A Series of Ni Complexes Based on a Versatile ATCUN-Like Tripeptide Scaffold to Decipher Key Parameters for Superoxide Dismutase Activity.

The cellular level of reactive oxygen species (ROS) has to be controlled to avoid some pathologies, especially those linked to oxidative stress. One strategy for designing antioxidants consists of modeling natural enzymes involved in ROS degradation. Among them, nickel superoxide dismutase (NiSOD) catalyzes the dismutation of the superoxide radical anion, O ₂ ^•- , into O ₂ and H ₂ O ₂ . We report here Ni complexes with tripeptides derived from the amino-terminal Cu ^II - and Ni ^II -binding (ATCUN) motif that mimics some structural features found in the active site of the NiSOD. A series of six mononuclear Ni ^II complexes were investigated in water at physiological pH with different first coordination spheres, from compounds with a N3S to N2S2 set, and also complexes that are in equilibrium between the N -coordination (N3S) and S -coordination (N2S2). They were fully characterized by a combination of spectroscopic techniques, including ¹ H NMR, UV-vis, circular dichroism, and X-ray absorption spectroscopy, together with theoretical calculations and their redox properties studied by cyclic voltammetry. They all display SOD-like activity, with a k _cat ranging between 0.5 and 2.0 × 10 ⁶ M ^-1 s ^-1 . The complexes in which the two coordination modes are in equilibrium are the most efficient, suggesting a beneficial effect of a nearby proton relay.