9 julio, 2024

Partition coefficient: partition, distribution, applications

He partition or distribution coefficient It is defined as the ratio of the concentration of a chemical species or solute between two equilibrium media. This medium can be a gas such as air; a liquid such as water or oil; or a complex mixture such as blood or other tissues.

The blood/air partition coefficient is important in explaining the gas exchange that occurs in the lungs between the blood and the atmosphere.

The image above demonstrates in a simplified and brilliant way the concept explained. Each figure represents an analyte, which is distributed and/or distributed between two immiscible phases: one upper and the other lower.

The green squares are located predominantly in the upper phase; while the red triangles dissolve more in the lower phase, and the purple circles choose to be located in the interface.

It can be seen how KD varies for each analyte. If KD is greater than 1, the analyte will partition further into the upper phase; if its value is close to 1, it will tend to be located in the interface; or if, on the contrary, KD is less than 1, it will be mainly in the lower phase.

One of the forms of partition coefficient is that existing between two immiscible liquids in equilibrium; as are the n-octane and water systems. This system has been used to establish an important property of a compound: its hydrophobic or hydrophilic character.

The value of the partition coefficient (P), or partition coefficient (K), serves to indicate the hydrophobic character of a drug. Thus it can be used to predict its process of intestinal absorption, distribution, metabolism and excretion.

[toc]

partition coefficient

Definition

The partition coefficient (K) of a substance, also called partition coefficient (P), is the ratio of dividing the concentrations of a substance into two phases; Consisting of the mixture of two solvents that are immiscible because they have different densities and natures.

The value of the partition (K) or partition (P) coefficient is related to the difference in solubility of the substance in the immiscible liquids that are part of the mixture.

K or P = [sustancia]1 / [sustancia]2

[sustancia]1 is the concentration of the substance in liquid 1. And [sustancia]2 is the concentration of the same substance in liquid 2.

Interpretation

If K or P has a value equal to 3, it indicates that the substance is 3 times more concentrated in liquid 1 than in liquid 2. But at the same time, it also indicates that the substance is more soluble in liquid 1.

Now, if the value of K or P is 0.3, the substance has a higher concentration in liquid 2; and therefore its solubility in liquid 2 is greater than in liquid 1.

Octanol/water partition coefficient

In some areas of research such as organic chemistry and pharmaceuticals, the mixture of liquids is made up of water and an apolar liquid such as n-octanol or 1-octanol, which is why we usually talk about the octanol partition coefficient. /water represented by Pow.

n-octanol has a density of 0.824 g/cm3; while water, as is known, has a density of approximately constant 1 g/cm3. Once the two liquids have equilibrated, n-octanol occupies the top of the mixture of immiscible liquids, which has been called liquid 1.

A hydrophobic substance will have a higher concentration in n-octanol, once the immiscible liquids have equilibrated. On the other hand, a hydrophilic substance will have a higher concentration in water.

restrictions

The partition or distribution coefficient is applied for non-ionized substances. In the event that the partition coefficient is being measured on an ionizable substance, the pH must be adjusted or a buffer used in the aqueous phase to ensure that the substance appears undissociated.

Surfactants or surfactants should not be used to determine the partition coefficient, since these substances, due to their amphiphilic nature, are located at the interface of immiscible liquids.

The n-octanol/water partition coefficient is usually expressed in logarithmic form; that is, as log P or log K, due to the range of the values ​​of P and K.

If the log of P for a substance is greater than 0, this is indicative that the substance is hydrophobic. Conversely, if the log of P is less than 0 (ie negative), then this indicates that the substance is hydrophilic.

Distribution coefficient (D)

The distribution coefficient (D) is the quotient between the concentration of all substances, ionized and non-ionized, in liquid 1 (n-octanol) and the concentration of the same substances in liquid 2 (water).

Once the value of the distribution coefficient (D) is obtained, it can be expressed as a logarithm of D due to the amplitude of the values ​​of D.

To obtain the distribution coefficient (D), the aqueous phase must be buffered; that is to say, at a certain pH, which must be indicated when referring to the value of the distribution coefficient obtained.

