Impact of the spatial distribution of positive charges on the catalytic activity of NiSOD bioinspired complexes

Abstract In order to mitigate superoxide-induced damage, cells rely on superoxide dismutases (SODs), a family of metalloenzymes that catalyze the dismutation of superoxide. These enzymes display a positively-charged substrate entrance channel for superoxide guidance to the active metal center. ATCUN-like Ni(II) complexes have been shown to mimic NiSOD effectively and benefit from versatile peptide structures, which are ideal for introducing positive charges through arginine residues at various positions to modulate catalytic properties. We describe here five novel ATCUN-like Ni(II) complexes, with arginines at various positions in close proximity to the metal center. All the peptides form monometallic square planar Ni(II) complexes in water at pH 7.4, with either a N 2 S 2 coordination ( S -series) or an equilibrium between N 2 S 2 and N 3 S 1 coordination modes ( N/S -series). The S -series demonstrates a clear beneficial effect of the charge increase from − 2 to + 2 on the pseudo-first order catalytic constant. Furthermore, the data obtained for the N/S complexes demonstrate that introducing an arginine residue in the central position of the ATCUN-like motif does not enhance activity, but actually impedes catalysis. These findings show that both the distance of the charged residues from the metal center and their positioning in space are of prime importance. Graphical abstract