Formation and spectral properties of metal ion complexes of tripeptides

Abstract

The aim of this study was to develop complexes that could be used to eleviate the inflammation associated with arthritis by facilitating the dermal absorption of copper. To this end, copper(II) complexes of two tripeptides sarcosyl-l-histidyl-l-lysine (L1) and sarcosyl-l-lysyl-l-histidine (L2) were studied using potentiometric and spectroscopic (UV–vis, ESR, 1H NMR) techniques as well as molecular mechanics (MM) calculations. Since Zn(II) and Ni(II) are in vivo competitors of Cu(II), equilibrium constants of H+, Cu(II), Ni(II) and Zn(II) with the peptides were measured in aqueous solution at 25±0.01°C and an ionic strength of 0.15M (NaCl) using glass electrode potentiometry. In the pH range 2.00–11.00, four species; MLH, ML, MLH−1, and MLH−2 were observed. 1H NMR identified the binding sites to be the imidazole nitrogen, the amide nitrogen and the terminal amino group. The ε-amino group of lysine did not coordinate to the Cu(II). The ML2H−2 species involved coordination of two deprotonated amide groups to give a neutral complex. UV/vis and EPR spectroscopy confirmed the mode of coordination, which was different in L1 and L2. Molecular mechanics calculations were used to support the structures postulated from potentiometric and spectroscopic data. Speciation calculations of Cu(II) using a computer model of blood plasma indicated that Sar-Lys-His (L2) was the best at mobilising copper in silico.