Summary: Proteins containing transition metal ions carry out a variety of important functions in biological systems. Consequently, understanding how these chemical transformations occur and what factors regulate their reactivity is an important research area. The focus of our research is to provide fundamental insight into the structure and function of metalloenzymes by using the synthetic modeling approach. The synthetic modeling approach involves the synthesis of low molecular weight complexes that model the structural and functional units of the enzymes. Useful information such as spectroscopic and structural data and identification of possible intermediates or pathways in the enzymatic cycle can be obtained through studies of the synthetic model complexes. The impact of our research includes possible development of new pharmaceuticals, bio-inspired catalysts with green chemistry applications and metal-based sensors that detect and quantify small molecules in biological systems.

Minimum Classes: General Chemistry

Projects: The function of DNA repair proteins are to protect cells against alkylating agents that can damage DNA. The N-terminal domain of Ada repair protein (Ada) in E. coli. contains an active site consisting of a zinc ion coordinated by four cysteine amino acid residues. The nucleophilic cysteine residues are responsible for repairing damaged DNA by irreversibly transferring the alkyl group from the alkylated DNA to the sulfur atom of the cysteine. However, the mechanism of the transfer step is controversial with two different mechanisms being proposed. Furthermore, the role of hydrogen bonding interactions at tuning the nucleophilicity of the cysteine residues remains unclear. A potential project a fellow would work on would be to synthesize zinc-thiolate complexes supported with ligands with and without hydrogen bond donors and to explore their reactivity with various alkylating agents. The mechanism of alkylation would be explored using kinetics and other physical inorganic methods. Fellows will also be exposed to a variety of characterization methods that include X-ray crystallography and NMR (1D and 2D), IR, and UV-Vis spectroscopies.

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