Département de chimie moléculaire

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 Ni(II) center with two thiolates, the terminal amine and an amidate. We report here a bioinspired Ni(II) complex built on an ATCUN-like binding motif modulated with one cysteine, which demonstrates catalytic SOD activity in water (kcat = 8.4(2) x 10⁵ M^-1 s^-1 at 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 [Ni(II)O₂^.-] species. This first species could then evolve into a Ni(III) hydroperoxo inner sphere species through a reaction driven by protonation that is thermodynamically highly favored according to DFT calculations.