte die Motilität auf weicheren Substraten jedoch stimuliert werden. Das hier entwickelte System ermöglichte damit erstmals einen experimentellen Nachweis der Synergie zwischen Adhäsionsbildung und der Aktinpolymerisation und trägt durch die Möglichkeit der Untersuchung zahlreicher Faktoren entscheidend zum besseren Verständnis des Bewegungsmechanismus der Malariaerreger bei.
In this work we constructed and optimized a label-free biosensor which is based on a combination of surface plasmon resonance and reflectometric interference. Both techniques have been utilized for label-free biosensing for more than two decades as the corresponding extinction spectra undergo a wavelength shift upon molecule binding. In the present study it has been demonstrated that a combination of both effects can significantly improve sensitivity. The developed biosensor consists of dielectric spheres of 400-500 nm diameters, deposited on a flat solid substrate and coated with gold nanoparticles. The spectrum of such structure exhibits multiple extinction peaks resulting from the interference of beams reflected between the flat substrate and the surface of the dielectric spheres. These peaks are enhanced by the presence of gold on top of the spheres due to coherent oscillation of the free electrons of the metal, i.e. plasmon excitation. In a systematic study, the optical properties of the sensing element have been optimized, and its sensitivity towards molecule binding has been tested by fibrinogen adsorption for the different sensor geometries developed. In the wavelength regime from 400-900 nm two dominant peaks are observed. It was shown, that the sensitivity of the peak between 600 and 900 nm exhibits the higher sensitivity compared to the peak between 400 and 600 nm. Different deposition techniques for the dielectric spheres have been tested to find the most reproducible one with closed packed coverage. Here, a technique, in which the dielectric spheres are first floated on a liquid subphase and then transferred to the solid support in a Langmuir-Blodgett like approach, yielded improved lateral homogeneity of the optical response and higher sensitivity than film of randomly deposited spheres. Two kinds of metallization have been studied (i) deposition of metal nanoparticles from solution (seeding) followed by an enlargement of the nanoparticles (plating), and (ii) evaporation of a metal thin film on the top of the spheres by physical vapor deposition (PVD). The resulting optical response and morphology were characterized by UV-Vis spectroscopy and scanning electron microscopy (SEM). For gold metal deposition from gold solution we found out that the sensitivity decreases with increasing plating time and is highest for purely seeded surfaces. For gold films deposited by PVD we identified an optimum gold thin film thickness of 50 nm to provide enhanced sensitivity. Effects of metal composition (gold and silver) on the optical properties and sensitivity have been investigated, showing significantly higher sensitivity for silver than for gold nanoparticle coatings of the same coverage in range from 400-600 nm. We also observed that the sensitivity is improved by the presence of a dielectric layer of silicon oxide/dioxide in between the substrate and the gold-coated spheres. Independent of the type of substrate used (i.e. metalized or not), an optimum layer thickness of 40 nm was found.
"Campus-Report" heißt die Radiosendung der Universitäten Heidelberg, Mannheim, Karlsruhe und Freiburg. Die Reportagen über aktuelle Themen aus Forschung und Wissenschaft werden montags bis freitags jeweils um ca. 19.10h im Programm von Radio Regenbogen gesendet. (Empfang in Nordbaden: UKW 102,8. In Mittelbaden: 100,4 und in Südbaden: 101,1) Uni-Radio Baden: ein gemeinsames Projekt der Universitäten Freiburg, Heidelberg, Karlsruhe und Mannheim in Zusammenarbeit mit Radio Regenbogen – unterstützt von der Landesanstalt für Kommunikation. Sendung vom 11. Februar 2011
In the present work experimental and numerical modeling studies of the heterogeneously catalyzed and electrochemical oxidation of CO at Nickel/yttria-stabilized zirconia (YSZ) solid oxide fuel cell (SOFC) anode systems were performed to evaluate elementary charge-transfer reaction mechanisms taking place at the three-phase boundary of CO/CO2 gas-phase, Ni electrode, and YSZ electrolyte. Temperature-programmed desorption and reaction experiments along with density functional theory calculations were performed to determine adsorption/desorption and surface diffusion kinetics as well as thermodynamic data for the CO/CO2/Ni and CO/CO2/YSZ systems. Based on these data elementary reaction based models with four different charge transfer mechanisms for the electrochemical CO oxidation were developed and applied in numerical simulations of literature experimental electrochemical data such as polarization curves and impedance spectra. Comparison between simulation and experiment demonstrated that only one of the four charge transfer mechanisms can consistently reproduce the electrochemical data over a wide range of operating temperatures and CO/CO2 gas compositions.
Fälschungen industrieller Produkte, die erhebliche ökonomische und auch Sicherheitsprobleme aufwerfen, nehmen für zahllose Produktkategorien kontinuierlich zu. Neben monetären Einbußen sind vor allem gesundheitliche Risiken für die Verbraucher eine große Gefahr, welche beispielsweise von gefälschten Medikamenten ausgeht. Die Hersteller versuchen als Gegenmaßnahme ihre Waren fälschungssicher zu markieren, aktuell mit DNA als Markierungssubstanz. In ähnlicher Weise können auch Peptidnukleinsäure (PNAs) eingesetzt werden, die erhebliche Vorteile gegenüber der DNA besitzen. Das Ziel der vorliegenden Arbeit ist die Etablierung eines solchen Systems für lipophile Medien, wie z.B. Öle und Künstlerfarben. Als Markierungssequenzen wählt man einsträngige 10- bis 25mere PNAs. Es werden durch beidseitig angehängte Phenylalaninreste lipophilisierte PNAs neben analogen, unmodifizierten PNAs, untersucht. Beide Substanzgruppen eignen sich gleichermaßen zur Dotierung lipophiler Flüssigkeiten, wie Nujol, Sonnenblumen-, Diesel- sowie Leinöl. Aus diesen Medien erfolgt die Extraktion mittels wässriger Säure. Die extrahierte PNA lässt sich im Anschluss am besten auf einer PEGMA-Microarray-Oberfläche detektieren, da diese eine ausreichende Passivierung gegenüber dem stark adsorbierenden Polymer aufweist. Mittels eines im Rahmen dieser Arbeit entwickelten Dreistranghybridisierungssystems,bestehend aus zwei weiteren Oligomeren, ist die PNA-Detektion bis zu 300 amol möglich. Das vorgestellte System wurde im Folgenden auf seine Tauglichkeit überprüft, um PNA-markierte Bleistifte von nicht markierten zu unterscheiden. Die Markierung wurde vom Hersteller (Faber-Castell) vorgenommen und war nicht bekannt. Die derart präparierten Stifte konnten mittels der beschriebenen Dreistranghybridisierung zweifelsfrei identifiziert werden.
In der vorliegenden Arbeit wurde die Dimethylether (DME)-Direktsynthese aus Synthesegas an einer Kombination aus Kupfer/Zinkoxid- und Dehydratisierungskatalysatoren untersucht. Hierbei lag der Schwerpunkt der Untersuchungen auf der Prüfung, ob die DME-Direktsynthese unter dem Einsatz von kohlenmonoxidreichem Synthesegas, wie es beispielsweise durch Vergasung biologischer Reststoffe hergestellt werden kann, sinnvoll durchführbar wäre. Zu diesem Zweck sind an einem kommerziell verfügbaren Katalysatorsystem, bestehend aus einem Cu/ZnO/Al2O3-Katalysator und gamma-Al2O3, eine Vielzahl reaktionstechnisch relevanter Untersuchungen durchgeführt worden. Neben den Einflüssen von Temperatur, Druck, Verweilzeit, Synthesegaszusammensetzung und -konzentration wurde die Wirkungsweise von zusätzlichem Wasser, Kohlendioxid und Katalysatorgiften (z.B. H2S, HCl, NaOH) auf das Katalysatorsystem geprüft. Die experimentellen Daten wurden durch die Modellierung der Reaktionskinetik, basierend auf einem umfangreichen Reaktionssystem unter Berücksichtigung unterschiedlicher Reaktionsbedingungen, ergänzt. Mit dem Ziel, die Effizienz des Prozesses zu erhöhen und das Katalysatorsystem auf ein kohlenmonoxidreiches Reaktionsmedium anzupassen, wurden neben den reaktionstechnischen Grundlagenuntersuchungen Modifikationen am Katalysatorsystem vorgenommen. Der Einsatz verschiedener Dehydratisierungskatalysatoren ergab, dass gamma-Al2O3 bzw. ein schwach saurer Zeolith des Typs H-MFI eine hocheffiziente und selektive Dehydratisierung des entstehenden Methanols zu DME gewährleisten. Diese beiden Katalysatoren eignen sich aufgrund ihrer tendenziell geringen Acidität und den vorwiegend schwachen Säurezentren an der Oberfläche besonders gut als Dehydratisierungskomponente für die DME-Direktsynthese. In Anlehnung an klassische Cu/ZnO-Systeme wurden verschiedene Methanolkatalysatoren hergestellt und hinsichtlich Aktivität und Stabilität in der DME-Direktsynthese getestet. Bezüglich ihrer Aktivität lagen alle Katalysatorsysteme in ihrer Leistungsfähigkeit unterhalb des kommerziell verfügbaren Katalysators. Dagegen stand die Stabilität der hergestellten Katalysatoren dem Referenzsystem über einen Zeitraum von 200 h nicht nach. Darüber hinaus konnte die Temperaturbeständigkeit und die Resistenz gegenüber dem Katalysatorgift HCl bei einigen Systemen (Cu/ZnO/Cr2O3 und Cu/ZnO/Al2O3/ZrO2) im Vergleich zum kommerziell verfügbaren Katalysator gesteigert werden.
Aspergillus-Spezies sind ubiquitär vorkommende Schimmelpilze. Bei immunsupprimierten Patienten wie Leukämie- und Transplantationspatienten verursachen Aspergillus-Spezies opportunistische Infektionen mit häufig letalem Ausgang. Die Diagnostik dieser Erkrankung beschränkt sich aktuell auf einen Aspergillus-Antigennachweis, molekularbiologische Diagnosemethoden und bildgebende Verfahren. Alle Methoden haben allerdings eine jeweils ungenügende diagnostische Sensitivität und/oder Spezifität. Zudem sind molekularbiologische Nachweismethoden durchgängig sehr aufwändige Verfahren mit noch mangelnder Standardisierung und daher in der Verbreitung auf wenige spezialisierte Laboratorien beschränkt. Ziel des durch die Deutsche José-Carreras-Leukämiestiftung geförderten Projektes war die Entwicklung und Validierung einer neuen, massenspektrometrie-basierten Diagnosestrategie, welche die Früherkennung von invasiven Aspergillus-Infektionen aus Serumproben von Hochrisikopatienten mit verbesserter diagnostischer Sensitivität und Spezifität ermöglichen soll. Der unmittelbare diagnostische Einsatz von massenspektrometrie-basierten Profiling-Untersuchungen ist aufgrund hoher präanalytischer Varianz und großer Abundanzunterschiede in der Proteinzusammensetzung von klinischem Probenmaterial bisher nicht möglich. Durch Reporter-Peptid-Spiking (RPS) können bisherige Limitierungen des MS-basierten Profiling überwunden werden. Grundlage des zu entwickelnden Verfahrens ist die Spaltung von Peptidsubstraten durch krankheitsassoziierte Proteasen in einer klinischen Probe wie etwa Serum. Proteasen spielen bei der Pathogenese vieler Erkrankungen, spezifisch auch bei der Entwicklung einer invasiven Aspergillose, eine entscheidende Rolle. Die sezernierten Proteasen des Aspergillus fumigatus wurden während dieser Arbeit direkt durch massenspektrometrische Proteomanalyse und indirekt durch funktionelle Untersuchungen charakterisiert. Für die direkte Charakterisierung der Proteasen wurde der Kulturüberstand mittels trägerloser Elektrophorese (FFE) getrennt. Anschließend wurde die Proteaseaktivität in den erhaltenen Fraktionen mit fluoreszenzmarkierten Peptiden bestimmt. Die höchste Proteaseaktivität wurde in Fraktionen des sauren pH-Bereiches detektiert. Parallel dazu wurden die Assays mit verschiedenen Proteaseinhibitoren durchgeführt. Die Ergebnisse des Inhibierungsmusters wiesen deutlich darauf hin, dass vorwiegend Metallo- und Serinproteasen die verwendeten Peptide abbauen. Die Fraktionen wurden einem tryptischen Verdau unterzogen und per LC-MS/MS Analyse untersucht. Die Identifizierung der im Kulturüberstand enthaltenen Proteine resultierte in der Detektion von vier Proteasen unter zahlreichen anderen Aspergillus-spezifischen Proteinen und Enzymen. Die systematische Substratsuche begann in silico in Substratbibliotheken wie Merops und Publikationen. Aus einer Vielzahl von synthetisierten Peptidsubstraten konnten fünf Substrate selektiert und für einen Proteaseassay mit massenspektrometrischer Detektion etabliert werden. Diese Substrate wurden spezifisch durch Aspergillus fumigatus abgebaut. Die Peptidfragmente wurden nach der Inkubation seriell mittels Affinitätschromatografie aufgereinigt und mit einem MALDI-TOF-Massenspektrometer gemessen. Der Assay wurde in einer umfangreichen Studie mit Patientenproben angewendet. Dabei wurden Proben von gesicherten Aspergillose-Fällen verwendet, sowie weitere Proben von Hochrisikopatienten. Die Sensitivität bzw. Spezifität des Assays betrug 41-81% bzw. 57-85% und war damit dem konventionellen Galaktomannan-Test in Bezug auf die Sensitivität für die verwendeten Modelle überlegen (27 bzw. 36% Sensitivität). Das Methodenprinzip ("proof-of-principle") konnte mit den Messungen bewiesen werden. Dennoch gilt es die Spezifität und Sensitivität zu verbessern, wie z. B. durch den Einsatz von komplexen randomisiertem Peptidbibliotheken oder durch weitere Modifikationen an den Schnittstellen der Peptide. Daraus kann dann ein Reporterpeptidmix aus mehreren Substraten (Multiplex-Ansatz) als Screening genutzt werden. Alternativ zur Massenspektrometrie wurde mittels Fluoreszenzkreuzkorrelationsspektroskopie versucht, ein weiteres Testsystem zur Signaldetektion von Proteaseaktivität zu etablieren. Dazu wurde ein Substrat aus den benutzten fünf massenspektrometrischen Substraten ausgewählt, und für diese Methode modifiziert. Eine Differenzierung durch den Diffusionskoeffizienten war nur bedingt möglich. Durch weitere Optimierung des Reporterpeptidformates und dem Einsatz von Fluoreszenzkreuzkorrelationsspektroskopie sollte es möglich sein, die diagnostische Leistungsfähigkeit des funktionellen Protease Profilings weiter zu verbessern.
Study and optimization of the physical and chemical processes that are involved in many applications in science and engineering are worthwhile, to ensure the stability and efficiency of their performance. Examples are combustion process in direct injection engines, gas turbine combustors, and liquid rocket propulsion systems. First step in understanding a spray must naturally be the understanding of its basic constituents: i.e. single droplets. Hence, it is important to develop good numerical models that can predict and simulate the process of evaporation of a single droplet accurately. Thus, computational investigation of the evaporation of water droplets induced by an infrared laser beam is performed. In particular, a single spherical droplet is considered, which is suspended on horizontal and vertical glass fibers in air under atmospheric pressure. The droplet heating and evaporation are induced by a pulsed CO2 laser. The fuels in liquid rocket propulsion systems, methane and kerosene, are being discussed as alternative fuels to hydrogen because of their high energy content. Methane has some advantages compared to kerosene because of its cleaner burning characteristics. The present study contributes to an improved understanding of methane/air, methane/oxygen and methane/LOX (liquid oxygen) combustion compared to the hydrogen/oxygen system. A numerical investigation of laminar CH4/air and CH4/O2 flames is performed, where different mixtures of nitrogen and oxygen in the oxidizer stream are studied. Moreover, liquid oxygen spray flames with carrier gas methane against an oxygen stream are investigated in the counterflow configuration. The obtained results may be used in (spray) flamelet library or computations of flamelet generated manifolds in turbulent combustion. The mathematical model is based on the two-dimensional conservation equations, which are transformed into one-dimensional equations using a similarity transformation. The numerical simulation concerns the axi-symmetric configuration with an adaptive grid for the gas phase. Detailed models of all relevant processes are employed; in particular, a detailed chemical reaction mechanism is used, which comprises 35 species involving 294 elementary reactions. The chemical reaction scheme presented in this work was developed in [1]. The thermodynamic data for CH4 and O2 between 100 and 300 K are implemented for normal and elevated pressures for use in computations of cryogenic CH4/LOX combustion. For the CH4/air laminar flame, the present results are compared with results from literature to verify the mathematical model, chemical mechanism and the numerical scheme. The CH4/O2 flame is studied for elevated pressures up to 2 MPa. Both extinction strain rates and the scalar dissipation rates at stoichiometric conditions are evaluated for use in future turbulent flamelet computations. It is shown that oxygen dilution, pressure, and strain rate have a pronounced effect on flame structures, which becomes evident by studying the effects of liquid oxygen compared to gaseous oxygen on flame structure. The combustion of CH4/LOX with preceding evaporation of liquid oxygen under cryogenic conditions has displayed a significant effect of the liquid phase on gas temperature. Moreover, the spray flame is broadened with increase of initial droplet size.
Ziel dieser Arbeit war die Synthese und die Untersuchung der magnetischen Eigenschaften mehrkerniger cyanoverbrückter Bispidinkomplexe. Zu diesem Zweck wurde zunächst eine Serie einkerniger Bispidinkomplexe (CrIII, MnII, FeII und NiII) dargestellt und bezüglich der auftretenden Anisotropie untersucht. Dadurch konnten direkte Zusammenhänge zwischen der Art des Bispidinliganden und der resultierenden Nullfeldaufspaltung gezogen werden. Ebenso zeigte sich, dass sowohl die Anisotropie als auch der Spingrundzustand eine starke Abhängigkeit von den Koliganden in diesen Systemen besitzen. Im zweiten Teil dieser Arbeit wurden homodinukleare CuII-Bispidinkomplexe eingehend bezüglich deren elektronischen Strukturen untersucht. Dazu wurden zwei verschiedene Bispidinliganden verwendet und, gestützt durch spektroskopische Daten (ESR- und UV/Vis-Spektroskopie), die Austauschmechanismen über einen ausführlichen ligandenfeld-theoretischen Ansatz beschrieben. Daraus ergibt sich, dass durch die unterschiedlichen Lagen der Jahn-Teller Achsen der einkernigen Untereinheiten, vor allem im Vergleich der Anteile der Nullfeldaufspaltung D und E, abweichende Anisotropien resultieren. Aufbauend auf diesen Ergebnissen wurden die Studien auf ferromagnetisch gekoppelte FeIII-CuII Spezies erweitert. Dabei ermöglichte der direkte Vergleich an zwei Jahn-Teller-isomeren Strukturen eine Korrelation zwischen der Lage der Jahn-Teller Achse am CuII-Zentrum und der Größe der Nullfeldaufspaltung dieser Systeme. Es konnte durch magnetische Messungen und ESR-Spektroskopie nachgewiesen werden, dass die Anisotropie derartiger zweikerniger FeIII-CuII Komplexe maximiert wird, wenn die Jahn-Teller Achse orthogonal zur FeIII-CuII Achse liegt. Sobald die Jahn-Teller Achse parallel zur FeIII-CuII Achse liegt, wird der anisotrope Austausch auf einen reinen dipolaren Anteil von D reduziert. Der letzte Abschnitt beschreibt die magnetischen Eigenschaften von dreikernigen bimetallischen Komplexen. Erneut konnte hier durch den Einsatz unterschiedlicher Bispidinkomplexe von NiII und MnII und eines FeIII-Vorläuferkomplexes die uniaxiale Nullfeldaufspaltung modifiziert. Auch in den dreikernigen Systemen ist durch die vorliegenden strukturellen Daten ein Zusammenhang der Lage der langen Achse am NiII-Zentrum, die durch die Präorganisation des Bispidinliganden zustande kommt, und der resultierenden Anisotropie möglich.
Cyclic pseudo peptides that can be isolated from the marine genus lissoclinum (ascidians) exhibit an interesting and versatile copper(II) coordination chemistry. They are highly preorganized, well suited for the complexation of copper(II) and are found to preferably form dinuclear copper(II) complexes. The accumulation of copper(II) in the ascidians and its complexation in the ascidians by cyclic pseudo peptides suggests a metabolic role of the copper(II) complexes of these interesting molecules. Recent findings imply the involvement of dinuclear copper(II) complexes in capture and/or hydrolysis of atmospheric CO2. This thesis deals with the synthesis of the cyclic pseudo peptides H3L1, H4L4, H4L4-bn, H4Lrs, and H4LascA and with the investigation of the mono- and dinuclear copper(II) complexes of the cyclic pseudo hexa- and octapeptides H3L1-3, H3Lwa, H4L4, H4Lrs, H4Lox, and H4LascA and their potential as model systems for the natural macrocycles. The main focus is on the investigation of the dinuclear copper(II) complexes of cyclic pseudo octapeptides, their reaction with atmospheric CO2 to the corresponding carbonato bridged species, and the differences in coordination chemistry that arise from their different molecular structures (Chapter 4).
"Campus-Report" heißt die Radiosendung der Universitäten Heidelberg, Mannheim, Karlsruhe und Freiburg. Die Reportagen über aktuelle Themen aus Forschung und Wissenschaft werden montags bis freitags jeweils um ca. 19.10h im Programm von Radio Regenbogen gesendet. (Empfang in Nordbaden: UKW 102,8. In Mittelbaden: 100,4 und in Südbaden: 101,1) Uni-Radio Baden: ein gemeinsames Projekt der Universitäten Freiburg, Heidelberg, Karlsruhe und Mannheim in Zusammenarbeit mit Radio Regenbogen – unterstützt von der Landesanstalt für Kommunikation. Sendung vom 30. Juni 2010
Zusammenfassung Die vorliegende Arbeit beschäftigt sich mit der Synthese und Charakterisierung von neuen heterobimetalischen Carbamat-Komplexen und ihren chemischen Eigenschaften. CO2-Fixierung durch Insertion in die Zn-N Bindung von EtZnN(iPr)2 führt zur Bildung des tetrameren Carbamat-Komplexes [ZnEt(O2CN(iPr)2)]4, welcher in dieser Arbeit als Ausgangsverbindung eingesetzt wurde. Die thermische Zersetzung dieses Carbamat-Komplexes wurde mit verschiedenen Methoden analysiert, wobei die Untersuchungen zeigen, dass der Komplex [ZnEt(O2CN(iPr)2)]4 eine gute Vorläuferverbindung für ZnO-Nanopartikel darstellt. Die ZnO-Nanopartikel mit einer Partikelgröße von ca. 10 nm können unter milden Reaktionsbedingungen erhalten werden, wobei die Sauerstoff-Atome des Oxids aus dem CO2 stammen. Das tetramere Carbamat [ZnEt(O2CN(iPr)2)]4 wurde mit den verschiedenen Stickstoffbasen Pyridin, N,N,N',N'-Tetramethylguanidin und bis-N,N,N',N'- Tetramethylguanidinonaphthalin umgesetzt, wobei eine Vielzahl neuer mono-, biund trinuklearer Zn-Carbamat-Komplexe erhalten werden konnte. Der erste strukturell charakterisierte mononukleare Zn-Biscarbamat-Komplex mit η1-koordinierten Carbamat-Liganden entstand bei der Reaktion von [ZnEt(O2CN(iPr)2)]4 und einer Guanidin-Base. Die Reaktion von [ZnEt(O2CN(iPr)2)]4 mit Co(II)- und Mn(II)-dichlorid-Komplexen, welche 2-(Methylamino)pyridin als weiteren Ligand enthalten, führt zu neuen tetraund oktanuklearen gemischten Zn/Co und Zn/Mn Carbamat-Komplexen. Im Fall von Kobalt entstanden tetranukleare ([M4R2(O2CN(iPr)2)6] (M =Zn, Co; R = Et, Me)) und oktanukleare Komplexe ([M8(my4-O)2(O2CN(iPr)2)6] (M =Zn, Co)), während mit Mn der oktanukleare Komplex [Zn2Mn6(my4-O)2(O2CN(iPr)2)6] gebildet wurde. Bei der Oxidation des oktanuklearen Zn/Mn-Komplexes [Zn2Mn6(my4-O)2(O2CN(iPr)2)6] mit Sauerstoff entsteht der neue Komplex [Zn2Mn6(my4-O)2(my3-O)(O2CN(iPr)2)6]. Die thermische Zersetzung der gemischten Zn/Co und Zn/Mn Carbamat-Komplexe unter milden Bedingungen (200-300°C) führt zu magnetischen gemischten Oxid-Nanopartikeln.
Ziel dieser Arbeit ist es, ein grundlegendes und detailliertes Verst¨andnis der strukturellen und elektronischen Eigenschaften neuer ein- und zweikerniger Bis- und Tetrakisguanidin-Ni(II)-Komplexe zu erlangen. Die Synthesen einer Reihe von Komplexen mit unterschiedlichen Koordinationsgeometrien sowie deren Molekülstrukturen in der kristallinen Phase, die mit Hilfe der Einkristallstrukturanalyse erhalten wurden, werden vorgestellt. Charakteristische strukturelle und elektronische Besonderheiten werden diskutiert. Dabei fließen auch die Ergebnisse quantenchemischer Rechnungenen (DFT) mit ein. Die magnetische Suszeptibilität wird mit Hilfe eines SQUID-Magnetometers (SQUID = Superconducting Quantum Interference Device) ausf¨uhrlich untersucht und es wird ein elektronischer high-spin Zustand jedes Nickelatoms in allen untersuchten Komplexen festgestellt. Zudem wird eine signifikante Nullfeldaufspaltung (ZFS) gefunden, die als Folge des durch die Spin-Bahn-Kopplung induzierten Einmischens der angeregten Zustände in den Grundzustand resultiert. Im Experiment werden die sich daraus ergebenden elektronischen Eigenschaften auf der Basis einer Ladungsdichte-Verteilung an dem System [(btmgb)NiCl2] (btmgb = 1,2-Bis(N,N,N’,N’ -tetramethylguanidino)benzol) bei tiefen Temperaturen (7K) untersucht. Die Betrachtung der Bindungssituation um das Nickelatom ergibt für die koordinativen N→Ni-Bindungen sowohl einen σ- als auch einen π- Donor-Anteil. Die Zonen erhöhter Ladungskonzentration an den koordinierenden Stickstoffatomen zeigen darin in einem Schl¨ussel-Schloss-Prinzip direkt auf die Bereiche der Ladungsauslöschungszonen am Nickelatom. Der starke Donor-Charakter des Bisguanidin-Ligandens wird best¨atigt. Es wird gezeigt, dass dieser Komplex ein Referenzsystem darstellt, der es ermöglicht, unbeeinflusst von jeglichem elektronischen Ligandeneinfluss, das Einmischen bestimmter angeregter Zustände in den Grundzustand zu untersuchen. Es werden zudem ausführliche 1H- und 13C-NMR-spektroskopische Untersuchungen an einer Auswahl dieser paramagnetischen und tetraedrisch koordinierten Bisguanidin-Ni(II)-Dihalogenid-Komplexe durchgeführt um die dynamischen Prozesse, die diesen Komplexen zueigen sind, aufzuklären. Aus den NMR-Spektren bei verschiedenen Temperaturen werden die Ratenkonstanten des Durchschwingmechanismus des Nickelions bestimmt. Es ergeben sich hierbei Werte für G‡ und S‡, die in der selben Größenordnung analoger Zn(II)-Komplexe liegen. Jedoch kann dieser Prozess, bedingt durch den Paramagnetismus, bereits bei einer um 40 ◦C höheren Temperatur beobachtet werden, was die Möglichkeit eröffnet, die Ratenkonstanten so schneller dynamischer Prozesse zu bestimmen, die mit Hilfe der diamagnetischen NMR-Spektroskopie nicht mehr auflösbar wären. In diesem Zusammenhang erfolgt für alle untersuchten Komplexe eine vollst¨andige Zuordnung der NMR-Signale, die durch Korrelationsspektren gestützt wird und es kann der Einfluss der Halogenid- Substitution und der Variation des Guanidin-Metall-Bisswinkels herausgestellt werden. Die aus dem Experiment erhaltenen paramagnetischen Verschiebungen, die mit Hilfe der NMR-Spektren analoger Zn(II)-Komplexe ermittelt werden, werden mit den aus der Theorie (DFT) erhaltenen Werten verglichen. Schließlich wird das katalytische Potential der Komplexe [LNiBr2] (L = chelatisierender Bisguanidin-Ligand) hinsichtlich der Polymerisation von Ethylen untersucht. Die theoretischen Ergebnisse (DFT) zeigen, dass der btmge-Ni(II)-Komplex (btmge = 1,2-Bis(N,N,N’,N’ -tetramethylguanidino)ethan) als Präkatalysator für die Polymerisation durchaus in Frage kommt.
Mit schwindenden Erdöl, Erdgas- und Kohleressourcen wird Biomasse als einzige erneuerbare Kohlenstoffquelle zukünftig wieder eine größere Rolle bei der Energieversorgung bzw. der Herstellung von organischen Chemikalien und Kraftstoffen spielen. Für die Optimierung bestehender Technologien und die Entwicklung neuer Technologien zur effizienten energetischen und stofflichen Nutzung von Biomasse werden immer häufiger Computersimulationen eingesetzt. Diese reduzieren die Zahl der zeit- und kostenintensiven Experimente für die Verfahrensoptimierung. Durch die zeitliche und/oder örtliche Auflösung aller chemischen und physikalischen Prozesse des Gesamtsystems wird zudem die Charakterisierung von Prozessgrößen ermöglicht, die mit experimentellen Methoden nicht oder nur unter erheblichem Aufwand zu bestimmen sind. Die vorliegende Arbeit mit dem Ziel der numerischen Simulation eines Flugstromvergasers für biomassestämmige Öl-Koks-Gemische ist Teil eines Verbundvorhabens des Bundesministeriums für Bildung und Forschung (BMBF) mit der Fördernummer 03SF0320D. In diesem soll der Vergasungsprozess des am Karlsruher Institut für Technologie (KIT) entwickelten bioliq-Verfahrens untersucht werden. Für die mathematische Abbildung des Vergasungsprozesses wird dieser als reaktive Strömung mit komplexen mehrdimensionalen und zeitabhängigen Wechselwirkungen zwischen einer großen Zahl von chemischen Reaktionen, diversen Transportvorgängen und Phasengrenzeffekten behandelt. Der Schwerpunkt der vorliegenden Arbeit liegt auf der Entwicklung detaillierter Modelle zur Beschreibung der Gasphasenkinetik, des Kokspartikelabbrandes und der Ablagerungsbildung im Vergasersystem. Der entwicklete Reaktionsmechanismus zur Beschreibung der Gasphasenreaktionen basiert auf Elementarreaktionen und umfasst 80 Spezies und 1243 Reaktionen. Simulationsergebnisse mit diesem Mechanismus werden mit experimentell bestimmten Flammengeschwindigkeiten, Zündverzugszeiten und Konzentrationsprofilen verglichen. Durch diese umfassende Validierung kann der Mechanismus für die Verbrennungs-/Vergasungssimulation unterschiedlicher, im Mechanismus enthaltener Brennstoffe wie Ethylenglykol, Ethanol, Ethan, Acetaldehyd oder Methan verwendet werden. Das Abbrandmodell der Kokspartikel berücksichtigt neben den chemischen Reaktionsgeschwindigkeiten für die heterogenen Reaktionen mit O2, H2O und CO2 den Einfluss von Diffusionsprozessen, die Überlagerung der heterogenen Reaktionen untereinander und die Kopplung mit Gasphasenreaktionen. Für das Modell wurde im Rahmen der vorliegenden Arbeit ein MATLAB- und ein C-Programm-Code zur Einzelkornbetrachtung von Kokspartikeln entwickelt, mit denen Sensitivitätsanalysen und Parameterstudien durchgeführt werden. Das Ablagerungsmodell beschreibt im Wesentlichen den Transport und die Anlagerung von Aschebestandteilen an Reaktorwände und ermöglicht die Berücksichtigung geänderter Wandparameter durch eine sich bildende Ablagerungsschicht. Die entwickelten Modelle für den Partikelabbrand und die Anlagerung von Aschebestandteilen werden zudem in einem Programmpaket zusammengefasst, das an die kommerzielle Strömungssimulationssoftware ANSYS FLUENT 12.0 gekoppelt werden kann. Dies ermöglicht die Durchführung von Parameterstudien und Sensitivitätsanalysen in turbulenten Strömungen. Mit den in dieser Arbeit entwickelten Programmpaketen werden somit die bereits etablierten Anwendungsmöglichkeiten der numerischen Strömungssimulation für die Verfahrensoptimerung von komplexen Vergasungsprozessen entscheidend verbessert.
The present thesis is concerned with the development and characterization of new diferric purple acid phosphatase (PAP) model systems, which include functional groups that are meant to act as a second coordination sphere in phosphoester hydrolysis. A short review on purple acid phosphatases, including the postulated reaction mechanisms in phosphoester hydrolysis, and published PAP model complexes is given in Chapter 2. Furthermore, important data regarding published bridged diferric complexes are presented, in order to have a basis for interpretation of the analytical data in the results part. In Chapter 3, the results on the new model complexes are presented and discussed. At first, the cyclam-based ligand L1 and its coordination chemistry are described (Chapter 3.1). The most important findings are the following: Ligand L1 predominantly forms a mu-oxo bridged diferric complex when reacted with [FeCl4]- in situ. This complex, called K1, can readily coordinate phosphate and inactive phosphoesters, also in partly aqueous solution. Interestingly, the inactive phosphodiester diphenylphosphate (DPP) coordinates in a monodentate mode to one FeIII, whereas the monoesters para-nitrophenylphosphate (pNPP) and 1-naphthylphosphate (1-NP) bind in a bridging mode to both FeIII centers. The monodentate coordination of DPP is encouraging in terms of the intended reactivity in phosphoester hydrolysis, as this coordination mode is believed to be the active one, leading to a terminal hydroxide as a possible nucleophile. Chapter 3.2 deals with the phenolate-based ligands HL2 and H3L3 and their coordination chemistry. These ligands are derivatives of the published HBPMP ligand and incorporate amino and amido functional groups as second coordination sphere mimics. Diferric complexes, called K2 and K3, are obtained by in situ reaction of the ligands with a ferric salt. A spectrophotometric pH titration was performed and revealed the pH dependent species distribution and the corresponding pKa values of the complex solutions. K2 has three equilibria between pH 4.6 and 11, where the second equilibrium is the deprotonation of the second coordination sphere amines. In contrast, K3 has only two equilibria due to the low pKa of the amido protons. Regarding the coordination of phosphoesters, K2 shows a similar behavior to K1. DPP is coordinated monodentately to one FeIII, whereas pNPP and 1-NP form bridging complexes. This is not observed with K3, which shows bridging coordination with both, mono- and diesters, possibly due to the lack of hydrogen bond donors in the second coordination sphere. The complexes K1, K2 and K3 were tested for hydrolytic activity towards the activated phosphoester substrates bis-(2,4-dinitrophenyl)phosphate (BDNPP) and 2,4-dinitrophenylphosphate (DNPP). The results of these experiments are presented in Chapter 3.3. K1 and K2 are the first examples of PAP model complexes that catalyze the hydrolysis of the phophomonoester DNPP. So far, only diester hydrolysis with PAP model complexes has been reported in literature, while the inactive bridging coordination mode is observed for phosphomonoesters. We draw the fact, that K1 and K2 can hydrolyze monoesters, back to the hydrogen bonding interaction of the coordinated substrates to the remote ligand parts. A closer analysis of the reactivity of K1 towards DNPP and BDNPP, based on DFT calculations, shows that 1) BDNPP is stabilized by the interaction with the protonated cyclam in the monodentate coordination mode, 2) the hydrolysis of DNPP has a significantly lower activation barrier with the hydrogen bonding interactions than without and 3) this barrier is lower than the energy barrier to a bridging coordination mode. As a conclusion, a mechanism is proposed, where the substrate binds in a monodentate coordination mode and is subsequently attacked by a terminal hydroxide. This active species is in equilibrium with the inactive bridging complex. In the case of the diester BDNPP, the equilibrium is shifted to the active species, while the monoester DNPP is more stable in the bridging coordination mode. The hydrolysis product remains bound to K1 and inhibits catalysis.
Ruß entsteht als Schadstoff bei der Verbrennung und hat einen negativen Einfluss auf Gesundheit und Umwelt. Die Vermeidung von Ruß stellt deshalb eines der Hauptziele in der aktuellen Rußforschung dar. Zusammenfassung In den letzten Jahren konnte hierbei durch Weiterentwicklungen in der Simulation und in der experimentellen Untersuchung große Fortschritte erreicht werden. Die genauen Abläufe der Rußbildung und ihre Abhängigkeit von den jeweiligen Verbrennungbedinungungen sind jedoch noch nicht vollständig verstanden und müssen darum weiterhin untersucht werden. Da dies mit Experimenten allerdings nicht immer möglich oder zu teuer ist, spielt die Simulation der Rußbildung eine zunehmend wichtigere Rolle. Zusammenfassung Eine detaillierte Modellierung der rußbildenden Vorgänge in komplexen technischen Systemen ist wegen des resultierenden großen Rechenaufwandes aber auch mit aktuellen Computern kaum möglich. Zusammenfassung Aus diesem Grund muss der rechnerischen Aufwand für die Simulation verringert werden. Hierfür sind zwei Ansätze möglich: Zum einen die Betrachtung eines einfachen Systems mit detaillierter Beschreibung der Rußbildung, zum anderen eine reduzierte Beschreibung der Rußbildung, was die Simulation der Rußentstehung in technischen Systemen erlaubt. Beide Ansätze werden in dieser Arbeit behandelt. Zusammenfassung Die Entstehung von Ruß wird hier in einer, als eindimensional angenommenen, laminaren Vormischflamme detailliert simuliert, wobei die einzelnen Vorgänge mit verschiedenen Schritten wiedergegeben werden. Dies stellt eine Weiterentwicklung des detaillierten Rußmodells dar, das bisher lediglich für die Simulation der Rußbildung in Stoßrohren und somit ohne die Berücksichtigung von Transportprozessen verwendet wurde. Dieses Modell dient dem besseren Verständniss der Vorgänge und der Verbesserung ihrere reaktionskinetischen Beschreibung. Zusammenfassung Für diese Simulationen wurde ein Programm entwickelt, das die Entstehung der Rußpartikel in der Flamme beschreibt. Die dabei stattfindenden Vorgänge sind im detaillierten Rußmodell als Polymerreaktionen formuliert, die mit Hilfe der Kompartiment-Methode berechnet werden. Daraus werden die interessierenden Rußeigenschaften, wie etwa der Partikeldurchmesser, ermittelt. Zusammenfassung Die mit dem neuen Programm erhaltenen Resultate werden zur Validierung überprüft und mit experimentellen Ergebnissen verglichen. Dabei werden für die erste Verwendung des reaktionskinetischen Modells unter Flammenbedinugen zufriedenstellende Übereistimmungen erzielt. Auf diesen Ergebnissen aufbauend kann das Programm somit für eine Weiterentwicklung des Rußmodells verwendet werden. Zusammenfassung Für die reduzierte Beschreibung der Rußbildung wird ein semi-empirisches Rußmodell verwendet, das die Entstehung der Partikel durch zwei zusätzliche Ratengleichungen beschreibt. Diese repräsentieren die Anzahl und die Masse bzw. das Volumen der Partikel. Dieses Modell wird erweitert um die Entstehung von Partikelkeimen aus Phenyl, da die bisherige Version des Modells Schwächen bei der Simulation der Rußbildung aus aromatischen Brennstoffen zeigte. Das erweiterte semi-empirische Modell wurde für die Simulation unter Stoßrohrbedingungen getestet, wobei eine deutliche Verbesserung bei der Beschreibung der Rußbildung erreicht wurde.
"Campus-Report" heißt die Radiosendung der Universitäten Heidelberg, Mannheim, Karlsruhe und Freiburg. Die Reportagen über aktuelle Themen aus Forschung und Wissenschaft werden montags bis freitags jeweils um ca. 19.10h im Programm von Radio Regenbogen gesendet. (Empfang in Nordbaden: UKW 102,8. In Mittelbaden: 100,4 und in Südbaden: 101,1) Uni-Radio Baden: ein gemeinsames Projekt der Universitäten Freiburg, Heidelberg, Karlsruhe und Mannheim in Zusammenarbeit mit Radio Regenbogen – unterstützt von der Landesanstalt für Kommunikation. Sendung vom 9. Dezember 2009
In the framework of this thesis, the polynuclear bismuth chemistry has been investigated from different perspectives with the main focus on four types of the chemical bonding. Thus, the section of bismuth–bismuth bonding affects redox/metathesis reactions of BiBr3 with bulky lithium silanide Li(thf)3SiPh2tBu in three different ratios, leading to the formation of a Bi–Bi bonded compound, (tBuPh2Si)4Bi2 as one of the reaction products. The quantum chemical study has been mainly performed to shed light on the processes of oligomerisation of R2Bi radicals and bismuth dimers. That is a major challenge in the context of ''thermochromicity'' and ''closed-shell interactions'' in inorganic chemistry of organobismuth compounds with homonuclear Bi–Bi bonds. The section of bismuth–transition-metal bonding gives a deep insight into the structures, the chemical bonding and the electronic behavior of heteronuclear bulky Bi–Fe cage-like clusters, cubic [Bi4Fe8(CO)28]4– and seven-vertex [Bi4Fe3(CO)9], on the experimental and theoretical level. The section of bonding in bismuth–cyclopentadienyl compounds represents a detailed theoretical and experimental study of molecular systems based on cyclopentadienyl bismuth units such as (C5R5)Bi2+, [(C5R5)Bi]n and (C5R5)BiX2 (R = H, Me; X = F, Cl, Br, I; n = 1-4) in order to develop an effective adjustment of their electronic and bonding behavior and then, to be able to manipulate highly fluxional Bi–C5R5 bonds. The experimental part of this section emphasizes the theoretical results by observation of the unprecedented nanoscopic supramolecular architecture [{(C5Me5)5Bi5Br9}{(CH2Cl2)(BiBr4)}]2, cationic molecule [(C5Me5)5Bi6Cl12]+ and zig-zag polymer chains [(C5Me5)BiX2] (X = Br, I). The section of icosahedral and macroicosahedral bismuthanediide oligomers is a conceptual approach to understand the structures and the electronic properties of highly symmetric molecules such as [RnBinM2n–4]4– (n = 12, 32, …) on the theoretical level. The obtained results open the way to their endohedral chemistry. To sum up, unique structural and bonding features of the molecular assemblies based on C5Me5-substituted bismuth halides, as well as the observed Bi−arene pi-complexations and inverted sandwich behavior found in the crystal cell of a Bi–Fe cluster, are an important step in the development of supramolecular chemistry and crystal engineering of the compounds of the heavy group 15 elements. Furthermore, the bismuth cage and cluster chemistry has taken one step forward. The largest cluster of the bismuth–iron family (Bi4Fe8) and the spherical aromaticity of seven-vertex Bi4Fe3 structure have been observed. The new examples of a Bi4 tetrahedron, stabilized by transition-metal groups, as well as bismuth’s square pyramidal (Bi5) nido-polyhedron-like and octahedral (Bi6) deltahedron-like cages, stabilized by C5Me5 and halo ligands, have been discovered. A new chapter in the theoretical chemistry of highly symmetric bismuth cage molecules (Bi12, Bi32) has been opened.
Wie entscheiden Sporen, wo sie siedeln? - Eine holographische Bewegungsanalyse von Ulva Zoosporen an Oberflächen mit unterschiedlichen physikochemischen Eigenschaften Ulva Sporen siedeln auf Oberflächen, um dann makroskopisch sichtbare Algen zu bilden. Dieser Bewuchs auf künstlichen Oberflächen (z.B. Bootsrümpfen) verursacht enorme Kosten, z.B. durch den erhöhten Treibstoffverbrauch von Schiffen. Um die initiale Phase der Besiedlung von Oberflächen, die schließlich zu dem Bewuchs führt, besser zu verstehen, wurde das Bewegungs- und Siedlungsverhalten von Ulva Sporen in Echtzeit und dreidimensional (3D) mittels digitaler in-line Holographie untersucht. Für diese Analyse wurde ein transportables, digitales in-line holographisches Mikroskop gebaut, mit dem die Bewegungsmuster der Algensporen aufgenommen wurden. Weiterhin wurde die Entwicklung, Programmierung und Anwendung einer Analysensoftware, die eine Rekonstruktion der Hologramme sowie eine automatisierte Bestimmung der Sporenpositionen erlaubt, durchgeführt. Auf diese Weise konnte erstmals das Schwimmverhalten von Ulva Sporen und deren Änderung in der Nähe von Oberflächen in 3D bestimmt und quantifiziert werden. Hierfür wurden funktionalisierte Glasoberflächen mit unterschiedlicher Benetzbarkeit sowie unterschiedlicher Attraktivität für Ulva Sporen untersucht: hydrophiles Poly(ethylene glycol) (PEG), hydrophiles Glas (AWG) und mit hydrophoben Fluorooctyltriethoxysilan (FOTS) funktionalisiertes Glas. Bei allen Oberflächen wurde eine Sporenanreicherung bis zu einer Entfernung von mindestens 200µm zur Oberfläche beobachtet. Eine Änderung der Bewegung findet ab einer Entfernung von 50µm zur Oberfläche statt und äußert sich zum Beispiel in einer ausgeprägten Schwimmbewegung parallel zur Oberfläche. Diese Änderung der Schwimmrichtung wird durch hydrodynamische Kräfte in der Nähe von Oberflächen induziert. Für die drei verwendeten Oberflächenchemien können deutliche Unterschiede im Besiedlungsverhalten in Oberflächennähe beobachtet werden: Auf AWG wird ein zeitunabhängiges Explorationsverhalten mit hoher Variabilität detektiert. Für PEG zeigt sich, dass sich die meisten Sporen nach einem kurzen Kontakt mit der Oberfläche wieder von ihr entfernen. Dies führt zu der Hypothese, dass die Algen auf die physikochemische Wechselwirkung ihrer Flagellen mit der Oberfläche reagieren. Das Verhalten auf der besiedlungsreichen FOTS Oberfläche ist zeitabhängig. In der Anfangsphase der Erkundungszeit werden die Sporen an der Oberfläche festgehalten, was vermutlich auf starke hydrophobe Wechselwirkungen zurückzuführen ist. Die meisten dieser „gefangenen“ Sporen schwimmen nach einer Weile wieder zurück in die Lösung. Dennoch werden, im Vergleich zu den anderen beiden Oberflächen, frühzeitig eine relativ große Anzahl permanenter Besiedelungsereignisse beobachtet. Das analysierte Erkundungsverhalten in der Nähe der Oberfläche kann gut mit der integralen Besiedelungskinetik korreliert werden. Mittels der Motilitätsanalyse kann nach einer Aufnahmedauer von nur 2min innerhalb der ersten 5min der Oberflächenerkundungsphase die Besiedelungskinetik sehr gut vorhergesagt werden, die sonst nur in einem 45 minütigen Besiedelungsversuch bestimmt werden konnte. Basierend auf den Ergebnissen der hier vorgestellten Bewegungsanalyse und auf Daten aus früheren Besiedlungskinetik-Studien wird ein Sporen Besiedelungsmechanismus postuliert, der besagt, dass die anfänglich adhärierende Sporen die weitere Sporen-Besiedlung der Oberfläche katalysieren
Diese Arbeit untersucht Rotations- und Schwingungsübergänge in Kollisionen zwischen H2-Molekülen, wobei die Methode der Wellenpaketpropagation mittels der Multi-Configuration Time-Dependent Hartree-Methode (MCTDH) zum Einsatz kommt. Dazu werden Korrelationsfunktionen zwischen dem zeitlichen Verlauf des Wellenpakets und diversen Endzustands-Wellenfunktionen gebildet, aus denen sich per Fourier-Transformation die Übergangswahrscheinlichkeiten und daraus schließlich die gewünschten integralen Wirkungsquerschnitte berechnen lassen. Im Gegensatz zu früheren theoretischen Arbeiten zum inelastischen H2-H2-Stoß werden in den hier vorgestellten Rechnungen alle (Translations-, Rotations-, Schwingungs-) Freiheitsgrade berücksichtigt, und es wird die vollständige Form des Hamilton-Operators verwendet, d.h. es wird auf Entkopplungsnäherungen wie Coupled States (CS) verzichtet. Zunächst werden Kollisionen zwischen para-H2 im Grundzustand bei Kollisionsenergien von bis zu 1.2 eV betrachtet, wofür integrale Wirkungsquerschnitte für Rotationsanregungen eines oder beider Moleküle berechnet werden. Für volldimensionale Rechnungen kommen sowohl die aufwändige ab-initio-Potentialenergiefläche (PES) von Boothroyd et al. (BMKP) zum Einsatz, wie auch Varianten davon mit reduzierter Anisotropie. Zusätzlich werden Vergleichsrechnungen im Rahmen der Rigid-Rotor-Näherung (RR) durchgeführt, wobei die ab-initio-PES von Diep und Johnson (DJ) sowie zwei RR-Varianten der BMKP-Fläche benutzt werden. Die berechneten Wirkungsquerschnitte stimmen insgesamt sehr gut mit früheren theoretischen Resultaten überein, solange man jeweils deren Näherungsmethoden anwendet. Die RR-Näherung erweist sich im betrachten Energiebereich als recht zuverlässig, während die CS-Näherung systematisch zu niedrige Querschnitte liefert. Es werden auch thermische Ratenkoeffizienten für T = 100...3000K ermittelt, wobei die Ergebnisse für die DJ-Fläche gute Übereinstimmung mit experimentellen Daten zeigen. Anschließend werden Kollisionen zwischen para-H2 und ortho-H2 untersucht, wobei diverse initiale Rotations- und Schwingungsanregungen betrachtet werden. Eine schwach anisotrope Variante der BMKP-Fläche wird benutzt, um integrale Wirkungsquerschnitte für Rotationsübergänge bei Kollisionen mit und ohne Vibrationstransfer zu berechnen, wobei die Kollisionsenergie zwischen 0.1 und 1.0 eV liegt. Für vibrations-elastische Stöße zeigt sich, dass die Vibration in einem H2-Molekül Rotationsübergänge im selben H2 (bis auf das ca. zweifache) verstärkt –- verglichen mit dem vibrationslosen Fall –- aber Rotationsübergänge im anderen H2 dämpft. Die Größe dieses Effektes hängt stark mit der Absolutänderung der Rotationsquantenzahlen zusammen. Für Stöße mit Vibrations-Transfer erweisen sich die Wirkungsquerschnitte für die begleitenden Rotationsübergänge als nahezu unabhängig von der Richtung des Transfers (vom ortho-H2 zum para-H2 bzw. umgekehrt). Insgesamt betrachtet sind Stoßprozesse mit Vibrationstransfer deutlich weniger wahrscheinlich als solche ohne; selbst der energetisch nahezu resonante reine Vibrationstransfer (ohne jeglichen Rotationsübergang) ist zwei Größenordnungen schwächer als die stärksten vibrations-elastischen übergänge.
In dieser Arbeit wird die Synthese eines biomimetischen Sulfitoxidase-Modells MoVI(TMSO−N∩N´)2O2 in homogener Phase beschrieben. An diesem Komplex wird der Sauerstoffatomtransfer (OAT) bezüglich der tertiären Phosphane PMenPh3-n (mit n = 0...3)untersucht. Mit einem halben Äquivalent der Phosphane entsteht in allen Fällen das entsprechende Phosphanoxid und ein zweikerniger sauerstoffverbrückter Komplex,wodurch eine echte Katalyse nicht möglich ist. Mit zwei Äquivalenten Phosphan PMenPh3-n (n = 1...3) entstehen die substratgebundenen Oxido-Phosphan-Mo(IV)-Komplexe MoIV(TMSO−N∩N´)2O(PMenPh3-n). Kinetische Untersuchungen zeigen Ähnlichkeiten zu anderen Sulfitoxidase-Modellen, z.B. einen assoziativen Mechansimus für den geschwindigkeits-bestimmenden Schritt des OAT. Durch Ein-Elektronen-Reduktion von MoVI(TMSO−N∩N´)2O2 mit Cobaltocen ist das Cobaltoceniumsalz des Anions [MoV(TMSO−N∩N´)2O2]− zugänglich. Dieses wird mit Trimethlysilylchlorid in [MoV(TMSO−N∩N´)2(OTMS)O] und durch Reaktion mit Trifluoressigsäure in [MoV(TMSO−N∩N´)2O(OH)] umgewandelt. Durch Ein-Elektronen- Oxidation der Komplexe MoIV(TMSO−N∩N´)2O(PMenPh3-n) (n = 1...3) mit Ferroceniumhexafluorophosphat gelingt die Sythese einkerniger Phosphan-Mo(V)- Verbindungen, wobei jeweils leicht das Phosphan dissoziiert. Alle Mo(V)-Komplexe werden EPR-spektroskopisch charakterisiert. Das Dioxido-Mo(VI)-System wird durch die Anknüpfung des Liganden an unlösliches Polystyren und anschließender Komplexierung zum MoVI(PSO−N∩N´)2O2 immobilisiert. Der OAT mit Trimethylphosphan ergibt einen analogen Komplex wie in Lösung. Durch Ein-Elektronen-Reduktion von MoVI(PSO−N∩N´)2O2 mit Cobaltocen und Ein- Elektronen-Oxidation von MoIV(PSO−N∩N´)2O(PMe3) mit Ferroceniumhexafluorophosphat sind immobilisierte einkernige Mo(V)-Verbindungen zugänglich, die mittels EPR-Spektroskopie charakterisiert werden. Durch die Umsetzung von [MoV(PSO−N∩N´)2O(PMe3)]+ mit H2O gelingt die Nachahmung eines Sulfitoxidaseähnlichen Katalysezyklus. Dieser wird unter Verwendung von MoVI(PSO−N∩N´)2O2 als heterogenem Katalysator, von PMe3 als Substrat, von H2O als Sauerstoffquelle, der Phosphazenbase P1-tBu und von Diacetylferroceniumtetrafluoroborat als Oxidationsmittel nachvollzogen, wobei OAT- und CEPT-Schritte durchlaufen werden. Das selektiv gebildete Produkt ist OPMe3. Markierungsexperimente unter Einsatz von H218O zeigen den Einbau des 18O in das Produkt 18OPMe3. Dies belegt, dass tatsächlich Wasser die Sauerstoffquelle ist, analog zu enzymatischen Systemen. Durch die Substution eines Sauerstoffatoms im Dioxido-Mo(VI)-Komplex durch den tert-Butylimidoliganden wird mit MoVI(CH3O−N∩N´)2(N-tBu)O ein Imido-Oxido-Mo(VI)-System in homogener Phase etabliert. Dieses wird auf seine OAT-Eigenschaften bezüglich PMenPh3-n (n = 0...3) untersucht, wobei keine Bildung zweikerniger Komplexe beobachtet wird. Mit einem Überschuss an PMenPh3-n (n = 1...3) entstehen die Phosphan-Imido-Mo(IV)-Spezies MoIV(CH3O−N∩N´)2(N-tBu)(PMenPh3-n) und unter Verwendung von PPh3 die fünffach-koordinierte Spezies MoIV(CH3O−N∩N´)2(N-tBu). Die Komplexe MoIV(CH3O−N∩N´)2(N-tBu)(PMenPh3-n) (n = 2, 3) werden durch Ein-Elektronen-Oxidation mit Ferroceniumhexafluorophosphat zu Phosphan-Imido-Mo(V)-Verbindungen umgesetzt. Durch Cobaltocen-Reduktion von MoVI(CH3O−N∩N´)2(N-tBu)O ist das Cobaltoceniumsalz des Anions [MoV(CH3O−N∩N´)2(N-tBu)O]− zugänglich, das durch Reaktion mit Trimethylsilylchlorid in die Chloro-Imido-Verbindung MoV(CH3O−N∩N´)2Cl(N-tBu) umgesetzt wird. Alle einkernigen Imido-Mo(V)-Komplexe sind EPR-spektroskopisch charakterisiert. Zusammenfassend lässt sich sagen, dass durch die Zweipunktfixierung von MoVIO2- Komplexen auf Polystyren der zum OAT-befähigte Komplex MoVI(TMSO−N∩N´)2O2 zum echten funktionalen biomimetischen Katalysator MoVI(PSO−N∩N´)2O2 ausgebaut werden kann, da die Bildung verbrückter Zweikernkomplexe zurückgedrängt wird. Durch die Erhöhung des sterischen Anspruchs der Zuschauer-Oxidoliganden durch die Substitution gegen einen tert-Butylimidoliganden kann eine Oligomerisierung ebenso verhindert werden. Eine biomimetische Katalyse ist durch die Hydrolyseempfindlichkeit des Imidoliganden jedoch nicht möglich.
Die vorliegende Arbeit behandelt die Synthese Bisterpyridin-funktionalisierter Oligonucleotide und die Anwendung ihrer ZnII- und CuII-Komplexe als Sonden für den amplifizierten sequenzspezifischen DNA-Nachweis. Durch Hybridisierung mit Target-DNA kommt es zur Destabilisierung des Metallkomplexes, so dass durch Zugabe geeigneter Präkatalysatoren katalytisch aktive Spezies gebildet werden. Der Einsatz chromogener oder fluorogener Substrate erzeugt nachfolgend ein Farb- oder Fluoreszenzsignal. Bisterpyridin-Metallkomplex-funktionalisierte Oligonucleotide unterschiedlicher Länge und Sequenz wurden zur Optimierung des Systems hinsichtlich ihrer thermodynamischen und kinetischen Stabilität charakterisiert. Die Signal¬amplifikation gelang erstmals durch eine zweistufige Kaskade, wobei zunächst ein chemischer CuII-Katalysator gebildet wird, der dann einen enzymatischen Cofaktor aktiviert und so eine Enzymkatalyse in Gang setzt. Weiterhin befasst sich die Arbeit mit der Synthese und Charakterisierung katalytisch aktiver Kupferkomplex-DNA-Konjugate. Diese sollen als immobilisierbare Redoxkatalysatoren die erstmalige Beobachtung einer Metallkomplex-Katalyse auf Einzelmolekülebene ermöglichen. Durch Hybridisierung mit einem Farbstoff-DNA-Konjugat können z. B. Änderungen der Oxidationsstufe des Kupfers direkt über Fluoreszenzfluktuationen des Farbstoffs beobachtet werden. Dazu wurde der Bisphenanthrolin-Ligand 3-Clip-phen kovalent an Oligonucleotide gekoppelt. Ein Hybrid mit Fluorophor-markierter DNA zeigt die Bindung eines CuII Ions durch 3-Clip-phen anhand von Fluoreszenzlöschung an, was auch auf Einzelmolekülebene bestätigt werden konnte. Die Komplexe sind Redox¬katalysatoren z. B. für die Oxidationen von Thiolen durch Luftsauerstoff oder von Hydrochinon durch Wasserstoffperoxid.
Die vorliegende Dissertation beschäftigt sich mit der Komplexierung von dreiwertigen Actiniden bei erhöhten Temperaturen. Die Motivation der Arbeit ist es, ein besseres Verständnis der geochemischen Prozesse, die für die Migration von Actiniden im Nahfeld eines nuklearen Endlagers von Bedeutung sind, zu erhalten. Abhängig von der Art des eingelagerten Abfalls können in der direkten Umgebung eines Endlagers Temperaturen bis 200°C auftreten, was eine starke Änderung der Geochemie von Actiniden zur Folge haben kann. Eine Vielzahl der relevanten Prozesse wurde bereits bei Raumtemperatur eingehend untersucht. Daten bei erhöhten Temperaturen sind jedoch kaum verfügbar. Eine umfassende Langzeitsicherheitsanalyse eines nuklearen Endlagers erfordert die exakte thermodynamische Beschreibung der relevanten geochemischen Prozesse sowohl bei Raum- als auch bei erhöhten Temperaturen. Der Fokus der im Rahmen dieser Dissertation durchgeführten Arbeiten liegt auf der Untersuchung der Temperaturabhängigkeit der Komplexierung von dreiwertigem Curium (Cm(III)) mit verschiedenen anorganischen Liganden. Dreiwertiges Curium wurde aufgrund seiner hervorragenden spektroskopischen Eigenschaften als Repräsentant für trivalente Actiniden ausgewählt. Die betrachteten Ligandensysteme sind Nitrat, Fluorid, Sulfat und Chlorid. Als hauptsächliche Untersuchungsmethode diente die zeitaufgelöste Laserfluoreszenzspektroskopie („TRLFS“). Die Untersuchungen zur Komplexierung von Cm(III) mit NO3-, SO42- und Cl- wurden in einer speziell entwickelten Hochtemperaturfluoreszenzzelle durchgeführt, welche spektroskopische Messungen im Temperaturbereich von 25 bis 200°C erlaubt. Das Cm(III)-Fluorid-System hingegen wurde in einer Quarzküvette im Temperaturbereich von 20 bis 90°C untersucht. Komplementäre Strukturuntersuchungen wurden mittels EXAFS-Spektroskopie (engl., Extended X-Ray Absorption Fine Structure) durchgeführt und durch quantenchemischen Rechnungen auf DFT-Niveau (Density Functional Theory) unterstützt. Die Ergebnisse der TRLFS-Untersuchungen zeigen eine generelle Verschiebung des chemischen Gleichgewichtes zugunsten der komplexierten Spezies bei erhöhten Temperaturen. So ist bei 25°C der Anteil der Komplexe Cm(NO3)2- und Cm(SO4)33- gering, während bei 200°C diese Komplexe die dominante Spezies des jeweiligen Systems darstellen. Im Falle des Cm(III)-Fluorid-System ist bereits im Temperaturbereich von 20 bis 90°C eine starke Zunahme der Molfraktionen der komplexierten Spezies zu beobachten. Auch hier wird der CmF2+-Komplex bei 20°C nur in geringen Mengen gebildet, während der Anteil dieser Spezies bei 90°C und [F-]eq > 3.0x10-3 m größer 50% ist. Anhand der Speziation der Systeme Cm(III)-Nitrat, Cm(III)-Fluorid und Cm(III)-Sulfat wurden die temperaturabhängigen konditionellen Stabilitätskonstanten log K’n(T) der schrittweisen Bildung der jeweiligen Komplexe ermittelt. Diese wurden mittels der SIT („specific ion interaction theory“) auf eine Ionenstärke von null (Im = 0) extrapoliert (log K0n(T)). Die log K0n(T)-Werte zeigen eine deutliche Zunahme mit steigender Temperatur, deren Ausmaß vom jeweiligen Ligandensystem abhängig ist. Die Temperaturabhängigkeit der einzelnen log K0n(T)-Werte wurde mittels geeigneter mathematischer Ansätze modelliert. Die hieraus gewonnenen thermodynamischen Konstanten zeigen generell positive Standardreaktionsenthalpien und -entropien. Somit ist die Triebkraft der untersuchten Komplexierungsreaktionen die Erhöhung der Entropie, was die Zunahme der Komplexierung mit steigender Temperatur erklärt. Eine weiteres Themengebiet, welches im Rahmen der vorliegenden Dissertation bearbeitet wurde, ist die Messung des pH-Wertes bei erhöhten Temperaturen. Der pH-Wert ist eine der Schlüsselgrößen von wässrigen Systemen und seine präzise Messung ist von entscheidender Bedeutung für die quantitative Beschreibung von Komplexierungsreaktionen. Die in dieser Arbeit angewandte Methode basiert auf der spektroskopischen Detektion des temperatur- und pH-abhängigen Gleichgewichtes der protonierten und deprotonierten Formen von verschiedenen Indikatorfarbstoffen (Acridin, Bromphenol Blau und Bromthymol Blau). Die Experimente wurden ebenfalls in einer Hochtemperaturzelle durchgeführt, welche mittels zweier Lichtleiter an ein UV/Vis-Spektrometer gekoppelt wurde. Die Ergebnisse zeigen eine gute Anwendbarkeit der Methode im Temperaturbereich bis ca. 100°C. So wurde der Indikatorfarbstoff Bromphenol Blau im Temperaturbereich von 20 bis 90°C verwendet, um den pH(T)-Wert von fluoridhaltigen Proben zu messen. Daraus wurde anschließend die freie Protonenkonzentration ([H+]eq) in Lösung ermittelt. Ein Vergleich der experimentell erhaltenen mit theoretisch berechneten [H+]eq-Werten zeigt eine gute Übereinstimmung im untersuchten Temperaturbereich. Somit kann die Temperaturabhängigkeit des pH-Wertes im Falle des Cm(III)-Fluorid-Systems sehr gut mittels theoretischer Rechnungen beschrieben werden.
Ziel der vorliegenden Arbeit war die Entwicklung hochempfindlicher Nachweisverfahren für proteolytische Enzyme. Viele Proteasen nehmen Schlüsselfunktionen in den Metastasierungsprozessen ein, dem größten Problem bei der Behandlung von Krebs. Sensitive Nachweismethoden für proteolytische Aktivität tragen zu einem tiefergehenden Verständnis der bei der Entstehung von Tochtergeschwüren beteiligten proteolytischen Prozesse bei und ebnen somit den Weg zur Entwicklung effektiver Antitumormedikamente. Unter Verwendung modifizierter natürlicher Proteine als Proteasesubstrate konnten zwei einzelmolekülspektroskopiebasierte Detektionsmethoden erarbeitet werden, welche einen sensitiven Nachweis proteolytischer Aktivität erlauben. Während sich das eine Verfahren der Detektion zeitlich korrelierter Fluoreszenzsignale bedient, nutzt das andere funktionalisierte Oberflächen zur Erkennung der Proteaseaktivität. Um Proteinsubstrate fluoreszent markieren zu können, musste eine neuartige Methode etabliert werden, welche die stöchiometrische Modifizierung von Proteinen unter Erhalt ihrer biologischen Funktion ermöglichte. Darüber hinaus gelang die Weiterentwicklung des Smart Probe-basierten Nachweisverfahrens zur sensitiven und spezifischen Diskriminierung von DNA-Punktmutationen durch den Einsatz von Oligonukleotiden, die zur Sonde bei der Anbindung an die Wildtypsequenzen in Konkurrenz stehen. Auf Grundlage der in diesen Arbeiten gesammelten Erfahrungen konnte zusätzlich eine neuartige, auf den speziellen Emissionseigenschaften des Coumarinfarbstoffs Dy-520XL beruhende DNA-Sonde konzipiert werden, welche ebenfalls eine eindeutige und einfache Diskriminierung von Punktmutationen mit hoher Sensitivität erlaubt.
In dieser Arbeit wird eine neuartige Syntheseroute zur Herstellung biokompatibler und hochstabiler Gold Nanopartikel-Peptid-Konjugate entwickelt, die der gezielten Untersuchung von Rezeptor-Liganden-Wechselwirkungen in hippocampalen Neuronen dienen. Aktivierte NMDA-(N-Methyl-D-Aspartat) Rezeptoren vermitteln vermutlich abhängig von ihrer räumlichen Lage in der postsynaptischen Zelle verschiedene Signalkaskaden: Die Aktivierung synaptischer NMDA-Rezeptoren fördert das Überleben der Zelle, während die Aktivierung der extrasynaptischen Rezeptoren zum programmierten Zelltod führt. Um diese Hypothese der positionsabhängigen Funktion der unterschiedlich lokalisierten NMDA-Rezeptoren zu untersuchen, werden Nanopartikel entwickelt, die aufgrund ihrer Ausdehnung nicht in den synaptischen Spalt diffundieren können. Werden diese Nanopartikel mit einem selektiven NMDA-Rezeptorantagonisten funktionalisiert, sollten ausschließlich die extrasynaptischen NMDA-Rezeptoren blockiert werden ohne die synaptischen NMDA-Rezeptoren zu erreichen. Zunächst wird daher in dieser Arbeit die gezielte Darstellung von Gold Nanopartikeln mit einem vorher bestimmbaren Durchmesser ( größer 30 nm) optimiert, die zudem eine geringe Größenverteilung besitzen. Um die synthetisierten Nanopartikel vor Aggregation zu schützen, werden sie mit einer gemischten Monolage aus Amino- und Carbonsäure terminierten thiolierten Polyethylenglykol (PEG)-Liganden versehen. Diese stabilisieren die Partikel einerseits aufgrund sterischer und elektrostatischer Effekte der Carbonsäure, während die Aminogruppen der weiteren Biofunktionalisierung dienen. Das synthetisierte Alkyl-PEG 600 System wird hierzu mit dem kommerziell erhältlichen PEG 3000 System verglichen. Die resultierenden Nanopartikel beider Systeme besitzen eine hohe Stabilität bezüglich Aggregation in hochkonzentrierten Salzlösungen sowie Zellkulturmedium. Neben der Charakterisierung der Schichtdicke der Polymere werden die Nanopartikel auf ihre chemische Zusammensetzung der Passivierungsschicht untersucht. Hierzu dient ein in der vorliegenden Arbeit entwickeltes, neuartiges fluoreszenz-basiertes Verfahren. Die Anzahl reaktiver Aminogruppen auf der Oberfläche kann so quantitativ bestimmt werden, wodurch die Desorption der thiolierten Liganden mit der Zeit von der Goldoberfläche beobachtet wird. Weiterhin wird gezeigt, dass die Anzahl der gebundenen Aminogruppen beeinflusst und kontrolliert werden kann. In einem analogen fluoreszenz-basierten Verfahren wird die durchschnittliche Anzahl an bioaktiven Peptiden pro Partikel bestimmt - eine wichtige Information zur Untersuchung von Rezeptor-Liganden-Wechselwirkungen im Hinblick auf multivalente Liganden. Das Verfahren zeigt erstmals, dass das Alkyl-PEG 600 System eine direkte Bindung der Peptide an die Oberfläche der Partikel unterbindet, während im kommerziellen PEG 3000 System eine solche unerwünschte direkte Bindung nicht verhindert werden kann. Damit ist das Alkyl-PEG 600 System für die kontrollierte und definierte Darstellung von Peptid-Nanopartikel-Konjugaten besser geeignet, als das kommerziell erhältliche PEG3000 System. Zur Untersuchung der Wechselwirkung der Peptid-funktionalisierten Nanopartikel mit NMDARezeptoren wird ein Modellsystem eingesetzt, in welchem HEK 293 Zellen transient mit Plasmiden der NMDA-Rezeptoruntereinheiten transfiziert werden. In diesen Zellexperimenten kann die spezifische Wechselwirkung der Peptid-funktionalisierten Gold Nanopartikel sowohl qualitativ mittels elektronenmikroskopischen Aufnahmen, als auch quantitativ in einer Bindungsstudie nachgewiesen werden. Zudem wird die Bindungskonstante der Konjugate bestimmt, die um einen Faktor 1000 größer ist, als die des löslichen Antagonisten. Damit wird bestätigt, dass die hergestellten biofunktionalisierten Nanopartikel für die Anwendung im biologischen System bestens geeignet sind.
In optical microscopy fluorescent molecules are used to label target structures like proteins or DNA.With confocal microscopy, a complex of multiple fluorescent molecules is detected as a point spread function due to the diffraction limit. A particular challenge is to determine the number of molecules hiding behind the point spread function. In this work an extended method for determining the number of fluorescent molecules is presented. The method is based on photon antibunching, which is the phenomenon that a single fluorescent molecule can emit only one photon at a time. A statistical analysis of coincidently detected photons can be used to determine the number of photon emitters. In previous works the maximal number of molecules that can be distinguished was about 3. This has now been extended by doubling the number of detectors from 2 to 4, so that up to 4 simultaneously emitted photons can be detected. A new data analysis procedure was established according to the changes of the scheme. Simulations have shown that in theory up to 50 molecules can be resolved under realistic conditions. These predictions were experimentally validated with immobilized dsDNA labeled with 5 fluorophores. The consideration of photobleaching in the data analysis and the use of a photo-stabilizer enable up to 15 molecules to be determined. Thus, this method provides a promising tool for determining the stoichiometry of various biomolecular complex, which can not be achieved by normal microscopic methods.
In der vorliegenden Arbeit wird die Komplexbildung von Cm(III) und Eu(III) mit BTP- und BTBP-Liganden, welche als potentielle Extraktionsmittel zur technischen Umsetzung des SANEX-Prozesses im Rahmen der Partitioning & Transmutation-Strategie diskutiert werden, untersucht. Beide Ligandenklassen vermögen trivalente minore Actiniden selektiv in Gegenwart von Lanthaniden zu extrahieren, die Ursache ihrer Selektivität ist jedoch bisher weitgehend unverstanden. Ziel der Arbeit ist es, die Komplexbildung von BTP- und BTBP-Liganden mit trivalenten minoren Actiniden und Lanthaniden unter prozessrelevanten Bedingungen zu unter¬suchen und hieraus bedeutende Erkenntnisse über die Triebkraft der Selektivität auf molekularer Ebene zu erhalten. Die spektroskopische Quantifizierung der Komplexspezies in Lösung erfolgte mittels der zeitaufgelösten Laserfluoreszenzspektroskopie (TRLFS), welche für die verwendeten Metall¬ionen Cm(III) und Eu(III) eine hochempfindliche und selektive Speziationsmethode darstellt. Anhand von spektroskopischen Untersuchungen zur Komplexierung von n-Pr-BTP in 1 Octanol wurde gezeigt, dass die Stabilitätskonstanten der extraktionsrelevanten 1:3-Komplexe im Falle des Cm(III) fünf Größenordnungen höher sind als die der entsprechenden Eu(III)-Komplexe, worin sich die Selektivität der Liganden bezüglich der Extraktion widerspiegelt. Anhand von Untersuchungen zur Komplexbildung im Wasser-Methanol-Gemisch wurden die höheren Stabilitätskonstanten auf Unter¬schiede in der Reaktionsenthalpie (ΔH) zurückgeführt. Erstmalig wurde der Einfluss elektronischer Parameter SANEX-relevanter Liganden auf Extraktion und Komplex¬bildung gezielt untersucht. Hierzu wurde n-Pr-BTP mit einer Methoxy- beziehungsweise Chlorofunktion in 4-Position derivatisiert. Die Basizität der Liganden steigt hierbei mit der Elektronendichte im aromatischen System an. Es wurde gezeigt, dass die Erhöhung der Basizität sowohl mit der Erhöhung der Stabilitätskonstan¬ten der 1:3-Komplexe als auch mit höheren Verteilungsverhältnissen und Trennfaktoren bezüglich der Extraktion einhergeht. Im Falle der Komplexierung von Cm(III) und Eu(III) mit BTBP-Liganden in 1-Octanol weisen die Stabilitätskonstanten der extraktionsrelevanten 1:2 Komplexe im Falle des Cm(III) um eine Größenordnung höhere Stabilitätskonstanten als die entsprechenden Eu(III)-Komplexe auf, was die Ursache ihrer Selektivität bezüglich der Extraktion darstellt. Durch Untersuchungen im Wasser-Isopropanol-Gemisch wurden Unterschiede in ΔH als thermodynamische Triebkraft der Selektivität bestimmt. Die erhaltenen Daten korrelieren sehr gut mit experimentell bestimmten Trennfaktoren. Darüberhinaus wurden zwei neue Extraktionsliganden entwickelt, deren Strukturen sich von den BTP-Liganden (CA-BTP) und den BTBP-Liganden (Me-BBTBP) ableiten. CA-BTP stellt hierbei eine bedeutende Entwicklung im Hinblick auf die technische Umsetzung des SANEX-Prozesses dar. Es handelt sich um den ersten unter prozessrelevanten Konditionen hydrolysestabilen selektiven Liganden, dessen schnelle Massentransferkinetik den Einsatz in einem technischen Einsatz ermöglicht. Me-BBTBP stellt dagegen das erste Mitglied einer neuen Ligandenklasse dar, welche nun bezüglich ihrer Extraktions- und Komplexierungseigenschaften weiter untersucht werden. Im Rahmen dieser Arbeit konnten erstmals durch Untersuchungen zur bevorzugten Komplexbildung von trivalenten Actiniden im Vergleich zu Lanthaniden mit BTP- und BTBP-Liganden unter vergleichbaren, prozessrelevanten Bedingungen wichtige Informationen über die molekulare Ursache der Selektivität dieser Ligandensysteme erhalten werden, die eindeutig auf Unterschiede in der Reaktionsenthalpie zurückgeführt werden kann. Dies stellt einen bedeutenden Baustein zum Verständnis der Selektivität dieser Ligandenklassen dar und ist unverzichtbar für eine Optimierung der Extraktionsmittel im Hinblick auf die zukünftige technische Umsetzung des SANEX-Prozesses.
The gel-like hyaluronan (HA) rich coat that surrounds many cells has been linked to a variety of vital cellular functions, but the regulatory mechanisms at the cell-HA matrix interface remain poorly understood. For the thorough investigation of specific interactions between the cell surface and HA as well as the structural properties of this supra-molecular matrix, it is desirable to switch from the complex cellular environment to simplified systems. This work aims to find routes towards the development of new in-vitro model systems of HA-rich coats. One approach relies on the immobilization of ectodomains of HA's main cell surface receptor, CD44, on supported lipid membranes (SLBs). Model surfaces with tunable receptor density are exploited to investigate the polyvalent interaction between HA and CD44 in a biologically relevant arrangement. On surfaces that provide a high density of receptors, HA binding increases in a sigmoidal fashion with molecular weight, and becomes reversible below 30 kDa. The physico-chemical properties of these HA films reveal many similarities between the binding behavior of HA chains and flexible polymer chains adsorbing to a homogeneously attractive surface. On surfaces with low receptor surface density binding of HA of sufficiently high molecular weight is irreversible for all, and proportional to the amount of receptors. Quantifying the number of receptors that are available per HA chain provides insight how polyvalent interactions stabilize HA binding on receptor covered surfaces. HA binding is though regulated by both polyvalency and the intrinsic affinity of individual receptors, and we outline a method to disentangle the contributions of both effects. Another approach envisages the immobilization of HA via a terminal biotin moiety at controlled anchor separation. The binding and activity of biotin-receptors on gold and silica is systematically examined with the objective to selectively functionalize gold nanostructured surfaces. We find that streptavidin adsorbs in a functional conformation on gold while resisting binding to silica. First attempts to exploit this selectivity on gold nanostructures are presented. The confinement of the model systems to solid supports enables qualitative and quantitative characterization by complementary surface sensitive techniques. Here, quartz crystal microbalance with dissipation monitoring and ellipsometry - alone or in combination - as well as microinterferometry provide detailed insight into the formation, stability and morphology of the model surfaces and the HA films, and involved molecular interactions. The developed model systems with tunable properties can serve as a well-controlled experimental platform for the investigation of the interactions between proteins and HA in a supra-molecular context, and between cells and HA-matrices.
Basierend auf der Tatsache, dass Ind2TiMe2 (Ind = η5-Indenyl) ein breit einsetzbarer Katalysator für die Hydroaminierung von Alkinen ist, wurde ein sehr einfaches "hydrieranaloges" experimentelles Protokoll für die Addition der gasförmigen Amine Methyl- und Ethylamin an Alkine entwickelt. Um effiziente Hydroaminierungsreaktionen zu erreichen, ist es ausreichend, eine Mischung aus dem Alkin und dem Katalysator Ind2TiMe2 in Toluol bei einer Temperatur von 80 °C (terminale Alkine) oder 105 °C (interne Alkine) unter einer Atmosphäre des jeweiligen Amins bei konstantem Druck (1 atm) zu rühren. Nach einer sich direkt anschließenden Reduktion der zunächst gebildeten Imine können als Endprodukte Methyl- und Ethylamin-Derivate erhalten werden. Insgesamt ist die komplette Hydroaminierungs-Reduktions-Sequenz als einfaches Eintopf-Verfahren durchführbar. Werden als Alkine unsymmetrisch substituierte 1-Phenyl-2-alkylalkine eingesetzt, so bilden sich mit dem neuen Verfahren mit guter bis sehr guter Ausbeute und mit meist sehr hoher Regioselektivität biologisch hoch interessante 2-Phenylethylamin-Derivate, die einen kleinen Methyl- oder Ethyl-Substituenten am N-Atom tragen. Im Rahmen einer nachfolgenden Studie wurde versucht, ein Verfahren zur enantioselektiven intramolekularen Hydroaminierung von Alkinen zu entwickeln. Zu diesem Zweck wurde zunächst eine Reihe prochiraler Aminodialkine synthetisiert und anschließend in Desymmetrisierungsreaktionen in Gegenwart von chiralen und enantiomerenreinen Ti-Katalysatoren eingesetzt. Hierfür kamen entweder kommerziell erhältliche chirale Ti-Komplexe zum Einsatz oder es wurden in situ generierte Mischungen aus Ti(NMe2)4 und etablierten chiralen Liganden verwendet. Da die hierbei erhaltenen Enantiomerenüberschüsse leider nicht sehr erfreulich waren (≤ 31 %), wurde ein neuer helicaler Dithiaalkanediylbis( phenolato)-Ligand vom [OSSO]-Typ, der ein trans-1,2-Cyclohexandiyl-Rückgrat besitzt, in zwei Stufen aus kommerziell erhältlichen Ausgangsmaterialien hergestellt. Erfreulicherweise zeigte sich, dass die bei der Mischung dieses Liganden mit Ti(NMe2)4 oder Zr(NMe2)4 gebildeten Bis(phenolato)-Komplexe als Katalysatoren für die Hydroaminierung von Alkinen und Alkenen eingesetzt werden können. Leider gelang die Trennung der Enantiomere des neuen Liganden vom [OSSO]-Typ bisher nicht, weshalb er noch nicht für die geplanten enantioselektiven Hydroaminierungsreaktionen eingesetzt werden konnte. Zusätzlich konnte gezeigt werden, dass aromatische Amine in Anwesenheit von katalytischen Mengen wässriger HI mit Alkenen zu den korrespondierenden Hydroaminierungs- und Hydroarylierungsprodukten reagieren. Während die Hydroaminierungsreaktion beim Einsatz aliphatischer Alkene der bevorzugte Reaktionsweg ist, kommt der Hydroarylierungsreaktion eine größere Bedeutung zu, wenn mit Styrolen gearbeitet wird. Generell haben die elektronischen Eigenschaften der Alkene und Amine einen großen Einfluss auf die Effizienz und Selektivität der Reaktion.
Stimulated emission depletion (STED) nanoscopy has emerged as a powerful far-field technique for subdiffraction optical imaging and is extensively used in the life sciences to investigate different protein species. In many cases, however, the relative assembly of two (or more) proteins is of interest and needs to be determined with nanometric resolution. Meanwhile, STED has also found its way into material science. Yet, the method’s potential for subdiffraction optical writing has so far remained unexplored. This work evidences the development of a dual-color STED setup with lateral resolving power of 30 nm in both color channels. The method is shown to be applicable to the study of double-stained neuronal proteins and aids in establishing a novel sample sectioning technique. As a result the first high-resolution three-dimensional reconstruction of dual-color STED images is rendered possible. Flexible operation of the individual color channels furthermore answers open questions in chemistry and biology. Another key point of this thesis is the realization of STED nanolithography. Subdiffraction-sized structures are written by bleaching a layer of fluorophores. The underlying concept of bleaching suppression through STED is experimentally introduced and theoretically described by a photophysical model. Numerical simulations corroborate the experimental findings. The presented studies take multicolor STED nanoscopy close to macromolecular resolution and thus open up new methodical perspectives in the life sciences. STED nanolithography, on the other hand, has the potential of becoming an alternative to classical photolithography, thus simplifying high-resolution optical data storage.
Prof. Dr. Lutz Gade und Prof. Dr. Peter Hofmann stellen in Campus-TV die Heidelberger Katalyseforschung vor Einblicke in die Spitzenforschung am Sonderforschungsbereich 623 „Molekulare Katalysatoren: Struktur und Funktionsdesign“ der Universität Heidelberg bietet Campus-TV in seiner Sendung von September 2009. Der Sonderforschungsbereich ist an der Fakultät für Chemie und Geowissenschaften angesiedelt und wird in einer dritten Förderperiode von der Deutschen Forschungsgemeinschaft gefördert. Prof. Dr. Lutz Gade und Prof. Dr. Peter Hofmann stellen in dem TV-Beitrag die innovative Heidelberger Katalyseforschung vor. Im Mittelpunkt des SFB 623 steht das Verständnis molekularer Katalysatoren. Die Forschung wird neue Erkenntnisse eröffnen, wie systematischer als bisher neue Katalysatoren entwickeln werden können. In dem von der Universität Heidelberg und der BASF gemeinsam betriebenen Forschungslabor „CaRLa“ sollen die Erkenntnisse aus der Grundlagenforschung des Sonderforschungsbereichs in Anwendungen umgesetzt werden.
