Baicalein Solubility in Several Nonaqueous and Aqueous Mixtures and a Quantum Chemistry Investigation

A technique, namely shake-flask, was applied in this work to experimentally determine the baicalein solubilities under isothermal conditions in methanol/isopropanol + water and ethyl acetate + isopropanol/methanol/ethanol mixtures. Baicalein crystals did not show any transition or solvation, according to the analysis of XRD profiles. The solubility data obtained here were mathematically correlated through three models (Jouyban–Acree, van’t Hoff–Jouyban–Acree, and Extended Hildebrand Solubility Approach), producing root-mean-square deviations of ≤5.70 × 10 –5 . The inverse Kirkwood–Buff integrals were experienced herein to explore the preferred solvation of baicalein at 298.15 K. Mixtures covering intermediate and rich methanol/isopropanol compositions in methanol/isopropanol + water and ethyl acetate compositions in ethyl acetate + isopropanol/methanol/ethanol had positive solvation parameters for baicalein, indicating that methanol/isopropanol preferentially solvated baicalein in aqueous solutions and ethyl acetate in ethyl acetate + alcohol solutions. Additionally, the electrostatic properties of baicalein were revealed with the help of the molecular surface electrostatic potential. The main targets of electrophilic and nucleophilic attack are the −C═O group and −OH group of the baicalein molecule. An IGMH analysis illustrated the weak interactions of baicalein and solvent species.