COPPER(III) COMPLEXES OF TRIPEPTIDES WITH HISTIDINE AND HISTAMINE AS THE 3RD RESIDUE

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) a re 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 fo r amine deprotonation to give-the triply-deprotonated copper(III) comp lexes are 2-3 pK(a) units lower for these complexes than for tripeptid es that do not contain histidine or histamine. Copper(III)-peptide com plexes with histidine as the third residue undergo very rapid oxidativ e decarboxylation, while the histamine-containing complexes decompose more slowly by proton abstraction of the alpha hydrogen on the histami ne residue. At p[H+] 7, first-order rate constants for self-decomposit ion of copper(III) histidine-containing complexes are 10(5) times grea ter than for those containing histamine. The observed first-order rate constants for the loss of copper(III) for the histidine-containing tr ipeptides have maximum values at pH 5-7 and decrease at lower pH due t o carboxylate protonation and decrease at higher pH due to amine depro tonation. The decomposition of Cu-III(H(-2)Gly(2)Ha)(+) is general-bas e assisted with a Bronsted beta value of 0.59. As the pH increases, th is effect is offset by amine deprotonation. All the peptides are oxidi zed at the third residue to give the peptide derivative of alpha-hydro xyhistamine,which dehydrates slowly to give an olefin, the peptide der ivative of alpha,beta-dehydrohistamine.