Um die Chemie auf Siliziumeinkristalloberflächen zu untersuchen wurden diese sowohl mit verschiedenen anorganischen Atommonolagen als auch mit organischen Submonolagen terminiert und mit spektroskopischen und massenspektrometrischen Methoden charakterisiert. Zunächst wurden die Anbindungsreaktionen der untersuchten Terminierungen mittels FTIR-Spektroskopie analysiert und optimiert. Die weitere Charakterisierung erfolgte mittels laserinduzierter thermischer Desorption (LITD), Röntgen-Photoelektronen-Spektroskopie (XPS) und spektroskopischer Ellipsometrie (SE). Zu den untersuchten Funktionalisierungen zählten die anorganischen wasserstoff- (Si(111):H) und halogenterminierten (Si(111):Cl, :Br, :I) Oberflächen sowie die organischen silylierten und methylterminierten(Si(111):CH3) Oberflächen. Erstmals gelang die Herstellung halogen- und methylterminierter Oberflächen mittels konventioneller Schutzgaschemie im Schlenk-Kolben. Eine photochemische Umsetzung der Si(111):H-Oberfläche mit den jeweiligen Dihalogengasen führte in Form einer radikalischen Substitution zur entsprechenden halogenierten Oberfläche. Eine nucleophile Substitution der Si(111):Cl-Funktionalität mit einem Grignard-Reagenz (CH3MgCl) endete in der methylierten Si(111):CH3-Oberfläche. Die mittels LITD ermittelten Flugzeitmassenspektren belegen die erfolgreiche Oberflächenanbindung der jeweiligen Halogene und der Methylgruppe. Die Halogene desorbierten atomar und mit steigender Elektronegativität als SiXn-Cluster, was zu einer Aufrauung der Oberfläche führte. Die Methylgruppen desorbierten sowohl als Methylfragmente als auch assoziativ in Form von Ethyl- und Propylfragmenten. Die zur Auswertung der LITD-Massenspektren benötigte Desorptionstemperatur wurde aus der numerischen Anpassung der gemessenen Flugzeitverteilungen der Si(111):H- und Si(111):CH3-Oberflächen ermittelt. Die Rechenroutine passte gleichzeitig vier, bei unterschiedlicher Laserfluenz gemessene,Desorptionsspektren an. Die Oberflächentemperatur bei der Desorption konnte mit einer Genauigkeit von ± 15 K abgeschätzt werden. Bei den organischen silylierten Terminierungen handelte es sich um Dialkyl und Diarylsilylfunktionalisierungen des Typs -R2SiH (R = Me, i-Pr, t-Bu, Ph). Eine Kondensationsreaktion mit den Silanolgruppen der natürlichen Oxidschicht der Siliziumoberfläche führte zur Ausbildung der Submonolagen. Die freie SiHFunktionalität zeichnete diese Oberflächenmodifikationen aus. Zum einen konnte die Lage ihrer Schwingungsbanden berechnet und zum anderen die selektive Oxidation in einer wässrigen KMnO4-Lösung zur SiOH-Gruppe erzielt werden. Diese an der Oberflächenfunktionalisierung neu gebildete Ankergruppe ermöglichte unter Ausbildung einer Siloxanbrücke die Anbindung eines weiteren Dialkyl- bzw. Diarylsilylbausteins. So war es möglich, auf der Siliziumoberfläche gezielt Siloxanketten wachsen zu lassen. Diese schrittweise eindimensionale bottom-up-Synthese wurde mit vier voneinander unabhängigen Methoden nachgewiesen: ATR-FTIR-Spektroskopie, XPS, SE und Kontaktwinkelmessungen.
All cells in our body are surrounded by Extra Cellular Matrix (ECM), from which they derive biochemical, structural and mechanical signals. One of the main fibrillar ECM protein components is Fibronectin (Fn), which is believed to act as a mechanochemical signal transducer. A current hypothesis is that Fn can undergo structural transitions upon stretching, which can alter Fn binding site accessibility and ultimately lead to an adapted cell response. While this hypothesis has existed for several years, the lack of suitable model systems prevented its proof. The aim of this work was to (i) produce regular arrays of Fn nanofibrils, (ii) control the alignment, diameter and tensile state of those nanofibrils, and (iii) to determine their structural and mechanical properties. During this work, a new method to create regular arrays of Fn nanofibrils was developed. This method allows the control of nanofibril directionality and diameter and can also be used to produce nanofibrils from other ECM proteins, such as Laminin (LM) and Collagen (COL). The method depends both on a protein’s ability to accumulate at the air-buffer interface and its ability to self-associate. The production of nanofibrils from various polymers that share these properties is thus possible. The resulting nanofibrillar arrays can be produced on a variety of mirostructured materials, ranging from Silicon over Poly(dimethylsiloxane) (PDMS) to Polyurethane (PU). The biofunctionality of different ECM nanofibrillar arrays was demonstrated by specific cell adhesion after nanofibril transfer onto non-fouling Polyethyleneglycol (PEG) hydrogels. An investigation of both the molecular structure and the mechanical properties of Fn nanofibrils was performed by Förster Resonance Energy Transfer (FRET) and Atomic Force Microscopy (AFM) experiments. Fn molecules form a surface film after application of Fn into a drop of Phosphate Buffered Saline (PBS). FRET analysis of Fn was performed to determine the degree of Fn molecular unfolding. It could be shown that Fn within surface films only unfolds upon surface dewetting, which coincides with nanofibril formation. The produced nanofibrils show an elongation at break of 200 %. Ruptured nanofibrils retract to 30 % of their original length, but the Fn molecules within nanofibrils do not re-fold completely, as derived from FRET measurements. The pre-strained Fn nanofibrils display a high effective Young’s modulus of E ~ 0.1 - 6 GPa, as determined by AFM experiments. In summary, the production, control and characterization of novel ECM models was accomplished in this work, which can be used to investigate cell adhesive response.
In der vorliegenden Arbeit wurden die Intermediate der Nichthäm-Eisen-Oxidationskatalyse mit den Eisenkomplexen von Bispidinliganden (substituierte 3,7-Diazabicyclo[3.3.1]-nonanone) untersucht. Diese Komplexe besitzen interessante katalytische Eigenschaften, durch die sie als funktionelle Modelle für eisenhaltige Monooxygenasen betrachtet werden können. Unter anderem katalysieren sie die hier beschriebene Oxidation von Olefinen zu Epoxiden und Dialkoholen. In einem ersten Kapitel wird die Oxidation des Komplexes [(L)Fe(H2O)](OTf)2 wobei L ein vierzähniger Bispidinligand ist, mit verschiedenen Oxidationsmitteln beschrieben. Hierbei konnte gezeigt werden, daß mCPBA und TBHP ls-Fe(III) -Alkyl- und Acylperoxo- Komplexe bilden, die zu Oxoeisen(IV)-Komplexen zerfallen. Mittels zeitabhängiger UV-Vis-Spektroskopie konnten ihnen Banden bei 610 nm (Alkylperoxo), 625 nm (Acylperoxo) und 768 nm (Oxo) zugeordnet werden. Mit PhI(OAc)2 entsteht hingegen direkt eine FeIV -Spezies mit einer Bande bei 715 nm. Die Anwesenheit von Cycloocten verschiebt diese Bande zu 737 nm. Außerdem ändert sich der Extinktionsverlauf hin zu einem exponentiellen Zerfall. Weiterhin wurden mit mCPBA und TBHP im ESR Singulett-Signale erhalten, die möglicherweise von Hydroxylradikalen stammen. Bei der Reaktion von [(Lo)Fe(X)](BF4)2 , wobei Lo ein fünfzähniger Bispidinligand ist, mit Cycloocten und H2O2 im Überschuß entsteht eine relativ langlebige violette Spezies mit einer Bande im UV-Vis-Spektrum bei 538 nm sowie einem ls-FeIII -Signal im ESR-Spektrum mit g-Werten im Bereich von 2,1. Dies deutet darauf hin, daß es sich um einen Fe(III) -Hydroperoxokomplex handelt. Diese Zuordnung wird durch ESI-MS-Spektrometrie bestätigt. Das Katalyse-System mit dem Liganden Lo , Cycloocten als Substrat sowie H2 O2 wurde mittels ESI-MS untersucht. Es wurde hierbei eine Reihe von Peaks identifiziert, die modifizierten metallfreien Liganden zuordenbar sind, was auf einen Zerfall des Komplexes hindeutet. Weitere Spezies konnten, auch mit Bestätigung durch Markierungsexperimente mit H2O2 , als Hydroperoxo und Hydroxokomplexe identifiziert werden. Koordiniertes Cycloocten konnte nicht beobachtet werden. Mit dem Komplex [(L)Fe(H2O)(MeCN)](BF4)2 wurden in einem Methanol-Wasser- Gemisch ebenfalls Derivate des freien Liganden detektiert, unter anderem N-Oxide der Pyridylgruppen, sowie einige FeIII -Superoxo-Komplexe Mit Cycloocten wurde eine Spezies mit m/z = 640 beobachtet, die als Verbindung der Form {Fen+ , L, Cycloocten, 2 H2, O} + identifiziert wurde, sowie ein Oxoeisen(IV)-Komplex. Im letzten Kapitel wird die Produkt-Verteilung der katalytischen Oxidation von Olefinen weiter untersucht. Durch Erhöhung der Wasserkonzentration konnte die Epoxid-Ausbeute mit dem Liganden L gesteigert werden. Die FeIV -Oxo-Aqua-Zwischenstufe, die das Olefin zum Epoxid oxidiert, wird also mit Wasser bevorzugt gebildet. Die bei diesen Experimenten festgestellte Differenz der Ausbeuten mit dem Triflatkomplex von L zu literaturbekannten Werten konnte hauptsächlich auf einen dämpfenden Effekt des Tetrafluoroborat-Anions zurückgeführt werden. Der Einsatz des an den Pyridylgruppen methylierten, vierzähnigen Liganden LMe in der Katalyse ergab keinen deutlichen Unterschied zu den Ausbeuten mit dem Liganden L. Die Blockierung der Koordinationsstelle trans zu N3 hat somit keinen Einfluß auf die Reaktivität. Mit dem Katalysatorsystem des Liganden Lo wurden Messungen der Sauerstoffbilanz mittels einer Clark-Elektrode durchgeführt. Hierbei zeigte sich, daß die Sauerstoffkonzentration in Anwesenheit von Cycloocten wesentlich schneller abnimmt als bei Durchführung der Reaktion lediglich mit dem Eisenkomplex und H2O2 . Die Sauerstoffkonzentration sinkt bereits nach fünf Minuten auf Null. Durch die katalytische Oxidation von cis-2-Hepten wurde abschließend die Regioselektivität und damit die Beteiligung eines kohlenstoffzentrierten Radikals an der Oxidation mit [(Lo)Fe(II)(X)2]2+ untersucht. Es wurde dabei cis/trans-Isomerisierung beobachtet, was die Beteiligung eines Radikals an der Katalyse unterstützt.
This work is concerned with the synthesis, chemical reactivity, and characterization of new binuclear boron compounds containing bridging guanidinate ligands. The guanidine-borane adducts H3B·hppH and H3B·N(H)C(NMe2)2, accessed by a base exchange reaction between H3B·NMe3 and the guanidine derivative hppH or N(H)C(NMe2)2, were targeted as precursors in thermal and catalytic dehydrogenations. The reaction mechanism for these experiments was elucidated by means of quantum chemical (DFT) calculations on the model H3B·N(H)C(NH2)2. In contrast to H3B·hppH, the thermal dehydrogenation of H3B·N(H)C(NMe2)2 is accompanied by decomposition, leading to methylimino borane oligomers, [HBNMe]n. The decomposition pathway was studied and understood with the aid of quantum chemical calculations. Faster dehydrogenation could be initiated by addition of a catalyst. The dehydrogenation of H3B·hppH in presence of a catalyst leads to the binuclear B(III) hydride [H2B(hpp)]2, containing two guanidinate (hpp)Ligands. Further (reductive) catalytic dehydrogenation of [H2B(hpp)]2 gave the double-base stabilized diborane(4) [HB(hpp)]2, featuring direct B-B bonding. Besides, [HB(hpp)]2 undergoes an oxidative addition reaction with HX (X = Cl- or I-), respectively which afforded [H3B2(hpp)2]X, representing a stable B2H5+ analogues. Quantum chemical (DFT) calculations were carried out to analyse the bond properties in the cationic binuclear B(III) hydride [H3B2(hpp)2]+. The reaction between BCl3 and hppH lead to [Cl2B2(hpp)3]BCl4 containing three guanidinate (hpp) ligands, which suggests that this reaction has a much more difficult mechanism than the H3B·NMe3/hppH reaction. B2Cl2(NMe2)2 reacts with hppH to yield [{(Me2(H)N)B(hpp)}2]Cl2, featuring the first representative of two B(II) cations with direct B-B bonding. Further reactions between [{(Me2(H)N)B(hpp)}2]Cl2 and AgOTf or Li[B(C6F5)4] yielded new salts with weakly coordinating anions. Additionally, thermal decomposition of [{(Me2(H)N)B(hpp)}2]X2 (X = Cl-, OTf- and [B(C6F5)4]-) was investigated on the basis of NMR experiments.
Im Rahmen dieser Arbeit wurde die Wechselwirkung dreiwertiger Actiniden und Lanthaniden mit Ca2+-haltigen Mineralphasen untersucht. Als Hauptuntersuchungsmethode diente die site-selektive zeitaufgelöste Laser-Fluoreszenzspektroskopie (engl.: time-resolved laser fuorescence spectroscopy, TRLFS). Mit Hilfe dieser Methode konnten insgesamt 19 Eu3+- und Cm3+-Spezies in acht verschiedenen Mineralphasen identifiziert und weitgehend charakterisiert werden. Aus den Beobachtungen in verschiedenen Systemen konnten zudem Mechanismen und Einflussgrößen abgeleitet werden, die die Sorptions- und Einbauprozesse steuern. Stets handelt es sich um direkt auf den spektroskopischen Daten beruhende Schlussfolgerungen, die ein molekulares Prozessverständnis ermöglichen. Auf diese Weise tragen die gewonnenen Erkenntnisse zur Verlässlichkeit eines Langzeitsicherheitsnachweises für ein Endlager für radioaktive Abfälle bei. Der Fokus der Studien lag auf der Bildung von "solid solutions" dem strukturellen Einbau eines Gastions in ein Wirtsgitter. Dieser Prozess ist von besonderem Interesse, da er bisher kaum untersucht, und daher auch kaum für Sicherheitsanalysen berücksichtigt ist. Trotz dieser Vernachlässigung stellt der strukturelle Einbau allerdings einen hocheffizienten Retardierungsmechanimus dar. Eine Remobilisierung des Actinids erfolgt bei Auflösung des Wirtskristalls oder wenn die Actinidkonzentration in der umgebenden Lösung unter einen bestimmten Wert absinkt. Somit wäre zur Remobilisierung eine drastische Änderung im geochemischen Milieu notwendig. Zudem ist die Bildung von "solid solutions" ein entropischer günstiger Prozess, der thermodynamisch favorisiert sein kann, wenn der mit der Bildung einhergehende Enthalpieverlust klein ist. Die Enthalpieänderung des Systems hängt zum einen von der im System induzierten Gitterspannung, also im Wesentlichen vom Verhältnis der Ionenradien von Gast- und Wirtsion und der Flexibilität des Gitters ab. Andererseits muss die Koordinationssphäre des Gastions durch diejenige des Kristallgitters ersetzt werden. Die durch die Gitterspannung verursachte positive Enthalpie ist für die untersuchten (und für das Endlager relevanten) verdünnten "solid solutions" bei günstigem Verhältnis der Ionenradien von Gast- und Wirtskation gering. Dies ist gegeben, da die Ionenradien von Cm3+ und Ca2+ nahezu identisch sind und die Konzentrationen der Gastkationen stets unter 1000ppm bleiben (im Falle des Cm3+ sogar unter 10ppm). Die Untersuchung der Ligandenaustauschkomponente der Enthalpie ist ein wesentlicher Bestandteil dieser Arbeit. Die untersuchten Mineralphasen sind Calcit, Aragonit und Vaterit CaCO3, sowie Gips CaSO4 2H2O, Fluorit CaF2, Apatit Ca5(PO4)3(OH, F), Powellit CaMoO4 sowie ein Ca2+/Eu3+-substituierter Sodalith der Zusammensetzung (Ca7,5Eu0,5)(OH)8 (Al8,5Si3,5O24). Alle zeigen Wechselwirkung mit den dreiwertigen Actiniden und Lanthaniden, die sich in ihrer jeweiligen Ausprägung jedoch unterscheiden. Bis auf Gips, zeigen alle Minerale die Bildung von "solid solutions", der Prozess ist aber nicht in allen Fällen identisch.
Um chemische Prozesse besser zu verstehen und zu optimieren sind systematische Studien des Reaktionsmechanismus von fundamentaler Bedeutung. Die Kenntnis der Kinetik spielt hierbei eine zentrale Rolle. Durch die Kombination von Reaktion und Analyse in einem chromatographischen Reaktor (on-column Reaktionskapillarelektrophorese ocRCE bzw. on-column Reaktionsgaschromatographie ocRGC) können Geschwindigkeitskonstanten und Aktivierungsparameter präzise und umfassend bestimmt werden. In der vorliegenden Arbeit wird diese Strategie angewendet, um kinetische und mechanistische Details verschiedener (katalytischer) Prozesse zu untersuchen, wobei unterschiedliche chromatographische Methoden zum Einsatz kommen. Nach einer Einleitung in Kapitel 1, die sich zunächst mit allgemeinen Aspekten der Reaktionskinetik und der on-column Reaktionschromatographie beschäftigt, wird in Kapitel 3 detaillierter auf die Berechnung kinetischer Daten aus experimentellen Chromatogrammen bzw. Elektropherogrammen für verschiedene Reaktionstypen eingegangen. In Kapitel 4 wird die Interkonversion chiraler Tris(1,10-Phenanthrolin)- und Tris(2,2’-Bipyridyl)-Übergangsmetallkomplexe mithilfe der dynamischen mizellaren elektrokinetischen Chromatographie (DMEKC) untersucht, die eine Trennung der Komplexe ermöglicht. Durch Anwendung der Unified Equation können aus den gemessenen dynamischen Elutionsprofilen, die sich typischerweise durch die Ausbildung eines Plateaus zwischen den Peaks auszeichnen, Geschwindigkeitskonstanten und aus temperaturabhängigen Messungen Aktivierungsparameter berechnet werden. Durch die systematische Variation der Reaktionsbedingungen (Laufpuffer, Temperatur) sowie des Übergangsmetalls und des Liganden werden umfassende Datensätze generiert, die zu einem besseren Verständnis des zugrunde liegenden Interkonversionsmechanismus beitragen. DesWeiteren wird die Synthese des Tris(1,10-Phenanthrolin)-Nickel(II)-Komplexes aus Ni(II)-Salzen und dem Liganden mit der ocRCE untersucht und aus den Elektropherogrammen wird der Enantiomerenüberschuss bestimmt. Die Untersuchung der katalytischen Hydrierungen ungesättigter Verbindungen über hoch aktiven Palladiumnanopartikeln (Pd-NP) mithilfe der ocRGC wird in Kapitel 5 beschrieben, wobei die Nanopartikeln in einer Polysiloxanmatrix stabilisiert und auf einer fused-silica Kapillare immobilisiert sind. Durch die systematische Variation der stabilisierenden Polysiloxanmatrix, des Beladungsgrads des Palladiumprekursors sowie der Katalysatorvorbehandlung wird anhand umfangreicher TEM-Messungen die Abhängigkeit der Größe und Morphologie der Nanopartikel von diesen Faktoren untersucht. Mit diesen katalytisch aktiven stationären Phasen werden Hydrierungen einer Substratbibliothek in ocRGC-Experimenten durchgeführt, um temperaturabhängige Geschwindigkeitskonstanten, Aktivierungsparameter sowie Diffusionskoeffizienten der Substrate in der Polysiloxanmatrix zu bestimmen. Kapitel 6 beschreibt die Derivatisierung von Aminosäuren (AS) mit L-Phthaldialdehyd (OPA) mithilfe der ocRCE. Bei diesem Konzept werden die Reaktanden sukzessive auf fused-silica Kapillaren injiziert, so dass aufgrund der unterschiedlichen Migrationszeiten im elektrischen Feld eine Überlappung der Substratvolumina und somit die Reaktion in der Kapillare stattfindet. Durch gezielte Variation der Eduktkonzentrationen können mechanistische Details anhand der Umsätze studiert werden. Darüber hinaus wird das neue Computerprogramm ocRCXplorer vorgestellt, mit dem Reaktionsgeschwindigkeitskonstanten für Reaktionen zweiter Ordnung aus ocRCE-Experimente auf der Basis des theoretischen Bodenmodells der Chromatographie bestimmt werden können.
Das Ziel dieser Arbeit waren Untersuchungen zum Einfluß von gezielten strukturellen Veränderungen an molekularen Katalysatoren auf die Reaktivität und Selektivität von homogenen katalytischen Reaktionen. Aufgrund ihrer speziellen strukturellen Eigenschaften und ihrer Starrheit haben Bispidine und ihre Übergangsmetallkomplexe interessante Eigenschaften in katalytischen Reaktionen. Auf der Basis konkreter Konzepte zur Synthese neuer Liganden wurden chirale Bispidine synthetisiert und deren Eigenschaften ausführlich untersucht. So konnte durch gezieltes Liganddesign in den Liganden L4 und L5 eine Versteifung der Koordinationsumgebung entsprechender FeII-Koordinationsverbindungen erreicht werden. Die damit einhergehende Erhöhung der Epoxidierungsaktivität ist durch zusätzliche Rigidität der Liganden und damit positivere FeIII/FeII Reduktionspotentiale verursacht. Durch die Synthese eines neuen chiralen, tricyclischen Bispidingerüstes gelang die Aufhebung der Spiegelsymmetrie in den Bispidinen. Die Eigenschaften der resultierenden Liganden L7-L9 wurden ausführlich untersucht. So gelang auch die Darstellung optisch reiner CuII-Koordinationsverbindungen mit chiralen, tricyclischen Bispidinderivaten. Weiterhin wird ein Konzept zur Anwendung von chiralen, optisch reinen Naturstoffen in der Bispidin-synthese vorgestellt, mit Hilfe dessen die modulare Synthese tetra- und pentadentater chiraler Liganden möglich ist. Die Ausweitung der Koordinationschemie der Bispidine auf Ruthenium erbrachte neue Einblicke in die Reaktivität und Stereoselektivität der Epoxidierungskatalyse im Vergleich zu Eisen. Desweiteren stellte sich die Verbindung [(L1)RuII(OH2)](ClO4)2 als hoch aktiver Sulfoxidationskatalysator heraus.
Der erste Teil der vorliegenden Arbeit behandelt sequenzspezifische DNA Nachweismöglichkeiten, basierend auf Reaktionen, welche durch Kupfer in drei unterschiedlichen Oxidationsstufen (0, I und II) hervorgerufen werden. Die Esterspaltungsreaktion eines an PNA gekoppelten N-Methyl-2 -imidazolylcarbonsäure-Derivates wurde untersucht. Die Spaltung erfolgte durch ein zweites PNA-Konjugat, welches mit einem Cu(II)-Komplex modifiziert worden war. Beide PNA-Fragmente binden an direkt benachbarte Stellen doppelsträngiger DNA, wodurch die reaktiven Gruppen in unmittelbare Nähe zueinander gebracht werden und somit die Esterspaltungsreaktion beschleunigt wird. Nach der Hydrolyse trat N-Methyl-2-imidazolyl-carbonsäure aus, was mittels MALDI-TOF Massenspektrometrie verfolgt werden konnte. Ein fluoreszenzspektroskopischer DNA-Nachweis gelang mit Hilfe der Cu(I)- katalysierten (2+3)-Huisgen-Cycloaddition, auch Click-Reaktion genannt. Hierzu wurden zwei kurze DNA-Stränge modifiziert. Der eine wurde am 5’-Ende mit einem nichtfluoreszenten, Acetylid-substituierten 1,8-Naphthalimidfarbstoff markiert. Der andere Strang wurde am 3’-Ende mit einem organischen Azid versehen. Beide DNAFragmente binden an direkt benachbarten Stellen an einzelsträngige DNA. Durch Zugabe von Cu(I) wurde das elektronenziehende Acetylid in ein elektronenschiebendes Triazol umgewandelt, was zu einer Zunahme der Fluoreszenz führte. Mit dieser Methode konnte DNA sequenzspezifisch bis zu einer Konzentration von 200 nM nachgewiesen werden. Bei Zugabe von 100 µM CuSO4 und 1 mM NaAsc konnte das Auftreten eines Peaks im Fluoreszenzspektrum bei 580 nm beobachtet werden. Diese zusätzliche Emission beruht auf der Bildung von Cu-Nanoteilchen, welche nur in Gegenwart doppelsträngiger DNA entstehen. Die Detektionsgrenze dieser Methode lag bei 1 nM dsDNA. Im zweiten Teil der Arbeit wird die Synthese, Charakterisierung und Anwendung auf Ferrocen basierender, zellspezifischer Cytostatika beschrieben. In Krebszellen, welche eine deutlich höhere Konzentration an reaktiven Sauerstoffspezies besitzen als gesunde Zellen, wird die synthetisierte Substanz in zwei Cytostatika-Typen mit unterschiedlichen Wirkmechanismen umgewandelt: einerseits entsteht ein Chinonmethid-Derivat, welches den antioxidativen Schutzmechanismus der Zelle beeinflusst. Andererseits werden Fe(II)-Ionen freigesetzt, was die Generierung zusätzlicher reaktiver Sauerstoffspezies katalysiert. Dieser duale Wirkmechanismus erzeugt sehr schnell einen Zustand hohen oxidativen Stresses, was zum Tod der Krebszelle führt. Der IC50-Wert der Substanz liegt bei ~100 µM. Eine ebenfalls auf Ferrocen basierende Kontrollsubstanz zeigt bei dieser Konzentration keine Toxizität.
Die vorliegende Arbeit beschäftigt sich mit der Entwicklung, Synthese und Testung neuartiger Katalysatorsysteme für die Gasphasenoxidation von o-Xylol mittels Hochdurchsatztechnologie. Unter Verwendung von Träger- und Vollkatalysatoren wurde versucht das Edukt o-Xylol mit hoher Selektivität zu einem Zwischenprodukt der Phthalsäureanhydrid-Synthese, bevorzugt o-Tolylaldehyd, umzusetzen. Aufbauend auf den vielversprechenden Ergebnissen der mit H4Mo12SiO40 und Kupfer imprägnierten Trägerkatalysatoren der ersten getesteten Bibliotheken, wurden binäre Kupfermolybdate als Vollkatalysatoren mit unterschiedlichen Stöchiometrien synthetisiert und in unimprägnierter sowie in mit weiteren Elementen (B, Sb, Pb, Mo...) imprägnierter Form für die Partialoxidation eingesetzt. Bei den experimentellen Untersuchungen der unimprägnierten Oxide erzielte das Kupfermolybdat CuMoO4 mit 64% bei 10-15% Umsatz die höchsten o-Tolylaldehydselektivitäten bei hohen Belastungen und o-Xylolkonzentrationen. Es zeigt sich eine starke Abhängigkeit der o-Tolylaldehydselektivität von der durch die Synthese- und Reaktionsbedingungen gebildeten Modifikation des Kupfermolybdats (Strukturwirkungsbeziehung). Die pulverdiffraktometrische Analyse des Oxides CuMoO4 nach der Synthese über Gefrier- und Sprühtrocknung bestätigt das Vorliegen der low pressure Phase (a-CuMoO4 JCPDS: 73-0488 (C)), die sich durch die Reaktionsbedingungen im Reaktor in die mid pressure Phase (CuMoO4-III JCPDS: 77-0699) umwandelt. Diese Umwandlung ist in der Literatur lediglich bei wesentlich höheren Temperaturen und Drücken bekannt. Für die beobachtete Phasenumwandlung spielt das verwendete Konditionierungsprogramm eine entscheidende Rolle, da bei einer zu reduktiven Anfahrweise die Umwandlung des Katalysors verhindert und dadurch die o-Tolylaldehydselektivität erniedrigt wird. Die direkt über hydrothermale Synthese hergestellte mid pressure Modifikation bleibt auch nach der Reaktion erhalten und zeigt ähnliche maximale Selektivitäten wie die durch die Reaktion umgewandelte low pressure Phase. Durch Imprägnierung des Kupfermolybdatgrundmaterials Cu6Mo5Ox mit einer Beladung von 0.095 wt.% Antimon kann die o-Tolylaldehydselektivität bei hohen Belastungen und o-Xylolkonzentrationen auf bis zu 71% bei Umsätzen zwischen 10-16% gesteigert werden. Die für die Kupfermolybdatsysteme erhaltenen Ergebnisse zeigen, dass durch geeignete Wahl der Synthesemethode, des Konditionierungsprogramms, eventuellen weiteren Imprägnierungen und der Reaktionsbedingungen Katalysatorsysteme erhalten werden, die in der Lage sind o-Xylol selektiv in o-Tolylaldehyd und Kohlenstoffdioxid umzusetzen, ohne dass weitere Partialoxidations- oder Zersetzungsprodukte gebildet werden. Wird die Eduktkonzentration erniedrigt oder die Temperatur erhöht, verringert sich die o-Tolylaldehydselektivität und es kommt zunehmend zur Bildung unerwünschter Nebenprodukte. Durch Weiterentwicklung der binären Kupfermolybdate in ternäre Oxide bestehend aus Kupfer, Molybdän und einem weiteren Element (Nb, W, Bi, V, Fe, P, Sb, Ag) konnte für die ternären Systeme Cu0.3Mo0.3Ag0.4 und Cu0.45Mo0.45Ag0.1 eine weitere Steigerung der o-Tolylaldehydselektivität auf bis zu 80% bei 10-15% Umsatz ohne das Auftreten weiterer Partialoxidations- oder Zersetzungsprodukte erzielt werden.
Diese Arbeit zeigt die Vielfältigkeit der Bispidine-Liganden als Bausteine in molekularen Magneten. Durch die Reaktion von Hexacyanometallaten mit Bispidinkomplexen konnte eine Reihe von heterotrinuklearen Verbindungen hergestellt werden. Diese Verbindungen wurden durch experimentelle Messungen und sorgfältige theoretische Betrachtungen untersucht. Die theoretische Analyse beinhaltet drei Modelle zur Simulation der experimentellen Daten. Das einfache Modell 1 basiert auf einem isotropen Austausch-Hamiltonian. Das Modell 2 bezieht auch die Aufspaltung des 2T2g-Grundzustands des Hexacyanoferrat(III)zentrums in die theoretische Betrachtung mit ein. Das Modell 3 wurde benutzt, wenn die experimentellen Daten das Auftreten einer starken Anisotropie zeigen und das Modell 2 aufgrund fehlender Strukturdaten nicht eingesetzt werden konnte. Durch die Verwendung des Modells 2 konnte gezeigt werden, dass eine Abweichung von der perfekten Oktaedergeometrie des Hexacyanoferrat(III)zentrums um wenige Grad eine Verringerung der magnetischen Anisotropie um eine Größenordnung zur Folge hat. Der zweite Teil der vorliegenden Arbeit beschäftigt sich mit mononuklearen Bispidinkomplexen als mögliche Einzelmolekülmagnete. Der Bispidinligand verursacht eine axiale Verzerrung des Metallzentrums, was eine Voraussetzung für das Auftreten einer Nullfeldaufspaltung darstellt und somit die Möglichkeit einer langsamen Relaxation der Magnetisierung eröffnet. Der letzte Teil beschäftigt sich mit einem neuen Bispidinligand, der durch eine Bipyridin Koordinationsstelle die Möglichkeit schafft, Fotoaktivität in eine Verbindung einzuführen. Der Ligand L3 besitzt außer dem Bipyridin-Substituenten eine weitere Koordinationsstelle in Form eines substituierten Bispidingerüsts. Die Untersuchungen des Fluoreszenzverhaltens und der magnetischen Eigenschaften durch ESR-Spektroskopie zeigen einen Energietransfer zwischen einem an das Bipyridin koordinierten Rutheniumion und einem durch den Bispidinbereich komplexierten Kupferion.
Abstract Im Rahmen dieser Arbeit wurde ein neuartiges Bispidinligandensystem der zweiten Generation entworfen und synthetisiert, welches mit Übergangsmetallen wie CoII, NiII, CuII und ZnII verzerrt trigonal-bipyramidale oder trigonal–prismatische Komplexe ausbildet. Hervorzuheben sind die Eigenschaften der Kupfer(II)-Komplexe. Sie weisen eine erstaunlich hohe Komplexstabilität auf. Die Stabilität des vierfach koordinierten Kupfer(II)-Komplex [CuII(L1)(NCCH3)]2+ mit logK = 26.4 bewegt sich in Größenordnung von [CuII(Cyclam)]2+ mit logK = 27.2. Durch die hohe Stabilität von [CuII(L1)(NCCH3)]2+ kann dieser gut in der Radiopharmazie eingesetzt werden. Für den Liganden L1 konnte ein Weg der Funktionalisierung aufgezeigt werden. In der katalytischen Aziridinierung ist [CuII(L1)(NCCH3)]2+ einer der effizientesten Katalysatoren mit 27 min Reaktionsdauer und 70 % Ausbeute bei 0.5 mol % Katalysator. Einblicke in den Mechanismus zeigen eine radikalische Reaktion ohne Änderung der Oxidationsstufe von Kupfer(II). Als Modellsubstanz für kupferhaltige Proteine zeigen die neuen Bispidinliganden eine Vielzahl an end-on-Peroxo, Superoxo- und Hydroperoxo-Verbindungen. Besonders hervorgetan hat sich [CuI(L2)]+, der einen stabilen end-on-Superoxo Komplex ausbildet und reversibel Sauerstoff bindet, [CuII2(L6)(O2)2]2+ bewirkt eine Oxidation seines Ligandengerüsts.
Eine Prozessentwicklung berücksichtigt für katalytische Reaktionen und Reaktionsschritte auch Möglichkeiten, wie der Katalysator rezykliert und seine Leistungsfähigkeit gesteigert werden kann. Die vorliegende Arbeit befasste sich am Beispiel der Hydroformylierung von 1-Octen in überkritischem Kohlendioxid (scCO2) mit der Untersuchung verschiedener Ansätze, wie dieses realisiert werden kann. ScCO2 als Reaktionsmedium bietet den Vorteil, dass durch seine Verwendung das Phasenregime der normalerweise in einem heterogenen Gas-Flüssig-Zweiphasengemisch ablaufenden Hydroformylierung derart eingestellt werden kann, dass sie homogen in der scCO2-Phase verläuft. Damit gleichzeitig die Vorteile einer homogenen Katalyse bestehen bleiben, sind für die Entwicklung entsprechender Verfahren, bzw. Verfahrensschritte auch Daten über die Löslichkeit der Katalysatoren in scCO2 nötig. In dieser Arbeit wurden die Löslichkeiten von Kobaltkomplexen des Typs Co2(CO)6(Phosphan)2 in scCO2 sowie unter Bedingungen, die die Zusammensetzung unter realen Reaktionsbedingungen simulieren, bestimmt. Ausgehend von den Ergebnissen dieser Löslichkeitsuntersuchungen wurde ein Derivat dieses Komplextyps ausgewählt, mit dem die Recyclingfähigkeit in der Katalyse in einer systematischen Reihe von Wiederholungsexperimenten getestet wurde. Das Abscheiden des Katalysators vom Reaktionsgemisch erfolgte durch Änderung der Zustandsvariablen Druck, mit anschließender Mikrofiltration. Die Ergebnisse zeigen, dass ein Katalysatorrecycling nur dann zu akzeptablen Umsatz- und Selektivitätswerten führt, wenn der entsprechende Phosphanligand nachdosiert wird, deutbar als ein Leaching des Liganden in der Sequenz von Reaktion und Trennung. Aus diesem Grund wurden in dieser Arbeit des weiteren Katalysatorsysteme berücksichtigt, von denen eine erhöhte Resistenz gegen Leaching vermutet wird. Grundkonzept dieser Überlegungen ist die Verknüpfung von scCO2 als Reaktionsmedium mit dem SILP-Konzept für die Hydroformylierung mit Rhodiumkomplexen. Die Ergebnisse belegen zunächst, dass das Recyclingverhalten der untersuchten Rhodiumkatalysatoren bereits alleine durch die Anwendung von scCO2 als Solvens deutlich verbessert wird. Die Applikation des SILP-Konzepts, d. h. die Immobilisierung homogener Katalysatoren in einer flüssigen ionischen Matrix auf der Oberfläche fester Trägerpartikel ergab in den vorliegenden Untersuchungen deutliche Hinweise darauf, dass teilweises Rhodium-Leaching die Ursache für eine langsame Abnahme der Aktivität bei wiederholter Verwendung war. Daher wurde im Folgenden untersucht, ob die Leaching-Tendenz durch die Verankerung der Metallzentren über bidendale Donorfunktionen direkt auf einem anorganischen Trägermaterial minimierbar ist. Die Experimente zeigten in diesem Fall, dass über eine Reihe von 14 Wiederholungsversuchen kein Aktivitäts- oder Selektivitätsverlust zu beobachten war. Allerdings wurde durch die Immobiliserung eine deutliche Aktivitätsabnahme verursacht; so sank die TOF50 von 30.000 h-1 (beobachtet für die homogenen Analoga) auf immer noch akzeptable 700 h-1 für den immobilisierten Komplex.
Die Arbeit behandelt die Entwicklung neuer Lanthanidsonden und ihre Anwendung zur Detektion von Nucleinsäuren und Enzymen durch zeitaufgelöste Lumineszenzmessungen. Zum einen wurden dazu Lanthanidkomplex-modifizierte fluorogene Peptidsubstrate, zum anderen Chelator-modifizierte Peptidnucleinsäuren (PNAs) synthetisiert. Im funktionalisierten Peptidsubstrat wird die Lumineszenz des Lanthanidkomplexes durch einen Bis-Azo-Farbstoff (Black Hole Quencher) vollständig gelöscht. Die enzymatische Spaltung des Substrats führt zu einer räumlichen Trennung von Komplex und Quencher und so zu einem deutlichen Signalanstieg. Durch zeitaufgelöste Messung der langlebigen Lanthanidlumineszenz kann Thermolysin sehr empfindlich nachgewiesen werden. Darüber hinaus wurden die besonderen photophysikalischen Eigenschaften der Lanthanidkomplexe zur Detektion von DNA eingesetzt. An beiden Termini mit Chelatoren modifizierte Peptidnucleinsäuren wurden entwickelt und ihre Wechselwirkung mit komplementärer DNA untersucht. Diese führt zur allosterischen Destabilisierung eines zuvor gebildeten zirkularen PNA-Lanthanidkomplexes, wodurch das Metallion freigesetzt wird und mit Hilfe von Sensitizern detektiert werden kann. In einem zweiten auf Signalverstärkung beruhenden Ansatz zur Detektion von DNA fungiert ein zirkularer DNA-Zink-Komplex als Primärsonde für eine komplementäre Ziel-DNA. Auch hier wird das Metallion durch Hybridisierung freigesetzt, jedoch anschließend nicht direkt, sondern indirekt über die Aktivierung eines Zn2+-Cofaktor abhängigen Enzyms Thermolysin nachgewiesen. Eine Signalamplifikation erfolgte katalytisch über die Spaltung des oben beschriebenen fluorogenen Peptidsubstrats, welches ein starkes Lumineszenzsignal erzeugt.
In all subdiffraction fluorescence microscopy techniques, the theoretically infinite attainable resolution is, in practice, limited by the photobleaching of fluorophores. Repetitive scans of the sample required for e.g. three dimensional recordings, increase photobleaching, dark state transitions and, in case of living cells, phototoxicity. To advance such experiments all possibilities to reduce the photobleaching must be explored. In this thesis, various chemical and physical approaches to tackle photobleaching are studied within the context of stimulated emission depletion (STED) microscopy, which is the first and most prominent method for subdiffraction imaging. The STED setup constructed for this purpose allows for the fast adaptation to new fluorescent dyes, and relies on a novel adaptive spectral and phase filter technique. Furthermore, the optical setup facilitates a gentle exposure strategy, in which the time that the dye is irradiated is significantly reduced. Three-dimensional images can therefore be recorded, and the palette of applicable dyes can be expanded to the blue-green regime by the so far unemployed coumarin derivatives, which are known to be prone to photobleaching. The label itself is another vantage point from which photobleaching limitations in subdiffraction microscopy can be circumvented. For the first time, light-driven modulation of the fluorescence from Mn-doped ZnSe quantum nanocrystals has been established through excited-state absorption (ESA). This enables a new type of far-field fluorescence microscopy with diffraction-unlimited resolution based on quantum dots, which are well known for their superior photostability. The correct sample embedding in the refractive index matching is also of high importance, if spherical aberrations and light scattering are to be minimized to optimize the fluorescence collection. For this purpose, an embedding medium, 2,2´-thiodiethanol (TDE) is introduced, which, by being miscible with water at any ratio, allows for refractive index matching up to that of immersion oil and making high resolution recordings deep within the sample feasible.
Guanidiniumsalze (GILs = Guanidinium Ionic Liquids) sind neuartige Ionische Flüssigkeiten mit besonderen Eigenschaften, die sie für eine breite Palette von Anwendungen in industriell relevanten Prozessen interessant machen. Hierzu zählen gute chemische und thermische Stabilität, hohe ionische Leitfähigkeit, sowie Resistenz gegenüber oxidativem Abbau. Das Ziel dieser Arbeit bestand darin zu untersuchen, inwiefern sich GILs in der Oxidationskatalyse in Mehrphasensystemen eignen. Hierbei sollte vorzugsweise Wasserstoffperoxid eingesetzt werden – ein aus ökonomischer und ökologischer Sicht sehr vorteilhaftes Oxidationsmittel. Weitere Möglichkeiten zur Anwendung von GILs sollten untersucht werden, wie der Einsatz von Guanidiniumhalogeniden als Katalysatoren in der Herstellung zyklischer Carbonate, oder als Beschleuniger in der Amin- bzw. Anhydrid-Härtung von Epoxidharzen. Die Kationen und Anionen von GILs wurden systematisch variiert, um deren Einflüsse auf die katalytische Epoxidierung von Cycloocten mit dem so genannten Venturello-Katalysator (Trioctylmethylammonium-Phosphorperoxowolframat) und 30% Wasserstoffperoxid zu untersuchen. Es konnte gezeigt werden, dass das Substitutionsmuster der Kationen und der Typ des Anions für die Selektivität der Oxidation von Cycloocten eine entscheidende Rolle spielt. Das Katalysatorsystem bestehend aus GIL mit darin gelöstem Venturello-Katalysator, konnte erstmalig in der Epoxidierung von Cycloocten wiedergewonnen und wiederverwendet werden, wobei hohe Selektivitäten und konstante Aktivitäten aufrecht erhalten wurden. Es wurden neue Katalysatoren auf Basis von Phosphorpolyoxowolframt mit Guanidinium Gegenionen synthetisiert und charakterisiert. Daher wurde das N,N,N’,N’-Tetrahexyl,N’’,N’’-dimethyl-guanidinium phosphorpolyoxowolframat erfolg¬reich in der Epoxidierung von Cycloocten mit 30% Wasserstoffperoxid in ver¬schiedenen Guanidiniumsalzen eingesetzt. Diese GILs mit den darin gelösten Katalysatoren ließen sich dann durch einfache Extraktion der Produkte recyceln. Die erzielten Ergebnisse wurden mit literaturbekannten Katalysatoren in der Epoxidierung von Cycloocten verglichen. Des Weiteren wurden katalytische Epoxidierungen in Acetonitril sowohl von cyclischen als auch acyclischen Alkenen mit dem neuen Katalysator N,N,N’,N’-Tetraoctyl,N’’,N’’-dimethyl-guanidinium phosphorpolyoxowolframat durchgeführt und mit Ergebnissen basierend auf einem literaturbekannten Katalysator 1N-Butyl,3N-methyl-imidazolium phosphorpolyoxowolframat verglichen. Sehr gute Umsätze und Epoxidselektivitäten wurden erhalten und der katalytische Einfluss des Kations [THMG]+ konnte in der Epoxidierung von Cyclohexen in Abwesenheit einer Metallkomponente nachgewiesen werden. Um die Anwendungsmöglichkeiten von Guanidiniumsalzen zu erweitern, wurden Guanidiniumhalogenide erfolgreich als Katalysatoren in der Additionsreaktion von CO2 mit Epoxiden zur Herstellung cyclischer Carbonate untersucht. Die besten Resultate ließen sich mit pentaalkylierten Guanidiniumiodiden erreichen. Zudem wurden diese mit literaturbekannten Imidazolium- und Pyridiniumhalogeniden verglichen. Als weitere wichtige Anwendungsmöglichkeit wurden verschiedene hexa- und pantaalkylierte GILs in der Amin- bzw. Anhydrid-Härtung von Epoxidharzen eingesetzt. Mit neuen pentaalkylierten Guanidiniumsalzen wurden effiziente Beschleuniger für die Epoxidharzhärtung entwickelt.
Eine Weiterentwicklung des SNAP-Tag Systems wurde erfolgreich eingesetzt, um das Chemotaxis Protein CheY in lebenden E. coli Bakterien hochspezifisch mit dem Farbstoff MR121 zu markieren. Unter Ausnutzung der Fluoreszenzlöschung des MR121 durch das Substrat Benzylguanin konnte die unspezifische Hintergrundfluoreszenz in lebenden Bakterien durch nicht gebundene Fluorophore um mehr als 90 % reduziert werden. Diese Reduktion ist ein sehr wichtiger Schritt im Hinblick auf die Anwendbarkeit hochspezialisierter fluoreszenzmikroskopischer Techniken und macht den SNAP-Tag zu einer sehr guten Alternative zu den fluoreszierenden Proteinen, deren mangelnde Photostabilität oftmals Einzelmolekülstudien entgegen steht. Unter Anwendung der bildgebenden Diffusionsmikroskopie (DIFIM) war es möglich, die Diffusionszeit des CheY innerhalb lebender E. coli Bakterien zu bestimmen und Heterogenitäten in verschiedenen Bereichen in den Zellen zu aufzulösen. Mit der Chemotaxis, die die Bewegung der Bakterien steuert, konnte mit dieser Methode erstmals eine biologisch hochrelevante Fragestellung bearbeitet werden. Zusätzliche Standard-FCS-Messungen in wässrigen Proteinlösungen in physiologischen Konzentrationsbereichen können zu einer Eichung der erhaltenen Diffusionszeiten dienen und somit die Interpretation von Messungen in biologischen Proben erleichtern. Untersuchungen der spektroskopischen Eigenschaften von Quantum Dots zeigten, dass auch sie grundsätzlich dazu genutzt werden können, intelligente, fluoreszenzgelöschte Sondensysteme zu entwickeln.
In this thesis, processes on a rhodium based catalytic NOx decomposition/reduction system operated under periodic lean/rich conditions are considered. The kinetic behavior of this system is simulated using a module of the CFD package DETCHEM, which treats the transient processes in the chemically reactive flow and couples those to microkinetic simulations based on multi-step reaction mechanisms. A detailed reaction mechanism over rhodium is extended and presented. The mechanism consists of oxidation reactions of CO and hydrogen and reduction reactions of NOx. The impact of temperature and temporal periods of the lean and rich phases on conversion of the pollutants is discussed. The trends of the experimentally observed and numerically predicted dynamic behaviors of the catalytic system agree well. The model could be applied in the design/optimization of catalytic exhaust after-treatment devices. Furthermore, this work potentially contributes to the development of applicable catalysts for vehicles equipped with diesel engines, lean-operated gasoline engines such as gasoline direct injection (GDI) engines.
In der vorliegenden Arbeit wurden flugzeuggetragene Messungen im Rahmen des "HOx OVer EuRope Projekts" (HOOVER) durchgeführt, welches dazu ausgelegt war, die saisonale Variation und räumliche Verteilung wichtiger troposphärischer Spurengase über Europa zu charakterisieren. In zwei Messzeiträumen im Oktober 2006 und Juli 2007 konnten Mischungsverhältnisse von Wasserstoffperoxid, Methylhydroperoxid und Formaldehyd von 40°N bis 75°N gemessen werden. Das nasschemische Verfahren zum Messen der Hydroperoxide basiert auf Fluoreszenzspektroskopie. Nach dem Überführen der Spezies von der Gas- in die Flüssigphase folgt eine enzymatische Derivatisierung der Peroxide und nachfolgend die Detektion der entstandenen Fluoreszenzfarbstoffe. Zum Umfang dieser Arbeit gehörte der Aufbau eines Einlasssystems zum Generieren eines konstanten Vordrucks für das Peroxidinstrument sowie die Modifikation und Instandhaltung des eigentlichen Messgerätes. Um Ansprüchen an zukünftige flugzeugbasierte Messkampagnen auf dem Forschungsflugzeug HALO zu entsprechen, wurde darüber hinaus ein neues Messgerät geplant und aufgebaut. Hydroperoxide und Formaldehyd haben einen signifikanten Einfluss auf das Budget von HOx (HO2+OH), den Hauptoxidantien der Troposphäre und damit auf die Selbstreinigungskraft unserer Atmosphäre. Die Analyse der gemessenen Profile zeigt für die Peroxide und das Formaldehyd eine Abnahme mit der Höhe und der Breite. Der Mittelmeerraum nimmt eine Sonderrolle in Europa ein, mit den jeweils höchsten Mischungsverhältnissen für die hier besprochenen Spezies. Ein Vergleich der Messungen mit den globalen Computermodellen MATCH-MPIC und EMAC zeigt eine gute Reproduktion der Trends innerhalb der Modelle, deckt aber auch signifikante Schwächen in der Reproduktion der absoluten Mischungsverhältnisse auf. Eine Sensitivitätsstudie mit EMAC zeigt das Auswaschen von Wasserstoffperoxid als eine potentielle Schwachstelle im Modell auf und demonstriert den Einfluss der Peroxide auf das Budget von HOx.
Optical tweezers are a versatile tool to apply and measure forces in the piconewton range on microscopic ob jects that are held by optical forces in a focussed laser beam. We employed holographic optical tweezers (HOT) to create extended force sensor arrays, consisting of multiple trapped particles that were controlled and probed individually. The combination of high-speed video microscopy with fluorescence imaging allowed the visualization of labeled protein structures in parallel with the tracking of multiple trapped particles for force measurements. Using this setup, we could perform quantitative force measurements on biological samples with HOT for the first time. To obtain reliable force measurements, calibration methods based on power spectra analysis were adapted for holographic optical tweezers. In microfluidic environments, biomimetic structures of the cellular cytoskeleton could be reconstituted between optically trapped microspheres. Flow cells and fluidic control, developed in this work allowed the exchange of solutions in the system and thus, the complete control of the chemical environment without generating forces that would affect the trapped particles. This provided the possibility to measure dynamic processes such as the contractility of two-dimensional cross-linked actin networks in the microfluidic flow cell. A network of actin fibers between seven trapped particles was created and the forces during cross-linking were obtained. To investigate bundling processes between filaments, a method has been established using dynamic HOT to manipulate zipper-like structures between trapped particles actively. Analysis of particle trajectories during zipping of filaments allowed the determination of binding energies between filaments. Unbundling forces between actin filaments were measured on trapped spheres during the active process of unzipping. Additionally, this system was transferred to actin networks on PDMS micropillar substrates to improve feasibility. In combination with the optical trap, this allowed for the investigation of unbundling forces for alpha-actinin as well as for magnesium ions as cross-linkers. In a different set of experiments, the adhesion process of the Malaria causing parasite Plasmodium was investigated. Adhesion and locomotion of the sporozoites is crucial for the infectivity of the parasite. A methodology for laser tweezer experiments with Plasmodium sporozoites was developed. Using optical tweezers, the formation of adhesion sites in the presence of actin disrupting drugs was probed and compared to knock-out parasite strains. We found the second step of sporozoite adhesion sequence to be significantly dependend on actin and a specific transmembrane protein named TRAP.
In der vorliegenden Arbeit wurde ein definiertes Beprobungsgebiet im südlichen Rhein- Neckar-Kreis auf Vorkommen und Verbleib von Arzneimittelrückständen aus den Wirkstoffgruppen Antipsychotika und Sulfonamidantibiotika untersucht, um das Kontaminationspotenzial von Kläranlagendirekteinleitungen für die als Vorfluter fungierenden Fließgewässer und die Trinkwasserförderung festzustellen. Grund hierfür war die Vermutung, dass die ausgewählten Substanzen über Patientenausscheidungen eines Landeskrankenhauses im Einzugsgebiet der Kläranlage Wiesloch durch diese nur unzureichend zurückgehalten bzw. abgebaut werden. Im Zeitraum von September 2006 bis Juni 2007 wurden vier Beprobungskampagnen durchgeführt deren jeweiliger Beprobungsumfang von der Punktquelle aus stetig erweitert wurde. In Kampagne IV konnte erstmalig eine Frachtbilanzierung der gesuchten Arzneimittelwirkstoffe für die bekannte Punktquelle und das übrige Einzugsgebiet des Abwasser- und Hochwasserschutzverband Wiesloch, die Kläranlage Wiesloch sowie die Vorfluter Leimbach und Hardtbach aufgestellt werden. Neben der Frachtbilanzierung wurden zusätzlich von den Fließgewässern tangierte Trinkwasserschutzgebiete mit den darin befindlichen Wasserwerken des Zweckverband Wasserversorgung Hardtgruppe (ZWH) und der Gemeinde Nußloch beprobt, um damit das Kontaminationspotenzial zum einen für die als Vorfluter fungierenden Fließgewässer zum anderen für die Trinkwassergewinnung, vor dem Hintergrund der behördlichen Richtwerte, lückenlos darzustellen. Des Weiteren wurde das Kontaminationspotenzial aus Regenüberläufen der Mischwasserkanalisation im Verbandsgebiet des Abwasser- und Hochwasserschutzverbands Wiesloch (AHW) untersucht, um Positivbefunde in den Fließgewässern vor der Direkteinleitungsstelle der Kläranlage Wiesloch erklären zu können. Für die Durchführung der Analytik wurde eine Multimethode für die Antipsychotika Perazin, Chlorprothixen, Zuclopenthixol, Haloperidol, Benperidol, Pipamperon, Melperon, Clozapin, Olanzapin, Risperidon und das Antibiotikum Sulfamethoxazol entwickelt. Die Quantifizierung erfolgte nach Anreicherung an einer Polymer-Festphase mit starken Kationentauschergruppen mittels HPLC-(ESI)-MS/MS-Gerätekopplung. Die angewandten Festphasenextraktionsvolumen lagen zwischen 250 mL und 1000 mL für Abwasserproben, 2000 mL für Oberflächenwasserproben und 3000 mL für Grund- und Trinkwasserproben. Die im Psychiatrischen Zentrum Nordbaden (PZN) verabreichten Wirkstoffmengen lagen im Untersuchungszeitraum zwischen 0,2 kg/a und 19,8 kg/a. Daneben wurden die aus Privathaushalten stammenden Arzneimittelfrachten durch gezielte Beprobung der Verbandskanäle untersucht, um die kommunale Grundbelastung gegenüber der Punktquelle PZN festzustellen. Die von der Kläranlage Wiesloch in den Leimbach abgegebenen Jahresfrachten lagen zwischen 16 g/a und 3459 g/a. In den Fließgewässern war keine vergleichbare Hochrechnung der in den Rhein abgegebenen Jahresmengen durchführbar, da erst in Kampagne IV die Mündungsgebiete von Leimbach und Hardtbach beprobt werden konnten. Die auf Stichproben und mittleren Tagesabflüssen basierende Tagesfrachten beider Fließgewässer lagen zwischen 1,6 mg/d und 5312 mg/d. II Im Trinkwasser der untersuchten Wasserwerke wurden die Wirkstoffe Haloperidol, Benperidol, Pipamperon, Melperon, Clozapin und Sulfamethoxazol mit Konzentrationen zwischen 0,2 ng/L und 18,7 ng/L nachgewiesen. Für Oberflächengewässer und Trinkwasser liegen aktuell zwei unterschiedliche Schwellenkonzentrationen für anthropogene Substanzen (auch pharmakologisch aktive) vor. Der behördlichen Richtwert von 0,1 μg/L für Trinkwasser bei lebenslanger Aufnahme durch den Menschen liegt jedoch höher als die aus dem Leitfaden der EMEA stammende Schwellenkonzentration zur ökotoxikologischen Unbedenklichkeit einer anthropogenen Substanz ohne vollständige Risikobewertung in Fließgewässern von 0,01 μg/L. Vor dem Hintergrund der laufenden Maßnahmen zur Umsetzung der Europäischen EG-WRRL sind in naher Zukunft verbindlich einzuhaltende Grenzwerte gleicher Größenordnung für pharmakologisch aktive Substanzen zu erwarten. Durch Ozonisierungsversuche konnte gezeigt werden, dass die untersuchten pharmazeutischen Wirkstoffe innerhalb kurzer Behandlungszeiten vollständig eliminierbar sind. Damit wurde der Beweis geführt, dass entweder beim Indirekteinleiter oder zentral im Klärwerk, jedoch spätestens in den Wasserwerken eine vollständige Entfernung der untersuchten pharmazeutischen Wirkstoffe möglich ist. Für den Abwasser- und Hochwasserschutzverband Wiesloch liefern die durchgeführten Expositionsanalysen die Grundlage für eine schnelle Planung und kostengünstige Durchführung weiterer Monitoringuntersuchungen, die zur Bewertung von Persistenz und Mobilität von Arzneimittelrückständen aus Kläranlagenabläufen zukünftig notwendig werden könnten. Des Weiteren wurde durch die Beprobung von Oberflächen, Grund- und Trinkwasser die Grundlage zur Beurteilung des Kontaminationspotenzials ausgesuchter Arzneimittelrückstände geschaffen.
The combination of catalysis and analysis in a single chromatographic reactor is an efficient method for the comprehensive kinetic characterization of catalysts and materials. This concept, called on-column reaction chromatography, incorporates catalytic activity and separation selectivity in the polymeric stationary phase of a chromatographic separation capillary. This thesis aims to study mechanistic details of (enantioselective) catalytic processes by applying this strategy. After an introduction about general aspects of on-column reaction chromatography in chapter 1, the combination of enantioselective hydrogenations of alpha-keto esters over quinine-modified Pt and Pd nanoparticles and the consecutive separation of the obtained enantiomers in microcapillaries is reported in chapter 3. This combination makes it possible to simultaneously determine enantiomeric excesses and reaction kinetics for entire substrate libraries by injecting a broad variety of different substrates at the same time. Chirally modified Pt and Pd nanoparticles, embedded in a stabilizing polysiloxane matrix, serve as catalysts and selective chromatographic stationary phases for these multiphase (gas-liquid-solid) reactions. These polymer embedded catalysts are coated as a thin film onto the inner surface of fused-silica capillaries. A systematic kinetic study for the Pt-catalyzed enantioselective hydrogenation of ethyl pyruvate (1) is presented. Furthermore, the high-throughput screening of a substrate library consisting of different alpha-keto esters over chirally modified Pt- and Pd-catalysts was investigated. A study about the activity of different ruthenium olefin metathesis catalysts in ring-closing metathesis (RCM) reactions is described in chapter 4. The Grubbs-type catalysts 1st (22) and 2nd generation (23) as well as Hoveyda-Grubbs-type catalysts 1st generation (24) were dissolved in polysiloxanes and coated onto the inner surface of microcapillaries. Temperature- and flow-dependent conversion measurements with Grubbs-type catalysts for RCM allowed the determination of reaction rate constants k and activation parameters. The obtained comprehensive experimental kinetic data are a prerequisite for a better understanding of catalytic mechanisms. In chapter 5, the concept of on-column reaction gas chromatography was used to combine separation selectivity of ionic liquids (ILs) and catalysis by Grubbs-type catalyst 1st generation (22) in RCM reactions. This combination allows the investigation of catalyst stability and recyclability, which are important aspects for future catalyst applications. With this combination, it is possible to investigate the catalyst stability and recyclability. Reaction rate constants k that are hardly accessible by other techniques can be efficiently determined for various substrates with this approach. Chapter 6 describes the synthesis and application of polysiloxane-immobilized chiral camphor-based transition metal catalysts. The enantioselective separation efficiency and catalytic activity of these novel stationary phases are investigated. The synthetic applicability of polysiloxane-supported chiral Co-salen-complexes is described in chapter 7. A modular, covalent immobilization method for monofunctionalized enantiopure unsymmetrical salen ligands by an ether linkage has been elaborated.
Microstructured interfaces such as micropillars made of polydimethyl-siloxane (PDMS) provide a novel approach both as topologically defined, force sensing substrates in cell culture as well as scaffolds for biomimetic protein assays. This work is divided into two parts. In the first part, PDMS micropillar arrays functionalized with fibronectin, are applied as a biomechanical microenvironment for immortalized human gingival keratinocytes (IHGKs) and gingival connective-tissue fibroblasts (GCTFs). IHGKs and GCTFs show successful adhesion and growth on the pillar heads and exert forces up to about 110 nN in the case of IHGKs and about 174 nN for GCTFs. Varying the interpillar distances affects the early keratinocyte differentiation and morphology. At decreasing inter-pillar distances the IHGKs show an increased keratin 1 (K1) extension in the cytoplasm, increased mRNA transcription of keratin 1 and a shape change from a more linear to a more round form. A novel GCTF-IHGK co-culture system is developed as a model of the epithelial tissue, to study explicitly the role of the GCTFs in the morphogenesis of the derived epithelial equivalents. The epithelial equivalents, cultured for 7 and 14 days on GCTF-populated pillar arrays, are found more similar to the in vivo phenotype than the GCTF-free cultures. These findings are confirmed by following the mRNA transcription levels for keratin 1. A novel, transparent microfluidic platform, based on PDMS pillars is developed in the second part of this work. It is designed to investigate actin cortex models and to provide control over the physicochemical environment, allowing simultaneous high resolution fluorescence microscopy. The formation of crosslinking networks is observed using various crosslinkers, such as filamin, myosin II, alpha-actinin and magnesium ions. Dependent of the geometric configuration of the actin filaments anchored to the pillar tops, so-called zipping crosslinks are observed. The zipping velocity is both influenced by the flow speed, as well as the number and the configuration of the filaments involved in the process. It is found to range between 2 - 15 µm/s. To further quantify the crosslinking process, the flow-cell is combined with an optical tweezers system. The unzipping forces are measured for the crosslinkers alpha-actinin and magnesium ions. Forces of about 17 - 20 pN are derived for magnesium ions and about 30-45 pN for alpha-actinin.
Diese Arbeit widmet sich der Anwendung der in den letzten Jahren entwickelten Bildgebenden Diffusionsmikroskopie (DIFIM) auf lebende Zellen. Die Methode erlaubt die Detektion von Intensitätsfluktuationen über einen großen, mehrere Mikrometer umfassenden Bereich. Sie ermöglicht zugleich die Diskriminierung des Fluoreszenzsignals von störender Hintergrundfluoreszenz anhand von Fluoreszenzlebensdauermessungen. DIFIM wurde an einem Testsystem in lebenden Zellen, bestehend aus einem farbstoffmarkierten Oligonukleotid, welches an den PolyA-Strang der zelleigenen mRNA hybridisieren kann, untersucht. Es wurde gezeigt, dass es mithilfe von DIFIM möglich ist, unterschiedliche Diffusionszeiten in lebenden Zellen zu visualisieren. Damit wurde der Grundstein gelegt, um Wechselwirkungen verschiedener Proteine innerhalb einer Zelle zu verfolgen. Zur Demonstration der Anwendbarkeit von DIFIM in der Biologie wurde der JAK-STAT-Signalweg genauer untersucht. Im Speziellen sollte die Diffusion des Proteins STAT5b verfolgt werden. Hierfür wurde zunächst die in vivo Markierung des Proteins mit einzelmolekültauglichen, rot fluoreszierenden Farbstoffen untersucht. Zur Markierung wurde ein Fusionsprotein mit dem sogenannten SNAP-Tag eingesetzt, der eine spezifische kovalente Bindung synthetischer Farbstoffe an gewünschte Proteine ermöglicht. Es stellte sich heraus, dass die Markierung mittels Inkubation unspezifisch war, weshalb die Markierung unter Verwendung von Transfektionsreagenzien durchgeführt wurde. Auch diese ermöglichten in lebenden Zellen keine charakteristische Markierung. Weiterführend wurden Zellen mit einem Fusionsprotein aus STAT5b und mCherry, ein Derivat des Rot-Fluoreszierenden Proteins, transfiziert. Derartig behandelte Zellen ermöglichten es erstmals, Unterschiede in Diffusionszeiten in in vivo DIFIM-Messungen zu beobachten.
Ladungstransport ist ein grundlegender Prozess in der Natur. Allgemein anerkannte Mechanismen erklären den Ladungstransport mithilfe von kerndynamischen Prozessen. Entgegen dieser Betrachtungsweise ist in den letzten Jahren ein Mechanismus entwickelt worden, der vollständig ohne Kerndynamik auskommt. Die Ursache dieser Ladungswanderung nach Ionisierung sind die rein elektronischen Vielteilcheneffekte, welche bisher nur in der inneren Valenz von Moleülen bekannt war. In dieser Arbeit wird sie zum ersten Mal in der äußeren Valenz beschrieben. Hier wird eindeutig gezeigt, dass die Vielteilcheneffekte Ladungswanderung nach Ionisierung verursachen können. Anhand verschiedener Systeme wird veranschaulicht, dass durch Ionisierung erzeugte Ladung in einem Molekül innerhalb weniger Femtosekunden über mehrere chemische Bindungen hinweg wandern kann. Desweiteren wird ein Bezug zu aktuellen pump-probe Experimenten hergestellt. Die hauptsächlich untersuchten Systeme sind peptidähnliche Moleküle, dabei wird das Strukturmerkmal Chromophor-Donor und Amin-Akzeptor als ein mögliches Konzept für Ladungswanderung in der äußeren Valenz identifiziert. Die Abhängigkeit der Ladungswanderung von der geometrischen Struktur wird eingehend untersucht.
Kurzfassung in Deutsch: In dieser Arbeit wird die Synthese verschiedener künstlicher Aminosäuren und deren Ethylester aus Bis(terpyridin)ruthenium-Komplexen beschrieben. So wurden [(ROOC–tpy)Ru(tpy–NH2)]2+, [(ROOC–C6H4–tpy)Ru(tpy–NH2)]2+, [(ROOC–tpy)Ru(tpy–C6H4–NH2)]2+ (R = H, C2H5) und [(HOOC–C6H4–tpy)Ru(tpy–C6H4–NH2)]2+ dargestellt und charakterisiert (MS, NMR, IR). Alle Komplexe lumineszieren bei Raumtemperatur in Lösung, wenn sie mit Licht der Wellenlänge der MLCT-Absorption (l ≈ 500 nm) angeregt werden. Das Verhalten von [(HOOC–tpy)Ru(tpy–NH2)]2+ gegenüber Säuren und Basen wurde genauso untersucht, wie seine photophysikalischen und elektronischen Eigenschaften. Dazu wurden UV/Vis-, CV-, Emissions- und Resonanzraman-Spektren gemessen sowie DFT-Modellierungen vorgenom-men. Redoxaktive Ferrocenyl-Bausteine wurden über Amidbrücken an [(HOOC–tpy)Ru(tpy–NH2)]2+ gebunden und die erhaltenen mehrkernigen Komplexe [(Fc–NH–CO–tpy)Ru(tpy–NH2)]2+, [(ROOC–tpy)Ru(tpy–NH–CO–Fc)]2+, [(ROOC–tpy)Ru(tpy–NH–CO–Fc–NH–COCH3)]2+ (R = H, C2H5) und [(Fc–NH–CO–tpy)Ru(tpy–NH–CO–Fc)]2+ wurden elektro-chemisch und photophysikalisch vollständig charakterisiert. Die Lumineszenz der Verbindun-gen mit N substituiertem Ferrocen ist durch Elektronentransfer von der Ferrocenyleinheit zum Rutheniumzentrum gelöscht. Photostrommessungen in einer Grätzel-artigen Zelle mit [(HOOC–tpy)Ru(tpy–NH2)]2+ als lichtsammelnden Farbstoff erreichten eine 5 – 10 Mal größere Photostrom-Effizienz (IPCE) als Messungen mit [(HOOC–tpy)Ru(tpy–NH–CO–Fc)]2+ und [(ROOC–tpy)Ru(tpy–NH–CO–Fc–NH–COCH3)]2+. Weitere über Amidbindungen verbrückte zweikernige Bis(terpyridin)ruthenium-Komplexe wurden dargestellt: ein Konjugat aus [(EtOOC–tpy)Ru(tpy–NH2)]2+ und einem Carbonsäure- und tert-Butylgruppe substituier-ten Bis(terpyridin)ruthenium-Komplex sowie einem „Dimer“ von [(HOOC–tpy)Ru(tpy–NH2)]2+. Dafür wurde der Boc-geschützte Komplex [(OOC–tpy)Ru(tpy–NHBoc)]+ dargestellt und mit [(EtOOC–tpy)Ru(tpy–NH2)]2+ umgesetzt, gefolgt von der Entschützung der funktio-nellen Gruppen. Diese zweikernigen Verbindungen absorbieren im Vergleich zu den Einker-nigen mit doppelter Intensität und können elektrochemisch zwei Mal reversibel oxidiert werden (RuII/RuIII). Die Oxidation bei niedrigem Potential wurde dem am N-Teminus gebun-denen Komplex zugeschrieben, die bei höherem Potential dem am C-Teminus gebundenen Fragment. Beide zweikernigen Konjugate lumineszieren bei Raumtemperatur. Die Emission des „Dimers“ ist, verglichen mit dem anderen zweikernigen Komplex, bathochrom verscho-ben, da durch die Aminogruppe des „Dimers“ ein Ligand-Ligand-Charge Transfer (LLCT) möglich wird. Licht sammelnde organische Chromophore (verschiedene Cumarinderivate, Naphthalin, Anthracen) und a-Aminosäuren wurden in Lösung sowie in Festphasenpeptid-synthesen (SPPS) an [(HOOC–tpy)Ru(tpy–NH2)]2+ gekuppelt. Dadurch wurden sehr reine Produkte erhalten. So wurden Dyaden mit und ohne Glycinmolekül als Abstandhalter zwi-schen dem Bis(terpyridin)ruthenium-Komplex und dem organischen Chromophor dargestellt und deren photophysikalische und elektronische Eigenschaften eingehend untersucht. In allen Verbindungen dieser Reihe mit organischem Chromophor wurde ein Energietransfer vom Chromophor zum Rutheniumkomplex beobachtet. Die Energietransfereffizienz wurde zu 86 – 99% bestimmt.
Intramolekulare Hydroaminierungen von Aminoalkinen mit unterschiedlichen Metallkomplexen sind in einer Vielzahl publiziert worden. Im Rahmen der vorliegenden Arbeit wurde gezeigt, dass man bei der intramolekularen Hydroaminierung von racemischen Aminoalkinen mit chiralen Titan(IV)-Katalysatoren einen Enantiomerenüberschuss erzielen kann. Bei den Hydroaminierungen mit den β-chriralen Aminoalkinen wurden keine ee-Werte beobachtet, was durch die zu hohen Reaktionsgeschwindigkeiten und die Entfernung des Chiralitätszentrums in β-Position und dem aktiven Zentrum der entsprechenden Katalysatoren hervorgerufen wurde. Diese hohen Reaktionsgeschwindigkeiten sorgten allerdings dafür, dass die intramolekularen Hydroaminierungen mit den eingesetzten Titan(IV)-Katalysatoren bei sehr geringen Temperaturen sehr schnell mit guten Ausbeuten abliefen. Die Reaktionen mit den α-chiralen Aminoalkinen lieferten im Gegensatz zu den β-chiralen Aminoalkinen erheblich bessere Ergebnisse. Erste Enantiomerenüberschüsse wurden mit α- chiralen Aminoalkin und entsprechenden chiralen Titan(IV)-Katalysatoren erzielt. Die Hydroaminierung zum 5-Ring erwies sich als ausgesprochen viel versprechend, da sich hier die Reaktionsgeschwindigkeiten der einzelnen Enantiomere zum Ringschluss ausreichend unterschieden. Auch hier verliefen die Hydroaminierungen bei niedrigen Reaktionstemperaturen und relativ kurzen Reaktionszeiten. Durch Einsatz entsprechender chiraler Katalysatoren konnte sogar eine teilweise dynamisch kinetische Racematspaltung beobachtet werden. Reaktionen mit α-chiralen Aminoalkinen, die zum 6-Ring hydroaminieren, erzielten keine Ergebnisse. Bei diesen Hydroaminierungen ist die Reaktionsgeschwindigkeit zu gering, so dass auch nach mehreren Tagen keine Cyclisierung erzielt wurde.
Ziel der hier vorliegenden Arbeit war Entwicklung und Etablierung einer auf Microarray basierenden Methode zur Bestimmung von Protein-DNA-Wechselwirkungen im Hochdurchsatz-Format. Hierzu wurde die Geniom-Plattform in Zusammenarbeit mit der febit biomed GmbH weiterentwickelt und für diese Experimente etabliert. Im ersten Teil der Arbeit stand die Entwicklung der Methode anhand des Transkriptionsfaktors Gli2 sowie ein Validierung der Ergebnisse mit anderen Methoden im Vordergrund (SPR und QCMD-Technologie). Im zweiten Teil der Arbeit wurden mit dieser Methode die Bindungsspezifitäten von 10 krebsrelevanten Transkriptionsfaktoren bestimmt. Ausgehend von der aus der Literatur bekannten Konsensus Sequenz wurden alle möglichen Ein- und Zweibasenpaarmutationen dieser Transkriptionsfaktoren untersucht. Die in dieser Arbeit erzielten Ergebnisse zeigen, dass die hier entwickelte Methode für die Messung von Protein-DNA-Wechselwirkungen im “high throughput” Format angewendet werden kann. Dies wurde als “proof of principle” anhand des Transkriptionsfaktors Gli2 mit zwei verschiedenen Tags sowie für 10 weitere Transkriptionsfaktoren gezeigt. Es konnten hierbei innerhalb der Bindemotive Gemeinsamkeiten aufgezeigt werden. Bei den C2H2-Zink-Fingerproteinen Gli2 und WT1 ist hauptsächlich die Base Cytosin für die DNA Bindung verantwortlich. Auch ein Vergleich der Sequenzlogos mit anderen aus der Literatur bekannten Zinkfingern wie Zif268 zeigt eindeutige Übereinstimmungen. Auffällig war weiterhin das Vorkommen von Kernsequenzen mit einer Länge von 2-3 Basenpaaren in der Mitte der Bindesequenz, die maßgeblich für die Bindung verantwortlich sind. Die Ergebnisse zeigen weiterhin, dass bei den meisten Transkriptionsfaktoren der Austausch dieser Basen hinsichtlich der Proteinbindung als besonders kritisch anzusehen ist. Dies lässt sich durch strukturelle Veränderung in der DNA erklären. Die Bindung des Proteins an die Bindedomäne funktioniert ähnlich dem Schlüssel-Schloss-Prinzip. Für die Spezifität und Stabilität der Bindung sind Wasserstoffbrücken, Ionenbindungen sowie hydrophobe Wechselwirkungen verantwortlich. Wird dieses perfekt aufeinander abgestimmte System verändert und die Struktur des DNA bindenden Motivs passt nicht mehr exakt zu der Form der DNA, ist die Affinität reduziert. Leicht vorstellbar ist dies beispielsweise bei einem Austausch eines Pyrimidins gegen ein Purin. Auch der gegenteilige Fall ist denkbar. Es ist also durchaus erklärbar, dass auch stärker bindende Sequenzen als die Konsensus-Sequenz gefunden wurden. Die häufigste natürlich vorkommende Bindesequenz muss nicht unbedingt die Stärkste sein. Wichtig ist, dass sie schnell und effektiv regulierbar ist. Mutationen in der Bindesequenz von Transkripionsfaktoren können somit weitreichende Folgen haben. Bis jetzt sind jedoch nur wenige Mutationen in diesen Regionen bekannt, die Krankheiten wie Krebs verursachen können. Mit den aus dieser Arbeit gewonnenen Daten können Vorhersagen getroffen werden, wie sich verschiedene Mutationen in den Promoterregionen hinsichtlich der Proteinbindung und somit auch auf die Expression auswirken können.
Die vorliegende Arbeit befasst sich mit der Synthese, Charakterisierung und quantenchemischen Berechnung von Verbindungen mit Übergangsmetall-Gallyl-Einheiten. Als Ausgangsstoffe werden die subvalenten, zweiwertigen Galliumverbindungen Ga2Cl4 x 2 Dioxan (2), [Ga(μ-Cl)Si(SiMe3)3]4 (3.1) und das dreiwertige tmp2GaFeCp(CO)2 (4.2) synthetisiert. Bei der Reaktion von 4.2 mit Phenol konnten Kristalle von [tmpH2]+ [(PhO)3GaFeCp(CO)2]– (4.3) erhalten werden. Dabei wurden die beiden tmp-Reste durch drei Phenolat-Reste substituiert und das Galliumatom koordinativ abgesättigt. DFT-optimierte Strukturen 4.3R - 4.12R werden für Vergleiche bezüglich der Bindungssituation herangezogen. Bei Umsetzungen von 2 mit Carbonylmetallaten konnte durch Einsatz von Tetracarbonylferrat, Ga4Cl4(OH)4Fe2(CO)8 (2.4) mit einer adamantanartigen Struktur erhalten werden. Die Synthese von Ga10Cl14(OH)16 (2.6) gelang durch die Reaktion von (2) mit Natriumwolframat. Bei der Verwendung von Collmanns Reagenz [Na2Fe(CO)4] kristallisierte Ga7Cl6(OH)9[Si(SiMe3)3]6 (3.3) nach Zugabe von 3.1 aus. Dabei handelt es sich um einen Chelatkomplex mit helikaler Struktur. Bei analogen Reaktionsbedingungen führte die Umsetzung von 3.1 mit K[Co(CO)4] zu [K(THF)][Ga{Co2(CO)6(μ-CO)}2] (3.5). Im Kristall bilden sich Kanäle die durch sechs Formelelemente gebildet werden, in welche Lösungsmittelmoleküle eingelagert werden können. Diese Struktur zeigt Verwandtschaft zu den Metal Organic Frameworks (MOFs) die u.a. in der Katalyse und Gasspeicherung Einsatz finden. Durch die hohe Disproportionierungsneigung von 3.1 und einhergehenden Redoxprozessen, wurden bei unterschiedlichen Umsetzungen von 3.1 mit Nukleophilen [Li (THF)4]+ [GaCl2{Si(SiMe3)3}2]- (3.2), [{Co6(CO)15} x 2 K (Donor)x] (3.4), [FeCp(CO)3]+ [GaCl4]- (3.8) und Ga4(OH)4O2[Si(SiMe3)3]4 (3.9) erhalten.
Artifizielle molekulare Elektronendonor-Elektronenakzeptor-Systeme sind Schlüsselverbindungen für die Aufklärung mechanistischer Details von photoinduzierten Elektronentransfer-Prozessen (PET-Prozessen) in der Chemie und in der Biologie. Sie stellen die Grundlage für die Entwicklung künftiger artifizieller Photosysteme dar und sie könnten zudem in molekularen optoelektronischen Bauteilen oder Sensoren Anwendung finden. In dieser Arbeit wird über die gezielte Synthese von trans-AB2C-substituierten meso-Tetraarylporphyrinen berichtet. Die Tetraarylporphyrin-Synthese wurde für die Kombination A = C6H4-NO2, B = C6H5 und C = C6H4COOMe unter Verwendung der entsprechend substituierten Dipyrromethane (A = C6H4-NO2,C = C6H4COOMe) optimiert. Die Nitrogruppe dieses Porphyrins lässt sich durch Zinn(II)chlorid zum Amin reduzieren und der Ester dieses Porphyrins lässt sich alkalisch zur Carbonsäure verseifen, wobei die Reihenfolge dieser Reaktionsschritte frei wählbar ist, so dass diese Reaktionen die trans-AB2C-substituierten meso-Porphyrine mit A = C6H4-NH2 / C = C6H4COOMe, A = C6H4-NO2 / C = C6H4COOH und A = C6H4-NH2 / C = C6H4COOH in guten Ausbeuten liefern. Die Metallierung dieser Porphyrine mit Zink(II)- und Kupfer(II)-Ionen gelingt ebenfalls in guten Ausbeuten. An den funktionellen Gruppen A = C6H4-NH2 bzw. C = C6H4COOH der Porphyrinbasen lassen sich gezielt Ferrocen-Bausteine (Ferrocencarbonsäure oder Aminoferrocen) über Amidbindungen anknüpfen, wobei eine Aktivierung der Carbonsäure mit Hydroxybenzotriazol oder über Säurechloride möglich ist. So wurden Ferrocen-Porphyrin-Dyaden mit folgendem Substitutionsmuster erhalten: A = C6H4-NH-CO-Fc / C = C6H4COOMe, A = C6H4-NO2 / C = C6H4CO-NH-Fc, A = C6H4-NHFmoc / C = C6H4CO-NH-Fc und A = C6H4-NH2 / C = C6H4CO-NH-Fc. In diesen Dyaden ist die Fluoreszenz des Porpyhrin-Chromophors teilweise gelöscht, was auf intramolekulare photoinduzierte Elektronentransfer-Prozesse vom Ferrocen-Donor zum angeregten Porphyrin zurückgeführt werden kann. Die Effizienz des PET in diesen Amid-verknüpften Dyaden ist abhängig vom Redoxpotential des angeknüpften Ferrocen/Ferriciniumpaares und der Umgebung (Lösungsmittel).
Das mechanisch stark beanspruchte Knorpelgewebe in Gelenken besteht zum überwiegenden Teil aus einer komplexen extrazellulären Matrix (ECM). Chondrozyten, spezialisierte in der Matrix eingebettete Zellen, erneuern diese fortwährend, um deren Abrieb und Verschleißzu verhindern. Die Zellen werden durch eine mikrometerdicke perizelluläre Matrix (PCC) geschützt, die ein Überleben und ein Teilen der Zellen trotz der hohen mechanischen Belastung ermöglicht. Die PCC ist von entscheidender Bedeutung für eine Vielzahl weiterer biologischer Prozesse, wie der Motilität, der Zellalterung und der Ostheoarthrose. Auf molekularer Ebene ist die Zusammensetzung und Wechselwirkung der verschiedenen PCC-Komponenten gut verstanden: Der überwiegende Teil der PCC besteht aus Wasser und ist damit mit lichtmikroskopischen Methoden nicht detektierbar. Das Rückgrat der PCC wird aus stark hydratisierten Hyaluronsäurepolymeren und daran angebundenen HA-Bindungsproteinen gebildet. Informationen über die mesoskopische Struktur der PCC sind allerdings kaum vorhanden. Diese ist jedoch von fundamentaler Bedeutung für das Verständnis der Kraftübertragung aus dem Knorpelgewebe auf die Zellen sowie zur Aufklärung des Mechanismus, der den Zellen eine aktive Anpassung der PCC ermöglicht Im Rahmen dieser Arbeit wurden daher neue Methoden zur Visualisierung der PCC etabliert, die eine dreidimensionale Darstellung, sowie die mikromechanische Charakterisierung der PCC lebender Zellen ermöglichen. Diese Methoden erlaubten die Untersuchung der dynamischen Anpassung der PCC bei Zellteilung, Motilität und Phagozytose. Die mesoskopische Struktur der PCC konnte von den erhaltenen Messdaten abgeleitet und durch entsprechende Modellsysteme aus endständig angebundenen HA Molekülen unterstützt werden. Darüber hinaus konnte das Wechselspiel von PCC und ECM mit Hilfe von Adhäsionsstudien auf homogenen sowie nanostrukturierten Oberflächen, welche die ECM-Wechselwirkungen kontrollieren, untersucht werden.
In der vorliegenden Arbeit wurde die Reaktivität von Gallium(I)verbindungen eingehend untersucht. Es konnte ausgehend von GaCp* subvalentes Galliumtriflat synthetisiert werden. Aus der komplexen Reaktionsmischung konnten verschiedene Verbindungen charakterisiert werden unter anderen [Ga4(OTf)4Cp*2] und [Ga6(OTf)6Cp*2]. Tetramere Gallium(I)amide [Ga4R4] (R = N(SiMe3)(dipp); 2,2,6,6-Tetramethylpiperidin) konnten synthetisiert und kristallographisch charakterisiert werden. Die beobachtete Monomerisierung in Lösung, erlaubte [Gatmp] als Ligand in Übergangsmetallkomplexen einzusetzen. Dabei diente [Gatmp] als terminaler oder verbrückender Ligand. In dem homoleptischen Komplex [Ni2(Gatmp)7] wurde diese Eigenschaft am Besten gezeigt. Für diese Komplexe als auch für die Gallium(I)amide wurde die Bindungssituation mittels DFT-Methoden untersucht. [Ga4R4] konnte durch elementare Chalkogenen zu den Cubanen [E4Ga4R4] (E = S, Se), oder zu dem hexagonalen Prisma [O6Ga6R6] oxidiert werden. Durch Reaktion von sterisch anspruchsvollen Lithiumsilaniden mit Galliumtriflat als auch mit Gallium(I)amid konnten Galliumcluster z.B. [Ga13{Si(SiMe3)}6]- synthetisiert werden. Es konnte gezeigt werden, dass Gallium(I)-diketoimidinate in der Lage sind, Reaktionen mit Element-Wasserstoff Bindungen einzugehen. Somit konnte exemplarisch erstmalig ein stabiles Stannylgallan dargestellt werden.
