Structural and electronic factors that influence ni versus thiolate redox from synthetic models of nisod
Steiner, Ramsey Alison
MetadataShow full item record
Superoxide (O2·‒) is a cytotoxic byproduct of aerobic metabolism. As a result, all aerobic organisms possess the metalloenzymes superoxide dismutases (SODs) to catalyze the disproportionation of O2·‒ into hydrogen peroxide (H2O2) and oxygen (O2) via alternate oxidation and reduction of their respective metal centers. In 1996, the most recent class of SOD was isolated from Streptomyces soil bacteria containing Ni (NiSOD) in an unusual, mixed N/S coordination sphere. The principal question remaining is how this unique coordination sphere promotes both Ni-based redox activity and S-oxidative-stability. We have successfully developed, synthesized, and characterized Ni complexes with mixed carboxamide/amine and thiolate ligands as low molecular weight synthetic analogues of NiSOD. We designed trimetallic systems to interact via unique inter/intra-molecular H-bonding networks, resulting in properties distinct from their monometallic counterparts. These complexes have shed light onto the role of hydrogen bonding (H-bonding) networks and steric bulk in modulating S-electron density in the frontier molecular orbitals (FMO) and preventing access of ROS to the Ni/S cluster. We propose that NiSOD employs both steric and electronic protection to avoid thiolate reactivity with ROS. Reactivity of low molecular weight complexes has also demonstrated reactivity with proton (H+) or methyl (CH3+) donors with NiN2S2 complexes containing mixed carboxamide/amine ligands. Our results indicate that S-nucleophilicity of this mixed N-donor set is quite different from the S-nucleophilicity of well-established diamine NiN2S2 complexes. We anticipated very little change in donor strength of thioether ligands, as modification of the S- thiolate weakens the σ-donor, but also reduced the Ni(dπ)-S(pπ) repulsive interactions, resulting in little change in bond distance between Ni and S. Coordination of the thioether-containing ligand (N2S2-CH3) to Ni, however, indicated that thioether coordination is not favored and isolation of the Ni-coordinated thiol or thioether is best achieved via modification of a NiN2/3S2 complex. Unlike reported diamine NiN2/3S2 complexes, where monomethylation is favored and dimethylation is unfavored, we observed exclusive dimethylation. Indeed no reaction was observed with stoichiometric H+/CH3+ or at low temperature. The mixed carboxamide/amine N- donor may have unique electronic properties about the Ni center that poise the Cys sulfurs for transient protonation in NiSOD.