Octanol-water partition coefficient explained

The n-octanol-water partition coefficient, K_ow is a partition coefficient for the two-phase system consisting of n-octanol and water.^[1] 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.^{[2] [3] [4]}

K_ow serves as a measure of the relationship between lipophilicity (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 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.^{[5] [6]}

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). Under the Stockholm Convention, chemicals with a log K_ow greater than 5 are considered to bioaccumulate.^[7]

Furthermore, the parameter plays an important role in drug research (Rule of Five) and toxicology. 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).^[8]

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.

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)^{[9] [10]} such as the Hammett equation.

A variant of the UNIFAC system can also be used to estimate octanol-water partition coefficients.^[11]

Equations

• Definition of the K_ow or P-value

The K_ow or P-value always only refers to a single species or substance:

K _{ow} = P = (c ^{S _{i}} _{o})/(c ^{S _{i}} _{w})

with:

c ^{S _{i}} _{o} concentration of species i of a substance in the octanol-rich phasec ^{S _{i}} _{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, i.e. Log P (also Log P_ow or, less frequently, Log pOW):

log {P} = log (c ^{S _{i}} _{o})/(c ^{S _{i}} _{w}) = log c ^{S _{i}} _{o} - log c ^{S _{i}} _{w} Log P is positive for lipophilic and negative for hydrophilic substances or species.

• Definition of the D-value

The P-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 = (c _{o})/(c _{w}) = (c ^{S _{1}} _{o} + c ^{S _{2}} _{o} + ... + c ^{S _{n}} _{o})/(c ^{S _{1}} _{w} + c ^{S _{2}} _{w} + ... + c ^{S _{n}} _{w})

with:

c _{o} concentration of the substance in the octanol-rich phasec _{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 {D} = log (c _{o})/(c _{w}) = 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).^[12]

The values listed here^[13] are sorted by the partition coefficient. Acetamide is hydrophilic, and 2,2′,4,4′,5-Pentachlorobiphenyl is lipophilic.

!Substance!log K_OW!T!Reference

Acetamide	−1.155	25 °C
Methanol	−0.824	19 °C
Formic acid	−0.413	25 °C
Diethyl ether	0.833	20 °C
p-Dichlorobenzene	3.370	25 °C
Hexamethylbenzene	4.610	25 °C
2,2′,4,4′,5-Pentachlorobiphenyl	6.410	Ambient

See also

• Hydrophobic effect
• Dortmund Data Bank

Further reading

• Goss KU . Der Oktanol/Wasser Verteilungskoeffizient — Das Allheilmittel der Umweltchemie? . The octanol / water partition coefficient - the panacea for environmental chemistry? . German . Umweltwissenschaften und Schadstoff-Forschung . July 2003 . 15 . 4 . 273–279 . 10.1065/uwsf2003.01.050. 102406251 .
• Heuel-Fabianek B . Partition Coefficients (Kd) for the Modelling of Transport Processes of Radionuclides in Groundwater . JÜL-Berichte, Forschungszentrum Jülich, Nr. 4375, 2014 . 0944-2952.

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

Notes and References

1. Book: Sangster J . Octanol-water partition coefficients : fundamentals and physical chemistry. 1997. Wiley. 0-471-97397-1. Chichester. 36430034.
2. Book: Mackay D . Multimedia environmental models : the fugacity approach. 2021. J. Mark Parnis. 978-1-000-09499-2. Third. Boca Raton, FL. 1182869019. Donald Mackay (scientist).
3. Hodges G, Eadsforth C, Bossuyt B, Bouvy A, Enrici MH, Geurts M, Kotthoff M, Michie E, Miller D, Müller J, Oetter G . 6 . 2019. A comparison of log Kow (n-octanol–water partition coefficient) values for non-ionic, anionic, cationic and amphoteric surfactants determined using predictions and experimental methods. Environmental Sciences Europe. 31. 1. 10.1186/s12302-018-0176-7. free.
4. Hendriks AJ, van der Linde A, Cornelissen G, Sijm DT . The power of size. 1. Rate constants and equilibrium ratios for accumulation of organic substances related to octanol-water partition ratio and species weight . Environmental Toxicology and Chemistry . 20 . 7 . 1399–420 . July 2001 . 10.1002/etc.5620200703 . 11434281 . 25971836 .
5. Lipnick RL . Narcosis, electrophile and proelectrophile toxicity mechanisms: Application of SAR and QSAR. . Environmental Toxicology and Chemistry . 1989 . 8 . 1 . 1–2 . 10.1002/etc.5620080101 . free .
6. Hansch C . The advent and evolution of QSAR at Pomona College . Journal of Computer-aided Molecular Design . 25 . 6 . 495–507 . June 2011 . 21678028 . 10.1007/s10822-011-9444-y . 2011JCAMD..25..495H . 1399290 .
7. Book: Stockholm Convention on Persistent Organic Pollutents (POPs). 2018. Geneva. Annex D . Secretariat of the Stockholm Convention . United Nations Environment Programme .
8. Book: Evers AS, Crowder M . Mechanisms of Anesthesia and Consciousness . 106 . Barash PG, Cullen BF, Stoelting RK, Catalan MK, Stock MC . https://books.google.com/books?id=-YI9P2DLe9UC&pg=PA106. Clinical Anesthesia. 2009. Lippincott Williams & Wilkins. 978-0-7817-8763-5. en.
9. Dearden JC . Partitioning and lipophilicity in quantitative structure-activity relationships . Environmental Health Perspectives . 61 . 203–28 . September 1985 . 3905374 . 1568760 . 10.1289/ehp.8561203 .
10. Kellogg GE, Abraham DJ . Hydrophobicity: is LogP(o/w) more than the sum of its parts? . European Journal of Medicinal Chemistry . 35 . 7–8 . 651–61 . July 2000 . 10960181 . 10.1016/s0223-5234(00)00167-7 .
11. Book: Gani R, Abildskov J, Kontogeorgis G . Application of property models in chemical product design . Kontogeorgis GM, Gani R . https://books.google.com/books?id=mE1R5Q-s-48C&pg=PA345. Computer Aided Property Estimation for Process and Product Design: Computers Aided Chemical Engineering . 2004-06-30. Elsevier. 978-0-08-047228-7. en.
12. Cumming H, Rücker C . Octanol-Water Partition Coefficient Measurement by a Simple ¹H NMR Method . ACS Omega . 2 . 9 . 6244–6249 . September 2017 . 31457869 . 6644330 . 10.1021/acsomega.7b01102 .
13. Web site: Dortmund Data Bank (DDB) . Dortmund Data Bank Software & Separation Technology (DDBST) GmbH . 2020-05-20.