The goal of this work is the deposition and growth of various nanoobjects on patterned surfaces. For this purpose, patterned surfaces function as a chemical template to direct the location and shape of the added nanoobjects. In particular, colloidal nanoparticles, viral particles and inorganic salts are used to assemble small structures along large areas of chemical surface patterns. The substrates for these assays are based on glass or silicon, which have been decorated with gold or platinum nanoparticles. These nanostructured substrates were obtained by block copolymer micelle nanolithography. The technology has been substantially improved for application to large-scale surface areas and optimum pattern quality. Here, the influence of trapped solvent vapor above the dipping solution on the thickness of the adsorbed polymer film was investigated. A higher amount of trapped vapor results in an increase of the lateral distance of the nanoparticles on the surface and a more reproducible pattern formation, which was shown by SEM analysis. Nanopatterned surfaces were then used as a chemical mosaic platform for the deposition and growth of different nanoobjects. CdSe-Au dumbbells, CoPt_3-Au heterodimers and Co-Au matchsticks were attached to gold nanoparticles which were deposited by block copolymer micelle nanolithography via a dithiol linker. The resulting patterns show a random orientation of the nanocrystals. The magnetic Co-Au matchsticks were additionally aligned in a magnetic field, resulting in an ordered surface. Furthermore, CdSe-Au dumbbells were immobilized by DNA assembly. Here, hybridization allowed for a controlled and reversible attachment of the nanocrystals on the surface. Direct assembly of spherical CdSe nanocrystals on a non-patterned surface was realized by block copolymer micelle nanolithography. Hydrophilic ligands enable the interaction between the nanocrystals as formed in organic solvents and the polar core of block copolymer micelles. Guided by the block copolymer micellar core the CdSe particles were hexagonally arranged on the substrate, with 3 or 4 particles being located in one micelle. The number of CdSe particles per micelle was investigated by electron and fluorescence microscopy and was found to be independent from the size of the polymer. In a solution-liquid-solid approach, CdSe rods and wires as well as Co rods were grown on the nanopatterned substrates. For the growth of the CdSe rods and wires, Au@Bi core shell particles on the surface were used as a catalyst. Interestingly, the Au@Bi core shell particles remained on the substrate while the tips of the wires were covered by the growth of bismuth. Layers of biotin modified cowpea mosaic viruses are formed on a biotin-doped lipid bilayer on a hydrophilic silicon oxide surface, connected by streptavidin. In quartz crystal microbalance studies, different biotin modifications were compared. The resulting films showed differences in their roughness and density. Thiol-modified streptavidin enabled the attachment of the virus nanoparticles to gold, where the resulting layer has the same density as on the lipid bilayer. In summary, nanostructured substrates are a versatile platform for the assembly of organic and inorganic nanoparticles as well as growth seeds for inorganic material. Several different methods to control the assembly of particles on a solid substrate were successfully investigated, demonstrating their potential for further application in nanotechnology.
Anthrachinonfarbstoffe zählen zu den stabilsten Verbindungen in der organischen Chemie und weisen besonders brillante Farben sowie eine hohe Lichtechtheit auf. Sie zeichnen sich durch gute photophysikalische Eigenschaften aus und sind heute als molekulare Sonden für bioanalytische Anwendungen und das zelluläre Imaging von großer Bedeutung. In dieser Arbeit wurden Derivate und Biokonjugate von nahinfrarot emittierenden Anthrachinonfarbstoffen entwickelt, die ungewöhnliche Akkumulation und subzelluläre Verteilungen in lebenden Zellen zeigen, die hochspezifische Markierungen in fixierten Zellen ermöglichen, die auf biologisch wichtige Metallionen ansprechen oder den programmierten Zelltod in lebenden Zellen auslösen. Die wichtigsten neu entwickelten Sonden und ihre Anwendungen sind hier zusammengefasst: •In vivo selektive Fluoreszenzfarbstoffe Die neu entwickelten Anthrachinonderivate 3, 13 und 15 erkennen selektiv die Plasmamembranen und den Nuclear Envelope (Zellkernmembran, Endoplasmatisches Retikulum) in lebenden Zellen, während Verbindung 12 eine hohe Affinität zum Zellkern aufweist. Infolge der sehr guten photophysikalischen Eigenschaften sind die Fluororophore für die modernen hochauflösenden Fluoreszenmikroskopiemethoden (4pi, STED, SMI-Vertico) geeignet. •Metallbindende Sonden Zur fluorometrischen Bestimmung von intrazellulären Zn2+-Ionen wurde das Ligandensystem 17 entwickelt. Die qualitative Bestimmung der Zn2+-Ionen erfolgte durch die Emissionsabnahme des nahinfrarot emittierenden Fluorophors infolge der Komplexierung von Zn2+-Ionen über die Bispicolylamineinheit des Ligandensystems. Aufgrund der zellulären, phototoxischen Eigenschaften von Trisbipyridylrutheniumkomplexen wurde ein mit Anthrachinonderivat funktionalisierter Trisbipyridylrutheniumkomplex synthetisiert. Das Konjugat zeigt im Vergleich zu den bekannten Trisbipyridylrutheniumkomplexen eine erhöhte Zellpermeabilität, eine erhöhte Phototoxizität und eine Zellakkumulation, die vom Anthrachinon dirigiert wird. •Biokonjugate (Protein- und Peptidnukleinsäurekonjugate) Die Spezifität der Aminoanthrachinon-Fluorophore wurden durch Konjugation an das Protein Wheat germ agglutinin (WGA) und an eine spezielle, repetitive Peptidnukleinsäuresequenz in fixierten Zellen verbessert. Das WGA-Konjugat stellt ein Beispiel aus dem Bereich der Immunofärbungen in der biotechnologischen Anwendung dar. Über die hochselektive Markierung der entwickelten PNS-Konjugate wurde mit Hilfe von Fluoreszenz in situ Experimenten und mittels Mikroinjektionstechnik die topologische Anordnung der Zentromerregion von Chromosom 9 in menschlichen Zellen quantifiziert. •Zytostatika Zwei etablierte und bekannte Zytostatika auf Anthrachinonbasis sind Doxorubicin und Mitoxantron. Ein weiteres Derivat wurde entwickelt, das eine hohe zytostatische Wirkung auf diverse Zellen zeigt. Die zelluäre Toxizität der Verbindung beruht auf Apoptosevorgängen.
Gelenkerkrankungen zählen in der heutigen Zivilisation zu den am weitesten verbreiteten Krankheiten. Die Haltbarkeit derzeit verwendeter künstlicher Gelenke liegt bei etwa 15 Jahren, was durch den Einsatz des Schmierungsprinzips der Natur, der Flüssigschmierung, deutlich verbessert werden könnte. Trotz zahlreicher Bemühungen ist das Prinzip der Flüssigschmierung bis heute nicht verstanden. Es wird angenommen, dass der lineare Polysaccharid Hyaluronsäure und oberflächenaktive Phospholipide eine wichtige Rolle für die Schmierung spielen. Derzeit werden verschiedene Schmierungsmechanismen diskutiert, die von intermolekularen Wechselwirkungen zwischen beiden Komponenten ausgehen. Um ein verbessertes Verständnis für die Schmierungsmechanismen in natürlichen Gelenken zu gewinnen, wurde ein Modellsystem aufgebaut, das aus einer Polyelektrolytunterlage mit einer darauf verankerten Lipiddoppelschicht besteht. Als Trägermaterial fand Silizium Verwendung. Zur Durchführung der Untersuchungen wurden je eine neuartige Scher- und Druckzelle für die Neutronenreflektometrie sowie eine temperierbare Flusszelle für die in situ Ellipsometrie entwickelt. Mittels QCM-D sowie Neutronen- und Röntgenreflektometrie wurde die erfolgreiche Bildung von Lipid-Doppelschichten aus 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholin (DMPC) sowie aus Mischungen mit DMPC und 1,2-Dioleoyl-3-Trimethylammonium- Propan (DOTAP) und Mischungen aus 1-Palmitoyl-2-Oleoyl-sn-Glycero-3- Phosphocholin (POPC) und DOTAP auf Polyelektrolytunterlagen gezeigt. Im Gegensatz zu früheren Untersuchungen lassen die Ergebnisse dieser Arbeit darauf schließen, dass keine Wechselwirkungen zwischen Hyaluronsäure und Lipiden existieren, sondern letztgenannte als freie Vesikel in der Synovialflüssigkeit vorliegen. Weitere Untersuchungen zeigten, dass die Lipide auch in Hyaluronsäurelösungen oberflächenaktiv sind. Schließlich konnte in Viskositätsmessungen die guten Schmiereigenschaften der Lipide demonstriert werden. Das Modellsystem wurde anschließend in Kontakt mit Hyaluronsäurelösungen gebracht und mittels Neutronenreflektometrie unter Druck und Scherung untersucht. Unter Sche- 8 - rung wurden keine wesentlichen neuen Erkenntnisse erlangt. Ein Erklärungsmodell, nachdem unter Scherung die Hyaluronsäurekonzentration in Grenzflächennähe zunimmt, konnte nicht bestätigt werden. Bei einem Druck von 50 bar entzog eine physiologische Hyaluronsäurelösung bei Abwesenheit von Lipiden einem Polyelektrolytfilm irreversibel Wasser. Dies wurde bei Anwesenheit einer Lipidmembran auf der Polyelektrolytoberfläche bis zu einem Druck von 600 bar nicht beobachtet. Diese Resultate können bedeutsam für das Verständnis der Entstehung von Gelenkserkrankungen sein. Es ist denkbar, dass der Knorpel bei einer abgelösten Lipidbeschichtung durch die hygroskopische Hyaluronsäure geschädigt wird.
Die vorliegende Arbeit beschäftigt sich mit der Analytik zweier Stoffgruppen anthropogenen Ursprungs in der aquatischen Umwelt, einerseits mit einer Auswahl antibiotisch wirkender Substanzen als Rückstände aus Arzneimittelanwendungen (Umweltproblem: bakterielle Resistenzen), andererseits mit der Stoffgruppe der perfluorierten Tenside (PFT) als Rückstände industrieller Verarbeitungs- und Veredelungsprozesse (Umweltproblem: Persistenz und Bioakkumulation). Der erste Schwerpunkt der Untersuchungen lag dabei auf der Entwicklung und Optimierung der Extraktions- und Anreicherungsmethoden in erster Linie aus wässrigen Matrizes sowie der Identifizierung und Quantifizierung dieser Substanzen mittels Kopplung von hochleistungsflüssig-chromatographischen Trenn- und massenspektrometrischen Detektionsverfahren. Das Untersuchungsspektrum ergab sich für die Antibiotika aus Datenerhebungen zum Antibiotikaeinsatz im Universitätsklinikum Bonn und aus der dokumentierten Verordnungspraxis innerhalb der gesetzlichen Krankenversicherung in Deutschland, für die perfluorierten Tenside (perfluorierte Alkylcarbonsäuren und perfluorierte Sulfonsäuren) anhand ihrer Leitsubstanzen PFOA (Perfluoroctansäure) und PFOS (Perfluoroctansulfonsäure) und deren kürzer- bzw. längerkettigen Homologen. Mit den jeweiligen Multikomponenten-Methoden (29 Antibiotika und 12 Perfluortenside) konnten Nachweis- und Bestimmungsgrenzen im ein- bis niedrigen zweistelligen ng/L-Bereich erreicht werden. Die Methoden wurden im Rahmen mehrerer, zum Teil bundesweiter Laborvergleichsuntersuchungen erfolgreich validiert. Den zweiten Schwerpunkt der Arbeit bildete die Anwendung der neuen Methoden bei der Untersuchung von Realproben: Im Bereich der Antibiotika wurde das Abwasser des Universitätsklinikums Bonn vom Ort seiner Entstehung über die Kläranlage bis in den Rhein untersucht. Zusätzliche Datenerhebungen erfolgten für weitere Kläranlagen und Oberflächengewässer in Nordrhein-Westfalen, ebenso wurden ein Talsperrenwasser (zur Trinkwassergewinnung) und einige oberflächenwasser-beeinflusste Roh- und Trinkwässer untersucht. Im gesammelten Abwasser des Universitätsklinikums konnten große Mengen der dort verordneten Antibiotika bestimmt werden. Die Antibiotikagehalte reduzierten sich bis in den Rhein durch Abbau, Adsorption an Feststoffe und Verdünnung um mehrere Zehnerpotenzen. Analoge Daten konnten für andere Kläranlagen und Oberflächenwässer ermittelt werden. Im Trinkwasser konnten keine Antibiotika nachgewiesen werden, nur die beiden Antibiotika Erythromycin und Sulfamethoxazol gelangten bis ins Rohwasser, konnten aber durch anschließende Trinkwasseraufbereitungstechniken entfernt werden. Die Substanz Sulfamethoxazol kann hier als Tracer dienen, um rechtzeitig eine Trinkwasserbelastung mit Antibiotikarückständen zu erkennen. Im Bereich der perfluorierten Tenside konnte im Rhein eine durchgehend niedrige Belastung des Wassers ermittelt werden, die Perfluorbutansulfonsäure (PFBS) bildete dabei die Hauptkomponente. Die Ruhr zeigte flussaufwärts stark ansteigende Belastungen mit perfluorierten Tensiden, wobei PFOA mit ca. 80% die Hauptkomponente bildete. Annähernd gleich hohe PFOA-Gehalte wurden auch im Trinkwasser gefunden, das durch künstliche Grundwasseranreicherung mit Ruhr-Wasser gewonnen wird. Durch diese Befunde wurden die Behörden auf eine illegale Industrieabfallentsorgung auf landwirtschaftlichen Flächen am Oberlauf der Möhne (Zufluss der Ruhr) aufmerksam, die zur Verunreinigung des Oberflächen- und des Trinkwassers führte, in deren Folge Konzentrationsobergrenzen für PFT beschlossen wurden, eine Nachrüstung der betroffenen Wasserwerke mit zusätzlichen Aufbereitungsschritten begonnen wurde und eine bundesweit Untersuchungstätigkeit auf perfluorierte Tenside ausgelöst wurde. Die Entdeckung der PFT-Belastung im Trinkwasser an der Ruhr führte zu einer weiteren Optimierung der Anreicherungsmethodik und einem beginnenden Normungsverfahren auf Basis dieser Methode. Durch die vorliegende Arbeit konnten zwei leistungsfähige Multikomponenten-Methoden zur Bestimmung von Antibiotika und perfluorierten Tensiden in wässrigen Matrizes entwickelt werden, mit deren Hilfe eine Belastung der Bevölkerung durch PFOA-kontaminiertes Trinkwasser erkannt und zur Behebung dieses Problems beigetragen werden konnte.
The goal of this thesis is the development of smooth and structured polyelectrolyte surfaces and to correlate the surface properties with their antifouling performance. Strategies in antifouling are focused on two aspects: surface chemistry and surface topography. Therefore, two types of surfaces, polysaccharide coatings with different chemistries and poly(acrylic acid)/polyethylenimine multilayers with different topographies, have been studied in this thesis. Three polysaccharides, hyaluronic acid (HA), alginic acid (AA) and pectic acid (PA), were covalently coupled on glass or silicon surfaces. The results of protein adsorption tests on these coatings indicate that surface charge, molecular conformation and reaction with calcium play important roles in the interactions between polysaccharides and proteins. The settlements of bacteria (Pseudomonas fluorescens, Vibrioalginolyticus, Cobetia marina and Marinobacter hydrocarbonoclasticus ), algae (Navicula perminuta and Ulva linza) and invertebrate cyprids (Balanus amphitrite) on polysaccharide coatings reveal that surface properties such as wettability, swelling in water and interactions with ions have great influence on biofouling. Polyelectrolyte multilayers were applied to study the effect of topography on marine biofouling. These multilayers were constructed by the deposition of the oppositely charged polyelectrolytes, poly(acrylic acid) (PAA) and polyethylenimine (PEI) through a layer-by-layer spray coating method. Hierarchical surface structures with different texture sizes and roughnesses were obtained by adjusting the pH of the polyelectrolyte solutions. Settlement of Ulva spores and barnacle cyprids was remarkably reduced by the multilayers with large texture size and high roughness. The effect of topography on biofouling is related to the attachment points between the surface and the fouling organisms. Surface modifications on polyelectrolyte multilayers with fluorinated silane and poly(ethylene glycol) (PEG) combined topography and chemistry. The antifouling performance of modified multilayers was determined by both the topography of the multilayer film and the chemistry of the surface. Several techniques were applied to analyze the surface properties of the coatings, including contact angle measurement, spectral ellipsometry, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and atomic force microscopy (AFM).
The main topic of this thesis is the comparative investigation of divalent selenium centers interactions in solids and solution. Therefore we decided to combine experimental and theoretical results in order to gather more insight into selenium – selenium interactions. The idea of using the chalcogen–chalcogen interactions as directional forces to obtain tubular structures was validated during recent experimental studies in which cyclic aliphatic diynes and dienes containing chalcogen atoms organized themselves in columnar structures. Moreover, theoretical investigations confirmed the description of divalent selenium interactions as a secondary interaction between an occupied p-type orbital of one chalcogen center (X) and the empty X-C sigma* orbital of the other, together with induction and dispersion forces. The first part of this work deals with the synthesis of three isomeric cyclophanes and their solid-state structures in comparison with previously synthesized similar cyclic compounds. The cycles investigated so far consisted of rigid units (e.g. X-CC-X, where X= S, Se, Te) and methylene chains as flexible parts. The inclusion of benzene rings into the methylene chains is expected to add more rigidity and also to open the possibility of pi-pi stacking. The synthesis of the three isomeric tetraselena-[6.6]cyclophanes 18(a-c) was achieved using a stepwise approach.Remarkable features of the solid-state structure of 18 a-c were analyzed and compared with other structural features of compounds that involved Se centers in Se•••Se interactions. The second part of this work investigates the presence and the strength of the Se•••Se interaction in solution. A series of model systems containing two selenium centers situated at a convenient distance, but also with significant internal motion ability, were synthesized. The NMR spectroscopy was the method of choice to investigate the interaction in solution. 77Se NMR chemical shifts are sensitive to the electronic environment around the Se atom, therefore their behaviour can be used as gauge for evaluating the strength of nonbonding interactions involving Se centers. Coupling constants (J coupling) and relaxation time determinations supported the findings from the investigations of 77Se NMR chemical shifts. Theoretical calculations at the MP2/6-311+g(d)//B98/6-311+g(d) level revealed the existence of four conformers for each of the investigated compounds, in which the Se•••Se interaction or the competing Se•••H bonding is the predominant force. Concluding, the investigation of the nature of the Se•••Se interactions show that the 77Se chemical shifts represent an useful tool in qualitatively assessing the strength of the interaction. The strength in the order MeSe•••SeMe < MeSe•••SeCCH < MeSe•••SeCN qualitatively revealed from the NMR chemical shifts is consistent with the nSe–sigma*Se-C orbital interaction model. It proves furthermore that electron correlation and dispersion forces play an intimately interconnected role in these interactions, that influence each other, therefore being difficult to analyze separately.
Im Rahmen dieser Arbeit wurden heteroleptische Diiminplatinkomplexe synthetisiert und charakterisiert. Anhand eines Dichloroplatin(II)-Komplexes wurde eine Festphasensynthese (auf der Basis eines Polystyrol-/Divinylbenzol-Copolymers, mit durch Fluoridionen spaltbarem Silyletherlinker) entwickelt und optimiert. Diese Synthesestrategie wurde anschließend auf die Synthese von ein- und mehrkernigen Catecholatoplatin(II)-Komplexen übertragen. Die Catecholatokomplexe wurden durch Oxidation in die entsprechenden Semichinonatokomplexe überführt, welche durch ESR- und UV/Vis/NIR-Spektroskopie charakterisiert wurden. Sowohl der Dichlorokomplex, als auch die Catecholatokomplexe zeigten in Lösung bei Raumtemperatur keine Lumineszenz. Deprotonierung der Komplexe führte bei den Catecholatokomplexen zu Lumineszenz, nicht jedoch beim Dichlorokomplex. Dieser Befund wurde mit Hilfe von DFT-Rechnungen erklärt, da eine Deprotonierung nur bei den Catecholatokomplexen zu einer Versteifung des Ligandensystems führt und somit möglicherweise eine strahlungslose Relaxation über eine Torsionsmode verringert wird. Durch die Kombination des Diiminfragments mit einem Ferrocenylsubstituenten und anschließender Koordination von Platinfragmenten wurden ein Dichloroplatin(II)-, ein Catecholatoplatin(II)- und ein Olefinplatin(0)-Komplex synthetisiert. Die Redoxeigenschaften dieser Komplexe wurden untersucht und aufgeklärt. Oxidation des Dichlorokomplexes mit [N(p-C6H4Br)3][SbCl6] („Magic Blue“) führte zu dem entsprechenden Ferroceniumkomplex. Einelektronenoxidation des Catecholatokomplexes führte zum Semichinonatokomplex. Ebenso wie beim Olefinkomplex führte eine Dreielektronenoxidation zur Dissoziation der Liganden und dem Entstehen des Dichlorokomplexes. Im ersten Fall wirkte „Magic Blue“ als unschuldiges Oxidationsmittel, im zweiten Fall wurde es jedoch nicht-unschuldig. Dies wurde durch NMR- und UV/Vis/NIR-Spektroskopie belegt. Das Dichlorodiiminplatin(II)-Fragment wurde mit einem photoaktiven Bis(terpyridin)ruthenium(II)-Baustein verknüpft, so dass ein potentieller Photokatalysator erhalten wurde. Tatsächlich wurde durch Bestrahlung in Gegenwart von Wasser und Triethylamin als Protonen- bzw. Elektronenlieferant eine Hydrierung von Tolan zu Stilben beobachtet. Mit Hilfe von DFT-Rechnungen wurden mögliche Wege des photoinduzierten Elektronentransfers bei dieser Reaktion analysiert.
The possible release of toxic and radioactive species from spent nuclear fuel in contact with water in a deep geological repository is expected to depend mainly on the rate of dissolution of the UO2 matrix. At the depth of the repository very low oxygen concentrations are expected. Moreover, large amounts of hydrogen are expected to be generated from the corrosion of iron containing canisters and containers. In this reducing groundwater environment UO2 has very low solubility. However, radiolysis of the ground water will produce reactive radicals and molecular products and can thereby alter the redox conditions. In this work different electrochemical techniques were used to study the corrosion behaviour of UO2 based materials in aqueous solutions in anoxic and reducing conditions. The possible influence of hydrogen on the corrosion mechanism of UO2 was investigated. In order to study the importance of the alpha activity level on the corrosion of the matrix, UO2 electrode samples doped with different concentrations of short-lived alpha emitters were used. In the frame of ACTINET Network of Excellence the collaboration between Institute for Transuranium Elements (ITU) in Karlsruhe, Germany and The Centre for Studies and Research by Irradiation (CERI) in Orléans, France made possible the use of a cyclotron generated He2+ beam to simulate high levels of alpha activities. Impedance Spectroscopy, together with potentiostatic polarization and cyclic voltammetry measurements were used on a variety of materials, ranging from depleted UO2 to 10% 233U doped UO2. A comparison was made between the electrochemical results and the results provided by the solution analysis and surface characterization. The good concordance of the results shows that the electrochemical techniques can be taken into consideration for the safety assessment of the final spent nuclear fuel repository.
Experimentelle Beobachtungen exotischer metabolischer Wellenphänomene zusammen mit gegenseitig phasengekoppelten NAD(P)H- und Calcium-Oszillationen in menschlichen Neutrophilen wurden publiziert. Da diese Phänomene Basis einer Kontroverse über ihre Charakteristiken und ihr Auftreten sind, stellt diese Arbeit eine mathematische Studie dieser Phänomene dar. Ziel des theoretischen raumzeitlichen Modellierungsansatzes ist es, einen plausiblen biochemischen Mechanismus zu entwickeln, der prinzipiell das Auftreten solcher Oszillationen und Wellenphänomene in Neutrophilen erklären kann. Das mathematische Modell schlägt dabei einen Calcium-kontrollierten Glucose-Einfluss in die Zelle als treibende Kraft der metabolischen Oszillationen vor und die reichhaltigen NAD(P)H-Wellenphänomene werden durch eine mögliche Rolle der Zellgeometrie und räumlich inhomogener Enzymverteilung erklärt. Die Modellierungsergebnisse sollen weitere Diskussionen zu den kontrovers diskutierten Phänomenen und experimentelle Bemühungen anregen, um die Existenz und die Charakteristiken von intrazellulären Dynamiken aber auch die biochemische Basis der zeitlichen und raumzeitlichen Calcium-Signalen und metabolischen Dynamiken in Neutrophilen aufzuklären. Unabhängig der experimentellen Beobachtungen in Neutrophilen stellt diese Arbeit eine generelle Studie zum Auftreten solcher Phänomene in Zellen dar, da keine Annahmen getroffen werden, die absolut spezifisch für Neutrophile sind.
Die vorliegende Arbeit beschäftigt sich mit der Koordinationschemie von makrozyklischen Peptiden, die aus Meeresorganismen, den Ascidien, isoliert werden können. Die strukturellen Eigenschaften dieser Verbindungen lassen einen Zusammenhang mit der hohen Metallionen-Konzentration, insbesondere von Kupfer(II), im Organismus der Ascidien vermuten. Ascidiacyclamid und die Patellamide A-F sind [24]Azakrone-8-Makrozyklen, die aus je zwei Oxazolin- und Thiazol-Einheiten aufgebaut sind. Westiellamid ist ein kleinerer [18]Azakrone-6-Makrozyklus, der aus drei Oxazolin-Einheiten aufgebaut ist. Die geringe natürliche Verfügbarkeit und die relativ aufwändige Synthese dieser sekundären Metaboliten erschwerte bisher detailierte Untersuchungen. Dennoch bestärken bereits veröffentlichte Studien die Vermutung, dass die oben genannten Makrozyklen im Metabolismus der Ascidien der Komplexierung von Metallionen dienen. Ziel dieser Arbeit war es, die Kupfer(II)-Koordinationschemie der natürlichen Makrozyklen mit Hilfe von geeigneten Modellverbindungen möglichst umfassend zu untersuchen. Der 24-gliedrige synthetische Makrozyklus H4L4, bestehend aus vier Imidazol-Einheiten, diente als Modellverbindung für Ascidiacyclamid und die Patellamide. Die Koordination von Kupfer(II) wurde mit Hilfe spektroskopischer und massenspektrometrischer Methoden (UV-Vis, CD, X-Band ESR, ESI-MS) untersucht und die Strukturen der Kupfer(II)-Komplexe auf Basis der experimentellen Ergebnisse mit Dichte Funktional Theorie Rechnungen (DFT) modelliert. Der Makrozyklus H4L4 koordiniert Kupfer(II) in einem komplementären NAzol-NAmid-NAzol-Bindungsmotiv. Durch Koordination eines einzelnen Kupfer(II)-Ions wird eine zweite Bindungsstelle präorganisiert. Die daraus resultierende Kooperativität führt zur stabilen Bindung eines zweiten Kupfer(II)-Ions. Die Reaktion des zweikernigen Kupfer(II)-Komplexes mit Base führt zu Hydroxo- und Oxo-verbrückten Kupfer(II)-Zentren. Durch Fixierung von CO2 aus der Luft bilden sich daraus Hydrogencarbonato- bzw. Carbonato-verbrückte Kupfer(II)-Komplexe. Bei hohen pH-Werten bildet sich eine violette Kupfer(II)-Spezies. Dabei handelt es sich vermutlich um einen einkernigen Hydroxo-Kupfer(II)-Komplex, der mit den oben beschriebenen Kupfer(II)-Komplexen im Gleichgewicht steht. Zusätzlich wurde die Synthese des neuen 24 gliedrigen Makrozyklus H4LascA entwickelt, der sich lediglich durch seine Alkylsubstituenten von den natürlichen Makrozyklen unterscheidet. Künftige Untersuchungen mit H4LascA werden Aufschluss über die Übertragbarkeit der beschriebenen Kupfer(II)-Koordinationschemie von H4L4 auf Ascidiacylamid und die Patellamide geben. Für Westiellamid (H3Lwa) mit drei Oxazolin-Einheiten wurden drei synthetische Analoga, bestehend aus je drei Imidazol- (H3L1), Oxazol- (H3L2) und Thiazol-Einheiten (H3L3), als Modellverbindungen verwendet. Die Koordination von Kupfer(II) an den 18-gliedrigen Imidazol-Makrozyklus H3L1 wurde ebenfalls mit Hilfe spektroskopischer und massenspektrometrischer Methoden (UV-Vis, CD, IR, X-Band ESR, ESI-MS) untersucht und die Interpretation der Ergebnisse durch zeitabhängige Studien (UV-Vis, X Band ESR, ESI-MS) unterstützt. Mit Westiellamid H3Lwa und den Makrozyklen H3L2-3 wurden die Untersuchungen aufgrund der geringen verfügbaren Menge auf ESR- und ESI-MS-Experimente beschränkt. Die Strukturen der Kupfer(II)-Komplexe wurden auf Basis der experimentellen Ergebnisse mit DFT Rechnungen modelliert. Im Gegensatz zu früheren Berichten komplexieren Westiellamid H3Lwa und die Makrozyklen H3L1-3 Kupfer(II) in einem präorganisierten und komplementären NAzol NAmid NAzol-Bindungsmotiv. Das Kupfer(II)-Ion hat darin eine verzerrt quadratisch pyramidale Koordinationsgeometrie, die im Fall der Makrozyklen H3L1-3 durch zwei koordinierte Methanol-Sauerstoffe und im Fall von Westiellamid H3Lwa durch einen koordinierten Methanol-Sauerstoff und einen weiteren NAzol-Stickstoff vervollständigt wird. Desweiteren konnte die Bildung zweikerniger Kupfer(II)-Komplexe beobachtet werden, in denen die Kupfer(II)-Zentren durch ein Methanolat oder Hydroxid verbrückt werden. Während die Kupfer(II)-Zentren in H3L1 stark antiferromagnetisch gekoppelt sind, kann für den zweikernigen Kupfer(II)-Komplex von H3L3 ein Dipol-Dipol gekoppeltes ESR-Spektrum beobachtet werden. Die unterschiedlichen strukturellen Eigenschaften der Makrozyklen und die unterschiedliche Nukleophilie der NAzol Stickstoffe führen zu einer geringeren Stabilität der zweikernigen Kupfer(II)-Komplexe von H3Lwa und H3L2, so dass in diesen Fällen kein ESR-Signal detektierbar ist.
Die vorliegende Arbeit behandelt die Untersuchung verschiedener mono- and disubstitutierter Gallylferrocene bzgl. ihrer Synthese und Struktur sowie der sich daraus ergebenden chemischen und physikalischen Eigenschaften. Das Bis(diaminogallyl)ferrocen [{Fe(eta 5-C5H4)2}{Ga(tmp)2}2] 8 und das monosubstitutierte Gallylferrocen [{(eta 5-C5H5)Fe(eta 5-C5H4)}{Ga(tmp)2}] 9 erwiesen auf Grund ihrer einfachen Synthese sich als die am besten geeigneten Startmaterialien zur Synthese von anderen gallyl-substitutierten Ferrocenen und Gallaferrocenophanen. Zudem wurden zwei weitere gallyl-substitutierte Ferrocene [{Fe(eta 5-C5H4)2}{Ga{N(SiMe3)2}2}2] 10 und [{(eta 5-C5H5)Fe(eta 5-C5H4)} {Ga{N(SiMe3)2}2}] 11 erhalten. Bei der Reaktion von 8 und 9 mit unterschiedlichen Säuretypen wurden verschiedene Reaktionsweisen beobachtet. Die Behandlung von 8 und 9 mit einprotonigen Säuren wie Essigsäure, Ethanol oder Phenol ergab die gallyl-substitutierten Ferrocene 14 – 17 und 20 – 22. Die so erhaltenen neuen gallyl-subtituierte Ferrocene wurden durch Protonierung und Abspaltung der tmp-Gruppen an den Gallium-Atomen gebildet. Dies sind [tmpH2]+2[{Fe(eta 5-C5H4)2}{Ga(O2CMe)3}2]2- 14 und [tmpH2]+[{(eta 5-C5H5)Fe(eta 5-C5H4)} {Ga(O2CMe)3}]- 20, [tmpH2]+2[{Fe(eta 5-C5H4)2}{Ga(O-C6H5)3}2]2- 16, [Li(thf)2]+2[{Fe(eta 5-C5H4)2}{Ga(O-C6H5)3}2]2- 17, [tmpH2]+[{(eta 5-C5H5)Fe(eta 5-C5H4)} {Ga(O-C6H5)3}]- 21, [Li(thf)2]+[{(eta 5-C5H5)Fe(eta 5-C5H4)}{Ga(O-C6H5)3}]- 22 und [{Fe(eta 5-C5H4)2}{GaOEt}2O]4 15. Die Reaktion von 8 oder 9 mit organischen Disäuren wie Malonsäure und Catechol führte unter Spaltung sowohl der GaN- als auch der GaC-Bindungen zu [tmpH2]+3[{CH2(COO)2}3Ga]3- 18 und [tmpH2]+2[(sigma-C6H4-O2)2Ga(OC6H4OH)]2- 19. Lässt man 8 mit Kohlenstoffdioxid reagieren, bildet sich unter Insertion in die GaN-Bindungen das Carbaminat [{Fe(eta 5-C5H4)2}{Ga(O2Ctmp)(µ2-O2Ctmp)}2] 13.
Die Einzelmolekülfluoreszenzspektroskopie wurde in den letzten Jahren erfolgreich zur Untersuchung biologischer Fragestellungen eingesetzt. Dynamische Wechselwirkungen kleiner Biomoleküle, wie z.B. DNS, RNS, Proteine oder enzymkatalytischer Reaktionen, konnten beobachtet werden. Aufbauend auf diesen Verfahren konnte in dieser Arbeit die Grundlage zur Untersuchung heterogener oder homogener katalytischer Reaktionen einfacherer organischer oder anorganischer Systeme geschaffen werden. Dazu wurde eine Fluoreszenzsonde entwickelt, deren Fluoreszenz durch Cu(II)-Ionen gelöscht wird. Die Sonde besteht aus einem DNS-Doppelstrang, welcher als starres Gerüst dient, und endständig mit einem Cu(II)-spezifischen Liganden 4,4’-Dicarboxy-2,2’-bipyridin (dcbpy) sowie einem Fluoreszenzfarbstoff markiert ist. Um einen geeigneten Fluoreszenzmarker zu finden, wurde eine Reihe Farbstoffe bezüglich ihrer Fluoreszenzlöschung durch Cu(II) charakterisiert. Als besonders geeignet wurden die Farbstoffe Tetramethylrhodamin (TMR), Atto620, MR121 und Atto635 ausgewählt und die Sonde damit markiert, eine bis zu 92-prozentige Fluoreszenzlöschung nach Bindung von Cu(II) am Liganden konnte beobachtet werden. Zur Untersuchung, ob die Ligand-Modifikation ursächlich für die verstärkte Löschung durch Cu(II) ist, wurden Kontrollmessungen mit einer Sonde ohne dcbpy-Modifikation durchgeführt. Mit Ausnahme der Atto635-markierten Sonde konnte bei allen Sonden eine verstärkte Löschung durch den dcbpy-Liganden beobachtet werden. Die beste Unterscheidbarkeit zwischen Ligand-markierter- und Kontrollsonde ergaben die Farbstoffe Atto620 und TMR. Zur quantitativen Bestimmung der Komplexgleichgewichtskonstante aus der Fluoreszenzlöschung wurde die Stern-Volmer Theorie auf die hier entwickelten Sonden angepasst, so dass eine Restfluoreszenz im gelöschten Zustand berücksichtigt werden konnte, und der experimentelle Kurvenverlauf erklärt werden konnte. Die Anpassung der Modellparameter erlaubt die Bestimmung der Gleichgewichtskonstante der Komplexbildung K, sowie der relativen Quantenausbeute des gelöschten Zustands Aus. Für die mit Atto620 markierte Sonde wurde K zu 5,9 ∙ 106 M-1 und Aus zu 35 % bestimmt, für die mit TMR markierte Sonde ergab sich K zu 8,5 ∙ 106 M-1 mit Aus = 8 %. Die Spezifität der Sonden wurde mit Löschexperimente in Gegenwart von Mn(II), Fe(II), Ni(II), und Co(II) an der TMR-markierten Sonde untersucht und mit dem modifizierten Stern-Volmer Modell ausgewertet. Mit Ausnahme von Ni(II), das eine relative Quantenausbeute im gelöschten Zustand Aus von 22 % zeigte, stören diese Ionen mit Aus von > 55 % die Messung von Cu(II) kaum. Mit Hilfe der Einzelmolekülspektroskopie wurde die Fluoreszenzlöschung durch Komplexbildung der TMR- und der Atto620-markierten Sonde mit Cu(II) untersucht. Dazu wurde die Sonde auf einer Glasoberfläche immobilisiert und die Fluoreszenz einzelner Sonden nacheinander mit einem konfokalen Mikroskop aufgezeichnet. Dies ermöglichte erstmals die direkte Beobachtung aufeinander folgender Assoziations- und Dissoziationsereignisse. Die Ereignisse sind als Sprünge zwischen zwei Fluoreszenzintensitätsstufen erkennbar, d.h. die Sonde wechselte durch Bindung von Kupfer(II) von einem stark fluoreszierenden An-Zustand in einen schwach fluoreszierenden Aus-Zustand. Dieses Verhalten wurde sowohl bei der TMR-Sonde als auch der Atto620-Sonde beobachtet, wobei sich die Fluoreszenzrate bei der TMR-Sonde um ~90 % verringerte und bei der Atto620-Sonde um ~66 %, in sehr guter Übereinstimmung mit den Ensemble-Messungen. Zur quantitativen Bestimmung der Assoziations- bzw. Dissoziationsraten wurde die Dauer dieser einzelnen Zustände mit Hilfe der Schwellwertanalyse ermittelt und schließlich aus der Häufigkeitsverteilung die Reaktionsraten bestimmt. Zur Verbesserung der Zeitauflösung wurden weitere Analysemethoden angewendet: die Autokorrelation des Fluoreszenzsignals sowie ein computergestützter Algorithmus auf Basis eines „Hidden Markov“ Modells (HMM). Beide Methoden zeigten eine weitere schnellere Kinetik mit An- und Aus-Zeiten von wenigen Millisekunden die in unregelmäßigen Abständen auftrat. Mit der auf HMM-basierten Methode konnten unter Vorgabe eines Drei-Zustandsmodells die kinetischen Parameter der Komplexbildung sowie die der schnellen Fluktuationen bestimmt werden. Die Aufklärung der Ursache dieser schnellen Fluktuationen sind Bestandteil weiterer Experimente. In dieser Arbeit wurden zwei Hauptgebiete realisiert: die Entwicklung einer Fluoreszenzsonde zur Untersuchung einfacher chemischer Reaktionen an einzelnen Molekülen, was der Ausgangspunkt für die Untersuchung komplexerer Systeme, wie z.B. Metallkomplex-katalysierte Reaktionen, darstellt. Mit der Entwicklung und Automatisierung von Methoden zur Auswertung zeitlich fluktuierender Fluoreszenzintensitäten wurde die Grundlage zur Bestimmung von Kinetiken mit Hilfe der Einzelmolekülspektroskopie gelegt. Dies ermöglichte die Bestimmung der Reaktionskinetik der Komplexbildung von Cu(II) mit einem Bipyridinderivat im thermodynamischen Gleichgewicht.
Biofunktionalisierte mikrostrukturierte Oberflächen wurden als ideales Plattformsystem zur Kultivierung permanenter, sowie primärer Zellkultursysteme und zur Analyse der zwischen ihnen ausgebildeten Tunneling Nanotubes (TNTs) etabliert, die eine neuartige Form interzellulärer Kommunikation darstellen. Um eine optimale Zellvereinzelung auf den Plattformen zu gewährleisten wurden unterschiedliche Zelltypen durch geeignete, kovalent an die Goldpunkte angebundene Liganden vereinzelt auf den Goldpunkten der mikrostrukturierten Oberflächen immobilisiert. Diese Vereinzelung stellt eine entscheidende Voraussetzung für die Detektion der TNTs dar. Die optimierten, mittels photolithographischer Verfahren hergestellten Plattformen wurden im Zuge der Arbeit zur präzisen Analyse einer sowohl chemischen, als auch mechanischen Beeinflussung der Bildung, bzw. Stabilität von TNTs herangezogen. Zudem wurden die Strukturen hinsichtlich ihrer strukturellen Eigenschaften durch kraftspektroskopische Messungen im Detail charakterisiert, wobei unter anderem erstmals die Kraft ermittelt werden konnte, die nötig ist, ein TNT zum Reißen zu bringen.
In the present work a chemical kinetic mechanism was developed, suitable for modeling combustion and partial oxidation processes of C1 – C4 alkanes. The gas-phase kinetic mechanism describes intermediate and high temperature chemistry. Accordingly, the formation and evolution of important intermediate gas-phase species: Olefins and oxygenates were described in terms of different pathways typical at those temperature regimes. A previously developed mechanism suitable for high temperature conditions was extended by including reactions which described the chemistry of total and partial oxidation of methane, ethane, propane, butane, lower alkenes and formation and consumption of their characteristic organic hydro-peroxide radicals and cyclical compounds. The kinetic mechanism was validated by comparing calculated results of ignition delay times, against experimental data obtained in shock tubes, for various hydrocarbons and their mixtures, over a wide range of reaction conditions (temperature, pressure and mixture composition). Further, the kinetic mechanism was evaluated by comparing numerical simulations against experimentally obtained concentration profiles of the main gas-phase species, measured in jet stirred reactors for different hydrocarbons and their mixtures during partial oxidation. Next, the mechanism was applied to get a better understanding of the interactions between flow, mass transfer and homogeneous-heterogeneous chemistries during the catalytic partial oxidation of methane in a short contact time reactor, which has recently attracted strong scientific and technological interest. The detailed study of the catalytic partial oxidation of methane to syngas in a single gauze reactor was based on three-dimensional numerical simulations of the flow field coupled with heat transport and multi-step gas-phase and surface reaction mechanisms, including the computation of the surface coverage. Results from the model were compared with experimental data reported in the literature. The gas-phase mechanism was modeled using a reduced mechanism, and for the surface a previously developed mechanism was adapted. The results from the simulation of the partial oxidation of methane in a short contact time reactor were carried out using the commercial computational fluid dynamics code Fluent, which was coupled with external subroutines to model the detailed gas-phase and surface chemistry. Today, the production of synthesis gas (carbon monoxide + hydrogen) is currently carried out via steam reforming. In that process steam passes over a carbon source, often methane or coal, and is heated to produce the synthesis gas. Synthesis gas is extremely valuable commercially for the production of methanol, hydrocarbons, higher alcohols for use in detergents, and ammonia to use in fertilizers. There is also a significant interest in the production of hydrogen for fuel cells. However, steam reforming has the major disadvantage of being endothermic and hence requires a large amount of wasted energy to drive the reaction. An alternative to steam reforming is the partial oxidation of the hydrocarbons, especially methane in short contact time reactors. This promising route for natural gas conversion into more useful chemicals has the advantage of being auto thermal.
In der vorliegenden Arbeit wurde ein Ansatz zur Überstrukturierung, von bereits mit Gold-Nanopartikeln dekorierten Oberflächen, entwickelt. Bei letzteren handelt es sich um Glasoberflächen, die durch die Methode der mizellaren Nanolithograpie mit Gold-Partikeln strukturiert wurden. Diese sogenannten Gold-Nanodots besitzen einen Durchmesser von etwa 5 nm und befinden sich in einem Abstand von etwa 58 nm, in einer hexagonalen Anordnung zueinander. Diese Gold-Nanostruktur wurde durch Adsorption einer photolabilen Thiolverbindung, die eigens synthetisiert wurde, auf photochemischen Wege im µm-Maßstab über¬strukturiert. Neben einer Thiol-Kopfgruppe, welche die Adsorption auf den Gold-Nanopartikel unter Ausbildung einer kovalenten Gold-Schwefel-Bindung ermöglicht, weist diese Verbindung als Kopfgruppe die photolablie MeNPOC-Schutzgruppe auf. Diese kann durch Bestrahlung mit Licht einer Wellenlänge von etwa 419 nm abgespalten werden. Hierbei wird eine Aminogruppe freigesetzt, welche für weitere Kopplungsreaktionen eingesetzt werden kann. Zur photochemischen Strukturierung wurden Photomasken verwendet, die eine reguläre Lochstruktur aufweisen und nach Adsorption der Thiolverbindung auf die Oberflächen aufgelegt wurden. Die Abspaltung der Schutzgruppe findet in diesem Fall nur an den freiliegenden Stellen statt, die der Strahlung exponiert sind. Auf diese Weise ist es möglich, die Struktur der Maske in eine äquivalente aminostrukturierte Oberflächenbeschichtung umzusetzen. Zur Strukturierung wurden hierbei u.a. Lochmasken eingesetzt, die einen Lochdurchmesser von etwa 1000 µm und einen Loch-zu-Loch-Abstand von etwa 1000 µm aufweisen. Die erzeugten Amino-Funktionalitäten wurden anschließend zur Protein-Immobilisierung genutzt. Hierzu wurde zunächst unter Ausbildung einer Amidbindung Biotin gekoppelt und anschließend mit Streptavidin umgesetzt. Letzteres besitzt insgesamt 4 Rezeptorstellen, an denen der Ligand Biotin durch nicht-kovalente Bindungskräfte spezifisch mit einer sehr hohen Bindungskonstante von etwa 1015 M-1 gebunden werden kann. Zur chemischen Charakterisierung der erzeugten Monolagen kamen unterschiedliche oberflächenanalytische Methoden, wie z.B. die XPS- und IRRA-Spektroskopie zum Einsatz. Auf diese Weise war es möglich, neben der Thioladsorption sowohl die Schutzgruppenabspaltung und anschließende Protein-Immobilisierung nachzuwei¬sen. Mittels XPS konnten zudem Schichtdicken für die einzelnen Umsetzungsschritte bestimmt werden, anhand derer die einzelnen Umsetzungsschritte ebenfalls gut belegt werden konnten. Diese zeigten zudem eine gute Übereinstimmung mit den entsprechenden Werten, die mittels QCMD bestimmt wurden. Durch den Einsatz von fluoreszenzmarkiertem Streptavidin war es darüber hinaus möglich, die unterschiedlichen Strukturierungsstufen neben rasterelektronenmikro¬skopischen auch durch fluoreszenzmikroskopische Aufnahmen bildgebend nachzuweisen. Insgesamt stellt die vorliegende Arbeit somit einen ersten Schritt zum Studium abstandsabhängiger Wechselwirkungen in komplexeren biologischen Verbundsystemen dar.
Ziel der hier vorliegenden Arbeit war die Entwicklung fluoreszenzgelöschter Sonden, welche auf der Fluoreszenzlöschung durch photoinduzierten Elektronentransfer basieren. Es wurden zwei molekulare Sonden weiterentwickelt, die durch Guanin gelöscht werden. Einerseits wurden (i) SMART PROBES zur schnellen und spezifischen Identifizierung verschiedener Mykobakterienspezies eingesetzt. Darüber hinaus konnten (ii) SNAP-TAGS zur selektiven Markierung von Proteinen in Säugerzellen und Bakterien angewendet werden. Die der Arbeit zugrunde liegende Idee war es, eine gesteigerte Sensitivität dieser Methoden durch gezielte Fluoreszenzlöschung und damit einhergehend eine Reduzierung von unspezifischer Hintergrundfluoreszenz zu erreichen. Die spezies-spezifische, sensitive, zuverlässige und kostengünstige Identifizierung bestimmter DNA-Sequenzen als Instrument der Diagnostik bakterieller Erreger ist aufgrund unterschiedlicher Behandlungsstrategien sowie des stetigen Auftretens neuartiger Erreger von großer Bedeutung für die Routinediagnostik. Eine besondere Herausforderung stellt hierbei das Genus Mycobacterium mit seinen aktuell mehr als 100 valide beschriebenen Arten dar. Die Identifizierung sowie die exakte Differenzierung dieser Erreger sind vor allem aufgrund des zumeist sehr langsamen Wachstums der Mykobakterien von zwölf bis 20 Stunden erschwert. Ein schnelles und kostengünstiges Verfahren ist daher dringend erforderlich. Traditionelle, auf biochemischen Merkmalen gründende Identifikationssysteme werden dabei in den letzten Jahren immer mehr von molekularbiologischen Verfahren abgelöst. Eines dieser neuen Verfahren basiert auf dem Einsatz von SMART PROBES. Sie können in einem neuen, hochempfindlichen DNA-Nachweisverfahren zur Früherkennung antibiotikaresistenter Erreger eingesetzt werden. SMART PROBES sind DNA-Haarnadelsonden, welche durch konformative Änderung der Struktur entweder im fluoreszenzgelöschten oder im fluoreszierenden Zustand vorliegen. Diese Sonden wurden am Physikalisch-Chemischen Institut der Universität Heidelberg entwickelt. Die räumliche Nähe des Farbstoffs zu mehreren Guanosin-Nukleobasen in der Stamm-Schleife-Struktur führt zu einer Löschung des Fluorophors. Bei Zugabe von Gegensequenz öffnet sich die SMART PROBE, was eine lokale Trennung von Farbstoff und Guanosin bewirkt, woraus ein messbarer Fluoreszenzanstieg resultiert. Der zweite Teil der Arbeit beschäftigte sich mit SNAP-TAGS. Diese stellen eine neue Methode zum kovalenten Markieren von Fusionsproteinen mit synthetischen Farbstoffen sowohl für in vitro wie auch für Anwendungen in lebenden Zellen dar. Herkömmliche Methoden zur Fluoreszenzmarkierung von Proteinen greifen auf reaktive Farbstoffe oder autofluoreszierende Proteine zurück. Diese Methoden sind jedoch beschränkt durch die fehlende Selektivität beziehungsweise durch die Größe (Green Fluorescent Protein (GFP) ~ 27 kDa) der fluoreszierenden Proteine, welche oftmals der Größe des zu untersuchenden Proteins entsprechen. Des Weiteren weisen autofluoreszierende Proteine oft eine komplizierte Photophysik sowie eine geringe Photostabilität auf. Invasive Methoden, welche organische Fluorophore durch Elektroporation, Mikroinjektion oder Endozytose in die Zelle schleusen, schädigen die Zelle, wodurch ihre Funktionalität oft nicht mehr gewährleistet ist. Die SNAP-TAG Markierung bietet hier eine nicht invasive Alternative. Sie basiert auf dem irreversiblen Transfer der Benzylgruppe von O6-Benzylguanin (O6-BG) auf das DNA-Reparaturprotein O6-Alkylguanin-DNA Alkyltransferase (AGT). Dieses Protein besitzt spezifische Aktivität für O6-BG-Derivate, die zum kovalenten Markieren von AGT-Fusionsproteinen in vitro und in lebenden Zellen eingesetzt werden. Um das Potenzial der AGT-Markierung zu testen, wurden in dieser Arbeit 30 BG-Farbstoffsubstrate synthetisiert, welche den gesamten sichtbaren Wellenlängenbereich abdeckten. Die BG-Substrate wurden zunächst hinsichtlich ihre photophysikalischen Eigenschaften, Lebensdauer und relativen Quantenausbeute untersucht. Hierbei konnten neun fluoreszenzgelöschte Substrate ermittelt werden, welche den Wellenlängenbereich von 425 nm bis 700 nm abdecken. Um den Fluoreszenzanstieg nach der Markierung von AGT zu ermitteln, wurden die Substrate mit isoliertem hAGT in in vitro Experimenten eingesetzt. Für die Anwendung der AGT-Markierung in lebenden Zellen wurden zum einen AGT-Fusionsprotein exprimierende Escheria coli eingesetzt, zum anderen AGT-defiziente CHO-Zellen (Chinesische Hamster Ovarien), welche mit Expressionsvektoren transfiziert waren, die das Gen eines AGT-Fusionsproteins enthielten. Bei letzteren war das Fusionsprotein im Nukleus lokalisiert.
Zusammenfassung In Rahmen dieser Arbeit wurde die Adsorption von Huminsäure auf Aluminiumoxidoberflächen in Abwesenheit (binäres System) und Gegenwart (ternäres System) von Gadolinium studiert. Die Untersuchungen stehen im Zusammenhang mit der Bewertung von Umweltrisiken, die mit dem Langzeitbetrieb eines Endlagers für radioaktive Abfälle verbunden sind. Zu diesem Zweck müssen die verschiedenen Wechselwirkungsprozesse zwischen Radionukliden und ihrer Umgebung, d.h. dem umgebenden Gestein oder Boden, im Detail untersucht werden. Das Grundwasser in solchen Endlagern ist üblicherweise mit organischen Stoffen aus biologischen Abbauprozessen angereichert, den sogenannten Huminstoffen. Da diese ausgeprägte Komplexierungs- und Redoxeigenschaften aufweisen, wird ihnen eine große Bedeutung für die Rückhaltung und den Transport von Radionukliden zugeschrieben. In der vorliegenden Untersuchung dient Aluminiumoxid als eine Modelloberfläche für Ton, eine der wichtigsten geologischen Barrieren, die für Endlagerstätten diskutiert werden. Gadolinium wird als Analogon für dreiwertige Aktinide verwendet. Die Haupttechnik, die in dieser Studie eingesetzt wurde, ist Gravimetrie mittels Schwingquarztechnologie (QCM-D, Quartz Crystal Microbalance with Dissipation Monitoring). Ellipsometrie und Röntgenphotoelektronenspektroskopie (XPS) ergänzen die Untersuchungen. Eine der größten Herausforderungen der Arbeit war die Herstellung stabiler Aluminiumoxidbeschichtungen für QCM-Sensoren. Hierzu wurden verschiedene Beschichtungsmethoden, wie Sputtern und thermische Bedampfung, getestet und optimiert, um schließlich vergleichsweise stabile Schichten zu erhalten. Unter Verwendung der QCM-D-Technologie konzentrierten wir uns auf das Studium der Adsorptionsprozesse als Funktion des pH-Wertes und der Huminstoffkonzentration. Die Variation des pH-Wertes ergab dabei einen interessanten Einfluss auf das Adsorptionsverhalten der multifunktionalen Huminstoffe. Adsorption bei pH 5, 6.8 und 9 führte nur zur Ausbildung einer Huminstoff-Monolage. Bei pH 3 wurde hingegen ein Zwei-Stufen-Prozess beobachtet, bei dem auf die Monolagenadsorption die Physisorption von Molekülaggregaten folgt. Eine Variation der Huminstoffkonzentration ergab, dass der größte Teil der Monolage bereits bei niedrigen Konzentrationen von 1-5 mg/l gebildet wird und bei einer Konzentration von 10-20 mg/l Sättigung auftritt. Obwohl sich die gemessenen Isothermen gut mit einem Langmuir-Mechanismus fitten lassen, widerspricht die Tatsache, dass die Huminstofffilme irreversibel adsorbiert sind, einer derartigen Dateninterpretation. Das Adsorptionsverhalten lässt sich besser durch die Entfaltung adsorbierter Huminstoffmoleküle erklären. Auf diese Weise bilden sich dünnere Schichten aus, wenn die Filme aus höher verdünnten Lösungen abgeschieden werden. Die Adsorptionsphänomene im ternären System zeigen ähnliche Tendenzen hinsichtlich pH- und Konzentrationseffekten, wie sie auch für das binäre System beobachtet werden. Die Struktur der Adsorbatschicht im ternären System besteht vermutlich aus einer Huminstoff-Monolage, an die über Gadoliniumbrücken eine zweite Huminstoffschicht gebunden ist. Dies kann auch die verlangsamte Adsorptionskinetik im ternären System erklären.
Im Rahmen der Arbeiten zu dieser Inaugural-Dissertation wurden Wege zur Synthese verschiedenster phosphorhaltiger, aromatischer Diamine aufgezeigt, die sowohl als Härter als auch als Flammschutzmittel für Epoxidharze Verwendung finden sollten. Unter anderem wurden Wege zur Darstellung von drei neuartigen phosphorhaltigen Diaminotriphenylderivaten mit unterschiedlicher chemischer Umgebung des Phosphors erarbeitet. Ergänzend wurden verschiedene Diaminotriphenylphosphinate dargestellt. Weiters konnte - ausgehend vom aus meta-Nitrobenzaldehyd und meta-Nitroanilin dargestellten Imin - mit 9,10-Dihydro-9-oxa-10-phosphaphenanthren-10-oxid (DOPO) das entsprechende Additionsaddukt synthetisiert und im Anschluss reduziert werden. Es wurden umfangreiche Untersuchungen zur zerstörungsfreien Nitrierung von alkylierten und alkoxylierten DOPO-Derivaten mittels Acetanhydrid und rauchender Salpetersäure unternommen. Die entstandenen Nitroverbindungen konnten teilweise in guten Ausbeuten gewonnen und zu den entsprechenden Aminoderivaten reduziert werden. Letztlich wurden kohlefaserverstärkte Verbundwerkstoffe auf Basis eines kommerziellen Epoxidharzes einerseits und phosphorhaltigen aminischen Härtern sowie Additiven andererseits gefertigt und ihr Brandverhalten im Cone-Kalorimeter untersucht.
Kurzzusammenfassung Xanthenfarbstoffe, die sich vom Rhodamin- und Fluorescein-Grundgerüst ableiten, zeichnen sich durch eine intensive Fluoreszenz aus und sind daher als molekulare Sonden für bioanalytische Anwendungen und das zelluläre Imaging von großer Relevanz. In dieser Arbeit wurden Derivate von Xanthenfarbstoffen synthetisiert, die auf biologisch wichtige Metallionen ansprechen, ungewöhnliche Akkumulation und subzelluläre Verteilungen in lebenden Zellen zeigen oder Fluoreszenzsensoren für Redoxpotentiale sind. Die wichtigsten neu entwickelten Sonden und ihre Anwendungen sind hier zusammengefasst: •Fluorogene Sonde für Cu2+-Ionen Während literaturbeschriebene Cu2+ Fluoreszenzsensoren durch Fluoreszenzlöschung auf Cu2+-Ionen ansprechen, ist das dargestellte Dipicolinoylfluorescein ein seltenes Beispiel für eine fluorogene Cu2+-Sonde. Durch Cu2+ vermittelte Esterhydrolyse wird Fluorescein gebildet. Das Detektionslimit liegt bei 100 nM Cu2+. Die literaturbekannte fluorogene Sonde Diacetylfluorescein wurde für ein Screening der Esteraseaktivität von Rinderserumalbumin eingesetzt. Durch Dotierung mit Cu2+ und anderen Metallionen konnte die sehr schwache Aktivität geringfügig gesteigert werden, jedoch nicht in einem für präparative Anwendungen ausreichenden Maß. •Metallbindende Sonde Terpyridinfunktionalisierte Rhodamine reichern sich ungewöhnlich stark in lebenden Zellen an. Dies könnte auf die intrazelluläre Assoziation der Terpyridin-Einheit mit Zn2+, das proteingebunden ist, aber noch über freie Koordinationsstellen verfügt, zurückzuführen sein. Extrazelluläres Zn2+ verhindert durch die Komplexierung die Aufnahme von terpyridin-funktionalisiertem Rhodamin in die Zelle. Die zelluläre Aufnahme kann folglich durch extrazelluläres Zn2+ gesteuert werden. •Redoxsensor Während es fluoreszierende molekulare Sonden für intrazelluläre pH-Wert Messungen bereits in zahlreichen Varianten gibt, besteht ein Bedarf an Fluoreszenzsensoren für biologische Redoxpotentiale. Ein Sensor für Redoxpotentiale wurde dargestellt, indem ein Hydrochinon an einen Rhodamin-Farbstoff gekoppelt wurde. Dem Design des Redoxsensors liegt zugrunde, dass Chinone oft gute Fluoreszenzlöscher sind, während die reduzierte Hydrochinonform die Fluoreszenz meist wenig beeinflusst. Die Fluoreszenz des Rodoxsensors wird reversibel gelöscht, wenn die Hydrochinonkomponente durch H2O2 zur Chinonform oxidiert wird. Mit Thiolen kann die Hydrochinonform und die Fluoreszenz regeneriert werden.
Neue phosphacyclische Flammschutzmittel wurden synthetisiert, in verschiedene Epoxidharze eingebracht und auf ihre Flammschutzmittelwirkung getestet. Hierbei offenbarten sich phosphacyclische Verbindungen als effektive Flammschutzmittel im Gegensatz zu nicht-phosphacyclische. Basierend auf diesem Vergleich wurden Studien zu den Wirkmechanismen durchgeführt und für die effektiven Flammschutzmittel eine Wirkung über die Gasphase festgestellt.
Ein ausf¨uhrliches, quantitatives Verständnis, welches durch Modellieren erzielt wird, sowie das Ermöglichen einer spezifischen externen Steuerung des zellularen Verhaltens sind allgemeine langfristige Ziele der modernen biowissenschaftlichen Forschung in der Systembiologie. Selbstorganisation ist möglicherweise ein allgemein gültiges Prinzip für die zelluläre Organisation, da viele dynamische Eigenschaften zellulärer Strukturen sowohl hinsichtlich ihrer Bildung, Aufrechterhaltung und Funktion diesem folgen. Die Steuerung selbstorganisierter Dynamiken eröffnet einen Weg zur Untersuchung von dynamischem Verhalten sowie zur Generierung des gewünschten Verhaltens. Um dieses Ziel zu verwirklichen, konzentriert sich diese Dissertation in erster Linie auf die gezielt orientierte Beeinflussung dieser Systeme durch optimale Steuerungsmethoden. Der Ansatz optimaler Steuerung bietet große Flexibilität hinsichtlich der Bestimmung der Zielfunktionen. Wir verwenden eine direkte, auf den Multiple-Shooting-Ansatz basierende numerische Optimiermethode, welche insbesondere auf nichtlineare selbstorganisierende Systeme verwendbar ist. Die vorliegende Arbeit zeigt, wie auf Modellen basierende optimale Steuerungsmethoden zum Erzeugen der gewünschten Systemdynamiken verwertet werden können. Im Fall des Circadischen Rhythmus und der Belousov-Zhabotinsky (BZ) Reaktion als Modellsysteme sind diese bezüglich der zeitabhängigen Steuerungsparameter nicht systemimmanent. Wir analysieren ein Circadisches Oszillatormodell des zentralen Uhrmechanismus für die Fruchtfliege Drosophila und zeigen, wie auf Modellen basierende optimale Steuerung, Phasenneueinstellung, Design von chronomodulierten Puls-Stimuli-Schemata zur Wiederherstellung des Circadischen Rhythmus in den Mutanten und optimale Phasensynchronisierung zwischen der Uhr und ihrer Umgebung erlaubt. Wir beziehen uns sowohl auf die optimalen Open-Loop- als auch auf die Rückkopplungssteuerungsmethoden. Circadische Rhythmen können das Timing und den Eintritt des Zellzyklus erheblich beeinflussen. Zur Untersuchung der auf Modellen basierenden optimalen Steuerungsszenarios sind ein detaillert gekoppelter Circadischer Zyklus und das Zellzyklusmodell f¨ur ein Säugetiersystem entwickelt worden. Erstergebnisse der numerischen Simulationen für den gekoppelten Circadischen Zyklus und das Zellzyklusmodell werden gezeigt. Insbesondere leicht zugängliche chemische Testrohrsysteme wie die BZ Reaktion sind für Untersuchungen der Steuerung selbstorganisierter Dynamiken sehr gut geeignet. Denn sie bieten ein Mittel für die Charkterisierung des Verhaltens, das für kompliziertere biologische Systeme relevant ist. Wir entwickeln ein ganz neuartiges detaillertes Modell für die lichtempfindliche BZ Reaktion, das auf einem Elementarreaktionsmechanismus beruht und reduzieren dieses aufgrund der Quasi-Steady-State- (QSSA) und partielle Gleichgewichtsnäherungen (PEA) explizit. Zur Stabilisierung instabiler stationärer Zustände sind systematische Analysen und auf Modellen basierende Steuerungen durchgeführt worden, woraus periodische Bahnen mit einer gewünschten Periode resultieren. Die Ergebnisse werden diskutiert und mit einem sehr einfachen 3-Variablen-Oregonator-Modell aus der Literatur verglichen.
This thesis describes the coordination chemistry and catalytic applications of the 1,1,1-tris(oxazolinyl)ethane (“trisox”) family of ligands. The studies described herein are primarily concerned with the effect of the threefold rotational symmetry of the ligands, as well as the role of the third oxazoline arm in catalytic reactions in which there are intermediates that possess a bidentate coordination of the trisox ligand. The syntheses of highly symmetrical chiral 1,1,1-tris(oxazolinyl)ethane ligands bearing phenyl, benzyl or indanyl substituents, and of mixed bis- and trisoxazolines is described. The isomerisation of the 2-bromooxazolines was observed, in which the thermally induced rearrangement generates the corresponding α-bromo-isocyanate derivatives. Reaction of the latter with phenylethylamine led selectively to the N-cyclised aziridines or to the O-cyclised 2-aminooxazolines, depending on the reaction conditions. The coordination chemistry of the trisoxazoline ligands with palladium is then described. Palladium(II) chloride and allyl complexes and a number of palladium(0) complexes were successfully synthesised. The dynamic behaviour of these complexes in solution was studied and activation parameters were determined for the exchange of the oxazoline moieties. The systematic comparison of the catalytic efficiency of trisox- and bisox-palladium systems in allylic substitution is described. It was demonstrated that the trisoxazoline-based complexes are superior catalysts in direct comparison to the corresponding bisoxazoline-based catalysts. The study showed that the additional donor function appears to play a role in the product/substrate exchange step as well as in the initial generation of the active catalyst. Finally, the exploitation of the dynamic coordination of the trisoxazolines to copper(II) in two copper-catalysed asymmetric reactions is described. It has been shown that C3-symmetric trisoxazolines form highly efficient enantioselective copper(II) Lewis acid catalysts, in which their success is based on the concept of a stereoelectronic hemilability of the divalent copper. In a direct comparison with the analogous bisoxazoline systems, the trisox/copper catalysts have proven to be more efficient in an enantioselective Mannich reaction as well as an enantioselective a-amination of prochiral b-ketoesters in presence of low catalyst loadings. To conclude the implications of the use of chiral tridentate podands in stereoselective catalysis compared to the more established bidentate chelates have been highlighted.
Today’s energy supply relies on the combustion of fossil fuels. This results in emissions of toxic pollutants and green-house gases that most likely influence the global climate. Hence, there is a large need for developing efficient combustion processes with low emissions. In order to achieve this, quantitative measurement techniques are required that allow accurate probing of important quantities, such as e.g. the gas temperature, in practical combustion devices. Diagnostic techniques: Thermocouples or other techniques requiring thermal contact are widely used for temperature measurements. Unfortunately, the investigated system is influenced by probe measurements. In order to overcome these drawbacks, laser-based thermometry methods have been developed, that are introduced and compared in this work. Special emphasis is set on a recently developed multi-line technique based on laser-induced fluorescence (LIF) excitation spectra of nitric oxide (NO). This calibration-free temperature imaging method was optimized within this thesis such that accurate temperature measurements are possible in practical, harsh environments. Numerical and experimental studies were conducted to identify ideal spectral excitation and detection strategies. The limited accuracy of this time-averaging technique in turbulent systems was investigated. In cooperation with T. B. Settersten (Sandia, USA), energy transfer processes during quenching of NO LIF were quantified. These processes are not understood so far and hamper the application of saturated LIF spectroscopy. In collaboration with Prof. R. K. Hanson (Stanford University, USA) a two-line thermometry sensor based on tunable diode-laser absorption spectroscopy (TDLAS) of water was optimized. Applications: NO LIF and H2O TDLAS were applied to quantitatively measure the gas temperature over a wide range of pressures (3 – 500 kPa) and temperatures (270 – 2200 K). With multi-line NO-LIF thermometry, gas-temperature fields in spray flames were obtained that have been used to validate numerical models for spray combustion developed by Prof. E. Gutheil (Heidelberg University). In cooperation with the Robert Bosch GmbH, Germany, this technique was used to quantify the evaporative cooling in internal-combustion (IC) engine-relevant pulsed fuel-sprays. NO-LIF thermometry was compared to soot pyrometry, has been applied to sooting high-pressure flames, and the data was taken to calculate soot-particle sizes with laser-induced incandescence. In collaboration with Toyota Central R&D Labs, Japan, the temperature distributions in boundary layers of solid-wall quenched flames were measured. This data enables quantitative LIF species measurements and optimization of the IC engine thermal management. In a nano-particle flame-synthesis reactor, both techniques were applied to measure the gas temperature, which is taken to validate numerical simulation codes for nano-particle formation developed at the University of Duisburg-Essen. In cooperation with Shinko Electric Industries, Japan, and Prof. J. Warnatz (Heidelberg University), H2O TDLAS was applied to optimize a direct-flame solid-oxide fuel cell system. The versatile measurement techniques developed and improved within this thesis enable quantitative probing of the gas temperature in practical combustion devices. Accurate knowledge of this important quantity allows developing efficient power plants and engines with low emissions of green-house gases and toxic pollutants.
Im Rahmen dieser Arbeit wurden Untersuchungen durchgeführt, die sich ausgehend von experimentellen Daten zur Kinetik der kobaltkatalysierten Hydroformylierung von langkettigen Olefinen in scCO2 über die Erstellung eines formalkinetisches Modells hin bis zur Entwicklung eines auf DFT-Rechnungen basierenden mikrokinetischen Modells erstrecken. Die Ergebnisse dienen einer späteren Prozessentwicklung basierend auf Laborexperimenten. Die Formalkinetik des Reaktionsablaufs wurde sowohl für kobalt- als auch rhodiumkatalysierte Umsetzungen von 1-Octen mittels systematischer Variation von Prozessparametern (p, T, ci, cKat) ermittelt. Die gefundenen Abhängigkeiten in Form der partiellen Reaktionsordnungen ordnen sich schlüssig in die Reihe literaturbekannter Untersuchungen ähnlicher Hydroformylierungs-Prozesse ein. Da das empirische formalkinetische Modell jedoch den Einfluss von CO nicht hinreichend beschreibt, wurde für die HCo(CO)4-katalysierte Hydroformylierung von 1-Octen in scCO2 ein mikrokinetisches Modell entwickelt. Dieses basiert auf thermodynamischen und kinetischen Parametern von Elementarreaktionen, die durch DFT-Berechnungen der Strukturen und Energien von Intermediaten und Übergangszuständen zugänglich waren. Das mittels komplexer mathematischer Verfahren entwickelte Modell beschreibt die Zeit-Konzentrations-Abhängigkeiten erheblich genauer als dies mit dem formalkinetischen Ansatz möglich wäre. Zusätzlich ermöglicht es auch die Extrapolation, das heißt die Vorhersage von Abhängigkeiten außerhalb des experimentell erfassten Parameterraums. Die Ergebnisse dieser Arbeit beinhalten auch Ansätze für eine Katalysatorrückführung. Experimentell konnte gezeigt werden, dass im Falle eines Phosphan-modifizierten Kobaltkatalysators die gezielte Änderung der Zustandsvariablen (p, T) das Phasenverhalten im Reaktionsgemisch derart ändert, dass der Katalysators nahezu vollständig präzipitiert. Daurch ist er mittels Mikrofiltration abtrennbar und kann wiederverwendet werden. In diesem Sinne repräsentieren die in dieser Arbeit vorgestellten Ergebnisse einen Beitrag zu einer Prozessentwicklung der Hydroformylierung in sc CO2.
Ziel dieser Arbeit war die Entwicklung theoretischer Modelle, die eine schnelle und zuverlässige Aussage über die Geometrieparameter und relativen Energien der aktiven Zentren zweier Enzyme in Bakterien und Archaea, der Nickel-Eisen und der Molybdän-Kupfer abhängigen Kohlenstoffmonoxid Dehydrogenase, erlauben. Diese Theoretischen Modelle stützen sich auf publizierte experimentelle Daten, insbesondere Röntgenstrukturen. Folgende Modelle wurden etabliert: a) Ein dinukleares Modell, in dem ein Eisen- und ein Nickelatom durch ein Cyclopropanderivat, das als Ersatz für die strukturelle Fixierung durch einen Eisen-Schwefel-Clusters dient, koordiniert sind. Obgleich dieses einfachste denkbare Modell sehr stark vereinfachend ist, erlaubt es Energie- und Geometrieparameter für verschiedenste Strukturvarianten, die für den Katalysezyklus relevant sein könnten, in einer relativ kurzen Zeit zu berechnen. Dadurch kann das Modell zur Evaluierung der geeignetsten Variante dienen, die an einem komplizierteren System untersucht werden kann. b) Ein polynukleares Modell wurde untersucht, das aus einer kubischen Eisen-Schwefel-Struktur mit einem Imidazolliganden besteht, der den Histidinrest des Proteins modelliert. Dieses Modell wurde aus den experimentellen Strukturen des aktiven C-Clusters in seiner reduzierten Form abgeleitet. Die Modellcluster wurden zum Vergleich des [NiFe4S4] und des [NiFe4S5] C-Clusters des aktiven Zentrums der CODH berechnet. Hierbei wurden verschiedene Oxidationszustände (vollständig oxidiert, einfach und doppelt reduziert) betrachtet und verschiedene zusätzliche Liganden, wie H2O, CO und H- berücksichtigt, jedoch ergab keine Geometrie eine konsistente Übereinstimmung mit den Geometrieparametern, die durch die Röntgenstrukturanalyse erhalten wurden. Hierbei ist zu berücksichtigen, dass die aus den Röntgenstrukturanalysen berechneten Geometrien schon von Präparation zu Präparation stark abweichend sind. Verschiedene stationäre Punkte des Katalysezyklus der CO-Oxidation wurden ebenfalls betrachtet. Dabei ergab die vollständig oxidierte Form des [NiFe4S4] Modells im Gegensatz zu denen des [NiFe4S5] Modells akzeptable Strukturen, sowie ein sinnvolles Energieprofil. Zusätzlich wurden mechanistische Varianten, wie die alternative Koordination des CO an das Eisenatom und des H2O an das Nickelatom betrachtet. Eine Hydridspezies, die als eine mögliche Alternative vorgeschlagen wurde, scheint energetisch möglich zu sein. Für den eigentlich vorgeschlagenen Reaktionszyklus berechnete, einfach und doppelt reduzierte Spezies, weisen dagegen kein sinnvolles Energieprofil auf. c) Ein dinuklearer Molybdän-Kupfer-Komplex [(Me2C2S2)Mo(O)2-SCuSMe] 2-, sowie seine protonierte Oxo-Hydroxo-Form, wurden berechnet, um einen Einblick in die bei der Molybdän und Kupfer abhängigen CODH beteiligten Reaktionsschritte zu gewinnen. Nur der Bisoxo-, nicht aber der Hydroxo-Oxo-Komplex, ermöglicht eine exotherme CO-Oxidation. Ein Thiocarbamatkomplex, der als Reaktionsprodukt des Enzyms mit dem Inhibitor n-Butylisonitril beschrieben wurde, ist thermodynamisch verifizierbar. Für die Bildung eines analogen Thiocarbonatkomplexes bei der CO-Oxidation dagegen konnte keine signifikante, thermodynamische Triebkraft gefunden werden. In die Proteinstruktur des Enzyms eingebettet sollte diese Spezies weiter destabilisiert werden, da der Abstand der Metallzentren für das freie Modell bei dessen Bildung deutlich vergrößert wird.
The innovative application of physical methods is required in order to gain comprehensive qualitative as well as quantitative insights into the structures and the properties of complex materials and systems. In this work, the novel hyphenation of synchrotron-based Fourier-transform infrared microspectroscopy with polarization modulation was implemented. The in this combination so far unique microprobe was designed for the non-destructive in situ study of the composition and the structural anisotropy in small or heterogeneous samples. A key feature demonstrated is the ability of the instrument to spatially resolve infrared linear dichroism down to the diffraction limit by using infrared synchrotron radiation. Another characteristic of great potential was shown to be the capability of obtaining orientation information in reference-free measurements. The reference-free and near-diffraction-limited mapping of infrared linear dichroism in fiber-reinforced polypropylene model composites was demonstrated. Measurements on single wood fibers illustrated the capabilities of the method to investigate (bio)polymeric multicomponent and multiphase systems. It was shown that the method can provide new insights into synthetic and biological polymer composites. It is more widely applicable to investigations of complex synthetic and biological materials. For a complete understanding of the structure and the function of biological macromolecules and complex biological systems it is necessary to measure them in their native environment. Therefore, a microfluidic infrared transmission cuvette for measurements of biological systems in aqueous medium was implemented in this work. This cuvette was used for the in situ study of wood polymers in the presence of liquids. Furthermore, it was suitable for the in situ measurement of living cells by infrared microspectroscopy. The microfluidic cuvette was shown to be a versatile device which may be used as a miniincubator and an infrared measurement chamber with varied possible further applications.
In environment studies as well as for technical application, the study of air-water gas exchange is crucial. For process studies, a novel visualisation technique of oxygen concentrations in water was realised with high spatial resolution. To resolve turbulent processes in water, also the temporal resolution was pushed to the limit of a imaging frame rate of 185 Hz. For this purpose, the well-established method of laser-induced fluorescence (LIF) was extended introducing in this type of studies a new phosphorescent ruthenium dye that is more than 15 times more sensitive to oxygen than the previously used indicator dye. The chemical synthesis of this metal-ligand complex MLC was adapted to a preparation without intermediate steps. The challenge of this imaging technique for small-scale interactions was to resolve a very thin boundary layer extending less than a millimetre below the water surface. An image processing algorithm was developed that allow the automatic detection of the exact location of the air-water phase boundary within the resolution of 25 um/pixel. Only by this step, an accurate direct determination of an important parameter for gas-exchange studies, the boundary-layer thickness, is feasible. The developed methods were applied to systematic gas-transfer measurements mostly with surfactants, conducted in a range of wind speeds between 0.8-7 m/s in a circular wind-wave facility. The measured gas-transfer velocities compared extremely well to exchange rates derived from mass-balance methods. The novel visualisation technique drastically increased the poor signal quality inherent to standard LIF techniques. This enabled accurate measurements of gas-transfer velocities from aqueous concentration profiles for the first time.
The mechanisms through which proteins achieve their functional three-dimensional structure starting from a string of amino acids, as well as the manner in which the interactions between different structural elements are orchestrated to mediate function are largely unknown, despite the large amount of data accumulating from theoretical and experimental studies. One clear view emerging from all these studies is that function is a result of the intrinsic protein dynamics and flexibility, namely the motions of its well-defined structural elements and their ability to change their position and shape in space to allow large conformational transitions necessary for the function. Simulation techniques have been increasingly used over the past years in the endeavour to solve the structure-function puzzle as they have proven to be powerful tools to investigate the dynamics of proteins. However, extracting useful dynamical information from trajectories thus generated in order to draw functionally relevant conclusions is not always straight forward, especially when the protein function involves concerted movements of entire protein domains. This is due to the high dimensionality of the energy surface the proteins can explore. Therefore, a decrease in complexity is to be desired and can be achieved in principle by reducing the number of dimensions to the ones capturing only the dominant motions of the protein. To this purpose, in this thesis two different dimensionality reducing techniques, namely Principal Component Analysis and Sammon Mapping are applied and compared on four proteins that undergo conformational changes with different amplitudes and mechanisms. In particular, the present thesis tackles the large conformational change occurring during the recovery stroke of myosin, using these methods and rigidity analysis algorithms in the attempt to elucidate in atomic detail the structural mechanism underlying the function of this protein that couples ATP hydrolysis to the mechanical force needed to achieve muscle contraction. The results presented in this thesis show the successful applicability of certain dimensionality reducing methods to large conformational changes and their suitability in analyzing and dissecting dynamical transitions in computationally generated trajectories. The findings regarding the recovery stroke step in the myosin cycle are consistent with experimental data coming from mutational studies and confirm the previously postulated communication mechanism between the active sites of the protein, thus representing a major contribution to the field of molecular motors and a strong evidence of the importance of theoretical studies in complementing the experimental investigations.
Annually 1000-3000 Tg mineral dust aerosol are emitted into the atmosphere, and transported over the oceans from one continent to the other. During the transport dust particles interact with components in the marine atmosphere and also with seawater as they fall into the ocean. Increased methyl iodide concentrations were observed during a field campaign on the Atlantic Ocean when dust storms occurred. Volatile halogenated organic compounds (VHOC) are photolyzed to produce reactive halogen species which are responsible for ozone depletion. An abiotic production mechanism for VHOC, involving humic-like substance (HULIS), iron and halide, was supposed to produce methyl iodide through the interaction of dust particles with seawater as all necessary ingredients were present. The main goal of this study was to test this hypothesis and to further elucidate the process. For this, simple dust-seawater addition experiments in headspace glasses were conducted in the laboratory, following a purge-and-trap GC-MS analysis of the headspace gas. Dust samples were collected in the source regions in southern Algeria and the Gobi Desert and, as representatives for aeolian dust, samples from Cape Verde Island and Lanzarote Island were used. To exclude the biological contribution, sterilized samples were also employed in this study. As assumed, methyl iodide was produced abiotically and the concentration increased tenfold after addition of Fe (III) within half an hour. Methylene chloride was also produced abiotically along with methyl iodide. In contrast to methyl iodide and methylene chloride, methyl chloride and isoprene were produced biologically, provided the production occurred after at least 24 hours of interaction of only non-sterilized samples with seawater. If the microorganisms responsible for the production of isoprene are common soil organisms found everywhere in the world, this process can be the reason for a hitherto not fully explained increase in atmospheric isoprene concentration during wet seasons, especially when the rain falls practically everyday. The results of this study show the importance of natural dust aerosols for the production and emission of volatile organic compounds to the atmosphere and open interesting questions for further studies.
Die Tatsache, dass nur sehr wenige Indiumclusterverbindungen bekannt waren, zeigt die Grenzen der bisher genutzten Darstellungsmethoden, die in der Gallium- und Aluminiumclusterchemie sehr erfolgreich waren. Das Ziel dieser Arbeit war es, mit InCp* und Intriflat als Indium(I)quelle und einer Variation unterschiedlich raumerfüllender Silylgruppen als Substituenten weitere Synthesewege aufzutun und neue Indiumclusterverbindungen zu synthetisieren und zu charakterisieren. Begleitende quantenchemische Rechnungen geben einen Einblick in die elektronischen Strukturen und Stabilitätsverhältnisse dieser Verbindungsklasse. Die wichtigsten Ergebnisse dieser Arbeit sind die Folgenden: Die Reaktion von InCp* mit LiSi(SiMe3)3·3THF in Toluol führte neben der Bildung eines neuen silylsubstituierten Monoindans In[Si(SiMe3)3]3 und einem weiteren Nebenprodukt [Li(OH)(OSiMe3)In{Si(SiMe3)3}2]2 zur Synthese des ersten silylsubstituierten Tetraindans In4[Si(SiMe3)3]4 1. Das grüne Tetraindan zeichnet sich durch die bislang kürzesten Indium-Indium-Abstände in Clusterverbindungen aus. Die erhöhte Stabilität von 1 im Vergleich zu bislang bekannten Indiumtetrameren wird, wie die quantenchemische Berechnungen belegen, durch den Silylsubstituenten hervorgerufen. Die verkürzten Indium-Indium-Abstände führen zu einem geringeren HOMO-LUMO-Abstand. Dies erklärt die unterschiedliche Farbe in den violetten alkylsubstituierten Indiumtetrameren und dem grünen silylsubstituierten Indiumtetramer 1. Durch die Umsetzung von InCp* mit LiSiPh3·3THF in Toluol gelang die Synthese einer weiteren Monoindanverbindung In(SiPh3)3·THF neben einem Triindanat [Na(THF)6][In3(SiPh3)6] mit einer linearen In3-Kette und zwei neuen Indiumclustern, dem neutralen precloso-Cluster In8(SiPh3)8 2 und dem dianionischen closo-Cluster [In8(SiPh3)8]2– 3. In 2 nehmen die acht Indiumatome die closo-Struktur eines Disphenoids an, in 3 die offene Struktur eines quadratischen Antiprismas. Während für den precloso-Cluster die dodekaedrische Struktur nach quantenchemischen Berechnungen anderen Strukturen gegenüber deutlich begünstigt ist, ist der berechnete Energieunterschied zwischen der dodekaedrischen und der quadratisch antiprismatischen Struktur des closo-Clusters nur gering. Das quadratische Antiprisma geht aus dem Dodekaeder durch Dehnung zweier gegenüberliegender Kanten hervor. Zwar konnte die Ladung von 3 nicht kristallographisch bestimmt werden, doch zeigt das Aufspaltungsmuster des Massenspektrums nach der Elektronenspray-Ionisations-Methode eindeutig, dass es sich um eine dianionische Verbindung handelt. Quantenchemische Berechnungen an monoanionischen Clustern des Typs [In8(SiPh3)8]– und [In8H(SiPh3)8]– zeigen in den Verhältnissen der Indium-Indium-Abstände mit den kristallographisch bestimmten Daten von 3 keine Übereinstimmung. Die Synthese und strukturelle Charakterisierung eines Redoxpaares in der Clusterchemie der höheren Homologen des Bors ist höchst selten und in der Indiumclusterchemie einzigartig. Die cyclovoltammetrische Bestimmung des Halbstufenredoxpotentials von E(1/2) = –2.40 V weist darauf hin, dass 2 tatsächlich durch Reaktion mit einem geeigneten Reduktionsmittel in 3 überführt werden könnte. Die Reaktion von InCp* mit LiNCtBu2 führte zur Bildung eines aminosubstituierten Diindans [LiNHCtBu2-m-(NCtBu2)2InNCtBu2]2 mit vierfach koordinierten Indiumatomen. In dieser Arbeit konnte nachgewiesen werden, dass Indiumtriflat als Indium(I)quelle ebenfalls geeignet ist, um niedervalente Indiumverbindungen wie 1 zu synthetisieren. Ein Monoindan, das als ionische [R2In(THF)]+[O3SCF3]– Verbindung beschrieben werden kann, konnte ebenfalls strukturell charakterisiert werden. Weiterhin wurden In[SiMe(SiMe3)2]3 und das Lithiumsilanolat [(LiOSiMe3)3OSiMe2·THF]2 strukturell charakterisiert. InCp* und In(I)-triflat sind also geeignet, um Indiumverbindungen in niedrigen Oxidationsstufen (+I und +II) zu synthetisieren. Die bei den Synthesen beobachteten Disproportionierungsreaktionen machen es aber auch wahrscheinlich, dass mit anderen Substituenten oder veränderten Reaktionsbedingungen weitere metallreiche Cluster InnRm (n>m) erhältlich sein werden. Geometrieoptimierungen auf DFT-Niveau an closo-Clustern [EnXn]2– (E = B, Al, Ga, In; n = 5 – 9) und an entsprechenden precloso-Clustern (n = 6, 8) zeigen, dass mit kleinen Substituenten für Indium in vielen Fällen andere Strukturen als die sphärischen closo-Strukturen energetisch begünstigt sind. Oft handelt es sich hierbei um „offene“ Strukturen, die durch Spaltung einzelner Kanten mit anschließender Verzerrung aus den closo-Strukturen entstehen. In einigen Fällen zeigen sich auch bei Gallium- und Aluminiumclustern ähnliche Tendenzen. Für Cluster wird der Aromatizitätsbegriff auf drei Dimensionen erweitert. Energetische und geometrische Kriterien für Aromatizität, ergänzt um die Berechnung von NICS (Nucleus-Independent Chemical Shifts) wurden auf Cluster [EnHn]2– der dritten Hauptgruppe angewandt. Dabei zeigte sich, dass die closo-Cluster unabhängig vom aufbauenden Element E dreidimensionale Aromaten sind. Ausnahme sind die closo-Cluster [E5H5]2– (E = B, Al, Ga, In), die als nichtaromatisch zu beschreiben sind. Weiterhin konnte ein Zusammenhang zwischen der Entwicklung der energetischen Stabilität für Cluster mit n = 5 – 9 Atomen und den bisher bekannten Clusterverbindungen des Typs [EnXn]2– gefunden werden.
