Dominant Carbons in trans- and cis-Resveratrol Isomerization

Abstract

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., trans-R rather than cis-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 trans-R forms a relatively rigid and less flexible conjugate network, but the nonplanar cis-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, C═C, and C, have a significant response to the geometric isomerization. Here C is related to the steric effect in cis-R, whereas C may indicate the isomerization proton transfer on C 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 34a, 35a, 46a, 55a, and 60a respond to the isomerization most significantly. The highest occupied molecular orbital (HOMO), 60a, of the isomer pair is further studied using dual space analysis (DSA) for its orbital momentum distributions, which exhibit p-electron dominance for trans-R but hybridized sp-electron dominance for cis-R. Finally, energy decomposition analysis (EDA) highlights that trans-R is preferred over cis-R by -4.35 kcal·mol, due to small electrostatic energy enhancement of the attractive orbital energy with respect to the Pauli repulsive energy.

Resveratrol in Cancer Patients: From Bench to Bedside

“…Its melting point is between 253 and 255 °C, and its solubility in water is very low (3 mg/100 mL) [8]. The ethylene bridge due to a limited degree of freedom generates two geometric isomers: cis-resveratrol and transresveratrol ( Figure 1) [5]. These isoforms co-exist in resveratrol extracts even if a greater biological activity and stability are attributed to trans-resveratrol.…”

“…Notably, resveratrol is one of the most studied polyphenols that naturally accumulates in plant cells, and probably its presence characterizes the antioxidant and anti-inflammatory properties of a specific food [2]. The first studies concerning its chemical-physical structure demonstrated its interaction with the electrons scattered in reactive species of oxygen or other pro-oxidant components [5][6][7]. The worthwhile interaction with the electrons scattered in reactive species of oxygen or other pro-oxidant components [5][6][7].…”

“…The first studies concerning its chemical-physical structure demonstrated its interaction with the electrons scattered in reactive species of oxygen or other pro-oxidant components [5][6][7]. The worthwhile interaction with the electrons scattered in reactive species of oxygen or other pro-oxidant components [5][6][7]. The worthwhile properties of resveratrol are, however, marked by a pharmacokinetic profile and by an unfavorable oral bioavailability, which requires a thorough analysis.…”

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Resveratrol (3,5, is a natural phytoalexin that accumulates in several vegetables and fruits like nuts, grapes, apples, red fruits, black olives, capers, red rice as well as red wines. Being both an extremely reactive molecule and capable to interact with cytoplasmic and nuclear proteins in human cells, resveratrol has been studied over the years as complementary and alternative medicine (CAM) for the therapy of cancer, metabolic and cardiovascular diseases like myocardial ischemia, myocarditis, cardiac hypertrophy and heart failure.

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“…Comparing to the geometric isomers, the nearly planar structure of trans-resveratrol is less flexible than the non-planar structure of cis-resveratrol, but it possesses a lower repulsive energy that ensures it, albeit small, higher stability. Isomerization of trans-resveratrol to cis-resveratrol occurs via molecule breakdown when trans-resveratrol is exposed to UV radiation at a wavelength of 254 or 366 nm, to high pH conditions or in plants during fermentation processes [5,9]. In analyzing some physical-chemical aspects of resveratrol, Zupancic et al showed how trans-resveratrol is rapidly degradable in high-pH solutions.…”