Predicting the activity of phenolic antioxidants: Theoretical method, analysis of substituent effects, and application to major families of antioxidants

A procedure based on density functional theory is used for the calculation of the gas-phase bond dissociation enthalpy (BDE) and ionization potential fur molecules belonging to the class of phenolic antioxidants. We show that use of locally dense basis sets (LDBS) vs full basis sets gives very simil ar results for monosubstituted phenols, and that the: LDBS procedure gives good agreement with the change in experimental BDE values for highly substi tuted phenols in benzene solvent. Procedures for estimating the O-H BDE bas ed on group additivity rules are given and tested. Several interesting clas ses of phenolic antioxidants are studied with these methods, including comm ercial antioxidants used as food additives, compounds related to Vitamin E, flavonoids in tea, aminophenols, stilbenes related to resveratrol, and ste rically hindered phenols. On the basis of these results we are able to inte rpret relative rates for the reaction of antioxidants with free radicals, i ncluding a comparison of both H-atom-transfer and single-electron-transfer mechanisms, and conclude that in most cases H-atom transfer will be dominan t.