Adiabaticity of the Proton-Coupled Electron-Transfer Step in the Reduction of Superoxide Effected by Nickel-Containing Superoxide Dismutase Metallopeptide-Based Mimics

Nickel-containing superoxide dismutases (NiSODs) are bacterial metalloenzymes that catalyze the disproportionation of O₂^–. These enzymes take advantage of a redox-active nickel cofactor, which cycles between the Ni­(II) and Ni­(III) oxidation states, to catalytically disprotorptionate O₂^–. The Ni­(II) center is ligated in a square planar N₂S₂ coordination environment, which, upon oxidation to Ni­(III), becomes five-coordinate following the ligation of an axial imidazole ligand. Previous studies have suggested that metallopeptide-based mimics of NiSOD reduce O₂^– through a proton-coupled electron transfer (PCET) reaction with the electron derived from a reduced Ni­(II) center and the proton from a protonated, coordinated Ni^II–S­(H⁺)–Cys moiety. The current work focuses on the O₂^– reduction half-reaction of the catalytic cycle. In this study we calculate the vibronic coupling between the reactant and product diabatic surfaces using a semiclassical formalism to determine if the PCET reaction is proceeding through an adiabatic or nonadiabatic proton tunneling process. These results were then used to calculate H/D kinetic isotope effects for the PCET process. We find that as the axial imidazole ligand becomes more strongly associated with the Ni­(II) center during the PCET reaction, the reaction becomes more nonadiabatic. This is reflected in the calculated H/D KIEs, which moderately increase as the reaction becomes more nonadiabatic. Furthermore, the results suggest that as the axial ligand becomes less Lewis basic the observed reaction rate constants for O₂^– reduction should become faster because the reaction becomes more adiabatic. These conclusions are in-line with experimental observations. The results thus indicate that variations in the axial donor’s ability to coordinate to the nickel center of NiSOD metallopeptide-based mimics will strongly influence the fundamental nature of the O₂^– reduction process.