Ruelle P, Kesselring U W
Institut d'Analyse Pharmaceutique, Section de Pharmacie, Université de Lausanne, B E P, CH-1015 Lausanne, Switzerland.
J Pharm Sci. 1998 Aug;87(8):998-1014. doi: 10.1021/js9702980.
The quantitative development of the nonergodic mobile order thermodynamics involving the new interpretation of the hydrophobic effect leads to a general solubility equation. This equation is applied to predict the aqueous and alcohol solubility of chemicals ranging from nonpolar or slightly polar with no H-bonding capacity to polyfunctional polar compounds including pharmaceuticals. The analysis of the relative importance of the contributions involved in the solubility model [i.e., the fluidization of the solute (for solids), the correction for the mixing entropy, the change of the nonspecific cohesion forces, and the formation of solvent-solvent (hydrophobic effect), solute-solute, and solute-solvent H-bonds] unambiguously demonstrates that the hydrophobic effect is essential for predicting the aqueous or alcohol solubility of any substance in general, and of nonpolar compounds in particular. The difference between the origin of the solubility of hydrocarbons in water and of water in hydrocarbons is furthermore presented. In both cases, the quasilinear solubility dependence on the molar volume of the hydrocarbon is of an entropic nature.
涉及疏水效应新解释的非遍历性移动有序热力学的定量发展导出了一个通用溶解度方程。该方程用于预测各类化学品在水和醇中的溶解度，这些化学品涵盖了从无氢键能力的非极性或弱极性化合物到包括药物在内的多官能团极性化合物。对溶解度模型中各贡献因素（即溶质的流化作用（对于固体）、混合熵校正、非特异性内聚力变化以及溶剂 - 溶剂（疏水效应）、溶质 - 溶质和溶质 - 溶剂氢键的形成）相对重要性的分析明确表明，疏水效应对于总体预测任何物质在水或醇中的溶解度，特别是非极性化合物的溶解度至关重要。此外，还阐述了烃在水中和水在烃中的溶解度起源之间的差异。在这两种情况下，溶解度对烃摩尔体积的准线性依赖具有熵的性质。
