Drastic Effect of the Peptide Sequence on the Copper-Binding Properties of Tripeptides and the Electrochemical Behaviour of Their Copper(II) Complexes

The binding and electrochemical properties of the complexes Cu-II-HAH, Cu-II-HWH, Cu-II-Ac-HWH, Cu-II-HHW, and Cu-II-WHH have been studied by using NMR and UV/Vis spectroscopies, CV, and density functional calculations. The results obtained highlight the importance of the peptidic sequence on the coordination properties and, consequently, on the redox properties of their Cu-II complexes. For Cu-II-HAH and Cu-II-HWH, no cathodic processes are observed up to -1.2V; that is, the complexes exhibit very high stability towards copper reduction. This behaviour is associated with the formation of very stable square-planar (5,5,6)-membered chelate rings (ATCUN motif), which enclose two deprotonated amides. In contrast, for non-ATCUN Cu-II-Ac-HWH, Cu-II-HHW complexes, simulations seem to indicate that only one deprotonated amide is enclosed in the coordination sphere. In these cases, the main electrochemical feature is a reductive irreversible one electron-transfer process from Cu-II to Cu-I, accompanied with structural changes of the metal coordination sphere and reprotonation of the amide. Finally, for Cu-II-WHH, two major species have been detected: one at low pH (< 5), with no deprotonated amides, and another one at high pH (> 10) with an ATCUN motif, both species coexisting at intermediate pH. The present study shows that the use of CV, using glassy carbon as a working electrode, is an ideal and rapid tool for the determination of the redox properties of Cu-II metallopeptides.