Nickel(II) Cys-Xaa-His peptide complexes

An introduction to the amino-terminal metal-binding motif of serum albumin is presented, with particular emphasis on the model sequence, Gly-Gly-His (GGH). Included is an overview of metal coordination and reactivity of GGH complexes and of nickel-thiolate complexes.; The synthesis and characterization of metal-peptide complexes containing a cysteine residue in tripeptide motifs, Cys-Xaa-His, where Xaa is any amino acid except proline, are described. Selective protection of the N-terminal cysteine residue in the sequence, Cys-Gly-His, led to either amino or thiolato binding to nickel(II), depending on the available donor.; A complex formed with the peptide sequence Ala-Cys-Gly-His-Ala indicated thiolato coordination is present in the context of a longer peptide chain. The use of S-(methyl)-cysteine gave metal ion complexation through a thioether moiety. Nickel(II) and copper(II) complexes of Gly-Lys-Met- CONH₂ were synthesized and characterized to use a different thioether donor and probe the necessity of histidine in these peptide complexes.; A free N-terminal cysteine gave rise to competition between amino and thiolato coordination to a nickel(II) center that is pH dependent and sensitive to dioxygen. Consequently, basic solution (>pH 8.5) or exposure to air leads to the formation of disulfide-linked peptide dimers. Using hexapeptides of the general sequence, Cys-Gly-His-Gly-Ser-Arg, rates of thiol alkylation in the absence and presence of nickel(II) and zinc(II) were determined, and were found to be consistent with thiolate versus amino coordination in N-terminal Cys-Xaa-His peptides. Nickel(II) mediated formation of cysteine sulfinic acids was observed in studies of air oxidation of these peptides in the presence of nickel(II) and zinc(II); Proline in the N-terminal position produced stable copper(II) and nickel(II) peptide complexes. Metal complexes with the peptide sequence Pro-Lys-His were synthesized and characterized. Guanine-specific chemistry was observed in the reaction of these complexes with DNA.; Finally, aqueous oxidation of alkanes, utilizing metal complexes, is introduced. The epoxidation of various water-soluble alkenes with KHSO ₅ was not significantly enhanced when certain nickel(II) complexes were included as catalyst. Cobalt(II), however, did enhance the conversion of substrates, but with a decrease in selectivity. Photolytic generation of sulfate radical and quenching studies suggest that radical processes cause lower selectivity in reactions with cobalt.