Date of Award

Summer 2014

Document Type

Thesis - Restricted

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Fiedler, Adam T.

Second Advisor

Yi, Chae

Third Advisor

Huang, Jier

Abstract

It is well-established that S-adenosylmethionine (SAM) serves as the methyl group donor in methylations of DNA, hormones, neurotransmitters and signal transduction systems. However, a new class of enzymatic reactions involving SAM has recently attracted considerable attention. In these systems, SAM initiates radical-based reactions at the active sites of enzymes via formation of an adenosyl radical, which further abstracts a H-atom from the substrate to initiate a radical-based mechanism. However, modeling studies of radical SAM enzymes have been hindered, by difficulties in preparing adequate synthetic [Fe4S4] clusters. We prepared a novel series of Fe(II) complexes with tripodal tris(2-hydroxybenzyl)amine ligands, which replicate the geometry of the unique Fe centers found in radical SAM enzymes. The resulting complexes were characterized by X-ray crystallography, paramagnetic 1H NMR spectroscopy, electronic absorption spectroscopy, and electrochemical methods. The complexes were evaluated by three criteria established to model the unique Fe site in radical SAM proteins: i) a high spin state, ii) a low redox potential near the value measured for the enzymes (ca. -0.70 V vs SCE), and iii) coordinative unsaturation, such that Fe center can bind exogenous ligands with sulfonium cations. To determine whether the resulting synthetic models are capable of reductively cleaving S-C bonds to generate radical species, we also prepared sulfonium salts that contain metal-binding moieties, such as a pyridyl group, which position the reactive sulfonium group close to the Fe(II) center. GC-MS and 1H NMR spectroscopy were used to characterize and quantify the resulting products. By monitoring changes in UV-visible absorption features as a function of time, we have measured reaction rates for the following sulfonium cations: S-(phenyl) tetramethylenesulfonium and S-(2-pyridylmethyl) tetramethylenesulfonium. These experiments allowed us to evaluate the effect of Fe∙∙∙S distance on the rate of electron transfer. Finally, density functional theory (DFT) calculations have been performed to further elucidate significant interactions within this synthetic modeling system.

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