Synthetic Analogues of Cysteinate-Ligated Metalloenzymes

University Of Washington, Seattle WA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Nitrile hydratase (NHase) and superoxide reductase (SOR) are a new class of non-heme iron enzymes that contain cysteinate sulfurs coordinated to iron. Their function varies enormously from nitrile hydration, with NHases, to superoxide reduction, with SOR. Although the structures of NHase and SOR have been defined, a number of unresolved questions concerning the mechanisms of action of both enzymes have yet to be adequately addressed. To this regard, the research described in this proposal will focus on modeling the reactivity of NHase in an effort to understand the mechanism of nitrile hydrolysis as well as the role that peptide amides and cysteinate sulfur ligand(s) might play in promoting function; determining whether the oxygenated sulfurs are necessary for NHase activity, or whether they are simply an artifact; understanding and determining how the electronic and reactivity properties of Pel 11-peroxides containing only nitrogen donors are affected by the incorporation of a thiolate sulfur and make direct comparisons between structurally related model systems that differ by only one ligand. To achieve these goals, different synthetic model complexes will be synthesized and their reactivity studied. [unreadable] [unreadable]