Aqueous solubility prediction of environmentally important chemicals from the mobile order thermodynamics

Applied to the aqueous solubility of only-sligthly polar compounds with no hydrogen bond donor capacity, the quantitative development of the thermodynamics of mobile order results in a very simple nearly linear predictive solubility equation requiring only the molar volume of the solute and its melting properties in the case of solids. Enhancement of the solubility by weak solvation effects associated to the proton-acceptor ability of the solute towards water is taken into account through standard stability constants reflecting the functionality, the degree of unsaturation and cyclization of the molecule. Accordingly, the molar aqueous solubility of a diverse set of 531 chemicals of environmental relevance is predicted with an average absolute error of 0.37 log units though the solubilities span over more than 12 orders of magnitude. The analysis of the relative importance of the terms contributing to the solubility demonstrates that the poor solubility of low-polarity compounds in water is merely the result of the hydrophobic effect and of its extremely rapid increase with the size of the solute. The mobile order thermodynamics also provides explanations for the empirically deduced solubility-volume linear relationships. (C) 1997 Elsevier Science Ltd.