Date of Award
Summer 2014
Document Type
Thesis
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.