Dominant Carbons in <i>trans</i>- and <i>cis</i>-Resveratrol Isomerization

A comprehensive analysis for isomerization of geometric isomers in the case of resveratrol (R) has been presented. As an important red wine molecule, only one geometric isomer of resveratrol, i.e., <i>trans</i>-R rather than <i>cis</i>-R, is primarily associated with health benefit. In the present study, density function theory (DFT) provides accurate descriptions of isomerization of resveratrol. The nearly planar <i>trans</i>-R forms a relatively rigid and less flexible conjugate network, but the nonplanar <i>cis</i>-R favors a more flexible structure with steric through space interaction. The calculated carbon nuclear magnetic resonance (NMR) chemical shift indicates that all carbons are different in the isomers; it further reveals that four carbon sites, i.e., C₍₆₎, C₍₈₎C₍₉₎, and C₍₁₁₎, have a significant response to the geometric isomerization. Here C₍₆₎ is related to the steric effect in <i>cis</i>-R, whereas C₍₁₁₎ may indicate the isomerization proton transfer on C₍₉₎ linking with the resorcinol ring. The excess orbital energy spectrum (EOES) confirms the NMR “bridge of interest” carbons and reveals that five valence orbitals of 34<i>a</i>, 35<i>a</i>, 46<i>a</i>, 55<i>a</i>, and 60<i>a</i> respond to the isomerization most significantly. The highest occupied molecular orbital (HOMO), 60<i>a</i>, of the isomer pair is further studied using dual space analysis (DSA) for its orbital momentum distributions, which exhibit p-electron dominance for <i>trans</i>-R but hybridized sp-electron dominance for <i>cis</i>-R. Finally, energy decomposition analysis (EDA) highlights that <i>trans</i>-R is preferred over <i>cis</i>-R by −4.35 kcal·mol^–1, due to small electrostatic energy enhancement of the attractive orbital energy with respect to the Pauli repulsive energy

Resveratrol’s Hidden Hand: A Route to the Optical Detection of Biomolecular Binding

Resveratrol is a stilbenoid phytoalexin with promising myriad health benefits predominantly contributed by the <i>trans</i> (<i>E</i>) diastereomeric form. A recent study has implicated the <i>cis</i> (<i>Z</i>) diastereomer in human health. This stereoisomer binds with high affinity to human tyrosyl-tRNA synthetase, initiating a downstream cascade that promotes the expression of genes associated with the cellular stress response. We discovered that the nonplanar structure of the <i>cis</i>-resveratrol conformer possesses certain chiral signals in its simulated vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectra. These features may be used for the optical detection of the binding event and in understanding the more diversified biological roles of <i>trans</i>-resveratrol over <i>cis</i>-resveratrol. We use a density functional theory model, which is validated against the known results for the <i>E</i> diastereomer. The <i>Z</i> diastereomer is significantly nonplanar and can exist in two helical atropisomeric forms. These forms exchange rapidly in solution, but only one is observed to bind with the synthetase. This suggests that the binding may generate an enantiomeric excess, leading to detectable changes in the vibrational optical activity spectra. We identify candidate features at 998, 1649, and 1677 cm^–1 in the ROA and at 1642 and 3834 cm^–1 in the VCD spectra of <i>Z</i>-resveratrol that may be useful for this purpose