QSAR and mechanisms of radical scavenging activity of phenolic and anilinic compounds using structural, electronic, kinetic, and thermodynamic parameters

QSAR study was performed on the DPPH radical scavenging activity of a wide range (51 compounds) phenolic and anilinic compounds; many of them are widely distributed in biological systems. The structural diversity includes phenols (1-3 OH groups) and anilines (1-2 NH2 groups) with many electron donating and withdrawing groups, aminophenols (o, m, p), phenolic acids (o, m, p) or esters, enols, and phenolic terpenoids. Independents used were electronic Brown parameter and the structural parameters i.e., the indicator variable Q for forming a stable quinone-like product and the number of alkoxy (RO) and alkyl (R) groups as well as the thermodynamic parameters, bond dissociation energy (BDE), proton dissociation energy of O–H or N–H bond and HOMO of the parent compounds, and the resulted radicals or radical cations. Radical scavenging activity gave fair correlation with electronic Brown and the structural Q parameters, while it gave strong correlation with the structural parameters (R, RO, and Q) and BDE (R 2 = 0.979, N = 49, SE = 5.94, p < 0.001). Hydrogen-atom transfer and single-electron-transfer mechanisms were discussed in accordance with the resulted correlations. Correlating the rate constant (ks) with the same independents retained only the structural parameters; the weighting value of each parameter confirms that forming semiquinone radicals has the highest impact in stabilizing transition state and increasing the reaction rates followed by the presence of the electron donating groups alkoxy and alkyl groups.