Metal-Siklen Destekli Reaktif Oksijen Türlerinin Oluşumuna ve Oksidatif Deboronasyon Tepkimesine Metal Etkisinin ve Optik Özelliklerinin Teorik İncelenmesi

Abstract

Throughout their life cycles, living organisms are exposed to a diverse array of biological/chemical agents that have the potential to inflict irreversible damage to their DNA, the fundamental building blocks. To minimize this potential harm, it is imperative to illuminate the molecular-level mechanisms of synthesis and degradation that protect the structure of DNA or activate repair pathways. Among the chemical agents that can lead to DNA damage, reactive oxygen species (ROT) - causing the oxidation of deoxyribose sugars and nucleotide bases - are prominent. It is known that in biological systems, the formation of ROT results from the complexation reaction of molecular oxygen with transition metals, and that metal-chelate complexes containing ROT can undergo oxidative deboronation in the presence of peptide boronic acid. The mechanistic investigation of this two-step reaction, which occurs successively, via Density Functional Theory (DFT) on different metal and chelate complexes forms the first part of this thesis work. In this regard, potential energy diagrams, including all transition states, intermediate and product structures involved in the mechanism proceeding from the formation of the corresponding ROT structures as a result of the interaction of the designed metal-cyclene complex models with molecular oxygen (O2), to the ultimate products formation via the oxidative deboronation reaction of this compound, have been prepared. For the investigation of the effect of the metal-chelate on ROT formation and oxidative deboronation reactions, cyclene chelate (1,4,7,10-tetraazacyclododecane) has been used with metal ions such as Fe2+/Fe3+, Mn2+/Mn3+, Ni2+/Ni3+, Co2+/Co3+, Cu+/Cu2+, Hg+/Hg2+ and Ti2+/Ti3+, which have one electron oxidation properties. The stabilities, electronic properties, molecular orbital analyses, and reaction activation energies of all selected structures have been determined. In the second part of the study, incorporating boronic acid groups in the molecular structure, in conjunction with fluorophore (imidazole, oxazole, thiazole) and chromophore (imidazole, oxazole, thiazole, donor-π-acceptor) units, as per the Time-Dependent Density Functional Theory (TD-DFT) investigations and the deboronation reaction mechanism has been thoroughly examined through their theoretical UV-vis spectra. This thesis work was carried out with the aim of developing a theoretical perspective for a comprehensive examination of the mechanisms leading to ROS formation that cause DNA damage and fragmentation. Using computational chemistry techniques, these mechanisms have been analyzed through mechanistic and spectroscopic reactions on various transition metal-chelate complexes.