Coordination of di-Histidine-containing hexapeptides with cupric ion and its application in electrochemical detection.

[Display omitted] • Position of His residues affect the coordination of peptide with Cu2+. • GHGGGH has the highest Cu2+ binding ability and forms a stable 4 N complex. • GHGGGH-modified gold electrode has a high sensitivity and a low detection limit to Cu2+. The lone pair electrons of nitrogen in imidazole ring enable His residue served as an anchor to bind metal ion or as a connector to regulate peptide-metal ions self-assembly. In this paper, a series of hexapeptides with two His residues of different locations in the sequences were synthesized and their coordination performance with Cu2+ were explored. The stoichiometric ratio, binding ability and coordination structures of the peptides with Cu2+ in aqueous solutions were characterized with isothermal titration calorimetry (ITC), 1H nuclear magnetic resonance (1H NMR), ultraviolet visible (UV–Vis) and visible circular dichroism (Vis-CD) spectroscopies. Furthermore, the di-His-containing peptides were immobilized on gold electrodes to detect Cu2+ through the high-efficiency complexation. The results indicated that the binding ability and coordination structures of di-His-containing peptides with Cu2+ were determined by the sequence. GHGGGH showed the highest binding constant with Cu2+ and formed a stable 4 N complex of {NH 2 , N-, 2N im }. GHGGGH modified electrodes had the highest sensitivity in the electrochemical detection of Cu2+ in aqueous solutions at neutral pH. This work provides us with a better understanding of the interaction of functional amino acids in peptide sequences with metal ions and offers constructive guidance in designing metal ion binding peptides. [ABSTRACT FROM AUTHOR]