Development of combined catalytic metallodrugs: Cu(II)-Acetyl-L-carnitine complex

Abstract

In this work, we have designed a copper(II) complex with acetyl-L-carnitine (CuALC), with the aim of developing a small molecule intracellular metal catalyst (SIMCat). The complex was thoroughly characterized using various techniques, including elemental analysis, FTIR, Raman, EPR, UV-Vis, NMR, XANES, EXAFS and mass spectrometry. It is known that antioxidant enzymes (SOD, CAT, and GPx) work cooperatively to scavenge reactive oxygen species, as no single enzyme can eliminate all forms of these reactive species alone. Thus, the objective was to develop a catalyst that integrates two or three catalytic capabilities and exhibits multifunctional activity. In this sense, CuALC was tested as SOD, GPx and peroxidase mimic. The results show that the complex exhibits all these catalytic activities. CuALC catalyzes the O2 •- dismutation reaction with an IC50 value of 2.89 μM and a kMcCF constant of 6.14×106 M-1 s -1. It also catalyzes the degradation of other endogenous substrates, such as H2O2. Catalytic activity assays have shown that CuAlc possesses haloperoxidase activity as it is able to catalyze the bromination of phenol red with high efficiency (kcat/km =1.62×105 M-1 min-1), the oxidation of pyrogallol with a high substrate affinity (km = 5.65×10-5 M) and is a better GPx mimic than the known selenide derivatives (kcat/km = 260. 48 M-1 min-1). Finally, as a small potential drug able to act in intracellular catalysis, it binds spontaneously to BSA (Kb=2×103 M− 1 , 303 K).