Equilibrium and structural studies on copper(II) complexes of tetra-, penta- and hexa-peptides containing histidyl residues at the C-termini.

The stoichiometry, stability constants and solution structure of the complexes formed in the reaction of copper(II) with oligopeptides containing histidyl residues at the C-termini (Gly3His, Gly4His and Gly5His) have been determined by potentiometric, UV-VIS and EPR spectroscopic methods. The formation of the species [CuHL]2+, [CuL]+, [CuH-1L], [CuH-2L]- and [CuH-3L]2- was detected in all cases. Binding modes of the species [CuL]+, [CuH-1L] and [CuH-2L]- were characterized by the metal ion co-ordination of the terminal amino group, carbonyl oxygen or one or two deprotonated amide nitrogens in joined five-membered chelates from the N-termini, while the fourth co-ordination site of the metal ion was occupied by nitrogen donors of imidazole in the form of a macrochelate. The stability of the macrochelate was decreased upon increasing the length of the peptide molecule. For the penta- and hexa-peptides the species [CuH-3L]2- was characterized as a 4N-complex with equatorial co-ordination of the terminal amino group and subsequent three deprotonated amide nitrogens, with unco-ordinated imidazolyl residues, while a 5N-species was suggested to form for Gly3His with axial interaction of the imidazole-N donor atom. Copper(II) complexes of Gly2His and pentaglycine were also investigated for reliable comparison.