Structural, dynamic, and hydration properties of quercetin and its aggregates in solution

Quercetin is a flavonoid present in the human diet with multiple health benefits. Quercetin solutions are inhomogeneous even at very low concentrations due to quercetin's tendency to aggregate. We simulate, using molecular dynamics, three systems of quercetin solutions: infinite dilution, 0.22 M, and 0.46 M. The systems at the two highest concentrations represent regions of the quercetin aggregates, in which the concentration of this molecule is unusually high. We study the behavior of this molecule, its aggregates, and the modifications in the surrounding water. In the first three successive layers of quercetin hydration, the density of water and the hydrogen bonds formations between water molecules are smaller than that of bulk. Quercetin has a hydrophilic surface region that preferentially establishes donor hydrogen bonds with water molecules with relative frequencies from 0.12 to 0.46 at infinite dilution. Also, it has two hydrophobic regions above and below the planes of its rings, whose first hydration layers are further out from quercetin (≈0.3 Å) and their water molecules do not establish hydrogen bonds with it. Water density around the hydrophobic regions is smaller than that of the hydrophilic. Quercetin molecules aggregate inπ-stacking configurations, with a distance of ≈0.37 nm between the planes of their rings, and form bonds between their hydroxyl groups. The formation of quercetin aggregates decreases the hydrogen bonds between quercetin and the surrounding water and produces a subdiffusive behavior in water molecules. Quercetin has a subdiffusive behavior even at infinite dilution, which increases with the number of molecules within the aggregates and the time they remain within them.