Octanol-water Partition Coefficient
   HOME

TheInfoList



OR:

The ''n''-octanol-water partition coefficient, ''K''ow is a partition coefficient for the two-phase system consisting of ''n''-octanol and water. ''K''ow is also frequently referred to by the symbol P, especially in the English literature. It is also called ''n''-octanol-water partition ratio. ''K''ow serves as a measure of the relationship between
lipophilicity Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipo ...
(fat solubility) and hydrophilicity (water solubility) of a substance. The value is greater than one if a substance is more soluble in fat-like solvents such as n-octanol, and less than one if it is more soluble in water. If a substance is present as several
chemical species A chemical species is a chemical substance or ensemble composed of chemically identical molecular entities that can explore the same set of molecular energy levels on a characteristic or delineated time scale. These energy levels determine the wa ...
in the octanol-water system due to association or dissociation, each species is assigned its own ''K''ow value. A related value, D, does not distinguish between different species, only indicating the concentration ratio of the substance between the two phases.


History

In 1899, Charles Ernest Overton and Hans Horst Meyer independently proposed that the tadpole toxicity of non-ionizable organic compounds depends on their ability to partition into lipophilic compartments of cells. They further proposed the use of the partition coefficient in an olive oil/water mixture as an estimate of this lipophilic associated toxicity. Corwin Hansch later proposed the use of n-octanol as an inexpensive synthetic alcohol that could be obtained in a pure form as an alternative to olive oil.


Applications

''K''ow values are used, among others, to assess the environmental fate of persistent organic pollutants. Chemicals with high partition coefficients, for example, tend to accumulate in the fatty tissue of organisms (
bioaccumulation Bioaccumulation is the gradual accumulation of substances, such as pesticides or other chemicals, in an organism. Bioaccumulation occurs when an organism absorbs a substance at a rate faster than that at which the substance is lost or eliminated ...
). Under the
Stockholm Convention Stockholm Convention on Persistent Organic Pollutants is an international environmental treaty, signed on 22 May 2001 in Stockholm and effective from 17 May 2004, that aims to eliminate or restrict the production and use of persistent organ ...
, chemicals with a log ''K''ow greater than 5 are considered to bioaccumulate. Furthermore, the parameter plays an important role in drug research ( Rule of Five) and
toxicology Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating expos ...
. Ernst Overton and Hans Meyer discovered as early as 1900 that the efficacy of an anaesthetic increased with increasing ''K''ow value (the so-called Meyer-Overton rule). ''K''ow values also provide a good estimate of how a substance is distributed within a cell between the lipophilic biomembranes and the aqueous
cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
.


Estimation

Since it is not possible to measure ''K''ow for all substances, various models have been developed to allow for their prediction, e.g. Quantitative structure–activity relationships (QSAR) or linear free energy relationships (LFER) such as the Hammett equation. A variant of the UNIFAC system can also be used to estimate octanol-water partition coefficients.


Equations

* Definition of the ''K''ow or P-value : The ''K''ow or P-value always only refers to a single
species In biology, a species is the basic unit of Taxonomy (biology), classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of ...
or substance: :K_\mathrm = P = \frac : with: :*c_o^ concentration of species ''i'' of a substance in the octanol-rich phase :*c_w^ concentration of species ''i'' of a substance in the water-rich phase : If different species occur in the octanol-water system by dissociation or association, several P-values and one D-value exist for the system. If, on the other hand, the substance is only present in a single species, the P and D values are identical. : P is usually expressed as a
common logarithm In mathematics, the common logarithm is the logarithm with base 10. It is also known as the decadic logarithm and as the decimal logarithm, named after its base, or Briggsian logarithm, after Henry Briggs, an English mathematician who pioneered ...
, i.e. Log P (also Log Pow or, less frequently, Log pOW): :\log = \log \frac = \log c_o^ - \log c_w^ Log P is positive for lipophilic and negative for hydrophilic substances or species. * Definition of the D-value : The D-value only correctly refers to the concentration ratio of a single substance distributed between the octanol and water phases. In the case of a substance that occurs as multiple species, it can therefore be calculated by summing the concentrations of all ''n'' species in the octanol phase and the concentrations of all ''n'' species in the aqueous phase: :D = \frac = \frac : with: :* c_o concentration of the substance in the octanol-rich phase :* c_w concentration of the substance in the water-rich phase : D values are also usually given in the form of the common logarithm as Log D: :\log = \log \frac = \log c_o - \log c_w : Like Log P, Log D is positive for lipophilic and negative for hydrophilic substances. While P values are largely independent of the pH value of the aqueous phase due to their restriction to only one species, D values are often strongly dependent on the pH value of the aqueous phase.


Example values

Values for log ''K''ow typically range between -3 (very hydrophilic) and +10 (extremely lipophilic/hydrophobic). The values listed here are sorted by the partition coefficient. Acetamide is hydrophilic, and 2,2′,4,4′,5-Pentachlorobiphenyl is lipophilic.


See also

*
Hydrophobic effect The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in an aqueous solution and exclude water molecules. The word hydrophobic literally means "water-fearing", and it describes the segregation of water and nonpola ...
* Dortmund Data Bank


References


Further reading

*
* {{refend


External links


Virtual Computational Chemistry Laboratory
interactive calculation and interactive comparison of several methods
LogP-Berechnungssoftware von ACD
(commercial)
Directory of reference works and databases with octanol-water partition coefficients

Comprehensive free database of evaluated octanol-water partition coefficients from Sangster Research Laboratories
Ecotoxicology Pharmacology Physical chemistry