Stacking interaction study of <i>trans</i>‐resveratrol (<i>trans</i>‐3,5,4′‐trihydroxystilbene) in solution by Nuclear Magnetic Resonance and Fourier Transform Infrared Spectroscopy

Bonechi, Claudia; Martini, Silvia; Magnani, Agnese; Rossi, Claudio

doi:10.1002/mrc.2217

Cited by 25 publications

(24 citation statements)

References 21 publications

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“…Summarizing, the results presented here prove that there is a π-π stacking interaction between t-RES molecules. This observation has been experimentally confirmed by Bonechi et al [37]. We hope that the stacking interactions studied here will help to explain the numerous biological properties of t-RES.…”

Section: Discussionsupporting

confidence: 78%

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

Mikulski

Molski

2012

J Mol Model

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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.

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Section: Discussionsupporting

confidence: 78%

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

Mikulski

Molski

2012

J Mol Model

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“…4a). This upfield shift suggests screening of aryl protons due to stacking of aromatic rings upon self-association of Phe molecules28. This is further supported by similar chemical shift for phenyl carbon in 13 C NMR (Fig.…”

Section: Resultssupporting

confidence: 71%

“…Concentration dependent 1 H and 13 C NMR analysis of Phe, further confirms the role of Phe ring in self-assembly process. Upfield chemical shift was observed which is attributed to the stacking intermolecular interactions between π-electron cloud of Phe ring, resulting in shielding and this effect becomes prominent at high concentration2840. Additionally, increase in particle size and decrease in diffusion coefficient was observed in 1 H DOSY experiment indicating the formation of higher order assemblies.…”

Section: Discussionmentioning

confidence: 91%

Therapeutic implication of L-phenylalanine aggregation mechanism and its modulation by D-phenylalanine in phenylketonuria

Singh

Kumar

Arora

et al. 2014

Sci Rep

112

145

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Self-assembly of phenylalanine is linked to amyloid formation toxicity in phenylketonuria disease. We are demonstrating that L-phenylalanine self-assembles to amyloid fibrils at varying experimental conditions and transforms to a gel state at saturated concentration. Biophysical methods including nuclear magnetic resonance, resistance by alpha-phenylglycine to fibril formation and preference of protected phenylalanine to self-assemble show that this behaviour of L-phenylalanine is governed mainly by hydrophobic interactions. Interestingly, D-phenylalanine arrests the fibre formation by L-phenylalanine and gives rise to flakes. These flakes do not propagate further and prevent fibre formation by L-phenylalanine. This suggests the use of D-phenylalanine as modulator of L-phenylalanine amyloid formation and may qualify as a therapeutic molecule in phenylketonuria.

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“…NMR chemical shift assignments of trans -resveratrol (resveratrol), or trans -resveratrol derivatives have been previously reported in acetone (58), chloroform (59), DMSO-d 6 (60), and in a DMSO-d 6 /D 2 O mixture (61). Resveratrol (figure 1) in D 2 O was assigned by one-dimensional 1 H, two-dimensional 1 H, 1 H-NOESY, and two-dimensional 1 H, 1 H-ROESY NMR experiments.…”

Section: Resultsmentioning

confidence: 99%

Structure of trans-Resveratrol in Complex with the Cardiac Regulatory Protein Troponin C

2011

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Cardiac troponin -a heterotrimeric protein complex that regulates heart contraction -represents an attractive target for the development of drugs to treat heart disease. Cardiovascular diseases are one of the chief causes of morbidity and mortality worldwide. In France, however, the death rate from heart disease is remarkably low relative to fat consumption. This so called "French paradox" has been attributed to the high consumption of wine in France; and the antioxidant transresveratrol is thought to be the primary basis for wine's cardioprotective nature. It has been demonstrated that trans-resveratrol increases the myofilament Ca 2+ -sensitivity of guinea-pig myocytes (Liew, R., Stagg, M.A., MacLeod, K.T., and Collins, P., (2005) Eur. J. Pharmacol. 519,[1][2][3][4][5][6][7][8], however, the specific mode of its action is unknown. In this study, the structure of transresveratrol free and bound to the calcium-binding protein, troponin C, was determined by NMR spectroscopy. The results indicate that trans-resveratrol undergoes a minor conformational change upon binding to the hydrophobic pocket of the C-domain of troponin C. The location occupied by trans-resveratrol coincides with the binding site of troponin I -troponin C's natural binding partner. This has been seen for other troponin C-targeting inotropes and implicates the modulation of the troponin C-troponin I interaction as a possible mechanism of action for trans-resveratrol. KeywordsTrans-resveratrol; troponin C; NMR spectroscopy; cardiac muscle; contraction; Ca 2+ -sensitizerThe physiological function of the heart is to pump blood throughout the body in order to fulfill the oxygen and nutrient demands of the organism. The thin filament in heart muscle is made up of actin, tropomyosin, and troponin. Troponin is a heterotrimeric protein complex formed by the Ca 2+ -binding subunit, troponin C (TnC); the inhibitory subunit, troponin I (TnI); and the tropomyosin-binding subunit, troponin T (TnT). Cardiac TnC (cTnC) has four EF-hand metal binding sites (I-IV) -two in each of its terminal domains. The C-terminal (cCTnC) and N-terminal (cNTnC) domains are connected by a flexible linker, as shown by the NMR (1) and X-ray structures (2). In cNTnC, site I is defunct and site II is a low-affinity Ca 2+ -binding site; on the other hand, both site III and site IV in cCTnC are functional and can bind either Mg 2+ or Ca 2+ . During the contraction-relaxation cycle, cytosolic Ca 2+ concentration dramatically oscillates: at high Ca 2+ levels, cNTnC becomes Ca 2+ -saturated, * CORRESPONDING AUTHOR FOOTNOTE: Phone Number: (780) 492-5460, Fax Number: (780) 492-0886, brian.sykes@ualberta.ca. § Both authors contributed equally to this work. Supporting Information Available:Data illustrating the oxidation rate of resveratrol; the resveratrol ROE intensities versus mixing time; the binding of resveratrol to cTnC; the ligand dependant chemical shift perturbations of cCTnC; the intramolecular NOEs of resveratrol in complex with cCTnC; and the structural statistics for ...

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Stacking interaction study of trans‐resveratrol (trans‐3,5,4′‐trihydroxystilbene) in solution by Nuclear Magnetic Resonance and Fourier Transform Infrared Spectroscopy

Cited by 25 publications

References 21 publications

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

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

Therapeutic implication of L-phenylalanine aggregation mechanism and its modulation by D-phenylalanine in phenylketonuria

Structure of trans-Resveratrol in Complex with the Cardiac Regulatory Protein Troponin C

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