Pyridinium Salts: from Photoinduced Through-Space Electron Delocalization to Novel Spontaneous Reactions Causing Thermal DNA Damage
Date of Award
Doctor of Philosophy (Ph.D.)
R. Marshall Wilson (Advisor)
Pavel Anzenbacher (Committee Member)
Hong Lu (Committee Member)
Kit Chan (Other)
The first chapter of this dissertation is devoted to the investigation of the pimerization and photo-induced electron-transfer processes in the series of bis(pyridinium) alkane salts and covalently linked monoquat. The DFT analysis of bis(pyridinium) alkane systems allowed us to compare the energies of the different conformations of dications and radical cations of these salts formed upon single electron reduction which is important for the determination of the conformations that favor the formation of the dimer radical cation. The results of these calculations made an important contribution to the studies of pimerization in bis(pyridinium)alkane salts. Reduction of monomeric and covalently linked monoquat (1-methyl-4-(4-pyridyl)pyridinium) was assessed experimentally by means of Cyclic Voltammetry and transient absorption spectroscopy. A number of interesting observations were made to provide a basis for the improved design of novel photochemical DNA damaging agents that contain electron-poor pyridinium or monoquat `arms’ able to undergo pimerization process.
The second part of the dissertation covers the spontaneous aerobic catalyst-free transition from 1,1,2,2-tetrakis(N-methylpyridin-4-ium)ethane iodide to the corresponding epoxide (major product) and alkene (minor product). This reaction represents a rare transition from a substituted alkane to the epoxide. The mechanism of the reaction was proposed based on the intermediates and products characterization and further supported by the kinetic modeling. It was demonstrated that the oxidation proceeds through the formation of the air sensitive monomethine cyanine dye dimer. This reaction intermediate was involved in the production of the Reactive Oxygen Species (ROS) that are known to induce DNA damage.
In light of this observation, the DNA toxicity of 1,1,2,2-tetrakis(N-methylpyridin-4-ium)ethane under aerobic aqueous conditions was examined. The results of this study are presented in the last chapter of the dissertation. DNA damage upon mixing of 1,1,2,2-tetrakis(N-methylpyridin-4-ium)ethane with DNA in air was demonstrated. This project has a promising potential for utilization in the areas of ROS-cancer treatment and biomedical research.
Tcyrulnikov, Nikolai, "Pyridinium Salts: from Photoinduced Through-Space Electron Delocalization to Novel Spontaneous Reactions Causing Thermal DNA Damage" (2019). Photochemical Sciences Ph.D. Dissertations. 110.