Copper(II)–Tripeptide Complexes as Potential Skin Healing Agents: Synthesis, Characterization, and Wound Repair Ability

Due to the rising incidence of skin diseases, the World Health Organization has emphasized the need for improved prevention and treatment strategies. The search for new compounds active against skin lesions and pathologies has attracted significant attention. This work reports the synthesis, analytical, spectroscopic, and electrochemical characterization of four copper(II)-tripeptide complexes using Gly-Gly-Ile (GGI), Ala-Ala-Ala (AAA), Phe-Gly-Gly (FGG), and Val-Tyr-Val (VYV) as ligands. Results show that GGI, AAA, and FGG monodeprotonate and coordinate to copper(II) through the aminic N and the adjacent carbonyl O, following a 1:2 metal-to-ligand stoichiometry. VYV doubly deprotonates and forms a 1:1 complex with the tripeptide coordinated through the aminic N atom a deprotonated amidic N and a carbonyl O. Aqueous solution studies confirm that the tripeptide stays coordinated in the major species in solution. Complexes are redox active in the biologically relevant window, with CuVYV presenting the most accessible Cu(III)/Cu(II) transition. The ability to promote wound healing was assessed through a scratch wound healing assay. CuAAA and CuVYV are promising inducers of wound healing by promoting migration in MRC-5 cells. Cytotoxicity assays confirm that the compounds are not cytotoxic at the doses used for wound repair, making CuAAA and CuVYV interesting candidates for further studies.