What is better to enhance the solubility of hydrophobic compounds in aqueous solutions: eutectic solvents or ionic liquids?†

Abstract

The solubilities of benzoic acid, (S)-hesperetin, and L-tryptophan in aqueous solutions of ionic liquids (choline glycolate and choline malonate) and the analogous eutectic solvents (choline chloride:glycolic acid and choline chloride:malonic acid) were studied. It is shown that while ionic liquids (IL) and eutectic solvents (ES) were able to increase the solubility of all compounds studied in aqueous solution, ionic liquids were much more efficient for neutral and acidic compounds, while eutectic solvents showed a better performance for the alkaline substances. The results reported here show that the solubility enhancement is related, in the first instance, to the pH of the aqueous solution, which is the dominant effect on the increase in solubility and the main parameter that must be taken into account when selecting a co-solvent to successfully achieve the solubilization of ionizable hydrophobic biomolecules in aqueous solution. In addition, a hydrotropy mechanism was identified when the pH effect was removed, supporting the idea that ionic liquids and eutectic solvents behave as hydrotropes in aqueous solutions. The results here reported show that rather than a focus on the type of solvents (IL vs. ES), the molecular mechanisms such as speciation and co-solvation/hydrotropy, which in some cases may have complementary and synergetic effects, are the parameters that must be addressed in the design or selection of the best solubility enhancer.