Modified quantum mechanical approach for the estimation of single-electron reduction potential of nitroaromatic compounds in aqueous medium

The midpoint single-electron reduction potential of nitroaromatic compounds in aqueous medium at pH 7.0 (potential of ArNO2/ArNO2 center dot(-) couple, E-m7) frequently determines their therapeutic and/or toxic properties. However, its estimation remains a complex problem. We propose a modified method of E-m7 estimation by quantum mechanical calculations, based on the use of the dielectric continuum model together with a certain number of H2O molecules at the vicinity of nitro group. The optimal number of H2O molecules corresponds to a minimal difference between the experimentally determined and calculated values of E-m7, and/or the most negative value of calculated E-m7. This enabled us to calculate the E-m7 values for a number of ArNO2 (n = 19) with the average deviation of 0.027 V from the experimentally determined ones. Apart from nitrobenzene derivatives, the application of this approach for the representatives of nitropyridines, nitrofurans, nitrothiophenes, and nitrothiazoles was demonstrated. In this case, nitroimidazole derivatives are an exception, evidently due to a strong proton accepting properties of N3 atom of their free radicals.