Unusual binding modes in the copper(II) and palladium(II) complexes of peptides containing both histidyl and cysteinyl residues

Two N-terminally free but C-terminally amidated peptides containing both histidine and cysteine (AAHAAC-NH2 and AHAAAC-NH2) have been synthesized and copper(II) and palladium(II) complexes were studied by potentiometry, various spectroscopic methods and DFT calculations. In the case of the copper(II)-AAHAAC-NH2 system the (NH2, N-, N-, N-im) coordination mode hindered the interaction between copper(II) and thiolate preventing the redox reactions in acidic and neutral solution. The suppression of redox reactions between copper(II) ions and the peptide AHAAAC-NH2 was also observed in equimolar samples but in this case the existence of Cu(II)-S(thiolate) binding was detected in the physiological pH range. For palladium(II) complexes the results unambiguously prove the predominance of the Pd-S(thiolate) binding mode over the formation of Pd-N(amide) bonds even if the thiolate residues are involved in various macrochelates only. The thiolate group of the cysteinyl residue was described as the primary ligating site of both peptides and the remaining coordination sites were occupied by the amino, imidazole and one amide nitrogen donor atoms in the palladium(II) complexes.