Nickel(III) oxidation of its glycylglycylhistamine complex

The doubly-deprotonated Ni(III) complex of Gly(2)Ha (where Ha is histamine) undergoes base-assisted oxidative self-decomposition of the peptide. At less than or equal to p[H+]7.0, a major pathway is a two-electron oxidation at the alpha-carbon of the N-terminal glycyl residue. Major products (up to 73%) of this two-electron oxidation are glyoxylglycylhistamine and ammonia. Glyoxylglycylhistamine will decay to give isocyanatoacetylhistamine and formaldehyde. Two-electron oxidations of the second glycyl and histamine residues occur as minor pathways (12% of the total possible reaction). Above p[H+] 8.5, two Ni(III)-peptide complexes form an oxo bridge in the axial positions to give a reactive dimer species. This proximity allows the resulting Ni(II)-peptide radical intermediates to undergo peptide-peptide cross-linking at the N-terminal glycyl residues. The products found below p[H+] 7.0 are observed above p[H+] 8.5 as well, although in lower yields. In contrast to this work, Ni-III(H(-2)Gly(2)HisGly) undergoes a four-electron oxidation at the N-terminal glycyl residue. Oxidation at the internal glycyl and histidyl residues are not observed. The reactivity of Ni-III(H(-2)Gly(2)Ha)(+) is also different than Cu-III(H(-2)Gly(2)Ha)(+), which undergoes a two-electron oxidation at the histamine group with no peptide-peptide cross-linking in basic solution.