Analysis of water solubility data on the basis of HYBOT descriptors

Abstract

Abstract Solubility data of 787 organic liquids (electrolytes and non‐electrolytes) with diverse structures has been quantitatively described by physicochemical property descriptors. Special effects like intra ‐ and inter molecular hydrogen bonds have been shown to be very important for water solubility. It is found that an important part of the solute‐solvent interaction is neglected in all correlations of logS with (only) logP, as in this case the solute H‐bond donor effect is not considered. As expected intramolecular hydrogen bonds lead to reduced solubility, whereas intermolecular hydrogen bonds (both HB donors and acceptors) of solutes result in higher solubility. An exception to the latter rule are carboxylic acids which due to intermolecular HB‐induced dimerization in the pure liquid phase of acids show a three times lower solubility as expected on the basis of their molecular properties. A volume‐related term (molecular polarizability α) was found to have an essential negative contribution to solubility. For the first time the solubility increasing effect of partial ionization of weak acids and bases in saturated aqueous solutions has been quantitatively considered for sets of compounds by exact calculation of the pH determined by the solutes aqueous solubility and pKa value(s).