Octanol-water partition coefficient

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.^{[citation needed]}

If a substance is present as several

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.^{[citation needed]}

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.^[9]

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:

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

with:

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

${\displaystyle \log {P}=\log {\frac {c_{o}^{S_{i}}}{c_{w}^{S_{i}}}}=\log c_{o}^{S_{i}}-\log c_{w}^{S_{i}}}$ Log P is positive for lipophilic and negative for hydrophilic substances or species.

• Definition of the D-value

The 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:

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

with:

• ${\displaystyle c_{o}}$ concentration of the substance in the octanol-rich phase
• ${\displaystyle c_{w}}$ 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:

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

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 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.

See also

• Hydrophobic effect
• Dortmund Data Bank

References