Characterization of Copper(III)-Tetrapeptide Complexes with Histidine as the Third Residue

Copper(III) complexes of Gly(2)HisGly and Aib(2)HisGly are characterized, where Gly is glycine, His is L-histidine, and Aib is alpha-aminoisobutyric acid. Their respective reduction potentials (V vs NHE) are 0.978 and 0.826. Both Cu(III) complexes undergo amine deprotonation with pK(a) values of 8.79 and 8.81, respectively. The influence of the 5-5-6 membered chelate rings on the E degrees ' and pK(a) values is examined relative to the Cu(III)-tripeptide complexes without histidine that have 5-5-6, 5-6-5, 6-5-5, and 5-5-5 membered linked-consecutive rings. The presence of a six-membered ring in the third peptide residue causes a decrease of approximately 1.0 pK(a) unit relative to a 5-5-5 membered ring system. Imidazole coordination from histidine compared to carboxylate coordination causes an additional decrease of 1.3 pK(a) units. Decompositions of Cu(III)(H(-2)Gly(2)HisGly) and Cu(III)(H(-2)Aib(2)HisGly) complexes are measured over the pH range 0.3-4.7. The kinetics and the reaction products show that abstraction of a proton at the alpha carbon of the histidyl residue is the rate-determining step. The initial decomposition product of Gly(2)HisGly is a tetrapeptide with an alpha-hydroxyhistidyl residue that dehydrates to give an alkene with an alpha,beta-dehydrohistidyl residue. UV-vis spectral properties are reported for the alkene as well as the Cu(III) complexes of Gly(2)HisGly and Aib(2)HisGly.