Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, Ukraine.
Department of Molecular Biotechnology and Bioinformatics, Institute of High Technologies, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine.
J Biomol Struct Dyn. 2020 Jul;38(10):2817-2836. doi: 10.1080/07391102.2019.1656671. Epub 2019 Sep 17.
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 in vacuum under normal conditions. Impact of the continuum with = 4 leads to the decreasing of the Gibbs free energies (-0.19-18.15 kcal·mol) 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.
本文重点研究了槲皮素分子的综合构象分析，槲皮素分子具有广泛的治疗和生物活性。通过逐步旋转其五个羟基以及相对彼此旋转其 (A + C) 和 B 环，获得了这些分子所有可能构象，这些构象对应于势能超曲面上的局部最小值。总共确定了 48 个稳定构象，其中 24 个构象具有平面结构，24 个构象具有非平面结构。详细研究了它们的结构、对称、能量和极性特征。量子力学计算表明，槲皮素分子的构象是具有偶极矩的极性结构，不同构象的偶极矩在 0.35 至 9.87 德拜之间变化。在正常条件下，真空中这些构象的相对吉布斯自由能位于 0.0 至 25.3 kcal·mol 之间。连续体的影响（ = 4）导致吉布斯自由能降低（-0.19-18.15 kcal·mol）和偶极矩增加（0.57-12.48 D）。结果表明，槲皮素分子的构象彼此之间通过分子内特定接触（两个或三个）不同，稳定分子的所有可能构象——氢键（经典的 OH…O 和所谓的不寻常的 C'H…O 和 OH…C'）和吸引力范德华接触 O…O。对槲皮素分子的构象分析使我们能够更深入地了解“结构-功能”关系，并提出其治疗和生物活性的机制。由 Ramaswamy H. Sarma 传达。
