Superoxide dismutases (SODs) are metalloenzymes that disproportionate superoxide (O2●—) into hydrogen peroxide (H2O2) and molecular oxygen (O2) via alternate oxidation and reduction of their metal cofactors. The most recently discovered SOD, namely NiSOD, has been isolated from Streptomyces soil bacteria and contains Ni(III/II) housed in an unusual N/S ligand set. This coordination sphere has prompted several investigations into the properties imparted by these donor atoms to favor Ni-based redox and Cys-S oxidative-stability. One potential defense against unwanted S-oxygenation/oxidation is though protonation of the coordinated Cys-S to result in a Ni-coordinated thiol. To examine the role of a coordinated thiol in the catalytic activity of NiSOD, we have constructed Ni-N/S complexes with mixed thioether/thiolate S-donors as synthetic analogues. The expectation is that selective S-alkylation will decrease S-character in the HOMO, reduce S-nucleophilicity, and promote axial binding of an N-donor to favor Ni-based redox chemistry. Our results indicate that the four-coordinate (4C) planar Ni-N2S2-CH3 complex exists in equilibrium between mononuclear and S,S-bridged dinuclear species due to the weaker thioether donor and propensity of metal-thiolate complexes to dimerize. This result suggests that incorporation of a covalently bound axial N-donor is necessary to sustain thioether coordination and prevent dimerization, in addition to stabilizing the Ni(III) oxidation state. The synthesis and characterization of these Ni-N2/3S2-CH3 models of NiSOD will be presented along with an assessment of their reactivity and SOD activity. These results offer new insight into thiol coordination in NiSOD and the role this mechanism may play in oxidative stability and catalysis for other metal-thiolate sites in biology that participate in proton-coupled redox chemistry.

NiSOD model complexes that probe the catalytic and electronic implications of a Ni-coordinated Cys-Thiol

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.