The Relationship Between Chemical Structure and the Logarithm of the Partition Coefficient

The relationship between chemical structure of a solute and the logarithm of its partition coefficient (log P) between the aqueous and a nonpolar phase is poorly understood. We have recently shown that the variation in log P data for 50 low molecular‐weight organic solutes in 6 aqueous‐non‐polar solvents is a function of two structural features. The main feature accounts for ≈︁60% of the variation in the log P data, and is uniformly weighted in all 6 nonpolar solvent systems. This suggests that it is related to the aqueous solution properties of the solute. The first feature is termed the isotropic surface area, or the surface area associated with the nonpolar portion of the solute when the solute is considered to be a hydrated complex. The hydrated solute complex is termed a supermolecule with waters of hydration occupying hydrogen bonding sites on the functional groups of the solute. Empirical rules for formation of the super molecule are discussed. In this report the analysis is extended to log P data for 72 solutes in the 6 nonpolar solvent systems. The results of the analysis are essentially unchanged for this more extended data set and the second factor is tentatively identified. The second structural feature accounted for ≈︁35% of the variation in the log P data was not equally weighted in all solvents and is difficult to interpret structurally.