The radical scavenging activity of a flavonoid is largely influenced by its structure. The effects of the substituents at C3 position on the antioxidant activity of naringenin were carried out using the density functional theory (DFT) method. The reaction enthalpies related with the three well-established mechanisms were analyzed. Excellent correlations were found between the reaction enthalpies and Hammett sigma constants. Equations obtained from the linear regression can be helpful in the selection of suitable candidates for the synthesis of novel naringenin derivatives with enhanced antioxidant properties. In the gas and benzene phases, the antioxidant activity of naringenin was enhanced by the electron-donating substituents via weakening the bond dissociation enthalpy (BDE). In the water phase, it was strengthened by electron-withdrawing groups—via lowering the proton affinity (PA). The electronic effect of the substituent on the BDE of naringenin is mainly governed by the resonance effect, while that on the ionization potential (IP) and PA of naringenin is mainly controlled by the field/inductive effect.

Flavonoids widely found in natural foods are excellent free radical scavengers. The relationship between the substituent and antioxidative activity of flavonoids has not yet been completely elucidated. In this work, the antioxidative activity of apigenin derivatives with different substituents at the C3 position was determined by density functional theory (DFT) calculations. The bond dissociation enthalpy (BDE), ionization potential (IP), and proton affinity (PA) were calculated. Donator acceptor map (DAM) analysis illustrated that the studied compounds are worse electron acceptors than F and also are not better electron donors than Na. The strongest antioxidative group of apigenin derivatives was the same as apigenin. Excellent correlations were found between the BDE/IP/PA and Hammett sigma constants. Therefore, Hammett sigma constants can be used to predict the antioxidative activity of substituted apigenin and to design new antioxidants based on flavonoids. In non-polar phases, the antioxidative activity of apigenin was increased by the electron-withdrawing groups, while it was reduced by the electron-donating groups. Contrary results occurred in the polar phase. The electronic effect of the substituents on BDE(4′-OH), BDE(5-OH), PA(4′-OH), and IP is mainly controlled by the resonance effect, while that on BDE(7-OH), PA(5-OH), and PA(7-OH) is governed by the field/inductive effect.