Part 1: Structure, stability and reactivity of small biologically-active organosulfur compounds. Part 2: Generation of reactive oxygen species in the enzymatic reduction of chromium(VI) and arsenic(V) and its implications in metal-induced carcinogenesis.
Date of Graduation
Structure, stability, kinetics and mechanisms of oxidation of some important organosulfur compounds (2-aminoethanethiolsulfuric acid, 4-methyl-3-thiosemicarbazide and thionicotinamide) have been investigated by using UV-VIS, NMR, stopped-flow, and qualitative analysis. Results obtained showed that oxidation occurs mainly at the reactive sulfur center of the molecules via successive addition of oxygen atoms. The oxidation of thionicotinamide, an important xenobiotic, gave different oxygenated products, depending on the oxidizing power of the oxidant used. The sulfinic acid of thionicotinamide is stable with mild oxidizing agents while stronger oxidants desulfurize the molecule to yield sulfate as observed with other organosulfur compounds studied. Mechanism of oxidation leading to sulfate formation was confirmed using numerical simulations of the reaction dynamics where possible. Mild oxidants give the first evidence of a stable sulfenic acid in the form of an S-oxide. The formation of reactive oxygen species in the enzymatic reductions of Cr(VI) and As(V) by nitric oxide synthase and glutathione reductase respectively, were investigated in the presence of NADPH as a cofactor. It was found that the mechanisms of reduction of these metal ions are very different; Cr(VI) reduction produced Cr(V) almost quantitatively with formation of superoxide ion radicals from molecular oxygen and hydroxyl radicals. As(V) reduction on the other hand, generated hydroxyl radical mostly via Fenton-like reactions from hydrogen peroxide. The two processes caused considerable DNA damages and the reduced ions are able to function as Haber-weiss catalysts for continuous generation of hydroxyl radicals.
Olojo, Oluwarotimi Odunayo, "Part 1: Structure, stability and reactivity of small biologically-active organosulfur compounds. Part 2: Generation of reactive oxygen species in the enzymatic reduction of chromium(VI) and arsenic(V) and its implications in metal-induced carcinogenesis." (2002). Graduate Theses, Dissertations, and Problem Reports. 9537.