The affinity of HGGG, GHGG, GGHG, and GGGH peptides for copper(II) and the structures of their complexes — An ab initio study

The structures and relative free energies in aqueous solution of the Cu(II) complexes of the “histidine walk” peptides, AcHGGGNH2, AcGHGGNH2, AcGGHGNH2, and AcGGGHNH2, were determined as a function of pH. Numerous structures of each species were found by gaseous- and solution-phase geometry optimization at the B3LYP/6–31G(d) level, and the effect of solvation estimated by the IEFPCM continuum solvation model. Free energies of solvation of the ionic species are large and favour structures with an extended peptide chain. In all Cu(II)–peptide complexes, deprotonation of two amide groups occurs readily at or below pH 7. In each system, the most abundant species at pH 7 is a neutral 1:1 complex with N3O1 coordination pattern. Binding in the forward direction toward the C terminus is preferred. The results are compared to recent experimental spectroscopic and potentiometric studies on related systems. Alternative explanations are offered for some of the experimental observations.