It is convenient to carry out the determination of D at pH 7.4. This pH corresponds to that of the blood and represents the conditions that the drugs or compounds will find in the intracellular environment and in the extracellular environment.

For a non-ionizable compound log D = log P, regardless of the pH used.

Experimental determination of a partition coefficient

There are several methods for the measurement of partition coefficient (P). Among them are the shake flask method and high performance liquid chromatography. Both require prior knowledge of the solubility of the test substance, both in n-octanol and in water.

shake flask method

The sample is dissolved in n-octanol saturated with water, which will be partitioned in a separation or decanting funnel with water saturated with n-octanol. Solvent saturation is necessary to avoid solvent transfer during the partitioning process.

The separating funnel is subjected to mechanical agitation for a certain time. It is then left to rest for a long time to ensure complete separation. To conclude, the phases are separated by settling.

Then, the concentration of the sample in each of the solvents is determined using a spectrophotometric method; eg UV-Visible or other method. Finally, with the data obtained, the partition coefficient and log P will be calculated.

This method has the advantage of being cheap, reproducible, and highly accurate. In short, it is the most reliable method for determining log P.

The main disadvantage of the method is that it is very time consuming: more than 24 hours to perform liquid equilibration, stirring and phase separation during the partitioning process. Furthermore, it is applicable only to substances soluble in n-octanol and water.

High Performance Liquid Chromatography Method

Log P can be obtained using the correlation of the retention time of the sample, with the retention time of a reference compound of similar chemical structure with a known P value.

It is a method in which the log P value is obtained in a duration of less than 20 minutes. It gives log p values ​​between 0 and 6, which corresponds only to hydrophobic substances.

The disadvantage is that the P value is determined by linear regression, so several compounds with a similar chemical structure to the sample and known log P values ​​must be used as reference.

Applications

Optimization of drug action

If a drug is ingested, it must reach the lumen of the small intestine, the site where most of the substances are absorbed. Then, it crosses the interior of the cells, dissolving in the lipid bilayer that is part of the membrane. This process is favored by the hydrophobic nature of the drug.

The drug must pass through the intestinal cells, crossing the basement membrane to reach the blood and reach the target receptors of the drug’s action. Some stages of the overall process are favored by the hydrophobic nature of the drug, but others are not.

A value of the partition coefficient must be found that allows all the processes necessary for the action of the drug and the physical well-being to be satisfactory.

The use of excessively hydrophobic drugs can be toxic, since their metabolism can produce potentially harmful metabolites. On the other hand, totally hydrophilic drugs present difficulty for their intestinal absorption.

agrochemicals

The activity of insecticides and herbicides is influenced by their hydrophobic character. However, hydrophobicity is associated with a longer half-life. Therefore, the polluting effect on the environment is prolonged, and may cause ecological damage.

Efficiently acting hydrophobic products with a shorter half-life must be produced.

Environmental care

Hydrophobic compounds are usually polluting the environment, since they are drained through the soil, being able to reach groundwater and later fluvial waters.

Knowing the partition coefficient of a compound, changes can be made to its chemical structure that modify its hydrophobicity in order to reduce its polluting action on the environment.

Hydrogeology uses the octanol/water partition coefficient (Kow) to control the flux of hydrophobic compounds, both in soil and groundwater.

References

Bannan, CC, Calabró, G., Kyu, DY, & Mobley, DL (2016). Calculating Partition Coefficients of Small Molecules in Octanol/Water and Cyclohexane/Water. Journal of chemical theory and computation, 12(8), 4015–4024. doi:10.1021/acs.jctc.6b00449 Wikipedia. (2019). Partition coefficient. Retrieved from: es.wikipedia.org National University of Colombia. (nd). Unit 8: Experimental determination of the distribution coefficient of barbiturates. [PDF]. Retrieved from: red.unal.edu.co The Sevier. (2019). Partition coefficient. Science Direct. Retrieved from: sciencedirect.com Seeboo Hemnath. (2019). Partition Coefficient: Definition and Calculation. Study. Retrieved from: study.com

Deja una respuesta

Tu dirección de correo electrónico no será publicada. Los campos obligatorios están marcados con *