Pollutant reduction of internal combustion engines plays an essential role in automotive industry research and development. Exhaust-gas after-treatment using catalytic converters is of key importance to this goal. Storage catalytic converters based on barium oxide are a technology with promising potential to meet current and future emission standards for nitric oxides (NOx) abatement of lean-burning gasoline and Diesel engines. The aim of this work was to develop elementary reaction steps and determine kinetic parameters for the NOx storage reaction mechanism by means of density functional theory (DFT). DFT has proven a powerful tool in investigating microscopic aspects of heterogeneous reactions. Electronic structure calculations were performed for adsorption of different molecules on two surfaces relevant in automotive exhaust gas purification: barium oxide and platinum.
Es wurden flammgeschützte Epoxidharzsysteme auf der Basis reaktiver, phosphorhaltiger Flammschutzmittel entwickelt. Als Hauptkriterium für die Qualität der flammhemmenden Eigenschaften wurde das Erreichen der UL 94 V0 Klassifizierung gemäß DIN IEC 60695-11-10 gewählt. Darüber hinaus wurde für ausgewählte Systeme der Sauerstoffindex (LOI) ermittelt und als entscheidende Materialeigenschaft die Glasübergangstemperatur mittels DSC bestimmt. Ein Hauptaugenmerk wurde auf die Art und Weise der Einbringung des Flammschutzmittels in das Polymer gelegt. Es wurde insbesondere die Modifizierung der Epoxidharzmonomere durch eine der Formulierung (Abmischen der Harzkomponente mit der Härterkomponente und einem entsprechenden Beschleuniger) zeitlich vorgelagerte Reaktion („Präformulierung“) als Methode der Wahl angewendet. Mittels dieser Präformulierungsreaktion gelang es die reaktiven Flammschutzmittel kovalent an die entsprechenden mehrfunktionellen Epoxidharze zu binden. Nach der Polymerisation wurde das Flammschutzmittel somit integraler Bestandteil des Polymernetzwerkes. Es wurden verschiedene Polymere, die monofunktionelle, phosphorhaltige Verbindungen als Flammschutzmittel enthielten, untersucht und entsprechend ihres Brandverhaltens klassifiziert. Es konnte gezeigt werden, dass 9,10-Dihydro-9-oxa-10-phosphaphenanthren-10-oxid (1) und seine Derivate sehr effektive Flammschutzmittel darstellten. Epoxidharze, die mit diversen Phosphiten und Phosphaten modifiziert wurden, die nicht über eine dem 9,10-Dihydro-9-oxa-10-phosphaphenanthren-10-oxid analoge phosphacyclische Struktur verfügten, wiesen keine ausgeprägten flammhemmenden Eigenschaften auf. Mit steigendem Flammschutzmittelgehalt nahmen die flammhemmenden Eigenschaften der Polymere erwartungsgemäß zu, allerdings sank im Gegensatz die Glasübergangstemperatur der modifizierten Polymere. Da die Glasübergangstemperatur die maximale Einsatztemperatur der Polymere markiert, sind möglichst hohe Glasübergangstemperaturen erstrebenswert. Durch die Ermittlung der Grenzgehalte an Flammschutzmittel, bei denen die UL 94 V0 Klassifizierung gerade erreicht wurde, konnte eine allzu starke Erniedrigung der Glasübergangstemperatur verhindert werden. So konnten mit dem Härter DETDA 80 (Diethyltoluoldiamin) außerdem ein System auf Basis von DEN 438, modifiziert mit 1 erarbeitet werden, das flammhemmend ausgerüstet war und eine sehr hohe Glasübergangstemperatur von 202°C aufwies. Dieses derartig modifizierte Epoxidharzsystem erreichte dabei die UL 94 V0 Klassifizierung ab dem niedrigen, absoluten Phosphorgehalt von 0.61%. Neben monofunktionellen, phosphorhaltigen Flammschutzmitteln wurden auch difunktionelle Phosphorverbindungen zur Präformulierung herangezogen. Diese besaßen den Vorteil, dass sie auch mit dem zweifunktionellen Standardharz DGEBA Präformulierungen ergaben, die effektiv polymerisiert werden konnten ohne zu ungenügenden Netzwerkdichten zu führen. Als Referenzflammschutzmittel wurde das Addukt von 1 an Benzochinon (15) herangezogen, da es sich im asiatischen Raum in den letzten Jahren in der Leiterplattenindustrie etabliert hatte. Es konnten durch den Einsatz der Addukte von Verbindung 1 an Dialdehyde, insbesondere Terephthaldialdehyd, Alternativen zu 15 entwickelt werden, die ebenfalls präformuliert werden konnten und nach der Polymerisation vergleichbare flammgeschützte Polymerkörper lieferten. Die Kompatibilität dieser Systeme mit verschiedenen Härtern wurde erfolgreich demonstriert und die resultierenden Materialeigenschaften verglichen. Um die unterschiedliche Effektivität der präformulierten Phosphorverbindung zu erklären, wurden 1, 2 und 3 sowie 8 und 9 als Reinsubstanzen mittels hochauflösender Sektorfeldmassenspektroskopie untersucht. Hauptaugenmerk wurde dabei auf die Hauptzersetzungsprodukte gelegt. Im Fall von 1 und seinen Derivaten 2 und 3 konnten plausible Fragmentierungs- und Zersetzungsschemata gefunden werden. Als treibende Kraft der dabei ablaufenden Reaktionen wurde die Bildung von stabilem Dibenzofuran identifiziert. Als Nebenprodukt konnte das PO-Radikal im Massenspektrometer hochauflösend nachgewiesen werden. Aufgrund ihrer chemischen Struktur konnten 8 und 9 dieses Radikal nicht bilden. Es wurde dementsprechend bei der Zersetzung im hochauflösenden Sektorfeldmassensprektometer nicht detektiert. Um nicht nur die Zersetzung der molekularen Substanzen zu detektieren, wurden auch gemahlene ausgehärtete Epoxidharzproben mittels thermischer Desorptionsmassenspekrometrie untersucht. Hierzu wurden Epoxidharzmaterialien, basierend auf DDM gehärteten Präformulierungen aus DEN 438 und 1 bzw. 8 herangezogen, sowie unmodifiziertes, DDM gehärtetes DEN 438 als Blindprobe. Es gelang bei der thermischen Zersetzung dieser Polymere konkrete Pyrolysegase zu analysieren. Das 1 modifizierte Polymer setzte PO Radikale frei, während bei der Blindprobe und dem mit 8 modifizierten Harz kein PO detektiert wurde. Die PO Radikale können bei erhöhter Temperatur gasförmig aus dem pyrolysierenden Polymer austreten und in einer Radikalfängerreaktion H- und OH- Radikale abfangen. Da diese hochreaktiven Radikale die thermische Zersetzung des Polymers in Brennstoff bewerkstelligen, zeigt die durch PO verursachte Abfangreaktion flammhemmende Wirkung. Im Gegensatz zu Verbindung 1 und seinen Derivaten, die ihre Wirkung in der Gasphase entfalten können, wirkten Verbindung 8 und vergleichbare Phosphorverbindungen ausschließlich in der kondensierten Phase.
Die vorliegende Arbeit untersucht die Erzeugung und Reaktivität der niedervalenten Template [TriphosCo0] I und [TriphosNi0] II (Triphos = CH3C(CH2PPh2)3). I und II erweisen sich als hochreaktiv in Umsetzungen mit Substraten, in denen zur reduktiven Spaltung geeignete Bindungen enthalten sind. Die Isolierung der Spezies I und II ist nicht möglich. Sie sind nur in Lösung stabil und handhabbar. Im Falle der diamagnetischen Spezies II kann mit Hilfe NMR-spektroskopischer Methoden die Formulierung von II als [Triphos4Ni3] belegt werden. Setzt man tertiäre Silane HSiR3 als Substrate in Umsetzungen mit I ein, bilden sich die oktaedrisch koordinierten Komplexe [TriphosCo(H)2(SiR3)] (R = Ph, Et). Aus Schwefelverbindungen mit reduktiv spaltbaren S-C-Bindungen erhält man [TriphosCoSCoTriphos], ein Komplex mit zwei S Co Dreifachbindungen und linearer Co-S-Co-Einheit. Verwendet man Substrate wie (RS)2 oder (RSe)2 in Umsetzungen mit I bzw. II, erhält man die pseudotetraedrisch koordinierten Komplexe [TriphosMIX] (M = Co, Ni; X = SPh, StBu, SePh). Die Stabilisierung des TriphosNickel0-Templats II gelingt durch Koordination von neutralen Zwei-Elektronen-Donorliganden L unter Bildung von Verbindungen des Typs [TriphosNiL] (L = PPh3, AsPh3, cHexNC, tBuNC, C2H4).
In der vorliegenden Arbeit wird die Synthese neuartiger cyclischer Phenothiazin-Verbindungen vorgestellt und deren elektronische Eigenschaften diskutiert. Phenylen-, ethenylen- oder heteroaryl-verbrückte dimere cyclische Phenothiazin-Systeme konnten über verschiedene Kreuzkupplungsreaktionen synthetisert werden. Des Weiteren wurden ethylenverbrückte Phenothiazinophane hergestellt. Durch Modifizierung der Brückeneinheiten konnten die elektronischen Eigenschaften der synthetisierten Phenothiazinophane variiert werden. Cyclovoltammetrische Messungen zeigen, dass es zu einer separaten Erstoxidation der beiden Phenothiazin-Einheiten kommt. Auf Grund der geringen Differenz der Halbstufenpotentiale kann eine Delokalisierung des Radikalkations über das gesamte Molekül ausgeschlossen werden. Die elektronische Kommunikation und damit die separate Erstoxidation kann somit auf eine Kombination aus sigma-pi-"through-bond"- und Coulomb-Wechselwirkung der radikalionischen Spezies zurückgeführt werden. Die Ergebnisse wurden mit den elektronischen Eigenschaften naphthalinverbrückter Phenothiazin-Diaden verglichen, in denen die Phenothiazin-Einheiten in räumliche Nähe zueinander gebracht werden. Die im Vergleich zu den Cyclophanen größere Differenz der Halbstufenpotentiale weist auf die stärkere Coulomb-Wechselwirkung der konformativ fixierten Phenothiazin-Einheiten hin. Interessante Ergebnisse zeigten die Kristallstrukturen der unterschiedlich verbrückten Phenothiazinophane. So ordnen sich die einzelnen Moleküle in einer pseudo hexagonal dichtesten Packung zueinander an. Auf Grund der elektrochemischen Eigenschaften und günstigen Festkörperstruktur könnten diese Cyclen als neuartige Lochtransportmaterialien für OFETs in Frage kommen. Neben cyclischen Phenothiazin-Derivaten wurden p- und s-System verbrückte Phenothiazin-Diaden und -Triaden über verschiedene Kupplungsreaktionen synthetisiert. Elektronische Untersuchungen zeigen, dass durch Wahl einer geeigneten verbrückenden Einheit die elektronischen Eigenschaften der Phenothiazin-Derivate gezielt modifiziert werden können. Des Weiteren wurden Bis(radikalkationen) verschiedener oligomerer und cyclischer Phenothiazin-Verbindungen hergestellt, um so einen Einblick in die elektronische Struktur dieser Verbindungen zu erhalten. Mit Hilfe quantenmechanischer Methoden wurde untersucht, ob es sich bei den bis(radikalkationischen) Phenothiazin-Systemen um Triplett- oder Singulett-Grundzustände handelt. Dabei zeigen die Energieunterschiede, dass die Singulett-Zustände energetisch geringfügig begünstigt sind.
The present work investigates the behaviour of actinides (An) of different oxidation states in the process of aquatic colloid formation, e.g. at the generation of aluminosilicates (HAS) by co-nucleation of Si and Al in absence or in presence of natural humic acid (HA). The study comprises three parts. The first part of the work concentrates on the interaction of tri-, tetra-, penta- and hexavalent actinide ions with HAS colloids. The HAS colloids are synthesized through heterogeneous nucleation of Si and Al in the pH region 4 to 9 at room temperature and atmospheric pressure. Si concentration is maintained either below or above the saturation concentration of amorphous silica (2x10-3 M). In the former case 10-3 M Si is mixed with 10-5 M Al and Si is present in solution as monosilicic acid. In the latter case, 10-2 M Si is mixed with 10-4 M Al and polysilicic acid prevails in solution. The following tracer nuclides are introduced in the co-nucleation process: 241Am(III), 234Th(IV), 237Np(V) and 233U(VI). Colloids are separated from solution and precipitate by sequential filtration and ultrafiltration. Definition of the optimum conditions for the formation of colloid-borne actinide species is ascertained by radiometric assay, determining the actinide fraction in the colloidal phase as a function of pH, conditioning time, concentration and concentration ratio of the involved components. Several methods are further applied for the appraisal of the chemical binding state of actinides in the HAS colloids as well as of Al in aluminosilicate solutions: TRLFS (time resolved laser fluorescence spectroscopy), EXAFS (extended X-ray absorption fine structure) spectroscopy and ligand displacement method (using EDTA as competing ligand). The affinity for conucleation with HAS appears to follow the element tendency toward hydrolysis. The second part of the work further concerns the behaviour of An(III, IV, VI) at the interaction with humate colloids. In addition to actinide activity measurements, 14C-labelled natural humic acid is used in order to facilitate the tracing of humic colloids behaviour. The conditions of colloid formation are investigated by radiometric assay as a function of pH (6.6-7.8), time, concentration of HA (0.6-8 mg/L), Al (1x10-5-1x10-4 M) and An (5x10-8-1x10-5 M). The generation of humate-colloid-borne species is distinctively favored for the non-hydrolyzed ionic species. Generation of humate-colloid-borne An(IV, VI) is enhanced by increasing HA concentration or decreasing the An/HA concentration ratio. The third part of the work follows the conditions for formation of colloid-borne An(III, IV, VI) in the mixed system containing the competing HAS and humic colloids. The simultaneous presence of HAS and HA generally enhances the stability region (in respect with pH and Si/Al concentration) of the colloid-borne An species. The formation of mixed HAS-humic colloids with synergic binding appears to be responsible for the stable incorporation of An into the colloidal phase, as ascertained for Cm(III) by TRLFS. Such a synergic effect is assumed to be related to the two different and complementary mechanisms exhibited by the HAS and HA colloids in binding the actinides.
Die Kupplungs-Isomerisierungs-Reaktion (KIR), eine schnelle Sonogashira-Alkinylierung von elektronenziehenden Halogeniden und Propargylalkoholen gefolgt von einer basenkatalysierten Carbinol-Allenol-Enon-Isomerisierung, stellt einen milden und effizienten Zugang zu Chalkonen dar. Innerhalb der vorliegenden Arbeit konnten neue Dominoreaktionen entwickelt werden, die methodische Erweiterungen der KIR darstellen. Es ist gelungen die zwingend notwendige Akzeptorfunktionalität in situ mittels einer intramolekularen Carbopalladierungsreaktion zu erzeugen. Terminale Acetylene reagieren mit N-Iodphenylalkinylamiden in einer Carbopalladierungs-Sonogashira-Alkinylierungs-Dominosequenz zu Inylidendihydroindolonen; der Alkinsäureiodphenylester konnte mit 4 Anisylpropargylalkohol in einer Insertions-Kupplungs-Isomerisierungs-Reaktion zum Oxobutenylidenbenzofuranon umgesetzt werden. Entgegen dem Postulat, dass intramolekulare 5-exo-dig-Cyclisierungsreaktionen streng syn-stereospezifisch verlaufen, wurden die Inylidendihydroindolone als E/Z-Doppelbindungsisomere und das Oxobutenylidenbenzofuranon anti-stereoselektiv als Z Isomer erhalten. Neben der Einbindung eines metallorganischen Insertionsereignisses konnte zudem die irreversible Allenol-Enon-Tautomerie durch die Inkorporation von Propargylethern anstelle der entsprechenden Alkohole erfolgreich unterbunden werden. Das bislang elusive, hoch reaktive Allenintermediat kann jetzt in einer kinetisch und thermodynamisch kontrollierten intramolekularen Abfangreaktion adressiert werden. Die Insertions-KI-Diels-Alder-Dominoreaktion der Akzeptoren bzw. mit Propargylallylethern liefert die bislang unbekannte, stark fluoreszierende Substanzklasse der Spirobenzofuranone und Spiroindolone in moderaten bis guten Ausbeuten. DFT- und MP2-Rechnungen der konkurrierenden produktbildenden Schritte der intramolekularen Diels-Alder-Reaktion vs. der Claisen-Umlagerung des Vinylallenylallyletherintermediats zeigen sowohl eine kinetische als auch thermodynamische Präferenz der [4+2]-Cycloaddition. Mit der Erkenntnis dieser Molecular-Modeling Studien konnten die elektronische Natur und die sterischen Eigenschaften der Akzeptor- und Alkinkomponente so modifiziert werden, dass nun eine Claisen-Umlagerung als Folgereaktion das Intermediat adressiert. Die Kupplungs-Isomerisierungs-Claisen-Dominoreaktion von elektronenarmen Arylhalogeniden bzw. aromatischen Säurechloriden mit Propargyltritylethern zeigt eine bemerkenswerte Dichotomie im finalen Schritt und resultiert, als Folge selbst kleinster elektronisch diverser Substituenteneffekte, in der Bildung von Tricyclooctenen, Chalkone, 1H-Iso¬chro¬menen und Indanen. Die Sonogashira-Reaktion von terminalen Phenylacetylenen mit N-Iodphenylalkinylamiden bzw. Alkinsäureiodphenylestern liefert in einer Carbopalladierungs-Alkinylierungs-Reaktion die entsprechenden internen vinylogen Alkinoylderivate. Erfolgt die Umsetzung der in situ generierten Alkinoylester bzw. -amide mit primären oder sekundären Aminen im Sinne einer Aza-Michael-Addition, ist ein eleganter Zugang zu vinylogen Enaminocarbonsäureestern und -amiden geschaffen. Unter Verwendung der hier vorgestellten Insertions-Sonogashira-Aminovinylierungs-Dreikomponentenreaktion können im Ein-Topf-Verfahren maßgeschneiderte orangefarben bis rot fluoreszierende Push-Pull-Chromophore und in guten bis exzellenten Ausbeuten erhalten werden.
Detailed mechanisms with hundreds of elementary reactions and species are now available for the combustion of alkanes as a result of the consistent pursuit of mechanism development over several decades. The chemical reaction scheme presented in this work was developed on the basis of a previously available one, V. Karbach (2006), and includes the oxidation reactions of high-temperature combustion of H2, CO, CH4, C2H6, C3H8 and C4H10. The mechanism consists of 412 elementary reactions and 61 species and is based on a rate-data compilation by Baulch et al. (2005). It is documented by Heghes et al. (2005) and Warnatz and Heghe¸s (2006). The approximate temperature range is from 900K to 2500K. To test the validity of the mechanism, for each fuel considered, premixed laminar flame velocities and ignition delay times have been calculated. The results were compared to experiments for the largest possible conditions range (initial temperature, pressure, equivalence ratio). The flame velocity is a function of fuel concentration, temperature and pressure of the unburnt mixture. The flame calculations are performed using the Mixfla code (J. Warnatz, Ber. Bunsenges. Phys. Chem. 82, 1978). The flame modelling was used for two purposes: to test the validity of experimental methods and to calculate flame velocities for comparison to experimental results. The ignition delay time is a characteristic quantity of the fuel and also depends on initial temperature, pressure and mixture composition. Homogenous simulations were performed using the code Homrea (U.Mass, Dissertation, University Heidelberg, 1988). Calculation of the dependence of the ignition delay time on temperature and reactant composition provides a powerful tool for modelling and understanding the combustion mechanism of a given fuel, in special at lower temperatures. It is known that the rates of elementary reactions in combustion processes differ greatly. For sensitive reactions, values for the rate coefficients have to be well-known. Sensitivity analysis has been performed in order to identify the rate-limiting reactions and to understand the behavior of the chemical system under different conditions. Furthermore, reaction flow analysis has been conducted to elucidate the important chemical pathways over a wide range of conditions. To demonstrate the capabilities of the mechanism proposed in this work, a comparison between experimental data and simulations of flame velocities and ignition delay times is presented. In summary, a detailed kinetic mechanism has been developed to simulate the oxidation of hydrocarbons up to C4 species under high-temperature conditions. The calculated ignition delay times and flame velocities are in a good agreement with experimental data for all hydrocarbon fuels studied in this work, except for the ignition delay time in case of acetylene, where our calculations show shorter ignition delay time at comparable conditions.
In order to develop a simple and reliable protocol for the immobilization of catalytically active metal species, epoxy resins containing d-block metal species were prepared via polyaddition or homopolymerization of the resins using metal complexes as initiators and evaluated in the epoxidation of alkenes, C-C coupling reactions and hydrogenation of unsaturated substrates. The resins TGMDA, TGAP, Novolac, ERL4221, or TGAP/PT30 were cured in the presence of Mo(OEt)5, Mo(EH)n, H3Mo12O40P•xH2O, MoO2(TMHD)2, W(OEt)5, Ti(EH)4, VO(OPr)3 or V(NAPH)n and the catalytic activities of the resulting materials were evaluated in the epoxidation of liquid alkenes and propene with organic hydroperoxides as oxidants. This part represents investigations on different curing methods, the relation between catalytic activity and metal species leaching, and the nature of true active species. Insights into long-term activities and stabilities of the catalysts were also taken into account. In the Suzuki and Heck coupling reactions, TGAP cured by using Pd(PPh3)4 as polymerization initiator was investigated. In order to optimize the reaction conditions, the influences of different solvents, bases and other factors were considered. Hot filtration, dissolving/redeposition and poisoning tests were also carried out to distinguish the true active species in these C-C coupling reactions. In addition, competition reactions were performed in the Suzuki coupling of different substituted substrates with phenylboronic acid to compare the influence of substituents. In the hydrogenation reactions, TGAP containing palladium or niobium species prepared by using Pd(PPh ) or Nb(OEt) as initiators was investigated. Unsaturated esters and aldehydes can be quantitatively converted to the corresponding hydrogenation products under mild reaction conditions. Metal species leaching is extremely low and a long-term application is possible. Different magnetic catalysts were also prepared via homopolymerization by inclusion of magnetic particles and evaluated in the epoxidation of cyclohexene, Suzuki coupling and hydrogenation reactions. The approach for the immobilization of d-block metal compounds via homopolymerization of epoxy resins seems to allow the use of further metal compounds and extension of the concept to other catalytic reactions.
Um die Vorgänge bei der Verbrennung in modernen Motorentypen, wie z.B dem direkteinspritzenden Benzinmotor, besser verstehen und optimieren zu können, haben sich in den letzten Jahren berührungsfreie, laserbasierte Diagnostik-Methoden als besonders vielseitig und hilfreich erwiesen. Die meisten Motorenentwickler benutzen heutzutage bei ihrer Arbeit optische Messtechniken. Um jedoch sicherzustellen, dass diese Methoden genaue und zuverlässige Ergebnisse liefern, ist es nötig, sie genau zu überprüfen und zu charakterisieren. In dieser Arbeit werden eine Reihe von optischen Diagnostiktechniken für die Sprayanalyse, die auf dem Prinzip der laserinduzierten Fluoreszenz (LIF) von Tracern basieren, auf ihre Anwendbarkeit und ihre Grenzen hin untersucht. Die Methoden wurden dazu auf unterschiedliche Spraysysteme angewendet: Von der Anwendung in einzelnen Tropfen über Modelsprays bis hin zu Kraftstoffsprays in Versuchsmotoren. Tracer-LIF basiert auf fluoreszierenden Substanzen, die dem Kraftstoff in geringen Mengen beigemischt werden. Deren Fluoreszenzeigenschaften werden dazu verwendet, lokale Größen wie Tropfentemperatur, -größe oder -geschwindigkeit mit hoher Zeitauflösung zu messen. Aus diesen Größen können wichtige Schlüsse über Wärmeund Stofftransportprozesse, die bei der Sprayverbrennung ablaufen, gezogen werden. Jedoch müssen die Eigenschaften der Tracer dazu sehr genau bekannt sein, um verwendbare und vergleichbare Ergebnisse zu garantieren. In dieser Arbeit wurden Tracer im Hinblick auf ihre Verdampfungseigenschaften und die Temperaturabhängigkeit der Fluoreszenzeigenschaften charakterisiert. Außerdem wurden die Farbstoffe Atto 680, Rhodamin 800 und Rhodamin B auf ihre Anwendbarkeit als Tracer in realen Kraftstoffen untersucht. Gepulste Lasersysteme und hochauflösende CCD oder CMOS-Kameras erlauben die detaillierte und zeitlich wie räumlich hochaufgelöste Untersuchung der Sprayentstehung, -verdampfung und -verbrennung mit Hilfe von Tracer-LIF. Durch Verwendung der sogenannten Laser-Lichtschnitt-Methode können die Signale in zweidimensionalen Schnittebenen simultan erfasst werden. Die Anwendung der zuvor charakterisierten Tracer auf eine Modell-Sayflammen erlaubte durch Vergleich mit den Ergebnissen neuer numerischer Spraymodelle, welche die Flammenchemie über einen Flameletansatz berücksichtigen, neue Einblicke ich diese Vorgänge. Um die Verdampfung eines einzelnen Tropfens zu untersuchen, wurde darüber hinaus eine elektrodynamische Falle konstruiert und aufgebaut, die geladene Tropfen in einem Hochfrequenzfeld über längere Zeit festhalten kann. Die Heizung der Tropfen erfolgte durch einen CO2-Laser. Der Vergleich mit einem neuen Tropfenverdampfungsmodell, das diese Bedingungen berücksichtigt, lieferte vielversprechende Ergebnisse In einem Versuchsmotor mit Benzin-Direkteinspritzung konnte außerdem die Wechselwirkung zwischen Kraftstoffspray und Zündkerze, die Beeinflussung des Zündfunkens, sowie die Auswirkungen von Schwankungen im Spraywinkel während der Einspritzung untersucht werden, was Aufschlüsse über die möglichen Ursachen von Fehlzündungen und unvollständiger Verbrennung lieferte. Laserinduzierte Exciplex- Fluoreszenz lieferte, zur weiteren Untersuchung dieses Sachverhalts, quantitative Informationen über die räumliche Verteilung des zündfähigen Gemischs bei verschiedenen Benzininjektoren unter variierenden Bedingungen.
Die vorliegende Arbeit beschreibt die Präparation und den Einsatz optisch aktiver Nanopartikeloberflächen in der Immundiagnostik. Diese Sensoroberflächen bestehen aus oberflächen-adsorbierten Core-shell Partikeln (Nanopartikel mit einem dielektrischen Kern und einer metallischen Hülle) und zeigen ausgeprägte Resonanzen im sichtbaren Spektralbereich, die auf eine Anregung von sowohl lokalisierten als auch propagierenden Oberflächenplasmonenresonanzen zurückgeführt werden können. Da die Resonanzlage empfindlich gegenüber Änderungen des umgebenden Brechungsindex reagiert, kann sie zu einer markierungsfreien Detektion und Quantifizierung von Bindungsereignissen eingesetzt werden. Durch die kombinierte Anregung von lokalisierten und propagierenden Plasmaschwingungen resultieren im Vergleich zur konventionellen SPR sowohl höhere optische Extinktionswerte (Steigerung um etwa 3 Größenordnungen), die ein verbessertes Signal/Rausch-Verhältnis zur Folge haben, als auch eine höhere Sensitivität gegenüber Änderungen der dielektrischen Eigenschaften ihrer unmittelbaren Umgebung; bezüglich der Adsorption von Oktadekanthiol konnte eine etwa 5-fache Sensitivitätssteigerung erzielt werden. Zudem bietet das Dicken¬verhältnis von Kern/Schale einen weiteren Parameter, durch den die Resonanzlage über den gesamten sichtbaren Bereich verschoben und somit gezielt außerhalb des Absorptionsfensters von Störkomponenten platziert werden kann. Anhand geeigneter Kalibrationsmessungen und Bindungsstudien wurde gezeigt, dass analog zur konventionellen SPR in dem analysierten Bereich von Massenbelegungen bis hin zu 600 ng/cm2 und einer lateral gemittelten Schichtdicke von 75 Å (lokale Maximalwerte ~ 24 nm) keine Minderung der Sensorantwort eintritt und eine lineare Beziehung zur Resonanzverschiebung besteht. In verschiedenen immunodiagnostischen Anwendungen (Antikörper-Antigen-, Peptid-Antikörper-Assays) konnten die Bindungsereignisse daher nicht nur detektiert, sondern mittels der zuvor bestimmten Eichwertfaktoren auch quantifiziert werden, wobei eine gute Übereinstimmung zu den anhand anderer Analysemethoden (XPS, ELISA) erhaltenen Massenbelegungen und Schichtdicken erhalten wurde. Im Vergleich zur konventionellen SPR besitzen diese Systeme weitere Vorteile, die vor allem einen Einsatz im Mikroarray-Format betreffen. Die Möglichkeit zu einer sehr viel höheren lateralen Auflösung (theoretisch im Nanometerbereich) sowie die technisch einfache Art der markierungsfreien Detektion sprechen für einen direkten Einsatz in hoch parallelisierten und miniaturisierten Biochips (DNA-, Peptid- und Protein-Arrays), in denen eine Vielzahl an Bin¬dungsereignissen ortsaufgelöst und simultan (bei Einsatz einer CCD-Kamera) bestimmt werden können. Zur Demonstration einer solchen Applikation wurden photochemisch strukturierte Oberflächenbeschichtungen erzeugt und mittels LSPR-Imaging ausgelesen; diese wurden anschließend fluoreszenzspektroskopisch visualisiert, wobei eine gute Übereinstimmung bezüglich Geometrie und Ausmaße der erzeugten Strukturen erhalten wurde. Eine eindeutige Detektion und Quantifizierung biomolekularer Wechselwirkungen setzt jedoch die Spezifität der beobachteten Bindungsereignisse voraus. Ein weiterer Schwerpunkt dieser Arbeit betraf daher die Erzeugung von Oberflächenbeschichtungen auf Polyethylenglykolbasis, die geeignete Funktionalitäten zu einer Integration von Rezeptoren für immunodiagnostische Anwendungen aufweisen, eine unspezifische Adsorption jedoch weitgehend unterdrücken. Hierzu wurden endgruppenfunktionalisierte (OH, COOH, NH2) Polyethylenglykolthiole unterschiedlicher Kettenlängen (15 – 40 EG-Einheiten) synthetisiert und nach der Adsorption auf Au-bedampften Si-Wafern hinsichtlich ihrer Bindungskapazität und Proteinresistenz untersucht. Unabhängig von der Art der Terminierung ergab sich eine deutliche Abhängigkeit der Resistenz von der Kettenlänge, wobei mit zunehmender EG-Anzahl ein Anstieg der Proteinresistenz beobachtet wurde. Aber auch die Endgruppe zeigte einen entscheidenden Einfluss auf die Adsorptionsrate; bezüglich der funktionellen Terminierung konnte folgende Resistenzreihe aufgestellt werden: NH2 < COOH << OH. Unabhängig von der Kettenlänge erfordert vollständige Proteinresistenz eine elektrostatische Neutralität der erzeugten Beschichtung. Im Fall durch Protolyse geladener Oberflächenfunktionalitäten resultieren höhere Adsorptionsraten bei positiver Ladung (protonierte Aminogruppen), die auf verstärkte Wechselwirkungen mit den üblicherweise negativ geladenen Proteinen zurückgeführt werden können. Weiterhin zeigte sich, dass eine Zunahme der Proteinresistenz mit einer abnehmenden Antikörper-Bindungsrate verbunden ist. In immunodiagnostischen Anwendungen muss daher über die Parameter der Endgruppenfunktionalität und Kettenlänge ein geeigneter Kompromiss zwischen Proteinresistenz und Rezeptor-Dichte eingestellt werden.
In dieser Arbeit wird die migratorische Insertion und die beta-Wasserstoffeliminierung für die Übergangsmetallkomplexe [CpM(PH3)H(C2H4)]+ quantendynamisch untersucht (M = Rh bzw. Co). Die Rechnung simuliert ein Experiment, bei dem ein geeigneter Laserpuls den Komplex in einen Übergangszustand anregt, von dem aus eine Nicht-Gleichgewichtsbewegung beginnt. Die Kerndynamik dieses Prozesses wird durch die Zeitentwicklung eines Wellenpakets mit bis zu drei Kernfreiheitsgraden beschrieben. Die zugrundeliegenden Potentialflächen für Rhodium und Cobalt haben drei Minima (Ethylenstruktur, beta-agostische Zwischenstufe, Ethylstruktur) und zwei verbindende Übergangspunkte. Übereinstimmend mit dem Experiment ist beim Rhodiumkomplex die Ethylenstruktur das globale Energieminimum (0 kcal/mol). Beim Cobaltkomplex hingegen ist es die agostische Struktur, die bei -3.5 kcal/mol liegt. Die Komplexe verhalten sich bei der beta-Wasserstoffeliminierung aus dem ersten Übergangszustand heraus qualitativ gleich: Das Wellenpaket oszilliert ellipsoid im agostischen Minimum und überwindet periodisch die Barriere des ersten Übergangszustands zur Ethylenstruktur hin. Die Lebensdauer einer Breitbandanregung in den ersten Übergangszustand beträgt beim Rhodiumkomplex 100 fs und beim Cobaltkomplex 130 fs. Es werden Photoelektronenspektren und Schwingungseigenfunktionen berechnet. Dabei konnten drei dominante Schwingungsmoden identifiziert werden: eine parallel und zwei senkrecht zum Reaktionspfad. Die Schwingung parallel zum Pfad kann mit nur wenigen kcal/mol aktiviert werden. Die höher angeregten Eigenzustände haben Lebensdauern zwischen zwanzig und einigen hundert Femtosekunden. Interessanterweise lässt sich die dreidimensionale Rechnung mit einem bestimmten zweidimensionalen Potential nähern, das in der vollen Potentialfläche enthalten ist. Auf der Grundlage dieses zweidimensionalen Potentials wurde ein analytisches Modell entwickelt, das Schlüsseldaten gut reproduziert. Es kann als Prototyp für bestimmte Komplexe mit Metallatomen der neunten Gruppe des Periodensystems angesehen werden. Der verwendete Ansatz für die kinetische Energie kann generell für die meisten chemischen Reaktionen mit vier reaktiven Zentren dienen.
Das molekulare Motorprotein Myosin wandelt chemische Energie aus der ATP Hydolyse in mechanische Arbeit um, die dazu genutzt wird um Myosin- und Aktin-Filamente gegeneinander zu verschieben und so z.B. die Muskelkontraktion zu ermoeglichen. Der Mechanismus dieser chemisch-mechanischen Kopplung, der fuer die Funktion von Myosin essenziell ist, ist nur in Ansaetzen verstanden. In dieser Arbeit wird ein rechnergesttzter Ansatz verwendet um den Mechanismus des recovery stroke'' zu verstehen. Der recovery stroke'' ist einer der fundamentalen Prozesse bei der Muskelkontraktion in lebenen Organismen. Waehrend des recovery stroke'' wird der Myosin Motor fuer den naechsten Kraftschlag vorbereited indem der Myosin-Kopf um 60 degree relativ zur Konverter-Domaene und dem Hebelarm gedreht wird. Der Drehpunkt ist mit der Bindetasche, in der die ATP Hydrolyse stattfindet, durch die sogenannte Relais-Helix verbunden. Waehrend des "recovery stroke" finden eine eine Reihe von strukturellen Aenderungen laengs dieser Helix statt. In der vorliegenden Arbeit wird der Kopplungsmechanismus zwischen der ATP Hydrolyse und der Drehbewegung mit Hilfe eines Minimum-Energie Pfades (MEP) simuliert. Der MEP verbindet die Roentgenkristallographischen End-Zustaende des Prozesses durch eine Kette von geometrieoptimierten intermediren Strukturen. Der "recovery stroke" beruht auf der Bildung zweier Wasserstoffbrueckenbindungen durch die "switch-2" Schleife, in Korrelation mit der Bewegung zweier Helices welche die Konverter-Domaene halten: der Relais-Helix und der SH1-Helix. Der MEP zeigt dass dieser Prozess aus zwei Phasen besteht. In der ersten Phase bildet sich eine Wasserstoffbrueckenbindung zwischen Gly457 am N-terminalen Ende der Relais-Helix und dem gamma-Phosphat des ATP, was eine Kipp-Bewegung der Relais-Helix zur Folge hat. Die zweite Phase wird durch die Bildung einer Wasserstoffbrueckenbindung zwischen der "switch-2" Schleife und Ser181 der P-Schleife initiiert. Dadurch wird eine weitere Schleifeaehnlich einem Keil gegen das N-terminale Ende der SH1-Helix geschoben, wodurch letztere parallel zur Relais-Helix verschoben wird. Die Kippbewegung der ersten Phase bewirkt eine Drehung der Konverter-Domäne um 30 degree, wahrend die Verschiebung der SH1-Helix eine Drehung um weitere 40 degree zur Folge hat. Der hier vorgeschlagene Kopplungsmechanismus ist konsistent mit verfuegbaren Mutations-Experimenten und erklaert zum ersten Mal die Rolle der hochgradig Sequenz-konservierten Schleife, die hier "Keil"-Schleife genannt wird. In einem weiteren Teil der Arbeit werden Molekulardynamik-Simulationen von Myosin II des Organismus Dictyostelium Discoideum in beiden End-Zustaenden des "recovery stroke" mit verschiedenen Nukleotid-Zustaenden (ATP, ADP.Pi, ADP) durchgefuehrt. Diese Simulationen zeigen dass die Seitenkette von Asn475 (welche die erste Phase des "recovery stroke" initiiert") sich durch die ATP-Hydrolyse von "switch-2" wegbewegt und eine Wasserstoffbrueckenbindung mit Tyr573 auf der Keilschleife bildet. Diese Abhaengigkeit vom Nukleotid-Zustand wird erklaert durch eine kleine Verschiebung des abgespaltenen beta-Phosphats hin zu Gly457 welches seinerseits Asn475 verschiebt. Die Sensitivitaet bezueglich des Nukleotid-Zustandes ist wichtig fuer (i) die Vermeidung einer unproduktiven Umkehrung des "recovery strokes" waehrend des ADP.Pi Zustandes, und (ii) die Entkopplung der Relais-Helix vom "switch-2", wodurch erreicht wird, dass der Kraftschlag nach der initialen Bindung an Aktin ausgelast wird, wobei Gly457 von "switch-2" weiterhin mit dem Pi interagiert,welches bekanntermass en erst nach der Bindung an Aktin freigelassen wird. Es wird beobachtet dass die katalytisch wichtige Salzbruecke zwischen Arg238 (in "switch-1") und Glu459 (in "switch-2"), welche die Bindetasche and der Hydrolysestelle bedeckt, durch die Bindung von ATP an die Struktur vor dem "recovery stroke" schnell gebildet wird. Diese Salzbrucke bleibt auch nach dem "recovery stroke" stabil, was darauf hindeuted dass sie die Rolle hat die ATP Bindetasche durch "induced fit" zu formen.
Cellular functions such as cell growth, adhesion and differentiation are essentially controlled by the surrounding extracellular matrix (ECM). The mechanical, chemical and structural properties of the ECM are consequently crucial for the selection of cells at interfaces and the formation of tissues. The objective of this thesis was to develop an artificial ECM to determine and control the parameters influencing the crosstalk between cells and their surroundings on a molecular level. Artificial ECMs which mimic the natural environment of cells enable precise insights into cell-ECM crosstalk; ultimately, we aim to trigger the crosstalk, such that specific cell functions are provoked. To this end, a modular ECM system was developed, consisting of (i) poly(ethylene glycol) (PEG) as the basic material, (ii) gold nano-particles as the structuring component, and (iii) bioactive molecules which are immobilized on the basic material and on the nano-structure, to equip these modules with a biological function. The mechanical, structural, and chemical properties of the artificial ECM, as defined by the respective modules, can be tuned independently from one another, enabling the customized tailoring of the artificial ECM for specific applications. PEG hydrogels, used as both the basic material and first module of the artificial ECM, were chosen because of their resistance to protein adsorption, as well as their elastic and swelling properties, which partly mimic the hyaluronan material surrounding the cell membrane. A photo-initiated crosslinking reaction of PEG macromers was used to obtain hydrogels with well-controlled physical properties, characterized in terms of the gel content, swelling ratio, and mesh size. Elasticity at the nanoscale was assessed by an indentation method using atomic force microscopy (AFM). In this way, we were able to prepare hydrogel surfaces covering the biologically relevant range of elasticities. Structuring the hydrogel substrates with nanoscale gold patterns as the second module of the artificial ECM was achieved by means of a newly-developed transfer lithography method. Gold particles of a particular size, and separated by a defined distance were obtained by using block copolymer micelle nanolithography, which itself is restricted to solid, inorganic, and planar surfaces such as glass slides; the gold particles are transferred to polymers by means of a thiol-gold coupling scheme. Depending on the polymer to be gold-decorated, an appropriate thiol linker molecule was incubated on the gold-patterned glass surface, and crosslinked to the PEG hydrogel during polymerization. The transfer resulted in a complete and accurate transfer of the nano-pattern to the polymer surface. Cryo-electron microscopy was used for structural characterization of the resulting surfaces, including watercontaining soft hydrogels. 2 The transfer nano-lithography technique is the first method to successfully nanostructure soft and polymeric materials with metal structures on a large scale, and can in principle be applied to the structuring of any organic planar and non-planar surface. The structural properties of the artificial ECM, controlling, e. g., the clustering of receptors at adhesion sites of adhering cells, can be adjusted by choosing the particle size and distance of the original gold pattern. Another structural parameter can be introduced by the non-planarity of the surfaces. Hydrogel-based microchannels have been developed that were internally decorated with gold nanoparticles, resulting in nanopatterned, tube-shaped artificial ECMs surrounding the cell in three dimensions, mimicking, for example, blood vessels. As a third module of the artificial ECM, the nanostructured hydrogel surfaces were chemically modified to provide the cell with biofunctions. Proteins were coupled to the gold particles or the hydrogel surface via Ni(II)-NTA complexes, and peptides were coupled to the gold particles via thiol groups, or to the hydrogel surface via amino groups. The four different schemes were developed to specifically couple the bioactive molecules at well-defined orientations and in their native conformation to either the hydrogel surface or the gold moieties, without introducing either cytotoxicity or loss of biocompatibility. The selective functionalization was tested for representative biomolecules, the adhesion receptor-binding peptide RGD, the cell-cell adhesion protein L1, and the green fluorescent protein. This concept enables selective modification of the gold particles or the inter-particle surface by coupling virtually any biomolecule to the aforementioned domains of the artificial ECM. The functionality of the three different components of the artificial ECM was tested in cell experiments. Experiments using substrates with various inter-gold particle spacing, biofunctionalizations, and cell types, demonstrated the applicability of the artificial ECM as such. Most importantly, for the first time, nanopatterned hydrogels were shown by cryo-SEM to be deformed by the adhering fibroblasts, thereby revealing the direct crosstalk between the cell and the ECM mimic on the molecular level. In addition, the functionality of non-planar substrates for cell experiments was demonstrated by means of micro-channels. In conclusion, the modular artificial ECM, as developed in this research project, meets the mechanical, structural, and biological requirements necessary to serve as a versatile and adjustable tool to investigate and provoke specific cell-surface interactions. The artificial ECM provides a useful means by which to influence cell adhesion and function, thereby enabling systematic selection of cell types for biotechnological and medical applications.
In this thesis, the differential effects of three closely-related sterols: ergosterol, cholesterol and lanosterol on the structural and dynamical properties of a model dipalmitoyl phosphatidylcholine (DPPC) membrane were examined using Molecular Dynamics (MD) simulations and Neutron Scattering (NS) calculations. As a necessary step towards realistic sterol:biomembrane simulations, molecular mechanics force field parameters for cholesterol, ergosterol and lanosterol, for the program package CHARMM are derived. Subsequently, MD simulations of hydrated sterol:DPPC lipid systems are performed at a biologically-relevant concentration (40\% mol.) at 309K and 323K. The simulations are compared with control simulations of the gel and liquid DPPC phases. All three sterols are found to order and condense the lipids relative to the liquid phase, but to markedly different degrees. Ergosterol is enhancing the packing of the lipids with each other and has a higher condensing effect on the membrane than the other two sterols. Moreover, ergosterol induces a higher proportion of trans lipid conformers, a thicker membrane and higher lipid order parameters, and is aligned more closely with the membrane normal. Ergosterol also positions itself closer to the bilayer:water interface. In contrast, lanosterol orders, straightens and packs the lipids less well, and is less closely aligned with the membrane normal. Furthermore, lanosterol lies closer to the relatively-disordered membrane center than do the other sterols. The behaviour of cholesterol in all the above respects is intermediate between that of lanosterol and ergosterol. The origins of the different membrane behavior upon addition of each sterol are discussed with respect to the sterol chemical differences. Ergosterol was also found to diffuse the slowest and cholesterol the fastest both in the xy-plane and the z-axis of the membrane among the three sterols studied. The findings here may explain why ergosterol is the most efficient of the three sterols at promoting the liquid-ordered phase and lipid domain formation, and may also furnish part of the explanation as to why cholesterol is evolutionarily preferred over lanosterol in higher-vertebrate plasma membranes.
This work focuses on laser-induced incandescence (LII) at elevated pressure. LII is a laser-based technique for measuring particle sizes and volume fractions of nano-sized particles in aerosols. These particles, as emitted by traffic in the form of soot, cause a significant health risk, as nano-sized particles can penetrate deeply into the lungs and are considered important for causing asthma, fibrosis and the development of tumors [1,2]. Over the past 20 years, LII has been developed and applied mainly for soot diagnostics in flames. However, only little work has been performed before on LII in sooting flames at elevated pressure. Nonetheless, this is important for applications in technical high-pressure environments, namely Diesel engines. Construction of a sooting high-pressure burner. In order to investigate the ability of LII as a tool for soot diagnostics at elevated pressure, a sooting high-pressure burner was constructed in coopera-tion with the research group of Prof. Dr. Dr. h.c. H. Gg. Wagner and Dr. H. Jander of the Universität Göttingen. Several improvements compared to previous burners were made. The burner produced long-term stable, laminar ethylene/air flames up to 10 bar with pressure fluctuations less than ± 2%. In LII diagnostics, this burner is unique in its performance world wide. Modeling laser-induced incandescence. The LII signal results from the heat-up of particles by a nanosecond laser pulse and subsequent cooling due to near-blackbody radiation and different compet-ing heat-loss paths. This process was modeled by setting up an energy and mass balance for the differ-ent heat- and mass-loss mechanisms. Recent advancements on the different sub-models were com-bined in a numerical model. This model, called LIISim, enables the modeling of LII signals as well as the fitting of experimental LII decay curves with a Levenberg-Marquardt non-linear least-squares fit-ting algorithm. Additionally, a perl script was written which allows the access to the LII model using a web browser. For the first time, an LII model was made available to the scientific community by a web interface. This will simplify the comparison of different LII models and reveal deficiencies in the underlying sub-models. LIISim is available at http://www.liisim.com. Particle sizing with LII at variable pressure. The log-normal size distribution of soot particles was measured in the new high-pressure burner at pressures of 1 – 10 bar using LII. The flame temperature as well as the peak particle temperature are required as input parameters for the data evaluation with LIISim. These parameters were determined by two-color pyrometry of non-laser-heated soot (flame temperature) and by two-color LII (peak particle temperature). Low laser fluences of 70 – 115 mJ/cm2 at 1064 nm were used to avoid evaporation. C2 fluorescence within the 550 nm detection channel might interfere with the LII signal. However, spectrally-resolved detection showed no narrow-band interferences in the region of 656 – 400 nm for the low laser fluences used in this study at all investi-gated pressures. Additional to the LII measurements, soot samples were taken from the flame and the particle-size distribution was determined from transmission-electron microscopy (TEM) images of these samples. For the first time, soot particle-size distributions obtained with LII could be compared with a second, independent method at elevated pressures. Moreover, a first comparison of different heat-conduction models used for the evaluation of experimental LII signals could be performed. The results show excellent agreement between the mean diameter of the particle-size distribution obtained by TEM analysis and LII for all pressures, if the LII data are evaluated with the model of Fuchs taking into account the reduced heat conduction of aggregated particles. This work significantly advanced the understanding of LII at high pressures which further improves the applicability of this diagnostics technique to in-situ particle-size measurements in practical high-pressure combustors like Diesel engines.
-Siehe Zusammenfassung-
Die Katalyse ist das ideale Instrument zur Erreichung der Ziele der „Green Chemistry“, weil Selektivität und Aktivität einer Umsetzung beeinflusst werden können. Der ideale Katalysator ist dabei komplett wiederverwendbar. Die Anwendung von Flüssig/flüssig-Zweiphasen-Systemen ist dafür eine gute Alternative, wobei die Natur des Solvents eine wichtige Rolle spielt. Die chemischen und physikalischen Eigenschaften von ionischen Flüssigkeiten variieren mit der Kombinationen von Kation / Anion in einem weiten Bereich; sie werden daher als „designer solvents“ bezeichnet. Das Ziel dieser Arbeit war die Synthese von Phosphino-modifizierten ionischen Flüssigkeiten, die als Liganden durch Komplexierung an Übergangsmetalle in der Zweiphasenkatalyse erfolgreich eingesetzt werden können. Ihre Anwendung in der Zweiphasenkatalyse, in SILP-Systemen und in der Optimierung der SILP-Katalyse durch den Einsatz von polaren organischen Polymeren, die die Langzeitstabilität der SILP-Systeme erhöhen sollten, wurde auch untersucht. Eine einfache, modulare und flexible Synthese für die eingesetzten Phosphino-funktionalisierten ionischen Flüssigkeiten wurde entwickelt. Im ersten Schritt werden, ausgehend von N-Methylimidazol, durch eine SN-Reaktion mit einem Alkylierungsagens, 3-Methyl-Imidazoliumhalogenide hergestellt, die in 1-Position über einen Spacer noch mit einer Halogenfunktion ausgestattet sind. Durch eine weitere SN-Reaktion dieses Halogens mit einem Phosphid können so die Phosphino-funktionalisierten Imidazolium-Salze hergestellt werden, welche ionische Flüssigkeiten darstellen, die über Phosphindonorgruppen verfügen, die ihrerseits zur Stabilisierung von Übergangsmetallfragmenten dienen. Die hergestellten Phosphino-funktionalisierten Imidazolium-Liganden wurden mit geeigneten Rh-Präkatalysatoren zuerst in der flüssigen, einphasigen Hydroformylierung eingesetzt, anschließend in der Flüssig/flüssig-Zweiphasenkatalyse mit ionischen Flüssigkeiten als zweiter Flüssigphase. Es folgte die Supported-Ionic-Liquid-Phasen-Katalyse, in denen der Präkatalysator auf einem anorganischen Träger durch Adsorption in Ab- und Anwesenheit eines polaren, organischen Polymers immobilisiert wurde. Das Polymer sollte dabei die Wechselwirkung zwischen der adsorbierten IL und dem anorganischen Trägermaterial erhöhen und so zu einer Verbesserung der Stationarität des Katalysators führen. Die Ergebnisse der verschiedenen Ansätze wurden hinsichtlich der Aktivität, Selektivität und des Recyclingverhaltens und somit hinsichtlich ihres Nutzens im Sinne der Nachhaltigkeit verglichen.
Aufbau und Untersuchung von elektronoisch aktiven Phenothiazinsystemen: Monodisperse Phenothiazinoligomere und Phenothiazin-Ferrocen-Hybridoligomere, Polymere und Copolymere und Donor-Akzeptorsysteme. Die Synthese der Zielverbindungen erfolgte über ein Baukastensystem aus unterschiedlich substituierten Phenothiazinderivaten mittels Suzuki-Kreuzkupplungsreaktion. Die Module wurden durch teils sequenzielle Reaktion (di)lithierter Vorstufen mit untzerschiedlichen Elektrophilen erzeugt.
An Borhydrid-Clustern wurden Dichtefunktional-Rechnungen durchgeführt um Regeln zu finden, die ihren Strukturen und relativen Stabilitäten zugrunde liegen. Dazu wurden Strukturinkremente für unvorteilhafte Strukturmerkmale ermittelt, und zwar in 11-Vertex nido- und 12-Vertex closo- Carboranen, -Heteroboranen und -Carbaheteroboranen sowie 12-Vertex closo- Cyclopentadienylmetallacarboranen. Sie reproduzieren die relativen Stabilitäten wie sie aus Dichtefunktional-Rechnungen resultieren sehr genau. Bemerkenswerterweise können die relativen Energien einer sehr großen Anzahl von isomeren Strukturen durch eine recht kleine Anzahl von Strukturinkremente mittels einfacher Summation ermittelt werden, da sich letztere höchst additiv verhalten. Strukturinkremente können als Energiedifferenz zweier Isomere erhalten werden, wenn diese sich in nur in dem einen relevanten Strukturmerkmal unterscheiden, oder durch eine statistische Fittprozedur basierend auf einer größeren Anzahl von verschiedenartigen Strukturen. Sie zeigen periodische Trends, wie zum Beispiel dass sie entlang einer Periode zunehmen und innerhalb einer Gruppe mit steigender Ordnungszahl abnehmen. Sie hängen in erster Linie von der Zahl der Gerüstelektronen ab, die eine bestimmte Heterogruppe zur Clusterbindung beiträgt, und in zweiter Linie von der Elektronegativität des Heteroatoms. Strukturinkremente können auch als Konnektivitätsinkremente ausgedrückt werden. Diese besitzen den Vorzug als einheitlicher Satz von Inkrementen gleichermaßen zur Bestimmung der relativen Stabilitäten von 11-Vertex nido- wie auch 12-Vertex closo-Clustern herangezogen werden zu können. Üblicherweise neigen elektronegativere (kleinere) Heteroatome dazu, in den thermodynamisch stabilsten closo-Diheterododecaboranisomeren nicht-benachbarte Clusterplätze einzunehmen, wohingegen weniger elektronegative (größere) Heteroatome benachbarte Vertices besetzen. Cyclopentadienyl-Übergangsmetallfragmente besitzen in Bezug auf die thermodynamisch stabilsten 12-Vertex closo-Cyclopentadienylmetallaheteroboran- Isomere einen spezifischen ortho-, meta- und para-dirigierenden Effekt auf ein Kohlenstoffatom. Des weiteren wurden Dichtefunktional-Rechnungen an Makropolyedern durchgeführt, und zwar an Strukturen in denen zwei reguläre Clusterfragmente an einer gemeinsamen Kante verschmolzen sind, sich also zwei Vertices teilen. Es wurde der Wendepunkt ermittelt, an dem die Präferenz bei den Boranen von Einfachcluster- zu Makropolyeder-Strukturen wechselt: Alle nido-Cluster sind thermodynamisch stabiler als entsprechende makropolyedrische Borane, solange die Zahl der Vertices kleiner als zwölf ist. Makropolyedrischen Boranen kommt erst bei größeren Molekülen (n ≥ 12) eine größere thermodynamische Stabilität zu. Bei den Anionen findet man eine deutliche Bevorzugung der Makropolyeder allerdings erst ab 17 Vertices. Die zusätzlichen Wasserstoffatome auf der offenen Fläche der Borane haben einen entscheidenden Einfluss auf die relativen Stabilitäten von Einfach- gegenüber makropolyederischen Clustern. Die arachno-9-Vertex und nido-10-Vertex Clusterfragmente sind bevorzugte Bausteine für Makropolyeder und sind meist in den thermodynamisch stabilsten makropolyedrischen Boranisomeren vertreten. Außerdem wurden die strukturellen Beziehungen zwischen den verschiedenen Klassen von Makropolyedern geklärt: Die thermodynamisch stabilsten Isomere von Makropolyedern leiten sich voneinander durch die Entfernung eines Vertexes von der offenen Fläche eines Clusterbausteins ab. Clusterinkremente wurden für verschieden große makropolyederische Borane mit zwei gemeinsamen Vertices ermittelt. Sie erlauben es, die relativen Stabilitäten von Makropolyedern leicht abzuschätzen.
Die Arbeit behandelt die Synthese Metallkomplex-funktionalisierter Oligonucleotide und Peptidnucleinsäuren (PNAs) und deren Anwendung als Sonden für den sequenzspezifischen DNA-Nachweis. Zum einen wurde dazu Metallkatalyse am DNA-Templat genutzt, zum anderen Signalverstärkung durch chemische oder enzymatische Katalyse. Eine Nucleinsäure kann als Templat funktionalisierte Oligonucleotide in räumliche Nähe zueinander bringen und deren intermolekulare Reaktion beschleunigen. Die im Rahmen dieser Arbeit untersuchte Redoxreaktion zwischen einer Metallkomplex- und einer Thiol-funktionalisierten Peptidnucleinsäure am DNA-Templat wurde fluorimetrisch verfolgt. Für die Nachweisreaktionen, die auf Signalverstärkung beruhen, wurden Konjugate von DNA-Oligonucleotiden mit Metallkomplexen synthetisiert, die bei Hybridisierung mit komplementärer DNA das Metallion (CuII, ZnII) freisetzen. Das CuII-Ion (bzw. ZnII-Ion) aktiviert als Cofaktor einen chemischen Präkatalysator (bzw. ein Apoenzym) und die anschließend durch den Katalysator (bzw. das Holoenzym) initiierten Reaktionen machen das DNA-Target durch Umsetzung fluoro- oder chromogener Substrate fluorimetrisch, photometrisch oder sogar für das Auge direkt sichtbar. Das DNA-Target konnte mithilfe dieser Signalwandlung (DNA - Metallion) mit hoher Empfindlichkeit und Sequenzspezifität nachgewiesen werden. Die verwendeten Metallkomplex-funktionalisierten Oligonucleotide wurden zum besseren Verständnis der Signalwandlung hinsichtlich ihrer thermodynamischen und kinetischen Stabilität charakterisiert. In einer Variante dieser Oligonucleotid-Konjugate wirkte das Metallion CuII als intramolekularer Fluoreszenzlöscher, sodass die Bindung einer komplementären Nucleinsäure in Form eines Fluoreszenzsignals verfolgt werden kann.
Im Rahmen dieser Doktorarbeit wurden selbstaggregierende Multischichten aus Alkyl-Siloxanen auf einer Biphenylthiol-Modelloberfläche auf Gold mit Hilfe verschiedener Meßmethoden wie Infrarot-Reflexions-Adsorptionsspektroskopie (IRRAS), Summenfrequenz-Spektroskopie (SFG), Röntgen-Photoelektronen-Spektroskopie (XPS), Ellipsometrie, Raster-Kraft-Mikroskopie (AFM) und Kontaktwinkelmessung charakterisiert. ω-Mercaptobiphenyle wurden benutzt, um stabile, auf Molekülebene manipulierbare OH-Oberflächen herzustellen, die man als Substrat für die Untersuchung des Selbstaggregationsmechanismus der Alkyltrichlorsilane verwenden kann. In der vorliegenden Arbeit wurde als Vertreter der n-Alkyltrichlorsilane n-Octadecyltrichlorsilan (OTS) herangezogen. Für die ω-Mercaptobiphenyl-Filme (4’-Hydroxy-4-Mercaptobiphenyl, HMBP; 4’Methyl-4-Mercaptobiphenyl, MMBP; Mercaptobiphenyl, MBP) auf Gold wurde gezeigt, dass sie eine vollständig ausgebildete, dichtgepackte Monolage auf Gold (111) bilden, in der die Moleküle nah zur Oberflächennormalen orientiert sind. Die gemischten HMBP/MMBP-Monoschichten haben sich als ein geeignetes System zur präzisen Modifizierung der Hydrophobizität einer Goldoberfläche erwiesen. Für die Qualität der darauf adsorbierten OTS-Schicht scheint der geschlossene Wasserfilm auf der Modelloberfläche verantwortlich zu sein. Die HMBP-Modelloberfläche auf Gold ermöglicht einen Zugang zur direkten spektroskopischen Untersuchung von OTS, da sie keine signifikanten Peaks im CH-Bereich der IRRAS- und SFG-Spektren zeigt. Als ein weiterer Vorteil erweist sich bei der Übertragung der OTS-Adsorption auf ein Goldsubstrat, dass dieses ein großes Signal/Rausch-Verhältnis bietet und dadurch die Verfolgung der Adsorption nicht nur im CH-Bereich sondern auch im „Fingerprint“-Bereich der IRRAS-Spektren ermöglicht. Wir haben die CO-Valenzschwingung der IRRAS-Spektren benutzt um zu zeigen, dass im Durchschnitt ca. 26 % der OTS-Moleküle an den OH-Oberflächengruppen chemisch gebunden sind. Da das zweidimensionale Siloxan-Netzwerk angeblich aus Trimeren besteht , zeigt dieses Ergebnis, dass nur ein Molekül pro Trimer an der Oberfläche gebunden ist, während die Restlichen frei sind, um an die Nachbartrimere zu binden und so ein Siloxan-Netzwerk auszubauen. Das breite Doppelsignal bei 1105 cm-1 und 1205 cm-1 ist ein Zeichen für OTS-Polymerisation auf der Oberfläche und kann benutzt werden um sie nachzuweisen. AFM-Aufnahmen haben gezeigt, dass die Bildung der OTS-Monoschicht sowohl auf einem Siliziumoxyd-Substrat als auch auf unserer HMBP/Au-Oberfläche mit Inselwachstum beginnt. Eine Nachbehandlung der OTS/HMBP/Au-Filme mit Ethanol/Toluol verdichtet den Film und führt zur Bildung von hochgeordneten OTS-Monolagen, in denen die Moleküle um 23º im Verhältnis zur Normalen verkippt sind. Die gewonnene Erfahrung mit den Mercaptobiphenyl-Filmen wurde weiter genutzt, um dünne Phenothiazin-Filme auf Gold spektroskopisch zu untersuchen (Kapitel 4). Alle drei untersuchten Moleküle (CSK 320c, CSK 320b, CSK 325) bilden Monolagen auf Gold und sind nah zur Normalen orientiert. Ein hoher Bedeckungsgrad wurde bei den CSK 320c- und -320b-Filmen festgestellt. Die schlechtere Ordnung und der niedrige Bedeckungsgrad bei CSK 325 wurde mit der störenden sterischen Wirkung der Hexankette erklärt.
Molecular motors are proteins that convert energy from nucleoside triphosphate hydrolysis into mechanical work. A prominent example is myosin which drives muscle contraction and a large number of additional cellular transport phenomena in all living organisms. While hydrolyzing ATP, myosin translocates along an actin filament. The catalytic cycle for ATP hydrolysis and the mechanical motor cycle are closely coupled. Although a large number of studies have been devoted to understanding the functioning of myosin since its isolation in the 19th century, the details of the chemical mechanism underlying ATP hydrolysis and its coupling to the necessary conformational changes of myosin are poorly understood. In this thesis, theoretical methods are developed and used to gain a detailed understanding of the mechanism of ATP hydrolysis in myosin and of mechanical events that immediately follow hydrolysis. Three different possible reaction routes are investigated using combined quantum mechanical and molecular mechanical (QM/MM) reaction path simulations. To include solvent screening effects in the calculations, a new approximate method "Non-Uniform Charge Scaling" (NUCS) was developed which scales the partial atomic charges on the molecular mechanical atoms so as to optimally reproduce electrostatic interaction energies between groups of protein atoms and the QM region as determined from an initial continuum solvent analysis with a simple Coulomb potential and scaled charges. NUCS is a generally-applicable method that is particularly useful in cases where an explicit treatment of water molecules is not feasible and interfaces to implicit solvent models are lacking, as is the case for current QM/MM calculations. Path optimizations were done using Hartree-Fock calculations with 3-21G(d) and 6-31G(d,p) basis sets, followed by point energy calls using density-functional theory B3LYP/6-31+G(d,p). Despite the inaccuracies inherent in this method, the present calculations currently represent the most accurate QM/MM theoretical investigation of an enzyme-catalyzed phosphoanhydride hydrolysis reaction. Possible methodological improvements for future investigations are discussed. The three pathways studied are isoenergetic within error and are thus equally likely to be populated. The 6-31G(d,p) basis set proved to be reliable in describing the geometries during the phosphate hydrolysis reactions, whereas the 3-21G(d) basis set was found to be too inaccurate. Although the energies were not sufficiently accurate, a number of structural conclusions on the mechanism of ATP hydrolysis can be drawn and related to experimental findings from isotope exchange and mutation studies. All three paths investigated follow a single-step associative-like mechanism (see movies at http://www.iwr.uni-heidelberg.de/groups/biocomp/fischer) and show very similar heavy-atom positions in the transition states regardless of the positions of the protons. In the product states, the coordination bond between Mg2+ and Ser237 (and thus the switch-1 loop) is broken. This indicates that product release is likely to occur via an exit route that opens by complete opening of the switch-1 loop ("trap door" mechanism). Moreover, the coordination distance between Mg2+ and inorganic phosphate (Pi) is extended. This indicates that after hydrolysis this bond may be completely cleaved as an early event necessary for phosphate exit. Inspired by the simulation results, a Network Hypothesis on the mechanism of ATP hydrolysis in myosin is put forward that combines previous mechanistic proposals and that is consistent with experimental data available from mutational and isotope exchange studies. Moreover, a mechanism is suggested to explain how the catalytic cycle is coupled to the motor activity of myosin.
Das Design und die Synthese von "Single-Site"-Katalysatoren für die Copolymerisierung von Kohlendioxids und Cyclohexenoxid (CHO), Untersuchungen zu ihrer Struktur-Reaktivitätsbeziehung sowie die Optimierung der Reaktionsparameter waren Hauptaugenmerk dieser Arbeit. Die Liganden für das Katalysator-Design beruhen auf 2,2'-Bisphenol-Derivaten, entweder Methylen- (1-6 basierte Systeme) oder Sulfid-verbrückt (7 basierte Systeme). Die meisten der verwendeten Liganden wurden bereits in der Literatur beschrieben. Ihre Reaktionen mit Aluminiumverbindungen (AlEt3, AlEt2Cl, AlEt2I erzeugt in situ und Al(OPri)3) führen zu Aluminiumbisphenoxid-Verbindungen mit reaktiven Al-Cl-, Al-C2H5- oder Al-OPri-Einheiten. Die Strukturen der isolierten Komplexe hängen im allgemeinen vom verwendeten Lösungsmittel und den Substituenten in der Ligandenstruktur ab (entweder klein oder sterisch anfordernd). Aus den Reaktionen von Al-Alkyl-Verbindungen mit in ortho-Position mit sterisch anspruchsvollen Substituenten ausgestatteten Bisphenolderivaten (1-5) in koordinierenden Lösungsmitteln werden monomere Komplexe gebildet (THF - 1-5 a-b oder Et2O - 1-4 c-d); in nicht-koordinierenden Lösungsmitteln (Pentan oder Hexan) werden dimere Komplexe (1-4 e-f, 5f) gebildet. Die Geometrie um die Aluminiumatome in den Methylen-verbrückten Komplexen zeigt verzerrt tetraedrische Eigenschaften und ist Lösungsmittel-unabhängig. Die Reaktion von 2,2'-Methylenbis(4-Phenol), 6, mit AlEt3 in Ether führt zu einem oligomeren Komplex mit verschiedenen Koordinationszahlen an den Aluminiumzentren. Ein monomerer Alkoxidekomplex, 7a, wurde im Laufe der Reaktion von AlEt3 mit 2,2'-Thiobis(4-tert-octylphenol), 7, in THF als Lösungsmittel erhalten; er zeigt eine trigonal-bipyramidale Geometrie; in Hexan wird ein dimerer Komplex 7c und sein Al-Cl Gegenstück, 7f, gebildet. Die Reaktion der Bisphenol Liganden mit Al(OPri)3 führt zu dimeren Komplexe, überbrückt durch Isopropoxid-Einheiten (1-7 g). Alle neuen Komplexe wurden strukturell charakterisiert mittels Einkristallröntgen-Beugung, und NMR- und IR-Spektroskopie. Die synthetisierten Aluminiumverbindungen wurden als Katalysatoren in der Copolymerisierung von Kohlendioxid und CHO eingesetzt. In allen Experimenten zur Optimierung der Reaktionsparameter und der Selektivität wird nur die Bildung von Polyethercarbonaten beobachtet.
Die Studien zur Optimierung der Kupplungƒ{Isomerisierungsƒ{Reaktion (KIR); Eintopf, MultikomponentSynthese von Heterozyklen
Die Bestimmung der Kinetik der (cyclopentadienyl)Cobalt- (CpCo–) katalysierten Cyclotrimerisierung von Phenylacetylen in überkritischen Medien wie überkritischem Kohlendioxid (scCO2) oder auch überkritischem Wasser (SCW) bildete den Schwerpunkt in vorliegender Arbeit. Die Messungen dazu wurden in einem 30 ml Fensterreaktor mit manuellem Probenahmesystem durchgeführt. Die erhaltenen Proben wurden via off-line GC analysiert. Da derzeit keine Daten zur Löslichkeit von Phenylacetylen und Triphenylbenzol in scCO2 vorliegen, wurden die Reaktionsbedingungen (c, p, T) experimentell so bestimmt, dass im Reaktor homogene Bedingungen vorlagen, so dass repräsentative Proben aus dem Reaktor entnommen werden konnten. Die Reaktionen wurden im Temperaturbereich von 130 – 170°C unter einem CO2-Druck von 380 bar durchgeführt mit konstanten Mengen an Phenylacetylen und unterschiedlichen Katalysatorkonzentrationen. Der CO-Einfluß auf die Umsätze wurde durch ein Experiment mit einem CO-Vordruck von 10 bar in scCO2 untersucht. Die erhaltenen Messdaten wurden im Rahmen eines gemeinsamen kinetischen Modells auf der Basis des Reaktionsmechanismus ausgewertet. Die Stoffstromanalysen zeigten, in Übereinstimmung mit den experimentellen Daten, dass eine Katalysatorumwandlung in eine weniger aktive Form ([CpCo(cyclobutadien)]) und eine katalytisch inaktive Form ([CpCo(cyclopentadienon)]) stattfand. Mit Hilfe des Modells wurden die Zeitkonstanten von 2.86.10-3 s-1(130°C), 1.11.10-2 s-1 (150°C) s-1, 3.74.10-2 (170°C) s-1 und eine Aktivierungsenergie von 96.8±1.4 kJ/mol berechnet. Analoge Messungen wurden in SCW durchgeführt. Die Reaktion verlief bei 400°C und 400 bar so schnell, dass nach 1 min Reaktionszeit kein Phenylacetylen mehr nachgewiesen werden konnte. Basierend auf den erhaltenen Daten von Messungen in scCO2, sollte die Zeitkonstante bei 400°C etwa 300 s-1 betragen.
Die Arbeiten von ERNST ABBE in der zweiten Hälfte des 19. Jahrhunderts brachten der Mikroskopie eine neue Leistungsfähigkeit und konnten so die Forschungs¬möglich¬keiten in der Biologie, vor allem in der Botanik, Zellbiologie und Mikrobiologie, und der Medizin deutlich verbessern. Im Jahr 1930 wurde die Fluoreszenzmikroskopie entwickelt und eröffnete völlig neue Möglichkeiten. Bis heute wurden zahlreiche Varianten der Fluoreszenzmikroskopie entwickelt. Hervorzuheben sind dabei die stimulierte Emissionslöschung (Abk.: STED), sowie die Einzelmolekül¬fluoreszenz¬spektroskopie (engl.: single molecule fluorescence spectroscopy, Abk.: SMFS), zu denen Methoden, wie Totalreflexions-Fluoreszenz Mikroskopie (engl.: total internal reflection fluorescence microscopy, Abk.: TRIFM) und die konfokale Einzelmolekül¬fluoreszenzmikroskopie gehören. Die Stärke der Einzelmolekülfluoreszenzmikroskopie liegt in der geringen Konzentration der verwendeten, fluoreszenten Sonden. Der Einsatz solcher Sonden kann wiederum als Reporter für molekulare Interaktionen dienen, oder strukturelle Änderungen, z.B. in der Nanoumgebung, aufzeigen, die eine Heterogenität besitzen. Die Entwicklungen im Bereich der optischen Techniken, ermöglicht eine höhere Auflösung sogar unter die Auflösungsgrenze von ABBE (STED). Dies eröffnet den Biowissenschaften neue Einblicke in molekulare Prozesse in Zellen und leistet somit einen wesentlichen Beitrag zum Verständnis der komplexen Vorgänge in lebenden Organismen. Im Gegensatz zu Ensemble-Methoden, welche nur einen Mittelwert wiedergeben, kann man durch Betrachtung einzelner Moleküle Subpopulationen auflösen. Zu den Parametern, die der SMFS zugänglich sind, gehören die Fluoreszenzintensität, die Fluoreszenzlebensdauer, Orientierung des Dipols oder die Wellenlänge. Die Verwendung der Fluoreszenz-Korrelations-Spektroskopie (engl.: fluorescence correlation spectroscopy, Abk.: FCS) ermöglicht eine Analyse der Dynamik innerhalb eines gewählten Zeitfensters. Dabei können Diffusions¬geschwindigkeit von Fluorophoren, aber auch photophysikalische Übergänge und der Konformation beobachtet werden. Das Ziel dieser Arbeit war die Entwicklung und Anwendung neuer Methoden der SMFS für Untersuchungen in lebenden Zellen, insbesondere von Transportprozessen. Daher setzt sich diese Arbeit im Wesentlichen mit zwei Schwerpunkten auseinander: (i) das gezielte Einschleusen fluoreszierender Sonden in lebenden Zellen, (ii) die Entwicklung einer Methode zur Beobachtung von schnellen Transport- und Diffusionsprozessen in lebenden Zellen. Die Verfügbarkeit endogen erzeugter Fluoreszenzfarbstoffe, also innerhalb der Zelle synthetisierter Farbstoff, ist begrenzt. Aufgrund der zusätzlichen geringen Photostabilität und komplizierter Photophysik, bedarf es hier alternativer Methoden. Organische Fluorophore, die entweder endogen oder exogen an den Protagonisten, z.B. ein Protein, gekoppelt werden, müssen die Zellmembran, entsprechend vor oder nach der Kopplung durchqueren. Dieser Transport wird durch die Zellmembran erschwert. Die Internalisierung solcher Stoffe kann z.B. durch Rezeptor vermittelten Transport oder Endozytose geschehen. Jedoch ist der Anspruch an den Transporter und seine Fracht in Bezug auf Größe und Form sehr hoch. Durch manuelle Methoden wie die Elektroporation oder Mikroinjektion werden die Zellen gestresst oder geschädigt und bieten nur bedingt eine Alternative mit Zukunft. Die Verwendung von zellmembrangängigen Proteinen ist in den vergangenen Jahren zu einer neuen Methode zur Aufnahme in Zellen gereift. Die Peptide sind für die pharmazeutische Industrie aufgrund der Zellmembrangängigkeit, die auch zur Überwindung der Blut-Hirn-Schranke ausgenutzt werden könnte und somit Arzneistoffe direkt in die entsprechenden Zellen transportiert, von großer Bedeutung. Zellmembrangängige Proteine, die in Viren oder auch in eukaryotischen Zellen vorkommen, gelangen durch die Zellmembran direkt in den Zellkern, um sich schließlich in den Nukleoli anzureichern. Bisherige Untersuchungen der viralen Proteine, wie z.B. das Tat-Protein des HI-Virus, haben gezeigt, dass die Aminosäuren Arginin und Lysin für den Erkennungs- und Aufnahmeprozess verantwortlich sind. Entsprechende Modifikationen des Tat-Proteins wurden teilweise sogar besser von den Zellen aufgenommen, als das Tat-Protein selber. Durch Verwendung von Homologen zu den nativen Aminosäuren besteht die Möglichkeit, die Peptide resistenter gegen einen möglichen Abbau durch Peptidasen zu machen. In Kooperation mit Prof Dr. D. SEEBACH, von der ETH-Zürich, wurden HeLa-Zellen mit Fluorescein markierten -Peptiden inkubiert. Die inkubierten -Peptide, basierend auf den -Aminosäuren, konnten mit Hilfe der Fluoreszenz des Farbstoffes mittels Fluoreszenz¬mikroskopie beobachtet und dokumentiert werden. Ebenso wie bei den -Peptiden konnte bei den -Peptiden das typische Anfärbungsmuster der Zellen ab einer Peptidlänge von acht Aminosäuren beobachtet werden. Das Dekamer wurde nahezu in allen Zellen vor allem in den Nukleoli gebunden. Die Aufnahmeeffizienz erfolgte nicht kontinuierlich über die Konzentration, sondern benötigte eine bestimmte Schwellenkonzentration, ab der der Internalisierungsprozess stattfindet. Durch die Experimente über das Aufnahmeverhalten der -Peptide in Zellen zeigten sich die Peptide als zuverlässige Transporter für molekulare Fracht durch die Zellmembran hindurch. Mit Hilfe dieses Transporters können neben Pharmazeutika, auch fluoreszente Sonden für die Diagnostik eingeschleust werden. Die Verwendung des Transporters für die Einschleusung fluoreszenter Sonden kann helfen, Signal- und Transportprozesse in der Zelle zu verfolgen. Durch Einschleusen einer Sonde und Aussetzen in der Nanoumgebung einer Zelle kann es, z.B. zur Verlangsamung durch Interaktionen, aber auch zu einer Erhöhung der Diffusion durch aktiven Transport kommen. Im Folgenden galt es eine Methode zu entwickeln, die derartige Unterscheide sichtbar machen. Die Kombination der konfokalen, zeitaufgelösten Einzelmolekül¬fluoreszenz¬mikroskopie (engl.: fluorescence lifetime imaging microscopy, Abk.: FLIM) mit der FCS ermöglicht die Verbindung der Vorteile zweier empfindlicher Methoden. Während FLIM mit einer hohen Empfindlichkeit Photonen einzelner Fluoreszenzfarbstoffe mit hoher zeitlicher und räumlicher Auflösung detektieren kann, liefert die FCS Informationen über die Dynamik in dem beobachteten Bereich. Durch die Beobachtung mehrerer diffundierender Moleküle, z.B. in Lösung lassen sich, durch die aus der Fluoreszenz¬fluktuation erhaltene Korrelation, Aufschlüsse über die Dynamik, z.B. die Wechselwirkungen zwischen der Sonde und der Nanoumgebung, in dem beobachteten System geben. Die Verbindung der beiden Techniken erzeugt eine Diffusionskarte des beobachteten Systems, wie z.B. einer Zelle. Unterschiede in der Diffusionszeit können so Aufschlüsse über die fluoreszenten Reporter geben, die z.B. durch Interaktionen der fluoreszenzmarkierten Protagonisten mit zellulären Komponenten auftreten oder aufgrund erhöhter Viskositäten längere Diffusionszeiten erfahren. Auch aktiver Transport z.B. entlang von Microtubuli ließe sich von der normalen Zelldiffusion diskriminieren. Bisherige Arbeiten, welche diese Techniken verknüpften brachten das Scanning-FCS hervor. Durch schnelles mehrmaliges Abtasten eines Bereiches einer Probe konnten bisher lediglich langsamere Diffusionsprozesse von Membranproteinen beobachtet werden. In dieser Arbeit wird die Entwicklung der bildgebenden Diffusions¬mikroskopie gezeigt, die eine Kombination aus FLIM und FCS darstellt und auch schnellere Diffusionsprozesse bis in den Mikrosekundenbereich abbilden kann. Die Methode der bildgebenden Diffusionsmikroskopie wurde an verschiedenen Systemen getestet, um die Anwendbarkeit abzuschätzen. Die ersten Versuche Heterogenitäten in Lösungen zu erkennen wurden mit einer Spitze einer Mikrokapillare erreicht, die in eine Lösung mit einem Farbstoff markiertem Oligonukleotid eintauchte. Zwei Elektroden, eine davon in der Mikrokapillare als Anode, sorgten für eine gerichteten elektrophoretischen Fluss der Oligonukleotide zur Öffnung der Mikrokapillare und auch hinein. Beobachtet wurde ein Anstieg der Diffusionszeit innerhalb der Kapillaröffnung. Da die Moleküle entlang der optischen Achse wanderten, befanden sie sich, auf Grund der ellipsenartigen Asymmetrie des Laserfokus, länger im Beobachtungsvolumen und ergaben so länger Diffusionszeiten. Diese Experimente zeigten dass es möglich ist in der Diffusion räumlich aufgelöst darzustellen. Die Entwicklung der bildgebenden Diffusionsmikroskopie für zelluläre Systeme eröffnet die Möglichkeit Diffusionsprozesse über eine ganze Zelle hinweg zu beobachten. Zu diesem Zweck wurden wiederum fluoreszente Farbstoffe, als Sonden an ein dT20-Oligonukleotid gekoppelt, eingesetzt. Die Analyse der mittels der bildgebenden Diffusionsmikroskopie zeigte Heterogenitäten in der Diffusion. Prinzipiell wurde damit die Möglichkeit geschaffen die Einschleusung fluoreszenter Sonden, wie z.B. beta-Peptiden, zu untersuchen
Die 3,7-Diazabicyclo[3.3.1]nonan (Bispidin) Derivate verfügen über ein starres Ligandgerüst, weisen jedoch eine elastische Koordinationssphäre auf. Daher sind sie in der Lage, eine Reihe verschiedener Übergansmetalle zu komplexieren, wobei spezifische Geometrien für die entsprechenden Koordinationsverbindungen erzwungen werden. Besondere Beachtung finden hierbei verschiedene Komplexe der biologisch relevanten Metalle Kupfer und Eisen. Das Hauptziel der vorliegenden Arbeit war die Berechnung von Strukturen and Eigenschaften von Kupfer- und Eisenkomplexen diverser 3,7 Diazabicyclo[3.3.1]nonan Derivate mittels Dichtefunktionaltheorie, um so auf mögliche Anwendungen zu schließen. Ein kurzer Überblick sowohl über grundlegende Konzepte der Koordinationschemie mit Bispidinliganden, als auch über die Eigenschaften substituierter Bispidine und ihrer entsprechende Metalkomplexe, wird in Kapitel 1 gegeben. Im ersten Teil dieser Arbeit (Kapitel 2 and 3) werden die bei Kupfer(I)- und Kupfer(II) Komplexen mit einer Reihe substituierter Bispidin-Derivate (basierend auf L1, siehe oben) beobachteten Isomerien diskutiert. Während für die Kupfer(I)-Komplexe strukturelle Isomerie des Metalzentrums erkennbar ist, können bei den Kupfer(II) Komplexen verschiedene “Jahn-Teller-Isomere” isoliert werden. Die relativen Energien der Kupfer(I)-Verbindungen mit unterschiedlichen Geometrien erweisen sich als abhängig von der Substituendenposition am Pyridinring (ortho oder meta) und/oder der Größe des ortho-Substituenden und können mit der Stabilität der entsprechenden oxidierten Spezies korreliert werden. Die “Jahn-Teller-Isomerie” der Kupfer(II)-Komplexe lässt sich einerseits durch gezielte ortho-Substitution der Pyridinringe, anderseits durch eine Veränderung der Größe, der elektronischen Eigenschaften und der Zähnigkeit des Koliganden kontrollieren. Um ein besseres Verständnis der spezifischen, vom Ligandengerüst erzwungenen Geometrien zu bekommen, und wie diese Geometrien Rückschüsse auf die Reaktivität der entsprechenden Komplexe zulassen, wird auch in Kapitel 3 anhand der elektronischen Struktur von Kupfer(II)-Chloro-Komplexen mit vierzähnigen Bispidinen genauer untersucht. Außerdem werden die Schwächen der Dichtefunktionaltheorie bei der Berechnung von Strukturen und Eigenschaften der Kupfer(II)-Verbindungen aufgezeigt und es wir die Möglichkeit angesprochen, diese Defizite durch die Anwendung von modifizierten Hydbridfunktionalen zu negieren. Gegenstand der Betrachtung im zweiten Teil dieser Arbeit ist die Anwendung von Eisen(II) Bispidin-Komplexen in der katalytischen Oxidation von Olefinen mit Wasserstoffperoxid. Basierend auf DFT-Rechnungen werden in Kapitel 4 Untersuchungen zu möglichen Mechanismen der Reaktion von Eisen(II) Komplexen mit L1, mit H2O2 angestellt. In Übereinstimmung mit experimentellen Ergebnissen wird ein Mechanismus postuliert, welcher auf der Bildung Fe(IV)-dihydroxo- und Fe(IV)-oxo-Intermediaten beruht. In den Kapiteln 5 und 6 werden die elektronischen Eigenschaften von biologisch relevanten Fe(IV)-oxo- und FeO2-Komplexen von vier- und fünfzähnigen Bispidin-Derivaten analysiert. Herausragende Ergebnisse hierbei waren zum Einen die Berechnung eines high spin Grundzustandes für Fe(IV)-oxo-Komplexe mit vierzähnigen Bispidinen, zum Anderen das auftreten eines lokalen Minimums für low-spin end-on hexacoordinierte FeO2-Komplexe mit Bispidin-Liganden, welche demnach eher als Fe(II)-superoxo-Spezies definiert werden können.
