A new stable Copper(III)/Cyclopeptide complex: structural characterization by XANES and EXAFS studies

We recently described the synthesis of some cyclic tetrapeptides bearing imidazole side chains and we analyzed, in detail, their copper(II) binding properties in aqueous solution. The copper(II) species obtained are of interest in relation to copper-protein active-site biomimetics. In particular, a 13-membered ring cyclic tetrapeptide c(Lys-DHis-ȕAla- His) (DK13) was synthesized by the solid-phase peptide synthesis method and its copper(II) coordination properties were studied. Surprisingly, all collected data strongly support the presence, at alkaline pH, of a stable peptide/copper(III) complex that is formed in solution by atmospheric dioxygen oxidation. In order to clarify the mechanism of the copper oxidation through the average Cu-N bond distance and to get information on the local geometry around copper, depending on the peptide sequence, we have collected experimental XANES and EXAFS spectra. The investigated cyclopeptide/copper complex shows pre-edge peak energy position and integrated intensity consistent with those of Cu3+ model compounds. Also, edge energy is consistent with the presence of trivalent copper. Then, calculations performed on the EXAFS measures should give information on the local geometry, confirming the square planar geometry proposed by us for this DK13/Cu(III) complex.