In order to evaluate the free radical scavenging potency of dihydroxybenzoic acids (DHBAs) the Density Functional Theory (DFT) was used. The M05-2X/6-311++G(d,p) and B3LYP-D2/6-311++G(d,p) theoretical models were applied. Three possible antioxidant mechanisms were examined: hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET) mechanisms. All of these mechanisms have been studied in nonpolar (benzene and pentylethanoate) and polar solvents (water) using an implicit solvation model (SMD). The following thermodynamic quantities related to these mechanisms were calculated: bond dissociation enthalpy (BDE), ionization potential (IP), and proton affinity (PA). The obtained results indicated the HAT mechanism as the most favourable reaction pathway for antioxidative action of DHBAs in benzene. On the other hand, SPLET is indicated as predominant reaction mechanism in polar solvent. The SET-PT mechanism was not favourable reaction path for antioxidative action in any of the solvents under investigation.

The quantitative structure–activity relationship (QSAR) of the free radical scavenging potency of 21 selected hydroxybenzoic acids and simple phenolics was examined. We found that descriptors related to the energetics and structural aspects of free radical scavenging processes enable the development of reliable QSAR models that possess better statistical characteristics than the models developed using more than thousand molecular descriptors from the large Dragon set. The lack of standardized antioxidant assays makes the successful use of the QSAR procedure doubtful. However, we showed that by taking into account some driving forces of free radical scavenging and the associated descriptors (bond dissociation enthalpy BDE, proton affinity PA, electron-transfer enthalpy ETE, and the number of vicinal phenolic OH groups, n OH _vic ), it is possible to generate fair antiradical QSAR models.