Turbulente magere vorgemischte Flammen spielen aufgrund ihres reduzierten Schadstoffausstoßes bei der Energieumwandlung eine bedeutende Rolle. Verbrennungsinstabilitäten bergen jedoch ein erhöhtes Risiko im technischen Einsatz, da z.B. thermoakustische Schwingungen in Gasturbinen zu verstärkter Materialbeanspruchung führen. Dies stellt auch im Bereich der Flugzeugturbinen eine erhebliche Gefahr dar. Numerische Simulationen erlauben, die Prozesse bei der Verbrennung besser zu verstehen, jedoch sind Direkte Numerische Simulationen technischer Flammen mit heutigen Computeranlagen noch nicht möglich. Vereinfachte Verfahren stützen sich daher häufig auf experimentelle Daten, welche helfen, den erforderlichen Rechenaufwand zu reduzieren. Dazu befasst sich diese Arbeit mit der Bestimmung von Spezieskonzentrationsverteilungen und deren Gradienten in turbulenten Flammen mittels abbildender laserinduzierter Fluoreszenz. Es wird eine Methodik beschrieben, die es ermöglicht, Gradienten im dreidimensionalen Raum für Punkte entlang der Schnittlinie zweier sich senkrecht schneidender Messebenen zu bestimmen. Mittels eines KrF-Excimerlasers mit einer Wellenlänge von 248 nm wurde der A–X(3,0)-Übergang von OH in einer vorgemischten staukörperstabilisierten Erdgas-Luft-Flamme angeregt und die Fluoreszenz in den zwei Messebenen bei 295 nm mit zwei bildverstärkenden CCD-Kameras detektiert. Simultane 1D-Raman-Messungen ermöglichten, die Daten entlang der Schnittlinie mit simultanen Temperatur und Majoritätenspezieskonzentrationen zu vergleichen. Aus den OH-Konzentrationsverteilungen wurden Konzentrationsgradienten im dreidimensionalen Raum berechnet und bezüglich ihrer Korrelation zur lokalen Konzentration untersucht. Solche Korrelationen können zur Vereinfachung von Simulationsansätzen und zu deren Validierung beitragen. Es wurde auch ein Vergleich des realen Gradienten mit seiner Projektion auf jede der Messebenen durchgeführt, da der Betrag durch die Projektion auf die Messebene vom Betrag des realen Gradienten abweicht. In einem zweiten Experiment wurden Messungen in einem einzelnen Modellbrenner einer stationären Gasturbine unter turbinennahen Betriebsbedingungen durchgeführt. In einer nicht-vorgemischten und einer vorgemischten Erdgas-Luft-Flamme mit und ohne Pilotierung wurde mittels eines XeCl-Excimerlasers bei 308 nm der A-X(0,0)-Übergang von OH angeregt. Die Detektion in einer Messebene entlang der Brennerachse erfolgte resonant bei 308 nm mit Hilfe einer bildverstärkenden CCD-Kamera. Anhand des steilsten Gradienten wurde aus den zweidimensionalen Konzentrationsverteilungen die Flammenfront bestimmt. Die statistische Auswertung der Flammenfronten erlaubte einen Vergleich der Charakteristika der untersuchten Flammen. Ein Vergleich mit der Simulation ergab gute Übereinstimmungen. Neben den stationären Flammen wurden auch zwei Betriebsbedingungen untersucht, bei denen Verbrennungsinstabilitäten auftraten. Kraftstoffschwankungen aufgrund von Strömungsfluktuationen führen zu Oszillationen der Verbrennung, die sich mit Geschwindigkeitsfluktuationen in der Brennkammer zu starken thermoakustischen Schwingungen verstärken können und das System mechanisch belasten. Ein besseres Verständnis der Wirkketten bei der Entstehung dieser Fluktuationen ist daher von grundlegender technischer und theoretischer Bedeutung.
A series of new 3,7-diazabicyclo[3.3.1]nonane (bispidone)-derived ligands with phenolic side chains were synthesized. The double Mannich condensation reaction to create the bicyclic bispidone was carried out successfully, though the isolation of the bispidones was not always straightforward. The preparation of the corresponding amine precursors was a very challenging task, which often led to more difficulties than the Mannich condensation itself. The preparation of the new bispidone ligands are described in Chapter 4. As structural models for the galactose oxidase enzyme, copper(II) complexes of the mononucleating phenol-bispidone ligands N2py2PhOH and vanilbis were prepared and structurally and spectroscopically investigated. These results are presented in Chapter 5. The crystal structure of the copper(II)-N2py2PhOH complex shows that the bispidone cavity is preorganized for copper(II) and that the incorporation of the phenolic moiety does not build up any strain in the ligand backbone (when compared to other known systems). The Cu(II)-N2py2PhOH complex disproportionates to a copper(I) salt and copper(II)-phenoxy radical. Dicopper(II) complexes with the dinucleating bispidone ligands cresbis and tBuBis, were designed as structural models of catechol oxidase (Chapter 5). A combined spectroscopic, magnetometric and computational study revealed that by tuning the reaction conditions (applying an organic base or a basic alumina in the synthesis), the distance between the copper(II) centers could be varied. Vanadyl-complexes with N2py2 and N2py2PhOH were also prepared and their spectroscopic properties compared to the known [V(IV)=O(N2py3o)]2+ complex (Chapter 6). Oxidation of the latter complex was shown to produce V(V)-oxo-peroxo species in high yields in methanol. To solve the inconsistency of the O-O distance and O-O stretching frequency for the side-on bound peroxo unit in the so formed [V(V)=O(O2)(N2py3o)]+ complex, a combined labeling and computational study was carried out. Further oxidation of this V(V)-oxo peroxo complex was possible using Ce4+, as indicated by the EPR spectra. A detailed spectrophotometric study was carried out to understand the nature of the reaction between the Co(II)-N2py2 complex with hydrogen peroxide (Chapter 7). The reaction products were both qualitatively and quantitatively analyzed using the hydrazine test reaction. Analogous reaction products were found when the complex of a structurally similar N2py2Bz ligand was used. Structural data obtained for complexes, which have been isolated from the reaction mixture, provided evidence on the dealkylation at the tertiary amine donor N7 in the ligand (Figure 1.3) Further details about the possible steps of the oxidative N-dealkylation were obtained from DFT calculations. From the results a mechanism was postulated (Figure 1.4). Moreover, the catalytic activity of Co(II)-N2py2 / H2O2 system in the oxidation of amines was investigated. Manganese(II) complexes of known bispidone-type ligands with N4 and N5 donor set were prepared and their reaction with hydrogen peroxide was studied, in order to ascertain whether there is analogy with divalent iron species and have catalytic activity in olefin oxidation. These results are presented in Chapter 8. Interesting spectroscopic features of the manganese complexes with phenol-bispidone ligands are also reported in this chapter. The UV-vis spectra of the manganese(III)-N2py2PhOH complex demonstrate slow decomposition and possible pathways are discussed.
The enantioselective synthesis of (+)-(S)-laudanosine (101) and (–)-(S)-xylopinine (102) were achieved successfully in 7 steps from commercially available homoveratylamine (86) in 62% and 51% yield, respectively. The key intermediate aminoalkyne 123 was accessed easily by coupling aryl iodide 115 and alkyne 121 using a Sonogashira reaction. Dihydroisoquinoline 124 was obtained by intramolecular hydroamination of the aminoalkyne 123. Employing Noyori´s reduction protocol, the absolute configuration at C-1 of the benzylisoquinoline was introduced with 93% ee. Finally, methylation of norlaudanosine (146) by a reductive amination protocol afforded (+)-(S)-laudanosine (101). Alternatively, formation of the berberin-bridge using a Pictet-Spengler reaction afforded (–)-(S)-xylopinine (102). The strategy was also applied to synthesize benzylisoquinolines with electron-deficient A-rings. 5-Trifluoromethyl-benzylisoquinoline (174) was successfully synthesized in 8 steps from commercially available 4-bromo-trifluorotoluene (162) in 20% yield. Both Sonogashira reaction and hydroamination gave the desired products in excellent yields. Moreover, 6,7-difluoro-benzylisoquinoline (182), was synthesized following a similar route from commercially available o-bromo-benzoic acid (175) in 19% yield for the seven steps.
Tissue formation and organ development in animals is a complex, lifelong process. The building blocks of tissue are living cells surrounded by secretion products, mostly proteins and polysaccharides. Aggregates of these proteins have different structural geometries and functionalities depending on localization and task in vivo. They form the extracellular matrix (ECM). The detailed quantitative evaluation of tissue construction and tissue-cell interaction is essential for a detailed understanding of organ development and its associated malfunctions which lead to different diseases. However, quantitative studies of cellular events in vivo are restricted since high resolution techniques characterizing cell functions are not suitable for living organism. In respect to tissue culture techniques, introduction of artefacts in mammalian cells cultured on flat, rigid and non-natural two dimensional surfaces is apparent. Such surfaces do not possess three dimensionality and variation of compliance on the micrometer scale as observed in the ECM. To circumvent this drawback new materials and techniques are needed, where surface compliance, structural geometry and chemical composition of ECM models can be adjusted independently. In addition, local force and compliance measurements should produce new insights in cell-ECM interaction and tissue development. The first two parts of this thesis describe a novel micro-engineered mechanical device which serves as a platform for constructing ECM models and as force sensor array. We developed a transparent elastic surface with arrays of micrometer scaled posts. The development process is based on standard photolithographic techniques. Typical structural dimensions of posts are a diameter of 2.5 micro m a height of 15 micro m. Physical properties of post arrays such as local and macroscopic substrate elasticity were investigated quantitatively. These posts were shown to be able to serve as a quantitative device measuring local forces down to the nanonewton range implied by the calibration analysis. The micro-array offers a template for constructing the ECM in vitro with different chemical and mechanical constitutions of the ECM as well as different geometries. The tops of posts were selectively functionalized with either a peptide sequences (arginine-glycine-aspartate, cRGD) or an amorphous matrix protein resulting in well defined surfaces suitable for quantitative force measurements of living cells. By exploring the impact of surface tension of air-water interfaces from protein solution in close contact with a micro-array, the force dependence of fibronectin fibre formation was shown. Part III describes the application of force sensor arrays for measuring an adherent cell’s spatial distribution of local forces along its membrane. Therefore rat embryonic fibroblasts with GFP fusion proteins to paxilin and beta3 integrin were used to localize the focal adhesions with fluorescence microscopy under physiological conditions. Correlation of patch size to generated force revealed local stress values from 0.1 ± 1.5 up to 115 ± 15.1 nN/micro m2 as a function of cell-state. Using surfaces with different pliabilities by variation of post height and chemical functionality, it was possible to investigate different morphological states of adhesion sites in human foreskin fibroblasts (HFF). The molecular composition of focal contacts strongly depends not only on local substrate stiffness but also on the global compliance of the surface. In the case of fibronectin coated microarrays development of focal contacts was strongly dependent on stiffness of the underlying support. However, post arrays with different compliance and coated with cRGD demonstrated that local mechanosensing capabilities of focal contacts is also assisted by different mechanisms which sense global mechanical properties of cell’s environment. The mechanical interplay in a multicellular system was investigated in the last part of this work. During organ development cells aggregate and form multicellular compartments in a very precise manner. In order to maintain regular organ function it is important that cell can communicate during organogenesis. The communication pathways based on biochemical signalling have been extensively investigated over the past twenty years. Madin-Darby Canine Kidney (MDCK) cells form functional cellular aggregates, termed cysts under special conditions in vitro. The conditions were adapted to induce cyst growth on force sensor arrays allowing precise force mapping during cyst development. These data were analysed to verify a computational model calculating of surface-forces generated by MDCK cysts inside a 3 dimensional cell culture system. Switching to a mechanical anisotropic environment meant that MDCK cysts no longer grew as round spheres. Instead cell aggregates generated tubular shapes. So far, tubulogenesis in vitro was only inducible by adding growth factors to the culture medium.
Turbulente Sprays werden häufig im praktischen Verbrennungsystem angetroffen. Die Eigenschaften der turbulenten Sprays, wie Verteilung der Tröpfchengrößen und die Vermischung von Kraftstoff und Luft sind für die Effizienz, die Stabilität, und das Emissionsverhalten der Verbrennungprozesse sehr wichtig. Dies stellt ein sehr komplexes Problem dar. Die Prozesse Turbulenz, Wärme- und Stoffübertragung und Phasenänderung müssen dazu behandelt werden. Für reagierende Stömungen müssen chemische Reaktionen berücksichtigt werden. Diese Prozesse sind stark mit einander gekoppelt und viele Aspekte dieser Prozesse sind bislang unbekannt. In dieser Arbeit werden turbulente Sprays mit Hilfe einer Wahrscheinlichkeitsdichtefunktion (PDF) dargestellt. Zwei Ansätze werden dabei verwendet, angenommene und transportierte PDF Methoden. Zunächst wird eine PDF für die Mischungsbrüche des turbulenten Sprays vorgeschlagen. Die PDF Transportgleichung wird dazu abgeleitet. Das molekulare Mischen wird mit einem erweitertem IEM Modell behandelt. Die PDF Transportgleichung wird mit einem erweiterten k-e Modell geschlossen. Es wird durch eine hybride Finite-Volumen/Lagrange Monte-Carlo Methode gelöst. Ein turbulentes, nicht reagierenden Sprays wird damit simuliert. Die numerischen Resultate der PDF Methode sind in guter Übereinstimmung mit den experimentellen Daten aus der Literatur und verbessern die des Momentenmodells. Außerdem werden die mittels der Monte-Carlo Methode berechneten Formen der Wahrscheinlichkeitsdichtefunktion des Mischungsbruchs in unterschiedlichen Positionen dargestellt und analysiert. Es ergibt sich, dass die Sprayquelle den Wert des mittleren Mischungsbruchs ändert, aber sie ändert nicht die Form seiner PDF. Ein Vergleich der Monte-Carlo PDF mit der Standard-Betafunktion zeigt, dass die Standard-Betafunktion die Form der PDF nicht beschreiben kann. Mit der Definition von geeigneten lokalen Maxima und Minima des Mischungsbruchs ist eine modifizierte Betafunktion mit vier Parametern sehr gut geeignet, die Form der Monte-Carlo PDF darzustellen. Weiterhin wird eine gebundene Wahrscheinlichkeitsdichteverteilung zwischen Geschwindigkeit und skalaren Größen für turbulente Sprays vorgeschlagen. Die Transportgleichung hierfür wird abgeleitet und modelliert. Ein vereinfachtes Langevin-Modell wird erweitert, um die Gasgeschwindigkeit zu modellieren. Das molekulare Mischen wird mit dem erweiterten IEM-Modell beschrieben. Simulationen des turbulenten nicht-reaktiven Sprays zeigen, dass die numerischen Resultate für die Gasgeschwindigkeit durch dieses Modell verbessert werden. Des Weiteren wird eine gebundene Enthalpie-Mischungsbruch-PDF für turbulente Sprayflammen vorgeschlagen. Die entsprechende Transportgleichung wird hergeleitet. Das molekulare Mischen wird mit dem modifizierten IEM-Modell beschrieben. Eine turbulente Methanol/Luft Sprayflamme wird simuliert. Der verwendete Methanol-Luft-Mechanismus umfasst 23 Spezies und 168 Elementarreaktionen. Er wird durch ein Sprayflammen-Schichtenmodell integriert. Die numerischen Resultate für die Gasgeschwindigkeit, die Gastemperatur, den Massenbruch des Kraftstoffdampfs und den Sauterradius werden mit experimentellen Daten aus der Literatur und den Resultaten der Momentenmethode verglichen. Es ergibt sich eine gute Übereinstimmung mit den experimentellen Daten. Die verwendete Methode verbessert die Resultate des Momentenmodells in Bezug auf den Massenbruch des Methanoldampfes. Die angenommene PDF des Mischungsbruchs, die im Momentenmodell verwendet wird, wird mit den berechneten-PDFs des Mischungsbruchs aus der transportierten PDF-Methode verglichen. Die Resultate zeigen, dass die letztere zuverlässiger ist. So sind die Zusammensetzung des Gemischs, die durch die verwendete PDF-Methode berechnet wird, genauer. Die Anwendungen der angenommene PDF Methode in den turbulenten Sprays werden diskutiert. Die Normalverteilung, logarithmisch-normal-Verteilung, Nukiyama-Tanasawa-Verteilung, Rosin-Rammler-Verteilung, Standard-Beta-Verteilung, modifizierte Vierparameter Beta-Verteilung werden besprochen und analysiert. Die Verbindungen zwischen ihnen werden dargestellt. Eine turbulente Ethanols/Luft-Spray wird sowohl experimentell, als auch durch numerische Simulation untersucht. Ein herkömmliches Euler/Lagrange Modell wird verwendet. Der mittlere Sauterradius, die mittlere Tröpfchengeschwindigkeit sowie die Verteilung der Tröpfchengrößen werden gut vorausgesagt. Der detaillierte Reaktionsmechanismus wird in der Simulation der Sprayverbrennung durch ein Sprayflammen-Schichtenmodell behandelt, in dem 38 Spezies und 337 Elementarreaktionen betrachtet werden. Es ergibt gute Übereinstimmung zu den experimentellen Daten. Zusätzlich wird ein implizites Schema entworfen, um die Partikelgeschwindigkeit des Sprays zu berechnen. Ein numerischer Test zeigt, dass der implizite Schema robuster, genauer und leistungsfähiger ist als ein herkömmliches explizites Schema.
Im Zuge dieser Arbeit wurde die Reaktivität von nicht-Häm Eisen(II)-Komplexen mit Sauerstoffderivaten untersucht. Die behandelten Systeme sind in der Lage katalytisch Olefine zu oxidieren. Hierbei beobachtet man bei Zugabe von Wasserstoffperoxid sowohl eine cis-Dihydroxilierung als auch die Epoxidierung der eingesetzten Substrate. Ein grosser Schwerpunkt lag in der Charakterisierung von reaktiven Eisen-Sauerstoff Intermediaten, wie Eisen(III)alkylperoxo- und hochvalente Eisen(IV)oxo-Verbindungen.
Die Arbeit umfasst die Synthese modifizierter Peptidnucleinsäuren und Metallkomplex-funktionalisierter Oligonucleotide und deren Anwendung für die sequenzspezifische Nucleinsäuredetektion
Die vorliegende Arbeit befasst sich mit der Untersuchung der Hydrosilylierung von CO2, einer atomeffizienten Synthesealternative zur Herstellung formoxyfunktionalisierter Silane, die alternativ zu Essigsäuresilylestern als Monomere in der Silikonherstellung verwendet werden könnten. Vorteile dieser Methode sind die Nutzung von CO2 als Synthesebaustein und die Verwendung einfach zugänglicher Katalysatoren sowie die milden Reaktionsbedingungen für die Hydrosilylierung.
Das Ziel dieser Arbeit war die Entwicklung einer neuen Reihe 3,7-Diazabicyclo[3.3.1]nonan Derivate, wo nur elektronisch (5-substituierte Pyridine), sterisch (pyridin und 6-methyl substituierte Pyridine) und beide Effekte gleichzeitig (quinolin derivative) an dem Metallzentrum einwirken könnten. Die Synthese der substituierten 3,7 Diazabicyclo[3.3.1]nonanone erfolgt über eine zweifache Mannich-Reaktion. Im Verlauf dieser Arbeit konnten zahlreiche neue Derivate dargestellt werden. Der Zweck solcher Modifikationen waren neue Kupfer(II) und Eisen(II) komplexe zu synthetisieren, wo die Elektronische Eigenschaften des Metallzentrums (Redoxpotentiale) modifiziert werden könnten, so dass eine neue Familie effektive und stabile Katalysatoren für die Aziridinierung von Olefine mit PhINTS als Nitrenquelle, beziehungsweise für die selektive Oxidation von Olefine, erreichbar werden könnte.
Der Zugang zur Untersuchung komplexer Mikrostrukturen, wie sie insbesondere durch biologische Systeme gebildet werden, verlangt spezielle Werkzeuge und Methoden, die eine aktive physikalische und chemische Kontrolle in diesem Größenbereich und die Erfassung systemspezifischer Parameter erlauben. Ein Teil dieser Anforderungen kann durch den Einsatz holographischer optischer Pinzetten (HOT) erfüllt werden, mit denen sich eine Vielzahl mikroskopischer Objekte nicht-invasiv manipulieren und Piconewtonkräfte messen lassen. In dieser Arbeit wurden die Anwendungsmöglichkeiten der HOT erstmals über eine reine Objektmanipulation hinaus durch Integration in eine neu entwickelte Mikrofluidikplattform erweitert und die HOT-Technologie in Hinblick auf komplexe Systemanwendungen weiterentwickelt: Verschiedene Algorithmen zur Hologrammberechnung wurden hinsichtlich ihrer Effizienz miteinander verglichen. Es konnte gezeigt werden, dass ein hier vorgestellter erweiterter Superpositionsansatz in den meisten Fällen zur Hologrammgenerierung ausreicht, womit die Verwendung zeitaufwändiger iterativer Verfahren entfällt. Die Abhängigkeit der Effizienz von Symmetrieeigenschaften der Fallenmuster wurde aufgezeigt und analysiert. Durch Verwendung der Superposition wurde eine Ortsauflösung der HOT-Positionierung im Nanometerbereich realisiert. Die Abhängigkeit der Auflösung von der Zahl der Bildpunkte und Phasenstufen der Hologramme konnte hergeleitet und experimentell demonstriert werden. Die HOT-Technologie ermöglicht die Erzeugung optischer Wirbelfallen, die gefangene Objekte durch Drehimpulsübertragung in Rotation versetzen. Eine neue Klasse modulierter optischer Wirbel wurde präsentiert, die eine Regulation des Drehimpuls optischer Wirbel erlaubt ohne die Laserintensität oder den Wirbelradius zu verändern. Die Fabrikation eines ultraflachen und optisch transparenten Mikrofluidiksystems stellt ein Werkzeug zur Kontrolle des chemischen Milieus zur Verfügung, das eine Integration der HOT erlaubte. Speziell auf die HOT angepasste Kanaldesigns wurden entwickelt, um Systemstabilität zu gewährleisten und gleichzeitig einen flexiblen Austausch von Substanzen zu ermöglichen. Dieses opto-mechanische Mikrolabor konnte schließlich zur Generierung biomimetischer quasi-zweidimensionaler Aktinnetzwerke auf durch HOT strukturierten Mikrokugeln genutzt werden: Es wurde zur Oberflächenstrukturierung, der Erzeugung kraftsensorischer Geloberflächen und der freien rein optischen Systemmanipulation eingesetzt.
In violett gefärbten Exemplaren der Crinoide Liliocrinus aus dem Oberen Jura der Schweiz wurde eine außergewöhnliche Serie von fossilen organischen Pigmenten aus der Gruppe der Phenanthroperylenchinone entdeckt. Mit den zur Zeit der Entdeckung verfügbaren analytischen Methoden konnte die genaue chemische Struktur dieser Verbindungen (Fringelite) allerdings nur unter Vorbehalt bestimmt werden. Crinoiden mit ähnlichen Färbungen wie bei Liliocrinus sind auch aus der Trias bekannt, wurden bislang aber nicht detailliert auf ihre organischen Inhaltsstoffe hin untersucht. Um die Struktur und die Verbreitung der Fringelite näher zu ermitteln, wurden in der vorliegenden Arbeit Proben der violett gefärbten Crinoiden Liliocrinus munsterianus vom ursprünglichen Vorkommen der Fringelit-Pigmente sowie von Carnallicrinus carnalli und Encrinus cf. spinosus aus der Mittleren Trias von Deutschland bzw. Polen untersucht. Dabei wurden die Proben nach Aufschluß mit Salzsäure mit organischen Lösungsmitteln sequentiell extrahiert und die Extrakte anschließend mit Hochleistungsflüssigkeitschromatographie (HPLC) und verschiedenen spektroskopischen Methoden (UV/Vis-Spektroskopie, Massenspektrometrie, Kernresonanzspektroskopie) analysiert. Durch Vergleich mit authentischen Referenzproben konnten die Pigmente schließlich als Hypericin (C30H16O8), Desmethylhypericin (C29H14O8) und Fringelit F (C28H12O8) identifiziert werden. Ein in geringen Mengen vorkommender Kohlenwasserstoff konnte als 1,2,3,4,5,6-Hexahydrophenanthro[1,10,9,8-opqra]perylen charakterisiert werden. Die analytischen Ergebnisse zeigen, daß es sich bei den sogenannten Fringelit-Pigmenten in Wirklichkeit um Hypericin und damit nahe verwandte Phenanthroperylenchinone handelt und daß die fossile Überlieferung dieser Pigmente viel weiter zurückreicht als bislang bekannt war. Hypericin ist vor allem durch sein Vorkommen im Johanniskraut (Hypericum perforatum), einer weit verbreiteten Heilpflanze, bekannt. Eine Gruppe bromierter Hypericin-derivate wurde allerdings auch in der rezenten Crinoide Gymnocrinus richeri gefunden. Letzteres Vorkommen läßt darauf schließen, daß es sich bei den Pigmenten der fossilen Crinoiden um nahezu original erhaltene Naturstoffe bzw. um nur gering veränderte Diageneseprodukte handelt.
The chemical properties of plutonium and zirconium are important in order to assess nuclear waste disposals with respect to isolation and immobilization of radionuclides. In this study, the hydrolysis, solubility and colloid formation of tetravalent plutonium and zirconium are investigated in 0.5 M HCl/NaCl solution using several complementary methods and the redox behavior of plutonium is investigated in acidic conditions as well. The solubilities of Pu(IV) and Zr(IV) are determined from the onset of colloid formation as a function of pH and metal concentration using LIBD (laser-induced breakdown detection). The investigation of the solubility of Zr(IV) is carried out at different concentrations (log [Zr] = -3 ~ -7.6) and in a wide pH range (pH = 3 - 9) yielding log K°sp(Zr(IV)) = -53.1 ± 0.5 based on the assumption that only mononuclear hy-drolysis species exist in solution. Comparing the present results with literature data, the solubilities of Zr can be split in two groups, a crystalline phase with lower solubility and an amorphous phase (Zr(OH)4(am)) with higher solubility. The data obtained in the present work set an upper limit for the solubility of freshly formed Zr(OH)4(am). To understand this difference of solubilities, the geometrical structure of the dominant solution species is investigated as a function of pH using XAFS (X-ray absorption fine structure). The samples at pH >2, still below the solubility limit determined by LIBD, contain the polynuclear Zr(IV) species probably due to the high concentration ([Zr] = 1 mM) and their structure do not resemble any reported simple ZrO2 structure. The Zr(IV) colloid species in oversaturated solution under this experimental condition resembles amorphous Zr(IV) hydroxide rather than crystalline ZrO2. The solubility of Pu(IV) is investigated in acidic solution below pH 2. Considering only mononuclear hydrolysis species, log K°sp(Pu(IV)) = -58.3 ± 0.4 is obtained. Since Pu(IV) is not redox stable even in acidic condition, the concentration of each oxidation state of Pu must be determined prior to each experiment. The solubility data are determined directly after preparation and then the redox reactions between four different plutonium oxidation states are observed at different pH and Pu concentrations as a function of time. The results indicate that the redox behavior of Pu cannot be described by disproportionation of Pu alone. Under the experimental conditions, the redox reactions of Pu seem to be divided into two groups, Pu(IV)aq <=> Pu(III)aq and Pu(IV)coll <=> Pu(V)aq <=> Pu(VI)aq. In the Pu solution containing initially only Pu(IV), the reduction of Pu(IV) to Pu(III)aq dominates rather than the oxidation to Pu(V)aq and Pu(VI)aq. The observed two groups of reactions show the dependency of pH due to the related hydrolysis and colloid formation of Pu(IV). With increasing pH, the [Pu4+] decreases either through its hydrolysis and colloid formation (increase of Pu(IV)coll) or through its reduction (increase of Pu(III)aq). The polymer species or colloids may dissolve to Pu(V)aq through the second reaction group (increase Pu(V)aq + Pu(VI)aq). Consequently, it is observed that with increase of pH, [Pu(IV)aq] decreases, [Pu(III)aq] increases, and [Pu(IV)coll]+[Pu(V)aq]+[Pu(VI)aq] increases. This study is also performed under inert gas conditions in order to investigate the influence of dissolved oxygen on the oxidation of Pu(IV) (Pu(IV)coll <=> Pu(V)aq). From the relative abundance of the Pu oxidation states, namely the couples PuO22+/PuO2+ and PuO2+/Pu(IV)coll, the redox potential Eh(V) can be obtained. The respective values agree well with the measured Eh values. In order to use the redox couple Pu4+/Pu3+, one has to take into account the strong hydrolysis of Pu(IV) which sets in below pH 1. When the abundance of Pu4+ is calculated from the amount of by use of hydrolysis constants from earlier solvent extraction stud-ies, deviations from the measured Eh arise. By use of slightly lower values for log β1y (y = 1-2) a good agreement between all calculated and measured Eh values is achieved, suggesting that at least the first and second hydrolysis constants should be corrected.
Im Rahmen dieser Arbeit wurden Amidkupplungsreaktionen der nicht-natürlichen Ferrocenaminosäure 1-Amino-1´-carboxy-ferrocen (Fca) in Lösung und unter Festphasenbedingungen untersucht. Für die Darstellung der Aminosäure wurde eine achtstufige Synthesesequenz ausgehend von Ferrocen entwickelt und optimiert. 1-Amino-1´-carboxyferrocen konnte erfolgreich durch eine Fmoc-Schutzgruppe geschützt werden und für Reaktionen in Lösung über das DCC/HOBt-Protokoll aktiviert werden. Die erhaltenen amidosubstituierten Ferrocene wurden im Festkörper und in Lösung mittels Kristallstrukturanalyse,NMR- und IR-Spektroskopie sowie durch DFT-Rechnungen auf charakteristische Faltungs- und Assoziationsphänomene untersucht, welche durch Ausbildung von Wasserstoffbrücken entstehen. Durch die Umsetzung der aktivierten, N-acylierten Ferrocenaminosäure mit 1-Aminoferrocen gelang die Darstellung eines Diferrocendiamids,welches im Festkörper durch die Ausbildung intermolekularer Wasserstoffbrücken eine Schichtstruktur aufweist, während in Lösung eine dynamische intramolekulare Wasserstoffbrücke zwischen den beiden Amid-Gruppen vorliegt. Diese intramolekulare Wasserstoffbrücke kann durch die Zugabe von Anionen wie Chlorid und Dihydrogenphosphat gebrochen werden. Es wurde gezeigt, dass beide Amidprotonen ein Chloridion auf kooperative Weise binden, wobei eine strukturelle Änderung des Diferrocendiamids und eine Veränderung des Redoxpotentials der Ferrocen-Einheiten induziert wird. Diese Änderungen sind reversibel und das Diferrocendiamid kann somit als molekulare Maschine bezeichnet werden, welche zwei spezifische Reaktionen auf einen einfachen Reiz zeigt. Mit den Methylestern der a-Aminosäuren L-Valin und L-Isoleucin wurden Konjugate der Ferrocenaminosäure in Lösung synthetisiert und strukturell charakterisiert. Durch eine Kombination von IR-, NMR- und CD-spektroskopischen Untersuchungen sowie DFT-Rechnungen konnte ein Hauptkonformer ermittelt werden, das eine intramolekulare Wasserstoffbrücke und P-helikale Chiralität am Ferrocen aufweist. Der Einbau der Ferrocenaminosäure in das Rückgrat eines Peptids gelang durch Nutzung der Festphasenpeptidsynthese nach dem Vorbild von Merrifield. Ebenso konnten andere Ferrocenbausteine an Ferrocenaminosäure unter Bildung von Oligoferrocen-Peptiden geknüpft werden
Seit die Festphasensynthese in den 60er Jahren von R. B. Merrifield entwickelt wurde, ist sie die Methode der Wahl zur Darstellung von Peptiden. Die Strategie wurde ursprünglich nur für die Synthese von Peptiden konzipiert, aufgrund ihrer Vorteile wird sie nun auch für die Festphasensynthese von Polyamiden, Polynukleotiden und Polysacchariden verwendet, indem unterschiedliche Monomereinheiten eingesetzt werden. Die Herstellung immobilisierter Metallooligomere und deren Gewinnung durch Festphasensynthese ist bis jetzt noch nicht durchgeführt worden. In dieser Arbeit wird die Übertragung der Festphasensynthese auf das Gebiet der metallorganischen Chemie für die Synthese von homo- und heteronuklearen Metallooligomeren behandelt. Durch die Funktionalisierung eines Polymers mit einem α-Diimin Liganden wird ein System entwickelt, in dem die Festphasesynthese von homo- und heteronuklearen metallorganischen Oligomeren, bestehend aus Chrom-, Molybdän- und Wolfram-Metallbausteinen, mit definierter Kettenlänge und Metallsequenz erfolgen kann. Ebenso wird die Festphasensynthese zur Herstellung von heterobimetallischen Komplexen, die eine Bindung zwischen einem d6-Metallatom [Mo(0), W(0)] und einem d8-Ion [Rh(I), Pt(II)] aufweisen, angewendet. Ein wichtiger Bestandteil dieser Arbeit ist der Vergleich zwischen der Festphasensynthese und der Synthese in homogener Phase, sowie eine Evaluierung der verfügbaren analytischen Methoden für die „on resin“ Verfolgung und Charakterisierung von Reaktionen an der Festphase.
Die vorliegende Arbeit beschäftigt sich mit der Analytik von 17alpha-Ethinylestradiol (EE2) in der aquatischen Umwelt. Der Schwerpunkt der Untersuchungen lag dabei in der Entwicklung und Optimierung von Enyzm-Immunoassays (ELISAs) zur direkten Bestimmung des Analyten im Konzentrationsbereich von 1 - 10 Nanogramm pro Liter. Es wurden drei neue ELISAs für EE2 entwickelt. Für den ersten Assay (Bio-LC EE2 ELISA) wurde ein biotinyliertes Ethinylestradiolderivat synthetisiert und im ELISA als Tracer verwendet. Durch Verwendung eines Streptavidin-Peroxidase-Konjugats und Ausnutzung der Biotin-Streptavidin-Wechselwirkung wurde anschließend Peroxidase an den Biotin-Tracer gebunden. Im zweiten Assay (EE2 ELISA) wurde ein direktes Enzymkonjugat des EE2 mit Meerrettichperoxidase synthetisiert. Dieses fungierte im EE2 ELISA als Tracer. Die Detektion erfolgte auch hier photometrisch. Im Vergleich zum Bio-LC EE2 ELISA wurde im EE2 ELISA das Protokoll vereinfacht und der Zeitbedarf konnte von 120 auf 70 Minuten reduziert werden. Der dritte Assay (EE2 CLEIA) leitete sich unmittelbar vom EE2 ELISA ab, es wurde das gleiche Enzymkonjugat verwendet. Zur weiteren Sensitivitätssteigerung wurde die Antikörperverdünnung von 1:50.000 auf 1:200.000 , und die Tracerverdünnung von 1:50.000 auf 1:500.000 erhöht. Eine typische Messung von 24 Realproben mit dem Chemilumineszenzassay (EE2 CLEIA) dauert nur noch 40 Minuten. Die Nachweis- und Bestimmungsgrenze (LOD bzw. LOQ), sowie die Messbereiche der drei Assay betragen: Bio-LC EE2 ELISA: LOD 2,6 ng/L / LOQ 21 ng/L / Messbereich 0,025 – 55 µg/L EE2 ELISA: LOD 0,5 ng/L / LOQ 6,0 ng/L / Messbereich 0,004 – 130 µg/L EE2 CLEIA: LOD 0,2 ng/L / LOQ 1,4 ng/L / Messbereich 0,8 –100 ng/L Diese drei Assays gehören damit zu den derzeit vier empfindlichsten Immunoassays für die Bestimmung von EE2. Mit Hilfe des EE2 CLEIA konnten erstmalig direkte Messungen im ökotoxikologisch relevanten sub ppt-Bereich realisiert werden. Neben der Steigerung der Assaysensitivität wurde eine umfassende Studie zur Selektivität und Stabilität der Assays durchgeführt. Zur Untersuchung der Selektivität dienten elf Steroidhormone bzw. Hormonderivate, darunter die häufig in Umweltproben vorliegenden Substanzen Estron und Estradiol. Das EE2-Antiserum zeigte hierbei ein extrem selektives Bindungsverhalten bezüglich EE2. Typische Kreuzreaktivitäten, beispielsweise für Estron und Estradiol, lagen zwischen 0,1 und 0,3 %. Nennenswerte Kreuzreaktivitäten traten lediglich für Konjugate des EE2 an der Ringposition drei auf (Glucuronsäureaddukte: 17-22 % und Sulfate: 34-37 %). Dies steht in Zusammenhang mit der Struktur des für die Immunisierung verwendeten BSA Konjugats des EE2. Die Matrixstabilität der ELISAs wurde anhand eines kommerziellen Huminsäurepräparates untersucht. Der Bio-LC EE2 ELISA erwies sich als störungsanfällig und nicht stabil bezüglich der verwendeten Huminsäure. Im Gegensatz dazu zeigte der EE2 ELISA und EE2 CLEIA ein robustes Verhalten und ermöglichten auch in Gegenwart erhöhter Huminsäurekonzentrationen die zuverlässige Bestimmung des EE2. Zusätzlich zu Aufbau und Optimierung der ELISAs wurde, ausgehend von bekannten Verfahren, eine SPE-Methode (solid phase extraction) zur Anreicherung und Aufreinigung von Wasserproben modifiziert und weiterentwickelt. Der wesentliche Vorteil der neuen Methode besteht in der geringeren Belastung der Extrakte durch Matrixkomponenten. Dies wurde ermöglicht durch die Verwendung eines neutralen pH-Werts zur Anreichung der Proben und der Einbeziehung spezieller Waschschritte mit organischen Lösungsmitteln zur Entfernung der Huminstoffe. Abschließend wurde die Praxistauglichkeit des EE2 ELISA und EE2 CLEIA im Rahmen einer Feldstudie untersucht und durch den Vergleich zu einem Referenzlabor validiert. Insgesamt wurden acht Proben aus Fließgewässern und zwölf Proben aus Kläranlagenabläufen gemessen. Für die Flussproben ergab sich eine Mediankonzentration von 0,6 ng/L und für die Proben aus Kläranlagenabläufen von 1,3 ng/L. Die Ergebnisse der Referenzmessungen (LC-MS/MS, LOD 1,0 ng/L) führten, bedingt durch die zu hohe Nachweisgrenze, meist zu (falsch-)negativen Befunden. Durch die vorliegende Arbeit konnte die Nachweisgrenze zur direkten Bestimmung von EE2 in Wasserproben (Oberflächenwasser und Kläranlagenablauf) erstmalig auf bis zu 0,2 ng/L abgesenkt werden. Gleichzeitig ist es gelungen, die Materialkosten für eine solche Bestimmung auf ca. 1,20 EUR zu reduzieren und die parallele Messung von 24 Proben in 40 Minuten zu ermöglichen. Es wurden somit die Grundlagen für eine sensitive und zugleich kosteneffiziente Routinemethode zur Bestimmung von EE2 in der aquatischen Umwelt geschaffen.
Bei der Stofftrennung von flüssigen organischen Gemischen durch das Membranverfahren der Pervaporation werden an die aktive Membran besondere Anforderungen gestellt. Zwei Faktoren sind neben der Langzeitstabilität von grundlegendem Interesse: der transmembrane Fluss und die Trennleistung. Die vorliegende Arbeit beschäftigt sich mit der Entwicklung und Charakteriserung von Hochfluss- wie auch hochselektiven Membranmaterialien für die Trennung azeotroper Aromaten/Aliphaten-Mischungen (Toluol/iso-Oktan). Im Rahmen der Arbeit wurden Blockpolymere aus Polyimiden und Polyvinylpyrrolidon synthetisiert und die Trenneigenschaften als Pervaporationsmembran in der Toluol/iso-Oktan-Trennung charakterisiert. Ebenso wurden Hochflussmembranen auf Basis von Copolymerisaten aus Ethylen und Methacrylsäure untersucht.
Motorproteine transportieren Makromoleküle oder Molekülverbände durch Umwandlung von chemischer in mechanische Energie. Homotetramere Motorproteine der Kinesin-5-Familie sind essentiell an der Bildung des Spindelapparats während der Mitose beteiligt. Ihre Fähigkeit, Mikrotubuli zu vernetzen, erschwerte bislang gängige Untersuchungsmethoden. In dieser Arbeit wurde erstmals das Motorprotein Eg5 durch seine systematische Dichtevariation auf Oberflächen untersucht. Möglich wurde dies durch die Entwicklung eines neuen Verfahrens auf der Basis nanostrukturierter und biofunktionalisierter Grenzflächen. Finales Ziel dieser Arbeit war es, eine kontrollierte Anbindung des Motorproteins Eg5 auf einer biokompatiblen Oberfläche zu ermöglichen, um sein biologisches Verhalten quantitativ zu untersuchen. Für eine kontrollierte Anbindung der Biomoleküle auf einer Oberfläche mussten sowohl proteinadhäsive wie auch proteinresistente Bereiche mit hoher Symmetrie generiert werden. Erstere wurden mittels quasi-hexagonaler Goldnanostrukturen auf Glas und letztere durch Funktionalisierung der noch freien Glasoberfläche mit Polyethylenglykol (PEG) erzeugt. Diese PEG-Schicht sollte zum einen gute proteinresistente Eigenschaften vorweisen und zum anderen möglichst dünn sein, um eine Biofunktionalisierung der Goldnanopartikel zu gewährleisten. Die Goldpartikeldurchmesser (5-7 nm) wurden der Größe einer Motordomäne des Proteins angepasst. Dadurch wurde die Wahrscheinlichkeit einer Mehrfachbelegung eines Goldpunktes mit Eg5 minimiert. Zentrale Frage zur Entwicklung geeigneter Oberflächen war die Generierung proteinresistenter Filme. Hierfür wurden unterschiedliche PEG-Funktionalisierungen durchgeführt und ihre Schichtzusammensetzung und –dicke untersucht. Dabei zeigten sich deutliche Vorteile einer Funktionalisierung mittels PEG-Alkoxysilylderivaten im Gegensatz zur Kopplung von PEG an aktivierte Oberflächen zur Herstellung dünner Filme (< 2.5 nm). Im Hinblick auf die Proteinresistenz der erzeugten PEG-Schichten konnte zudem gezeigt werden, dass besonders im Falle dünner Filme Packungsdichten wie auch Präparationsmethoden maßgeblichen Einfluss auf ihre zellabstoßenden Eigenschaften haben. Zudem wurde anhand von Zelladhäsionsexperimenten verdeutlicht, dass mit zunehmender Schichtdicke des PEGs größere Abschirmung eingebetteter Goldnanostrukturen erfolgte. Im Mittelpunkt der Anwendung stand die Fragestellung, ob und in welcher Form die Partikeldichte das Verhalten des Motorproteins beeinflusst. Hierfür wurde Eg5 auf Goldnanostrukturen mit unterschiedlichen Partikelabständen (45, 58, 73, 90, 110 nm) eingebettet in eine PEG-Matrix immobilisiert. Es konnte gezeigt werden, dass die Eg5-Anbindung zum einen spezifisch auf diesen Partikeln erfolgt und zum anderen die Menge des immobilisierten Proteins in direktem Zusammenhang mit der vorgegebenen Partikeldichte steht. Die ermittelten Gleitgeschwindigkeiten von Mikrotubuli, welche aktiv durch Eg5 unter ATP-Verbrauch transportiert wurden, stiegen mit zunehmender Motorkonzentration auf der Oberfläche. Weiterhin konnte bei geringen Goldpunktdichten (110 nm Abstände) eine Zunahme der Gleitgeschwindigkeit mit wachsender Länge der Mikrotubuli beobachtet werden. Dieses Verhalten steht im Einklang mit der Dichteabhängigkeit der Nanopartikel: Je mehr Eg5 am Transport der Mikrotubuli beteiligt sind, umso schneller werden sie, bis eine Sättigung erreicht ist. Diese Erkenntnis lässt vermuten, dass es sich bei Eg5 um ein nicht prozessives Motorprotein handelt, d. h. nach jedem getätigten Schritt auf dem Filament löst es sich ab. Weitere Geschwindigkeitserhöhungen konnten durch Anheben der Salzkonzentration in den verwendeten Puffern erzielt werden, wobei die Abhängigkeit der Geschwindigkeit von der Eg5-Oberflächenkonzentration gewahrt wurde. Diese Studie verknüpft anorganische Oberflächen mit organischen Beschichtungen zur Untersuchung biologischer Systeme mittels physikalischer Methoden. Sie eröffnet durch diese Symbiose der Naturwissenschaften neue Möglichkeiten in der Erforschung von Motorproteinen. Ebenso ist die Erweiterung auf andere molekulare Biosysteme wie DNA oder Enzyme denkbar.
Die Steigerung der Komplexität von Peptidbibliotheken bzw. Peptidarrays ist ein wichtiger Schritt bei der Identifizierung von bislang unbekannten Ursachen und Verläufen häufiger Krankheiten. Die bereits erfolgreich vollzogene Weiterentwicklung der etablierten Tintenstrahl-Drucktechnik zu laser- und tonerbasierten Systemen hinsichtlich Druckauflösung und Druckgeschwindigkeit könnte ein möglicher Ansatzpunkt für zukünftige Peptidarrayproduktionen dazu sein. Zu diesem Zweck wurden Aminosäuretoner entwickelt und charakterisiert, die mit einem technisch modifizierten Laserdrucker auf Trägeroberflächen gedruckt und mit ihnen zur Reaktion gebracht werden können. Die Entwicklung geeigneter Trägeroberflächen stand dabei im Mittelpunkt dieser Arbeit. (1.) Oberflächenmodifikationen: Es konnten proteinresistente Glasoberflächen als Trägermaterialien für die kombinatorische Peptidsynthese im Arrayformat mit Hilfe einer UV-induzierten Graftpolymerisation von Poly(ethylenglykol)methacrylat (PEGMA) erzeugt werden. Zuvor werden dazu auf Glasträgern Monoschichten aus 7-Octenyltrichlorosilan hergestellt, auf denen anschließend durch Ozon photosensitive, oberflächengebundene Radikalstarter generiert wurden. Die Ozonisierung der Silanfilme wurde mittels XP- und IR-Spektroskopie sowie Messungen des Kontaktwinkels zeitlich verfolgt. Die Optimierung der Graftfilmdicke geschah durch Variation von Bestrahlungsdauer und Monomerkonzentration und erfolgte durch ellipsometrische Schichtdickenmessungen an Siliziumoberflächen. Die Einführung von Aminogruppen mit einer variablen Funktionalitätsdichte erfolgte über die Veresterung von Carbodiimid-aktiviertem Fmoc-ß-Alanin. Die erzeugten Filme sind gegenüber 91 %iger Trifluoressigsäure (TFA) stabil und darüber hinaus resistent gegenüber unspezifischer Proteinadsorption. Die Verifizierung der Proteinresistenz erfolgte durch Inkubation mit vier verschiedenen Proteinlösungen (Fibrinogen, Lysozym, BSA und g-Globulin) in PBS-Puffer und anschließender Auswertung von N1s-XP-Detailspektren. (2.) Aminosäure-Tonerpartikel: Es konnten mit allen zwanzig voraktivierten, proteinogenen Aminosäuren (Fmoc-L-Aminosäure-Pentafluorphenylester) Tonerpartikel auf der Basis von OKI-Farbtonern synthetisiert und charakterisiert werden, die vergleichbare Größenverteilungen im Bereich von 9 µm und Ladungseigenschaften wie ihre Vorbilder aufweisen. Ihre Fähigkeit zur qualitativen Kopplung an aminoterminierte Glasoberflächen konnte über ein Anfärben der entschützten Aminogruppen nach der Reaktion mit der Oberfläche gezeigt werden. (3.) Peptidsynthesen mit Aminosäuretonern: Drei verschiedene Peptidepitope (DTYRYIDYA, YPYDVPDYA und DYKDDDDK) wurden mit Aminosäuretoner (und zum Vergleich aus einer Lösung in DMF) auf mit Rink-Linker modifizierten, PEG-gegrafteten Glasobjektträgern großflächig synthetisiert. Die Kopplungsausbeuten der einzelnen Syntheseschritte wurden UV-spektroskopisch verfolgt. Nach Abspalten der Peptide vom Träger mit TFA konnten alle drei Sequenzen durch MALDI-TOF-Messungen als Amide identifiziert werden. (4.) Peptidlaserdrucker und Peptidarray: Der entwickelte Peptidlaserdrucker ist in der Lage, innerhalb von ca. 70 Sekunden einen derivatisierten Glasträger (21 cm x 20 cm) mit ca. 155.000 Spots (Ø ca. 250 µm) zu bedrucken. Er basiert auf der Technik der Farblaserdruckerserie C7200 von OKI und besteht aus zwanzig hintereinander angeordneten Tonerkartuschen in einer Rahmenkonstruktion. Der zu bedruckende Träger wird auf einem Schlitten mit präzisem Linearantrieb bewegt. Ein erster Test-Array vor Inbetriebnahme des Druckers, bestehend aus den schachbrettartig angeordneten Epitopen YPYDVPDYA und DYKDDDDK, wurde durch Ausdruck der Aminosäuretoner auf Laserdruckerfolien und anschließenden Transfer auf den Glasträger synthetisiert. Der Nachweis erfolgte durch eine Inkubation des Trägers mit Mischungen aus den spezifischen Erst- und den fluoreszenzmarkierten Zweitantikörpern und Auswertung mit einem Fluoreszenzscanner.
Sprays in praktischen Anwendungen bestehen aus vielen Troepfchen. Das Verhalten eines Troepfchens haengt stark von den benachbarten Troepfchen ab, wenn der Abstand zwischen beiden in der Groessenordnung des Troepfchendurchmessers liegt. In Spray-Berechnungen wird die Interaktion zwischen Troepfchen waehrend Aufheizung, Verdampfung, Zuendung und Verbrennung normalerweise vernachlaessigt. Diese Annaeherung ist unzureichend, da benachbarte Troepfchen sowohl eine Energiesenke als auch eine Brennstoffquelle fuer das umgebende Gas darstellen. Numerische Untersuchungen von Troepfchenwechselwirkungen wurden bisher meist in einer zweidimensionalen axialsymmetrischen Konfiguration durchgefuehrt. Diese Konfiguration vernachlaessigt die Tatsache, dass hydrodynamische Wechselwirkungen meist dreidimensionaler Natur sind. Ausserdem haben numerische Untersuchungen in der Vergangenheit viele wichtige Eigenschaften wie die Abbremsung der Troepfchen sowie Zirkulationen innerhalb der Troepfchen vernachlaessigt. In einigen Faellen wurden grundlegende Details des numerischen Loesungverfahrens wie die Berechnung der korrekten Gleichungen fuer bewegte Gitter nicht beachtet. Es wurde eine numerische Methode entwickelt, um die Wechselwirkungen zwischen Troepfchen waehrend der Zuendung in drei Dimensionen zu untersuchen. Dabei wurden hydrodynamische Wechselwirkungen, Zirkulationen innerhalb der Troepfchen, Abbremsung durch das umgebende Gas, detaillierte Chemie, sowie weitere zuaestzliche Bedingungen des numerischen Loesungsverfahrens beruecksichtigt. Die Einzelheiten fuer die Beruecksichtigung der korrekten Gleichungen fuer bewegte Gitter wurden erlaeutert. Ein modifiziertes Mehrgitterverfahren wurde fuer die Berechnung der Verdampfung der Troepfchen angewandt. Nachdem sichergestellt wurde, dass das Programm die Interaktion zwischen Troepfchen zuverlaessig simuliert, wurden diese Effekte fuer ein einzelnes Ethanol-Troepfchen und fuer zwei gleich grosse Ethanol-Troepfchen in Tandem-Konfiguration durch numerische Simulation untersucht. Die berechnete Zuendverzoegerung fuer wechselwirkende Troepfchen stimmt gut mit den experimentellen Daten ueberein.
Im Rahmen dieser Doktorarbeit wurden selbstaggregierende Monolagen (SAM) proteinresistenter ethylenglykolterminierter (EG) Alkanthiole auf Metallsubstraten mit Hilfe verschiedener Meßmethoden, wie der Summenfrequenzspektroskopie (SFS), der Neutronenreflektometrie, aber auch der Ellipsometrie und der Infrarotspekroskopie charakterisiert. Da seit Beginn der 80er Jahre aus den Arbeiten von Jeon und Andrade et al. bekannt ist, daß die starke Wechselwirkung des Wassers über Wasserstoffbrückenbindungen mit Poly(ethylenglykol) (PEG) eine entscheidende Rolle für die Proteinrepulsion von PEG-beschichteten Oberflächen nach dem Mechanismus der sogenannten „sterischen Repulsion“ spielt, wurde in dieser Arbeit besonders die Wechselwirkung des Wassers mit PEG- bzw. oligo(ethylenglykol)terminierten (OEG) Alkanthiol-SAMs untersucht. [Ref. 1-3] Bei der Optimierung der PEG- und OEG-SAM-Präparation auf Gold wurde nachgewiesen, daß die Gegenwart von Sauerstoff in der Reaktionslösung die Bildung dichtgepackter OEG-SAMs fördert und bei PEG-SAMs erst ermöglicht. Dies wurde dadurch interpretiert, daß der bei der Reaktion von Thiol mit Gold frei werdende Wasserstoff mit dem Sauerstoff reagiert und sich dadurch günstig auf die Reaktionsenthalpie auswirkt. Des weiteren wurden die Banden der SFS-Spektren von SAMs bestehend aus methoxyhexa(ethylenglykol)terminiertem Undekanthiol (EG6OMe) auf Gold zugeordnet und für die Interpretation anderer Messungen verwendet. Zu diesen zählen Experimente an EG6OMe-Alkanthiolmischfilmen, die bei Erhöhung der Temperatur einen Phasenübergang aufweisen, durch den sie ihre Proteinresistenz verlieren. Außerdem wurde die These aus früheren Experimenten von Herrwerth et al. bestätigt, daß die Proteinresistenz von dichtgepackten, kristallinen OEG-SAMs hauptsächlich von deren lateralen Packungsdichten und folglich von deren Hydratisierbarkeit abhängt. [Ref. 4] Bei der Untersuchung von EG-Filmen in wassergesättigter Stickstoffatmosphäre wurde eine Schichtdickenzunahme durch Bildung einer 2 3 nm dicken Wasserschicht auf PEG-SAMs und einer etwas dünneren Wasserschicht auf OEG-SAMs gemessen, die bei anderen hydrophilen Oberflächenbeschichtungen nicht gefunden werden konnte. Ferner war es möglich die feste Bindung von Wassermolekülen an die Endgruppen von OEG-SAMs mit Hilfe von SFS indirekt durch Untersuchung der Konformationsänderungen der Filme vor und nach Wasserkontakt nachzuweisen. Diese Resultate wurden als Hinweis auf die Bildung einer geordneten Wasserstruktur gedeutet, die nach Arbeiten von Kushmerick et al. einen möglichen Mechanismus der Proteinresistenz von dichtgepackten OEG-SAMs darstellt. [Ref. 5] Die feste Bindung bestätigt allerdings auch Arbeiten von Kreuzer et al. [Ref. 6] und Chan et al. [Ref. 7], die die Bildung und Immobilisierung von Hydroxidionen als Grund für die Proteinabstoßung sehen. Diese beiden Mechanismen der Proteinresistenz von OEG-Filmen werden im Rahmen dieser Arbeit diskutiert. Referenzen: [1] J. D. Andrade, V. Hlady, Adv. Polym. Sci., 1, 1986 [2] S. I. Jeon, J. H. Lee, J. D. Andrade, P. G. De Gennes, J. Colloid Interface Sci., 142, 149-158, 1991 [3] S. I. Jeon, J. D. Andrade, J. Colloid Interface Sci., 142, 159-166, 1991 [4] S. Herrwerth, W. Eck, S. Reinhardt, M. Grunze, J. Am. Chem. Soc., 125, 9359-9366, 2003 [5] H. I. Kim, J. G. Kushmerick, J. E. Houston, B. C. Bunker, Langmuir, 19, 9271-9275, 2003 [6] H. J. Kreuzer, R. L. C. Wang, M. Grunze, J. Am. Chem. Soc., 125, 8384-8389, 2003 [7] Y.-H. M. Chan, R. Schweiß, C. Werner, M. Grunze, Langmuir, 19, 7380-7385, 2003
Phosphoryl transfer reactions are ubiquitous in biology and are usually catalyzed by metalloenzymes. For a number of phosphoryltransfer enzymes, including the exonuclease subunit of DNA polymerase I, a mechanism involving two metal ions and double Lewis-acid activation of the substrate, combined with leaving group stabilisation, has been proposed. Aim of this thesis was the study of low-molecular-weight models of phosphoryl transfer metalloenzymes. The focus was in particular on the macrocyclic dicopper(II) complex LCu2, which is the first transesterification catalyst for highly inert dialkyl phosphates and a mimic of the exonuclease subunit of DNA polymerase I. For the first time, a crystal structure of LCu2 with a coordinated phosphodiester was obtained. [LCu2(1,3-µ-DMP)(NO3)](NO3)2 (2) contains a 1,3- bridging phosphodiester. By extensive UV-Vis and pH metric titrations, the metal complex species present in methanolic LCu2/DMP solution have been identified. In particular it has been shown, that [LCu2(DMP)(OCH3)]2+ is the active species and that coordinated methanolate (and not free methanol or methanolate) is the nucleophile which attacks the P-atom of the substrate. DFT calculations (in cooperation with the group of Prof. Smith, IWR Heidelberg) confirm that the 1,3-DMP bridged complex is the dominant species in solution. By extensive kinetic studies including rate dependence on catalyst concentration, saturation kinetics, pH dependence on rate and dependence on rate on substrate structure, solid experimental data have been obtained which support the proposal of a reaction mechanism related to exonuclease subunit of DNA polymerase I. The applicability of LCu2 as a catalyst for the phosphorylation of various alcohols by dimethyl phosphate has been evaluated. A unique functional group tolerance of the catalyst and selectivity for dialkyl phosphates over alkyl carboxylates is observed. Screening of ATP hydrolysis by Zr(IV) and Eu(III) complexes was examined using a robotic liquid-handling workstation. It was found that a phosphate detection assay using molybdate is compatible with the presence of these high-valent metal ions. ATPase activity of the metal is modulated by the ligands, and the most efficient catalyst is the Zr complex of the tetracarboxylate ligand L6 at both pH 4 and pH 7. This is in contrast to Zr promoted DNA hydrolysis where polycarboxylate ligands have been shown to quench strongly the phosphoesterase activity of the metal ion.
A mechanism generator code to automatically generate mechanisms for the oxidation and combustion of large hydrocarbons has been successfully modified in this work. The modification was through: (1) improvement of the existing rules such as cyclic-ether reactions and aldehyde reactions, (2) inclusion of some additional rules to the code, such as ketone reactions, hydroperoxy cyclic-ether formations and additional reactions of alkenes, (3) inclusion of small oxygenates, produced by the code but not included in the handwritten C1-C4 sub-mechanism yet, to the handwritten C1-C4 sub-mechanism. In order to evaluate mechanisms generated by the code simulation of observed results in different experimental environments has been carried out. The simulation of auto-ignition of n-pentane in a rapid-compression machine shows good agreement with experimental results. Experimentally derived and numerically predicted ignition delays of n-heptane/air and n-decane/air mixtures in high-pressure shock tubes in a wide range of temperatures, pressures and equivalence ratios agree very well. Concentration profiles of the main products and intermediates of n-heptane, iso-octane and n-decane oxidation in jet-stirred reactors at a wide range of temperatures and equivalence ratios are generally well reproduced. Sensitivity and reaction flow analyses were performed for shock tube and jet-stirred reactor environments, respectively, in an attempt to identify the most important reactions under the relevant conditions of study. In addition, the ignition delay times of different normal alkanes was numerically studied.
Charged species occur in all combustion systems. Chemical pathways which involve ions are known to contribute to the formation of air pollutants like soot and aerosols. The appearance of electrical charges, which are closely related to the combustion process itself, offers the opportunity of their use for sensing purposes in a variety of applications. Reliable models for the chemical reaction network and the transport processes are required for numerical simulations in these fields of research. Laminar flat flames have proven to be suitable systems for the development and validation of chemical reaction mechanisms. In this work, the concentrations of charged species along a flat, fuel-lean, and laminar methane-oxygen flame are calculated and compared to experimental results. For the first time, these simulations also include negative ions. Existing software was enhanced to enable the inclusion of these ions. The chemical reaction mechanism of the charged species is compiled from different sources found in according literature. Altogether, the model contains 65 reversible reactions involving 11 charged species. Also special emphasis is put on the diffusion processes of the ions. A model is developed and discussed which describes the mutual interactions of the charged species during diffusion. It allows an arbitrary fraction of negative ions, because it does not depend on the assumption that the electrons dominate this process. The simulations are used to validate the reaction mechanism. Reaction flow analyses show which chemical pathways are taken. Reactions which were suggested in the literature are discussed quantitatively. The influence of charged species diffusion on the simulation results as well as their sensitivities to uncertainties in the input data of the transport model are analyzed.
Carbon dioxide in the middle atmosphere shows an increasing enrichment in the heavy oxygen isotopes with altitude which preferential enrichment for 17O according to d17O =1.7 d18O. This is contrary to tropospheric CO2 where d17O ~ 0.5d18O. These isotope enrichments are transferred from O3 into CO2, but details of the mechanism are not understood yet. A systematic study was carried out using O2 and CO2 gases of different isotopic composition. Results show the existence of a photochemical isotope equilibrium between O2 and CO2, which is independent of the initial isotopic composition and shows equal enrichments for 17O and 18O. Additional experiments were conducted to investigate the effect of temperature, pressure and O2/CO2 ratio. Data revealed that the magnitude of enrichment at photochemical equilibrium depends on pressure and on O2/CO2 ratios with a decrease in enrichment at higher pressures. Also, the enrichment in CO2 showed a positive temperature dependence. The measurement of asymmetric O3 in one experiment yields additional insight into the isotope exchange mechanism and shows the absence of anomalous fractionation steps in the CO3* intermediate. The experimental data were modeled with the chemical kinetics software Facsimile. In addition, a large set of new measurements of the isotopic composition of stratospheric CO2 are presented, extending the earlier data down to the tropopause.
The feedstocks of natural gas exceed the resources of crude oil by far. Therefore, there is a strong interest in the utilisation of natural gas with its main component methane for the production of more useful chemicals. This leads to a strong demand for compact and low-capital-cost reactors for the conversion of natural gas to methanol and liquid hydrocarbons and the production of H2. The combustion of natural gas is also considered for power generation in catalytic devices, because the flameless catalytic process results in lower emissions of NOx. Noble metals such as Pt, Pd, and Rh are very active catalysts for the conversion of CH4. However, the processes occurring during the partial and complete oxidation of CH4 on these catalysts are not completely understood. A detailed understanding of the reactor behaviour at all possible conditions is crucial for the technical realisation of these catalytic processes, because explosive mixtures are handled. In particular it is necessary to control the operation of the reactors at transient conditions such as light-off and shut-down. The objective of this work is to study total and partial oxidation of methane over Pt, Pd, and Rh catalysts for a wide range of operating conditions. Therefore, an experimental setup, which is easily applicable for modelling and numerical simulation, has to be developed. The experiment and analysis has to be arranged in a way that allows studies of transient processes such as light-off. Based on the experimentally derived conversion and selectivity surface-reaction schemes, available in literature, have to be evaluated. Available computational tools have to be used for numerically predicted reactor performance and compare these results with the experimental data. Crucial conditions, at which the reaction models need improvement, have to be found, and if necessary and possible improved. A flow reactor with associated analysis is designed to meet these requirements. In order to facilitate the simulation of the system catalysts exhibiting a simple geometry such as monolithic structures are used. The reactor consists of a 40 cm long quartz tube with varying inner diameters. Honeycomb catalysts coated with Rh, Pd, or Pt are placed inside. The gas temperature at the exit of the catalytic monolith and outside the quartz tube is. The reaction is ignited by heating up the reactor by a furnace, in which the flow system is integrated. After ignition, in the case of autothermal operation, the furnace can be switched off. The gases are premixed at room temperature and flow into the quartz tube at atmospheric pressure. The product composition is quantitatively analysed by a quadrupole mass spectrometer (QMS) in order to study transient phenomena. For the evaluation of reaction mechanisms, detailed numerical simulations of the physical and chemical processes using the computer program package DETCHEM and the commercially available CFD code FLUENT are applied. The numerical codes take into account detailed mechanisms of surface and gas-phase reactions as well as mass and heat transport processes in the channels and heat transport in the solid monolithic structure. The channels are simulated under steady-state conditions in a 3D elliptic approach using FLUENT and in two dimensions by a parabolic approach using DETCHEMCHANNEL. Transient phenomena are simulated by DETCHEMMONOLITH with 2D parabolic flow field simulations of a representative number of single channels including transient heat balances of the monolithic structure. First, the ignition of catalytic combustion of CH4 on a Pt loaded monolith is investigated. The conversions of CH4 and O2 as well as the product selectivities are experimentally determined and the results numerically simulated. The influence of H2 addition on the combustion is investigated. Reaction-rate oscillations of the catalytic combustion of methane on a Pd based catalyst are found experimentally at lean conditions in Pd coated monoliths and simulated with a surface-reaction mechanism. The second set of experimental focuses on CPO of CH4 over Rh coated monoliths. The experimentally derived conversion and selectivities are used to improve a detailed reaction mechanism. Next, the influence of the support material on the ignition process is investigated. In the experiment, either -alumina or cordierite as support material is applied and coated with Rh. The models are able to describe the light-off behaviour and are applied for catalyst design: The ignition behaviour of a set of virtual catalytic monoliths exhibiting varying physical properties is modelled. In addition, catalysts coated with Rh-nanopowder produced by laser ablation is experimentally examined and compared with wet coated catalysts. Finally, the CPO of methane is carried in a Pt, presenting an even more well-defined configuration for modelling. At CH4/O2 ratios above 1.9 complex patterns of oscillation in conversion and selectivity occur.
In palladium- und rhodiumkatalysierten Alder-En-analogen Reaktionen wurden In-Allylalkohol-Substrate cycloisomerisiert, die dann in einer anschließenden Tautomerie zu den entsprechenden y,d-Enalen umlagerten. Daneben wurden in Heck-Carbopalladierungsreaktionen ebenfalls In-Allylalkohole eingesetzt, die in einer Folge aus Carbopalladierung, Heck-Reaktion und anschließender Tautomerie ebenfalls y,d-Enale bildeten. Diese so gebildeten y,d-Enale wurden als Diversitätsmodule benutzt, um Konsekutivreaktionen im Ein-Topf-Verfahren anzuschließen. Hier konnte eine Reihe von Konsekutivreaktionen durchgeführt werden, darunter Wittig-Olefinierungen, reduktive Aminierungen und Knoevenagel-Kondensationen, die die Diversität und Komplexität der Reaktionsprodukte enorm erhöhten.
Im Verlauf dieser Arbeit wurden Metallkomplex-funktionalisierte Peptidnukleinsäuren und intern modifizierte Peptidnukleinsäuren synthetisiert und deren Anwendung zur sequenzspezifischen DNA-Analyse untersucht. Ligationsreaktionen modifizierter Oligonukleotide (und deren Analoga) am Nukleinsäure-Templat finden Anwendung zur Detektion von DNA. Die Produkte dieser Reaktionen binden dabei deutlich stärker an das DNA-Templat als die Edukte. Daher sind diese Umsetzungen meist stöchiometrisch. Katalytische, Templat-gesteuerte Reaktionen wären für die Analyse wesentlich interessanter, da dann ein DNA-Molekül zur Umsetzung einer Reihe von Edukten führen könnte. Durch diesen Effekt wäre die Analyse geringer Mengen von DNA möglich. In dieser Arbeit wurde die katalytische Hydrolyse einer Ester-PNA durch ein Cu2+-Komplex-PNA-Konjugat untersucht, die sowohl durch Einzelstrang-DNA als auch durch Doppelstrang-DNA gesteuert werden kann. Die Hydrolyse einer Ester-PNA am Einzelstrang-DNA-Templat, die durch den Kupferkomplex einer Katalysator-PNA katalysiert wird, erreicht eine > 100-fache kinetische Diskriminierung zwischen DNAs, die sich nur an einer einzigen Nukleotid-Position unterscheiden. Auf Basis dieser Reaktion konnte eine vollständig homogene, empfindliche Methode zur sequenzspezifischen Detektion von Einzelstrang-DNA (10 fmol DNA) entwickelt werden. In einem einzelnen Experiment ist mit dieser Methode die Erkennung einer von vier DNAs, die sich nur in einer einzelnen Position unterscheiden, möglich. In Gegenwart eines Doppelstrang-DNA-Templates, welches zu der Ester-PNA und der PNA LCu komplementär ist, ist die anfängliche Spaltgeschwindigkeit 7-mal höher als in Abwesenheit eines Templates. Durch „mismatch“-Doppelstrang-Template, die entweder auf der Seite, an der die Ester-PNA bindet, oder auf der Seite, an der die PNA-LCu bindet, Fehlbasenpaarungen enthalten, wird die Ester-Hydrolyse im Vergleich zur Hintergrund-Hydrolyse (ohne Templat) nicht wesentlich beschleunigt. Da das Cu2+-Ion vermutlich fest an ein Assoziat gebunden ist, das aus der Substrat-PNA, der Katalysator-PNA und dem Einzelstrang- bzw. Doppelstrang-DNA-Templat besteht, kann diese Analysenmethode auch bei Systemen mit Puffern, die Cu2+-bindende Liganden enthalten, angewendet werden, wie z. B. PCR-Puffer und physiologischer Puffer. Zur DNA-Analyse können auch Reaktionen komplementärer Peptidnukleinsäuren verwendet werden, die durch Hybridisierung nicht beschleunigt, sondern inhibiert werden. In dieser Arbeit wurde die Spaltung einer intern Disulfid-modifizierten PNA untersucht. Als Spaltreagenzien wurden verschiedene Phosphine und Thiole getestet. Die beste Selektivität konnte mit Tris-(carboxyethyl)-phosphin erreicht werden. Dieses Phosphin spaltet die Einzelstrang-Disulfid-PNA 33-mal schneller als die Disulfid-PNA in der PNA / DNA-Duplex.
Das Verständnis atmosphärischer Prozesse ist in der heutigen Zeit steigender Umweltverschmutzung wichtiger den je. Die präzise Untersuchung der Reaktions-systeme, welche auf die Chemie der Atmosphäre Einfluß nehmen, ist deshalb ein Bereich, in dem nahezu alle Disziplinen der modernen Naturwissenschaften ver-treten sind. Die Analyse atmosphärischer Prozesse bei hohen Temperaturen dient in diesem Zusammenhang dazu, den aktuellen Forschungsstand zu ergänzen. Im Rahmen dieser Arbeit wurde ein Hochtemperaturströmungsreaktor konstruiert und aufgebaut. Mit diesem System können Geschwindigkeitskoeffizienten von Elementarreaktionen bei hohen Temperaturen studiert werden. In der vorliegenden Untersuchung wurden mit diesem Strömungsreaktor die Geschwindigkeits-konstanten der Reaktion O (1D) + H2 erstmals bei hohen Temperaturen untersucht. Zur korrekten Auslegung dieses Reaktors wurden Strömungssimulationen durch-geführt, um Temperaturverlauf und Mischprozesse untersuchen zu können. Neu-artige Ansätze im Design und in der Auswahl bestimmter Einzelteile waren erforderlich, um den gestellten Anforderungen zu genügen und den Hochtem-peraturreaktor zu realisieren. Durch Kombination mit einem optischen System zur Generierung vakuum-ultravioletter (VUV) Laserstrahlung, wurden unter Verwendung eines "pump-probe"-Verfahrens Messungen atomarer Spezies bei hohen Temperaturen ermöglicht, die in Elementarreaktionen produziert werden. Durch zeitaufgelöste Detektion dieser Spezies kann die Geschwindigkeitskonstante dieser Reaktionen bei verschiedenen Temperaturen bestimmt werden. Als Testreaktion für die Funktionsfähigkeit des experimentellen Aufbaus wurde die Umsetzung von elektronisch angeregtem Sauerstoff mit Wasserstoff untersucht. O(1D) + H2(1Sg+) ® OH(2P) + H(2S) Der elektronisch angeregte Sauerstoff wurde mittels Laserphotolyse von Distick-stoffmonoxid (N2O) bei einer Wellenlänge von 193 nm erzeugt. Mittels eines Vier-wellen-Mischprozesses wurde die VUV-Strahlung generiert, die für die Detektion des atomaren Wasserstoffs benötigt wurde. Dabei wird über die Kopplung der Strahlung zweier Farbstofflaser durch resonant verstärkte Summen-Differenz-Mischung in einem Krypton/Argon-Gasgemisch Laserstrahlung im Bereich des Wasserstoffs-La-Übergangs bei 121,56 nm erzeugt. Die erhaltenen zeitaufgelösten Wasserstoffatom-Konzentrationsprofile wurden durch eine der Reaktionskinetik angepaßten Funktion ausgewertet, wodurch Geschwindigkeitskonstanten pseudo-erster-Ordnung erhalten wurden, aus welchen dann die Geschwindigkeitskonstante der Reaktion für die entsprechende Tem-peratur berechnet werden konnte.
Gegenstand der vorliegenden Arbeit ist die theoretische Untersuchung eines neuartigen Abgas-Nachbehandlungssystemes unter Verwendung eines Multiskalen-Modellierungsansatzes. Prozesse vom Nanobereich (chemische Reaktionen) bis zum Makrobereich (zeitabhängige Umsätze im katalytischen Einzelkanal) wurden durch verschiedene Modellierungstechniken beschrieben. Diese unabhängigen Techniken wurden im Rahmen eines Multiskalen-Modellierungsansatzes vereint, um ein umfassendes Modell eines Autoabgas-Katalysators zu erreichen. Das untersuchte Rhodium-basierte Abgaskatalysator-System reduziert giftige Stickoxide (NOx, x = 1,2) selektiv zu Stickstoff (N2) in einem Sauerstoff-reichen Abgas, in welchem kurzzeitig (0,1 s – 5 s) reduzierende Bedingungen generiert werden. Experimentelle Untersuchungen von Stickoxiden und Sauerstoff auf gestuften und nieder-indizierten Rhodium-Oberflächen weisen darauf hin, dass diese Oberflächen Stickoxide nicht zersetzen können, da sie umgehend Sauerstoff-vergiftet sind. Um ein genaueres Verständnis der relevanten Oberflächenprozesse zu erreichen, wurden Oberflächenreaktionen sowie Oberflächenmobilitäten mittels quantenchemischer Dichtefunktional (DFT)-Berechnungen untersucht. Es wurde gezeigt, dass die vorherrschende Oberflächenfacette auf Katalysatorpartikeln, die (111)-Oberfläche, relativ inaktiv bzgl. der NO-Zersetzung ist. Die Oberfläche wird zusätzlich durch die Präsenz einer Sauerstoff- Vorbelegung deaktiviert. Des Weiteren wurde gezeigt, dass Sauerstoff sich anfänglich sehr schnell auf Rhodium(111) zersetzt, während dieser Prozess selbsthemmend ist; die Aktivierungsenergie steigt mit steigender Sauerstoffbedeckung. Die Vermutung, dass die Deaktivierung in beiden Fällen (NO und O2) auf die dem Rhodium Elektronen-entziehende Wirkung der Sauerstoffvorbelegung zurückzuführen ist, wird durch Ladungsanalysen unterstützt. DFT-Untersuchungen von monoatomaren Stufen, dem häufigsten Defekt auf Katalysatorpartikeln, zeigten, dass die NO-Zersetzung hier wesentlich wahrscheinlicher ist, während der Prozess ebenfalls durch Sauerstoffvorbelegung deaktiviert wird. Es wurde aufgezeigt, dass, obwohl elektronische Effekte die Reaktionswahrscheinlichkeit beeinflussen, sterische Effekte einflussreicher sind. Das qualitative Wissen, welches aus diesen DFT-Studien gewonnen wurde, war die Basis von zeitabhängigen Simulationen der reaktiven Strömung in Autoabgaskatalysatoren mittels DETCHEMTRANSIENT. DETCHEMTRANSIENT ist ein Modul von DETCHEM (O. Deutschmann et al.), welches als Teil der vorliegenden Arbeit entwickelt wurde. Es simuliert das instationäre Verhalten von reaktiven Strömungen mittels eines hierarchischen Modellierungsansatzes. Zeitabhängige Umsätze simuliert durch DETCHEMTRANSIENT, basierend auf Elementarreaktions-Mechanismen, welche durch DFT-Berechnungen optimiert wurden (s.o.), konnten experimentell bestimmte Umsatzkurven erfolgreich reproduzieren. Die vorliegende Arbeit ist ein wichtiger Schritt zu einer detaillierten Multiskalen- Modellierung von Autoabgaskatalysatoren. In einem umfassenden Ansatz müssen Prozesse auf den relevanten Skalen vom Mikroskopischen zum Makroskopischen (von der Quantenchemie zum Strömungsverhalten) beschrieben werden. Im Speziellen konnten Erkenntnisse aus der Quantenchemie dazu beitragen, Prozesse auf höheren Zeit- und Längenskalen zu verstehen.
Im Rahmen dieser Arbeit konnte gezeigt werden, dass FRET und PET zwei komplementäre Techniken zur Verfolgung der Konformationsdynamik von Biopolymeren sind. Es konnten DNA-Hairpins synthetisiert werden und deren Konformationsdynamik zwischen geschlossener und geöffneter Form mit Hilfe der Einzelmolekülfluoreszenzspektroskopie direkt verfolgt werden. Die in der vorliegenden Arbeit untersuchten DNA–Hairpins sind einzelsträngige DNA–Sequenzen, die eine Komplementarität an beiden Enden der Sequenz aufweisen. Dadurch kommt es zur intramolekularen Hybridisierung, d.h. es bildet sich eine Stamm/Schleife-Struktur. Die DNA–Hairpins wurden unter unterschiedlichen Bedingungen vermessen, die dazu führen, dass die geöffnete oder geschlossene Konformation stabil ist, oder dass es zu thermisch induzierten Fluktuationen der Konformation kommt. In Gegenwart von Gegensequenz wird der DNA-Hairpin durch Hybridisierung mit der komplementären Sequenz dauerhaft geöffnet. Ziel der Arbeit war die direkte Verfolgung der Konformationsdynamik einzelner DNA– Hairpins im Laserfokus. Spezielles Interesse galt hierbei der Bestimmung der Assoziations- und Dissoziationsraten unter Berücksichtigung des PET als neue Methode zur Bestimmung von konformativen Änderungen. Als Standartmethode zur Bestimmung von konformativen Änderungen wurde FRET verwendet. Bei diesem Hairpin wurden sowohl der Donor-, als auch der Akzeptorfarbstoff an den beiden Enden des Hairpins angebracht, so dass im geschlossenen Zustand eine hohe Energietransfer-Effizienz resultiert. Im geöffneten Zustand ist der Abstand zwischen Donor und Akzeptor so groß, dass nur noch wenig Energie vom Donor auf den Akzeptor transferiert wird. Unter Hochsalzbedingungen ist der Hairpin geschlossen und der Abstand zwischen Donor und Akzeptor ist optimal für einen effektiven Energieübertrag. Erniedrigt man die Salzkonzentration, sieht man immer wieder Wechsel in der FRET-Effizienz der Fluoreszenz – teilweise erhält man hauptsächlich Akzeptorfluoreszenz, die anzeigt, dass der Hairpin geschlossenen ist, andererseits erhält man donordominierte Fluoreszenz, die anzeigt, dass der Hairpin geöffnet ist. Durch Zugabe von Gegensequenz wird der Hairpin dauerhaft geöffnet. Bestimmt man die Zeiten, in denen der DNA-Hairpin offen ist, d.h. kein FRET zwischen dem hier verwendeten Donor Cy3 und Akzeptor Cy5 stattfindet, kann die Kinetik des Prozesses bestimmt und dadurch die Geschwindigkeitskonstante der Öffnung des Hairpins berechnet werden. Für das Schließen des Hairpins konnte hierbei eine Geschwindigkeitskonstante von k = 1,3 ± 0,13 1/s bei 22°C bestimmt werden. Die Öffnungskinetik ist wesentlich langsamer und konnte deshalb nur indirekt bestimmt werden, da diese von der Photozerstörung überlagert ist. Die Geschwindigkeitskonstante der Öffnung des Hairpins wurde deshalb über die Gleichgewichtskonstante aus der Schmelzkurve des Hairpins im Ensemble errechnet. Sie beträgt k* = 10,8 ± 2 1/s. Vergleicht man dies mit der Proteinfaltung, so verlaufen Konformationsänderungen an DNA-Hairpins um einige Größenordnungen langsamer, was mit der Aufgabe der DNA als Informationsspeicher zu dienen und der dafür notwendigen größeren Starrheit erklärbar ist. DNA–Hairpins auf Basis des Photoinduzierten Elektronen Transfer (PET) zeigen ein wesentlich komplexeres Verhalten. Aufgrund der wesentlich stärkeren Abstandsabhängigkeit bei PET als FRET, sieht man kleinste Änderungen der Konformation, wie z.B. Interkalation und Furchenbindung. Dadurch ändert sich der Betrag des Überlappungsintegrals und das Quenchverhalten des Farbstoffes ändert sich. Autokorrelationen der Fluoreszenzintensität zeigen, dass der Farbstoff nur für Millisekunden bis Mikrosekunden einen Komplex mit dem Quencher bildet und dann wieder dissoziiert. Frühere Studien haben diese Fluktuationen als Öffnungs- und Schließungskinetik interpretiert. Im Rahmen dieser Arbeit konnten erstmals Einblicke in die Funktionsweise von DNA-Hairpin–Farbstoffkonstrukten gewonnen werden. Des Weiteren konnte gezeigt werden, dass die entwickelte Technik ebenso erfolgreich für diagnostische Anwendungen verwendet werden kann. So konnten bestimmte DNA – Sequenzen spezifisch bis zu einer Konzentration von 10-13 M mit Hilfe der Einzelmolekülspektroskopie durch Einschränkung der Konformationsdynamik nach erfolgreicher Hybridisierung nachgewiesen werden. Durch die Bestimmung der Konformation (geöffnet oder geschlossen) auf Einzelmolekülebene konnten erstmals bestimmte Zielsequenzen im subpikomolaren Bereich nachgewiesen werden.
