Date of Award


Publication Type

Doctoral Thesis

Degree Name



Chemistry and Biochemistry

First Advisor

Gauld, James


Computational Chemistry, DFT, Enzymology, QM/MM, Quantum Mechanics, Sulfur Chemistry




In biochemistry, sulfur-containing biomolecules enrich the chemical diversity in cells. This occurs via their participation in several reactions including disulfide formation, metal-binding and redox catalysis. Since sulfur occurs in various oxidation states, it exhibits interesting chemistry and reactivity. In this Dissertation computational modeling techniques have been used to investigate several aspects of sulfur's unique chemistry. Particularly, previously proposed mechanisms for sulfenic acids formation and reduction/overoxidation pathways have been examined In detail. A holistic picture of sulfur/sulfenic acid chemistry in biochemistry has been portrayed. For instance, the importance of non-covalent interaction in stabilizing the unstable sulfenic acid intermediates has been highlighted. Furthermore, the mechanism of Thiol activation in several active sites as well as the factors affecting thiolate stabilization has been determined in several enzymes. The role of protein dynamics and possible effects on catalysis has been emphasized. Moreover, a novel antioxidant pathway has been proposed. Computationally, the effect of choosing starting structure for modelling was also stressed.