Investigation on Dissolution of Chrysin in Acetone + Water Mixed Solvents from 293.15 K to 333.15 K: Solubility Determination, Model Correlation, Thermodynamic Analysis, and Microscopic Solvation Mechanism

The solubility of chrysin in acetone–water binary mixtures (a polar protic–polar aprotic solvent system) was determined across the full acetone mole fraction range (0 to 1) and at temperatures of 293.2 K to 333.2 K. The solubility increases with temperature and shows a pronounced non-monotonic dependence on solvent composition, reaching a maximum at an acetone mole fraction of 0.80, characteristic of co-solvency behavior. A clear solvation transition was observed: acetone preferentially solvates chrysin at intermediate compositions, whereas water dominates in both water-rich and acetone-rich regions. The solubility of chrysin was correlated using 11 thermodynamic models, classified into empirical/semi-empirical models, local-composition activity coefficient models, and COSMO–RS-based quantum chemical models. The Modified Apelblat and van’t Hoff equations showed the best performance. Thermodynamic analysis based on the van’t Hoff equation indicates that the dissolution process is endothermic and non-spontaneous, governed primarily by enthalpy. Integrated molecular-level analysis based on COSMO-RS σ-profiles and ESP further elucidates that macroscopic solvation behavior across the entire composition range arises from microscopic solute–solvent and solvent–solvent interactions.