Enhanced Solvation of Hydrophobic Molecules in Aqueous Cygnet Mixtures Explored Through Their Solubility Isotherms

Herein, we report the apparent aqueous solubilization of acetylsalicylic acid, ciprofloxacin, quercetin, thiabendazole, and vanillin in the presence of a solubilizer, the dioxolane Cyrene derivative, Cygnet. To understand its driving force (i.e., the competitive interactions) within the ternary analyte-Cygnet-water mixtures, experimental data is fit to quadratic solubility isotherms derived recently from statistical thermodynamic fluctuation theory. The insights from the solubility isotherm parameters are (i) attractive Cygnet-analyte preferential interaction for solubilization and (ii) Cygnet-Cygnet self-interaction around the analyte that distinguishes weak synergistic or cooperative solubilization mechanisms. A preferential interaction exists between Cygnet-analyte for all analytes, with synergistic solvation observed for acetylsalicylic acid, ciprofloxacin, thiabendazole, and vanillin; here, maximum, normalized, enhanced solubility increases with analyte hydrophobicity, with thiabendazole experiencing the largest enhancement (17×) and ciprofloxacin the lowest (2.3×). Quercetin undergoes apparent cooperative hydrotropy and displays the largest solubility enhancement overall (41×). Despite these mechanistic differences, analyte-dependent solvation behavior for all analytes can be understood through the same theoretical principle.