Equilibrium solubility of 7-amino-4-methylcoumarin in several aqueous co-solvent mixtures revisited: Transfer property, solute-solvent and solvent-solvent interactions and preferential solvation

Abstract

The preferential solvation analysis was carried out by the inverse Kirkwood–Buff integrals method on available solubility data of 7-amino-4-methylcoumarin in four aqueous co-solvent mixtures of ethylene glycol (EG, 1) + water (2), isopropanol (1) + water (2), ethanol (1) + water (2) and DMF (1) + water (2). Results show that the drug is preferentially surrounded by water in water-rich regions, and by organic solvents in other composition ranges. Among these binary mixtures, the highest preferential solvation magnitude was recorded for isopropanol solutions. Selective solvation of the drug by organic solvents may be owing to the higher basicity of solvents that facilitates interactions with the Lewis acidic groups of 7-amino-4-methylcoumarin. A solvent effect analysis was performed by using the linear solvation energy relationships to unravel the relative importance of solute-solvent and solvent-solvent interactions on the solubility variation. In addition, the transfer properties, e.g. transfer Gibbs free energy (ΔtrGo), transfer enthalpy (ΔtrHo) and transfer entropy (ΔtrSo) were derived in terms of the accessible solubility data, indicating more favorable solubilization ability in the intermediate compositions of co-solvents.