Improvement of antioxidative activity of resveratrol by calix[4]arene-like tetramer: A theoretical study

Resveratrol is a natural antioxidant in a wide variety of plant species, developing an effective strategy to further improve its antioxidative activity has attracted enormous research attention in recent years. In this work, tetra-(3,5-dihydroxy)styryl-calix[4]arene (TSC, a calix[4]arene-like tetramer of resveratrol) has been theoretically studied at the DET-BP86/6-311 + G(d,p) level of theory. The results demonstrates that TSC has highly symmetrical molecular geometry with four equivalent resveratrol units, the 4'-O-H and 4'-C-O bonds were elongated and distinct deviation from planarity was observed in four resveratrol units in TSC. More interestingly, TSC has remarkably lower 4'-OH BDE, IP, and PA of 4'-phenolate than those of resveratrol, indicating that TSC exhibits much more excellent antioxidative activities than resveratrol. Spin density in 4'-phenoxyl radical and cation radical are delocalized over whole molecular skeleton of TSC, thus leading to more stable radical species than that of resveratrol. The topologies analysis of unpaired electron occupying orbitals reveals that calix[4]arene skeleton plays very important role in delocalization of unpaired electron. Molecular simplification studies proved that the synergistic effect of calix[4]arene skeleton, the A benzene ring and C-C double bonds on the upper rim were responsible for the higher activity of TSC, and calix[4]arene skeleton amongst played the most important role.