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.
PLoS One. 2019 Nov 21;14(11):e0224762. doi: 10.1371/journal.pone.0224762. eCollection 2019.
Quercetin molecule (3, 3', 4', 5, 7-pentahydroxyflavone, C15H10O7) is an important flavonoid compound of natural origin, consisting of two aromatic A and B rings linked through the C ring with endocyclic oxygen atom and five hydroxyl groups attached to the 3, 3', 4', 5 and 7 positions. This molecule is found in many foods and plants, and is known to have a wide range of therapeutic properties, like an anti-oxidant, anti-toxic, anti-inflammatory etc. In this study for the first time we have revealed and investigated the pathways of the tautomeric transformations for the most stable conformers of the isolated quercetin molecule (Brovarets' & Hovorun, 2019) via the intramolecular proton transfer. Energetic, structural, dynamical and polar characteristics of these transitions, in particular relative Gibbs free and electronic energies, characteristics of the intramolecular specific interactions-H-bonds and attractive van der Waals contacts, have been analysed in details. It was demonstrated that the most probable process among all investigated is the proton transfer from the O3H hydroxyl group of the C ring to the C2' carbon atom of the C2'H group of the B ring along the intramolecular O3H…C2' H-bond with the further formation of the C2'H2 group. It was established that the proton transfer from the hydroxyl groups to the carbon atoms of the neighboring CH groups is assisted at the transition states by the strong intramolecular HCH…O H-bond (~28.5 kcal∙mol-1). The least probable path of the proton transfer-from the C8H group to the endocyclic O1 oxygen atom-causes the decyclization of the C ring in some cases. It is shortly discussed the biological importance of the obtained results.
槲皮素分子（3,3',4',5,7-五羟基黄酮，C15H10O7）是一种重要的天然来源的类黄酮化合物，由通过中环的内环氧原子和连接的 A 环和 B 环以及分别连接在 3、3'、4'、5 和 7 位的 5 个羟基组成。这种分子存在于许多食物和植物中，具有广泛的治疗特性，如抗氧化、解毒、抗炎等。在这项研究中，我们首次通过分子内质子转移揭示并研究了分离的槲皮素分子（Brovarets' & Hovorun，2019）最稳定构象的互变异构转化途径。详细分析了这些转变的能量、结构、动力学和极性特征，特别是相对吉布斯自由能和电子能、分子内特定相互作用 - H 键和吸引力范德华接触的特征。结果表明，在所研究的所有过程中，最可能的过程是质子从 C 环的 O3H 羟基转移到 B 环的 C2'碳原子，沿着分子内 O3H…C2' H 键形成 C2'H2 基团。已确定，质子从羟基到相邻 CH 基团的碳原子的转移在过渡态中受到强的分子内 HCH…OH 键（~28.5 kcal∙mol-1）的辅助。质子从 C8H 基团转移到内环氧 O1 氧原子的可能性最小，在某些情况下会导致 C 环的去环化。简要讨论了所获得结果的生物学重要性。
