Superoxide, an inevitable by-product of aerobic respiration, causes oxidative damage to biological molecules and has thus been implicated in many different disease states. A family of metalloenzymes known as superoxide dismutases (SODs) prevent the oxidative damage caused by superoxide through disproportionation of superoxide to oxygen and hydrogen peroxide. NiSOD is the latest addition to the SOD family. During turnover, NiSOD cycles between a square-planar Ni(II)-N2S2 coordination environment and a square-pyramidal Ni(III)-N3S2 coordination environment with the incorporation of the axial N-ligand from the imidazole of His1. Previously, we have successfully synthesized and characterized a square-planar Ni-N2S2 complex featuring a pendant pyridine the axial position ([Ni(N3S2)]–). A transient Ni(III) species is observed by EPR; however, the ultimate end-product is a disulfide-bridged Ni(II)-N3S complex due to thiolate oxidation. Since [Ni(N3S2)]– was insufficient to promote purely Ni-based oxidation and SOD activity, we have constructed two new synthetic analogues of NiSOD: (i) [Ni(N3S2Me2)]– which features additional steric protection adjacent to the S-donor to prevent disulfide formation, and (ii) ([Ni(N2S2-NEM)]–) which features a N-ethyl morpholine (NEM) moiety in the axial position instead of the pendant pyridine. In this presentation, the syntheses, spectroscopic/electrochemical properties, and reactivity of these NiSOD model complexes will be discussed.
Department of Chemistry