Copper(III) doubly-deprotonated tripeptide complexes of Aib(2)His, Ala(2)His, Gly(2)His, Aib(2)Ha, and Gly(2)Ha are characterized, where Aib is alpha-aminoisobutyric acid, Ala is L-alanine, Gly is glycine, His is L-histidine, and Ha is histamine. Reduction potentials (V vs NHE) are evaluated : Cu-III(H(-2)Aib(2)His) = 0.785, Cu-III(H(-2)Aib(2)Ha)(+) = 0.772, Cu-III(H(-2)GlyHa)(+) = 0.925, Cu-III(H(-2)Ala(2)His) = 0.86, and Cu-III(H(-2)GLY(2)His) = 0.94. The pK(a) values of 8.2 to 8.7 for amine deprotonation to give-the triply-deprotonated copper(III) complexes are 2-3 pK(a) units lower for these complexes than for tripeptides that do not contain histidine or histamine. Copper(III)-peptide complexes with histidine as the third residue undergo very rapid oxidative decarboxylation, while the histamine-containing complexes decompose more slowly by proton abstraction of the alpha hydrogen on the histamine residue. At p[H+] 7, first-order rate constants for self-decomposition of copper(III) histidine-containing complexes are 10(5) times greater than for those containing histamine. The observed first-order rate constants for the loss of copper(III) for the histidine-containing tripeptides have maximum values at pH 5-7 and decrease at lower pH due to carboxylate protonation and decrease at higher pH due to amine deprotonation. The decomposition of Cu-III(H(-2)Gly(2)Ha)(+) is general-base assisted with a Bronsted beta value of 0.59. As the pH increases, this effect is offset by amine deprotonation. All the peptides are oxidized at the third residue to give the peptide derivative of alpha-hydroxyhistamine,which dehydrates slowly to give an olefin, the peptide derivative of alpha,beta-dehydrohistamine.