chapter  5
26 Pages

Octanol/Water Partition Coefficients

The usefulness of the ratio of the concentration of a solute between water and octanol as a model for its transport between phases in a physical or biological system has long been recognized(Leo 1971, 1981). It is expressed as: P

= C


= K

This ratio is essentially

independent of concentration, and it usually is given in logarithmic terms (log P

or log K

) which are better suited for use as a free-energy based parameter in ‘extra-thermodynamic’ equations of the Hammett-Taft type (Hansch, 1995). The importance of bioconcentration in environmental hazard assessment (Kenaga, 1972) and the utility of the hydrophobic parameter in its prediction (Neely, 1974) led to an intense interest in the measurement of P

and also its prediction from structure. (Leo, 1993; Hansch, 1995). Persistence is also a serious concern in the assessment of the environmental hazard of

organic chemicals and a major pathway by which they are eliminated is through biodegradation. A great deal of biodegradation, from simple bacteria to whole animals, involves oxidation via the P-450 family of enzymes, the activity of which depends greatly upon hydrophobicity expressed as log P. (Hansch and Leo, 1995, Chapter 8). In 3,500 QSARs of biological activity of all sorts, 85% show a significant dependence upon log P. (Hansch, Hoekman, and Gao, 1996).