Dipeptide-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 O_2 and H_2O_2 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-SOD_(red)), Ni(II) 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 NiN_2S_2 square-planar coordination motif. Utilizing the dipeptide N_2S~(2-) ligand, H _2N-Gly-l-Cys-OMe (GC-OMeH_2), an accurate model of the structural and electronic contributions provided by His1 and Cys2 in Ni-SOD _(red), we constructed the dinuclear sulfur-bridged metallosynthon, [Ni_2(GC-OMe)_2] (1). From 1 we prepared the following monomeric Ni(II)-N_2S_2 complexes: K[Ni(GC-OMe)(SC _6H_4-p-Cl)] (2), K[Ni(GC-OMe)(S~tBu)] (3), K[Ni(GC-OMe)(SC_6H_4-p-OMe)] (4), and K[Ni(GC-OMe)(SNAc)] (5). The design strategy in utilizing GC-OMe~(2-) is analogous to one which we reported before (see Inorg. Chem.2009, 48, 5620 and Inorg. Chem. 2010, 49, 7080) where Ni-SOD_(red) active site mimics can be assembled at will with electronically variant RS~- ligands. Discussed herein is our initial account pertaining to the aqueous behavior of isolable, small-molecule Ni-SOD model complexes (non-maquette based). Spectroscopic (FTIR, UV-vis, ESI-MS, XAS) and electrochemical (CV) measurements suggest that 2-5 successfully simulate many of the electronic features of Ni-SOD_(red). Furthermore, the aqueous studies reveal a dynamic behavior with regard to RS~- lability and bridging interactions, suggesting a stabilizing role brought about by the protein architecture.