A Hidden Side of the Conformational Mobility of the Quercetin Molecule Caused by the Rotations of the O3H, O5H and O7H Hydroxyl Groups: In Silico Scrupulous Study

Abstract

In this study at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of quantum-mechanical theory it was explored conformational variety of the isolated quercetin molecule due to the mirror-symmetrical hindered turnings of the O3H, O5H and O7H hydroxyl groups, belonging to the A and C rings, around the exocyclic C–O bonds. These dipole active conformational transformations proceed through the 72 transition states (TSs; C1 point symmetry) with non-orthogonal orientation of the hydroxyl groups relatively the plane of the A or C rings of the molecule (HO7C7C8/HO7C7C6 = ±(89.9–93.3), HO5C5C10 = ±(108.9–114.4) and HO3C3C4 = ±(113.6–118.8 degrees) (here and below signs ‘±’ corresponds to the enantiomers)) with Gibbs free energy barrier of activation ΔΔGTS in the range 3.51–16.17 kcal·mol−1 under the standard conditions (T = 298.1 K and pressure 1 atm): ΔΔGTSO7H (3.51–4.27) < ΔΔGTSO3H (9.04–11.26) < ΔΔGTSO5H (12.34–16.17 kcal mol−1). Conformational dynamics of the O3H and O5H groups is partially controlled by the intramolecular specific interactions O3H…O4, C2′/C6′H…O3, O3H…C2′/C6′, O5H…O4 and O4…O5, which are flexible and cooperative. Dipole-active interconversions of the enantiomers of the non-planar conformers of the quercetin molecule (C1 point symmetry) is realized via the 24 TSs with C1 point symmetry (HO3C3C2C1 = ±(11.0–19.1), HC2′/C6′C1′C2 = ±(0.6–2.9) and C3C2C1′C2′/C3C2C1′C6′ = ±(1.7–9.1) degree; ΔΔGTS = 1.65–5.59 kcal·mol−1), which are stabilized by the participation of the intramolecular C2′/C6′H…O1 and O3H…HC2′/C6′ H-bonds. Investigated conformational rearrangements are rather quick processes, since the time, which is necessary to acquire thermal equilibrium does not exceed 6.5 ns.

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

“…In this study, which is a logical continuation of our previous works on this topic [16][17][18][19][20][21], new pathways of the transformations of the conformers of the quercetin molecule into each other were found, which occurred due to the torsional mobility of the O3 H and O4 H hydroxyl groups.…”

“…In this study, we logically continued to investigate the conformational mobility [16][17][18] of the quercetin molecule and extend this approach to the rotations of the hydroxyl groups in the 3 and 4 positions, which are carefully presented in Tables 1-3 and Figures 1-3. The most obvious methods of the conformational interconversions between the 48 conformers [16] of the quercetin molecule were considered and investigated in detail through the rotations of the O3 H and O4 H hydroxyl groups around the exocyclic C-O covalent bonds.…”

“…Also, it was theoretically modeled the conformational interconversions [17][18][19][20][21] in the 24 pairs of the conformers of the quercetin molecule through the rotation of its almost non-deformable (A+C) and B rings around the C2-C1′ bond through the quasi-orthogonal transition state (TS) with low values of the imaginary frequencies (28-33/29-36 cm −1 ) and Gibbs free energies of activation in the range of 2.17 to 5.68/1.86 to 4.90 kcal•mol −1 in the continuum with dielectric permittivity ε = 1/ε = 4 under normal conditions. Also, we studied the changes of the number of physico-chemical characteristics of all intramolecular specific contacts-hydrogen bonds and attractive van der Waals contacts during these conformational rearrangements.…”

“…This study is a logical development of the previous investigations [16][17][18] and is devoted to the novel interconversions between the conformers of the quercetin molecule due to the rotations of the O3 H and O4 H hydroxyl groups around the exocyclic C-O bonds outside.…”

On Prototropy and Bond Length Alternation in Neutral and Ionized Pyrimidine Bases and Their Model Azines in Vacuo

“…Presently, quantum-chemical methods can be used not only for structural (isomeric) analyses, but also for investigations of various physicochemical properties and reaction mechanisms, even for more complex molecules than nucleic acid bases (see, for example, refs. [44][45][46][47]).…”