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RESEARCH ARTICLE
Contents Vol 74(8)

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

Ahmed N. Hammouda https://orcid.org/0000-0002-7816-0261 A B D , Fatin M. Elmagbari A B , Graham E. Jackson A , Giselle M. Vicatos A , Raffaele P. Bonomo C and Gabriele Valora C
+ Author Affiliations
- Author Affiliations

A Department of Chemistry, University of Cape Town, Rondebosch 7700, South Africa.

B Department of Chemistry, Faculty of Science, University of Benghazi, Qar Yunis, Benghazi, PO Box 9480, Libya.

C Department of Chemical Sciences, University of Catania, Viale A. Doria 6, 95125, Italy.

D Corresponding author. Email: Ahmed.hammouda@uct.ac.za

Australian Journal of Chemistry 74(8) 613-622 https://doi.org/10.1071/CH21040
Submitted: 5 February 2021  Accepted: 31 May 2021   Published: 22 June 2021

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 0.15 M (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 %.

Keywords: rheumatoid arthritis, anti-inflammatory drugs, CuII tripeptide complex, dermal absorption.


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