Complex formation processes of terminally protected peptides containing two or three histidyl residues. Characterization of the mixed metal complexes of peptides

Copper(ii), nickel(ii) and zinc(ii) complexes of the peptides Ac-HVVH-NH(2) and Ac-HAAHVVH-NH(2) have been studied by potentiometric, UV-vis, CD, EPR and NMR spectroscopic measurements. Both tetra and heptapeptides can form relatively stable macrochelates with copper(ii), nickel(ii) and zinc(ii) ions, in which the ligands are coordinated via the side-chain imidazole functions. Formation of the macrochelates slightly suppresses, but cannot prevent the copper(ii) and nickel(ii) ion promoted deprotonation and coordination of the amide functionalities. The overall stoichiometry of the major species is MH(-3)L](-) with a 4N (= N(-),N(-),N(-),N(im)) coordination mode. In the case of Ac-HAAHVVH-NH(2), coordination isomers of this species can exist with a preference for copper(ii) or nickel(ii) binding at the internal histidyl residue. In the copper(ii)-Ac-HAAHVVH-NH(2) system, the presence of the two anchoring sites results in the formation of dinuclear complexes. The existence of these species requires the involvement of amide functions in metal binding. Both equilibrium and spectroscopic data support the fact that the copper(ii) ions of the dinuclear species are independent from each other providing a good chance for the formation of various mixed metal complexes. It was found that zinc(ii) is not able to significantly alter the copper(ii) binding of the heptapeptide, but it can occupy the uncoordinated histidyl sites. The formation of the copper(ii)-nickel(ii) mixed species was obtained in alkaline solutions and CD spectra suggest the statistical distribution of the two metal ions among the histidyl residues. The binding of HAAHVVH to palladium(ii) is exclusive below pH 8 and the mixed metal species of palladium(ii) and copper(ii) ions are formed only in slightly basic solutions.