Date of Award
Spring 2018
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
First Advisor
Fiedler, Adam T.
Second Advisor
Reid, Scott
Third Advisor
Gardinier, James
Abstract
Mononuclear non-heme iron dioxygenases (MNIDs) are a class of enzymes that catalyze a variety of reactions, from amino acid catabolism to bioremediation using molecular oxygen. This work focuses on three types of MNIDs: thiol dioxygenaes (TDOs), aminophenoldioxygenases (APDOs), and sulfoxide synthases (SOSs). TDOs, found in mammals, regulate the levels of cysteine along with other thiol-containing molecules, using molecular oxygen to convert them into their corresponding sulfinic acids. APDOs catalyze the oxidative ring cleavage in the biodegradation of nitroaromatics. SOSs are involved in the biosynthesis of large biologically relevant molecules in humans. Although this class of enzymes has gained more attention in recent years, their catalytic mechanism is still not well understood. In order to gain more insight into these procedures, synthetic models have been prepared and studied. This is a common strategy used to learn more about the structural and electronic properties of enzymes as well as their reactivities because small-molecule metal complexes are generally easier to prepare, handle, and characterize. Also, it is possible to trap reactive species and catalytic intermediates in synthetic systems due to greater flexibility in structure and reaction conditions. There have been previously published synthetic models of TDOs and APDOs, but they lack the correct coordination, charge, or reactivity to mimic the active sites of the enzymes. There have been no reports of synthetic models of SOSs in literature to date. Series of iron-containing biomimetic complexes were made to mimic the active site structures of these enzymes. A variety of spectroscopic techniques were used to characterize these complexes – these techniques include 1H NMR, UV-Vis, infrared, electron paramagnetic resonance, and resonance Raman spectroscopies. Computational studies, elemental analyses, and electrochemical studies were also performed. The reactions of these complexes with O2were studied extensively, using the techniques mentioned above. Other small molecules that mimic the binding of O2 were also used to probe the metal center – including nitric oxide, cyanide, and azide. Additionally, cobalt was substituted for the iron center because it is more spectroscopically accessible, giving even more insight into the active site structure.