In nature, enzymes with thiolate coordinated mononuclear non-corrinoid Co(III) or non-heme Fe(III) metal ion active sites, notably iron-sulfur centers, are generally found to use RedOx-based mechanisms of action in their catalysis function. However, there exist a few enzymes to which such mononuclear metal active sites do not appear to participate in RedOx-based catalysis mechanisms including our enzyme of interest: nitrile hydratase (NHase). The structure and chemistry of the NHase active site has drawn significant attention in the past few decades owing to its unique features that include: i) redox-inactive metal ion bound to cysteine thiolates, ii) backbone carboxamido nitrogen coordination to the metal ion, and iii) asymmetric oxidation of the cysteine bound thiolates. Our group has been working on developing structural and functional models of NHase in order to better understand its chemistry. Specifically, our investigations are performed through the development of small molecular models of the 1<sup>st</sup> coordination sphere of the NHase active site using the synthetic analog approach. Herein, we report on our progress towards the development of synthetic analogs that model the asymmetric, diamidatodicysteinate tetradentate plane framework of the active site in their Co(III)- and Fe(III)-NHase form, both in the pre- and post-translationally modified configurations (selective thiolate oxidation to sulfenate and sulfinate) of the native enzyme. Of note, specific structural models were designed to develop a better understanding of potential hydrogen-bonding within the 1<sup>st</sup> coordination sphere of the active site. The synthesis and characterization of the complexes are reported with the latter using standard techniques (NMR, UV Vis, FTIR, cyclic voltammetry (CV), and ESI-MS) and x-ray crystallography, where possible.

Studies toward the development of a more accurate structural model of the nitrile hydratase active site

254th National Meeting (2017)

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