Electrochemical characterization of para- and meta-nitro substituents in aqueous media of new antichagasic pharmaceutical leaders

Abstract

Abstract The electrochemical reduction mechanism of two isomers of position drug leaders against Chagas disease, p-nitrosulfonylhydrazine derivative (p-NSF), and m-nitrosulfonylhydrazine derivative (m-NSF), was investigated in aqueous media and in the absence of oxygen using voltammetric techniques. The main reduction process was attributed to the reduction of the nitro group (Epc (p-NSF)\u202f=\u202f-0.58 V and Epc (m-NSF)\u202f=\u202f-0.62 V), generating nitroso derivative in intermediate and higher values of pH and hydroxylamine in lower values of pH. Another reduction process in a less negative potential value was only observed for p-NSF and attributed to the generation of the nitro radical anion. The difference in the reduction potentials between both compounds and the presence of another reduction process for p-NSF was associated with the position of the nitro group, due to the distinct stabilization of the reduction intermediates by the aromatic ring. A catalytic response for the reduction process of the nitro anion radical was observed for p-NSF in the presence of oxygen, given that its magnitude of current increased when increasing the oxygen availability. Also, for m-NSF, this reduction process could be detected, even though it was not observed in the voltammograms in the absence of oxygen. This further confirmed the generation of the nitro radical anion, since it reacts with molecular oxygen and regenerates the initial nitro compound. The interaction with cysteine was also evaluated, which favored the reduction process towards the generation of the nitroso derivative due to adduct formation, destabilizing the reduction process regarding the nitro radical anion. Therefore, electrochemical experiments can evaluate how different isomers of position and other coupled functional groups affect the reduction of the nitro group and, consequently aid in the design of new classes of antichagasic pharmaceuticals, with improved stability of reactive intermediates that are often correlated with the degree of injury towards the parasite.