Conformational diversity of the quercetin molecule: a quantum-chemical view

Abstract

This paper focuses on the comprehensive conformational analysis of the quercetin molecule with a broad range of the therapeutic and biological actions. All possible conformers of these molecule, corresponding to the local minima on the potential energy hypersurface, have been obtained by the sequential rotation of its five hydroxyl groups and also by the rotation of its (A + C) and B rings relatively each other. Altogether, it was established 48 stable conformers, among which 24 conformers possess planar structure and 24 conformers – nonplanar structure. Their structural, symmetrical, energetical and polar characteristics have been investigated in details. Quantum-mechanical calculations indicate that conformers of the quercetin molecule are polar structures with a dipole moment, which varies within the range from 0.35 to 9.87 Debay for different conformers. Relative Gibbs free energies of these conformers are located within the range from 0.0 to 25.3 kcal·mol⁻¹ in vacuum under normal conditions. Impact of the continuum with ε = 4 leads to the decreasing of the Gibbs free energies (–0.19–18.15 kcal·mol⁻¹) and increasing of the dipole moment (0.57–12.48 D). It was shown that conformers of the quercetin molecule differ from each other by the intramolecular specific contacts (two or three), stabilizing all possible conformers of the molecule – H-bonds (both classical ОН…О and so-called unusual С′Н…О and ОН…С′) and attractive van-der-Waals contacts О…О. Obtained conformational analysis for the quercetin molecule enables to provide deeper understanding of the ‘structure-function’ relationship and also to suggest its mechanisms of the therapeutic and biological actions.

Communicated by Ramaswamy H. Sarma

Keywords:

• Quercetin molecule
• conformational diversity
• intramolecular specific contact
• dipole moment
• Gibbs free energy
• quantum-mechanical calculation
• quantum theory of atoms in molecules

Acknowledgements

Authors sincerely grateful for technical support and computational facilities of joint computer cluster of SSI ‘Institute for Single Crystals’ of the National Academy of Sciences of Ukraine (NASU) and Institute for Scintillation Materials of the NASU incorporated into Ukrainian National Grid. Authors also wish to thank Dr Ivan Voiteshenko for the technical assistance.

DrSci Ol’ha O. Brovarets’ expresses sincere gratitude to the U.S.-Ukraine Foundation (USUF) Biotech Initiative for a travel grant (‘2018 Emerging Biotech Leader of Ukraine’; https://www.usukraine.org/biotechnology-initiative/), enabling to participate in the ‘63^rd Annual Meeting of the Biophysical Society BPS’2019’ (Baltimore, Maryland, March 2–6, 2019; https://www.biophysics.org/2019meeting#/; https://bioukraine.org/news/emerging-biotech-leader-olha-brovarets-attends-63rd-biophysical-society-meeting-in-baltimore/; https://bioukraine.org/news/emerging-leader-olha-brovarets-shares-her-us-experience-with-bionity-student-biotech-club/).

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Additional information

Funding

DrSci Ol’ha O. Brovarets’ was supported by the Grant of the President of Ukraine to support the research of young scientists (Ministry of the Education and Science of Ukraine) and by the Scholarship of Verkhovna Rada (Parliament) of Ukraine for the talented young scientists given in 2019 year.