Temperature Dependence of Hydrotropy.

The solubility of hydrophobic solutes increases dramatically with the temperature when hydrotropes are added to water. In this paper, the mechanism of this well-known observation will be explained via statistical thermodynamics through (i) enhanced enthalpy-hydrotrope number correlation locally (around the solute) that promotes the temperature dependence and (ii) hydrotrope self-association in the bulk solution that suppresses the temperature dependence. The contribution from (i), demonstrated to be dominant for urea as a hydrotrope, signifies the weakening of interaction energies around the solute (local) than in the bulk that accompanies incoming hydrotrope molecules. Thus, studying hydrotropic solubilization along the temperature and hydrotrope concentration provides complementary information on the local-bulk difference: the local accumulation of hydrotropes around the solute, driven by the enhanced local hydrotrope self-association, is also accompanied by the overall local weakening of energetic interactions, reflecting the fluctuational nature of hydrotrope association and the mediating role of water molecules.