Theoretical investigation of the conformational, electronic and antioxidant properties of azaleatin, isorhamnetin and quercetagetin

Gas phase and solvent phase reaction enthalpies related to the individual steps of three phenolic antioxidants in the view of action mechanisms - hydrogen atom transfer (HAT), single electron transfer-proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) - have been calculated using DFT/B3LYP/6-311++G** method. The analysis of the theoretical bond dissociation enthalpy (BDE) values for all OH sites of studied compounds clearly shows the importance of ring B, the presence of a catechol moiety in ring A and the 3-OH group in which the C2=C3 double bond is present. The analysis of structure-acidity and structure-activity relationships for these flavonoids clearly indicates that the hydroxyl group at position 7 to be the most acidic site except for that of azaleatin. The analysis also includes the heat of formation, highest occupied molecular orbital and spin density distribution for the radicals formed after H-removal on each OH site. The calculated ionisation potential, BDE and proton dissociation enthalpy values suggest that one-step H-atom transfer, rather than SPLET or SET-PT, would be the most favourable mechanism for explaining the antioxidant activity of considered molecules in the gas phase. From the thermodynamic point of view, SPLET mechanism represents the most probable process in water and HAT mechanism in represents the most probable process benzene. On the basis of computed reaction enthalpies, the most active system able to transfer a hydrogen atom seems to be the quercetagetin followed by azaleatin and isorhamnetin.