A Bioinspired NiIISuperoxide Dismutase Catalyst Designed on an ATCUN-like Binding Motif

Nickel superoxide dismutase (NiSOD) is an enzyme that protects cells against O2·–. While the structure of its active site is known, the mechanism of the catalytic cycle is still not elucidated. Its active site displays a square planar NiIIcenter with two thiolates, the terminal amine and an amidate. We report here a bioinspired NiIIcomplex built on an ATCUN-like binding motif modulated with one cysteine, which demonstrates catalytic SOD activity in water (kcat= 8.4(2) × 105M–1s–1at pH = 8.1). Its reactivity with O2·–was also studied in acetonitrile allowing trapping two different short-lived species that were characterized by electron paramagnetic resonance or spectroelectrochemistry and a combination of density functional theory (DFT) and time-dependent DFT calculations. Based on these observations, we propose that O2·–interacts first with the complex outer sphere through a H-bond with the peptide scaffold in a [NiIIO2·–] species. This first species could then evolve into a NiIIIhydroperoxo inner sphere species through a reaction driven by protonation that is thermodynamically highly favored according to DFT calculations.