Intramolecular tautomerization of the quercetin molecule due to the proton transfer: QM computational study

Abstract

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.

The Flow of the Redox Energy in Quercetin during Its Antioxidant Activity in Water

“…Therefore, we considered that deprotonation of the 7-OH group is the first step in the antioxidant activity of Q. The DFT calculation shows that after deprotonation, a tautomer of 7DE can be formed by in which the proton of the 3-OH group is transferred to the 4 oxygen atom (7DE-ITPT) [ 26 ]. Therefore, the formation of this tautomer is also considered.…”

“…Recently, a quantum chemical computational study by Brovarets et al [ 26 ], on the tautomerization of Q by intramolecular proton transfer, revealed 48 stable conformers (24 planar and 24 non-planar) with relative Gibbs free energies within the range of 0.0 to 25.3 Kcal/mol. This included conformers formed by proton transfer from the 3-OH group to the 4 oxygen atom with a Gibbs free energy change of around 13 Kcal/mol.…”

Intramolecular Hydrogen Bond Energy and Its Decomposition—O–H∙∙∙O Interactions

“…The methods based on equations 1, 3 or 4 may be classified as the FBA approaches while the method proposed by Gadre and co-workers [42,43] may be classified as the MTA approach. One can also mention the relationships between the hydrogen bond energy and the electron density at the corresponding proton-proton acceptor distance [50,51], which may be classified as the FBA approaches, the following hydrogen…”

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

“…In the case of the quercetin molecule, both of these tasks are overcomplicated. The reason is that the conformational mobility of this molecule is closely connected with its prototropic tautomerism [40,41]. It is known that the quercetin molecule has 202 molecular prototropic tautomers [40].…”