Einfache und effiziente Synthesen neuartiger Heterocyclen sind von großem synthesechemischen Interesse. Kupfervermittelte oxidative Cyclisierungsreaktionen bieten eine elegante Möglichkeit zur Knüpfung von Kohlenstoff-Stickstoff-Bindungen und ermöglichen somit den Zugang zu zahlreichen stickstoffhaltigen Heterocyclen. Eine Reihe verschiedener heterocyclisch substituierter Hydrazone (1 und 3) wurden kupferassistiert zu den entsprechenden 1,2,4-Triazolo[4,3-a]pyridinen 2 und 1,2,4-Triazolo[4,3-a]quinoxalinen 4 oxidiert. Durch Einführung unterschiedlicher Funktionalitäten in das Substratmolekül wurde eine breite Produktvielfalt erhalten. Am Beispiel der Verbindung 5 wurde außerdem gezeigt, dass auch 3-Aminoacrylate in einer Zweielektronen-Oxidation mittels stöchiometrischer Mengen an Kupfer(II)-chlorid zu Imidazo[1,5-a]pyridin-2H-ylidenen (6) reagieren. Bei der kupferassistierten Umsetzung der heterocyclischen Aldimine (10 und 13) von 1-Pyridin-2-ylethanamin (9a) sowie 1-(1-Methyl-1H-imidazol-2-yl)ethanamin (9b) wurden neben den Imidazo[1,5-a]pyridinen 11 und 14 auch heterocyclisch substituierte Pyridine (12 und 15) gebildet. Diese entstehen in der Koordinationssphäre des Kupfers durch aufeinanderfolgende Sequenzen von Oxidations- und [4+2]-Cycloadditionsreaktionen zweier Aldiminmoleküle. Durch Einsatz des 1-Pyridin-2-ylpropanamins (9c) im Substratmolekül wurde zudem die Bildung des 1,4-Diazatricyclo-[3.2.1.02,7]oct-3-ens 18 beobachtet, dessen tricyclische Grundstruktur bisher noch nicht beschrieben wurde. Die exakte Analyse sowie Strukturuntersuchungen an Kupferkomplexen führten zu Mechanismusvorschlägen. Einige der dargestellten Pyridinderivate wurden pharmakologisch untersucht und wiesen zytostatische Wirkung auf. Dabei stellten sich 12a sowie die Platin(II)-Komplexe 23 und 24 als besonders wirksam gegenüber einzelnen Tumorzelllinien heraus. In Anlehnung an den postulierten Reaktionsmechanismus der Pyridinbildung wurde die kupferassistierte Umsetzung von heterocyclisch substituierten Aldiminen mit verschiedenen Dienophilen untersucht. Bei der Reaktion mit Dimethylacetylendicarboxylat, 1,4-Naphthochinon und 1,4-Benzochinon erhielt man Produkte, die infolge oxidativer [3+2]-Cycloadditionsreaktionen entstanden. Die 2H-Pyrrole (25), Isoindol-4,9-diole (29) und Benzo[f]isoindol-4,9-diole (30) konnten zudem auch kupferkatalysiert in Gegenwart von Luftsauerstoff selektiv und in guten Ausbeuten erhalten werden.
In der vorliegenden Arbeit wurden elektronische Relaxationsprozesse Valenz-ionisierter Moleküle und Cluster mittels quantenchemischer ab-initio Verfahren untersucht. Als zentrales Resultat dieser Studien konnte ein neuartiger elektronischer Relaxationsprozess für die Inner-Valenz-ionisierten Zustände schwach gebundener Cluster aufgezeigt und analysiert werden. Während die Valenz-ionisierten Zustände isolierter atomarer und kleiner molekularer Systeme (Monomere) aus energetischen Gründen nur im Rahmen relativ langsamer Photonemissions- bzw. Kerndynamik-Prozesse relaxieren können, eröffnet die "Einbettung" dieser Monomere in einen schwach gebundenen Cluster einen äußerst effizienten elektronischen Zerfallsprozess der Inner-Valenz-ionisierten Zustände. Das Ergebnis der Analyse des Zerfallsmechanismus läßt sich in einem vereinfachten schematischen Bild darstellen: Ein Inner-Valenz-ionisierter Ausgangszustand mit lokalisierter Lochladung an einem der schwach gebundenen Clustermonomere zerfällt, indem ein Elektron aus der äußeren Valenz des selben Monomers das ursprüngliche Inner-Valenz-Loch "auffüllt". Die dabei freigesetzte Überschussenergie wird im Rahmen eines effizienten interatomaren bzw. intermolekularen Kopplungsmechanismus zu einem Nachbarmonomer transferiert. Dort führt die Überschussenergie zur Emission eines Elektrons aus der äußeren Valenz. Der resultierende doppelionisierte Zerfallskanal besitzt jeweils eine lokalisierte Lochladung an den beiden benachbarten Monomereinheiten. Die reduzierte Coulomb-Abstoßung der räumlich verteilten Lochladungen führt zu einer drastischen energetischen Absenkung der Doppelionisierungsschwelle gegenüber der Lage in den isolierten Monomereinheiten, und somit zur Öffnung der Zerfallskanäle für die Inner--Valenz--ionisierten Clusterzustände. Der interatomare bzw. intermolekulare Mechanismus des elektronischen Zerfalls der Inner--Valenz--ionisierten Clusterzustände steht in deutlichem Gegensatz zur ausgeprägt intraatomaren Natur des elektronischen Zerfalls elektronisch hochangeregter, Core-ionisierter Zustände (Auger-Zerfall). Auf Grund der dominierenden Coulomb-Wechselwirkung zwischen den Elektronen der am Zerfallsprozess beteiligten Nachbarmonomere wurde der elektronische Zerfall Inner-Valenz-ionisierter Clusterzustände als Interatomic bzw. Intermolecular Coulombic Decay (ICD) bezeichnet. Die große Effizienz des ICD-Prozesses spiegelt sich in den berechneten kurzen Lebensdauern der zerfallenden Inner-Valenz-ionisierten Ausgangszustände im Größenbereich von ca. 1-100 Femtosekunden wieder. Die enorme Bedeutung des ICD-Prozesses für schwach gebundene Systeme zeigt sich im Rahmen der exemplarischen Analyse H-verbrückter Molekülcluster (z.B. H2O- und HF-Cluster) und van-der-Waals-Cluster (Neon-Cluster). Im Detail untersucht wurde unter anderem die Größen- und Abstandsabhängigkeit des elektronischen Zerfallsprozesses. Am Beispiel der heterogenen NeAr- und NeCO-Systeme konnte eine für kurze Monomerabstände relevante Elektrontransfer-vermittelte Variante des ICD-Prozesses aufgezeigt und analysiert werden. Für doppelionisierte Clusterzustände mit mindestens einem Inner-Valenz-Loch wurde das Auftreten eines ICD-analogen elektronischen Zerfallsprozesses vorhergesagt. Die mit der Betrachtung schwach gebundener Cluster begonnenen ab-initio Studien der elektronischen Relaxationsprozesse Valenz-ionisierter Zustände wurden auf molekulare Systeme ausgeweitet. Für Inner-Valenz-ionisierte Zustände "ausgedehnter" molekularer Systeme, sowie kleiner molekularer Anionen konnte eine intramolekulare Variante des ICD-Prozesses aufgezeigt werden. Darüber hinaus wurde die Möglichkeit eines ultraschnellen rein elektronischen Loch-Ladungstransferprozesses für nicht-stationäre Valenz-ionisierte Ausgangszustände molekularer Systeme nachgewiesen. Der im Rahmen der vorliegenden Arbeit erstmals postulierte ICD-Prozess konnte mittlerweile im Rahmen von Photoionisierungsstudien an Neon- und gemischten Neon/Argon-Clustern experimentell nachgewiesen werden. Die Ergebnisse dieser experimentellen Untersuchungen bestätigen die theoretischen Vorhersagen der hier vorgelegten ab-initio Studien.
Im Rahmen dieser Arbeit wurde die Reaktivität ungesättigter organischer 4-Elektronen-Donorliganden gegenüber dem TripodCobalt(I)-Templat (Tripod = CH3C(CH2PAr2)3) untersucht. 1,3-Diene koordinieren an das TripodCobalt(I)-Templat unter Bildung von [TripodCobalt(hapto4-Dien)]+-Komplexen, die auf ihre strukturellen und dynamischen Eigenschaften untersucht wurden. Die Reaktion des TripodCobalt(I)-Templats mit alpha,beta-ungesättigten Aldehyden zeigt eine Selektivität in Abhängigkeit vom Substitutionsmuster des Aldehydes. Während Acrolein und seine alpha-substituierten Derivate in THF stabile [TripodCobalt(hapto4-Heterodien)]+-Verbindungen bilden, sind analoge Komplexe von beta-substituierten Derivaten weniger stabil und reagieren unter Decarbonylierung des Aldehydes und Bildung von [TripodCobalt(CO)2]+. Die beobachtete Selektivität beruht offensichtlich auf einer sterischen Differenzierung. Im stärker koordinierenden Lösungsmittel Acetonitril wird die Bildung von [TripodCobalt(CO)(CH3CN)]+ beobachtet. Diese Zwischenstufe der Decarbonylierung ist ausreichend stabilisiert, so dass der Acetonitril-Ligand durch andere Zweielektronen-Donorliganden unter Bildung von Verbindungen vom Typ [TripodCobalt(CO)(L)]+ (L = PMe3, P(OMe)3, CyNC) verdrängt werden kann.
Anhand von zweifach negativ geladenen Halogenoplatinaten und organischen Verbindungen mit delokalisierten pi-Elektronen demonstriert diese Arbeit unkonventionelles Verhalten von Dianionen. Zum einen zeigte die Studie der Metallkomplexe, dass deren Orbitalreihenfolge sich fundamental von der in Standardbüchern gelehrten unterscheidet. Weiterhin wurde bei den untersuchten radartigen Kohlenstoffdianionen (CC2)n^{2-} (n=3...6) eine Antikorrelation von Aromatizität und elektronischer Stabilität beobachtet. Um die Größen des Molekülgerüsts als Stabilisierungsfaktor auszuschließen, studierte ich die Dianionenreihe (C2-C6H{2n}-C2)^{2-} (n...5). Auch hier korrelierte verminderte Delokalisierung der Elektronen mit erhöhter elektronischer Stabilität. Bei obigen Studien kam einmal mehr das Problem auf, Energien und Lebensdauern von metastabilen, (mehrfach) negativ geladenen Systemen akkurat zu bestimmen. In dieser Arbeit wird die neue Methode CAP/Sigma^(2) vorgestellt, die aufgrund ihrer Effizienz und einfachen Implementierbarkeit das Potential bietet, eine Standardmethode für die Lösung dieses Problems zu werden. Nicht nur größere Systeme bis zu Trichlorbenzol konnten damit untersucht werden, sogar die Berechnung von komplexen Potentialenergieflächen ist nun möglich, wobei der Imaginärteil die Lebensdauer des metastabilen Systems in Abhängigkeit von den Kernkoordinaten beschreibt. Die Berechnung dieser Flächen für die Anionen von Chlorethen und Tris(boramethyl)amin erlaubte die Überprüfung von theoretisch getroffenen, universellen Vorhersagen über neuartige Phänomene bei der vibronischen Wechselwirkung von Resonanzzuständen. Für nicht-entartete, wechselwirkende Zustände fand ich, dass im Gegensatz zu der bei elektronisch stabilen Zuständen auftretenden konischen Kreuzung hier zwei komplexe Durchschneidungspunkte auftreten und die Real- bzw. Imaginärteile der Energie sich sogar entlang eines ganzen Saumes schneiden. Auch bei entarteten Resonanzzuständen zeigte der Imaginärteil der Energie eine deutliche Abhängigkeit von der Molekülstruktur, ähnlich der des Realteils.
Die Eigenschaften des überkritischen Kohlendioxids, wie z. B. die Mischbarkeit sowohl mit Gasen als auch mit organischen Reaktanden, sollte sich besonders für katalysierte Reaktionen zwischen festen/flüssigen und/oder gasförmigen Reaktionspartnern eignen, insbesondere auch wegen der günstigen Stofftransporteigenschaften von überkritischem Kohlendioxid. Eine Eigenschaft des Kohlendioxids, die sein Potenzial als Reaktionsmedium begrenzen könnte, ist die niedrige Polarität, und die daraus resultierende verminderte Löslichkeit von konventionellen, meistens eher polaren, homogenen Katalysatoren. Hauptziel der Arbeit ist die Untersuchung des Einflusses der chemischen Struktur von Liganden auf die Löslichkeit von Komplexen in überkritischem Kohlendioxid, gezeigt an Derivaten des Typs Co2(CO)6[P(Alkyl)n(Aryl)m]2 (n = 0, 1, 2, 3; m = 3–n). Diese Komplexe könnten als Präkatalysatoren für eine Hydroformylierung längerkettiger Olefine in überkritischem Kohlendioxid dienen. Es wurden zunächst Phosphanliganden mit fluorierten Substituenten synthetisiert, weil literaturbekannt war, dass die fluorierten Substituenten einen positiven Einfluss auf die Löslichkeit der Phosphane in überkritischem Kohlendioxid besitzen. Ein Teilaspekt der Synthese fluormodifizierter Phosphanliganden zielte auf den Erhalt der Eigenschaften von Liganden, die essenziell für die Katalyse sind. Es wurden Kobaltkomplexe des Typs Co2(CO)6[P(Alkyl)n(Aryl)m]2 (n = 0, 1, 2, 3; m = 3–n), sowohl mit den in dieser Arbeit dargestellten als auch mit kommerziell erhältlichen Phosphanliganden synthetisiert und charakterisiert. Hierbei wurde gefunden, dass sich manche Komplexe unter erhöhtem Kohlendioxiddruck unterhalb ihres Schmelzpunktes verflüssigen. Dieser Effekt ist für das Komplexderivat mit Tri(n-butyl)phosphan (n = 3) mit einer Differenztemperatur von 85 K zum Schmelzpunkt bei Atmosphärendruck am ausgeprägtesten, während für Triarylphosphan-Komplexe (n = 0) keine Verflüssigung eintritt. Eine Messapparatur zur Löslichkeitsbestimmung in überkritischem Kohlendioxid wurde konzipiert und aufgebaut, die speziell den Anforderungen von Metallkomplexen Rechnung trägt und wahlweise die Messung von festen, flüssigen oder von sich unter Druck verflüssigenden Substanzen gestattet. Die Apparatur erlaubt Messungen bis zu einem Druck von 300 bar, und zu einer Temperatur von 80°C. Die Löslichkeiten von Kobaltkomplexen in überkritischem Kohlendioxid wurden vermessen. Es wurde gefunden, dass für die Löslichkeit von Kobaltkomplexen in überkritischem Kohlendioxid die chemische Struktur des Phosphanliganden eine wesentliche Rolle spielt und sich durch die chemische Modifikation des Liganden die Löslichkeitscharakteristika der Komplexe einstellen lassen. Es wurde gezeigt, dass die Löslichkeit von Metallkomplexen mit Phosphor-ständigen Alkylgruppen höher ist als die Löslichkeit von Komplexen mit Phosphor-ständigen Arylgruppen. Dieser löslichkeitsvermindernde Einfluss in Arylphosphanen lässt sich durch die Verankerung fluorierter Substituenten im Ligandgerüst abschwächen, wobei die Löslichkeit bei den hier untersuchten Komplexen immer noch niedriger ist, als die des nicht fluorierten Komplexes mit Tri-n-butylphosphanliganden. Der Trialkylphosphan-Komplex mit perfluorierter Endgruppe in einer Alkylkette weist die beste Löslichkeit unter allen untersuchten Komplexen auf. Der Verlauf der Löslichkeitsisothermen der Kobaltkomplexe ist jeweils durch die Kohlendioxiddichte bedingt und lässt sich mittels eines thermodynamischen Ansatzes modellieren. Die experimentell bestimmten Daten stimmen sehr genau mit der theoretischen Voraussage dieses Modells überein und zeigen, dass für die Löslichkeit von Kobaltkomplexen in überkritischem Kohlendioxid nicht die Solvatationszahl sondern enthalpische Effekte die entscheidende Rolle spielen. Zusammen mit der Beobachtung, dass sich die in Kohlendioxid sehr gut löslichen Komplexe unter Kohlendioxid-Atmosphäre deutlich unterhalb ihrer Schmelzpunkte verflüssigen, und dass während der Verflüssigung eine Volumenvergrößerung der entstehenden flüssigen Komplex-Phase einsetzt, lässt sich ebenfalls ableiten, dass für die Löslichkeit der Komplexe in überkritischem Kohlendioxid die Solvatationsenthalpie ausschlaggebend sein sollte. Es liegt nahe, dass die Entstehung von Kohlendioxid-Komplex-Aggregaten durch die Kohlendioxid–Philie von Alkyl- und/oder fluor-modifizierten Substituenten des Liganden vermittelt wird. Die Löslichkeitsisothermen der sich während der Messung verflüssigenden Komplexe im Vergleich mit literaturbekannten Löslichkeiten von anderen Übergangsmetallkomplexen weisen jedoch darauf hin, dass die langen, linearen Kohlendioxid-philen Substituenten in der Peripherie der Liganden, höchstwahrscheinlich aufgrund der Wechselwirkung mit Ketten benachbarter Komplexe, löslichkeitshemmend wirken.
Das Ziel der Einzelmolekülexperimente in dieser Arbeit ist, Lösungen auf dem Weg zu einer Einzelmolekül-DNS-Sequenzierung zu finden. Zunächst wird die Frage nach der Ausdehnung des Detektionsvolumens in Relation zur Kapillare mit Hilfe der Fluoreszenzkorrelationsspektroskopie beantwortet. Dazu wird eine Theorie der FCS mit einem ellipsoid-gaussförmigen Detektions-volumen unter der Randbedingung zylindrischer, undurchdringbarer Wände abgeleitet. Die entwickelte Modellfunktion wird gemessenen Korrelationskurven angepaßt. Das Ergebnis ist, daß die Detektionsempfindlichkeit am oberen und unteren Kapillarrand auf etwa 68 %, an den seitlichen Kapillarrändern auf 19 % des Maximalwertes abgefallen ist. Bei den eingesetzten Fluoreszenzfarbstoffen Cy5 und Mr121 ist es mit der entwickelten Ereigniserkennungssoftware demnach möglich, mehr als 99 % der aus der Kapillare austretenden Moleküle zu erfassen. Dank des niedrigen Untergrundsignals und der Rauschunterdrückung durch geeignete Filter ist die Zählrate falsch-positiver Ereignisse mit 7,9E-19 Hz vernachlässigbar. Es wurde ein Verfahren zur elektrophoretischen Selektion einzelner DNS-Stränge erprobt. Die Sequenzierversuche an Modelloligonucleotiden, statistisch markierten PCR-Produkten und an an zwei Basen vollständig markierter DNS ergab mittlere Schneideraten von E. coli-Exonuclease I am Einzelmolekül von 280 Hz bei 3,6 % Markierungsdichte und 3 Hz bei 50 % Markierungsdichte. Es konnte auf einem 99,75 %-Signifikanzniveau nachgewiesen werden, daß die gemessene Sequenz Information aus der abgebauten Sequenz enthält, die erreichte Leselänge betrug 31 Basen. In der vorliegenden Arbeit konnten wichtige Ergebnisse auf dem Weg zur Einzelmolekülsequenzierung erzielt werden, die Steigerung der Leselänge bleibt aber ein wichtiger Bestandteil zukünftiger Forschung.
It was shown that arylbromides bearing electron-withdrawing groups in appropriate positions can be subjected to Sonogashira coupling with terminal alkynes, producing internal alkynes that can now undergo a Michael addition with suitable secondary amines. This coupling-aminovinylation sequence can be performed in a one-pot fashion, providing a straightforward access to push-pull chromophores. By applying acid chlorides instead of arylbromides, it was possible to synthesize ynones that are highly reactive and valuable intermediates. Furthermore, we succeeded in directly converting these building blocks into beta-enaminones, pyrimidines and halofurans in a one-pot three-component fashion.
The dissertation describes work on organoborane/carborane compounds (Chapters 3.1, 3.2, 3.3, 3.5), on the reactivity of 2,3-dihydro-1,3-diborolyl complexes of ruthenium (3.4), and on aminoborane derivatives (3.6). In Chapter 3.1, a one-pot synthesis of 1,6-diiodo-2,3,4,5-tetracarba-nido-hexaborane(6) derivatives (nido-(RC)4(BI)2, R = Et, Me, Ph, 5a-c) is reported, involving disubstituted alkynes and BI3 (in 1:1 ratio) and NaK2.8 at low temperature. Whereas the reaction of 3-hexyne, BI3 (2 equiv.) and NaK2.8 at r.t. affords a mixture of 5a, nido-(EtC)4(BI)4 (4) and closo-(EtC)2(BI)5 (6). A possible mechanism of the formation of 5a is proposed and studied. The reactivity of 5a towards various nucleophiles has been investigated. In most cases, the substitution occurs regiospecifically at the basal boron atom. Replacement of the ‘inert’ apical iodine is realized by a Pd(0)-catalyzed Negishi-type cross-coupling, as demonstrated by the synthesis of apically alkynyl-substituted nido-(RC)4(BC2Ph)(BC2R) (R = SiMe3, Ph, 5q,r). A series of linked clusters with different types of linkages (via B–C bond, a C6H4C6H4 unit, a C2(CH2)4C2 unit, and an oxygen atom) are obtained. In Chapter 3.2, treatment of the nido-2,3-Et2C2B4H42- dianion with the reagents BX3 (X = Br, I) and PhC2Bcat lead to apically functionalized closo-1-R-2,3-Et2C2B5H4 derivatives (19a-c). A more efficient pathway is developed by the Pd-catalyzed cross-coupling reactions of 19b with R’C2ZnCl to give closo-1-C2R’-2,3-Et2C2B5H4 (R’ = SiMe3, Me, tBu, 19d-f). The reac- tions of the carboranyl-acetylenes with Co2(CO)8 and CpCo(C2H4)2, respectively, afford dicobaltatetrahedrane compounds 21c,d and CpCo(cyclobutadiene) complex 23. In Chapter 3.3, a series of C-boryl-o-carborane derivatives are reported by reacting dilithio-o-carborane and the corresponding aminochloroboranes, respectively. In Chapter 3.5, the unprecedented transformation of 1,3-diiodo-1,3-diborole 37d into the known 2,3,4,5,6-pentacarba-nido- hexaborane(6) cation (63+) is observed. A possible mechanism for its formation is proposed. In Chapter 3.4, the long-sought crystal structure of the (pentamethylcyclopentadienyl)(2,3-dihydro-1,3-diborolyl)-ruthenium derivative 35b is described. It finally confirms the folding along the B…B vector (40.7º) which is similar to the iron analog (41.3º). DFT calculations (by Dr. I. Hyla-Kryspin) on the electronic structures of the model sandwiches Ru (35) and Fe (36) indicate that the folding of the 1,3-diborolyl ligands is of electronic origin, and the parent compounds 35 and 36 with a folded 1,3-diborolyl ligand are more stable in energy (24.5 and 24.9 kcal/mol for Ru and Fe structures, respectively) than 35’ and 36’ with a planar ligand. The reactivity of 35 is studied with respect to insertion of terminal alkynes into its C3B2 heterocycle which results in novel 18 VE ruthenocene analogs Cp*Ru(C5B2) (38) with seven-membered 4-borataborepines as ligands. Additionally, boratabenzene complexes 39 and triarylbenzene species (in some cases) are identified as byproducts, the formation of 39 is a result of elimination of one boranediyl moiety [:BR2] from the intermediate 4-borataborepine complexes. The 4-borataborepine functions as 6e ligand and exhibits a reduced folding along the B…B vector (folding angle = 12.5º in 38a, 26º in 38b, and 15.2º in 38c) compared with 40.7º in 35b. The boratabenzene complexes 39f,g are formed as the main products in the reactions of 35a and disubstituted alkynes (3-hexyne and di-p-tolylacetylene, respectively). The comparative study on the reactivity of the [(1,3-diborole)RhCl]2 dimer 48 with PhCH2C2H is carried out, in which the cyclotrimerization occurs to give (1,3-diborolyl)Rh(arene) 49. The complex reaction of 35a with allylchloride in hexane affords a mixture of products, one is the novel complex 58 [Cp*Ru(C3B2Me5)(RuCp*)n] (n > = 2). Its identity and formation mechanism are not yet clear, however, the results from MS studies and two independent but only partially solved X-ray diffraction analyses indicate that it has a stack of ruthenium atoms with bridging Cp* and 1,3-diborolyl ligands. The stacks are along a threefold axis which would be consistent with either extensive disorder or a tripling of the crystals. In Chapter 3.6, the reactivity of (Me2N)2B4[B(NMe2)2]2 (70) with a rhombohedral B4 unit is studied, and some pyrrolidinoborane derivatives are prepared for new cyclo or polyhedral boranes.
Der Inhalt der vorliegenden Arbeit lässt sich unter dem übergeordneten Thema „Synthese elongierter Diaza-p-Donor Cavitäten“ einordnen. Die Verbindungsklasse der elongierten Diaza-p-Donor Cavitäten stellt eine Weiterentwicklung der in der Arbeitsgruppe Gleiter untersuchten monocyclischen und bicyclischen Diaza-p-Donor Systeme dar. Thematisch kann man die Arbeit in zwei organischen-präparative Teile untergliedern. Der erste Teil beschäftigt sich mit der Synthese der neuartigen p-Donor Cavitäten. Aus der Klasse der dreifachverbrückten, elongierten Diaza-p-Donor Cavitäten wurde die Synthese der bicyclischen Systeme 48, 53 und 59 untersucht, wobei die Struktur von Verbindung 53 röntgenstrukturanalytisch aufgeklärt werden konnte. Bei den Verbindungen 48, 53 und 59 handelt es sich um eine neue Verbindungsklasse bicyclischer Diaza-Butadiin-Systeme, die sowohl Aromaten als auch Heteroaromaten beinhalten. Als Vertreter der zweifachverbrückten elongierten Diaza-p-Donor Cavitäten wurden die monocyclischen Verbindungen 37 und 43 synthetisiert. 37 und 43 stellen eine neue Gruppe von Diaza-Butadiin-Monocyclen dar. Die Verbindungen 48, 53, 37 und 43 konnten durch tripodale bzw. dipodale Alkin-Alkin-Kupplung hergestellt werden. 59 war ausgehend von 22 in einer siebenstufigen Synthese zugänglich. Bei den im Rahmen der Arbeit dargestellten Verbindungen 21, 25, 26 und 31 handelt es sich um acyclische elongierte Diaza-p-Donor Cavitäten. Darüberhinaus wurde die offenen elongierten Aza-p-Donor Cavitäten 67, 68 und 69 synthetisiert. Für die synthetisierten p-Donor-Systeme war zunächst die Darstellung der endständigen Amine und Bromide 4, 5, 11, 12, 16, 17, 64 und 65 notwendig. Diese wurden über Dreikomponentenkondensationen zu den tertiären Aminen 18, 22, 27, 34, 39, 45, 49 und 66 umgesetzt. Ausgehend von den tertiären Aminen waren die elongierten Diaza-p-Donor und Aza-p-Donor Cavitäten durch Reaktionssequenzen von Iodierung, Sonogashira-Reaktion, Entschützung und Alkin-Alkin- bzw. Alkin-Aromat-Kupplung zugänglich. Im zweiten Teil der Arbeit wurden die Komplexierungseigenschaften der synthetisierten -Donor-Systeme untersucht. Dabei konnten die einkernigen Silberkomplexe 49∙Ag+, 66∙Ag+, 67∙Ag+, 68∙Ag+ und 69∙Ag+ sowie die zweikernigen Silberkomplexe 21∙Ag2OTf+, 26∙Ag2OTf+ und 31∙Ag2OTf+ detektiert werden. Der Komplexierungsversuch von 25 führte ebenfalls zu einem einkernigen Silberkomplex. Die Silberkomplexe der p-Donor Cavitäten 49, 67 und 21 konnten isoliert und NMR-spektroskopisch untersucht werden. Die Struktur des Silberkomplexes 49∙Ag+ konnte röntgenstrukturanalytisch aufgeklärt werden. Bei dem Silberkomplex 49∙Ag+ handelt es sich um den ersten Thiophen--Donor Komplex mit Silber. Es ist darüber hinaus der erste synthetisierte -Prismand, in dem anstelle eines Benzols ein Thiophen als p-Donor wirkt.
In Kapitel 2 wird über die Synthese und die Eigenschaften von verschiedenen vier-, fünf- und sechszähnigen Bispidinliganden berichtet, welche eine rigide Struktur besitzen und durch zweifache Mannich-Kondensation aus den entsprechenden Aldehyden und Aminen dargestellt wurden. In Kapitel 3 wird über die Selektivität und Stabilität von Bispidinkomplexen diskutiert. Durch potentiometrische Messungen der Stabilitätskonstanten wurden mit makrocyclischen Liganden vergleichbare Stabilitäten erhalten. Interessant hierbei ist, dass ein Verhalten gemäß der Irving-Williams Reihe nicht auftritt, sondern die Stabilitäten (KML) die Reihenfolge Zn(II)>Cu(II)>>Co(II)>Ni(II) befolgen. Dies wird auch durch Kraftfeldrechnungen vorausgesagt, welche zeigen, dass kurze Metall-Donor-Abstände zu Spannung im Liganden führen und dass es keine Größenselektivitäten für große Metallionen gibt. Weiterhin wurden pKs-Werte von 5 Arten von Bispidinliganden bestimmt, wobei der “proton sponge“ Effekt beobachtet werden konnte. Der erste logKs-Wert aller Liganden wurde im Bereich 11,2 bis 12,2 gefunden. Die Liganden können in zwei Gruppen eingeteilt werden. Zur ersten Gruppe gehören N2Py2, N2Py3, N2Py3u und 6Me-N2Py2, welche einen Methylsubstituten am N7 haben; in die zwei Kategorie fallen N2Py3o und N2Py4, welche mit einer Picolylgruppe am N7verbunden sind. In Kapitel 4 wird über die Oxidation von Bispidinkomplexen berichtet. Ihre Kristallstrukturen zeigen eine oktaedrische Koordinationsgeometrie. Wird der Co(III) N2Py2-Komplex durch Oxidation mit H2O2 dargestellt, verschwindet die Methylgruppe. Dies wird jedoch nicht bei anderen Co(III)-Komplexen beobachtet, wie z.B., N2Py3u und N2Py3o. Diese Reaktivität ist vermutlich ein intramolekularer Effekt des Kobaltzentrums. Die Oxidation von Co(II) Bispidinkomplexen (Bindungsabstände von Co(II)-N: 2,13-2,21Å) führt zu einer Verkürzung der Co-N Abstände(Co(III)-N: 1,93-2,05Å) Die Oxidation of Co(II) Bispidinkomplexen mit H2O2 wurde spektrometrisch verfolgt. Das Spektrum zeigt eindeutig die Bildung von Co(III)-Komplexen an. Die Reaktion ist pseudo-erster Ordnung. In Kapitel 5 wird über die Synthese von V(IV) Komplexen mit einem fünfzähnigen Bispidinliganden (N2Py3o) und dessen Oxidation bereichtet. Der Vanadium (V) Komplex besitzt eineη2-side-on Peroxo-Einheit. Der dritte Pyridindonor des Picolylarms ist nicht koordiniert. Die Oxidation von Vanadium (IV) zu Vanadium (V) wurde erfolgreich mit Hydrogenperoxid durchgeführt und spektrophotometrisch untersucht.
Das Ziel dieser Arbeit bestand darin, die Koordinationschemie einer neuen Klasse von tripodalen Liganden auf der Basis von Triphenylamin-Derivaten zu untersuchen. Das besondere an diesem Ligandensystem ist das Vorhandensein eines Brückenkopf-Triphenylamin-Stickstoffatoms, das ein schwacher Donor ist und dessen Koordinationsfähigkeit stark von den elektronischen Eigenschaften des Metallions abhängt und entsprechend beeinflussbar ist. Der in dieser Arbeit verwendete tripodale Ligand 2,2’,2’’-Nitrilotribenzoesäure (H3L1) ist ein Triphenylaminderivat mit einem zentralen Brückenkopf-Stickstoffatom, als potentiell axialem Donor und drei Carboxylatgruppen, die äquatorial an Metallionen koordinieren können. Somit kann sich ein relativ stabiler Komplex bilden, der aber noch über 1-3 freie Koordinationsstellen verfügt, was unter anderem für katalytische Anwendungen interessant ist. Ausgehend von Anthranilsäuremethylester und 2-Iodbenzoesäuremethylester wurden die Triphenylaminderivate über Ullmann-Stickstoff-Arylierungen synthetisiert. Diese wurden in ortho-Position mit Säurechlorid-, Carbaldehyd und Aminofunktionen funktionalisiert und spektroskopisch sowie kristallographisch charakterisiert. Im Mittelpunkt dieser Arbeit stand die Koordinationschemie der 2,2’,2’’-Nitrilotribenzoesäure (H3L1). Durch Reaktion von H3L1 mit Cobalt(II)-, Kupfer(II)- und Zink(II)-Ionen in Gegenwart einer Base wurden 1:1 Komplexe erhalten, in denen das Metallion trigonal-bipyramidal koordiniert ist. Bei Reaktion von H3L1 mit Eisen(II)-, Kupfer(II)- und Nickel(II)-Ionen liegen dimere Strukturen vor. Bei Umsetzung mit den “härteren“ Eisen(III)-Ionen wurde in Acetonitril ein dimerer Eisenkomplex [Fe2(L1)2(µ-O)]2- erhalten, in dem die Metallionen fünffach koordiniert und über eine Oxobrücke verbunden sind. Dagegen bildet sich bei Umsetzung von H3L1 mit Eisen(III)-Ionen in Wasser ein monomerer, oktaedrischer Komplex, in dem das Stickstoffatom nicht mehr an das Metallion koordiniert. In den tripodalen Komplexen [M(L1)]- wird eine unerwartet große Variation der Bindung des Metallions zu dem Brückenkopf-Stickstoffdonor beobachtet (M-N: 2.09 – 3.29 Å), so dass die Koordination je nach Bindungsabstand in “On“, “Off“ und “Intermediate“ eingestuft werden kann. Der erhaltene Eisenkomplex von H3L1 ist ein hocheffektiver Redoxkatalysator für die H2O2-Oxidation von Hydrochinon zu Benzochinon. Die röntgenographisch abgeleiteten Strukturen der Komplexe von H3L1 konnten auch in Lösung über UV/Vis-Spektroskopie bestätigt werden. Im weiteren konnte gezeigt werden, wie die M-N-Bindung durch externen „chemischen Input“ wie Coliganden, Lösungsmittel oder Veränderung des pH-Wertes beeinflusst werden kann. Im Falle der Eisenkomplexe ist sogar ein “Schalten“ zwischen “Intermediate“- und “Off“-Zustand möglich. Mit “härteren“ Metallionen wie Calcium(II) und Gadolinium(III) konnten oligomere Carboxylatstrukturen beschrieben werden, in denen entweder Dimere vorlagen oder wie im Fall von Calcium(II) eindimensionale, kettenartige Strukturen ausgebildet werden, eine Koordination des Brückenkopf-Stickstoffatoms wurde nicht beobachtet. Mit Nickel(II)-Ionen wurde neben der dimeren Struktur [M(L1)]22- auch eine hexamere Struktur [Ni6(L1)4(µ3-OH)2(µ-OH2)2]2- erhalten, in der vier Liganden und sechs Nickelatome jeweils über Sauerstoffatome von Wasser- bzw. Hydroxidmolekülen verbrückt sind und eine dicubanartige Struktur ausbilden. Magnetische Untersuchungen dieses Nickelclusters zeigen ferromagnetische Wechselwirkungen zwischen den Nickelatomen. Im weiteren konnte ausgehend von 2,2’,2’’-Nitrilotribenzoesäurechlorid bzw. 2,2’,2’’-Nitrilotribenzaldehyd durch Umsetzung mit Tris(2-aminoethyl)amin (tren) die homotopen Kryptanden L2 und L3 erhalten werden. L2 zeigt eine deutliche Fluoreszenz, zeigt aber kaum Neigung zur Wechselwirkung mit Metallionen. L3 dagegen lagert in den Hohlraum selektiv Kupfer- und Zinkionen ein, was UV/Vis-spektroskopisch und für Zink kristallographisch belegt werden konnte. Des weiteren wurden größere, ditope Makrocyclen synthetisiert, die bis zu zwei Metallionen komplexieren können. Ausgehend von 2,2’,2’’-Nitrilotribenzaldehyd und verschiedenen Diaminen bzw. 2,2’,2’’-Nitrilotriphenylamin und verschiedenen Dialdehyden konnten sechs Makrocyclen L4 - L9 hergestellt werden. Durch Variation der Spacer (Dialdehyde und Diamine) können die Größe der Makrocyclen und damit ihre Koordinationseigenschaften gesteuert werden. Auffällig war dabei das Koordinationsverhalten von L4 mit Kupferionen: der Makrocyclus bildet mit Kupfer(I)-Ionen einen zweikernigen Komplex und mit Kupfer(II)-Ionen, auch wenn diese im Überschuß eingesetzt werden, einen einkernigen Komplex. Der zweikernige Kupfer(I)-Komplex von L4 konnte mittels Röntgenstrukturanalyse charakterisiert werden und enthält zwei Kupfer(I)-Ionen mit einem relativ kurzen Metall-Metall-Abstand von 2.59 Å.
Um die photochemisch induzierte Oxidation von Silizium zu untersuchen, wurde in dieser Arbeit eine Messapparatur für in situ und Echtzeit-Diagnose geplant und aufgebaut. Der Prozess wurde durch die direkte Bestrahlung der Probenoberfläche mit einem Fluorlaser oder einem ArF-Laser induziert. Durch die hohe Photonenenergie dieser UV-Laser von 7,9 eV Fluorlaser) bzw. 6,4 eV (ArF-Laser) wurden bei diesen Experimenten Moleküle in der Gasphase dissoziiert, wobei atomarer Sauerstoff erzeugt wurde. Dieser war für die Oberflächenoxidation verantwortlich. Es wurden Oxidationsatmosphären mit verschiedenen Konzentrationen an O2 oder N2O verwendet und die Probentemperatur wurde über einen großen Bereich variiert. In den Oxidationsexperimenten wurde das Wachstum ultradünner Oxidfilme (< 6 nm) auf H-terminierten Siliziumoberflächen untersucht. Dabei kamen amorphe Siliziumfilme, Si(100)-Einkristalle und Si(111)-Einkristalle zum Einsatz. Der Oxidationsprozess wurde mit FTIR-Spektroskopie und mit spektroskopischer Ellipsometrie in Echtzeit charakterisiert. Mittels FTIR-Spektroskopie konnte die Abnahme der H-Terminierung und das Wachstum der Oxidstruktur beobachtet werden. Für die Modellierung der ellipsometrischen Messungen wurde ein 3-Lagen-Modell entwickelt. Zwischen dem amorphen Siliziumdioxidfilm (a-SiO2) und dem Siliziumsubstrat enthält dieses Modell eine Grenzschicht. Diese setzt sich aus einer ultradünnen Lage aus dichtem, amorphem Silizium (a-Si) und aus einer Suboxidlage (SiOx, x = 0..2) zusammen. Der Aufbau der Oxidstruktur auf den drei verschiedenen Siliziumsubstraten wurde untersucht. Dabei stellte sich heraus, dass die Oxidationsbedingungen wenig Einfluss auf die Oxidstruktur hatten. Vielmehr war der Aufbau des Oxids charakteristisch für das verwendete Substrat. Auf den amorphen Siliziumfilmen wuchs direkt ein a-SiO2-Film ohne die Ausbildung eine Grenzschicht. Im Gegensatz dazu bildete sich auf den Si(100)-Substraten eine Grenzschicht aus, die aus einer (0,1 ± 0,1) nm dicken dichten a-Si-Lage und aus einer (0,40 ± 0,15) nm dicken SiOx-Schicht (x = 0,15 ± 0,10) besteht. Die dickste Grenzschicht wurde auf den Si(111)-Oberflächen gemessen. Sie setzte sich aus einer (0,2 ± 0,1) nm dicken dichten a-Si-Lage und aus einer (0,85 ± 0,25) nm dicken SiOx-Schicht (x = 0,40 ± 0,15) zusammen. Es wurde der Schluss gezogen, dass die Aufgabe der Grenzschicht darin besteht, die geordnete, kristalline Struktur des Substrats mit der amorphen Struktur des Oxids zu verbinden und Spannungen bei diesem Übergang abzubauen. Es zeigte sich, dass sich die Grenzschicht in der ersten Oxidationsphase aufbaute und sich während des weiteren Oxidwachstums kaum mehr änderte. Die Kinetik des SiO2-Filmwachstums hängt von den Reaktionsbedingungen ab. Es hat sich herausgestellt, dass die Oxidation bei hohen Drücken (~ 1000 mbar) stark gehemmt war. Mit höheren Temperaturen (32 °C - 300°C) nahm die Wachstumsrate zu, was bei einem diffusionskontrollierten Prozess zu erwarten war. Der Wachstumsverlauf lässt sich mit dem klassischen Deal-Grove-Modell nicht beschreiben. Die Wachstumsrate ist im frühen Stadium des Oxidationsexperiments größer, und die Selbstlimitierung des Wachstums ist bei dickeren Filmen stärker. Unter Berücksichtigung der Rekombination von atomarem Sauerstoff während der Diffusion im Oxid konnte ein Wachstumsmodell erstellt werden, mit dem das Wachstumsverhalten sehr gut beschreibbar ist. Daraus konnte die Aktivierungsenergie für die Diffusion von Sauerstoffatomen in a-SiO2 bestimmt werden (ED = 0,15 eV). Dieser niedrige Wert erklärt, warum es mit atomarem Sauerstoff möglich ist, selbst bei geringen Konzentrationen und niedrigen Temperaturen SiO2-Filme zu erzeugen. Es wurden Versuche durchgeführt, in einer ozonhaltigen Atmosphäre die Oberflächenoxidation photochemisch zu induzieren. Aufgrund des hohen Drucks und der Rekombination von Sauerstoffatomen mit Ozon konnte jedoch kein photoinduziertes Oxidwachstum beobachtet werden.
Im Rahmen dieser Arbeit sind 2,5-Dihydroxy-p-benzochinone mit langkettigen Alkyl- und Alkoxy-Substituenten in der 3,6-Position synthetisiert worden. Das Koordinationsverhalten dieser doppelt-bidentaten Liganden wurde durch Umsetzungen mit Metall-Templaten von Co(II)-, Ni(II)- und Pd(II)-Ionen mit Phosphan-Abschluss-Liganden untersucht. Der Einfluss der Seitenketten auf die physikalisch-chemischen und strukturellen Eigenschaften der resultierenden Komplexe wurde mit Hilfe von IR-, UV/Vis/NIR-, NMR-spektroskopischen und elektrochemischen Methoden sowie der Röntgenstrukturanalyse aufgeklärt. Interessanterweise bilden die zweikernigen Ni-Komplexe [(triphos)Ni(II)(µ-C6O4R2)2-Ni(II)(triphos)]2+ (R = H, Cl, octyloxy) in Lösung ein temperaturabhängiges Gleichgewicht zwischen einem diamagnetischen Isomer und einer paramagnetischen Spezies, wobei der paramagnetische Anteil in der Reihe octyloxy < H < Cl zunimmt. Die Koordinationsgeometrie der Isomere wurde röntgenspektroskopisch bestimmt.
The proceeding evolution in molecular biology and biochemistry led to groundbreaking results in the recent years, like the mapping of the human genome. The consequence of the rising knowledge of biological structures and mechanism is that gradually smaller and infrequent units, which are not resolvable by common methods anymore, are subject to investigation. In principle there are two question in the structural exploration of biological systems: Where are the single components localized, or what distances do they have in respect to each other, and from which or how many units are they composed? To solve these questions single-molecule spectroscopy is an excellent tool. The localization of dye-labeled biomolecules is easy, as long as the distance between the single fluorophores exceeds the optical diffraction limit of about 200 nm. For distances between 1 and 10 nm the FRET-effect can be exploited. In the intermediate range of 10 to 200 nm, the so-called resolution gap, only few methods for distance determinations are available, which are usually technically demanding and limited to two dimensions. Since many biological relevant molecules, for example biomolecular machines, are exactly in this order of magnitude, it is of major importance to have a simple 3-dimensional method at hand, which closes the gap. For this purpose an algorithm based on confocal imaging microscopy has been developed, which facilitates the separation of colocalized dyes by their fluorescence lifetimes and spectral characteristics. The accuracy and applicability of the method was in this work using biological calibration compounds. Therefore DNA molecules of different lengths, whose double-stranded backbone is known to be very rigid, were terminally labeled with the dyes Bodipy 630 and Cy 5.5 and immobilized in a 3-dimensional matrix, a cell-like but homogenous inclusion reagent. Comparison with "worm-like chain" model calculations showed that the measured lengths were in good agreement with the model. Furthermore, measurements in cells were accomplished, which affirmed the suitability of the method in biological environment. Beside the localization of biomolecules more and more quantitative investigations of complex cellular units come to the fore. Often the matter is not exclusively anymore the determination of various subunits, which can be discriminated against each other by different dyes, but rather the detection of identical molecules, which assemble or are generated within a cell compartment. For example the read-out and transduction of the genetic information by polymerases, the transcription, takes place in so called transcription factories. A typical HeLa cell contains about 8.000 of such 40 to 80 nm sized centers each containing on average 8 polymerase II enzymes. The reason for the accumulation, as well as the exact number of polymerases, could not be determined so far due to a lack of suitable techniques. However, for the comprehension of the cell function it is of great importance to study these basic units. The first step in this direction, the counting of polymerase II molecules in transcription sites, ought to be conducted in the second part of this work. To be able to quantify colocalized molecules, the analysis of interphoton times deduced from antibunching experiments can be used. Therefore dyes are located in a microscopic image, subsequently singly positioned in the laser focus and the fluorescence is collected until photodestruction. Especially the carbopyronine derivatives Atto 620 and Atto 647 turned out to be best suitable for the experiments because of their high photostability and emission rate. To investigate the applicability of the method in cellular environment, dye labeled oligomers consisting of 40 thymines were incorporated into cells. It was shown that these units selectively and partly multiply hybridize to the up to 200 basepair long adenosine ends of mRNA. By coincidence it was possible to analyze up to four molecules in a single image spot. To reduce the density of the transcription centers for imaging and to enable molecule counting for the 3.000 transcription factories per nucleus, so called "cryosections", cell slices with a thickness of 100 nm, were introduced. The simplest method to label polymerase II molecules uses specific dye labeled antibodies, which singly bind to the polymerases. A fundamental requirement for the success of the experiment is a stoichiometric labeling of the antibodies with the dyes, i.e. no multiply- or unlabeled compounds are allowed to be present. Therefore a new method was developed, which allows preparing one to one labeled proteins and quantum dots by the introduction of an affine group at the dye. It could be shown that the antibodies selectively bind to their targets and first experiments with these probes towards the success of the experiment could be initiated.
Durch die Reaktion der Silanide Tris(trimethylsilyl)silykalium und {Methylbis[trimethylsilyl]silyl}lithium mit niedervalenten Galliumhalogeniden konnten die dreiwertigen Galliumsilanide Ga{Si(SiMe3)2Me}3, [Ga{Si(SiMe3)2Me}3I]- sowie das Hexagallan [Ga{Si(SiMe3)2Me}]6 isoliert werden. Die Stabilisierung dieses hexameren Gallium(I)silanids wurde durch die Verwendung der maßgeschneiderten Silanide erst ermöglicht. Die Einkristall-Röntgenstrukturanalyse zeigt für den Hexagallan-Cluster eine Jahn-Teller-verzerrte oktaedrische Struktur auf. Mit nur sechs Gerüstelektronenpaaren wäre nach dem Wade-Mingos-Konzept auch ein überkappter trigonal-bipyramidaler Cluster zu erwarten gewesen. Weiterhin konnte das Galloxan [Ga{Si(SiMe3)2Me}O]6 das als oxidierte Form des o. g. Hexagallans, in einer sog. �Trommelstruktur� vorliegt, sowie eine weitere käfigartige Galliumoxoverbindung (Me3Si)3SiGa(OtBu)3K2Si(SiMe3)3 mittels Einkristall-Röntgenstrukturanalyse charakterisiert werden. Natrium/Gallium-Oligosiloxane, die ebenfalls komplexe, käfigartige Strukturen aufweisen, konnten ebenfalls dargestellt werden.
Nachdem Vanadium in verschiedenen Organismen als essentieller Bestandteil unter anderem in Haloperoxidasen nachgewiesen werden konnte, stieg das Interesse an Struktur und Funktion vanadiumabhängiger Enzyme. Wasserstoffbrückenbindungen spielen im aktiven Zentrum eine wichtige Rolle, sowohl bei der Fixierung einer Vanadat-Gruppe als auch bei der Aktivierung des Peroxid-Substrats. Synthetische Modellverbindungen für das Zusammenwirken von Metallionen und funktionellen Gruppen bei der Hydrolyse von Phosphosäureestern wurden von der Arbeitsgruppe Krämer bereits beschrieben. Speziell in vanadiumabhängigen Haloperoxidasen wird die heterolytische Spaltung von koordiniertem Peroxid durch die Wasserstoffbrücke zu einem Imidazol-Rest begünstigt. Das Ziel dieser Arbeit bestand darin, Koordinationsverbindungen von Vanadium zu synthetisieren, die Modellcharakter für die Struktur des aktiven Zentrums und die katalytische Funktionsweise dieser Enzyme besitzen. Ausgehend von 6-Phenyl- und 6-(2-Hydroxyphenyl)-salicylaldehyd sowie Bisalicylaldehyd wurden neue Salicylaldimin-Liganden und deren pentakoordinierte mononukleare Oxovanadium(V)-Komplexe mit verzerrt tetragonal-pyramidaler Umgebung synthetisiert. Die Komplexe sind bifunktionell und verfügen neben der mononuklearen Lewis-aciden Metalluntereinheit über distale Hydroxyfunktionen, die als Brönsted-Säuren mit dem Koordinationszentrum im Festkörper und in Lösung in Wechselwirkung treten. Die Komplexe 11 und 13 stellen geeignete Strukturmodelle für das aktive Zentrum vanadiumabhängiger Haloperoxidasen dar. Die Komplexe sind in der Lage, die Peroxid-vermittelte Oxygenierung von Sulfiden zu Sulfoxiden zu begünstigen, wobei sich die Systeme mit NO2-Liganden-Donorumgebung deutlich von denjenigen mit N2O-Umgebung abheben. Im Vergleich mit 14 ist die durch den hydroxyfunktionalisierten Komplex 13 katalysierte Oxygenierung von Ethylphenylsulfid etwa doppelt so schnell, die Hydroxyfunktion hat also eine aktivierende Wirkung auf die Katalyse. Die Wechselwirkung der distalen Hydroxyfunktionen mit der pentakoordinierten Vanadium-Einheit über intramolekulare Wasserstoffbrückenbindungen wurde anhand der Oxovanadium(IV)- sowie Kupfer(II)-Salenkomplexe durch Vergleich ihrer Redoxpotentiale bestätigt. Im Vergleich zu 11-18 waren die Vanadium-Verbindungen 19-22 jedoch deutlich weniger aktiv in der Oxygenierung von Sulfiden. Siderophorartige, catecholfreie Liganden mit drei Biphenyluntereinheiten wurden durch Reaktion von Phenyl-substituierten Salicylaldehyden mit Tris(2-aminoethyl)-amin dargestellt. Der Ligand H3L13 kann Metallionen sechzähnig über drei Iminostickstoff und drei Phenolatsauerstoffdonoren koordinieren. Dies wurde durch die Kristallstruktur des Eisen(III)-Komplexes 28 von H3L13 bestätigt. Wiederum werden intramolekulare Wasserstoffbrücken zwischen koordinierten Phenolat- und freien Phenol-Hydroxygruppen beobachtet.
Due to the importance of alpha-olefin oligomers as intermediates and polymer building blocks for the chemical industry, new single-site catalysts systems that are more active and more selective are constantly being sought. Inserted in this context, we investigated the syntheses of novel organic ligands and the respective metal complexes, to be applied for ethylene and propylene oligomerisation. A group of tridentate imino-ligands was synthesised, which includes the 2,6-bis(imino)pyridines 1-2, the 2,6-diacetyl-monoiminopyridine 3, the iminophosphines 16, and the imidazo[1,5-a]pyridines 23c and 24a, and others, obtaining a range of different N,N,N- or N,N,O- or N,N,P-ligands through variation of the coordinating backbone and of the substituents. The corresponding iron(II) complexes were then prepared and tested for the ethylene oligomerisation in the presence of MAO as co-catalyst. The 2,6-bis(imino)pyridyl-, the 2,6-diacetyl-monoiminopyridyl-, and the iminophosphine iron(II) complexes 5-7, 17 were active catalysts and gave only linear olefins. Furthermore, different classes of bidentate ligands for nickel(II) complexes were synthesised, which are easily tuneable in their steric and electronic properties; for instance the imidazo[1,5-a]pyridines 23a-b and 24b-f, the 3-aminoacrylates 28, 29, and 31, the 3-aminoiminoacrylates 35 and 37. In particular, the syntheses of the differently substituted 3-aminoiminoacrylates required to be developed and optimised according to the different substituents at the acrylic backbone and at the aryl rings. The bidentate N,N-ligands 23a, 24b-d, 40, and 42 were used in their neutral form to yield the corresponding nickel(II) dibromide complexes. The rest of the ligands was deprotonated with sodium bis(trimethylsilyl)amide to yield their monoanionic form that next reacted with [(PPh3)2Ni(Mes)Br]. Two different classes of neutral nickel(II) complexes were obtained: in one class (45 and 46) the ligands actually coordinate as monodentate through their CN-group, while in the latter class of complexes (47-50 and 53) the ligands coordinate as bidentate chelate to the nickel centre. The nickel complexes tested for ethylene oligomerisation gave the best results in the presence of MAO as co-catalyst. Due to the chain-running at the nickel centre, not only linear olefins were formed, but also branched isomers. The propylene dimerisation tests gave the best results with EASC as co-catalyst, and the main products generally consisted of dimers, the fraction C6 always being about 90%. Among the dimers, methylpentenes were the main products in most cases, followed by linear hexenes and small amounts of dimethylbutenes.
In dieser Arbeit wurde die Wechselwirkung zwischen den AP-1-Komponenten c-Fos und c-Jun mit der so genannten �Zwei-Hybrid�-Fluoreszenzkreuzkorrelations-spektroskopie in vivo nachgewiesen. Des Weiteren wurden die Mobilität und die Dynamik dieses Komplexes in lebenden Zellen charakterisiert. AP-1 (Aktivator Protein-1) ist ein Transkriptionsfaktor, dessen Komponenten nur als Dimere ihre Funktion ausüben können, wobei c-Jun und c-Fos die Hauptkomponenten sind. Mit der FCCS können Wechselwirkungen zweier Fluorophore aufgrund ihrer korrelierten Bewegung nachgewiesen werden. Das Prinzip der FCCS beruht auf der gleichzeitigen Anregung und Detektion zweier Fluorophore in einem konfokalen Mikroskopaufbau. Die Intensitätsfluktuationen in beiden Kanälen werden über Kreuz korreliert. Zur Kreuzkorrelation tragen nur Teilchen bei, die in beiden Kanälen gleichzeitig ein Signal erzeugen, d.h. die beide Farben simultan durch das Beobachtungsvolumen tragen. In der �Zwei-Hybrid�-FCCS werden als Fluorophore ausschließlich autofluoreszierende Proteine (AFP) statt organisch-chemischer Farbstoffe eingesetzt. Dies hat den großen Vorteil, dass die Proteine nicht aufgereinigt, dann chemisch markiert und schließlich in die Zelle mikroinjiziert werden müssen, sondern direkt von der Zelle als Fusionsprotein in vivo exprimiert werden und ohne weitere Eingriffe in die Zelle gemessen werden können. Unter den getesteten AFPs (EYFP, ECFP, EGFP, DsRed2, mRFP1 und eqFP611) war das Chromophorpaar EGFP-mRFP1 das einzige, das zum Erfolg führte. Der FCCS-Aufbau wurde in vivo einerseits mit einem Fusionsprotein aus EGFP und mRFP1 als Referenz für 100 % Kreuzkorrelation und andererseits mit den zwei über einen IRES-Vektor getrennt exprimierten EGFP und mRFP1 als Negativkontrolle für fehlende Wechselwirkung kalibriert. Es wurden Fusionsproteine von c-Jun und mRFP1 bzw. c-Fos und EGFP, sowie von deren Deletionsmutanten c-JunDD und c-FosDD, denen die Dimerisierungs- und DNA-Bindungsdomäne fehlte, hergestellt. Während die AP-1 Deletionsmutanten eine Kreuzkorrelationsamplitude von 18 % ± 4 % lieferten, vergleichbar mit der Negativkontrolle von 13 % ± 3 %, zeigte das AP-1-System eine signifikante Kreuzkorrelationsamplitude von 31 % ± 6 %. Im Vergleich dazu lieferte die Positivkontrolle, das Fusionsprotein aus EGFP und mRFP1, eine Amplitude von 45 % ± 4 %. Außerdem zeigte das AP-1-System nur eine langsam diffundierende Komponente, was darauf schließen lässt, dass alle markierten Fos-Jun Dimere an DNA gebunden sind. So konnte mit der �Zwei-Hybrid�-FCCS sowohl die Wechselwirkung zwischen c-Jun und c-Fos als auch die Bindung dieses Komplexes an DNA nachgewiesen werden. Diese Methode eignet sich somit sehr gut, um Protein-Protein-Wechselwirkungen in vivo zu charakterisieren.
Der vorgeschlagene Mechanismus der an Bismutmolybdat-Katalysatoren durchgeführten Oxidation von Propen zu Acrolein (SOHIO-Verfahren) postuliert als Intermediat pi-Allyl-Mo(+V/+VI)-Komplexe in einer sauerstoffreichen Umgebung. Thema der vorliegenden Arbeit ist die Synthese von Verbindungen, die ein solches Intermediat strukturell modellieren können. Die Schwierigkeiten bei der Darstellung solcher Verbindungen liegen in den unterschiedlichen Bindungseigenschaften von weichen pi-Allyl-Liganden und harten Mo(+V/+VI)-Kernen. Zwei unterschiedliche Strategien wurden ausgearbeitet und neue Erkenntnisse bzgl. der Synthese der oben genannten Verbindungsklasse gewonnen. Zum einen wurden pi-Allyl-Mo(+II)-Komplexe, die über eine stabile pi-Allyl-Mo-Bindung verfügen, mit sauerstoffhaltigen Nukleophilen umgesetzt. Zum anderen konnten unter Ausnutzung des Chelat-Effektes hochvalente pi-Allyl-Molybdän-Verbindungen dargestellt werden. So wird die dreistufige Synthese eines bemerkenswert stabilen Komplexes mit einem chelatisierenden pi-Allyl/PPh2-Liganden und einem Mo(+IV)-Kern beschrieben. In ähnlichem Zusammenhang wurde die Verbindung [Li(12-Krone-4)2][MoO2(PO)3] (PO-=2-propenylphenolat) (10) hergestellt, das erste Beispiel eines fünffach koordinierten MoO22+-Komplexes mit einer quadratisch-pyramidalen Struktur.
Die Arbeit umfasst die Synthese Metallkomplex-funktionalisierter Oligonucleotide und Peptidnucleinsäuren und deren Anwendung als Sonden für den sequenzspezifischen DNA-Nachweis. Die Ligation chemisch modifizierter Oligonucleotide (bzw. deren Analoga) am Nucleinsäure-Templat ist ein etabliertes Detektionsverfahren mit hoher Sequenzselektivität, aber geringer Sensitivität aufgrund starker Produkthemmung. Durch Entwicklung einer katalytischen Variante der templatgesteuerten Reaktion konnte die Sensitivität des Verfahrens durch Signalamplifikation gesteigert werden. Dazu wurden terminale Esterkonjugate (Substrate) und Metallkomplexkonjugate (Katalysatoren) von Peptidnucleinsäuren (PNAs) synthetisiert. Die Ester-PNA und die Metallkomplex-PNA wurden am komplementären DNA-Templat in räumliche Nähe gebracht, wodurch die metallkatalysierte Spaltung des Esters stark beschleunigt wurde. Durch den Templateffekt wurde eine Reaktionsbeschleunigung um den Faktor 150 gegenüber der Hintergrundreaktion erzielt. Bei 100fachem Esterkonjugat-Überschuss konnten 35 Umsätze erreicht werden. Eine Fehlbasenpaarung der komplementären DNA erniedrigte die Reaktionsgeschwindigkeit bis zu 15fach. �Molecular Beacons� (Molekulare Leuchtfeuer) sind Oligonucleotid-Sonden mit Haarnadelstruktur, die bei Hybridisierung fluoreszieren, da eine intramolekulare Fluorophor-Quencher-Wechselwirkung unterbunden wird. Im Rahmen der Arbeit wurden �Molecular Beacons� entwickelt, in denen ein Metallkomplex durch koordinative Bindung an den Fluorophor als fluoreszenzlöschende Komponente wirkt. Dazu wurden 3´-Fluorescein und 5´-Ligand modifizierte DNA-Oligonucleotide mit Haarnadelstruktur synthetisiert. Im nicht-hybridisierten Zustand ist die Fluoreszenz der Kupfer(II)-komplexierten Oligonucleotid-Sonden effektiv gelöscht. Durch Hybridisierung mit komplementärer DNA wurde der Metallkomplex vom Farbstoff räumlich getrennt. Dadurch konnte eine 14fache Erhöhung der Fluoreszenz und eine Diskriminierung einer einzelnen Fehlbase um den Faktor 40 erzielt werden. Das Potential dieses neuen Sondentyps liegt in der Möglichkeit, die Stärke der Fluorophor-Quencher-Wechselwirkung abzustimmen, und damit die Hintergrundfluoreszenz zu minimieren und unspezifische, störende Wechselwirkungen zu blockieren.
This thesis presents the first application of the stimulated emission depletion (STED) technique to the field of single-molecule fluorescence spectroscopy. It is demonstrated that fluorescence quenching induced by STED is reversible and can be repeated a large number of cycles on a single molecule. Being ideal point-like probes, single molecules can therefore be used to characterize the resolution of STED microscopes. In a spectroscopic study, two simplifed models of the photophysical processes involved in STED are analyzed and applied to the experimental determination of the stimulated emission cross sections on a single-molecule level. In addition, the STED concept as applied in subdiffraction-resolution microscopy is transferred to fluorescence fluctuation spectroscopy. A successful implementation promises to expand the possibilities particularly of fluorescence correlation spectroscopy (FCS) which is already the most widely used fluctuation technique today but is restricted to concentrations on the nanomolar scale. Reducing the detection volume beyond the diffraction limit could render the micromolar range accessible and could thus open up new applications in the life sciences.
Im Rahmen dieser Arbeit wurden Siliziumdioxidoberflächen funktionalisiert. Die thermische sowie die mechanische und chemische Stabilität der Terminierung mit verschiedenen Alkylsilanen wurde untersucht. Durch eine Kondensationsreaktion von Monochlorsilanderivaten mit Silanolgruppen an der Oberfläche wurden die Gruppen kovalent gebunden. Als Substrat dienten nasschemisch oxidierte Siliziumwafer. Die Reaktionen wurden in Lösung und bei Raumtemperatur durchgeführt. Innerhalb weniger Minuten war die Reaktion abgeschlossen. Die Addition von Alkoholen an die Isocyanogruppe der Isocyanopropyldimethylsilylterminierten Oberfläche wurde mit ATR-FTIR-Spektroskopie verfolgt, ebenso die Degradierung der Terminierung in Wasser durch Ultraschallbehandlung. Methylierte Silylgruppen wurden mit Sekundärionenmassenspektrometrie (SIMS) detektiert. Fluorierte Silanderivate wurden mit Photoelektronenspektroskopie (PES) nachgewiesen. Die thermische Desorptionsspektroskopie (TDS) wurde eingesetzt, um die thermische Stabilität der Terminierungen zu ermitteln. Für vier Terminierungen wird ein Desorptionsmechanismus vorgeschlagen. Die trimethylsilylterminierte Oberfläche ist thermisch sehr stabil. Die Benetzbarkeit der verschieden präparierten Oberflächen wurde mit Kontaktwinkelmessungen verglichen.
Der Mechanismus der Cp2TiMe2-katalysierten intermolekularen Hydroaminierung von Alkinen wurde am Beispiel der Addition von p-Toluidin an 1-Phenylpropin anhand von kinetischen Messungen untersucht. Die im Vorfeld festgestellte Dimerisierung der katalytisch aktiven Spezies konnte durch die Vervollständigung der kinetischen Daten bestätigt werden. Zudem konnte der Mechanismus um einen Ligandenaustausch am Titan erweitert und durch den erfolgreichen Einsatz verschiedener Titanspezies, die als Intermediate des Katalysezyklus angenommen werden, gestützt werden. Neben Titanocenkomplexen konnten auch Halbsandwichkomplexe des Titans, sowie Cp-freie Ti-Komplexe erfolgreich in der intermolekularen Hydroaminierung von Alkinen eingesetzt werden. Im Rahmen dieser Arbeit konnten auch ansa-Komplexe des Typs Me2Si(Cp)(NR)TiX2 als aktive Katalysatoren für die intermolekulare Hydroaminierung von Alkinen identifiziert werden. Diese Komplexe zeichnen sich durch eine in den meisten Fällen deutlich höhere Aktivität im Vergleich zu Cp2TiMe2 und einem deutlich verbesserten Anwendungsspektrum aus. So konnten beispielsweise auch sterisch wenig anspruchsvolle Amine wie Ethylamin oder n-Propylamin mit hohen Ausbeuten umgesetzt werden, deren Addition an Alkine in Gegenwart von Cp2TiMe2 nur schlecht verläuft. Des Weiteren konnte die Cp2TiMe2-vermittelte Hydroaminierung von terminalen Alkinen durch eine gezielte Optimierung des Reaktionsprotokolls deutlich verbessert werden. Bezüglich der Regioselektivität der Hydroaminierung von terminalen Acetylenen konnte eine starke Abhängigkeit von der Natur des eingesetzten Amins und dessen Raumanspruch festgestellt werden. Bei der Hydroaminierung von terminalen Alkinen mit Alkylaminen wurde generell die bevorzugte Bildung des Anti-Markovnikov-Produktes beobachtet. Dagegen wurde bei der Addition von Arylaminen an terminale Alkylalkine die Bildung des Markovnikov-Produkts favorisiert. Ferner wurde gezeigt, dass beim Einsatz von enantiomerenreinen alpha�chiralen Aminen in der Ti-katalysierten Hydroaminierung generell die Gefahr einer partiellen Racemisierung des Amins besteht. Die bei der Hydroaminierung gebildeten Imine unterliegen dagegen keiner Racemisierung. Mit Cp*2TiMe2 und Me2Si(Cp)(NtBu)Ti(NMe2)2 wurden allerdings zwei Katalysatoren identifiziert, welche eine Verwendung von alpha-chiralen Aminen ohne den teilweisen Verlust der Stereoinformation ermöglichen. Durch Zusatz von Pyridin konnte auch bei der Verwendung weiterer Katalysatoren die Racemisierung des enantiomerenreinen alpha�chiralen Amins weitestgehend unterdrückt werden.
Im Rahmen dieser Arbeit konnten verschiedene neue aktive Katalysatoren für die intermolekulare Hydroaminierung von Alkinen vorgestellt werden. Mit Cp2*TiMe2 und Ind2TiMe2 gelang die Identifikation zweier besonders aktiver Verbindungen. Durch die Verwendung von Cp2*TiMe2 konnte zum ersten Mal die Addition sterisch wenig anspruchsvoller Amine (z. B. Benzylamin) an verschiedene Alkine mit sehr guten Ausbeuten realisiert werden. Das Problem der geringen Regioselektivität bei der Hydroaminierung von unsymmetrisch substituierten Alkinen bei Verwendung dieses Katalysators konnte durch den Einsatz von Ind2TiMe2 als Hydroaminierungskatalysator effektiv gelöst werden. Ind2TiMe2 zeichnete sich im weiteren Verlauf dieser Arbeit als ein Katalysator mit hoher Aktivität und ungemein großer Anwendungsbreite aus. So gelang die Addition verschiedenster Amine unabhängig von ihrem jeweiligen sterischen Raumanspruch sowohl an interne als auch an terminale Aryl- und Alkylacetylene mit guten bis sehr guten Ausbeuten. Aufgrund der hohen Regioselektivität der Ind2TiMe2-katalysierten Hydroaminierung von unsymmetrisch substituierten Phenylalkylalkinen, bildete diese Reaktion den Schlüsselschritt bei der Synthese einer kleinen Substanzbibliothek von biologisch interessanten Phenylethylaminen. Desweiteren gelang erstmals die Kombination der intermolekularen Hydroaminierung von Alkinen mit einer anschließenden Hydrosilylierung der primär gebildeten Imine. Sowohl Cp2TiMe2 als auch Me2Si(Cp)(NtBu)Ti(NMe2)2 sind in der Lage beide katalytisch verlaufenden Prozesse, die Hydroaminierung und die Hydrosilylierung, effizient in einem Eintopfverfahren zu katalysieren. Mit dem bislang entwickelten System können die Produkte bei Verwendung von Arylaminen in hohen Ausbeuten erhalten werden. Erste positive Ergebnisse zeigten, dass eine Übertragung auf Alkylamine durchaus in naher Zukunft realisierbar sein sollte.
Oxidische Verbindungen des Platinmetalls Rhodium sind ausschließlich synthetische Produkte und neben ihren katalytischen Anwendungen auch wegen ihrer elektrischen Eigenschaften interessant. In Ihnen liegt Rhodium vorwiegend in dreiwertiger, in vierwertiger, sehr selten auch in fünfwertiger Form vor und ist - unabhängig von seiner Wertigkeit - fast ausnahmslos oktaedrisch von Sauerstoffen koordiniert. Es besteht hierbei die Möglichkeit zu einem Nebeneinander von drei- und vierwertigem Rhodium in ein- und derselben Verbindung bei unveränderter Koordination, was in "gebrochenen" Wertigkeiten resultieren kann. Diese Arbeit soll einen Beitrag zur Kristallchemie des Rhodiums in oxidischer Bindung leisten. Hierzu wurden zahlreiche Syntheseversuche durch Festkörperreaktion von pulverförmigen Proben in offenem Tiegel an Luft bei Temperaturen zwischen 700°C und 1200°C unternommen. Die gefundenen Verbindungen wurden dann einer strukturellen Untersuchung mittels Rietveldverfeinerung an Röntgenpulverdaten unterzogen und auf Mischkristallbildung, Kationenverteilung, Geometrie der Koordinationspolyeder etc. untersucht. Substitutionsversuche in bekannten, geeignet erscheinenden Strukturtypen, wobei insbesondere Verbindungen des kristallchemisch ähnlichen Cr3+ als Vorlage dienten, erbrachten erstmals Rhodiumverbindungen mit Langasitstruktur: Sr3RhAlGe4O14, Sr3RhGaGe4O14, Sr3RhFeGe4O14, Ba3RhGaGe4O14 sowie Pr1,4Sr1,6(Rh0,65Al0,45)Al1,8Ge3,2O14 und Pr0,9Sr2,1(Rh0,43Ga0,57)Ga2Ge3O14 mit nur teilweisem Rh-Einbau. Weiterhin konnten die Verbindungen Sr3TmRhO6, Sr3LuRhO6 und Sr3(Nd0,707Sr0,293)RhO6 (K4CdCl6-Typ) erstmalig synthetisiert und beschrieben werden. Für das bislang nur widersprüchlich beschriebene Ba(Rh0,275Ti0,725)O3 konnte der Grad des Rh-Einbaus bestimmt und, wie für den bereits bekannten Granat Cd3Rh2Ge3O12, erstmals ein Strukturdatensatz erstellt werden. Die Suche nach neuen Rhodium-Verbindungen durch die systematische Untersuchung binärer und ternärer Mehrstoffsysteme mit Rh2O3 als Komponente in isothermen Schnitten erbrachte in den bei 860°C (Synthesetemperatur) untersuchten Systemen CdO - Rh2O3 - SiO2/GeO2/TiO2 sowie ZnO - Rh2O3 - SiO2 (1000°C) keine bislang unbekannten Phasen. Im System ZnO - Rh2O3 - GeO2 trat bei 1000°C begrenzte Mischbarkeit zwischen ZnRh2O4 (Spinellstruktur) und dem bei Normaldruck in der Willemitstruktur vorliegenden Zn2GeO4 bis hin zu einer Einbaugrenze von ca. 60 mol% Zn2GeO4 auf. Im System ZnO - Rh2O3 - TiO2 (1000°C) hingegen wurde vollständige Mischbarkeit zwischen dem Normalspinell ZnRh2O4 und dem inversen Spinell Zn2TiO4 vorgefunden. Im quasiternären System ZnRh2O4 - Zn2TiO4 - ZnCr2O4 wurde ebenfalls vollständige Mischbarkeit zwischen allen drei Endgliedern festgestellt. Mittels Strukturverfeinerungen an Mischkristallen der Randsysteme ZnRh2O4 - Zn2TiO4, ZnRh2O4 - ZnCr2O4 und Zn2CrO4 - Zn2TiO4 konnte gezeigt werden, daß der jeweilige Einfluß der beiden Koordinationspolyeder in der Spinellstruktur auf die Größe der Elementarzelle bzw. deren Gitterkonstante für die drei untersuchten Randsysteme unterschiedlich und nicht allein auf die Oktaederposition und die Größe ihres Koordinationspolyeders beschränkt ist. Im bei 750°C untersuchten System Rh2O3 - Kupferoxid - Bi2O3, in dem Kupfer in zwei Wertigkeitsstufen auftritt, wurden zwei bislang unbekannte Verbindungen gefunden, wovon eine, Cu0,96Bi0,016Rh2O4, exakt bestimmt und ihre Struktur aufgeklärt werden konnte. Trotz sehr ähnlicher Summenformel, fast gleich großer Elementarzelle sowie gleicher Anzahl von Formeleinheiten Zellinhalt weist Cu0,96Bi0,016Rh2O4 eine von CuRh2O4 (tetragonale Spinellstruktur) völlig unterschiedliche, durch den geringen Bi-Anteil stabilisierte Struktur auf. Im System Rh2O3 - Bi2O3 traten bei einer Synthesetemperatur von 1000°C entgegen den Angaben in der Literatur überaschenderweise zwei neue Verbindungen auf, von denen wiederum eine, Bi6Rh12O29, strukturell charaktrisiert werden konnte. Aufgrund der Stöchiometrie muß bei Bi6Rh12O29 von einer formalen Wertigkeit von +3,33 für das Rhodium ausgegangen werden. Die Strukturen der beiden neuen Verbindungen Cu0,96Bi0,016Rh2O4 und Bi6Rh12O29 sind in der Literatur bislang nicht beschrieben. Eine vergleichende Betrachtung des Deformationsgrades der Rh-O-Oktaeder aller untersuchten Verbindungen zusammen mit ausgewählten Beispielen aus der Literatur ergab einen allgemeinen Trend zur Zunahme der Oktaederdeformation bei gleichzeitiger Abnahme der Symmetrie, von dem jedoch Ausnahmen möglich sind.
The human immunodeficiency virus (HIV) is the causative agent of the acquired immunodeficiency syndrome (AIDS). Despite more than twenty years of intense research still no vaccine or curing therapy has been found. For the development of novel antiviral compounds, understanding of the HIV lifecycle as well as the molecular mechanisms of host pathogen interactions are a prerequisite. Like all viruses, HIV subcontracts cellular machineries for efficient replication and production of new progeny. A particular feature of lentiviruses is the active transport of the pre-integration complex (PIC) into the nucleus. The mechanism remains elusive, yet in the case of HIV the viral protein R (Vpr), a small 14kDa accessory protein, is one candidate possibly implicated in the process. The protein stays associated to the PIC until nuclear translocation. Furthermore it has been shown, that Vpr binds to the nuclear pore complex (NPC). This interaction might therefore be the link mediating nuclear import of the PIC. Moreover the cytoskeleton has been shown to play a major role in cytoplasmic transport of viral particles. In this context, we observed the nuclear envelope (NE) to be embedded in a perinuclear actin shell and displaying highly dynamic nuclear invaginations. We developed a novel approach to visualize actin inside living cells based on a fluorescent analog of cytochalasin D (CD-BODIPY). Due to specific binding to free-barbed-ends of short actin fibers, we could show that this compound visualizes a high turnover actin pool around the NE and inside NE-membrane invaginations of living cells. Although reported in many different cell types, the possible role of perinuclear actin filaments in the dynamic structural plasticity of the NE remains unresolved. We could show that NE-membranes alone are sufficient to nucleate polymerizing actin filaments in vitro, involving both actin recruitment to their surface, and filament growth. Accordingly, our results demonstrate that perinuclear actin dynamics are orchestrated by the NE itself. Therefore, by binding of Vpr to the NPC, the virus could possibly exploit this pool of polymerizing actin as a new strategy to overcome the nuclear membrane. Furthermore, we tested peptide nucleic acids (PNAs) as new compounds to inhibit viral spread at different stages of the lifecycle. PNAs have been developed recently and dispose of several features to be a powerful tool for a novel antisense approach. We synthesized a series of PNAs directed against crucial sequences in the HIV genome and tested them under various conditions. This showed in particular, that infectivity of virions produced in the presence of PNAs was significantly diminished. In another viral system, PNAs targeted against the borna disease virus (BDV), could provide evidence for the requirement of the surface glycoprotein (GP) in BDV infection. Moreover, the treatment could effectively inhibit viral spread in primary neurons. These results demonstrate PNAs to be a powerful molecular tool and a potential antiviral drug candidate.
Der erste Teil der vorliegenden Dissertationsschrift widmet sich der mehrdimensionalen konischen Durchschneidung, welche durch die beiden tiefsten elektronischen Zustände des Butatrien Kations gebildet wird. Diese konische Durchschneidung liegt energetisch tief und räumlich in der Nähe des Franck-Condon Bereichs des Grundzustandes des neutralen Moleküls. In diesem Molekül wird deshalb die Dynamik des Ionisierungsprozesses durch diese konische Durchschneidung dominiert. Dies ist ein besonders interessanter Vertreter vibronisch gekoppelter Systeme, da ein eigenes strukturiertes Band im Energiespektrum erscheint. In dieser Arbeit haben wir die Potentialenergieflächen und ihre Durchschneidung mittels ab initio Methoden bestimmt. Ein diabatischer Modell-Hamiltonoperator, unter Berücksichtigung aller linearen, quadratischen und bilinearen vibronischen Kopplungstermen, wird hergeleitet. Die Kopplungsterme werden über einen Fit an die ab initio Daten bestimmt. Die Kerndynamik aller 18 Schwingungsmoden wird mittels Wellenpaketpropagation unter Zuhilfenahme der multikonfigurellen zeitabhängigen (multiconfiguration time-dependent) Hartree (MCTDH) Methode untersucht. Das Photoelektronenspektrum von Butatrien wird berechnet und mit experimentellen Daten verglichen. Der zweite Teil der Arbeit widmet sich der Erweiterung der MCTDH-Methode auf die Propagation von Dichteoperatoren. Mit dieser Methode haben wir Relaxationsprozesse eines schwingungsangeregten CO-Moleküls, adsorbiert auf einer Cu(100)-Metalloberfläche, untersucht. Für das CO/Cu(100)- Wechselwirkungspotential passten wir ein in der Literatur vorhandenes Potentialmodell für unsere Bedürfnisse an. Die Oberfläche betrachten wir als externes Wärmebad, welches durch einen Relaxationsoperator beschrieben wird. Das CO-Molekül beschreiben wir durch eine reduzierte Dichte, deren Propagation berechnet wird. Um Infrarotanregungen im MCTDH-Dichteformalismus zu berechnen, wurde eigens eine iterative Methode entwickelt und implementiert. Es wurden Oberflächen-Relaxationsprozesse, Thermalisierungen und Haftungsprozesse behandelt. Die Haftungsprozesse eines Oberflächen-Atom-Modells wurden in Abhängigkeit von der Oberflächenkorrugation und der Einschussenergie des einfallenden Teilchens untersucht.
Gegenstand der vorliegenden Arbeit ist die mathematisch-numerische Modellierung katalytischer Monolithreaktoren unter Berücksichtigung detaillierter Transportmodelle in Gasphase und Festkörper sowie auf Elementarreaktionen aufbauenden Mechanismen für homogene und heterogene Reaktionen. Zuerst wird ein hierarchisches Modell der Prozesse, die in detaillierter Form für die Beschreibung des Monolithen herangezogen werden, entwickelt. Ausgehend vom Begriff der Spezies, werden die Transport- und die thermodynamischen Eigenschaften von Gasphasen- und Oberflächenensembles betrachtet. Zur Beschreibung der Stoffumwandlungen dienen Reaktionsmechanismen, die aus Elementarreaktionen aufgebaut sind. Darauf wiederum bauen Modelle der reaktiven Strömung auf. Die oberste Hierarchiestufe bildet das Modell des monolithischen Festkörpers. Eine zentrale Stellung in dieser Arbeit nimmt die numerische Implementation der Modelle ein. Dazu wurde das Programmpaket DETCHEM komplett neu strukturiert und um die Modelle der Kanalströmung sowie des Monolithen erweitert. Basis der detaillierten Simulation ist eine Programmbibliothek mit Funktionen zur Berechnung der thermodynamischen Größen und Transportkoeffizienten sowie der Reaktionsgeschwindigkeiten in der Gasphase und auf Oberflächen. Zur Simulation einer stationären laminaren Kanalströmung wird das Modell der Grenzschichtnäherung herangezogen. Unter der Annahme separierter Zeitskalen für die Durchströmung eines Einzelkanals und für die darauf erfolgende thermische Reaktion des Monolithen baut auf den Simualtionsergebnissen mehrerer unabhängiger Kanäle die Simulation des Gesamtmonolithen auf. Um den Zeitaufwand zu begrenzen, werden repräsentative Kanäle nach einem Cluster-Agglomerations-Algorithmus ausgewählt. Die Programmteile zur Simulation der Strömung bzw. des Gesamtmonolithen werden durch Vergleich mit Experimenten zur oxidativen Dehydrogenierung von Ethan bzw. zur wasserstoffunterstützten Verbrennung von Methan auf Platin validiert. Die experimentellen Ergebnisse werden mit guter Übereinstimmung reproduziert. Vorallem ist es durch die Simulation möglich, eine Erklärung der auf molekularer Ebene ablaufenden Prozesse zu geben. Mit dieser Simulation gelang es erstmalig, einen transienten Prozess des gesamten Monolithen auf Grundlage detaillierter Modelle sowohl für die Kanalströmung als auch für die Oberflächenreaktionen darzustellen. Vergleiche instationärer Prozesse in Experiment und Simulation erfolgen für die Zündung der vollständigen bzw. partiellen Oxidation von Methan in einem Platin- bzw. Rhodium-beschichten Monolithen. Es wird gezeigt, dass es für solche Systeme sinnvoll ist, ein über das Einkanalmodell hinausgehendes Modell des Monolithen heranzuziehen. Die vorhergesagten Zeitskalen werden anhand globaler Eigenschaften (Temperatur, Spezieszusammensetzung) überprüft. Die Simulation liefert Erkenntnisse über den inneren Ablauf der Zündung und dessen Ursachen. Die Vorteile des dargestellten Modells für den Monolithen werden sichtbar, wenn man räumlich veränderliche Eingangsbedingungen, wie sie in der technischen Anwendung aufgrund konstruktiver Randbedingungen vorkommen, betrachtet. Der Einfluss der Anströmung wird anhand der katalytischen Verbrennung von Methan untersucht.
