Are thiophenol based small molecular weight nickel complexes sufficient mimics of the NiSOD enzyme?

Based on detailed studies in non-aqueous media, it has been claimed earlier that nickel complexes formed with thiophenol type ligands are functional mimics of nickel containing superoxide dismutase enzymes (NiSOD). Now we report an in-depth study on the formation of nickel(II) complexes with thiophenol-based ligands, <i>N</i>,<i>N</i>'-bis(2-mercaptophenyl)pyridine-2,6-dicarboxamide (PyPS) and 2-aminothiophenol (AT), and their role in the dismutation of the superoxide anion in aqueous solution under physiological conditions. At pH ∼ 7.0, PyPS coordinates to nickel(II) <i>via</i> the (S^-,N_py,N^-) donor set, while the bis-complex of AT features the 2 × (S^-,N) coordination environment. The SOD activity of these complexes was tested by using the McCord-Fridovich assay and dedicated sequential stopped flow experiments. The complexes show structural similarity to the binding site of the native NiSOD enzyme, but they are not able to model its catalytic activity. The reaction of the superoxide anion radical with the PyPS complex yields a disulfide-bridged species, while oxidation of the nickel(II) complex of AT leads to the formation of a Ni(II)-thiyl ↔ Ni(III)-thiolate species. The results confirm that these types of complexes cannot act as functional NiSOD mimics in aqueous media.