Analytical Sciences

Prediction of the 1-Octanol/H₂O Partition Coefficient, Log P, by Ab Initio MO Calculations: Hydrogen-Bonding Effect of Organic Solutes on Log P

Hiroshi CHUMAN,  Atsushi MORI, and Hideji TANAKA

Faculty of Pharmaceutical Sciences, The University of Tokushima, Schomachi, Tokushima 770-8505, Japan

To predict the 1-octanol/H₂O partition coefficient, log P, based on molecular structures, we calculated the solvent accessible surface area and the solvation energy difference of 166 organic molecules between 1-octanol and water environments with the ab initio molecular orbital self-consistent reaction field method, and then analyzed the relationships among the measured log P values with these two structural quantities by multiple linear-regression analyses. Physicochemically meaningful correlations were obtained, suggesting that non-hydrogen bonding and hydrogen-acceptor molecules behave similarly to each other in partitioning, but that hydrogen-donor molecules behave differently from the former molecules. The results provide a new computational approach for predicting log P.

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