Quantum-mechanical computations on the electronic structure of trans-resveratrol and trans-piceatannol: a theoretical study of the stacking interactions in trans-resveratrol dimers.

Accurate quantum-chemical calculations based on the second-order Møller-Plesset perturbation method (MP2) and density functional theory (DFT) were performed for the first time to investigate the electronic structures of trans-resveratrol and trans-piceatannol, as well as to study the stacking interaction between trans-resveratrol molecules. Ab initio MP2 calculations performed with using standard split-valence Pople basis sets led us to conclude that these compounds have structures that deviate strongly from planarity, whereas the DFT computations for the same basis sets revealed that the equilibrium geometries of these bioactive polyphenols are planar. Furthermore, the results obtained at the MP2(full)/aug-cc-pVTZ and B3LYP/aug-cc-pVTZ levels indicated that the geometries of trans-resveratrol and trans-piceatannol are practically planar at their absolute energy minima. The relative energies of the equilibrium geometries of trans-resveratrol on its potential energy surface were computed at the MP2(full)/aug-cc-pVTZ level. According to the results obtained, a T-shaped (edge-to-phase) conformer of trans-resveratrol dimer is the most stable in vacuum. This T-shaped conformer is mainly stabilized by strong hydrogen bonding and weak C-H...π interactions. Stacked structures with parallel-displaced trans-stilbene skeletons were also found to be energetically stable. The vertical separation and twist angle dependencies of the stacking energy were investigated at the MP2(full)/aug-cc-pVTZ, B3LYP/aug-cc-pVTZ, and HF/aug-cc-pVTZ levels. The standard B3LYP functional and the Hartree-Fock method neglect long-range attractive dispersion interactions. The MP2 computations revealed that the London dispersion energy cannot be neglected at long or short distances. The stacked model considered here may be useful for predicting the quantum nature of the interactions in π-stacked systems of other naturally occurring stilbenoids, and can help to enhance our understanding of the antioxidant and anticancer activities of trans-resveratrol.