Cu(II)–disulfide complexes display simultaneous superoxide dismutase- and catalase-like activities

Abstract

Superoxide is a potentially toxic by-product of cellular metabolism.We have addressed here the in vitro ability of complexes formed between copper(II) ions and various biologically-occurring disulfides (RSSR: oxidized glutathione, cystine, homocystine and α-lipoic acid) to reactwith superoxide. The studied complexeswere found to react with superoxide (generated by a xanthine/xanthine oxidase system) at rate constants (kCu(II)–RSSR) close to 106 M−1 s−1,which are three orders of magnitude lower than that reported for superoxide dismutase (SOD) but comparable to that of several other copper-containing complexes reported as SODmimetics. The interaction between the tested Cu(II)–RSSR and superoxide, led to the generation and recovery of concentrations of hydrogen peroxide and oxygen that were, respectively, below and above those theoretically-expected from a sole SOD mimetic action. Interestingly, oxygen was generated when the Cu(II)–RSSR complexes were directly incubated with hydrogen peroxide. Taken together, these results reveal that the Cu(II)–RSSR complexes not only have the capacity to dismutate superoxide but also to simultaneously act like catalase mimetic molecules. When added to superoxide-overproducing mitochondria (condition attained by its exposure to diclofenac), three of the tested complexes were able (2–4 μM), not only to totally restore, but also to lower below the basal level the mitochondrial production of superoxide. The present study is first in reporting on the potential of Cu(II)– disulfide complexes to act as SOD and catalase like molecules, suggesting a potential for these types ofmolecules to act as such under physiological and/or oxidative-stress conditions.