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

•Complexes of copper and biologically-occurring disulfides react with superoxide.•Cu(II)-disulfide complexes display superoxide dismutase-like activity.•Cu(II)-disulfide complexes have the ability to act like catalase mimetic molecules.

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 react with superoxide. The studied complexes were 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 SOD mimetics. 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 of molecules to act as such under physiological and/or oxidative-stress conditions.

Graphical abstractComplexes formed between copper(II) ions and biologically-occurring disulfides (RSSR: oxidized glutathione, (Homo)cystine and α-lipoic acid) were found to simultaneously display superoxide dismutase- and catalase-like activities. The antioxidant properties of Cu(II)—RSSR were seen at very low micromolar concentrations and were demonstrated both, in non-cellular ROS-generating systems and in superoxide-generating mitochondria.Figure optionsDownload full-size imageDownload as PowerPoint slide