<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "The Mode of Action of Embelin as an Alternative Photosensitizer for Photodynamic Therapy"^^ . "Effective treatment of cancer using existing drugs remains a challenge due to side \r\neffects experienced by cancer patients during therapy. Research towards discovering \r\nnew anticancer agents with less side effects is an ongoing effort which unfortunately \r\nrequires huge investments from lead compound discovery to clinical trials. \r\nConventional methods used in treating cancer include chemotherapy, radiation, as \r\nwell as surgery. These methods have seen tremendous improvements, but a lot \r\nremains to be done to slay the cancer dragon. In the recent past, attention has turned \r\nto exploring the use of photo active molecules to treat cancer and other ailments such \r\nas microbials in a process known as photodynamic therapy (PDT). These molecules \r\nare commonly known as photosensitizers (PS) and should possess adequate structural \r\ncharacteristics that promote synergy effects when exposed to certain wavelengths of \r\nlight. \r\nIdeally, the absorption wavelength of PS should range between ~ 500-800 nm which \r\nis critical for tissue penetration. Popular PS include Porphyrin whose derivatives have \r\nbeen successfully applied in PDT treatment. Alternatives to the widely studied\r\nporphyrin scaffold also exist, and more scaffolds need to be added onto the wide \r\ntherapeutics required to treat cancer. In this work, a theoretical investigation of \r\nembelin which has a benzoquinone scaffold has been carried out. Interesting \r\nproperties are explored including electronic resonance, proton transfer pathways and \r\nthe ability to generate singlet oxygen. Furthermore, its ability to bind the X-linked \r\ninhibitor of apoptosis is investigated and the binding mechanisms as well as binding \r\nenergies are reported. Advanced hybrid QM/MM studies have also been carried out \r\nto investigate its spectral signatures within the protein environment. \r\nThis work begins by addressing embelin’s ground- and -excited state properties in \r\nchapter 3. The aim of this chapter is to highlight embelin’s individual molecular \r\nproperties. The calculations are carried out with and withoutsolvation models. Results \r\nobtained are the excitation energies of embelin, the nature of its geometrical \r\nparameters in the ground and excited state potential energy surfaces (PES), and its \r\ngeneral ability to generate singlet oxygen. The Algebraic Diagrammatic Construction \r\nii\r\n(ADC) and Time-dependent Density Functional Theory (TD-DFT) methods are \r\nextensively used to approximate the excitation energies and molecular properties of \r\nembelin. Particularly, ADC(3) accurately reproduces the excitation energy at 4.32 eV \r\ncompared to the experimental absorption energy of 4.31 eV. In the ground state, \r\nembelin is found to exhibit a weak intramolecular hydrogen bond confirming previous \r\nreported results on the existence of electronic resonance within its structure. This \r\nproperty is enhanced on photon absorption by hyperbonds within the structure, \r\nmeaning that photon absorption stabilizes embelin in the exited state and promotes \r\nresonance. In fact, a detailed investigation using potential energy surface (PES) scans \r\nresulted in intermediates which are in complete agreement with the excited state \r\nstabilizations which favor excited state intramolecular proton transfer (ESIPT). The \r\nintermediates formed in the excited state further promote efficient intersystem \r\ncrossing to the triplet state with enough excess energy to generate reactive oxygen \r\nspecies (ROS) such as singlet oxygen. \r\nIn chapter 4, the binding pattern of embelin against X-linked Inhibitor of apoptosis\r\n(XIAP) is presented. Here, focus is turned towards identifying the “active site” where \r\nembelin prefers to bind the baculoviral inhibitor of the apoptosis (BIR3) domain of \r\nXIAP. XIAPs are known to bind caspases hence interfere with normal cell death \r\nwhich results in proliferation of abnormal cells. Embelin is found to bind mostly to \r\nGlu and Tyr residues (which have been experimentally identified as one of the critical \r\namino acids in embelin’s binding pattern). The binding is measured as a function of \r\nthe hydrogen bonding percentage with values as high as 60%. The dominating binding \r\npattern is a hydrogen donating mechanism with the protein residue pairs acting as \r\nproton acceptors. The binding energy is calculated to be -24.7 kJ/mol which agrees \r\nnicely with -25.1 kJ/mol (the experimental value of Human serum albumin). \r\nSince the overall aim of the thesis is to address the applicability of embelin in PDT \r\nwhich occurs within a protein environment, advanced hybrid QM/MM calculations \r\nare presented in chapter 5. The major results in this chapter are the spectral signature \r\nof embelin embedded within the BIR3 environment. The reported vertical excitation \r\nenergies are comparable to the values obtained in chapter 3. More importantly, \r\nembelin is stable within the protein environment and absorbs light with similar \r\nwavelengths reported by experiment. The absorption wavelengths are however \r\niii\r\nslightly shifted when only electrostatics are taken into consideration. Inclusion of \r\npolarization effects simulated using PE-ADC resulted in slightly red-shifted\r\nexcitation energies. In general, the results obtained within this chapter are consistent \r\nand predict the ability of embelin to generate singlet oxygen."^^ . "2021" . . . . . . . "Michael Rogo"^^ . "Opata"^^ . "Michael Rogo Opata"^^ . . . . . . "The Mode of Action of Embelin as an Alternative Photosensitizer for Photodynamic Therapy (PDF)"^^ . . . "Michael_Rogo_opata_Phd_Thesis.pdf"^^ . . . "The Mode of Action of Embelin as an Alternative Photosensitizer for Photodynamic Therapy (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "The Mode of Action of Embelin as an Alternative Photosensitizer for Photodynamic Therapy (Other)"^^ . . . . . . "medium.jpg"^^ . . . "The Mode of Action of Embelin as an Alternative Photosensitizer for Photodynamic Therapy (Other)"^^ . . . . . . "preview.jpg"^^ . . . 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