Conformational transitions of the quercetin molecule via the rotations of its rings: a comprehensive theoretical study.

Quercetin is an important flavonoid compound, usually extracted from plants, vegetables and fruits such as blueberries, apples, green tea, wine, onions and possessing broad range of pharmacological properties, in particular, powerful antioxidant, antitoxic, antiinflammation and antimicrobial effects due to its various reactive sites. The structure of this phenolic compound consists of three (A + C) and B rings, bearing five hydroxyl groups. Primarily, the chemical structure of quercetin determines its physico-chemical properties. Earlier, it was established that isolated quercetin molecule can acquire 48 stable conformations (24 planar and 24 non-planar) due to the mobility of its hydroxyl groups and (A + C) and B rings with relative Gibbs free energies in the range of 0.0-25.3 kcal·mol-1 under normal conditions (Brovarets' et al., 2019c). In this work by quantum-mechanical calculations at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory and Bader's 'Quantum Theory of Atoms in Molecules', we have theoretically modeled the interconversions in the 24 pairs of the conformers of the quercetin molecule, occuring via the rotation of its non-deformable (A+С) and B rings around the С2-С1' bond through the quasi-orthogonal transition state with low values of the imaginary frequencies (28-33/29-36 cm-1) and Gibbs free energies of activation in the range of 2.17-5.68/1.86-4.90 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.Communicated by Ramaswamy H. Sarma.