Partition coefficients

Partition coefficients are defined as the concentration ratio of a chemical between two media at
equilibrium (see also Chapter 1.04). The media can be gases such as air, liquids such as water or
olive oil, or complex mixtures such as blood or other tissues. In the physical sciences, a partition
coefficient (P) or distribution coefficient (D) is the ratio of concentrations of a compound in a
mixture of two immiscible solvents at equilibrium. This ratio is therefore a comparison of the
solubilities of the solute in these two liquids. The partition coefficient generally refers to the
concentration ratio of un-ionized species of compound, whereas the distribution coefficient refers
to the concentration ratio of all species of the compound (ionized plus un-ionized).[1]

In the chemical and pharmaceutical sciences, both phases usually are solvents.[2] Most
commonly, one of the solvents is water, while the second is hydrophobic, such as 1-octanol.[3]
Hence the partition coefficient measures how hydrophilic ("water-loving") or hydrophobic
("water-fearing") a chemical substance is. Partition coefficients are useful in estimating the
distribution of drugs within the body. Hydrophobic drugs with high octanol/water partition
coefficients are mainly distributed to hydrophobic areas such as lipid bilayers of cells. Conversely,
hydrophilic drugs (low octanol/water partition coefficients) are found primarily in aqueous regions
such as blood serum.[4]

If one of the solvents is a gas and the other a liquid, a gas/liquid partition coefficient can be
determined. For example, the blood/gas partition coefficient of a general anesthetic measures how
easily the anesthetic passes from gas to blood.[5] Partition coefficients can also be defined when
one of the phases is solid, for instance, when one phase is a molten metal and the second is a solid
metal,[6] or when both phases are solids.[7] The partitioning of a substance into a solid results in a
solid solution.

Partition coefficients can be measured experimentally in various ways (by shake-flask, HPLC,
etc.) or estimated by calculation based on a variety of methods (fragment-based, atom-based,
etc.).The partition coefficient, abbreviated P, is defined as a particular ratio of the concentrations
of a solute between the two solvents (a biphase of liquid phases), specifically for un-ionized
solutes, and the logarithm of the ratio is thus log P.[10]:275ff When one of the solvents is water
and the other is a non-polar solvent, then the log P value is a measure of lipophilicity or
hydrophobicity.The distribution coefficient, log D, is the ratio of the sum of the concentrations of
all forms of the compound (ionized plus un-ionized) in each of the two phases, one essentially
always aqueous; as such, it depends on the pH of the aqueous phase, and log D = log P for non-
ionizable compounds at any pH.[13][14]A number of methods of measuring distribution
coefficients have been developed, including the shake-flask, separating funnel method, reverse-
phase HPLC, and pH-metric techniques.[10]:280

Separating-funnel method Edit

In this method the solid particles present into the two immiscible liquids can be easily separated
by suspending those solid particles directly into these immiscible or some what miscible liquids

Shake flask-type Edit

The classical and most reliable method of log P determination is the shake-flask method, which
consists of dissolving some of the solute in question in a volume of octanol and water, then
measuring the concentration of the solute in each solvent.[38][39] The most common method of
measuring the distribution of the solute is by UV/VIS spectroscopy.[38]

HPLC-based Edit
A faster method of log P determination makes use of high-performance liquid chromatography.
The log P of a solute can be determined by correlating its retention time with similar compounds
with known log P values.[40]The magnitude of (K) is determined by the relative affinity of the
solute for the two phases. Those solutes interacting more strongly with the stationary phase will
exhibit a larger distribution coefficient and will be retained longer in the chromatographic system.
Molecular interaction results from intermolecular forces of which there are three basic types.
Molecular Forces

All intermolecular forces are electrical in nature. The three different types are termed dispersion
forces, polar forces and ionic forces. All interactions between molecules are composites of these
three forces.

Dispersion Forces
Dispersion forces were first described by London (3), and for this reason were originally called
'London's dispersion forces'. London's name has now been dropped and they are now simply
referred to as 'dispersion' forces. They arise from charge fluctuations throughout a molecule
resulting from electron/nuclei vibrations.

Polar Forces
Polar interactions arise from electrical forces between localized charges resulting from permanent
or induced dipoles. They cannot occur in isolation, but must be accompanied by dispersive
interactions and under some circumstances may also be combined with ionic interactions. Polar
interactions can be very strong and result in molecular associations that approach, in energy, that
of a weak chemical bond. Examples of such instances are 'hydrogen bonding' and in particular the
association of water with itself.