Quinoxaline-1,4-dioxide: Substituent effects on the N–O bond dissociation enthalpy

DFT calculations have been performed to investigate the effect of several different substituents on the N–O bond dissociation enthalpies of 2-substituted-quinoxaline-1,4-dioxides. Further, the influence of electron and proton affinities and also of N–O bond dissociation enthalpies on the antitumor activity of selected compounds is analyzed. In agreement with experimental data, the calculations suggest that Tirapazamine is more active than Quindoxin due to a much easier reduction and protonation of the former species accompanied by a weaker N–OH bond.