Ursolic Acid and Oleanolic Acid Dissolved in Methanol/Acetone + Water Blends: Thermodynamic Solubility, Intermolecular Interactions, and Solvation Behavior

With the purpose of qualitative characterization of the electrostatic properties of the acidity and basicity of ursolic acid (UA) and oleanolic acid (OA), quantitative analyses of the molecular surface were employed in this contribution. The −OH and −COOH groups on the molecules of OA and UA took precedence over establishing hydrogen bonds with the solvents acetone/methanol/water. In addition, the intermolecular interactions of OA and UA with acetone/methanol/water were investigated using an independent gradient model based on the Hirshfeld partition of molecular density. In solutions of OA/UA dissolved in methanol/acetone/water, attractive interactions, including the hydrogen-bond force and van der Waals (vdW) force, occur. The shake-flask technique was applied to evaluate the equilibrium solubility of UA and OA in acetone + water and methanol + water at 101.2 kPa and elevated temperatures covering from 278.15 to 323.15 K. Solvent–solvent interactions accounted by the solubility parameter of solutions had a significant domination in the variability of solubility magnitudes. The van't Hoff–Jouyban–Acree, Apelblat, and Jouyban–Acree models revealed a good correlation for the measured solubility, with a relative mean deviation of no more than 7.73%. The Kirkwood–Buff integral approach was utilized to determine the preferred solvation of UA and OA by solvent species. In both the rich- and intermediate-composition regions of methanol/acetone, UA or OA is preferentially solvated with positive preferential solvation parameters by methanol/acetone.