Dioxygen and superoxide stability of metallopeptide based mimics of nickel containing superoxide dismutase: The influence of amine/amidate vs. bis-amidate ligation

Abstract

Nickel containing superoxide dismutase (NiSOD) is a metalloenzyme that catalyzes the disproportionation of O2−. In its reduced state, the Ni(II) ion is coordinated by two cis-cysteinates, an amine nitrogen and an amidate nitrogen atom. It thus bears a resemblance to the distal bis-cysteinate bis-amidate ligated nickel center of acetyl coenzyme A synthase. Using metallopeptide based NiSOD mimics derived from the first 12 residues of the NiSOD sequence we demonstrate that altering the primary coordination sphere from a bis-thiolate amine/amidate motif to a bis-thiolate bis-amidate motif changes the O2 and ROS stability of the metallopeptide. Using FT-IR, ESI-MS and S K-edge XAS we show that the bis-amidate bis-thiolate ligated metallopeptide {NiII(SODm1-Ac)} (SODm1-Ac=AcHN-HCDLPCGVYSPA-COOH) undergoes oxidation at one thiolate ligand in the presence of O2, converting it into a coordinated sulfinate. Upon exposure of {NiII(SODm1-Ac)} to O2− the metallopeptide undergoes extensive sulfur oxidation. This can be contrasted with the unacylated metallopeptide {NiII(SODm1)} which does not undergo sulfur based oxidation under these conditions. The biological implications of these findings are discussed.