In this paper, the antioxidant activity of 6-hydroxy-2,5,7,8-tetramethylchromane- 2-carboxylic acid (Trolox) derivatives were investigated by the density functional theory and the polarization continuum model as a solvent model in order to propose novel derivatives with a higher antioxidant activity from a theoretical viewpoint. The effects of various ortho and meta substituents on the reaction enthalpies of the antioxidant mechanisms of Trolox derivatives were investigated. In addition, the effect of reducing the number of atoms in the heterocyclic ring and the effect of replacing the oxygen heteroatom of Trolox with other heteroatoms on the antioxidant activity of Trolox derivatives were evaluated. The results showed that NH2, OH and NHMe substituents in the meta and ortho positions decreased the homolytic bond dissociation enthalpy (BDE) and adiabatic ionization potential (IP) values and increased the antioxidant activities of the Trolox derivatives from the theoretical viewpoint. The derivatives e, c and d with NH, S and Se instead of O, respectively, had higher antioxidant activities from the theoretical viewpoint. The obtained results showed that reducing the number of atoms in the heterocyclic ring (derivatives a and b) decreased the BDE and IP values and increased the antioxidant activities of the Trolox derivatives from the theoretical viewpoint. The linear dependencies between BDE of the O–H bond and IP values of the studied Trolox derivatives and the corresponding EHOMO and R(O–H) values could assist in the proposal of novel derivatives with higher antioxidant activity from the theoretical viewpoint.
