title: Dipeptide-based models of nickel superoxide dismutase: solvent effects highlight a critical role to Ni-S bonding and active site stabilization.
abstract: Nickel superoxide dismutase (Ni-SOD) catalyzes the disproportionation of the superoxide radical to O(2) and H(2)O(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(2)S(2) square-planar coordination motif. Utilizing the dipeptide N(2)S(2-) ligand, H(2)N-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(2)S(2) complexes: K[Ni(GC-OMe)(SC(6)H(4)-p-Cl)] (2), K[Ni(GC-OMe)(S(t)Bu)] (3), K[Ni(GC-OMe)(SC(6)H(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.
authors.affiliation: Department of Chemistry, The University of Georgia, 1001 Cedar Street, Athens, Georgia 30602, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Gale
authors.forename: Darin M
authors.initials: DM
authors.lastname: Cowart
authors.forename: Robert A
authors.initials: RA
authors.lastname: Scott
authors.forename: Todd C
authors.initials: TC
authors.lastname: Harrop
mesh_terms: D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry*; D020134:Catalytic Domain; D004151:Dipeptides / Q000737:chemistry*; D004563:Electrochemistry; D004795:Enzyme Stability; D008958:Models, Molecular; D009532:Nickel / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013455:Sulfur / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D004151:Dipeptides; D009942:Organometallic Compounds; D012997:Solvents; D014867:Water; D013455:Sulfur; D009532:Nickel; D013482:Superoxide Dismutase