Probing Variable Axial Ligation in Nickel Superoxide Dismutase Utilizing Metallopeptide-Based Models:  Insight into the Superoxide Disproportionation Mechanism

Nickel superoxide dismutase (NiSOD) is a bacterial metalloenzyme that possesses a mononuclear Ni-center and catalyzes the disproportionation of O2 •- by cycling between NiII and NiIII oxidation states. Herein we present evidence from several SOD active metallopeptide maquettes ([Ni(SODM2H(1)X)]; SODM2H(1)X = H2N-XCDLPCG-COOH; X = H, D, or A) that the Ni-center of NiSOD most likely remains five-coordinate during SOD catalysis using thin-film voltammetry. N3− and CN− titration studies suggest that O2 •- disproportionation by [Ni(SODM2H(1)X)] proceeds via an outersphere mechanism. Computationally derived values for the nuclear reorganization energy of the [NiII(SODM2)]/[NiIII(SODM2)] self-exchange reaction combined with the experimentally determined value for k o (∼450 s-1) suggest that axial ligation enhances the O2 •- disproportionation reaction in [Ni(SODM2)] (and NiSOD by analogy) by optimizing the NiII/NiIII redox couple such that it is close to the midpoint of the O2 •- reduction and oxidation couples.