A density functional theory study of structure-activity relationships in caffeic and dihydrocaffeic acids and related monophenols

Structure-activity relationships in the antioxidants caffeic acid and dihydrocaffeic acid as well as in the monophenols isoeugenol, eugenol, and dihydroeugenol were investigated by using the density functional theory (DFT). The higher antioxidant activity of caffeic acid, among the rest, could be attributed to its lower difference in the heat of formation (DeltaHOF) value. Dihydrocaffeic acid exhibits less antioxidant activity than caffeic acid, owing to both its higher DeltaHOF value and its limited spin delocalization. These two latter findings could also account for the lower antioxidant activity of both eugenol and dihydroeugenol as compared to isoeugenol. DFT calculations afford a good molecular descriptor, DeltaHOF, that correlates well with the antioxidant activity in molecules exhibiting similar structural characteristics. The presence of a simple double bond in the side chain makes a difference in the antioxidant activity only if it leads to an extended conjugation. Calculated dipole moment values for both the parent molecules and the respective phenoxyl radicals correlate well with their antioxidant efficiency in some instances.