Enhanced self-assembly for the solubilization of cholesterol in molecular solvent/ionic liquid mixtures

Abstract

The development of new solvents combining greatly enhanced solubility for sparingly soluble compounds and good kinetic properties is challenging. In this study, we constructed a family of new molecular solvent/ionic liquid (IL) mixtures with amphiphilic, anionic functional long-chain carboxylate ionic liquids (LCC-ILs) as a key component for the solubilization of sparingly soluble compounds, using cholesterol as a model solute. Polarized optical microscopy (POM), wide angle X-ray diffraction (WAXD), Fourier-transform infrared (FTIR) spectra and ¹H NMR showed that ordered mesoscopic structures, such as liquid crystals (LCs), were formed when cholesterol was dissolved in the mixtures, presenting a self-assembly induced dissolution mechanism driven by H-bond interaction and van der Waals forces in the mixtures. A synergistic effect between the molecular solvents and LCC-ILs was revealed, which contributed to enhanced solute–solvent self-assembly in dissolution over pure LCC-ILs and thus elevated solubility. Additionally, the effect of IL concentration, solvent type and anionic alkyl-chain length on self-assembly and solubility was investigated. These mixtures showed unparalleled solubilities for cholesterol, while maintaining a low viscosity. The quantitative solubilities (g g⁻¹) of cholesterol were as high as 0.70, 0.84 and 0.82, respectively, at 25 °C in ethyl acetate/[P₄₄₄₄][C₁₅H₃₁COO] (50 wt%), n-heptane/[P₄₄₄₄][C₁₅H₃₁COO] (40 wt%) and ethyl acetate/[P₄₄₄₄][C₁₇H₃₅COO] (50 wt%) mixtures, which were the highest solubilities of cholesterol ever reported, six- to 980-fold higher than traditional molecular solvents and even one- to seven-fold higher compared to pure LCC-ILs. These results demonstrated the considerable potential of molecular solvent/LCC-ILs mixtures as promising solvents for solubilization and advanced separation processes.