Dargestellt wurden Zink/Mangan-Schichten auf Stahl durch Gasphasenabscheidung der Schichtmetalle mit PVD- und IBAD-Verfahren. Es wurden Schichtsysteme entwickelt, die trotz einer geringeren Dicke die Korrosionsbeständigkeit eines konventionell (elektrogalvanisch) verzinkten Stahls erreichten bzw. übertrafen. Die Schichten waren mechanisch belastbar, insbesondere verformbar, steinschlagresistent und gut schweißbar. Gute Haftung einer im Anschluß aufgebrachten Lackschicht war eine Grundvoraussetzung im Hinblick auf mögliche Anwendungen des Schichtsystems in der Automobilindustrie. Folgende Arten von Schichtsystemen wurden dargestellt: •Legierungen: durchgängige Zn/Mn-Legierungsschichten. •Toplayer: Zn-Schichten mit reinen Mn-Deckschichten, Zn-Schichten mit legierten Zn/Mn-Deckschichten. •Multilayer: Zn-Mn-Multilagensysteme mit reinen Mn-Zwischen- und Deckschichten, Zn-Zn/Mn-Multilagensysteme mit legierten Zwischen- und Deckschichten (typischerweise 4 - 6 Einzelschichten). •Reine Zn-Schichten als Vergleichssysteme: mit und ohne Ionenstrahlunterstützung aufgebracht. Die Korrosionsbeständigkeit der Schichten wurde mit Salzsprühverfahren (Salzsprühtest nach DIN 50021, Wechseltest nach VDA 621-415), elektrochemisch durch Potential-Zeit-Messungen, in praxisnahen Bewitterungs- und Fahrversuchen (DYKO-Test) und durch Bestimmung der Kontaktkorrosion im Verbund mit Aluminium und Stahl untersucht. Adhäsions- und Steinschlagtests wurden zur Prüfung der mechanischen Belastbarkeit eines Schichtsystems durchgeführt. Schweißversuche ergänzten die industriellen Prüfverfahren. Topographie, Morphologie, Mikrostruktur und Zusammensetzung eines Schichtsystems wurden mit Schichtdickenmessungen, Rasterelektronenmikroskop-Aufnahmen und EDX-Analysen bestimmt. Einige der industriellen Testverfahren wurden an lackierten Proben vollzogen. Um die potentielle Anwendbarkeit eines Schichtsystems in der Automobilindustrie beurteilen zu können, diente eine industriell gefertigte, elektrogalvanisch abgeschiedene 8 µm dicke Zn-Schicht als Referenz. Es zeigten sich folgende Trends hinsichtlich der Korrosionsbeständigkeiten: •Die Schichtdicke war, besonders bei lackierten Proben, ein entscheidendes Kriterium der Korrosionsbeständigkeit, mit wachsender Schichtdicke nahm die Beständigkeit eines Systems zu. •Ionenbeschuß während der Beschichtung wirkte sich günstig auf das Korrosionsverhalten einer Schicht aus. •Reine Zn-Schichten bis 5 µm Zn übertrafen die Beständigkeit der dickeren galvanischen Referenz nicht. •Beimischungen von Mn (Legierungsschichten) bewirkten eine geringe Steigerung der Korrosionsbeständigkeit. •Multilagensysteme konnten die Beständigkeit der Referenz nicht ganz erreichen. •Toplayer mit reinem Mn oder 75 % Zn und 25 % Mn in der Deckschicht erzielten die besten Resultate, einige Systeme übertrafen die Korrosionsbeständigkeit der Referenzproben deutlich. •Die mittels Salzsprühverfahren bestimmten Korrosionsbeständigkeiten der Schichtsysteme korrelierten qualitativ sehr gut mit den durch elektrochemische Messverfahren gewonnenen Erkenntnissen. Danach lässt sich eine Reihe aufstellen, in der die Korrosionsbeständigkeit wie folgt zunimmt: Zn Zn/Mn-Legierungen Zn/Mn-Multilayer < Referenz Zn/Mn-Toplayer Den industriellen Praxistests wurden in erster Linie die sehr korrosionsbeständigen Toplayer-Systeme unterzogen. Sie zeigten keine Mängel und genügten den industriellen Anforderungen. Adhäsionsmessungen ergaben sehr gute Haftungen der aufgebrachten Zn/Mn-Schichten. Der Steinschlagtest wurde von allen untersuchten Proben bestanden. In Schweißversuchen erwies sich ein Multilagensystem der Schichtfolge (2 µm Zn + 0.5 µm Mn) x 3 als besonders gut schweißbar. Andere Schichtsysteme zeigten eine mit der galvanischen Referenzprobe vergleichbare Schweißbarkeit. Morphologie, Mikrostruktur und Topographie der Schichtsysteme wurden durch REM-Aufnahmen und EDX-Analysen charakterisiert. Im Hochvakuum aufgedampftes Zn wuchs weitgehend kolumnar und sehr homogen auf und kristallisierte hexagonal. Die Verzahnung des Zn mit dem Stahlsubstrat war weniger ausgeprägt als bei der elektrogalvanisch beschichteten Referenzprobe. Der Ionenstrahl wirkte sich positiv aus, indem er die Schichten glättete und feinkörniger gestaltete. Bei Toplayer- und Multilayer-Systemen konnte man die Einzelschichten im Bruchbild deutlich voneinander unterscheiden. EDX-Analysen liessen zudem die leichte Oxidierbarkeit von Mn erkennen. Bei Top- und Multilayern sah man in den Spektren die Schichtübergänge mit ihren Grenzbereichen sehr gut, wobei dünne Mn-Zwischenschichten durch den Ionenstrahl mit Zn aus den darüber- und darunterliegenden Schichten legiert wurden. Potentielle Anwendung in der Automobilindustrie könnten besonders Toplayer-Systeme der Schichtfolge Zn + Mn und Zn + Zn/Mn (75/25) mit einer Basisdicke von 4 - 5 µm Zn und jeweils einer 1 µm dicken Deckschicht finden.
In der Kohleverbrennung werden Stickoxide, zusammenfassend als NOx bezeichnet, entweder bei hohen Temperaturen durch Reaktionen von N2 der Verbrennungsluft oder durch die Oxidation des Stickstoffs, der in der Kohle chemisch gebunden ist, gebildet. Diese Stickoxide können mit Koks, der bei der Verbrennung von Kohle entsteht, reagieren und dadurch die NO-Konzentration reduzieren. Bei den Bildungs- und Abbauprozessen von Stickoxiden sind CN- und NH2-Radikale wichtige Zwischenprodukte. Bislang konnte jedoch noch kein detaillierter Reaktionsmechanismus für den NO-Abbau durch Koks aufgestellt werden. Die Verbrennung von Graphit unter wohldefinierten Bedingungen kann als einfachstes Modellsystem zur Untersuchung der chemischen Vorgänge und des möglichen NO-Abbaus durch Kohlenstoff in Koks betrachtet werden. Im Rahmen dieser Arbeit wurden NO-dotierte, vorgemischte, laminare Niederdruck-H2/O2-Flammen während der Verbrennung von Graphit untersucht, um quantitative Informationen über diese Prozesse zu erhalten. Absolute CN- und absolute NH2-Radikalkonzentrationen sowie Temperaturprofile wurden in situ während der Verbrennung eines Graphitsubstrats in Knallgasflammen bei einem Druck von 4 kPa für zwei unterschiedliche H2/O2-Stöchiometrien, für die stöchiometrische und eine brennstoffreiche Flamme, und für drei verschiedene Abstände zwischen Graphitsubstrat und Brenner (15, 20 und 25 mm) unter Verwendung von berührungsfreien laserspektroskopischen Methoden bestimmt. Die CN-Konzentrationen wurden mit Hilfe der cavity ring-down spectroscopy (CRDS) und die NH2-Konzentrationen mittels der intracavity laser absorption spectroscopy (ICLAS) gemessen. Die Temperaturen wurden über laserinduzierte Fluoreszenz (LIF)Anregungsspektren von OH-Radikalen ermittelt. Die CN-Profile wurden mit eindimensionalen Berechnungen für die freie CO/NO/H2/O2Flamme bzw. CH4/NO/H2/O2-Flamme, die auf dem GRI 3.0- und dem Miller-BowmanMechanismus basieren, die Temperaturprofile mit eindimensionalen Berechnungen für die freie und undotierte H2/O2-Flamme, die auf dem MixFla-Code basieren, verglichen. Die erhaltenen quantitativen Informationen können als ein erster Kalibrationspunkt für detaillierte numerische Simulationen der Graphitverbrennung dienen, die auf dem Konzept von homogenen und heterogenen Elementarreaktionen basieren.
Die Eigenschaften von Molekülkristallen werden nicht nur durch die Eigenschaften der Moleküle bestimmt, welche die Kristallpackung aufbauen, sondern ebenso durch die Art der Packung im Kristall. Während die Eigenschaften der Moleküle im allgemeinen gut verstanden sind, ist die Art der Packung von Molekülen in einem Kristall wesentlich weniger gut bekannt. In vielen Fällen wird sie auch nicht weiter analysiert. Dies liegt wenigstens zum Teil daran, daß geeignete Werkzeuge für die Analyse molekularer Packungsmuster fehlen. Die vorliegende Arbeit beschreibt die Entwicklung von Algorithmen und Werkzeugen für die automatische Packungsanalyse großer Datenbestände. Von den verschiedenen Ansätzen, die hierbei verfolgt wurden, hat sich die Klassifzierung von Packungen in Bezug auf das Vorliegen und die Stapelung von dichtest gepackten Schichten besonders bewährt. Eine Korrelation zwischen der Molekülform, angenähert durch das Ellipsoid der zweiten Momente, und dem Packungsmuster läßt sich in vielen Fällen auffinden. Das aufregendste Ergebnis dieser Untersuchung ist die Erkenntnis, daß über 30% der analysierten Packungsmuster (130 000 Strukturen der Cambridge Structural Database) durch das Vorliegen dichtest gepackter Ebenen charakterisiert sind.
Im ersten Teil dieser Arbeit wurden Inhibitoren zuckerbindender Oberflächenproteine des Polyomavirus synthetisiert. Anhand der Kristallstruktur des Kapsidproteins pv1 und der darauf lokalisierten Lektindomänen konnten optimierte multivalente Inhibitoren modelliert werden. Durch Verwendung langer, rigider Ketten (ca. 30Å) auf Basis von Carotinoiden sollten Inhibitoren über Sialinsäuren gleichzeitig mehrere Bindungsstellen blockieren können. Drei gänzlich verschiedene Synthesestrategien wurden ausgearbeitet und die hierzu nötigen Synthesebausteine dargestellt. Die Kopplungen zwischen den jeweiligen Sacchariden und Carotinoiden erwiesen sich als problematisch: Weder durch direkte Glycosilierung noch durch eine Amidbildung oder eine Wittig-Horner-Reaktion konnten entsprechende Konjugate aus Carotinoiden und Sacchariden erhalten werden. Im zweiten Teil der Arbeit wurden Glycosidmimetika auf Basis von Furanen synthetisiert, um die Adhäsion von metastasierenden Zellen untersuchen und inhibieren zu können. Mono- und Diglycoside mit Fucose, Galactose und Lactose, sowie Kombinationen dieser Saccharide konnten durch direkte Glycosilierung von 3,4-Bishydroxymethylfuran dargestellt werden. Glycoside 2,5-substituierter Furane waren ausgehend von 5- Hydroxymethylfuran (HMF) zugänglich. Als tumorassoziierte Saccharidmimetika konnten vier verschiedene Sialoside, sowie verschiedene sulfatierte Glycoside dargestellt werden. 3-β-D-Galactopyranosyl-oxymethyl-4-sulfato-oxymethyl-furan (GSF) konnte für biologische Untersuchungen via Diels-Alder-Reaktion mit Biotin und Fluorescein markiert werden. Weiterhin konnten durch geeignete Schutzgruppenstrategien strukturell komplexere Mimetika dargestellt und verschiedene Fucosyldonoren zur Synthese von α- Fucosiden evaluiert werden. Per Molecular Modelling konnte gezeigt werden, daß die Struktur der Saccharidmimetika der des Tetrasaccharides sLewisx entspricht. GSF zeigte im Rahmen einer weiteren Arbeit in verschiedenen Assays eine erfolgreiche Inhibition der Adhäsion von Melanomzellen. Zur genaueren Untersuchung der Zell-ECM– Wechselwirkungen wird das Fluorescein-gekoppelte Derivat derzeit eingesetzt. Durch eine bausteinartige Synthese konnten relativ einfach Mimetika mit einer hohen Diversität darstellt werden. Ferner konnte gezeigt werden, daß diese Mimetika nicht nur gute Inhibitoren der Zelladhäsion sind, sondern auch als wirksames diagnostisches Werkzeug eingesetzt werden können.
1. Aus literaturbekannten Verbindungen wurden Phenothiazinboronsäureester und ethinylierte Phenothiazine als Ausgangsmaterialien für die Suzuki- und Sonogashira-Kupplung dargestellt. Arylierte und alkinylierte Phenothiazine waren in guten Ausbeuten zugänglich. Die grünlich fluoreszierenden arylierten und alkinylierten Phenothiazinderivate weisen Stokes-Shifts im Bereich von 5000-9000 cm-1 auf. Aufgrund des Schweratomeffekts beträgt die Quantenausbeute maximal 40 %. Es ergibt sich eine gute Korrelation zwischen den längstwelligen Absorptionsmaxima und den sigma-p-Parametern der Substituenten, sowohl in der Reihe der Aryle als auch in der Reihe der Alkine. Die Verbindungen wurden elektrochemisch reversibel oxidiert. Dabei zeigte sich, dass das Potential wesentlich von der Art des Substituenten und des elektronegativen Brückenelements Acetylen beeinflusst wird. Nitroarylierte Verbindungen, welche sowohl reversibel reduziert als auch oxidiert werden können, können als Modelle für molekulare Gleichrichter betrachtet werden. 2. Des weiteren wurde ein Pool von unsymmetrisch substituierten Bausteinen für die Synthese von Oligomeren gewonnen. Die Phenothiazindimere und –trimere erweisen sich als potente Fluorophore mit Stokes-Shifts von 5000-9000 cm-1. Die höchsten Quantenausbeuten erreicht man mit starren Butadiinen und alkinverbrückten Oligomeren. Die elektrochemischen Untersuchungen ergaben, dass in direkt verknüpften Phenothiazinoligomeren die größte elektronische Kommunikation zwischen den Einheiten herrscht, in biphenylen- und thiophenethinylenverknüpften Bisphenothiazinen hingegen sind die Phenothiazinkörper elektronisch vollständig entkoppelt. 3. Die großen Abstände im Kristall ließen keine topchemische Polymerisation von Phenothiazinbutadiinen zu. Hingegen gelang die thermische Polymerisation zu Oligomeren mit 3-5 Monomereinheiten. 4. Zum ersten Mal konnten Phenothiazinderivate auf HOPG selbstorganisiert und mit Hilfe eines Rastertunnelmikroskops abgebildet werden. Bedingt durch pi-pi-Wechselwirkungen zwischen den pi-Elektronen des Moleküls und der Bandstruktur des Graphits liegen die Moleküle flach auf der Oberfläche. Die Moleküle ordnen sich zueinander in Abhängigkeit von der Sperrigkeit des N-Alkylrestes leicht versetzt an. 5. In unterschiedlichen OLED-Anordnungen zeigt eine Triade in ihrer Funktion als Lochleiter beim Anlegen einer Spannung reversibel einen exponentiellen Anstieg der Stromdichte. Elektrolumineszenz wird nicht beobachtet. 6. Zur in situ Chemisorption auf Gold wurden fünf Phenothiazinderivate mit Thioester Termini synthetisiert. In zwei Fällen kann für eine auf eine Goldelektrode chemisorbierte Substratschicht im cyclovoltammetrischen Experiment reversible Oxidationen beobachtet werden.
Zum besseren Verständnis der Zusammenhänge des Gemischbildungs- und Verbrennungsprozesses bei Brennver-fahren mit Direkteinspritzung müssen zeitaufgelöste, berührungslose Messungen direkt im Brennraum unter mög-lichst realistischen Bedingungen erfolgen. Das im Rahmen dieser Arbeit angewandte zweidimensionale Verfahren zur Messung mittlerer Tropfengrößen, basierend auf unterschiedlichen Durchmesserabhängigkeiten von laserinduzierter Fluoreszenz (LIF) und Mie-Streuung, kann im Gegensatz zu konventionellen Verfahren auch in Bereichen hoher Spraydichte eingesetzt werden. Die Fluoreszenz stammt dabei von Farbstoffen, deren Fluoreszenzintensität in Abhängigkeit von Konzentration, Temperatur und Sauerstoffkonzentration untersucht wurde. Um für die Anwendung in verdampfenden Systemen das dynamische Verhalten der Fluoreszenz relevanter Tracer in Abhängigkeit von der Temperatur detailliert untersuchen zu können, wurde das Fluoreszenzsignal an langsam verdampfenden Einzeltropfen beobachtet. Rhodamin 6G-dotierte Wassertropfen wurden mit einem CO2-Laser geheizt. Der Farbstoff reicherte sich während der Verdampfungsphase vollständig in der flüssigen Phase an. Ein Tracerkonzept mit Anregung im roten Spektralbereich verwendet die Tracermoleküle Rhodamin 6G und Rho-damin 800 und nutzt den transparenten Spektralbereich von Realkraftstoffen für Anregung und Emission und ermög-licht somit die selektive Beobachtung auch in kommerziell erhältlichen Kraftstoffen. Mit Hexanol als Lösungsver-mittler konnten die Tracer in unpolarem Dieselkraftstoff gelöst, charakterisiert und unter Brennkammerbedingungen getestet werden. Für die Anregung im UV wurden die Tracer Fluoranthen und BBQ (4,4-Bis-(2-butyloctyloxy)-p-quaterphenyl) gewählt, da sie eine simultane Anregung des OH-Radikals ermöglichen. Zur weiteren Charakterisie-rung der Temperaturabhängigkeit und des Verdampfungseinflusses, auch bei Flüssigkeitstemperaturen über dem Sie-depunkt des Kraftstoffs bei Atmosphärendruck, wurde in einem technisch relevanten Spray die Tracerfluoreszenz von BBQ und Fluoranthen in Hochtemperatur-Hochdruck-Umgebung unter Verwendung eines nichtfluoreszierenden Multikomponenten-Ersatzkraftstoffs für Kerosin untersucht.
Epidermis-Typ-Lipoxygenasen bilden zusammen mit den konventionellen Isoenzymen die Familie der Säuger-Lipoxygenasen. Als Dioxygenasen katalysieren sie die stereo- und regiospezifische Insertion molekularen Sauerstoffs in 1,4-cis,cis-Pentadienstrukturen, wie sie in mehrfach ungesättigten Fettsäuren enthalten sind. Die Metabolite der konventionellen Lipoxygenasen dienen als primäre oder sekundäre Mediatoren in Signalkaskaden innerhalb und außerhalb des Ursprungsgewebes. In der vorliegenden Arbeit wurden die epidermalen Lipoxygenasen, insbesondere die e-LOX-3, näher charakterisiert. Während für die epidermalen Enzyme im Vergleich zu konventionellen Lipoxygenasen geringe Enzymaktivitäten mit typischen Lipoxygenasesubstraten, wie Arachidonsäure, nachgewiesen wurden, war die e-LOX-3 inaktiv. Weitere Untersuchungen bestätigten jüngste Befunde, wonach e-LOX-3 eine Hydroperoxid- isomerase ist. In eukaryotischen Zellen exprimiertes e-LOX-3-Protein metabolisierte 12(R)- und 15(S)-HPETE zu Expoxyalkoholen, die durch HPLC und Massenspektrometrie identifiziert wurden. Der e-LOX-3 und ihren Produkten scheint eine kritische Rolle bei der Fettzelldifferenzierung zuzukommen. Zwei Modellsysteme der Adipogenese, 3T3-L1-Zellen und Retinoblastomdefiziente MEFs, bei denen die Hemmung der Adipozytendifferenzierung durch Transduktion des Transkriptionsfaktors ADD-1 aufgehoben werden konnte, wurden verwendet. ADD-1 wird eine Rolle bei der Kontrolle der Synthese eines Liganden für PPARγ, einem Schlüsselfaktor der späten Fettzelldifferenzierung, zugesprochen. Die Bildung dieses Faktors, der in das Medium abgegeben wird, kann durch LOX-Inhibitoren unterdrückt werden. Als dafür verantwortliche LOX wurde in beiden Zellinien die e-LOX-3 nachgewiesen. In der Tat wurde in Medien ADD-1 induzierter Rb-/- MEFs Produkte isoliert, die den von e-LOX-3 gebildeten Epoxyalkoholen nach analytischen und massenspektrometrischen Befunden sehr ähnlich waren. Diese Ergebnisse weisen die e-LOX-3 Produkte als mögliche, physiologische Liganden des Transkriptionsfaktors PPARγ aus, dem eine essentielle Rolle bei der Fettzelldifferenzierung zukommt. Damit wurden erstmalig Evidenzien für eine physiologische Funktion der e-LOX-3 und ihrer Produkte erhalten.
Enzymkatalyse wird in der Natur oftmals durch allosterische Regulation kontrolliert. Bei synthetischen Katalysatoren ist diese Regulation noch nicht näher untersucht worden. Im Rahmen der Arbeit wurden drei– und vierkernige Metallkomplexe verschiedener Liganden (L1 – L3) als Modellsysteme für allosterische Metalloenzyme untersucht. Die Metallkomplexe sind aus einer allosterischen Untereinheit und einer katalytischen Untereinheit aufgebaut. Ein mononuklearer Co(III)-Komplex des Liganden L3 konnte isoliert und kristallographisch charakterisiert werden. Dadurch konnte ein Einblick in die Rolle des allosterischen Metalls bei der Präorganisation der funktionellen Untereinheiten gewonnen werden. Die Komplexe [(L3-3H)Co]Cu3 und [(L3-2H)Cu]Cu3 wurden in Lösung hergestellt. Sie unterscheiden sich durch das allosterische Metallion (CuII bzw. CoIII), enthalten aber die gleichen funktionellen Metallionen (CuII). Das allosterische Metall kontrolliert die katalytische Aktivität: während [(L3-2H)Cu]Cu3 ein effizienter Katalysator für die Spaltung des Phosphodiesters 2-Hydroxypropyl-p-Nitrophenylphosphat (HPNP) ist, ist [(L3-3H)Co]Cu3 praktisch inaktiv. [(L3-3H)Co]Cu3 ist ein selektiver allosterischer Rezeptor für Aminosäuren.
Es wurden Metallkomplex-Konjugate von Peptidnucleinsäuren (PNAs) synthetisiert und in zwei Projekten angewendet: als “künstliche Restriktionsenzyme“ für die sequenzselektive Spaltung von Einzelstrang-DNA sowie als Komponenten einer DNA-templatvermittelten Metallkatalyse. Im ersten Projekt konnte durch MALDI-TOF MS und HPLC der Zr(IV)-Komplex des Tris(hydroxymethyl)-aminomethan-PNA-Konjugats (Zr(IV)-15) als aktivste Spezies zur Spaltung komplementärer DNA identifiziert werden. Die Spaltung der Ziel-DNA erfolgte sequenzselektiv zu 91% (nach 164 Stunden) in unmittelbarer Nachbarschaft des Metallkomplexes. Konjugate einer Cu(II)-Pyridylpyrazol-modifizierten PNA (Cu(II)-31) wurden für die DNA-templatvermittelte Spaltung estermodifizierter PNAs eingesetzt. Als Substrat-PNAs wurden die PNA-Ester-Konjugate 16 und 17 synthetisiert, in denen die Cu(II)-Ankergruppe (Chinolin-N) in die Alkohol-PNA-Komponente integriert ist. Es kann im Grunde mit beliebigen Carbonsäuren kombiniert werden. Die Spaltreaktionen wurden durch eine Kombination aus MALDI-TOF MS- und HPLC-Analyse untersucht. Es konnte gezeigt werden, dass die Reaktion durch das DNA-Templat etwa 100-fach beschleunigt wird. Des weiteren wurden nach 10 Stunden 12 Turnover bei einem 100-fachen Substratüberschuss erzielt.
We attempted to obtain a large amount of solvates of 2,4,6-tris(isopropylamino)-1,3,5-trinitrobezene 1 and tried to embark on a systematic study (both experimentally and theoretically) of conformational effects of crystal packing. Here we describe their investigation by X-ray diffraction, thermal analysis, and computational methods (force field and ab-initio). The crystal and molecular structures were determined by X-ray diffraction. For thermal analysis investigations a combination of Differential Scanning Calorimetry (DSC) and Thermogravimetry (TG) measurements were done. In our work we have calculated the electrostatic potential (ESP) charges and the molecular energies of the experimental molecular structures after the correction of the hydrogen atomic positions, using the Density Functional Theory (DFT) electronic structure program DMOL3 (2.2), with DNP basis set and GGA-BLYP functional. The molecular structures with the calculated charges then have been used to calculate: the crystal, the lattice and individual interaction energies in each structure, within the molecular simulation program Discover, using COMPASS force field. A wide range of small molecules were found to be incorporated into crystals of 1.The crystal and molecular structures of the first dimorph 1a of 1 has been found previously. Six different packing arrangements, which have been divided into four groups, for the cosolvates of 1 were found. For the conformations of the six-membered ring of 1 in the different cosolvates, we have found that: three different conformations can be adopted by the host molecule 1: boat form with two short and four long C—C bonds in the six-membered ring (quinonoid character), twist form with two long and four short C—C bonds (cyanine character) and intermediate twisted-boat form. The following results were obtained from both DSC experiments and the theoretical calculations of the lattice energy: 1.Substantially high dissolution energy Ediss (obtained from DSC measurements) and lattice energy/molecule ELM (obtained from force field calculations) were found for the solvates that have host-guest intermolecular hydrogen bonds, for solvates that have methyl group in the para position and for inclusion crystals with benzonitrile and nitroethane. 2.Form 1a, which has chain character of the intermolecular hydrogen bonds system, is more stable than 1b, which have a dimer character of the intermolecular hydrogen bonds system. 3.The stabilities of the structures with isomeric inclusion molecules are in the following sequence: cosolvates with para > ortho > meta substitution pattern. 4.The close packing structure is always more stable then the other structure. For every structure powder diffraction measurements have been performed at room temperature and at temperature higher than the guest dissolution temperature. All the cosolvate structures changes to structure 1a after the evaporation of the solvent, except that of anisole which change to structure 1b. Detailed calculations of the interaction energies between the different molecules in each structure have been done to understand the factors affecting the crystal packing forces. The following results have been found: ·In the structures without solvent (the dimorphs) the largest interaction in the crystal has been calculated to be between the pair of molecules that connected with intermolecular hydrogen bonds. ·For the cosolvate structures in group 2, there are a dimer (two neighbouring molecules that are connected with intermolecular hydrogen bonds) or a pair (two neighbouring molecules sitting in the analogue position as the dimer but not connected with intermolecular hydrogen bonds) character structure of the host molecules. The largest interaction has been calculated to be between the host molecules of different dimers or pairs, which are not connected with intermolecular hydrogen bonds. This is because the intermolecular hydrogen bonds within the dimer are of week type, their lengths (NH—O) range between 3.20 Å and 3.43 Å. On the other hand, strong dispersion interactions in addition to considerable electrostatic interactions, have been calculated between the molecules of the different dimers or pairs, which can be attributed to the many close contacts between the methyl…methyl, nitro…methyl and nitro…nitro groups of these molecules. The nitro group free of intramolecular hydrogen bond and the methyl groups of the neighbouring isopropylamino groups are generally the groups that responsible for this interaction. ·The twist or the twisted boat six-membered ring conformations of the host 1, which are the forms adopted by 1 in the most cosolvates structures, are very suitable for the generation of many van der Waals interactions between the different layers within the packing patterns of our cosolvate structures.
In dieser Arbeit werden grundlegende Untersuchungen zum Synthesepotential von überkritischem Wasser (SCW, p > 250 bar, T > 374 °C) bei metallorganischen Reaktionen durchgeführt. Besonderer Wert wird dabei auf bisher wenig bis gar nicht beachtete Eigenschaften des überkritischen Wassers (z.B.: hohe Raum-Zeit-Ausbeuten oder sein ausgezeichnetes Lösevermögen für gasförmige Substanzen) gelegt. Um effektive Synthesestrategien aufbauen zu können, ist es wichtig, eine klare mechanistische Vorstellung über die ablaufende Reaktion zu besitzen. Daher wird in dieser Arbeit großer Wert auf die Aufklärung der Mechanismen der untersuchten Reaktionen gelegt. Um das Potential von SCW hinsichtlich gleichzeitiger Löslichkeit von organischen Stoffen, Gasen und Präkatalysatoren sowie Beschleunigung von Reaktionen voll ausschöpfen zu können, wird die Hydroformylierung von Alkenen mit diversen kobalt- bzw. rhodiumhaltigen Präkatalysatoren untersucht. Die benötigte Reaktionszeit wird dabei stark verkürzt. Die Produktverteilung und der Einfluß der Substrate darauf werden im Detail untersucht. Ein weiterer Schwerpunkt dieser Arbeit liegt in der Cyclotrimerisierung von mono- und disubstituierten Acetylenen in SCW unter Aspekten wie der Variation der Acetylene oder des Katalysatorsystems von kobalt- auf rutheniumhaltige Katalysatorvorstufen. Dabei wird besonderer Wert auf die Erklärung ihrer unterschiedlichen Reaktivität und den Vergleich der Produktverteilungen mit Ergebnissen aus analogen Umsetzungen in organischen Solventien gelegt. Die bei diesen Reaktionen auftretenden stabilen metallorganischen Komplex-verbindungen werden nachgewiesen und charakterisiert. Außerdem wird die übergangsmetallkatalysierte Metathese untersucht und die organische Produktverteilung verschiedener Metathese-Präkatalysatoren aufgeklärt und verglichen. Die in der Hydroformylierung intermediär auftretenden Metall-Hydrid-Bindungen sind unter den Bedingungen des überkritischen Wassers nicht stabil und führen zur Zersetzung der verwendeten Katalysatorsysteme. Dagegen erweisen sich die bei der Alkenmetathese und der Cyclotrimerisierung eingesetzten Katalysatoren als stabil, bei der Cyclotrimerisierung mono-substituierter Acetylene können zusätzlich metallorganische Zwischenprodukte aus dem Reaktionsgemisch isoliert werden.
Colloidal semiconductor nanocrystals (NCs) have recently been introduced as novel fluorescent labels for various biological applications. Their unique optical properties — tunable narrow emission spectrum, broad excitation spectrum, high photostability and long fluorescent lifetimes (on the order of tens of nanoseconds) — make them attractive probes in experiments involving long observation times, multicolor and time-gated detection. Photophysical properties were investigated at the ensemble and single-molecule level for CdSe or CdTe core, CdSe/ZnS core-shell and surface-modified NCs. The use of NCs as fluorescent probes in biological applications requires various synthesis routes and surface modifications to enable solubility in aqueous solution and to allow labeling of biological macromolecules. Due to NC’s sensitivity to surface-defects chemical treatments have a significant influence on photophysical properties and need to be thoroughly monitored. Single-molecule fluorescence detection was used to characterize NC fluorescence, observe intermittency in the emission (blinking), and unravel a non-fluorescent subpopulation of NCs whose fluorescence can be restored through photo-induced activation. Stage-scanning confocal, epifluorescence and objective-type total-internal-reflection microscopy, were applied to observe surface-immobilized NCs. Fluorescence lifetimes were determined to be around 20 ns for single particles showing deviations from a mono-exponential decay. This observation was proven to be characteristic of single particles by monitoring photon antibunching. Fluorescence correlation spectroscopy (FCS) was used to characterize photophysical and colloidal properties in solution. It was shown to be a powerful technique to rapidly evaluate information on synthesis and surface modifications. These are essential to achieve water-solubility and bio-conjugation and dramatically influence the optical performance. FCS allows measuring concentration of fluorescent particles, an average brightness and particle size. From these observables, the brightness per particle can be estimated, something not possible in ensemble measurements due to the presence of absorbing but dark particles. The ratio of dark to fluorescent NCs was estimated and concentration changes due to photo-induced activation were observed. Particle sizes measured by FCS were compared to transmission electron microscopy and found in good agreement down to 7 nm. The correlation amplitude was observed to be excitation power dependent which was attributed to saturation and optical trapping effects. An electronic polarizability was evaluated and found to be two orders of magnitude larger than reported for measurements at non-resonant wavelength. Monte-Carlo simulations (MCS) were performed to compute autocorrelation functions under the influence of power-law blinking. Diffusion through a confocal volume, excitation-emission cycles with defined rate constants and on/off blinking were incorporated into MCS and used to investigate influences of saturation, size-distributions, photobleaching and blinking. The results were compared to experimental data of various NCs. Simulations account for both types of experimentally observed effects of blinking in FCS curves: significant deviation from a diffusion-model observed at high excitation powers; and no deviation from a diffusion-model despite the existence of blinking, observed at low excitation powers. Simulations showed that blinking does not influence FCS data for certain power law parameters.
Diese Arbeit beschäftigt sich mit Selbstorganisationsprozessen auf strukturierten Substraten mit dem Ziel der Darstellung leitfähiger Strukturen, die in neuartigen Verschaltungen im Kraftfahrzeug Anwendung finden könnten. Ein Ansatz basiert auf leitfähigen Kolloiden, die mittels Layer-by-Layer-Assembly (LbL) mit einer leitfähigen Goldschale versehen wurden. Die Leitfähigkeit wurde mittels UV/Vis- und XP-Spektroskopie untersucht. Derartig leitfähige Partikel konnten einer selektiven Oberflächenadsorption auf mittels Mikrokontaktdrucken strukturierten Goldoberflächen unterzogen werden. Die Strukturierung war z.B. eine abwechselnd methyl- und carboxylterminierte Oberfläche. Es bildeten sich dichtgepackte Drähte aus den Partikeln in den carboxylterminierten Bereichen aus. Auch in elektrophoretischen Prozessen sind diese Kolloidpartikel steuerbar, da sie eine geladene Oberfläche besitzen. Der zweite Ansatz beschäftigt sich mit selektiven elektrochemischen Metallabscheidungen an unterschiedlich strukturierten Substraten. Als Substrate dienten hochorientierter pyrolytischer Graphit (HOPG), selbstaggregierte Thiolmonolagen auf Gold und Hydroxybiphenylmonolagen auf Silicium. Die Monolagen konnten hier mittels Bestrahlung mit niederenergetischen Elektronen strukturiert werden. Auf derartigen Substraten kann eine selektive elektrochemische Metallabscheidung im Nanometermaßstab ausgeführt werden. Im Mikrometermaßstab führt die optische Lithographie auf Siliciumwafern zu Mikrokanalstrukturen, die elektrochemisch mit Metallen wie Silber und Palladium beschichtet wurden. Palladium-Mikrokanäle können als Wasserstoffsensoren, Silber-Mikrokanäle als Ammoniaksensoren dienen. Es wurden Konzepte erarbeitet, die derartige Prozesse für eine Realisierung im Kraftfahrzeug theoretisch möglich erscheinen lassen.
Gegenstand der Arbeit war die Synthese und Charakterisierung von Hartstoffschichten mit einer definierten Zusammensetzung im übergeordneten System Ti-B-C-N. Die Abscheidung der Schichten erfolgte mit der ionenstrahlgestützten Beschichtungstechnik (IBAD). Bei den untersuchten Hartstoffen handelt es sich um Karbide und Nitride bzw. Karbonitride von Titan und Bor sowie Boride von Titan, die der Zusammensetzung folgend formal in die ternären Schichtsysteme B-C-N, Ti-C-N und Ti-B-C eingeordnet bzw. zum Gesamtsystem Ti-B-C-N zusammengefasst werden können. Die Adhäsion der abgeschiedenen Schichten war auf allen Substraten mit Ausnahme einiger Glassubstrate sehr gut, was auf eine geeignete Vorbehandlung schließen lässt und durch den Aufbau eines breiten Schichtinterface bedingt durch den Ionenbeschuss zu erklären ist. Die härtesten Schichten wurden im System Ti-B-C und B-C-N abgeschieden. Das beste Verschleißverhalten besitzen die stickstoffhaltigen Schichten im System Ti-C-N, die unter N2+-Ionenbeschuss synthetisiert wurden. Hinsichtlich des Korrosionsschutzvermögens schneiden die TiBC-Schichten am besten und die TiCN-Schichten nur wenig schlechter ab. Die Eisenauflösung des Stahlsubstrates ist um ca. den Faktor einhundert gegenüber dem unbeschichteten Stahl reduziert. Die BCN-Schichten weisen eine vergleichsweise schlechte Schutzwirkung gegen korrosiven Angriff auf. Dies zeigt sich besonders im Langzeitverhalten, wo die TiBC- und TiCN- Schichten eine gute Schutzwirkung demonstrieren. Für eine Kombination von gutem Verschleißverhalten und wirksamem Korrosionsschutz sind Schichten im Ti-B-C-System am besten geeignet. In den Systemen B-C-N und Ti-C-N wurden bei einigen der Schichten außerdem Hinweise auf die Bildung von ternären Verbindungen ("BCN", "TiCN") gefunden. Es bestehen Bindungen zwischen den Schichtatomen B bzw. Ti, C und N und es deuten sich im XRD nanokristalline Phasen der ternären Verbindungen h-BCN und TiCN (kfz) in den betreffenden Schichten an. Die ternäre Phase liegt jeweils neben binären Phasen (Borkarbid, BN bzw. TiN, TiC) in der Gesamtschicht vor. Eine eindeutige Zuordnung zu den ternären Verbindungen ist jedoch aufgrund der vorliegenden Daten noch nicht möglich. Dazu sind weitere Untersuchungen und Vergleiche mit Ergebnissen anderer Autoren notwendig.
Der Komplex L2Cu2 ist ein erstes funktionelles Modellsystem für die DNA-Polymerase I und weitere Phosphoryltransferenzyme, die nach analogem Mechanismus arbeiten. Die Komplexe der makrocyclischen Liganden L1 und L2 wurden wegen der bereits bekannten Metall-Metallabstände und der hohen Affinität gegenüber verbrückenden Substraten gewählt. Neben der kristallographischen Charakterisierung der Komplexe L1M2 und L2M2 wurde ihre katalytische Aktivität bei der Umesterung von Phosphodiestern untersucht. Der Kupfer(II)-Komplex von L2 ist der katalytisch aktivste LM2-Komplex und beschleunigt spezifisch die Umsetzung kleiner nichtaktivierter Dialkylphosphate. L2Cu2 estert als erstes veröffentlichtes Beispiel den nichtaktivierten Phosphatester Dimethylphosphat in Deuteromethanol mit k(cat) = 9*10^-6/s um (Hydrolyse: K = 10^-18/s). Die Ergebnisse unterstützen einen Reaktionsmechanismus, der für die Hydrolyse der Phosphodiesterbindung in DNA durch die 3',5'-Exonucleaseeinheit der DNA-Polymerase I vorgeschlagen wird. Die Röntgenstruktur [L2Cu3(m-OH)(m-CH3O)2(CH3CN)2]3+ kann als erstes Analogon des Übergangszustandes der Phosphatumesterung dienen. Der Ligand L3 wurde als Monomerbaustein für geprägte Polymere synthetisiert. Bei der Polymerisation wird durch ein Templatmolekül eine spezifische Reaktionstasche vorgebildet, in der nach Entfernen des Templats eine Reaktion beschleunigt ablaufen kann. Da Phosphate strukturell dem Übergangszustand der Esterhydrolyse ähneln, können mit ihnen geprägte Polymere für diese Reaktion als Katalysatoren dienen. L3, die Metallkomplexe L32Cu und L3Cu sowie der doppelt substratverbrückte Komplex L32Cu2(m-P(O)2(CH3)2)2 wurden als Einkristall erhalten. Nach der Polymerisation der L3Cu-Komplexe mit einem Copolymer konnte Cu2+ reversibel entfernt werden, d.h. die Reaktionstaschen sind sterisch zugänglich. Vorläufige Untersuchungen zeigten auch eine katalytische Aktivität der geprägten Polymere bei der Hydrolyse von Carbonsäureestern.
Synthese, Charakterisierung und kristallogrpahische Studien von 2,5-Dimethoxyphenyl- und Chinon-substituierten Octa-3,5-diinen. Untersuchungen zur Topochemie zeigten eine ausgeprägte Festkörperphotoreaktivität einiger hergestellter Derivate.
Im Rahmen dieser Arbeit wurde zunächst ein Strömungskanal zur Untersuchung einer statistisch stationären turbulenten Strömung aufgebaut. Der Kanal besteht aus einem Beobachtungsbereich einer Länge von 18 cm, der so konstruiert ist, dass die Bodenplatte des Kanals problemlos ausgetauscht und durch Platten unterschiedlicher Beschaffenheit ersetzt werden kann. Durch ein sehr großes Seitenverhältnis (Faktor 12) ändert sich die Strömungsgeschwindigkeit nur in Abhängigkeit der Höhe über der Bodenplatte. In dem Strömungskanal lassen sich turbulente Luft- und Stickstoffströmungen bei Reynolds-Zahlen zwischen Re = 6000 und 15500 mit korrespondierenden mittleren Maximalgeschwindigkeiten zwischen 18 und 47 m/s realisieren. Unter Anwendung der am Physikalisch-Chemischen Institut entwickelten Strömungsmarkierungstechnik wurden, basierend auf der Erzeugung von linienförmigen Stickstoffmonoxid-Strukturen, verschiedene turbulente Strömungen untersucht. Die bestehende Technik wurde dahingehend weiterentwickelt, dass die Erzeugung einer Struktur aus drei parallelen NO-Linien möglich ist. Ein detaillierter Vergleich der experimentellen Ergebnisse mit einer am Interdisziplinären Zentrum für wissenschaftliches Rechnen der Universität Heidelberg ausgeführten direkten numerischen Simulation (DNS) zeigt eine sehr gute Übereinstimmung der Verschiebung und der großskaligen Verformung der erzeugten Linienstrukturen durch die turbulente Strömung. Zum Vergleich der in der Simulation initialisierten Turbulenz mit der im Experiment realisierten Strömung wurden simultane Messungen der Linienverschiebung mit Hilfe der Strömungsmarkierungstechnik und des 2-dimensionalen Strömungsgeschwindigkeitsfeldes unter Einsatz der Particle Image Velocimetry (PIV) durchgeführt. Um die in der DNS dargestellte zeitliche Entwicklung der Turbulenzstrukturen experimentell verifizieren zu können, wurde anschließend ein System zum mehrfachen Nachweis einer erzeugten Stickstoffmonoxid-Linie aufgebaut. Experimente zum doppelten Nachweis einer Linienstruktur ermöglichen einen Vergleich der zeitlichen Entwicklung der Linienstruktur zwischen Experiment und Simulation. Die zeitliche Entwicklung selbst kleinskaliger Strukturänderungen lässt sich mit dem aufgebauten System erfolgreich nachweisen. Das Verfahren ermöglicht außerdem die Bestimmung der Dicke der Geschwindigkeitsgrenzschicht, d.h. des Bereiches der größten Geschwindigkeitsänderung zwischen Wand und turbulenter Pfropfenströmung in der Kanalmitte. Aus dem beobachteten Transport der Linie in dieser Geschwindigkeitsgrenzschicht wurde die Verteilung der Strömungsgeschwindigkeiten in Abhängigkeit vom Wandabstand bestimmt. Parallel dazu wurden unterschiedliche Verfahren zur inhomogenen Strömungsdotierung mit molekularen Tracern angewandt. Die Verfahren ermöglichen zum einen, ausschließlich die Grenzschicht mit Naphthalin und Stickstoffmonoxid zu markieren und zum anderen eine Wolke aus Stickstoffmonoxid-Molekülen in der turbulenten Strömung zu verfolgen. Durch die in der Strömung entstehenden Konzentrationsgradienten erlauben diese Verfahren jeweils die Identifizierung der reibungsbestimmten Grenzschicht direkt an der Wand, eine Visualisierung des diffusiven Spezies-Transportes durch diese Grenzschicht hindurch und eine Visualisierung des turbulenten Spezies-Transportes aus dieser Grenzschicht in die turbulente Strömung hinein.
Die allosterische Regulation der katalytischen Aktivität ist ein in der Enzymkatalyse weit verbreitetes Phänomen, wurde aber bei synthetischen Katalysatoren bisher nicht untersucht. Im Rahmen der Arbeitmehrkernige Metallkomplexe als Modellsysteme für allosterische Metalloenzyme untersucht. Die Katalysatoren sind durch eine dinukleare, katalytische Untereinheit und eine allosterische Untereinheit mit strukturellem Metallion (MS=M(II)) charakterisiert. Von den isolierten Komplexen, darunter 4 mononukleare ((L2-2H)Ms, Ms=Cu(1), Ni (3) und Pd (4)) und (L3-2H)Cu (2), wurden 3 (1,5,6) kristallographisch charakterisiert, wodurch Einblicke in die strukturelle Rolle von MS erhalten wurden. 5 (dachförmig) und 6 (helical), welche die trinuklearen Einheiten mit verbrückenden Anionen (Oxalat, Glycinhydroxamat) enthalten, konnten ein Gefühl für den zugänglichen Konformationsraum der (L2-2H)Cu3-Untereinheiten vermitteln. Reaktionskinetische Untersuchungen zur katalytischen Spaltung RNA-Analogons 2-Hydroxypropyl-p-nitrophenylphosphat (HPNP) zeigten, daß das allosterische Metallion in den Komplexen (L2-2H)MSCu2 starken Einfluß auf die Aktivität hat. Mit MS=Cu ist die Aktivität doppelt so hoch wie mit MS=Pd. Auch die Struktur und Flexibilität des Liganden bestimmt die Aktivität: Der etwas flexiblere Komplex (L2-2H)Cu3 katalysiert die Spaltung des koordinierten HPNP 2.3 mal schneller als (L3-2H)Cu3, während dieser das Substrat besser bindet. Die kompetitive Hemmung dieser Reaktion durch verbrückend koordinierende Anionen ist besonders effizient bei Oxoanionen mit einem O...O-Abstand ("Bißweite") von 2.5 - 2.8 A, der etwa dem des Oxalats in 5 entspricht. (L2-2H)Cu3 wird durch größere Anionen wie ReO4-, (L3-2H)Cu3 dagegen durch kleinere stärker gehemmt. Hieraus wird die Hypothese abgeleitet, daß (L2-2H)Cu3 den sterisch anspruchsvollen Übergangszustand der Spaltreaktion besser stabilisiert, weil Konformationen mit größerem Abstand der funktionellen Cu2+-Ionen, bedingt durch die Rückgrat-Flexibilität von L2, besser zugänglich und damit energiegünstiger sind als in (L3-2H)Cu3.
Im Rahmen dieser Arbeit wurden Gemischbildung, Verbrennung und Schadstoffbildung eines Dieselsprays experimentell an einer weltweit neuartigen Hochdruck- und Hochtemperatur-Zelle unter motortypischen Bedingungen untersucht. Dabei wurden eine Vielzahl laserdiagnostischer Techniken an den Versuchsträger adaptiert, die eine berührungsfreie, örtlich und zeitlich aufgelöste und quantitative Messung von Treibstoffdampfverteilung und Rußkonzentration sowie eine qualitative Messung der Rußpartikelgröße, NO-, und Formaldehyd-Konzentration (HCHO) und der Konzentration von polyzyklischen aromatischen Kohlenwasserstoffen (PAH) in gezündeten und ungezündeten Dieselsprays ermöglichten. Bei diesen laseroptischen Verfahren handelte es sich um planare Rayleigh-Spektroskopie (Rayleigh-Lichtstreuung), planare laserinduzierte Inkandeszenz (LII) und planare laserinduzierte Fluoreszenz (LIF) an NO, PAH und HCHO. Erstmals wurde zudem 5-Nonanon als fluoreszierender Treibstoffmarker zur Beobachtung der Kraftstoffverteilung eingesetzt. Gleichfalls zum ersten mal wurden Rußvolumenbruch, Treibstoffdampfdichte via Rayleigh-Lichtstreuung, relative NO-Konzentration und die Rußpartikelgröße D63 simultan gemessen. Die gleichzeitige Abbildung der beiden antagonistischen Spezies NO und Ruß ist dabei von großem Interes-se für die technische Anwendung. Ebenso wurden die Konzentrationen an HCHO, PAH und Treibstoff (via Tracer-LIF an 5-Nonanon) simultan abgebildet. HCHO gilt als guter Indikator für das Vorliegen des sogenannten kalten Verbrennungsprozesses. PAHs sind bekannt als Grundbausteine und Vorläufer von Rußpartikeln. Alle Messungen wurden an mehreren Messpositionen zeitaufgelöst unter systematischer Variation verschiedener experimenteller Parameter durchgeführt, wie Umgebungsdruck, Temperatur, Injektionsdruck, zeitliche Injektionssteuerung, Typ der Einspritzdüse und Sauerstoffkonzentration in der Verbrennungskammer. Anhand spektral aufgelöster Voruntersuchungen des gezündeten und ungezündeten Dieselsprays wurden Anregungs- und Detektionsschemata dieser laserdiagnostischen Experimente überprüft, vom Detektionszeitpunkt abhängige Untergrundsignale aufgeklärt und die Fluoreszenzeigenschaften des neuen Kraftstoffmarkers 5-Nonanon unter motorischen Bedingungen charakterisiert. Im Rahmen dieser Arbeit gelang ein umfangreicher Einblick in die Natur dieselmotorischer Verbrennungsprozesse. Die experimentellen Befunde wurden zur Überprüfung gängiger, konzeptioneller Verbrennungsmodelle herangezogen und erwiesen sich als wichtige Grundlage zur Entwicklung und Validierung zukünftiger numerischer Simulationsverfahren.
Die Optimierung von Verbrennungssystemen durch empirische Methoden stößt immer wieder an ihre Grenzen. Um weitere Fortschritte in der Entwicklung effizienter Verbrennungssysteme zu gewährleisten, ist deshalb das Verständnis der dem Verbrennungsprozess zugrunde liegenden mikroskopischen Vorgänge unerlässlich. Im Rahmen dieser Arbeit wurden laserdiagnostische Untersuchungen in drei Teilgebieten der motorischen Verbrennungsforschung durchgeführt. Die verwendeten Methoden beruhen auf der Nutzung moderner leistungsfähiger Lasersysteme. Der entscheidende Vorteil von optischen Verfahren ist, dass sie berührungsfrei arbeiten und das zu untersuchende System daher nicht beeinflussen. Für die Messungen im Versuchsmotor und für das Experiment zur Messung der lokalen Sauerstoffkonzentration wurde der Laserstrahl zu einem Lichtblatt geformt, wodurch sich das jeweilige Messobjekt zweidimensional beleuchten ließ. Mittels bildverstärkender Kameras wurden in dieser Ebene freigesetzte Fluoreszenzsignale beobachtet. In einer Hochdruckzelle wurden die Kalibrationsdaten mittels einer Punktmessungen generiert. Der erste Schwerpunkt, welcher in dieser Arbeit gesetzt wurde, waren Untersuchungen des Verbrennungsprozesses in einem HCCI?Motor (homogeneous charge compression ignition). Im Rahmen eines EU-Projektes (4?Space) konnten mittels zweidimensional aufgelöster laserinduzierter Fluoreszenz (2D?LIF) Messungen an einem HCCI?Versuchsmotor am Institut Français du Pétrole durchgeführt werden. Hauptziel war die Lokalisierung der Zündzonen sowie die Charakterisierung ihrer Struktur und deren Entwicklung. Beim HCCI-Motor waren zwei Möglichkeiten denkbar, wie die Mischung zünden könnte: Das Gemisch könnte aufgrund der hohen Temperatur im gesamten Brennraum simultan zünden oder aber bevorzugt in einzelnen Regionen, von denen aus sich die heiße Flamme dann ausbreitet. Es wurden 2D-LIF?Messungen an 3?Pentanon durchgeführt, welches dem Kraftstoff als Tracer beigemischt wurde. Diese Messungen dienten der Untersuchung der Vorgänge im frühen Kompressionszyklus. Weil 3?Pentanon in der cool-flame-Phase zerstört wird, musste für die Untersuchung der Zündung und der anschließenden Verbrennung ein anderer Tracer gefunden werden. Hier bot sich das in der sogenannten kalten Flamme in großen Mengen gebildete Formaldehyd an, welches dann in der heißen Reaktionszone verbrennt, und das so als Marker für die Grenzschicht zu den Zonen der heißen Verbrennung dienen konnte. Es wurde gezeigt, dass die Zündung in diesem HCCI?Versuchsmotor nicht überall zugleich einsetzt, sondern dass sie an bestimmten Punkten beginnt. Die Startpunkte der Zündung wurden lokalisiert und ihre statistische Verteilung berechnet. Der zweite Schwerpunkt dieser Arbeit ergab sich durch eine Kooperation mit General Motors. Dort waren bereits 2D?LIF?Messungen an einem bis dahin noch nicht verwendeten Exciplex (excited complex)?System, bestehend aus Fluorbenzol und N,N?Diethylmethylamin in n?Hexan, durchgeführt worden. Mittels dieser Messungen wurden verschiedene Einspritzsysteme in einem DI?Motor untersucht. Die Verwendung von Tracer?Mischungen, welche einen Exciplex bilden, ermöglicht, Gas? und Flüssigphase getrennt voneinander zu detektieren, da der dominante Emitter in der Gasphase eines der Monomere ist, in diesem Fall Fluorbenzol. In der Flüssigphase bildet angeregtes Fluorbenzol mit dem anderen Monomer, N,N-Diethylmethylamin (DEMA), einen Exciplex. Dessen Signal ist relativ zum Fluorbenzol-Signal rotverschoben und kann so unter Verwendung geeigneter Filter getrennt vom Monomer?Signal detektiert werden. Des Weiteren sollen diese Messdaten zur Modellierung eines verdampfenden Treibstoff?Sprays dienen. Bei der Auswertung der Messdaten stellte sich das Problem, dass im Signal der Gasphase zu verschiedenen Zeitpunkten nach der Einspritzung Fehlsignale auftreten, welche durch die Überlappung der Spektren von Exciplex? und Monomer?Signal entstehen. Um dieses Fehlsignal eliminieren zu können, wurden Kalibrationsdaten benötigt. Grundsätzlich muss also die Intensität und Temperaturabhängigkeit des Störsignals relativ zum Exciplex?Signal bekannt sein. Diese Parameter wurden im Rahmen dieser Arbeit experimentell ermittelt. Darüber hinaus wurde gezeigt, dass auch das Exciplex?Signal stark temperaturabhängig ist und dies in die Korrektur der Messdaten mit eingehen muss. Diese Informationen sind ein wichtiger Beitrag zur Auswertung von Daten, welche mit diesem Exciplex?System aufgenommen werden. Im letzten Teilgebiet dieser Arbeit wurde die Gemischbildung in Verbrennungssystemen untersucht. Zu deren Bestimmung in einem Treibstoff-Luftgemisch konnte in unserer Arbeitsgruppe bereits ein Zwei-Tracer-Verfahren entwickelt und angewendet werden. Es basiert darauf, dass die Fluoreszenz des einen Tracers effektiv von Sauerstoff gelöscht wird, die des anderen hingegen nur sehr schwach. Wenn man die Fluoreszenzsignale der beiden Tracer spektral getrennt voneinander detektiert, kann man aus dem Signalverhältnis die lokale Sauerstoffkonzentration ermitteln. Leider sind die Fluoreszenzsignale der verwendeten Tracer auch bei optimalem Mischungsverhältnis nicht gänzlich unabhängig voneinander, so wie es eigentlich erwünscht wäre. Dieser Effekt lässt sich zwar rechnerisch korrigieren, aber diese Korrektur ist sehr aufwändig. Es wurde deshalb in dieser Arbeit gezeigt, wie diese Methode auch unter Verwendung nur eines Tracers durchgeführt werden kann. Dies ist möglich, wenn die verschiedenen spektralen Bereiche des Fluoreszenzsignals dieses Tracers verschieden stark gelöscht werden. Eine weitere Bedingung ist die getrennte Detektion des Teils des Spektrums, der sehr stark durch Sauerstoff gelöscht wird und des Teils, der praktisch nicht gelöscht wird. Aus dem Signalverhältnis kann man die lokale Sauerstoffkonzentration bestimmen. Kennt man die lokale Sauerstoffkonzentration kann man die Tracerkonzentration bestimmen. Damit ist dieses Messverfahren den bisher verwendeten Verfahren, die nur einen Tracer verwenden überlegen. Diese konnten nur entweder die lokale Sauerstoffkonzentration oder die Tracerkonzentration bestimmen. In dieser Arbeit wurden die für diese Messmethode nötigen Kalibrationsdaten an der statischen Hochdruckzelle gemessen. Anschließend wurde die zweidimensionale Anwendung an einem Messobjekt erfolgreich durchgeführt. Mit dieser Methode steht für zukünftige Untersuchungen der Gemischbildung in Verbrennungsmotoren ein wertvolles Instrument zur Verfügung.
Work developes method of scanning and viewing molecules.
Es wurden stickstoffhaltige sowohl makrocyclische als auch offenkettige Liganden, die entweder Metallocen- oder Ruthenium(II)-Bipyridin-Einheiten enthalten, synthetisiert. Die Übergangsmetallkomplexe dieser Liganden wurden mittels CV, Röntgenstrukturanalyse,UV-Vis-, IR-, ESR- und Mössbauer-Spektroskopie auf eine elektronische Wechselwirkung zwischen den beiden Metallzentren untersucht. Zusätzlich wurden potentiometrische Titrationen durchgeführt, um die Stabilitäten der Komplexe zu bestimmen. Es zeigte sich, dass die Metallocenhaltigen Liganden Fcmac und Rcmac als Kupfer(II)-Sensoren fungieren, da die Stabilitäten der Kupfer(II)-Komplexe beispielsweise 11 Grössenordnungen über denen der korrespondieren Nickel(II)-Komplexe liegen. Die Eisenkomplexe des Ferrocenhaltigen Liganden Fcmac können als molekulare Schalter fungieren.
Zur Optimierung großtechnischer Verbrennungsprozesse werden schnelle In-situ-Gassensoren benötigt. In dieser Arbeit wurden basierend auf der Absorptionsspektroskopie mit Nahinfrarot-Diodenlaser berührungsfrei arbeitende Multispezies-Spektrometer zur simultanen In-situ-Detektion von CO, O2 und H2O entwickelt. Dazu mussten neue Methoden zur Unterdrückung der starken optischen Störeinflüsse der Verbrennungsprozesse entwickelt, sowie Lösungen für zahlreiche technische Probleme gefunden werden. Verschiedene Spektrometervarianten konnten in technischen Müllverbrennungsanlagen und einem Braunkohlekraftwerk getestet und erfolgreich eingesetzt werden.
Im Rahmen dieser Arbeit konnten die Strukturen der GTPase-Domäne von Dynamin 1 aus Rattus norvegicus sowie der Motordomäne von Myosin II aus Dictyostelium discoideum in atomarem Detail aufgeklärt werden. Die vorgelegte Kristallstruktur der nukleotidfreien GTPase-Domäne von Dynamin 1 zeigt, daß die GTPase-Domäne in Säugerdynamin sehr ähnlich gefaltet ist wie in Dynamin A aus D. discoideum. Das vorgelegte Strukturmodell enthält alle Schlaufenbereiche und erlaubt somit erstmals die vollständige Beschreibung der Nukleotidbindungsregion eines Dynamins. Im Gegensatz zu anderen GTPasen ist das switch I-Threonin, das für die GTP-Koordination wichtig ist, in Dynamin 1 in seiner katalytisch aktiven Konformation gehalten. Desweiteren konnte anhand des Strukturmodells für Arg59 eine Funktion als Beschleuniger der GTP-Hydrolyse vorgeschlagen werden. Die Kristallstruktur der Myosin-Kopfdomäne zeigt eine neue Konformation des Motorproteins, in der sich beide nukleotidbindenden Schalter in der offenen Stellung befinden. Dieser bislang nicht beobachtete Zustand wird in einer neuen Nomenklatur als O/O-Konformation bezeichnet. Aus dem Strukturmodell wird deutlich, daß Nukleotid- und Aktinbindungsstelle nicht nur über switch II, sondern auch über switch I miteinander kommunizieren können. Umschalten von switch I verändert über das zentrale Faltblatt die Geometrie der Aktinbindungsstelle am äußeren Ende der 50K-Spalte. Dabei sind die Schalterstellungen nicht vollständig entkoppelt. Switch I kann erst öffnen, wenn switch II bereits offen ist. In der O/O-Konformation ist switch II weiter geöffnet als bisher beobachtet, was in Kombination mit der offenen Stellung von switch I zur Freisetzung von ADP führen kann. Durch die Ergebnisse der vorliegenden Arbeit konnte das bisherige Bild des Akto-Myosin-ATPase-Zyklus ergänzt werden, indem neben der Stellung von switch II auch die Stellung von switch I berücksichtigt wird. Nach dem Kraftschlag und der Dissoziation von Phosphat durch Öffnen von switch II muß switch I öffnen, um auch ADP freizusetzen. Nach Erreichen des Rigorzustands schließt sich switch I mit der Bindung von ATP und der Myosinkopf dissoziiert vom Aktinfilament. Die O/O-Konformation kann im Akto-Myosin-ATPase-Zyklus in unmittelbarer Nähe zum Rigorzustand eingeordnet werden.
Diese Arbeit beschäftigt sich mit dem Aufbau, der Struktur und Reaktivitätsuntersuchung monomerer Imidazolylborane sowie der Synthese von 2,3-Dihydroimidazolylborane
Die Arbeit beschäftigt sich mit der Reaktivität von Diboraruthenocen sowie mit dem Aufbau und den Eigenschaften von 2,3-Dihydro-1,3-diboroliridium-Komplexen.
Komplexe chemische Reaktionssysteme setzen sich aus einer Vielzahl von Elementarreaktionen zusammen. Während sich die chemische Kinetik mit der Geschwindigkeit der Produktbildung und dem Einfluss äußerer Parameter wie Druck und Temperatur auf die Reaktion beschäftigt, beschreibt die Reaktionsdynamik den Ablauf der Reaktionen auf molekularer Ebene. Dabei wird die Reaktion nicht bei einer bestimmten Temperatur, bei der die Reaktanden immer einer breiten thermischen Energieverteilung unterliegen, sondern unter energetisch scharf definierten Anfangsbedingungen untersucht. Die Entwicklung leistungsfähiger Lasersysteme, die eine gezielte Anregung von Molekülen erlauben, war deshalb eine wichtige Voraussetzung für die Entwicklung der experimentellen Reaktionsdynamik. Der Einsatz von gepulsten Lasern erlaubt sowohl die zustandselektive Erzeugung von Reaktanden in Nicht-Gleichgewichtsverteilungen als auch die Analyse der Zustandsverteilung der entstehenden Produkte. In sogenannten „pump and probe“-Experimenten können so kurze Zeitauflösungen erreicht werden, dass Elementarreaktionen ohne Störung durch schnelle Folgereaktionen untersucht werden können. Mit Hilfe der laserinduzierten Fluoreszenzspektroskopie wurden für die Abstraktions- und die Isotopenaustauschreaktion des H + DCl-Reaktionssystems erstmals Gesamtreaktionsquerschnitte bestimmt und damit der nicht-adiabatische Reaktionskanal, der zur Bildung von spin-bahnangeregten Chloratomen führt, quantifiziert. Die experimentellen Ergebnisse wurden mit Resultaten aus quasiklassischen Trajektorienrechnungen auf den BW1 und BW2 Potentialenergieflächen verglichen. Bei der Abstraktionsreaktion zeigen sich Abweichungen, die darauf zurückgeführt werden, dass in den Potentialflächen der experimentell beobachtete Einfluss des nicht-adiabatischen Reaktionskanals unberücksichtigt bleibt. Für die Austauschreaktion dagegen zeigen Experiment und Theorie eine gute Übereinstimmung. Viele Reaktionen in der Atmosphäre werden durch die Photolyse von Molekülen eingeleitet, die nach UV-Anregung ein reaktives Atom verlieren. Große atmosphärische Relevanz besitzen chlorhaltige Verbindungen wegen ihres negativen Einflusses auf den Ozonkreislauf. Die quantitative Beschreibung dieser photochemischen Prozesse erfordert genaue Kenntnis der Quantenausbeuten dieser Reaktionskanäle. Im Zuge dieser Arbeit wurden die absoluten Chloratom-Quantenausbeuten von Tetrachlormethan (CCl4) und 1,1-Dichlor-1-fluorethan (HCFC-141b, CH3CFCl2) bei verschiedenen Photolysewellenlängen bestimmt. Für Acetylen und 1,1-Dichlor-1-fluorethan wurden die Wasserstoffatom-Quantenausbeuten ermittelt. Von besonderem Interesse ist der Zusammenhang zwischen dem spezifischen Anregungszustand und der photochemischen Reaktivität eines Moleküls. Durch die Kombination der gezielten Anregung von definierten Quantenzuständen durch geeignete Lasersysteme mit zustandsauflösenden Nachweismethoden (z.B. laserindizierte Fluoreszenz, LIF) ist dieser Zusammenhang experimentell zugänglich. Mittels der LIF-Technik wurde die Photodissoziation von hoch schwingungsangeregtem Wasser (vier OH-Streckschwingungsquanten) untersucht. Die Reaktivität selektiv angeregter Moleküle liefert wichtige Information über die Dynamik der Photodissoziationen, die wiederum als Grundlage für die Entwicklung und Validierung neuer theoretischer Methoden und Modellrechnungen dienen.
Hydration forces between organic solid surfaces were investigated by grand canonical Monte Carlo simulations. Our interests are forcued on the hydration forces at separation enough large for the water layering to decay. My work is devided into two parts. First, in order to investigate what kind of factors governs the sign and magnitude of hydration force, we model strucureless walls. We found that hydration force is determined not only the strength of surface-water interection, but also orienting effect of water. In the second part, we simulated the interface of water and oligo(ethylene glycol) terminated alkanethiol SAMs. We found that hydration force is not responsible for the resistance of surfaces to protein adsorption. Hydroxyl ions are responsible for long-ranged repulsion between proteins and the surface.
Die Einzelmolekülspektroskopie hat sich seit der ersten erfolgreichen Detektion von einzelnen, fluoreszierenden Molekülen in Lösung durch Hirschfeld [Hirschfeld 1976] zu einer eigenständigen Disziplin innerhalb der Fluoreszenzspektroskopie entwickelt. Im Gegensatz zu Ensemblemessungen, mit denen nur die durchschnittlichen Eigenschaften einer Probe bestimmt werden können, gewinnt man bei Einzelmolekülmessungen Informationen über die Eigenschaften einzelner Moleküle und deren Verteilungen und zeitlichen Fluktuationen, die sonst nicht zugänglich sind. Dies beruht auf der hohen Sensitivität und der betrachteten Zeitskala der Fluoreszenz, die sich typischerweise in der Größenordnung von Nanosekunden abspielt. Während dieser Zeit können in der Umgebung eine Reihe von molekularen Prozessen stattfinden, welche die Fluoreszenzeigenschaften wie Intensität, spektrale Verteilung, Polarisation und Lebensdauer der angeregten Moleküle beeinflussen. Im Rahmen dieser Arbeit ist es erstmals gelungen, einen Fluoreszenzmikroskopaufbau mit zwei konfokalen Detektionseinheiten in Submikrometerkanälen unter Elektrophoresebedingungen zu realisieren. In Mikrokapillaren mit einem Innendurchmesser von 500 ± 200 nm können hiermit einzelne farbstoffmarkierte Analytmoleküle in variablen zeitlichen Abständen doppelt detektiert werden. Da der Innendurchmesser der Kapillare kleiner als der Durchmesser des konfokal beobachteten Laserfokus (1 µm) ist, werden alle Analytmoleküle, die sich in diesem Mikrokanal gerichtet bewegen, effizient doppelt nachgewiesen und aufgrund ihrer Fluoreszenzabklingdauer identifiziert. Die zwei Anregungs- bzw. Detektionseinheiten sind mit zueinander variablen Abständen (4-10 µm) aufgebaut, was in elektrophoretischen Versuchen je nach angelegter Spannung variablen Zeitabständen von 5-300 ms entspricht. Die Doppeldetektion von einzelnen Molekülen in Mikrokanälen ist bisher von einigen Gruppen bis zu einem minimalen Kanaldurchmesser von 10 µm bei einem Abstand von 10 bis 25 µm zwischen den beiden Detektionsvolumina gezeigt worden [Brinkmeier 1999; LeCaptain 2002]. Die Auswertung der Daten erfolgte mittels einer Hardware-Korrelatorkarte, die ausschließlich eine Kreuzkorrelationsanalyse durchführt. Dieses Analyseverfahren beruht darauf, dass die wechselseitige Beziehung zweier Detektionssignale aufgedeckt wird. Zwei ähnliche Detektionssignale liefern hohe Werte innerhalb der Kreuzkorrelationsfunktion, während niedrige Werte bei nicht korrespondierenden Signalen berechnet werden. Die errechnete Verteilung gibt die Wanderungsgeschwindigkeit der Analytmoleküle zwischen den beiden Detektionsvolumina wieder. Es zeigt sich jedoch, dass die Kreuzkorrelationsanalyse zu einer fehlerhaften Interpretation führt, wenn die Intensität der Bursts einzelner farbstoffmarkierter Analytmoleküle stark in Breite und Höhe variieren. Daher ist ein neues Auswerteverfahren entwickelt worden, das die Formen der Photonenschauer auf Breite und Höhe normiert. Die Ergebnisse belegen, dass die Hardware-basierte Kreuzkorrelation ohne Berücksichtigung der originalen Zeitspuren nicht vertrauenswürdig ist. Diese Aussage gilt umso stärker je geringer die Statistik ist, d. h. je kürzer die Messdauer ist. Die Normierung der Breiten und Höhen der Photonenschauer ist dagegen auch für kürzere Messungen geeignet und liefert darüber hinaus die quantitative Information über die Anzahl der Burstpaare. Während die Analyse ohne Normierungen zu dem Resultat führt, dass fälschlicherweise zwei Komponenten mit unterschiedlichen Transitzeiten vorhanden sind, wird bei einer Normierung der Photonenschauer das erwartete einzelne Maximum gefunden. Durch die außen angelegte Spannung werden die Molekülgeschwindigkeiten in der Kapillare gesteuert. Hierzu ist eine effiziente Unterdrückung des elektroosmotischen Flusses (EOF) unabdingbar. Der EOF und die unspezifische Adsorption der Analytmoleküle an die Kapillarwände werden durch den Einsatz von dynamischer und statischer Wandbelegungsverfahren unterdrückt. Es konnte gezeigt werden, dass durch Zugabe von Detergenzien eine effiziente dynamische Wandbeschichtung realisierbar ist. Darüber hinaus konnte ein Beschichtungsverfahren von Submikrometerkanälen, das eine statische Wandbeschichtung mit Polyethylenglykol ermöglicht, entwickelt werden. Messungen mit Fibronektin, das als Adhäsionsmolekül in der extrazellulären Matrix bekannt ist, belegen die wirksame Unterdrückung der Adsorption von Analytmolekülen an Glasoberflächen und sogar in Submikrometerkanälen. Dies zeigt, dass auch ultrasensitive Messungen mit biologisch relevanten Proben in Dimensionen von Submikrometern möglich sind. Gleichzeitig werden unerwünschte Wechselwirkungen mit Detergenzien vermieden und Messungen in wässriger Lösung ermöglicht. Durch die Möglichkeit, einzelne Analytmoleküle in statisch beschichteten Submikrometerkanälen zu untersuchen, werden neue biologische Anwendungen und Diagnostikverfahren erschlossen.
Detaillierte Reaktionsmechanismen, die auf Elementarreaktionen beruhen, umfassen für Verbrennungssysteme höherer Kohlenwasserstoffe oft mehr als 100 Spezies. Solche komplexen Reaktionssysteme können nicht zur Simulation von technischen Verbrennungssystemen verwendet werden, da der Rechenzeitbedarf für eine CFD-Rechnung zu hoch wäre. Eine Möglichkeit zur Reduktion chemischer Reaktionsmechanismen stellt die ILDM-Methode dar. Sie beruht auf einer mathematischen Analyse der lokalen Zeitskalen des chemischen Quellterms und der Annahme, dass das chemische System bereits auf eine niedrig-dimensionale Mannigfaltigkeit relaxiert ist. Die Bestimmung der niedrig-dimensionalen Mannigfaltigkeit ist rechenzeitaufwendig. Daher wird die Mannigfaltigkeit in Tabellen gespeichert, die allerdings sehr groß werden können (einige 100 MB). Es wurde eine effiziente Tabellierungsmethode entwickelt, die einen schnellen Zugriff auf die Daten erlaubt. Um die Tabellenerzeugung zu beschleunigen, wurde an Algorithmus entwickelt, der die Erstellung einer ILDM-Tabelle auf einem Parallelrechner ermöglicht. Die erstellten Tabellen wurden zur Simulation räumlich homogenen Reaktionssysteme und freier laminarer Vormischflammen verwendet.
Thema dieser Arbeit ist die Synthese und das Komplexierungsverhalten von chiralen Phosphanliganden ausgehend von enantiomerenreinem Epichlorhydrin. Die Liganden unterscheiden sich in systematischer Weise im sterischen Anspruch eines Phosphandonors. Es konnte gezeigt werden, dass die resultierenden, pseudotetraedrischen Rutheniumkomplexe während der Synthese ohne Steuerung von außen in nur einem von vier möglichen Diastereomeren entstehen. Die Komplexverbindungen zeigen katalytische Aktivität in vielen Reaktionstypen. Der Einfluß der systematischen Änderungen am Ligandphosphan auf die Selektivität während der Katalyse wurde anhand der Diels-Alder-Reaktion, der Redoxisomerisierung von Allylalkoholen zu den entsprechenden gesättigten Aldehyden bzw. Ketonen und der Transferhydrierung von Ketonen untersucht. Dabei zeigte sich gute katalytische Aktivität in allen drei Testreaktionen, wobei bei der Redoxisomerisierung der stärkste Einfluß des Ligandphosphans auf die Produktbildung beobachtet wurde. Gleichzeitig wurde die gute Eignung dieses Ligandsystems für die Untersuchung von Struktur- und Wirkungsbeziehungen in der metallorganischen Komplexchemie dokumentiert.
ABSTRACT This thesis deals with organohalogen compounds and their formation by natural abiotic soil processes, providing a framework in which a literature survey and a resume of the multitude of laboratory experiments are integrated. In the first chapter the literature on the sources, occurrence and sinks of halogenated acetic acids (HAAs), which are phytotoxic, and probably related to forest dieback, is summarized. They are ubiquitous in precipitations and are accumulated in coniferous needles. Next to anthropogenic sources there have also been indications of a natural biotic formation of HAAs in soil. In the following main segment experiments on the abiotic formation of HAAs in soils are presented. This process is probably due to a coupled oxidation/halogenation of organic matter. Experiments with soils, humic acid and phenolic model compounds show that HAAs are generated abiotically. In the case of ethoxyphenol, this occurs through the oxidation of a C2-unit, and in the case of the other model substances probably through the breakdown of the aromatic ring system. More dichloroacetic acid (DCA) than trichloroacetic acid (TCA) is formed. The addition of iron and H2O2 leads to a further increase in formation of HAAs. Probably a Fenton reaction (Fe(II) + H2O2 -> Fe(III) + OH. + OH-) occurs between the iron and the H2O2, forming OH radicals which oxidize the Cl-, leading to the chlorination of organic matter. In the forth chapter the formation of OH radicals, measured by the 2-deoxy-D-ribose method, in aquatic systems with humic acid or soil is investigated; neither sunlight, nor the addition of H2O2 or iron is required. The in vitro formation of OH radicals increases linearly with the amount of soil or humic acid employed. In the fifth chapter the abiotic formation of alkyl iodides in soil is studied. Soils, humic acid and model substances were employed. Similar to the formation of HAAs, two reaction pathways are possible: either, in the case of guiacol, the splitting off of a methyl group and/or the fragmentation of an aromatic system. Probably an oxidation of organic matter with iron is induced. An addition of iron leads to an increase of the production of homologous alkyl iodides from C1 to C4; this confirms the redox-induced mechanism of this reaction. In summary the results of this study indicate that organohalogen compounds are produced abiotically in soil. Their formation is dependent on environmental conditions, e.g. iron content, pH and organic carbon (Corg).
In der vorliegenden Arbeit wurden molekülmechanische Kraftfelder für fünffach koordinierte tripod-Metall-Template des Typs RCH2(CH2X)M mit der Donorgruppe X=Aryl2 entwickelt. Die Beschreibung der beiden Koliganddonoren durch Valenzwinkelpotenziale, die einer Bestimmung der Donoratompositionen in Polarkoordinaten gleicht, erlaubte die Erfassung der gesamten konformativen Vielfalt der zusammen mit dem tripod-Liganden gebildeten Fünffachkoordination am Metallatom. Unter Verwendung von Genetischen Algorithmen zur Parameteroptimierung wurden drei Kraftfelder für drei unterschiedliche Basisdatensätze von Festkörperkonformationen optimiert. Die optimierten Kraftfelder sollten jeweils den gesamten zu Grunde gelegten Basisdatensatz reproduzieren können. Dabei wurde der Schwerpunkt auf die richtige Wiedergabe der gebildeten Koordinationspolyeder bei der Fünffachkoordination gelegt. Für einen Basisdatensatz mit neun Festkörperkonformationen von tripod-Kobalt-Templaten mit Aminocarboxylaten als Koliganden betrug durchschnittlich die mittlere quadratische Abweichung der Atompositionen für das Koordinationspolyeder 8,5 pm. Diese Abweichung betrug beim Kraftfeld für ein- und zweikernige Komplexe mit oxo- und amidatosubstituierten Aromaten als Koliganden 14,4 pm. Dabei lagen der Parameterentwicklung vierzehn Festkörperkonformation zu Grunde. Ein Kraftfeld für Komplexe mit side-on-koordinierten Butadienderivaten am tripod-Kobalt-Templat auf der Basis von zehn Festkörperstrukturen beschreibt die Koordinationspolyeder mit einer durchschnittlichen Abweichung von 7,2 pm. Die anschließende Analyse des Konformationsraumes zweier Vertreter der Dien-Komplexe erlaubte die separate Betrachtung der sterischen Präferenzen dieser Verbindungen.
Die beiden Spurengase Wasserdampf und Methan sind sowohl für den Strahlungshaushalt der Erde als auch für die Chemie der Atmosphäre von großer Bedeutung. Bisher bestehende Messinstrumente können keine simultane Messung der Wasser- und Methankonzentrationen durchführen oder sind durch extraktive Messverfahren limitiert. Darüber hinaus können sie nicht selektiv zwischen den Wasseranteilen in fester, flüssiger und gasförmiger Phase unterscheiden. In dieser Arbeit wurde ein sehr leichtes, besonders kompaktes und trotzdem robustes Diodenlaserspektrometer zum quantitativen In-situ-Nachweis von Wasser und Methan in der Stratosphäre entwickelt. Das Instrument besteht aus dem Spektrometerkopf, der alle optischen Komponenten einschließlich der beiden Diodenlaser aufnimmt, sowie einer offenen Langwegzelle zur Vergrößerung der Absorptionsstrecke. Durch die Neukonstruktion aller optisch-mechanischen Komponenten konnte ein sehr kompakter Aufbau des Spektrometers realisiert werden. Alle zur Zweispeziesmessung notwendigen Komponenten innerhalb des Spektrometerkopfes benötigen zusammen nur eine Fläche von wenig mehr als 400 cm2. Bei einer Gesamtlänge von ca. 75 cm beträgt die Masse lediglich 6,6 kg. Die Gesamtmasse inkl. Spektrometersteuerung und Stromversorgung liegt unter 20 kg. Aufgrund der kleinen Abmessungen und der geringen Masse ist eine leichte Integration des Instruments in bestehende Ballongondelsysteme möglich. Die Absorptionsstrecke wird mit Hilfe einer neu entwickelten Herriott-Multireflexzelle verlängert. Durch Ausnutzung der sphärischen Aberration konnten innerhalb einer Herriott-Zelle simultan zwei verschieden lange Absorptionsstrecken eingestellt werden. Bei einer Basislänge von 55 cm betragen die Längen der Absorptionsstrecken 75 m bzw. 36 m. Aufgrund der kompakten Bauweise werden die beiden Laserstrahlen 136 mal bzw. 66 mal zwischen den beiden Spiegeln reflektiert. Durch das dabei entstehende enge Spotmuster auf den beiden Spiegeloberflächen reagiert die Justage empfindlich auf eine Änderung der Basislänge. Zur Minimierung von thermisch bedingten Längenänderungen wurden verschiedene Legierungen zum Aufbau der Langwegzelle verwendet. Zusätzlich wurde ein passives Kompensationssystem entwickelt, das durch gegenseitigen Ausgleich der thermischen Ausdehnungen verschiedener Materialien für eine weitere thermische Längenstabilisierung sorgt. Erste Tests des entwickelten Ballonspektrometers erfolgten im Rahmen zweier Messkampagnen in Südwestfrankreich. An Bord einer Stratosphärenballongondel wurden bei Temperaturen bis –56 °C bis in eine Höhe von 32 km erfolgreich atmosphärische Wasser- und Methankonzentrationen gemessen. Die Zeitauflösung lag dabei, je nach Flughöhe, zwischen 1,5 s und 200 s. Die Nachweisgrenzen der Methan- bzw. Wassermessung liegen bei 100 ppb bzw. 300 ppb. Anhand der aufgezeichneten Spektrometerdaten konnte die außergewöhnliche thermische Stabilität der entwickelten Langwegzelle validiert werden. Prozesse, die zur Bildung von atmosphärischen Partikeln führen, können mit Hilfe von In-situ-Messungen nur unzureichend untersucht werden. Eine Schwierigkeit besteht z.B. darin, dass sich ein bestimmtes Volumenelement nicht über einen längeren Zeitraum beobachten lässt. Deshalb führt man in der Aerosolkammer AIDA (Aerosol Interactions and Dynamics in the Atmosphäre) u.a. Laboruntersuchungen zur Dynamik von Gefrierprozessen durch. Bisher war dabei die Bestimmung der Partitionierung des Wassers in die feste, flüssige und gasförmige Phase nicht möglich, da bestehende Hygrometer nur den Gesamtwassergehalt aller drei Phasen bestimmen können. Daher wurde im Rahmen dieser Arbeit ein Diodenlaserspektrometer zur In-situ-Bestimmung von Wasserdampfspuren in der AIDA entwickelt. Während der Messungen treten im Probenvolumen Temperaturen bis zu –90 °C auf. Um die Emissionswellenlänge des Diodenlasers stabil halten zu können und gleichzeitig den hohen Wassergehalt der Umgebungsluft außerhalb der Probenvolumens zu unterdrücken, wurde ein Glasfaser-gekoppeltes Spektrometer aufgebaut. Der Laser wird bei Raumtemperatur betrieben und der Laserstrahl mit einer Faser durch die feuchte Umgebungsluft an das kalte Probenvolumen herangeführt. Als Absorptionsstrecke wurde eine White-Multireflexzelle mit einer Weglänge von 82 m verwendet. Bei einer Zeitauflösung von 1,5 s liegt die erreichte Nachweisgrenze bei 23 ppbv. Ein Vergleich der Messergebnisse unter definierten Bedingungen mit einem Lyman-alpha-Spektrometer zeigt für kleine Konzentrationen (1,6 ppmv) nur relative Unterschiede von 2,4 %. Bei der Durchführung von Experimenten hat sich gezeigt, dass mit dem entwickelten TDL-Spektrometer in Kombination mit den bestehenden Hygrometern nun erstmalig eine genaue Bestimmung der Wasseranteile in der kondensierten und in der Gasphase möglich ist.
In dieser Arbeit wurde die optische Summenfrequenz-Spektroskopie (SFG) verwendet, um ausgehend von einer Kalibrierung der CO SFG-Spektren gegen die absolute Oberflächenbedeckung mittels kombinierter TPD-, LEED- und SFG-Messungen sowie kinetischer Modellrechnungen die CO-Adsorption auf Pt(111)-, Rh(111)- und polykristallinen Pt- und Rh-Oberfläche über einen Druckbereich von pCO = 10-8 - 1000 mbar und unter praxisrelevanten Oxidationsbedingungen zu untersuchen. Mit Hilfe eines Modells, das die CO-Adsorption über den gesamten Druck- und Temperaturbereich beschreibt, konnte die CO-Adsorption und insbesondere der beobachtete Dissoziationsvorgang auf der Pt(111)-Oberfläche vollständig beschrieben werden. Demnach hat die CO-Dissoziation auf der Pt(111)-Oberfläche die Ablagerung von Kohlenstoff und Sauerstoff zur Folge. Im Gegensatz dazu ergaben Untersuchungen auf den Rh-Oberflächen, dass die erstmals beobachtete CO-Dissoziation über die Boudouard-Reaktion 2CO -> C(s) + CO2 abläuft. Abschließend konnte erstmals die Oxidation von CO auf einer Rh(111)-Oberfläche bzw. einer polykristallinen Rh-Folie mittels der SFG-Methode unter praxisrelevanten Bedingungen untersucht werden. Dabei gelang es, mit Hilfe eines Mean-Field-Ansatzes, basierend auf einem Langmuir-Hinshelwood-Reaktionsmechanismus und den aus den Adsorptionsmessungen gewonnenen kinetischen Parametern, die Gesamtreaktion auf der Rh(111)-Oberfläche vollständig zu modellieren.
In dieser Arbeit wurden Grenzflächenphänomene zwischen Polymeren und Oberflächen von Festkörpern wie Glas und Metallen in situ (im wesentlichen mit spektraler Ellipsometrie) untersucht. Dabei stand insbesondere die Frage nach einer Segregation von Entformungsmitteln in Polycarbonat an der Grenzfläche zum Metall bzw. nach einem neuen Meßkriterium für die entformende Wirkung der Additive im Vordergrund. Zunächst wurde mittels einem wohldefinierten dünnen organischen Film (Alkylsilan) an der Grenzfläche zwischen flüssigem Polycarbonat und Glas nachgewiesen, daß man mit der gewählten experimentellen Anordnung in der Tat auf sehr dünne segregierte Filme typischer Entformungsmittel im Nanometerbereich sensitiv ist. Anhand eines Polycarbonat/Entformer-Gemisches in hoher Konzentration (Makrolon® + 1% Pentaerythrittetrastearat) wurde die Segregation des Entformungsmittels unter dem Einfluß von Scherkräften untersucht. Eine Segregation wurde nicht beobachtet, womit die Dicke einer möglicherweise dennoch vorhandenen segregierten Schicht auf maximal ~1 nm abgeschätzt werden konnte. Durch Betrachtung der Grenzfläche während Abkühlung der Polymerschmelze und Phasenübergang flüssig->fest konnte eine Meßgröße, basierend auf den an der Grenzfläche nach Erstarren der Schmelze entstehenden Spannungen, gefunden werden, die es erlaubt, die entformende Wirkung von Additiven zu beurteilen. Anhand der vorliegenden Makrolon®/Entformer-Systeme wurde gezeigt, daß die vorgestellte Methode als neuer "Schnelltest" bei der Suche nach neuen Entformungsmitteln eingesetzt werden kann. In weiteren Experimenten wurde die Polymer-Adsorption aus Lösung auf eine Goldoberfläche untersucht. Dabei stand die Kinetik der Adsorptionsprozesse selbstorganisierender Monolagen ("SAM") im Vordergrund. Nachdem zunächst als Modellsystem die Adsorption von Oktadekanthiol aus ethanolischer Lösung auf Gold beobachtet wurde, wurde das Wachstum einer "Polymerbürste" eines Alkanthiol-terminierten Poly(ethylenglykol)-Polymers ("PEG2000-SH") aus Dimethylformamid untersucht. Die Kinetik der Oktadekanthiol-Adsorption läßt sich phänomenologisch am besten mit zwei unterschiedlich schnellen Langmuir-Adsorptionsschritten beschreiben (wie aus der Literatur bekannt). Simultan zu den Ellipsometrie-Messungen an den gleichen Proben durchgeführte Frequenzverdopplungs (SHG)-Messungen zeigten eine wesentlich schnellere Kinetik als die Ellipsometrie-Messungen. Mögliche Gründe für die Unterschiede werden diskutiert. Bei der Adsorption des PEG2000-SH konnten ebenfalls zwei Adsorptionsschritte beobachtet werden: ein erster Schritt, in dem das Polymer relativ schnell die Goldoberfläche in einer "pilzartigen" Konformation bedeckt, sowie ein zweiter Schritt, in dem ein Übergang zu einer gestreckten Konformation verbunden mit weiterem Filmdickenwachstum bei Adsorption weiterer Moleküle stattfindet. Der Filmbildungsmechanismus läßt sich mit einer statistisch-mechanischen Theorie von Kreuzer et al. quantitativ interpretieren.
