About Partition Coefficients

What they are

The term partition coefficient commonly refers to the equilibrium distribution of a single substance between two solvent phases separated by a boundary. The phases may be pure substances or solutions. One or both solvents are condensed phases. Partition coefficients are sometimes called distribution coefficients.

A few well-known examples may be mentioned. When one phase is a gas above its critical temperature and the other is a liquid, the partition coefficient is known also as Henry's constant or simple solubility. It is tacitly assumed here that solute concentration is low and is effectively at "infinite dilution". In vapour-liquid equilibrium, the corresponding quantity is the activity coefficient at infinite dilution.

The two solvents may be immiscible liquids, an application readily recognizable as liquid-liquid extraction, used widely in organic synthesis. Use of the octanol-water pair arose in a different context.

What they are used for

Over a century ago, it was discovered that the narcotic action of many simple organic solutes was reflected rather closely by their oil-water partition coefficients (1a). Later, "oil" was replaced by octanol, which better represents the physicochemical environment a foreign substance encounters in living tissue (2a).

In the present Databank, the octanol-water partition coefficient is designated by K_ow. It is the equilibrium ratio of solute concentrations in the two solvents:

K_ow first found application in medicinal chemistry and drug design, but it has proved useful in other seemingly unrelated areas as well (1b, 3). For example, K_ow (or rather log K_ow) correlates with toxicity, soil-water partition coefficients, bioaccumulation and sediment-water partition coefficients. It is as important a parameter as water solubility and vapour pressure in the modelling of the fate of organic pollutants in the environment (4). Such diverse applicability is no accident, because K_ow is a quantitative thermodynamic measure of the hydrophilic/lipophilic balance of an organic compound (2a).

How they are measured

K_ow is measured in the laboratory often by the "shake-flask" method, as in ordinary liquid-liquid extraction. This is a direct method; a number of indirect methods are also used (1b, 2b, 5).

How good are the measurements

As in other areas of science, K_ow measurement methods vary greatly in accuracy and difficulty (2c). The uncertainty of the measured datum may be large, and this sometimes compromises its usefulness in application (6). This is why, in LOGKOW ^©, experimental details of measurement are given for reported K_ow values.

How K_ow can be predicted

K_ow can be calculated from the molecular structure of the compound (1c, 2d). There are a number of methods extant, a few of which are available for use on a personal computer. For some purposes, calculated K_ow data are sufficiently reliable. For accurate work, the limitations of calculation methods must be considered (1d, 2e, 7). Log K_ow may be predicted using various algorithms. See http://www.vcclab.org/lab/alogps.

REFERENCES

1. C. Hansch and A. Leo, Exploring QSAR: fundamentals and applications in chemistry and biology, American Chemical Society, Washington (1995). (a) p. 99; (b) Chapters 6-12; (c) pp. 103-124; (d) Chapter 5.
2. J. Sangster, Octanol-water Partition Coeffcients: fundamentals and physical chemistry, John Wiley & Sons, Chichester (1997). (a) Chapter 1; (b) Chapter 3; (c) Chapter 4; (d) Chapter 5; (e) Chapter 6.
3. A. Leo, C.Hansch and D. Elkins, "Partition Coefficients and Their Uses", Chem. Rev. 71(6), 525-616 (1971).
4. D. Mackay, W.-Y. Shiu and K.-C. Ma, Illustrated Handbook of Physical-Chemical Properties and Environmental Fate of Organic Chemicals, 5 volumes, Lewis Publishers, Chelsea, MI (1992-1997).
5. J. Sangster, "Octanol-water Partition Coefficients of Simple Organic Compounds", J. Phys. Ref. Data 18(3), 1111-1129 (1989).
6. R. Renner, "The K_ow Controversy", Environ. Sci. Technol. 36(21), 410A-413A (2002).
7. A. J. Leo, "Calculating log Poct from Structures", Chem. Rev. 93(4), 1281-1306 (1993).