Universal model based on the mobile order and disorder theory for predicting lipophilicity and partition coefficients...

The quantitative thermodynamic development of the mobile order and disorder theory in H-bonded liquids has been extended in order to predict partition coefficients. The model enables "a priori" estimation of the partition coefficient (log P) of neutral solutes, not only in the conventional 1-octanol/water reference but also in all mutually saturated two-phase systems made up of largely immiscible solvents. The model is obtained from the thermodynamic treatment of the various physicochemical free energy processes encoded in the overall distribution process and accordingly provides a useful tool for better understanding both the origin and the factors, such as the solute molar volume, that determine the partition coefficient of nonelectrolytes in a given system. From the comparison of the relative magnitude of the processes contributing to the log P value, a lot of information can also be gained regarding the variation in log P of the same substance partitioned between different solvent systems. As a demonstration, the model has been successfully applied to predict the log P of a great number of chemicals of varying structure, size, and chemical nature partitioned in a large set of essentially immiscible solvent pairs, differing either by their nonpolar or by their polar phase. In the systems involving water as the polar phase, the hydrophobic effect is always the driving force that governs the distribution process irrespective of the interacting or noninteracting nature of the substances studied. In the other two-phase systems, the partitioning of complexing solutes in particular appears to be ruled rather by their hydrogen-bonding capabilities than by their hydrophobicities.