Free radical formation evidence from Nimorazole electrochemical reduction in aqueous media

The nitroimidazole derivatives have an active broad spectrum, being toxic to anaerobic bacteria and protozoa. Nimorazole (NMZ) belongs to this group of drugs, and its proposed mechanism of action predicts the formation and stabilization of the nitro-anion radical (R - NO2 center dot-). Cyclic voltammetry was applied in aqueous media to study NMZ reduction, being a pH-dependent process. Only one irreversible diffusion-controlled cathodic process was noticed in an acidic medium, involving four electrons for the hydroxylamine derivative formation. Square wave voltammetry data confirmed this behavior. In alkaline media (pH > 8), the NMZ reduction occured in two steps, the first one being associated with the nitro-anion radical formation in a one-electron reversible process. Then, the hydroxylamine derivative was formed at more negative potential values in a three-electron cathodic process. The number of electrons involved was determined by chronoamperometry. The presence of molecular oxygen in the solution indicated that the superoxide anion could be produced from the nitro-anion radical in a futile cycle. Moreover, the use of Digisim software corroborated the reversible voltammetric mechanism regarding the R - NO2/R - NO2 center dot- couple. The current ratio (Ipa/Ipc) was used to evaluate the radical kinetic stability, as the electrogenerated nitro-anion radical underwent a second-order disproportionation chemical reaction. The rate constant of this reaction, k(2), was determined in 0.1 mM and 0.5 mM NMZ solutions, and the values were found to be 29987 and 7621 L/mol s, respectively, and the half-life times, t(1/2), 0.33 and 0.26 seconds, respectively. The kinetic values obtained were compared with those of other similar compounds. This is the only work involving the nitro-anion radical stability generated from a nitroimidazole derivative in a 100% aqueous media. (C) 2021 Published by Elsevier Ltd.

Automated summary

The reduction behavior of nimorazole (NMZ) was investigated using cyclic voltammetry in different pH conditions. The results showed that in acidic medium, an irreversible cathodic process involving four electrons occurred, leading to the formation of hydroxylamine derivative. In alkaline medium, the reduction process occurred in two steps, with the formation of nitro-anion radical in a reversible one-electron process followed by the formation of hydroxylamine derivative. It was also observed that the nitro-anion radical could generate superoxide anion through a futile cycle with molecular oxygen.