Stability, Structure, and Permeability Studies of Copper Tripeptide Species in Aqueous Solution

Abstract

The use of copper complexes to alleviate inflammation associated with rheumatoid arthritis (RA) is well known. This study focuses on designing a new drug that could be used to increase the bioavailability of copper and hence be more effective. The ligand chosen was sarcosyl-l-lysyl-l-lysine (Sar-Lys-Lys). The thermodynamic stability of H+, CuII, NiII, and ZnII complexes of Sar-Lys-Lys was measured in an aqueous solution at 298±0.01°C and an ionic strength of 0.15M (NaCl) using glass electrode potentiometry. UV-Vis, ESR, and 1H NMR spectroscopy was used to investigate the solution structures of the different species. At physiological pH, the ligand was found to coordinate via two amide nitrogens, the terminal amine, and the terminal carboxy group. The ε-amino group of lysine did not coordinate with the metal ion. Dermal absorption is the preferred method of administration and so this study used partition coefficients and tissue permeability studies to assess the bioavailability of the different complexes. Sar-Lys-Lys was found to increase the copper lipophilicity by a factor of 10 and increased tissue permeability by 30%.