Die Kenntnis der Transportkoeffizienten ist eine wesentliche Voraussetzung in numerischen Simulationen von reaktiven Strömungen. Typische industrielle Anwendungen, in denen ionisierte Spezies vorkommen, sind Hyperschallströmungen um Wiedereintrittsflugkörper, Zündprozesse der technischen Verbrennung, Plasmaätzverfahren der Halbleiterherstellung und das Kurzschlußverhalten von strombegrenzenden Leistungsschaltern. Der Nachteil aller bisherigen Transportmodelle ionisierter Spezies ist die aufwendige Ermittlung der binären Transportgrößen: Die Anzahl der Kombinationen steigt quadratisch mit der Gesamtzahl der Spezies in der Mischung. Aus diesem Grund sind Modelle entwickelt worden, die nur für eine feste Gasmischung oder bei bestimmten Bedingungen von Druck, Temperatur und Ionisationsgrad gültig sind. Ziel dieser Arbeit ist die Entwicklung eines universell einsetzbaren Transportmodells ionisierter Spezies, um genau dieses Problem zu umgehen. Das neue Transportmodell basiert auf der klassischen Theorie verdünnter Gase von Chapman und Enskog. Die Transportkoeffizienten der Multikomponenten-Mischung werden aus Potentialfunktionen (Stockmayer-, Born-Mayer-, (n,6,4)- und Debye-Hückel-Potentiale) bzw. Wirkungsquerschnitten (Elektronen-Schwerteilchen-Stöße) berechnet. Inelastische Stöße, die Effekte des resonanten Ladungstransfers und ambipolare Prozesse finden Berücksichtigung. Kombinationsregeln werden benutzt, um die Potentialparameter aus molekularen Eingabedaten der reinen Stoffe zu bestimmen. Dies reduziert den Aufwand der Suche und Ermittlung der Eingabedaten, welcher nun nur noch linear mit der Zahl der Spezies steigt. Das Beispiel "dissoziierter und ionisierter Luft" wird gewählt, um das neue Transportmodell zu validieren, weil Referenzwerte in der Literatur vorhanden sind. Für ein 15-Spezies-Modell (N2, O2, NO, N, O, N2+, O2+, NO+, N+, O+, N++, O++, N+++, O+++ und e-$ werden bei den Drücken 0,0001, 1 und 100 bar im Temperaturbereich von 300 bis 30000 K die Gleichgewichtzusammensetzungen als stationäre Zustände eines homogenen Systems berechnet. Sensitivitäts- und Reaktionsflußanalysen werden durchgeführt, um den Reaktionsmechanismus zu untersuchen. Zwischen den auf Basis dieser Gleichgewichtzusammensetzungen berechneten Transportkoeffizienten und den experimentellen und theoretischen Literaturwerten konnte eine gute "Ubereinstimmung erzielt werden.
Direkte Absorptionsspektroskopie mit abstimmbaren Diodenlasern (TDLAS) diente dem kalibrationsfreien quantitativen Analyse gasförmiger Stoffe, deren Nachweis mit extraktiven Methoden nicht oder nur eingeschränkt möglich ist. Verschiedene Diodenlasertypen (Fabry-Pérot (FPDL), Distributed Feedback (DFB), External Cavity (ECDL) und Vertical Cavity Surface Emitting Laser (VCSEL)) wurden eingesetzt, charakterisiert und verglichen. Die In-situ-Meßtechnik wurde für drei Anwendungsbereiche optimiert: (1.) Für die Bewertung der Wirksamkeit verschiedener Feuerlöschsysteme wurde in Zusammenarbeit mit dem Naval Research Laboratory (Washington, DC, USA) ein Spektrometer im Multireflex-Freistrahl-Aufbau (Herriott-Design: 1,8 m Absorptionsweg, 30 cm Basislänge) zur Ermittlung des In-situ-Sauerstoffgehalts bei Feuerlöschübungen im Realmaßstab entwickelt. Ein DFB-Diodenlaser (761 nm) erlaubte auch zum Zeitpunkt der Wassernebelfreisetzung mit starken Transmissionsschwankungen eine Meßgenauigkeit von besser als 1 vol\%. Im Vergleich mit extraktiven Sensoren konnte die Verdrängung von Sauerstoff durch Wasserdampf quantifiziert werden. (2.) Für die Entwicklung eines Kalium-Schwellwertsensors wurden hochreaktive freie Kaliumatome, die unter den Bedingungen der Kohlestaubverbrennung in geringen Mengen aus den im Brennstoff enthaltenen Verbindungen freigesetzt werden, empfindlich (10 ppt) in situ unter industriellen Bedingungen nachgewiesen. Bei der Druckkohlenstaubverbrennung herrschten bis zu 1600 K, 12 bar, starke thermische Strahlung sowie schnelle und große breitbandige Transmissionsschwankungen vor. Durch Ausnutzung der schnellen und weiten Abstimmbarkeit (>15 Wellenzahlen) der VCSEL konnten die stark druckverbreiterten D-Linien von Kalium (767 nm, 770 nm) vollständig erfaßt und charakterisiert werden. Die erreichte Nachweisgrenze bei einer Absorptionsstrecke von 14 cm lag bei 10 ng/m³ i.N. und Konzentrationen bis zu 10 mg/m³ i.N. wurden beobachtet. Die Abhängigkeit der Kaliumatom-Konzentration von den Anlagenparametern, besonders der Temperatur, dem Sauerstoffgehalt und der korrosionsfördernden Kaliumverbindungs-Konzentration wurde untersucht. Dazu wurde simultan die Sauerstoffkonzentration in situ mittels Time Domain Multiplexing oder extraktiv bestimmt. (3.) Der Alkaliatomnachweis anhand der D-Linien wurde auf Lithium, Rubidium und Cäsium ausgedehnt und damit - in Zusammenarbeit mit dem Forschungszentrum Karlsruhe - eine neue Methode zur Ermittlung von Verweilzeiten in Hochtemperaturprozessen erfunden. In einem halbtechnischen Drehrohrofen (THERESA, 3\/~MW) wurden geringe Mengen gelöste Alkalisalze (~100 mg) eingedüst und die Konzentration der freien Alkaliatome (Dissoziationsrate 1 bis 100ppm) bei einer Zeitauflösung von 0,4 s verfolgt. Aus den Verweilzeitverteilungen wurden je nach Betrieb und Anlagenabschnitt mittlere Verweilzeiten von 6 s bis 16 s erfolgreich bestimmt.
Der erste Teil dieser Arbeit beschäftigt sich mit der Darstellung und Strukturaufklärung makrocyklischer Imidazolylborane. Die Synthese erfolgt in hohen Ausbeuten über eine Cyclooligomerisierung von 1-Trimethylsilylimidazolen mit Halogenboranen unter hoher Verdünnung. Aus der Produktverteilung kann ein qualitativer Zusammenhang aus der bevorzugt gebildeten Ringgröße und den Substituenten in 4,5-Stellung der Imidazolringe sowie an den Boratomen abgeleitet werden. Im zweiten Teil wird die Synthese bor-, silicium- und kohlenstoffverbrückter, N-boran geschützter Bisimidazole als Vorstufen chelatisierender Dicarbenliganden beschrieben. Bis(3-boran-4,5-dimethyl-1-imidazolyl)methan wird in 2,2‘-Stellung zweifach zum dianionischen Dicarben deprotoniert, das mit Metallocendihalogeniden in die entsprechenden Titanocen- sowie Zirkonocendicarbenkomplexe überführt wird. Die Charakterisierung der Komplexe erfolgt durch Kristallstrukturanalyse. Inhalt des abschließenden Kapitels sind Umsetzungen von Porphyrinen mit Borhalogeniden (B2Cl4; BX3, X = F, Cl, Br, I). Durch die Reaktion von Dilithio-5,10,15,20-tetra-para-tolylporphyrin (Li2TTP) mit Dibortetrachlorid gelingt erstmals die Darstellung eines Porphyrins, das unter rechtwinkliger Verzerrung eine (Element)2-Einheit koordiniert (Cl2B2TTP). Die Chlorsubstituenten dieser Verbindung werden unter anderem durch nButylgruppen substituiert und können als Chloridionen abstrahiert werden. NMR-Daten und DFT-Berechnungen belegen, dass aus der reduktiven Eliminierung der Chloratome in Cl2B2TTP ein Diboranyl(4)-isophlorin resultiert, welches durch einen 20Pi-Perimeter antiaromatischen Charakter aufweist.
Der Oxidationszustand der anorganischen Arsenspezies (As(III) und As(V)) hat einen entscheidenden Einfluss auf die Toxizität und Mobilität des Elements. Im Grundwasserleiter finden eine Vielzahl von Sorptions- und Redoxreaktionen zwischen Feststoffen und den gelösten Arsenspezies statt. Manganoxide und Eisenhydroxide spielen hierbei eine entscheidende Rolle. Mangan(IV)oxide sind starke Oxidationsmittel bezüglich des As(III), während Eisen(III)hydroxide beide Arsenspezies schnell und stark sorbieren. Diese Arbeit beschäftigt sich mit dem Redox- und Transportverhalten von Arsen in Wechselwirkung mit Manganoxiden und Eisenhydroxiden. Zur Prozessuntersuchung wurden Batchversuche mit beiden Arsenspezies und MnO2 bzw. FeOOH unter definierten geochemischen Bedingungen (Probenzusammensetzung, pH-Wert, Sauerstoffeinfluss) durchgeführt. Durch den Einsatz von Elutionsmethoden sowie Feststoffuntersuchungen mit XANES konnte das Sorptions- und Redoxverhalten von Arsen charakterisiert werden. Die an den Feststoffoberflächen sorbierten Arsenspezies wurden bestimmt, um den Einfluss der Feststoffe auf die Redoxspezies des Arsens zu verdeutlichen. Sorptionsprozesse des Arsens an MnO2 und FeOOH laufen schnell ab, wobei durch MnO2 eine schnelle Oxidation des As(III) zu As(V) stattfindet. Die Sorption des Arsens an MnO2 ist im Gegensatz zur Sorption an FeOOH schwach. Redoxreaktionen zwischen Eisenhydroxid und an der Feststoffoberfläche gebundenem Arsen wurden von bisherigen Untersuchungen ausgeschlossen. Die Ergebnisse dieser Arbeit zeigen jedoch, dass eine langsame Oxidation von As(III) zu As(V) an der Eisenoberfläche stattfindet. Die Oxidation ist abhängig vom pH-Wert, der As(III) Konzentration an der Oberfläche und dem As/Fe - Verhältnis. Mit Hilfe von Langzeit-Batchversuchen mit Sorptionszeiten von 22 Tagen konnte die langsame Reaktionskinetik beobachtet und Reaktionsraten in erster Näherung berechnet werden. Weiterhin wurde der Transport von As(III) in Säulenversuchen untersucht
In dieser Arbeit wurde im Rahmen einer Zusammenarbeit mit der 'University of California at Berkeley' ein Zerstäuberbrenner entwickelt und mittels laserspektroskopischer Methoden untersucht. Er besteht aus einer kommerziell erhältlichen Spraydüse, welche von einem Hüllstrom aus Luft umgeben ist. In den Ethanol-Sprayflammen wurden zweidimensionale Verteilungen des OH-Radikals durch Laserinduzierte Fluoreszenz (LIF) nachgewiesen. Die Geschwindigkeit der Tropfen im Spray wurde mittels der Particle-Image-Velocimetry (PIV) bestimmt. Darüber hinaus wurde durch ein kombiniertes LIF-Streulicht- (Mie-Streuung) Verfahren der Sauterdurchmesser (SMD) des Sprays ermittelt.
Die vorliegende Dissertation beschreibt die Synthesen und Reaktivität von Dibora- und Tetraboraporphyrinogenen. Diboratetrathiaporphyrinogene werden durch [2+2] und [3+1] Zyklisierungen erhalten. In ihnen sind zwei der vier Brücken-Methylene durch Borylgruppen ersetzt. Durch [3+1] Zyklisierung konnten gemischte Diboraporphyrinogene synthetisiert werden, die neben dem Heterozyklus Thiophen auch Furan oder N-Methylpyrrol enthalten. Untersuchungen zur Reaktivität führten in einer Umsetzung mit Natrium/Kalium-Legierung zu Mono- bzw. Dianionen von arylsubstituierten Diboraporphyrinogenen. Tetraboratetraazaporphyrinogene werden durch Umsetzung von CO2Li-geschützten Pyrrolderivaten und einem Dichlorboran erhalten. Sie zeigen eine größere Reaktivität als die Diboraporphyrinogene. Durch Umsetzung mit CH3I und HF lassen sich Tetramethyl- bzw. Tetrawasserstoff-tetraboratetraazaporphyrinogene herstellen.
Der erste Teil der Arbeit beschäftigt sich mit Hydroborierungsreaktionen von Fischer-Carbin Komplexen. Hierbei werden Verbindungen des Typs [TpX(CO)2W(CR)] (TpX = verschieden substituierte Hydrotrispyrazolylborat-Anionen; R = Aryl- bzw. Alkylsubstituenten) mit Hydroboranen zur Reaktion gebracht. Untersucht wird der Einfluß sterischer Effekte auf den Reaktionsverlauf und das entstehende Reaktionsprodukt. Die Umsetzungen mit Diethylboran führen zur Zersetzung der Edukte. Mit Phenylboran erhält man in einigen Fällen neue Borylmetallkompexverbindungen. Im zweiten Teil wird die Synthese und Reaktivität von Carbonylclusterkomplexen der Übergangsmetalle Rhodium und Iridium mit flächenüberbrückenden Cyclooctatetraen-Liganden beschrieben. Es werden Reaktionen von [Rh4(CO)6(C8H8)2] mit 14 Valenzelektronenfragmenten beschrieben. Diese führen entweder zur Substitution des 'apicalen' cyclischen Olefins oder aber zu neuen, aufgestockten Clusterkomplexen.
Im Rahmen dieser Arbeit wurde die Kernspinrelaxation von Formaldehyd (H2CO) an Oberflächen und in der Gasphase gemessen. Durch selektive Photolyse von ortho-Formaldehyd bei 339,022nm wurde das 3:1-Gleichgewicht zwischen ortho- und para-H2CO gestört und die Geschwindigkeit k1 der darauf einsetzenden Relaxation para-H2CO --> ortho-H2CO bestimmt. Für Formaldehyddrücke p-->0 wird die Relaxationsgeschwindigkeit durch Stöße von H2CO mit den Wänden der Messzelle bestimmt. An Messing-, Kupfer-, und Edelstahloberflächen beträgt k1 316, 465 bzw. 918 (+-10) 1/s. Unbeantwortet bleibt die Frage, worin sich diese Wandmaterialien im Bezug auf die Kernspinrelaxation unterscheiden. Weiterhin wurde die Kernspinrelaxation von H2CO in Mischungen mit H2 bzw. SF6 bei kurzen Stoßzeiten (hohen Drücken) gemessen und mit den Vorhersagen der Theorie der Spin-Rotationswechselwirkung [Kasper et al., 1967; Chapovsky, 2001] verglichen. Um die Messwerte beschreiben zu können, muss der theoretisch vorhergesagte Wert des Matrixelement <H_IR> mit einem Faktor 1,7 (1,25 Chapovsky) für Mischungen mit H2 und mit 2,0 (Chapovsky 1,5) für Mischungen mit SF6 multipliziert werden. Die Abhängigkeit des Korrekturfaktors vom Puffergas ist mit der Theorie nicht in Einklang zu bringen. Die für die Kernspinrelaxation effektiven Wirkungsquerschnitte betragen: H2CO-H2CO = 10nm^2 (110nm^2 Chapo.), H2CO-H2 = 0,22nm^2 (2,4nm^2 Chapo.), H2CO-SF6 = 12nm^2 (120nm^2 Chapo.). Das deutet darauf hin, dass schon sehr geringfügige Wechselwirkungsenergien zwischen zwei Molekülen ausreichen, eine Umwandlung zu bewirken.
Das Ziel dieser Arbeit war die Modellierung und die Simulation von zwei Problemen aus dem komplexen Themengebiet der reaktiven Strömung. Beide Fälle wurden mit Hilfe von detaillierten Reaktionsmechanismen und Transportmodellen behandelt. Zunächst wurde eine laminare Flamme in einem industriellen Lamellenbrenner untersucht. Der zweite Schwerpunkt der Arbeit stellt die Oxidation von Ammoniak in einem Diffusionsreaktor dar. Gemeinsames Ziel beider Themen ist die Reduzierung von Schadstoff-Emissionen durch Optimierung von Reaktionsbedingungen. Während der Lamellenbrenner ein Beispiel einer vorgemischten Methan-Flamme mit großen Temperaturgradienten darstellt, zeichnet sich der Diffusionsreaktor durch ein Mischungsproblem von verdünntem Ammoniak unter isothermischen Bedingungen aus. Folgende wichtigen Ergebnisse in Bezug auf den Brenner werden herausgearbeitet: Die Schadstoff-Emissionen steigen mit wachsender Eintrittsgeschwindigkeit. Die Temperatur an den Lamellen und die Luftzahl sind wichtige Parameter für die Flammenstabilität: Höhere Temperaturen an den oberen Lamellenkanten erhöhen die Flammenstabilität. Die optimale Luftzahl bezüglich der Schadstoff-Emissionen liegt zwischen 1,15 und 1,30. Eine Geometrieoptimierung des Brenners wird in der Arbeit ebenfalls durchgeführt. Unterschiedliche Lamellenlängen haben einen positiven Effekt auf die Abgastemperatur und auf die Schadstoff-Emissionen. Weiterhin erhöht sich damit die Flammenstabilität. Eine Verminderung der Schadstoff-Emissionen kann durch längere und dünnere Lamellen sowie durch größere Abstände erzielt werden. Im Fall des Diffusionsreaktors wird der Einfluss der Temperatur und der NH3-Konzentration auf die NO-Emissionen und auf die Mischungszone untersucht. Eine bekannte Eigenschaft der NH3-Oxidation, die sogenannte Selbsthemmung, wird durch die Simulationen richtig reproduziert.
Thema dieser Arbeit ist die Untersuchung der Reaktivitäten verschiedener Oxo-Komplexe der Metalle Vanadium, Chrom und Mangan gegenüber organischen Verbindungen sowie die Isolierung und Charakterisierung dabei auftretender reaktiver Intermediate. Der erste Teil basiert auf der Untersuchung der Reaktion von Chromylchlorid mit tetrasubstituierten Epoxiden. Der erste Schritt der Reaktion mit Bisadamantylidenepoxid ist eine Cr(VI)-katalysierte Epoxid/Keton-Isomerisierung. Nach einem protonengekoppelten Elektronentransfer und dem Abfangen des entstandenen organischen Radikals wird ein O=Cr(V)-Alkoxid gebildet. Mit dessen röntgenographischer Identifizierung konnte erstmals in dieser Form auf molekularer Ebene ein Beleg dafür erbracht werden, dass d0-Metalloxo-Funktionen als Radikalfänger dienen können. Diese Reaktivität war vorgeschlagen worden, um das Auftreten von Alkoholen bei Alkanoxidationen durch Chromylchlorid zu erklären. Der vorgeschlagene Bildungsmechanismus des O=Cr(V)-Alkoxides wurde durch die Synthese und röntgenographische Charakterisierung eines VOCl3-Komplexes als Derivat eines reaktiven Intermediates untermauert. Der zweite Teil der Arbeit basiert auf den bis zum heutigen Tage nicht endgültig geklärten Fragen bezüglich des Mechanismus’ der Oxidation von Olefinen mit Permanganat. Um Derivate der Primärprodukte dieser Reaktion zu isolieren, wurde die Reaktivität des flüchtigen Permanganylchlorid gegenüber Olefinen mittels Matrixisolationsmethoden untersucht. Bei der Umsetzung von MnO3Cl mit Tetramethylethylen wurde selektiv ein Produkt gebildet. Dieses war nicht das bei einem Reaktionsverlauf in Analogie zur Permanganat-Oxidation zu erwartende Glycolat, sondern ein Komplex aus Tetramethylethylenoxid und MnO2Cl. Um diese unerwartete Reaktion zu erklären, wurden DFT-Rechnungen hinsichtlich der Thermodynamik und der elektronischen Aktivierungsbarrieren durchgeführt. Die bevorzugte Epoxidierung wurde durch präparative Umsetzungen bestätigt.
Im Rahmen dieser Arbeit wurden thermochrome Vanadiumdioxidschichten auf Glas abgeschieden. Die Abscheidung erfolgte durch ionenstrahlgestütztes Aufdampfen im Vakuum (IBAD). Die Filmeigenschaften wurden mittels XRD, AFM, XPS, UV-VIS-NIR, RBS, REM, Profilometrie und in temperaturabhängigen Widerstandsmessungen verifiziert.
In dieser Arbeit geht es um die Modifizierung der Oberflächeneigenschaften des austenitischen Edelstahls X2CrNi18-9 zur Verbesserung seiner tribologischen Eigenschaften und seines Korrosionsverhaltens. Dafür wurden Proben des Werkstoffs mit gepulsten Ionenstrahlen behandelt, wobei Stickstoff, Neon und Argon als Arbeitsgase eingesetzt wurden. Eine Ionenpulsimplantationsanlage wurde am Physikalisch-Chemischen Institut der Universität Heidelberg im Rahmen dieser Arbeit aufgebaut. Die Analyse und Charakterisierung der behandelten Proben erfolgte zum großen Teil am Physikalischen Institut der Staatlichen Universität in Porto Alegre (Brasilien). Zum Einsatz kamen dabei mikroskopische Methoden (SEM, AFM), Ionenstrahlanalytik (NRA, RBS), röntgenographische Methoden (GXRD, XRD), Mößbauer (CEMS), Härte- und Verschleißmessungen, sowie Korrosionsuntersuchungen (Zyklovoltametrie). Es zeigte sich bei der Analyse der behandelten Proben, dass in Abhängigkeit der verwendeten Strahlbedingungen Phasentransformationen stattfinden. Einige Proben zeigten lokale Aufschmelzungen. Die mechanischen Eigenschaften konnten erheblich verbessert werden, wobei man eine Härtezunahme von bis zu 100 in einer Tiefe von 50nm im Vergleich zur Referenzprobe beobahtet wurde.
Inhalt dieser Dissertation ist die Synthese neuer Bausteine und die Entwicklung von Syntheserouten von Tetraboraporphyrinogenen und analogen Macrocyclen. In Tetraboraporphyrinogenen sind die meso-Kohlenstoffatome durch Boratome ersetzt. Für eine [2+2]-Cyclisierung zu Tetrathia-Macrocyclen sind Di(2-thienyl)boran-Derivate notwendig, deren Darstellung ausgehend von 2-Lithiumthienyl in guten Ausbeuten gelingt. Die Dilithiierung der Di(2-thienyl)borane mit LiTMP und Umsetzung mit dem entsprechenden Dichlorboran führt in zwei Fällen zur Bildung von Tetraboratetrathiaporphyrinogenen, die strukturell charakterisiert wurden. Über die aus der klassischen Porphyrinchemie übernommene [3+1]-Cyclisierungsmethodik sind erstmals pyrrolenthaltende Tetraboraporphyrinogene erhältlich. In diesem Zusammenhang wird über die 2,5-Diborylierung von Heteroarenen berichtet. Die Umsetzung dieser mit zwei Äquivalenten 2-Lithiumthienyl führt zu strukturell charakterisierten Dreicyclen-Bausteinen, die nach Dilithiierung und erneuter Umsetzung mit 2,5-diborylierten Heteroarenen zu Pyrrol/Thiophenenthaltenden Tetraboraporphyrinogenen führen. Versuche durch Zweielektronen-Reduktion zu aromatischen Tetraboraporphyrinogen-Anionen zu gelangen scheiterten ebenso wie Versuche zur Derivatisierung der meso-Positionen. Durch Umsetzung von 1-Trimethylsilylimidazol mit 2,5-bis-chlorborylierten Heteroarenen können Bisimidazolylborylpyrrole hergestellt werden, deren Boranaddukte hinsichtlich der Bildung von Carbenen untersucht wurden. Die Deprotonierung führte zum Abbau der Moleküle. Die Cyclisierung dieser Imidazolenthaltenden Dreicyclen-Bausteine gelang nicht.
In der vorliegenden Arbeit werden Synthese und Eigenschaften von Tris(3,3-dimethyl-1-butinyl)boran, des ersten donorfreien Trisalkinylborans, und seiner Addukte (Donor = Pyridin, Triphenylphosphin, Tetrahydrofuran) beschrieben. Die Röntgenstrukturanalysen zeigen, daß die B-C-Bindungslängen im donorfreien Trisalkinylboran kürzer und die CC-Dreifachbindungsabstände im Bereich der Donor-stabilisierten Verbindungen liegen. Die Umsetzung von 3,3-Dimethyl-1-butinyllithium mit BCl3 und anschließender doppelten Hydroborierung mit HBCl2 führt zu 1,1,1-Tris(dichlorboryl)-3,3-dimethylbutan, dessen Catecholderivat strukturell untersucht ist. Bei der analogen Reaktion ausgehend von Trimethylsilylacetylid erhält man ein Produktgemisch, das aus drei Isomeren besteht, die durch Derivatisierung mit Brenzcatechin identifiziert wurden. Beim Erhitzen von 1,1,1-Tris(dichlorboryl)-3,3-dimethylbutan bildet sich unter Abspaltung von BCl3 2,3,4-Trichloro-1,5-dicarba-closo-pentaboran(5). Die Funktionalität der borständigen Chloratome lässt sich für Substitutionsreaktionen ausnutzen. So führt die Umsetzung des gebildeten closo-C2B3-Carboran mit MeLi und AlMe3 sowie mit Pentamethylsilazan und Acetyliden zu den entsprechenden Carboranderivaten. Die Hydroborierung von (3,3-Dimethyl-1-butinyl)dichlorboran mit nur einem Äquivalent HBCl2 führt zu 1,1-Bis(dichlorboryl)-3,3-dimethylbuten. Nach Halogen-Austausch mit BI3 und anschließender Cyclisierung mit 3-Hexin wird das asymmetrische 1,3-Dihydro-1,3-diiod-1,3-diborapentafulven erhalten. Die folgende Umsetzung mit AlMe3 bildet das methylierte Produkt, welches instabil ist und sich einerseits zu nido-C4B2-Carboranen umlagert und andererseits zu polymeren Produkten unbekannter Zusammensetzung weiterreagiert. Wird frisch synthetisiertes 1,3-Dihydro-1,3-dimethyl-1,3-diborapentafulven mit HBEt2 bzw. Mo(CO)6 zur Reaktion gebracht, erhält man das erwartete nido-C3B3-Carboran bzw. den Metallkomplex, die jedoch nicht isoliert werden können.
In dieser Arbeit wurde die Druckverbreiterung einer Spektrallinie von Formaldehyd gemessen. Ziel war es, zu klären, welche Faktoren die Druckverbreiterung begünsti-gen. Deshalb wurde hier die Verbreiterung einer Formaldehydlinie bei ansteigendem Eigendruck und die Verbreiterung bei konstantem Formaldehyddruck und ansteigen-dem Druck eines Fremdgases bestimmt. Die verwendete Linie war ein 414 ?515 -Übergang. Folgende Ergebnisse lassen sich feststellen. §Eher sterische Gründe als die Masse begünstigen die Druckverbreiterung. §Dipolmomente beeinflussen die Druckverbreiterung am stärksten. Anhand der gemessenen Gase konnte folgende Reihenfolge der gemessenen Gase in Punkto Wechselwirkung getroffen werden: Edelgase < O2< D2< SF6 ? CH4 ? CF4 < N2 < NO< HCl < H2 < N2O <C2H4 < CO2 < C2H2 < CH3F < CHF3 < CH2F2
Zur Identifizierung der partikelgebundenen, genotoxisch wirksamen Luftschadstoffe wurden kommerzielle, zertifizierte Standardstäube (NIST SRM1649, NIST SRM1648, NIST Vehicle Exhaust Particulate Matter), Luftstaubproben aus 8 verschiedenen Städten Baden-Württembergs (Deutschland) sowie Industrieabgaspartikel aus Kosice (Tschechien) und Ostrava (Slovakei) untersucht. Eine Charakterisierung der Säure/Base-Eigenschaften der genotoxischen Verbindungen wurde über eine Flüssig/Flüssig Trennung der acetonischen Luftstaubextrakte vorgenommen. Die Fraktionen der untersuchten Luftstaubmaterialien zeigten unterschiedliche Verteilungsmuster der biologischen Aktivität im Ames-Test. Für die Extrakte von atmosphärischen Luftstäuben zeigte die Fraktion der stark sauren Verbindungen die höchste genotoxische Aktivität. Die Kfz- bzw. Kokereiabgaspartikelextrakte wiesen die höchste Genotoxizität in der Fraktion der neutralen Substanzklassen auf. Zur weiteren Fraktionierung und Charakterisierung der partikulären Luftschadstoffe wurde die Hochleistungsflüssigkeitschromatographie (HPLC) eingesetzt. Die Trennung erfolgte über eine semi-präparative, cyanopropylmodifizierte Silicagelsäule mittels eines n-Hexan/1,4-Dioxan-Gradienten. Das Eluat wurde über einen automatischen Fraktionsprobensammler im Minuten-Takt einzeln aufgefangen. Die einzelnen Fraktionen wurden im Ames-Test auf ihre mutagene Wirksamkeit untersucht. Die erhaltenen zeitlichen Mutagenitätsprofile „Mutagramme“ der Luftstaubproben aus den verschiedenen Probenahmestandorten sowie der Referenzstäube NIST SRM1649 und (NIST SRM1648 zeigten ein ausgeprägtes Maximum der biologischen Aktivität in einem für polare Substanzklassen charakteristischen Retentionszeitbereich. Die Identifizierung der Inhaltsstoffe der genotoxisch aktiven Fraktionen wurde mit gaschromatographischen Gerätekopplungen wie GC/EI-MSD, GC/EI-MS (Iontrap) und GC/EI-MS² durchgeführt. Die Fraktionen wurden in unbehandelter sowie in methylierter Form untersucht.
Die vorliegende Arbeit beschäftigt sich mit dem neuen (8-Chinolyl)cyclopentadienyl-Liganden. Durch die starre Geometrie des Chinolylgerüsts ist die für eine Stickstoff-Metall-Koordination im Komplex nötige Geometrie im Liganden schon vorgebildet. Die Synthese des Liganden gelingt entweder durch Palladium-katalysierte Kreuzkupplung metallierter Cp-Komplexe mit 8-Bromchinolin oder durch nukleophile Addition von 8-Lithiochinolin an das Cobalticinium-Kation. Durch oxidative Dekomplexierung der entstandenen Cobaltverbindung und nachfolgender Deprotonierung mit Alkalimetallhydriden kann der Ligand in Form seiner Alkalimetallsalze erhalten werden. Diese können zur Synthese verschiedener Metallkomplexe verwendet werden. Mit Lewis-sauren Metallkationen bildet der Ligand stabile Chelatkomplexe, wobei sich sein Dichlorochromkomplex nach Aktivierung mit Metylaluminoxan als aktiver Katalysator zur Polymerisation von Ethen erweist. Bei weichen Metallkationen tritt dagegen keine oder nur eine schwache Wechselwirkung auf. Am Beispiel von Rhodium(I)- und Iridium(I)komplexen konnte somit die hemilabile Koordinationsfähigkeit des Liganden gezeigt werden. Diese Komplexe sind zur photochemisch induzierten C-H-Aktivierung in der Lage. Die Bis(8-chinolyl)metallocene der Elemente Eisen und Ruthenium können als tridentate Liganden gegenüber Lewis-sauren Metallkationen wie Zn2+ oder Cu+ fungieren. Die Koordination der Metallionen in den resultierenden heterobimetallischen Verbindungen erfolgt über die beiden Chinolylstickstoffatome sowie über das Metallocenzentralmetall. Somit gelang erstmals die strukturelle Charakterisierung von Ferrocen- und Ruthenocenderivaten mit einer Metall-Zink-Bindung. Addukte von Ferrocen- und Ruthenocenderivaten mit Kupfer waren zu Beginn dieser Arbeit völlig unbekannt.
Die Modifizierung von Platinoberflächen unter Verwendung zweier ausgewählter Ionenstrahltechniken, mit dem Ziel, die elektrokatalytische Aktivität zu erhöhen. Mit Hilfe der Cyclovoltammetrie wurden die veränderten elektrokatalytischen Eigenschaften bei der Ameisensäureoxidationsreaktion untersucht.
Aufgabe dieser Arbeit war es zu zeigen, dass man sowohl unterschiedlich markierte Peptide, als auch gleich markierte Peptide mit und ohne Tryptophan in ihrer spezifischen Umgebung anhand ihrer Fluoreszenzlebensdauer auf Einzelmolekülebene mit hoher Sicherheit identifizieren und unterscheiden kann. Zu diesem Zweck wurden Markierungsfarbstoffe in Lösung und kovalent auf amino-modifizierte Glasoberflächen gebunden untersucht. Ein Peptid enthält Trp, das andere eine nicht-kopplungsfähige Aminosäure. Der Farbstoff wurde an einen zur variablen Aminosäure benachbarten Lys-Rest gebunden. Die farbstoffmarkierten Peptide wurden dann über ihren C-Terminus an amino-modifizierte Glasoberflächen gekoppelt. Die auf trockenen Glasoberflächen gebundenen Fluoreszenzfarbstoffe und farbstoffmarkierten Peptide wurden mittels konfokaler spektral-auflösender Fluoreszenz-Lebensdauer-Mikroskopie (SFLIM) untersucht. Weitere Messungen erfolgten nach Zugabe einer Flüssigkeit (FTP), die die auf der Oberfläche liegenden Moleküle aufrichtet und damit eine andere Farbstoffumgebung schafft. An den Farbstoff-Peptiden von MR121 war ein markanter Abfall der Lebensdauer durch die Wechselwirkung mit Trp zu beobachten. Carbocyanin-Farbstoffe wie Cy5 zeigten keine spektroskopischen Unterschiede durch die Nähe zu Trp. Allerdings muss sich Trp in unmittelbarer Nachbarschaft zum Farbstoff befinden. Schon eine Aminosäure mehr zwischen Trp und Lys-MR121 verringert die gegenseitige Wechselwirkung so stark, dass praktisch kein Unterschied mehr in den Lebensdauern mit und ohne Trp erkennbar ist. Die reinen Farbstoffe, gemischt auf Glasoberflächen gekoppelt, konnten auf Einzelmolekülebene mit einer Zuordnungssicherheit, aus der Überlappung der Gauß-Kurven ihrer Lebensdauerverteilungen errechnet, von 92 für Cy5/MR121 insgesamt unterschieden werden. Für unterschiedlich markierte Peptide wurden Sicherheiten von 99 für Uni370-Cy5/Uni370-MR121 insgesamt und von 98 für Uni371-Cy5/Uni371-MR121 insgesamt gefunden.
Zweite Virialkoeffizienten sind von technischem und wissenschaftlichem Interesse. Im Bereich nicht zu hoher Drücke beschreiben sie das reale Verhalten von Gasen und stellen eine Informationsquelle über das zwischenmolekulare Potential dar. In den letzten Jahren wurden weltweite Anstrengungen unternommen, die thermophysikalischen Eigenschaften fluorierter Kohlenwasserstoffe, die als Ersatzstoffe für Fluorchlorkohlenwasserstoffe in Frage kommen, zu messen. Diese Fluorchlorkohlenwasserstoffe wurden in vielen technischen Prozessen eingesetzt; sie zerstören aber die schützende Ozonschicht der Erde. Im Verlauf dieser Untersuchungen wurden einigen Mischungen gefunden, die stark vom idealen Mischverhalten abweichen. Im Fall der Mischungen CCl2F2/CHClF2 und CH4/CF4 verlaufen die Mischvirialkoeffizienten in einem bestimmten Temperaturbereich positiver, bei der Mischung CH2FCF3/CHF2CH3 hingegen negativer als die Virialkoeffizienten der Reingase. Um Gründe für dieses ungewöhnliche Verhalten zu finden, wurden im Rahmen der vorliegenden Dissertation systematisch die zweiten Virialkoeffizienten von Methan, seiner fluorierten Derivate CH4-xFx (x = 0-4) und aller binären Mischungen dieser Gase im Temperaturbereich von 296 K bis 463 K bestimmt.
In dieser Arbeit wurde der Einfluss verschiedener Lösungsmittel auf selbstorganisierende Monolagen funktionalisierter und unfunktionalisierter Alkanthiole mittels nichtlinear-optischer Schwingungsspektroskopie (Summenfrequenzspektroskopie, SFG) untersucht. Die Spektren von Undekanthiol-Monolagen im Kontakt mit den untersuchten Lösungsmitteln (D2O, CCl4, Hexan) zeigen dabei nur geringe Unterschiede zu den Spektren der Monolage an Luft. Die Filme bleiben auch im Lösungsmittel gut geordnet. Bei der quantitativen Auswertung wurden der Einfluss linear-optischer Effekte sowie der Winkel zwischen Methyl-Endgruppe und Oberflächennormale bestimmt. Nur in Hexan zeigt sich eine Abweichung von der an Luft beobachteten Orientierung. Im Unterschied zu diesen Filmen zeigen sich bei Monolagen oligo(ethylenglykol)-terminierter Alkanthiole (EG3-OMe) drastische Aenderungen beim Kontakt mit den Lösungsmitteln. In einem ersten Schritt wurde durch die Aufnahme von Spektren unterschiedlich deuterierter EG3-OMe-Monolagen sowie durch den Vergleich mit ab-initio-Berechnungen eine Zuordnung der Schwingungsbanden in den Spektren durchgefuehrt. Die Monolagen auf Goldsubstraten zeigen im Lösungsmittel eine deutliche Amorphisierung, die Ordnung geht verloren, während die Monolagen auf Silbersubstraten einen deutlich geringeren Einfluss der Lösungsmittel zeigen.
Bei der Verbrennung von Kohlenwasserstoffen entstehen unter ausreichend brennstoffreichen Bedingungen neben den Hauptprodukten Kohlendioxid und Wasser auch Ruß. In Verbrennungssystemen ist Ruß aus technischen und umweltpolitischen Gründen unerwünscht. Schärfere zukünftige Gesetzgebungen lassen deutlich niedrigere Grenzwerte erwarten, so daß die Erforschung der Rußbildung detailliert vorangetrieben werden muß. In der vorliegenden Arbeit wird zur Modellierung der Rußbildung zunächst ein aus 164 Spezies bestehender chemischer Reaktionsmechanismus entwickelt und getestet. Er beschreibt die Gasphase mit Hilfe von Elementarreaktionen und berücksichtigt dabei die Bildung von polyzyklischen aromatischen Kohlenwasserstoffen (PAK) bestehend aus bis zu drei Ringen. Der darauf aufbauende Rußmechanismus, der durch Polymerreaktionen die charakteristischen Schritte der Rußbildung (Keimbildung, Oberflächenwachstum, Koagulation und Oxidation) nachbildet, wird mit der in den letzten Jahren entwickelten diskreten Galerkin-Methode behandelt. Bei dieser Technik werden für makromolekulare Polymere auf der Basis einer Gewichtungsfunktion orthogonale Polynome einer diskreten Variablen (Kettenlänge) konstruiert. Zusätzlich zum zeitlichen Verlauf der Konzentration der Rußteilchen erhält man damit Informationen über die Größenverteilung der Rußteilchen, so daß die Berechnung von charakteristischen Meßgrößen, wie z.B. Teilchendurchmesser, Rußausbeute und Rußvolumenanteil möglich ist. Die verwendete diskrete Galerkin-Methode wird zur Anwendung auf die Rußbildung weiterentwickelt und zunächst an einfachen Reaktionssystemen (Fe(CO)5, C3O2) verifiziert. Anwendung findet das entwickelte Modell schließlich in der Simulation eines Stoßwellenrohrversuches unter hohen Drücken und brennstoffreichen Bedingungen.
Ausgangspunkt und Zielsetzung dieser Arbeit ist die Oberflächenmodifikation von Materialien mittels Ionenstrahlen im Hinblick auf Mikro- und Nanostruktu-rierung. Dabei wurden zum einen die Parameter für die Bildung von Platinnanoclustern in einer Siliziumdioxidmatrix untersucht, zum anderen Oberflächenmodifikationen von Polymeren am Beispiel von Polyethersulfon (PES) im Hinblick auf eine chemische Mikro-Strukturierung mit den Reaktivgasen Ammoniak und Sauerstoff durchgeführt. Hierfür wurde eine Niederenergie Ionenstrahlquelle mit Extraktionsenergien bis 1000 eV vom Typ der Kaufmanquelle entwickelt. Desweiteren wurden orientierende Untersuchungen mit einer massenselektiven Ionenstrahlquelle (RAH 20 der Fa. Jenion) mit dem Ziel durchgeführt, reaktive Zwischenprodukte organischer Substanzen im Plasma herzustellen und sie auf einem Target abzuscheiden. Von Interesse waren hierbei die unter Nichtgleichgewichtsbedingungen entstandenen Produkte.
Die Arbeit befaßt sich mit der Entwicklung neuer bimetallischer Komplexsysteme, in denen ein Pyrazolat die präorganisierende Brückenfunktion zwischen zwei chelatisierenden Ligand-Kompartimenten übernimmt. Die neu synthetisierten Bimetallsysteme orientieren sich an analogen einkernigen Koordinationsverbindungen: als Vorbilder dienen einkernige Diaminkomplexe, Diiminkomplexe und N-donorfunktionalisierte Cp-Halbsandwichkomplexe (sog. Komplexe mit eingeschränkter Geometrie, 'constrained geometry'). Innerhalb der Arbeit gelang die Synthese und die Untersuchung des Koordinationsverhaltens verschiedener neuartiger, präorganisierter Kompartiment-Ligandsysteme. Die strukturellen und physikalisch-chemischen Eigenschaften der resultierenden Bimetallkomplexe wurden mit Hilfe von IR-, UV/Vis/NIR-, NMR-spektroskopischen und elektrochemischen Methoden sowie der Röntgenstrukturanalyse aufgeklärt. Zweikernige Komplexe mit chelatfixierten Metallionen eignen sich insbesondere zur Untersuchung von ligandvermittelten Wechselwirkungen zwischen den benachbarten Metallzentren. Solche ligandvermittelte 'Kommunikation' konnte im Rahmen dieser Arbeit am Beispiel einer besonders stabilen, gemischtvalenten Dimangan(I,II)verbindung mit Hilfe von Cyclovoltametrie, Spektroelektrochemie, IR-, UV/Vis/NIR- und temperaturabhängiger ESR-Spektroskopie eingehender untersucht werden.
In der vorliegenden Dissertation wurde untersucht, ob deprotonierte Phenylessigsäureamide in SET-gestützten C-C-, C-N- oder C-O-Verknüpfungsreaktionen einsetzbar sind. Als potentieller Ein-Elektronenakzeptor fand N,N-Dimethylformamid (DMF) Verwendung. Obwohl bei den Umsetzungen der Amide mit NaH in DMF unter Argon in einem Temperaturbereich von 20-154 °C keine Produkte gewonnen werden konnten, die auf SET-gestützte Reaktionsfolgen zurückzuführen waren, entstanden zahlreiche Verbindungen, deren Bildungssequenzen auf außergewöhnlichen „Methylen“-Insertionen mit DMF als C1-Synthon basieren. So entstehen bei der Umsetzung von Phenylessigsäureamid unter Rückfluß aus jeweils zwei Edukt- und einem DMF-Molekül neben 3,5-Diphenylpyridin-2,6-diol und 3,5-Diphenylpyridin-2-ol (I) die methylenverbrückten Dimere racem- und meso-3,5-Diphenylpiperidin-2,6-dion sowie 3,5-Diphenyl-3,4-dihydropyridin-2(1H)-on (II). Der postulierte Entstehungsweg von I bzw. II schließt die direkte Reduktion einer amidischen Carbonylgruppe durch NaH ein. Dieses Reaktionsverhalten zeigt deutlich, daß sich die Reduktionskraft von NaH in DMF erheblich steigern läßt. Die beobachteten „Methylen“-Insertionen ließen sich auf Phenylessigsäure bzw. deren Esterderivate sowie auf 3-Phenylpropionsäureamid ausdehnen. Im Anschluß an diese Versuchsreihen konnte gezeigt werden, daß in Anwesenheit von Luftsauerstoff intramolekular verlaufende, SET-vermittelte C=C- bzw. C=N- Doppelbindungsbildungen realisierbar sind. So entsteht bei der Umsetzung von Biphenyl-2,2'-diacetamid mit NaH in DMF bei 70 °C Phenanthren-9,10-dicarboxyimid. Benzol-1,2-diacetamid reagiert mit NaH in DMF bei Raumtemperatur unter Bildung von 3-Hydroxyisochinolin-1-carboxamid. Dabei findet die unter synthetischen Gesichtspunkten sehr reizvolle Verknüpfung einer CH-aciden Methylengruppe mit einer amidischen NH2-Gruppe statt. Wird N-(Phenylacetyl)phenylessigsäureamid mit NaH in DMF bei Raumtemperatur umgesetzt, entsteht Diphenylmaleinsäureimid.
Die vorliegende Arbeit befasst sich mit der chemisch und physikalisch fundierten Modellierung und numerischen Simulation der Abgaskonversion in einem Wabenkanal monolithischer Abgaskatalysatoren. Zur Beschreibung der auftretenden chemischen Reaktionen wird ein elementarkinetischer Ansatz gewählt. Der Stofftransport im Kanal wird durch detaillierte Modelle für den Transport in der Gasphase und im Washcoat beschrieben. Es werden unterschiedliche Transportmodelle miteinander verglichen, die sich im Detaillierungsgrad und Rechenzeitbedarf unterscheiden. Als Katalysatorsystem wird zunächst Pt/Al2O3 betrachtet. Es werden die Elementarreaktionen und dazugehörigen Geschwindigkeitsparameter des Reaktionssystems C3H6, CO, CO2, NO, NO2, N2O, N2, O2 auf Platin unter mageren Bedingungen zusammengestellt. Das erstellte Gesamtmodell wird anhand experimenteller Daten validiert und zur Simulation der HC-SCR auf Pt/Al2O3 eingesetzt. Mithilfe der Simulationsergebnisse werden die Umsatzverläufe erklärt und die relevanten Transportprozesse identifiziert. In einem zweiten Schritt wird der erstellte Reaktionsmechanismus auf Platin um Oberflächenreaktionen von NO, CO und O2 auf Rhodium erweitert. Dieser erweiterte Reaktionsmechanismus wird zur Simulation eines kommerziellen 3-Wege-Katalysators verwendet. Der Vergleich zwischen Simulationsergebnissen und gemessenen Werten zeigt eine gute quantitative Übereinstimmung, lediglich für sehr fette Gemischzusammensetzungen ergibt sich eine größere Abweichung. Die gute Übereinstimmung zwischen Simulation und Experiment bestätigt die Übertragbarkeit des Platin-Reaktionsmechanismus auf verschiedene Katalysatorsysteme und Reaktionsbedingungen. Die Simulationsergebnisse zeigen die Wechselwirkung zwischen dem Bedeckungszustand der katalytischen Oberfläche und dem Umsatzverhalten im Kanal auf.
Ziel dieser Arbeit war die Charakterisierung reaktiver Spezies wie sie bei der Verbrennung von Kohlenstoff (im einfachsten Fall: Graphit) unter dem Einfluß einer Niederdruck-Wasserstoffflamme variabler Stöchiometrie auftreten. Zur Messung der CN-Radikale wurden der Wasserstoffflamme definierte Mengen NO beigemischt, die sich im weiteren Verlauf zu CN-Radikalen umsetzten. Mit Hilfe der berührungsfreien linearen laserinduzierten Fluoreszenzspektroskopie (LIF) konnten räumlich aufgelöste 2-D-Konzentrationsprofile von CH- und CN-Radikalen gemessen werden, ohne die chemisch-physikalischen Gasphasenprozesse zu beeinflussen. Unter Einsatz der Ramankalibration mit Stickstoff, der Messung effektiver Lebensdauern und der Gasphasentemperaturbestimmung aus aufgelösten Rotationsspektren, wurden erstmals absolute Konzentrationen von CH- und CN-Radikalen für verschiedene Verbrennungsbedingungen ermittelt.
Zirconium(IV)-Verbindungen zählen zu den aktivsten nicht-enzymatischen Reagentien für die Phosphodiester-Spaltung. Im Rahmen der vorliegenden Arbeit wurde die Spaltung verschiedener Nucleinsäure-Substrate durch Zirconium-Salze und durch Zirconium-Komplexe untersucht. Die aktivierten Substrate Bis(p-nitrophenyl)phosphat (BNPP) und 2-Hydroxypropyl-p-nitrophenylphosphat (HPNP) werden durch Zirconium(IV) in schwach saurer Lösung mit hoher Geschwindigkeit gespalten. Unter optimalen Bedingungen läuft die Reaktion etwa 10^9-mal schneller ab als die Spontanhydrolyse. Während Zr(IV)-Salze bei neutralem pH-Wert Hydroxid-Niederschläge bilden, werden in Gegenwart bestimmter Chelatliganden homogene Lösungen erhalten. Mit carboxylathaltigen Liganden nimmt die Spaltungsgeschwindigkeit stark ab. Im Gegensatz dazu bleibt die Aktivität mit bestimmten Aminoalkoholen annähernd erhalten. Auch das DNA-Dinucleotid Thymidyly(3'-5')thymidin (TpT) und das RNA-Dinucleotid Uridinyl(3'?5')uridin (UpU) werden durch Zr(IV)-Verbindungen hydrolytisch gespalten. Die Aktivität vieler Enzyme wird durch allosterische Regulation gesteuert. In der Arbeit wurden dreikernige Metallkomplexe untersucht, die die ersten nicht-enzymatischen, allosterisch regulierten Katalysatoren repräsentieren. Ein strukturelles Metallion beeinflusst die Konformation des Katalysators und damit die Präorganisation von zwei funktionellen, an der Katalyse beteiligten Cu(II)-Ionen. Mit den mehrkernigen Komplexen wurden kinetische Untersuchungen zur HPNP-Spaltung durchgeführt. Die Aktivität hängt stark von der Art des strukturellen Metallions ab: Die höchste Reaktionsgeschwindigkeit erhält man mit Cu(II), dagegen ist mit Ni(II) und Pd(II) die Geschwindigkeit der Phosphodiester-Spaltung 3- bzw. 10-mal geringer.
Aluminium und Aluminiumlegierungen besitzen eine geringe Dichte und ein gutes Härte-zu- Gewicht Verhältnis. Diese Eigenschaften und die hervorragende Bearbeitbarkeit prädestinieren sie für viele Anwendungsbereiche. Obwohl in den letzten Jahren das Interesse an dieser Werkstoffgruppe stark zugenommen hat, können aufgrund der geringen Härte, der unzureichenden Beständigkeit gegenüber Verschleiß und des niedrigen Schmelzpunkts, die industriellen Einsatzmöglichkeiten dieser Materialgruppe nicht voll ausgenutzt werden. Randschichtmodifikationen des Grundmaterials sowie, nachfolgende Beschichtungen sind prinzipiell geeignet, um diese Nachteile zu verringern. Das Ziel der vorliegenden Arbeit war daher eine grundlegende Untersuchung zur Nitrierung von Aluminium mit gepulsten Ionenstrahlen. Zu diesem Zweck wurden Aluminiumsubstrate einer Ionenstrahlpulsbehandlung im msec- und nsec - Bereich unterzogen, bei der zum einen die diffusionsgesteuerte Synthese einer Aluminiumnitridschicht, und zum anderen der thermische Einfluss auf das Diffusionsverhalten und die mikrostrukturelle Veränderungen untersucht werden sollten. Zunächst wurden grundsätzliche Überlegungen zur thermischen und ionenstrahlinduzierten Diffusion angestellt, sowie ein vereinfachtes Diffusionsmodell zur Beschreibung der experimentellen Diffusionsprozesse entwickelt. Die Durchführung der Ionenstrahlpulsexperimente erfolgte zum einen an der GSI-Darmstadt am Hochstromionenquellenteststand, der mit einer MUCIS-Ionenquelle ausgerüstet war. Hier wurden Pulsbestrahlungen mit Leistungsdichten ? 0,5 kW/(cm²?Puls) und Pulslängen zwischen 0,5 –25 msec durchgeführt. Weitere Experimente mit gepulsten Ionenstrahlen wurden in Verbindung mit dem Institut für Plasmaphysik (IPP) München, mit Leistungsdichten im Bereich von 1 – 4 kW/(cm²?Puls) und mit Pulslängen von 1 – 100 msec, durchgeführt. In Zusammenarbeit mit der Polytechnischen Universität Tomsk (Russland) konnten auch exemplarische Ionenstrahlpu
Die vorliegende Arbeit beschreibt die Präparation funktionalisierter, mikrostrukturierter Hydrogele zum Nachweis von pH-Änderungen und enzymatischen Reaktionen mittels beugungsoptischer Methoden. Hydrogele sind dreidimensionale elastische Polymernetzwerke, die überwiegend aus einer Flüssigkeit bestehen, die vom Polymernetzwerk umschlossen wird. Hydrogele sind umgebungssensitiv, d.h. sie reagieren mit einer Änderung ihres Quellungszustan-des, wenn sich die Umgebungsbedingungen verändern. Je nach ihrer Zusammensetzung reagieren Hydrogele auf die Änderung der Lösungsmittelzusammensetzung, der Tem-peratur, der Ionenstärke oder des pH-Werts. Das in dieser Arbeit eingesetzte pH-sensitive Hydrogele wurde durch den Einbau der Enzyme Glucoseoxidase und Katalase um eine Selektivität gegenüber Glucose erweitert. Die Funktionsweise des beugungsoptischen Sensors beruht auf der Wechselwirkung eines einfallenden Laserstrahls mit der im Mikrometermaßstab regelmäßig strukturi-erten Hydrogelmatrix. Durch die Beugung des Laserlichts an dem mikrostrukturierten Hydrogel entstehen mehrere Beugungsreflexe. Im Gegensatz zur Lage variieren die Intensitäten der einzelnen Beugungsordnungen, wenn die Hydrogelmatrix ihre Form ändert. Das Quellverhalten des pH-sensitiven Hydrogels wurde vor der Verwendung im Sensor an makroskopischen Gelproben in Abhängigkeit von der Ionenstärke und des pH-Werts untersucht. Mit dem beugungsoptischen Sensor und pH-sensitiven Hydrogel wurden Messungen mit unterschiedlich konzentrierten Natriumchlorid-Lösungen und Lösungen mit ver-schiedenen pH-Werten bei konstanter Ionenstärke durchgeführt. Mit dem enzymhalti-gen Hydrogel wurden Messungen mit unterschiedlich konzentrierten Glucoselösungen durchgeführt.
Die vorliegende Arbeit beschreibt die Auswirkungen von hohem hydrostatischem Druck auf Konidiosporen der Schimmelpilze Aspergillus fumigatus, Botrytis cinerea, Cladosporium herbarum und Penicillium expansum sowie auf die Syntheserate des Mycotoxins Patulin durch Penicillium expansum. Die Hochdruckinaktivierung von Konidiosporen verläuft in den meisten Fällen zweipha-sig. Diese Inaktivierungskurven können in guter Näherung durch eine Überlagerung zweier Reaktionen 1. Ordnung beschrieben werden. Bei tiefen Temperaturen (4 °C) werden die Spo-ren vollständig abgetötet, während bei höheren Temperaturen (25-55 °C) bei einem kleinen Teil der Sporen Druckresistenz auftreten kann. Behandlungstemperaturen oberhalb der opti-malen Wachstumstemperatur führen immer zu druckresistenten Fraktionen von Sporen. Eine Druckerhöhung reduziert den Anteil der stabilen Fraktion. Die Freisetzung von Patulin durch P. expansum wurde in Apfelsaft untersucht. Das Ana-lyseverfahren mittels HPLC wurde neu entwickelt. Durch diese Methode läßt sich Patulin vollständig von 5-Hydroxymethylfuraldehyd (5-HMF), einem in Apfelsaft vorkommenden Zersetzungsprodukt von Kohlenhydraten, trennen. Die Wiederfindungsrate beträgt bei Patulin > 96 , bei 5-HMF ~ 80 Die Nachweisgrenze beider Substanzen ist 2 µg/l. Die Syntheserate von Patulin ist abhängig von dem Verkeimungsgrad des Apfelsaftes. Bei 103 Keimen/ml Saft wird mehr Patulin freigesetzt als bei 106 Keimen/ml. Druckbehandlungen können in Abhängigkeit von Druckhöhe und Temperatur die Patulinsynthese fördern oder hemmen. Die höchste Patulinkonzentration von 122,1 mg/l wurde nach einer Druckbehand-lung bei 40 °C mit 350 MPa gemessen. Eine Zugabe von Cystein reduziert die Toxizität von Patulin. Diese Adduktbildung wird durch Druck gefördert. Die Aktivierungsenergien und die Aktivierungsvolumina dieser Reak-tion wurden im Druckbereich von 0,1 bis 500 MPa bei 4 °C, 25 und 40 °C bestimmt.
In der vorliegenden Arbeit wird anhand verschiedener organometallischer Komplexverbindungen gezeigt, wie sich die Methoden der quantitativen NMR-Strukturanalyse und der dynamischen NMR-Spektroskopie dazu nutzen lassen, um die Konformationen 'kleiner' Moleküle und die Dynamik ihrer gegenseitigen Umwandlungen aufzuklären. Da die meisten Reaktionen der Koordinationschemie, insbesondere die der homogenen Katalyse, in Lösung durchgeführt werden, ist eine umfassende Beschreibung des Verhaltens von Koordinationsverbindungen unverzichtbar, wenn der Versuch unternommen wird, einen Zusammenhang zwischen einzelnen Strukturmerkmalen und den beobachteten Reaktivitäten der Ligand-Metall-Template herzustellen. Im ersten Teil der Arbeit werden verschiedene Aspekte der innermolekularen Beweglichkeit von Übergangsmetallkomplexen tripodaler Liganden mit dynamischen NMR-Methoden (Linienformanalysen, EXSY-Experimente, Koaleszenzmessungen) aufgezeigt und quantitativ untersucht. Außerdem wird beschrieben, wie mit den Methoden der NOE-basierten quantitativen NMR-Strukturanalyse in Verbindung mit Distanzgeometrierechnungen und Kraftfeldmodellierungen die Konformationen von Tripod-Metall-Komplexen in Lösung ohne Rückgriff auf explizite Festkörperstrukturdaten mit hoher Genauigkeit ermittelt werden können. Der zweite Teil der Arbeit beschreibt die detaillierte NMR-Analyse chiraler Bisphosphan-Rhodiumkomplexe. Die Komplexe des Typs HOCH(CH2PR2)(CH2PR’2)Rh(COD) können als Katalysatoren in der enantioselektiven Hydrierung eingesetzt werden. Die Flexibilität des von Ligand und Zentralmetall gebildeten Chelatsechsringes verursacht dynamische Effekte, deren Mechanismen mit zweidimensionalen NMR-Experimenten aufgeklärt werden. Darüber hinaus wird untersucht, inwieweit die erarbeiteten quantitativen Daten zur Konformation und Dynamik der Komplexe mit den in den katalytischen Reaktionen erzielten Enantioselektivitäten korreliert werden können.
In der vorliegenden Arbeit wurde das konformative Verhalten von chiralen Rhodium-Bisphosphan-Komplexen des Typs HOCH(CH2PR2)(CH2PR'2)Rh(I)C8H12 mit molekularmechanischen Methoden untersucht. Dazu wurde ein Kraftfeld für diese reaktiven Präkatalysatoren mit einem Gentischen Algorithmus auf der Basis von elf Festkörperstrukturen entwickelt. Mit dieser Methode werden die fehlenden metallinvolvierenden Kraftfeldparameter so angepaßt, daß das zugehörige Kraftfeld möglichst gut Festkörperkonformationen reproduzieren kann. Auf diese Weise konnten zwei Kraftfelder optimiert werden, die die Festkörperstrukturen mit einer mittleren quadratischen Abweichung der Atompositionen zwischen berechneter und beobachteter Konformation von nur 26pm wiedergeben können. In der daran anschließenden Untersuchung des dynamischen Verhaltens dieser reaktiven Präkatalysatoren konnte die konformative Isomerisierung dieser Komplexe ermittelt werden. Die dabei aus dem Modell erhaltenen Reaktionswege und Aktivierungsenthalpien stimmen in allen Teilen und insbesondere im Quantitativen außerordentlich gut mit den experimentellen Daten überein, die durch eine vollständige NMR-Analyse dieser Verbindungen in Lösung unabhängig gewonnen werden konnte.
In dieser Arbeit wurde an der Weiterentwicklung einer neuen Methode zur Strukturaufklärung von Makromolekülen gearbeitet. Holographie mit niederenergetischen Elektronen ist eine Mikroskopietechnik, die ohne Linsen und aus Linsen resultierenden Fehlern arbeitet. Hologramme können mit einer nominellen Vergößerung von M > 106 aufgenommen werden. Eine ultrascharfe Wolframspitze liefert dabei die zur Holographie benötigte kohärente Strahlung. Die Elektronenquelle wird in einem Elektronen-Projektionsmikroskop bis auf Abstände < 1 mm an ein semitransparentes Objekt angenähert. Ein Teil der aus der Punktquelle emittierten Wellenfunktion eines Elektrons wird an dem Objekt gestreut (Objektwelle). Dieser interferiert mit dem ungestreuten Anteil der Wellenfunktion (Referenzwelle) und es entsteht ein Hologramm. Um daraus Informationen über die Lage der Streuzentren zu gewinnen, muß die Wellenfront in der Objektebene rekonstruiert werden. Dazu muß das Hologramm mit kohärenter Strahlung beleuchtet werden. Dies kann numerisch mit einem Rekonstruktionsalgorithmus beruhend auf der Kirchhoff-Helmholtz-Transformation erfolgen. Die zur Rekonstruktion verwendete Software LEEPS bietet auch die Möglichkeit, Hologramme zu simulieren, mit denen die Abbildungen im Elektronen-Projektionsmikroskop verglichen werden können. Phthalocyaninatopolysioloxan, DNA und das cis-Platin-Addukt an DNA wurden auf unterschiedlichen Objektträgern präpariert und holographisch abgebildet. Die Hologramme der stäbchenförmigen Moleküle rekonstruieren als Stränge mit einem Durchmesser von ca. 2 nm, was sehr gut dem Moleküldurchmesser entspricht. Die Doppelhelix der DNA konnte ebenfalls aufgelöst werden. Die zu den Experimenten durchgeführten Simulationen bestätigten die experimentellen Ergebnisse. Weitere Simulationen zeigten, daß bei Verwendung eines größeren Bildschirms und höherer Energie eine Auflösung im Subnanometer-Bereich möglich sein sollte.
Thema der Dissertation war die Entwicklung der Ir-katalysierten allylischen Alkyl-ierung als Methode für die enantio-selek-tive Synthese. Allylische Alkylierungen gehören zu den etablier-testen katalytischen asymmetrischen Reaktionen, und mittlerweile gibt es viele Arbeiten auf diesem Gebiet. In den meisten dieser Publikationen beschäftigen sich die Autoren jedoch mit symmetrisch substituierten Allylsystemen. Bei unsymmetrisch substituierten Allyl-systemen tritt das zusätzliche Problem auf, den Angriff an das höher substituierte Allylende zu lenken, das mit dem häufig verwendeten Palladium als katalysierendes Metall nur für spezielle Substrate gelöst werden kann. Daher war es notwendig, eine neue Methode zu entwickeln. Das Katalysesystem [Ir(COD)Cl]2-P(OPh)3 liefert sehr gute Regioselektivitäten für aryl- und die anspruchsvolleren alkylsubstituierten Substrate. Diese Reaktion wurde 1997 erstmals von Takeuchi beschrieben. Bei der Entwicklung einer asymmetrischen Variante dieser Reaktion für alkyl- substituierte Allylsubstrate wurden zunächst grundlegende Fragen nach Ligandenbeschleunigung und optimalen Versuchsbedingungen beantwortet, bevor Liganden optimiert und neue Substrate getestet wurden. Phosphoramidite erwiesen sich als effektivste Liganden in Bezug auf Reaktivität und Regioselektivität. Mit diesen Liganden konnten Regioselektiviäten von 99:1 und Enantioselektivitäten von bis zu 94 ee für alkylsubstituierte Substrate erzielt werden. Einige Reaktionsprodukte können durch wenige Modifikationen in wichtige chirale Bausteine überführt werden.
Die vorliegende Arbeit beschäftigt sich mit der Darstellung und Charakterisierung von zweifach borylierten Diazomethan-Verbindungen. Bis(trimethylstannyl)diazomethan (1) reagiert mit Catecholchlorboranen und Bis(dimethylamino)chlorboran zu den entsprechenden zweifach borylierten Diazomethan-Verbindungen. Die Verbindungen sind luftempfindlich, nicht explosiv und sehr reaktionsfreudig. (1) reagiert mit Bis(dicyclohexylamino)chlorboran und Bis(cyclohexyl,phenyl-amino)chlorboran zum zweifach borylierten Nitrilimin. Bei dem elektrophilen Angriff am C- oder N-Atom handelt es sich um zwei konkurrierende Prozesse. Sterische Gründe sind verantwortlich dafür, ob die Diazoverbindung oder das Nitrilimin entsteht. Die Molekülstrukturen wurden mittels Kristallstrukturanalyse, NMR und IR-Spektroskopie aufgeklärt.
Die vorliegene Arbeit beschäftigt sich mit der Reaktivität von Boriranyliden-boranen. Im ersten Teil werden Umsetzungen mit B2Cl4 und B2Br4 beschrieben. Die dabei isolierten Tetraborylmethane und die ebenfalls gebildeten isomeren Diborylmethylenborane erhält man in guten Ausbeuten. Im weiteren Verlauf ergeben Substitutionen mit Aminen oder Amidüberträgern Triborylmethane oder auch aminoüberbrückte Homoaromaten. Der zweite Teil ist der Adduktbildung am exocyclischen Boratom der Boriranylidenborane gewidmet. Als Addukte kommen dabei Alder-, Arduengo-Carbene und N-tert.butylisonitril zum Einsatz. Im letzen Abschnitt steht die Umsetzung mit Metallcarbonylen im Mittelpunkt. Hierbei wird überraschenderweise ein metallfreies Diborylketen isoliert.
Reaktionsmechanismen, die aus Elementarreaktionen bestehen, werden zur Beschreibung der Oxidationsprozesse von gasfoermigen Kohlenwasserstoffen erstellt. Fuer kleinere Kohlenwasserstoffe (C < 5) erfolgt die Erstellung der einzelnen Elementarreaktionen und der zugehoerigen Geschwindigkeitskoeffizienten manuell. Elementarreaktionen zur Oxidation von hoeheren Alkanen (C > 4) wurden automatisch mit Hilfe eines Generierungsprogramms erzeugt. Zur Ueberpruefung der erstellten Mechanismen wurden Zuendverzugszeiten und laminare Flammengeschwindigkeiten von Brennstoff/Luft-Mischungen berechnet und mit experimentellen Daten aus der Literatur verglichen. Die untersuchten Temperatur- und Druckbedingungen orientieren sich an den motorisch relevanten Bedingungen, d.h. Temperaturen von 500 K - 1400 K und einem Druckbereich von 1 bar - 50 bar.
Ausgehend von 1,3,5-Trichlor-2,4,6-trimethyl-1,3,5-triboracyclohexan (1a) werden durch Substitution an den Borzentren neue Ringderivate synthetisiert, darunter die dreifach n- bzw. t-butylierten Verbindungen 1b und c. Die Vakuumthermolyse von Bis(dihalogenboryl)methanderivaten (Halogen = Cl [a], Br [b], I [c]) führt unter Abspaltung von Bortrihalogeniden zu den 1,3,5-Trihalogen-1,3,5-triboracyclohexanen 2a-c. 2c läßt sich als kristalliner Feststoff isolieren und mit Trimethylaluminium an den Borzentren zu 2d methylieren. 1b, 1c sowie das literaturbekannte 1,2,3,4,5,6-Hexamethyl-1,3,5-triboracyclohexan (1e) werden mit Lithium in donierenden Lösemitteln (THF, THP, Et2O) reduziert. Es entstehen die trishomoaromatischen Dianionen 3b, c und e mit einer Dreizentrenzweielektronenbindung zwischen den Boratomen. Bei den reduzierten Ringen handelt sich um Analoga des Trishomocyclopropenyliumkations, alternativ ist eine Interpretation als hypho-Cluster möglich. Mit Li reduziertes 1e läßt sich in Gegenwart von THP kristallisieren. Die Röntgenstrukturanalyse (RSA) zeigt tetramere Aggregation von 3e-Einheiten, die über C2B-Flächen mit Li verbrückt sind und in terminaler Stellung C2B-verknüpfte Li(THP)2-Fragmente tragen. In Anwesenheit des Kronenethers [12]cr-4 bildet sich ebenfalls ein cyclisches Tetrameres, bei dem aber die terminalen Li-Zentren durch Komplexierung mit [12]cr-4 fehlen. Reduktion von 1e mit anderen Alkalimetallen liefert ebenso 3e: Im Falle von Na bilden sich aus der Reaktionslösung (THF) kristalline, mäanderförmig gewundene Poymerketten; mit [18]cr-6 kristallisiert ein Tetrameres von außergewöhnlicher Struktur. Mit Kalium bildet sich in THF ein Reduktionsprodukt, das mit [18]cr-6 Kristalle ergibt, die Zickzack-Polymerketten aus K-verbrücktem 3e enthalten. Trishomoaromaten werden auch durch die Reduktion eines alkylierten 1,3,5-Triboracycloheptens und eines neuen, acyclischen, mehrfach methylierten 1,3,5-Triborapentans mit Li erhalten.
Thema dieser Dissertation war die Untersuchung des Einflusses von Cholylsarcosin-Na auf die Aufnahme von Peptiden aus dem Darm. Vergleichend dazu sollten natürliche Gallensalze als Resorptionsenhancer getestet werden. Die resorptionsverbessernden Eigenschaften von Cholylsarcosin-Na (CS-Na) wurden im Verhältnis zu CDCA-Na, TC-Na und UDCA-Na beurteilt. Es konnte gezeigt werden, daß eine 1 ige Lösung von CS-Na den Transport der Modellpeptide, Desmopressin und Octreotid, durch CaCo-2 Monolayer verbessert.
Diese Arbeit beschäftigt sich mit Clusterkomplexen der Übergangsmetalle Cobalt und Rhodium mit facialen Cyclooctatetraen(cot)-Liganden. Es werden Reaktionen von [Co2(CO)8], [Rh4(CO)12], [Co3Rh(CO)12] bzw. [Co2Rh2(CO)12] mit cot und bis-Trimethylsilyl-cyclooctatetraen (Si2cot) (Gemisch der 1,4- und 1,6-Isomeren) beschrieben, die in hohen Ausbeuten zu vierkernigen Clusterkomplexen mit flächenüberbrückenden cot- oder (Si2cot)-Liganden führen. Durch selektive Liganden-Substitution bzw. Addition am „apicalen“ Metallatom werden weitere Derivate mit der gleichen Grundstruktur hergestellt. Die Molekülstrukturen und Ligandendynamik der neuen Clusterkomplexe werden durch Röntgenstrukturanalyse, NMR- und IR-Spektroskopie charakterisiert. Das Redoxverhalten wird durch elektrochemische Messungen (cyclische Voltammetrie, Polarographie und Coulometrie) untersucht.
Die Arbeit befasst sich mit der Modellierung und Simulation der heterogenen Vorgaenge beim Abbrand einer Koksoberflaeche. Als Modellsystem hierfuer wird die Oxidation einer Graphitoberflaeche verwendet. Es wird ein Reaktionsmechanismus aufgestellt, der die Bildung der verschiedenen Oberflaechenkomplexe, den Einfluss der Oberflaechengeometrie und die direkte Reaktion zwischen Gasphasenmolekuelen und Oberflaechenkomplexen beruecksichtigt. Die Geschwindigkeitskoeffizienten der Oberflaechenreaktionen werden mit Methoden aus der mikrokinetischen Analyse von heterogenen Katalysereaktionen abgeschaetzt.
Rußpartikel sind ein Produkt der unvollständigen Verbrennung von Kohlenwasserstoffen. Sie stellen einen wichtigen Bestandteil des atmosphärischen Aerosols dar. Die Oxidationskapazität der Troposphäre sowie die Stickoxid- und Ozonchemie der Stratosphäre werden durch Rußaerosole möglicherweise signifikant beeinflusst. Es wurde die Zersetzung bzw. Reduktion der Spurengase O3, NO2, N2O5/NO3, HNO3 und HOONO2/HO2 an luftgetragenen Rußpartikeln in der Aerosolkammer AIDA bei atmosphärisch relevanten Bedingungen untersucht. Nach dem schnellen Anfangsverlust von etwa einem Monolagen-Äquivalent Ozon sinkt die Reaktionswahrscheinlichkeit auf einen Wert, der um mindestens 3 Größenordnungen unter den in Modellrechnungen angenommenen liegt. Die Zersetzung von Ozon an Rußaerosol spielt demnach weder in der Troposphäre noch in der Stratosphäre eine Rolle. Auch für alle übrigen untersuchten Spurengase ergaben sich Reaktionswahrscheinlichkeiten, die um Größenordnungen unter den Schwellenwerten lagen, die einen Einfluss auf die Oxidationskapazität der Atmosphäre erwarten lassen. Die Oxidation durch Spurengase kann für die Entfernung von Rußablagerungen aus Katalysatoren genutzt werden. Der Abbau von Rußpartikeln durch 1 Ozon in Luft verläuft bereits bei Zimmertemperatur mit messbarer Geschwindigkeit. Der Prozess spielt allerdings in der Atmosphäre keine Rolle, da die Abbauzeit dann mehrere tausend Jahre beträgt. Unter den Bedingungen eines Diesel-Katalysators (350°C, 500 ppm NO2) werden Rußpartikel durch NO2 innerhalb von 3 h abgebaut. Zur Interpretation der Messergebnisse wurden ESR-Spektren locker abgeschiedener Funken- und Dieselrußpartikel herangezogen. Durch teilweise Oxidation von Funkenruß wird das ESR-Spektrum dem von Dieselruß immer ähnlicher. Ein Vergleich hochaufgelöster TEM-Aufnahmen lässt den Schluss zu, dass die beiden Signale unterschiedlichen Domänen der Rußpartikel zuzuordnen sind, die sich in ihrer Reaktivität deutlich unterscheiden.
Die vorliegende Arbeit beschäftigt sich mit der Synthese von nido-Hexaboranen mit den Gerüstatomen C2B3N, C2B3S und C5B. Während größere Aza- und Thiacarborane (n = 10 - 12) in der Literatur beschrieben werden und gut charakterisiert sind, kennt man von den kleineren Systemen nur weinige Beispiele (C2B3N und C2B3S), die zudem nur unvollständig untersucht sind. Der hier beschriebene Zugang zu dieser Gruppe der Heterocarborane erfolgt durch eine Hydroborierung von exocyclisch ungesättigten Heterodiborolanen. Sterisch anspruchsvolle Substituenten an den Boratomen setzen dabei die Reaktivität herab und ermöglichen die Entstehung von kristallinen, für Strukturuntersuchungen geeignete Verbindungen. Die einzelnen Schritte der Hydroborierung werden durch ab initio Rechnungen an leicht vereinfachten Modellsystemen nachvollzogen. Nido-Pentacarbahexaborane(6) sind bisher nur in Form von kationischen Derivaten oder als Donor in einem Metallkomplex bekannt. Bei den Reaktionen der niedrigvalenten Verbindungen Cp*2Si und Cp*Ga mit B2Cl4 entstehen durch Insertions- und Austauschprozesse verschiedene neutrale Produkte mit C5B-Substrukturen. Die Verbindung hapto5-Cp*B-BCl2SiCl3 wurde vollständig charakterisiert und ihre Konstitu-tion durch eine Kristallstrukturuntersuchung aufgeklärt. Ab initio Rechnungen rechtfertigen die Beschreibung der neuen Verbindungsklasse als Addukte des Borylens (Borandiyls) Cp*B: an ein Boran, z. B. BCl2SiCl3, wobei das Borylen als ein sehr starker, reiner sigma-Zweielektronen-Donor fungiert.
Three models were implemented, which are important for pollutant prediction in Diesel engines: ignition, chemistry and radiation. Ignition was tracked by means of a representative species (here CO), whose concentration remains small during the ignition period and which shows an increase at ignition. Its reaction rate was obtained from a detailed mechanism and combined with a presumed probability density function (pdf). The intrinsic low-dimensional manifold (ILDM) method was used as a chemistry model. It is an automatic reduction of a detailed chemical mechanism based on a local timescale analysis. It was also combined with a presumed pdf method. NOx and soot were predicted using a Zeldovich model and a phenomenological two-equation model, respectively. The radiative properties of the gases were described with a weighted sum of grey gases model (WSGGM). The radiative properties of soot were described by a grey model. The RTE was solved using the discrete ordinates method (DOM), which involves solving the RTE in discrete directions. The ignition and chemistry models were implemented in a standard CFD code, KIVA and used to simulate the combustion in a Caterpillar engine, for which experimental data were available. Ignition was observed to occur at the edge of the spray, in the lean region. Simulated pressure curves and mean NO concentrations were compared to experimental data and showed good agreement. Soot was strongly under-predicted due to the inability to identify the ILDM in the rich region. The DOM radiation model was tested in a furnace, and the wall fluxes were compared to analytical data. It was not used in the engine due to low quantities of soot predicted. Instead, an optically thin model was used in the engine and the radiative losses were seen to be negligible.
Mit den Bor-t-butylierten Diborolen wurden neue Diborol(yl)rhodium-Komplexe dargestellt, die für die Synthese neuer Oligo- bis Polydecker-Sandwich-Komplexe geeignet sein sollten, wobei der sterische Anspruch dieser neuen Liganden untersucht wurde. Desweiteren wurden temperaturabhängige NMR-spektroskopische Untersuchungen an Diborol/Alkyllithium/THF-Reaktionsmischungen durchgeführt, um den Reaktionsmechanismus des zweifachen Me/t-Bu-Austauschs bei der Darstellung von (1,3-Di-t-butyl-4,5-dimethyl-2,3-dihydro-1,3-diborolyl)-(toluol)rhodium aus dem Tetramethyldiborol, t-BuLi, Bisethenrhodiumchlorid-Dimer und Toluol zu klären.
Kurzfassung der Dissertation Angesichts der zur Neige gehenden weltweiten Erdölressourcen und der Tatsache,daß das Erdöl nich nur als Energieträger sondern auch als Rohstoffbasis in der chemisch-pharmazeutischen Industrie dient, rücken mögliche Alternativen in den Mittelpunkt des Interesses. Erdgas mit seinem Hauptbestandteil Methan stellt eine solche Alternative dar.Aufgrund der großen Be- deutung die dem Erdöl als Rohstoffpool zukommt, beschäfftigte sich diese Arbeit mit der kata- lytsichen Konversion von Methan zu höheren Kohlenwasserstoffen (C 2+). Katalytische Verfahren zur Konversion von Methan zu höheren Kohlenwasserstoffen (C 2+) lassen sich grundsätzlich unterteilen in die sauerstoffreie Konversion (dehydrierende Kopplung oder Non-Oxidative Conversion of Methane ,kurz:NOCM)und die sauerstoffhaltige Kon- version ( Oxidative Conversion of Methane ,kurz:OCM). Während bei letzteren die Pro- duktausbeuten (CH 4 -Umsätze)wesentlich höher sind als im sauerstoffreien Fall,liegen die Pro- duktselektivitäten bzgl.der favorisierten höheren Kohlenwasserstoffe bei der sauersto reien Konversion zumeist bei ¨uber 90Die Selektivitäten der OCM-Verfahren bzgl.höherer Koh- lenwassersto e sind verglichen damit bescheiden.Das Hauptprodukt der OCM-Verfahren ist, je nach Reaktionsbedingung und Katalysator,Synthesegas,was in einem katalytischen Fol- geschritt mittels Fischer-Tropsch-Verfahren in höhere Kohlenwassersto en umgesetzt werden kann. Der Vorteil der sauersto reien Methankonversion (NOCM)im Vergleich zur partiellen Oxi- dation (OCM)ist ihre große C 2+-Selektivität,ihr größter Nachteil der zu geringe CH 4 -Umsatz (10gilt als guter Wert [18 ]).Aus ökonomischer Sich wäre der NOCM-Prozeß erst ab 50 Methanumsatz rentabel. Im Rahmen des Sonderforschungsbereichs Reaktive Strömungen wurden Arbeiten zur Steuerungsoptimierung katalytisch chemischer Prozesse aufgenommen. Die Voraussetzung für die Prozeßoptimierung ist
Oligosaccharide, die an Proteine gebunden oder in Zellmembranen verankert sind, spielen eine wichtige Rolle bei der Wechselwirkung zwischen Zellen, Zellen und Viren bzw. Bakterien. Im Rahmen dieser Arbeit wurden Simulations-Strategien und Analyse-Methoden entwickelt, die es ermöglichen, in effizienter Weise Konformationsanalysen von Oligosacchariden im solvatisierten freien und gebundenen Zustand durchzuführen. Eines der wichtigsten Ergebnisse der vorliegenden Arbeit ist die Entwicklung von neuen Strategien und Methoden zur Berechnung der relativen freien Enthalpien aller Konformationen eines potentiellen Liganden basierend auf Moleküldynamik(MD)-Simulationen. Freie Enthalpiedifferenzen lassen sich nur für Konformationen berechnen, die sich im Gleichgewicht befinden, daher wurde ein empirischer Parameter (EQ Faktor) entwickelt, der es erlaubt, das Erreichen des Konformationsgleichgewichts während einer MD-Simulation anzuzeigen. Es konnte weiterhin gezeigt werden, dass Hochtemperatur-MD-Simulationen (HTMD) mit Simulationstemperaturen bis zu 1000 K geeignet sind, um den Konformationsraum von Oligosacchariden im freien Zustand innerhalb einer CPU-Zeit von wenigen Tagen effizient zu durchsuchen und ein Gleichgewicht zwischen den Konformationen einzustellen. Die berechneten Konformationskarten der Freien Enthalpie sind über weite Temperaturbereiche reproduzierbar. Basierend auf der Temperaturabhängigkeit der mittleren Lebensdauer der Konformationen wurde ein Verfahren entwickelt um die Übergangsbarrieren zwischen den Konformationen aus Trajektorien-Daten zu berechnen (Arrhenius-Analyse). Durch eine detaillierte Wechselwirkungsanalyse eines repräsentativen Ensembles von MD-Strukturen ist es gelungen einen sinnvollen Strukturvorschlag für den Hevein-Chitotriose-Komplex zu machen. Weiterhin wurden NMR-Methoden eingesetzt um den Einfluss des Lösungsmittels (Wasser-DMSO-Mischungen) auf die Bindungsaffinität zu untersuchen.
Im Rahmen dieser Arbeit werden verschiedene erweiterte Zweiteilchen-Greensfunktionen und die sogenannte dynamische Greensfunktion vorgestellt. Diesen Propagatoren ist gemein, daß sie eine Dyson-Geichung definieren und damit eine Selbstenergie definieren. Die Selbstenenergie übernimmt die Funktion eines optischen Potentials, das zur effektiven Beschreibung von Vielteilchenproblemen in einer stark reduzierten Anzahl von Koordinaten geeignet ist. Die erweiterten Zweiteilchen-Greensfunktionen und die dynamische Greensfunktion erlauben damit eine Ausweitung der für die Einteilchen-Greensfunktion bekannten Eigenschaften auf zusätzliche Freiheitsgrade. Um die Konstruktion der erweiterten Greensfunktionen zu motivieren, werden zunächst am Beispiel der Einteilchen-Greensfunktion die der Dyson-Gleichung zugrundeliegenden Prinzipien demonstriert. Dabei wird gezeigt, daß es im Wesentlichen darauf ankommt, daß die Greensfunktion sich als Projektion einer Vielteilchenresolvente auf einen vollständigen, orthonormalen Satz von Zuständen formulieren läßt. Im ersten Teil dieser Arbeit wird eine allgemeine Theorie der erweiterten Zweiteilchen-Greensfunktionen vorgestellt und als exemplarische Anwendung der Theorie ein Näherungsschema erster Ordnung für Anregungsenergien und Übergangsmomente (das FOSEP-Schema) vorgestellt und näher untersucht. Im zweiten Teil dieser Arbeit wird eine exaktes optisches Potential für die gekoppelte Bewegung des Projektilelektrons und der Atomkerne in der Elektron-Molekülstreuung hergeleitet.