Di-peptide Based Models of Nickel Superoxide Dismutase: Solvent Effects Highlight a Critical Role to Ni-S Bonding and Active Site Stabilization

摘要

Nickel superoxide dismutase (Ni-SOD) catalyzes the disproportionation of the superoxide radical to O2 and H2O2 utilizing the Ni(III/II) redox couple. The Ni center in Ni-SOD resides in an unusual coordination environment that is distinct from other SODs. In the reduced state (Ni-SODred), the Ni(II) center is ligated to a primary amine-N from His1, anionic carboxamido-N/thiolato-S from Cys2, and a second thiolato-S from Cys6 to complete a NiN2S2 square-planar coordination motif. Utilizing the dipeptide N2S²⁻ ligand, H2N-Gly-L-Cys-OMe (GC-OMeH2) that accurately models the structural and electronic contributions provided by His1 and Cys2 in Ni-SODred, we have constructed the dinuclear sulfur-bridged metallosynthon, [Ni2(GC-OMe)2] (>1). From >1 we have prepared the following monomeric Ni(II)-N2S2 complexes: K[Ni(GC-OMe)(SC6H4-p-Cl)] (>2), K[Ni(GC-OMe)(S^tBu)] (>3), K[Ni(GC-OMe)(SC₆H₄-p-OMe)] (>4), and K[Ni(GC-OMe)(S-NAc)] (>5). The design strategy in utilizing GC-OMe²⁻ is analogous to one which we have reported before (see Inorg. Chem. >2009, 48, 5620 and Inorg. Chem. >2010, 49, 7080) wherein Ni-SOD_red active site mimics can be constructed at will with electronically variant RS⁻ ligands. Discussed herein is the first account pertaining to the aqueous behavior of isolable, small molecule Ni-SOD model complexes (non-maquette based). Spectroscopic (FTIR, UV-vis, XAS) and electrochemical (CV) measurements suggest that >2–5 successfully simulate many of the electronic features of the Ni-SOD_red active site but also reveal, in conjunction with ¹H NMR and ESI-MS studies, that these models are dynamic species with regards to RS⁻ lability and bridging interactions in aqueous media suggesting a stabilizing role brought about by the protein architecture.