A deep insight into the structure-solubility relationship and molecular interaction mechanism of diverse flavonoids in molecular solvents, ionic liquids, and molecular solvent/ionic liquid mixtures

The dissolution behavior and structure-solubility relationships of diverse flavonoids in various solvent systems, including the pure molecular solvents, pure ionic liquids (ILs), and molecular solvent/IL mixtures, are investigated in conjunction with experiments as well as quantum chemical and COSMO-RS calculations. The dissolution of flavonoids is a complex process. The dissolution difference of various flavonoids is ascribed to the synergistic influence of multiple factors, including the structure and planarity of the diverse flavonoid molecules, the extent of delocalization, the type, number, and position of functional groups, properties of the various solvents, and inter/intramolecular interactions. The planarity of flavonoid molecules is usually the most critical of these factors. The degree of nonplanarity of flavonoids follows the order flavanone > isoflavone > flavone > flavonol, which basically coincides with the solubility ranking of diverse flavonoids. Additionally, the type, number, and position of functional groups capable of forming hydrogen bonds also significantly affect flavonoid dissolution in solvents. The dissolution sequence of different flavonoids in various solvents varies with the structure and configuration of flavonoids. Of all the investigated solvents, flavonoid compounds are the least soluble in water because of their hydrophobicity, and they are most easily soluble in ILs with higher HBA basicity due to solute–solvent hydrogen-bond interactions, such as [Bmim]Ac and [Bmim]NO3. Adding ILs into molecular solvents or water has a significantly enhanced solubilization effect for the poorly soluble flavonoid compounds. In addition, water can act as an effective antisolvent, allowing for efficient recovery of flavonoids and ILs.