Octanol-water partition coefficient

The octanol / water 2-phase system without additives

The n- octanol-water distribution coefficient K _ow is a distribution coefficient for the two-phase system of n- octanol and water. In the English-language literature in particular, the K _ow value is also referred to as the P value.

K _ow serves as a measure of the ratio 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 in the octanol-water system through association or dissociation in several species , each species is assigned its own K _ow value. Related to the K _ow value is the D value, which, dispensing with the distinction between different species, always only indicates the concentration ratio of the substance.

Applications

K _ow values ​​are used, among other things, to assess the environmental behavior of long-lived organic pollutants . Chemicals with high coefficients, for example, tend to accumulate in the fatty tissue of organisms ( bioaccumulation ).

In addition, the parameter plays an important role in drug research ( Rule of Five ) and in toxicology . Ernst Overton and Hans Meyer discovered as early as 1900 that anesthetics were more effective the higher their K _ow value ( Meyer-Overton rule ).

Furthermore, K _ow values ​​are very well suited to assess how a substance is distributed within a cell between the lipophilic biomembrane and the aqueous cytosol .

appraisal

Since the K _ow cannot be measured for all substances , there are various models for the prediction, e.g. B. through Quantitative Structure-Activity-Relationships ( QSAR ) or through Linear Free Energy Relationships ( LFER ).

There is also a variant of the UNIFAC model for estimating the octanol-water distribution coefficient.

Equations

• Definition of the K _ow or P value

The K _ow or P value only ever relates to one species of a substance:

${\displaystyle K_{\mathrm {ow} }=P={\frac {c_{o}^{S_{i}}}{c_{w}^{S_{i}}}}}$

With:

• ${\displaystyle c_{o}^{S_{i}}}$Concentration of the species i of a substance in the octanol-rich phase
• ${\displaystyle c_{w}^{S_{i}}}$Concentration of the species i of a substance in the water-rich phase

If different species appear in the octanol-water system as a result of dissociation or association, a distinction must be made between several P values ​​and one D value. On the other hand, if the substance is only present in a single species, the P and D values ​​are identical.

P is usually given in the form of the decadic logarithm as Log P (also Log P _ow or more rarely Log pOW):

${\displaystyle \log {P}=\log {\frac {c_{o}^{S_{i}}}{c_{w}^{S_{i}}}}=\log c_{o}^{S_{i}}-\log c_{w}^{S_{i}}}$

Log P is positive for lipophilic and negative for hydrophilic substances or species.

• Definition of the D value

The D value is always just the simple concentration ratio of a substance distributed between the octanol and water phases. It can also be calculated by adding up the concentrations of all n species in the octanol phase and the concentrations of all n species in the aqueous phase:

${\displaystyle D={\frac {c_{o}}{c_{w}}}={\frac {c_{o}^{S_{1}}+c_{o}^{S_{2}}+\dots +c_{o}^{S_{n}}}{c_{w}^{S_{1}}+c_{w}^{S_{2}}+\dots +c_{w}^{S_{n}}}}}$

With:

• ${\displaystyle c_{o}}$ Concentration of a substance in the octanol-rich phase
• ${\displaystyle c_{w}}$ Concentration of a substance in the water-rich phase

D-values ​​are also usually given in the form of the decadic logarithm as log D:

${\displaystyle \log {D}=\log {\frac {c_{o}}{c_{w}}}=\log c_{o}-\log c_{w}}$

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 the restriction to only one species , there is often a strong dependence on the pH-value of the aqueous phase for D-values.

Sample data

The values ​​listed are sorted according to the size of the distribution coefficient. Acetamide is hydrophilic, 2,2 ', 4,4', 5-pentachlorobiphenyl lipophilic.

material	log K OW	T	literature
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	Surroundings

See also

• Hydrophobic effect
• Dortmund database

literature

• Kai-Uwe Goss: The octanol / water partition coefficient - the panacea of ​​environmental chemistry? UWSF-ESPR series of articles: Persistent Organic Pollutants (POPs), UWSF 15 (4), pp. 273–279; doi : 10.1065 / uwsf2003.01.050 .
• Burkhard Heuel-Fabianek: Partition Coefficients (Kd) for the Modeling of Transport Processes of Radionuclides in Groundwater (PDF; 9.4 MB), JÜL reports, Forschungszentrum Jülich, No. 4375, 2014, ISSN  0944-2952 .

Individual evidence

1. Jump up ↑ J. Sangster: Octanol-Water Partition Coefficients: Fundamentals and Physical Chemistry , Vol. 2 of Wiley Series in Solution Chemistry , John Wiley & Sons, Chichester, 1997 .
2. ^ BW Urban: The Meyer-Overton Rule: What's Left? (PDF; 305 kB).
3. ^ John C. Dearden: Partitioning and Lipophilicity in Quantitative Structure-Activity Relationships . Environ. Health Perspect. 1985 September; 61: 203-228; PMC 1568760 (free full text, PDF).
4. ↑ GE Kellogg G, DJ Abraham: Hydrophobicity: is LogP (o / w) more than the sum of its parts? , in: Eur. J. Med. Chem. , 2000 , 35 , 651-661. PMID 10960181
5. ↑ Gudrun Wienke: Measurement and precalculation of n-octanol / water distribution coefficients , doctoral thesis, Univ. Oldenburg, 1-172, 1993.
6. ↑ Dortmund database
7. ↑ R. Wolfenden, in: Biochem. J. , 1978 , 17 , 201-204.
8. ↑ ^{a b} R. Collander, in: Acta Chem. Scand. , 1951 , 5 , 774-780.
9. ↑ KE Whitehead, CJ Geankoplis in: Ind. Eng. Chem. , 1955 , 47 , 2114-2122.
10. ↑ ^{a b} S. P. Wasik, YB Tewari, MM Miller, DE Martire, NBS Techn. Rep., Rep.No. NBSIR 81-2406, pp. 1-56, 1981.
11. ^ J. Brodsky, K. Ballschmiter, Fresenius Z. Anal. Chem. , 1988 , 331 , 295-301.

Web links

• Virtual Computational Chemistry Laboratory interactive calculation and interactive comparison of several methods
• ACD's LogP calculation software (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