Mononuclear Ni(II) Complexes with a S3O Coordination Sphere Based on a Tripodal Cysteine-Rich Ligand: pH Tuning of the Superoxide Dismutase Activity.

The superoxide dismutase (SOD) activity of mononuclear Ni complexes, whose structures are inspired by the NiSOD, has been investigated. They have been designed with a sulfur-rich pseudopeptide ligand, derived from nitrilotriacetic acid (NTA), where the three acid functions are grafted with cysteines (). Two mononuclear complexes, which exist in pH-dependent proportions, have been fully characterized by a combination of spectroscopic techniques including H NMR, UV-vis, circular dichroism, and X-ray absorption spectroscopy, together with theoretical calculations. They display similar square-planar S3O coordination, with the three thiolates of the three cysteine moieties from coordinated to the Ni ion, together with either a water molecule at physiological pH, as [Ni(OH)], or a hydroxo ion in more basic conditions, as [Ni(OH)]. The H NMR study has revealed that contrary to the hydroxo ligand, the bound water molecule is labile. The cyclic voltammogram of both complexes displays an irreversible one-electron oxidation process assigned to the Ni/Ni redox system with = 0.48 and 0.31 V versus SCE for Ni(OH) and Ni(OH), respectively. The SOD activity of both complexes has been tested. On the basis of the xanthine oxidase assay, an IC of about 1 μM has been measured at pH 7.4, where Ni(OH) is mainly present (93% of the Ni species), while the IC is larger than 100 μM at pH 9.6, where Ni(OH) is the major species (92% of the Ni species). Interestingly, only Ni(OH) displays SOD activity, suggesting that the presence of a labile ligand is required. The SOD activity has been also evaluated under catalytic conditions at pH 7.75, where the ratio between Ni(OH)/ Ni(OH) is about (86:14), and a rate constant, = 1.8 × 10 M s, has been measured. Ni(OH) is thus the first low-molecular weight, synthetic, bioinspired Ni complex that displays catalytic SOD activity in water at physiological pH, although it does not contain any N-donor ligand in its first coordination sphere, as in the NiSOD. Overall, the data show that a key structural feature is the presence of a labile ligand in the coordination sphere of the Ni ion.