Emulsifier-phenol bioconjugates as antioxidants. Molecular descriptors based on density functional theory in quantitative structure-activity relationships

For 27 members of a combinatorial library of antioxidant bioconjugates of Trolox, dihydroferulic acid, dihydrocaffeic acid and gallic acid combined with serine ethyl ester, serine lauryl ester, lauroyl serine, serine capryl ester, and N-capryl serine, including the parent phenols and their non-reduced forms, bond dissociation enthalpy (BDE), energy of highest occupied orbital (E-HOMO), energy of lowest unoccupied orbital (E-LUMO) and dipole moment (mu) were calculated according to density functional theory (DFT) as molecular descriptors. For each series of parent phenols, the lag phase for formation of conjugated dienes in unilamellar phosphatidylcholine liposomes with radical initiation from the aqueous phase was found to correlate with BDE. Rate of scavenging of the beta-carotene radical cation was found to correlate with g for the Trolox bioconjugates in homogeneous solution. Rate of scavenging of the semi-stable radical DPPH by the bioconjugates was found to increase with hydrophobicity in aqueous micelles. The difference in structure-activity relationship reflects changes in antioxidant mechanism. (C) 2013 Elsevier Ltd. All rights reserved.