A Never-Ending Conformational Story of the Quercetin Molecule: Quantum-Mechanical Investigation of the O3′H and O4′H Hydroxyl Groups Rotations

Abstract

The quercetin molecule is known to be an effective pharmaceutical compound of a plant origin. Its chemical structure represents two aromatic A and B rings linked through the C ring containing oxygen and five OH hydroxyl groups attached to the 3, 3′, 4′, 5, and 7 positions. In this study, a novel conformational mobility of the quercetin molecule was explored due to the turnings of the O3′H and O4′H hydroxyl groups, belonging to the B ring, around the exocyclic C-O bonds. It was established that the presence of only three degrees of freedom of the conformational mobility of the O3′H and O4′H hydroxyl groups is connected with their concerted behavior, which is controlled by the non-planar (in the case of the interconverting planar conformers) or locally non-planar (in other cases) TSsO3′H/O4′H transition states, in which O3′H and O4′H hydroxyl groups are oriented by the hydrogen atoms towards each other. We also explored the number of the physico-chemical and electron-topological characteristics of all intramolecular-specific contacts—hydrogen bonds and attractive van der Waals contacts at the conformers and also at the transition states. Long-terms perspectives for the investigations of the structural bases of the biological activity of this legendary molecule have been shortly described.

Computational Structural Assessment on the Stereochemistry of the Transition Metal Complex Formed by a Naphthalene-1,4-dione Based Ligand with Divalent Nickel

“…Many chemical structures exhibit conformational mobility due to their various degrees of freedom [16].…”

Inhibitory Effect of Quercetin on Oxidative Endogen Enzymes: A Focus on Putative Binding Modes

“…Jaguar (Schrödinger Release 2022-1: Jaguar, Schrödinger, LLC, New York, NY, USA, 2022) [45] was utilized to conduct the DFT calculations [28] using the B3LYP (Becke's three-parameter exchange potential and Lee-Yang-Parr correlation function) method [46] in conjunction with the 6-311++G** (d, p) basis set, which successfully recommended itself for similar tasks and objects [47,48]. The calculations included the determination of the following properties: HOMO, LUMO, their energy gap (∆E), ESP, ALIE, NBO, and ED.…”

Special Issue on “The Application of Quantum Mechanics in Reactivity of Molecules”

“…Brovarets et al [2] addressed the conformational diversity of the quercetin molecule, an effective pharmaceutical compound of plant origin. In particular, the authors employed DFT(B3LYP) and MP2 to investigate the conformational mobility of quercetin, focusing on the rotation of the hydroxyl groups in the 3 and 4 positions.…”