Binary and ternary mixed metal complexes of terminally free peptides containing two different histidyl binding sites

Copper(II), nickel(II) and zinc(II) complexes of the terminally free peptides AHAAAHG and AAHAAAHG have been studied by combined applications of potentiometric and various spectroscopic techniques, including UV–visible, CD and EPR for copper(II) and UV–visible, CD and NMR for nickel(II). It was found that the octapeptide AAHAAAHG can easily bind two equivalents of copper(II) or nickel(II) ions and the amino terminus was identified as the primary ligating site of the molecule. On the other hand, this peptide has a relatively low zinc(II) binding affinity. Mono- and di-nuclear copper(II) and nickel(II) complexes were also formed with the heptapeptide AHAAAHG but this peptide can effectively bind one equivalent of zinc(II) ions, too, with the involvement of the deprotonated amide nitrogen in zinc(II) binding. The enhanced stability of the [MH−1L] species of AHAAAHG was explained by the tridentate (NH2,N−,Nim) coordination of the amino terminus supported by the macrochelation of the internal histidyl residue. Mixed metal copper(II)–nickel(II) complexes were also formed with both peptides and copper(II) ions were coordinated to the amino terminal, while nickel(II) ions to the internal histidyl sites. •The peptides can bind two equivalents of copper(II) or nickel(II) ions.•Deprotonation and coordination of amide nitrogens occur in the Zn(II)-AHAAAHG system.•Mixed metal copper(II)-nickel(II) complexes are formed with both peptides.•Copper(II) prefers the amino terminus, while nickel(II) occupies the internal histidyl sites. The outstanding stability of the copper(II), nickel(II) and zinc(II) complexes of [MH−1L] species of the terminally free heptapeptide AHAAAHG can be explained by the tridentate (NH2,N−,Nim) coordination of the amino terminus supported by the macrochelation of the internal histidyl residue. [Display omitted]