Oxidative Self-Decomposition of the Nickel(III) Complex of Glycylglycyl-l-histidylglycine

Self-decomposition of the nickel(III) doubly deprotonated peptide complex of Gly₂HisGly occurs by base-assisted oxidation of the peptide. At ≤p[H⁺] 7.0, the major pathway is a four-electron oxidation (via 4 Ni(III) complexes) at the α carbon of the N-terminal glycyl residue. The product of this oxidation is oxamylglycylhistidylglycine, which hydrolyzes to yield ammonia and oxalylglycylhistidylglycine. Both of these peptide products decompose to give isocyanatoacetylhistidylglycine. A small amount (2%) of oxidative decarboxylation also is observed. In another major pathway above p[H⁺] 7.0, two Ni(III)−peptide complexes coordinate via an oxo bridge in the axial positions to form a reactive dimer species. This dimer generates two Ni(II)−peptide radical intermediates that cross-link at the α carbons of the N-terminal glycyl residues. In 0.13 mM Ni(III)−peptide at p[H⁺] 10.3, this pathway accounts for 60% of the reaction. The cross-linked peptide is subject to oxidation via atmospheric O₂, where the 2,3-diaminobutanedioic acid is converted to a 2,3-diaminobutenedioic acid. The products observed at +] 7.0 are observed here as well, although in lower yields. The reactivity of Ni^III(H_-2Gly₂HisGly) is significantly different than that of Cu^III(H_-2Gly₂HisGly), which undergoes a two-electron oxidation at the histidyl residue with no peptide−peptide cross-linking in basic solution.