On the mechanism of biological activity of hydroquinone derivatives that inhibit tumor cell respiration. A theoretical study

A simple mechanism to understand the biological activity of a series of hydroquinone derivatives is proposed. To validate this proposition Gibbs free energies of formation of the different species involved were calculated. The calculations were performed using density functional theory (DFT) at B3LYP/6-31++G(2df,p) level of theory, including solvation effect. The results show that two important variables to examine are the equilibrium phenol-phenoxide and the solvation energy of neutral species, since the balance between both variables affects the capability of the molecules to cross membranes. Once the molecule crossed the membrane, the formation of radical species shows a qualitative correlation with the magnitude of IC50 values. This provides a reasonable criterion to search for more efficient anticancer drug.