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LogP is a measure of differential solubility of a compound in two solvents. The log ratio of the concentrations of the solute in the solvent is called LogP or the Partition Coefficient. The most well known of these partition coefficients is the one based on the solvents Octanol and Water. The octanol-water partition coefficient is a measure of the hydrophobicity and hydrophilicity of a substance. In the context of drug-like substances, hydrophobicity is related to absorption, bioavailability, hydrophobic drug-receptor interactions, metabolism and toxicity. A solvent is a liquid that dissolves a solid, liquid, or gaseous solute, resulting in a solution. ...
A chemical compound is a chemical substance formed from two or more elements, with a fixed ratio determining the composition. ...
A solvent is a liquid that dissolves a solid, liquid, or gaseous solute, resulting in a solution. ...
This page refers to concentration in the chemical sense. ...
A substance is soluble in a fluid if it dissolves in the fluid. ...
Octanol is a higher alcohol with eight carbon atoms and a general formula of C8H18O. H H H H H H H H | | | | | | | | H - C - C - C - C - C - C - C - C - OH | | | | | | | | H H H H H H H H Water/Octanol Partitioning Octanol and water are immiscible. ...
A falling water droplet Water (from the Anglo-Saxon and Low German wæter) is a colourless, tasteless, and odourless substance that is essential to all known forms of life and is the most universal solvent. ...
In chemistry, hydrophobic or lipophilic species, or hydrophobes, tend to be electrically neutral and nonpolar, and thus prefer other neutral and nonpolar solvents or molecular environments. ...
The adjective hydrophilic describes something that likes water (from Greek hydros = water; philos = friend). ...
Absorption has a number of meanings: In physics absorption is a process in which particles of some sort encounter another material and are taken up by or even disappear in it. ...
In pharmacology, bioavailability is a term used to describe a pharmacokinetic property of drugs, namely, the fraction of a dose which reaches the systemic circulation. ...
Receptor may refer to: In telecommunication, a receiver. ...
Santorio Santorio (1561-1636) in his steelyard balance, from Ars de statica medecina, first published 1614 Metabolism (from μεταβολισμος(metavallo), the Greek word for change), in the most general sense, is the ingestion and breakdown of complex compounds, coupled with the liberation of energy, and the consequent generation of waste...
Toxicity is a measure to the degree to which something is toxic or poisonous. ...
Application
Shake Flask Method The classical and most reliable method of LogP determination is the Shake-flask method, which consists of mixing a known amount of solute in a known volume of octanol and water, then measuring the distribution of the solute in each solvent. The most common method of measuring the distribution of the solute is by UV/VIS spectroscopy. There are a number of pros and cons to this method: Ultraviolet-Visible spectroscopy or Ultraviolet-Visible spectrophotometry (UV/VIS) involves the spectroscopy of photons (spectrophotometry). ...
Pros:
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- Most accurate method
- Accurate for broadest range of solutes (neutral and charged compounds applicable)
- Chemical structure does not have to be known beforehand.
Cons: -
- Time consuming (>30 minutes per sample)
- Octanol and water must be premixed and equilibrated (takes at least 24hrs to equilibrate)
- Complete solubility must attained.
- The concentration vs. UV-Vis response must be linear over the solute's concentration range. (See Beer-Lambert law)
In optics, the Beer-Lambert law, also known as Beers law or the Beer-Lambert-Bouguer law is an empirical relationship in relating the absorption of light to the properties of the material the light is travelling through. ...
HPLC determination A faster method of LogP determination makes use of high-performance liquid chromatography. The LogP of a solute can be determined by correlating it's retention time with similar compounds with known logP values. Chromatography is a family of analytical chemistry techniques for the separation of mixtures. ...
(Note: The term correlation is sometimes used to specify the cross-correlation of two functions, and sometimes to specify the correlation coefficient between two random variables. ...
Pros:
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- Fast method of determination (5-20 minutes per sample)
Cons: -
- The solute's chemical structure must be known beforehand.
- Since the value of LogP is determined by linear regression, several compounds with similar structures must have known logP values.
- Different chemical classes will have different correlation coefficients, between-class comparisons are not significant.
Chemical structure is the arrangement of atoms within a molecule, usually linked by covalent bonds. ...
In statistics, linear regression is a method of estimating the conditional expected value of one variable y given the values of some other variable or variables x. ...
In probability theory and statistics, correlation, also called correlation coefficient, is a numeric measure of the strength of linear relationship between two random variables. ...
Prediction Computer programs calculate logP several different ways: - It has been shown that the logP of compound can be determined by the sum of its fragments. Fragmentary logP values have been determined statistically. This method gives mixed results and is generally not trusted to have accuracy of more than +/- 0.1 units.
- Neural networks are usually very successful for calculating logP values when trained with compounds that have similar chemical structures and known logP values.
- Many programs utilize combinations of the above two methods. Other methods include Kohonen maps.
A neural network is an interconnected group of neurons. ...
The self-organising map (SOM) is a method for unsupervised learning, based on a grid of artificial neurons whose weights are adapted to match input vectors in a training set. ...
See also ADME, CLogP, QSAR ADME is an acronym for Absorption, Distribution, Metabolization and Excretion and describes the effectiveness of a pharmaceutical compound within an organism. ...
CLogP is shorthand for computed LogP, a measure of differential solubility or rather hydrophobicity as the octanol/water partition coefficient. ...
QSAR (Quantitative Structure-Activity Relationship, sometimes the A stands also for Affinity=reactivity) is the quantitative correlation of the biological (ecological, toxicological or pharmacological) activity to the structure of chemical compounds, which allows the prediction of the so-called drug efficacy of a structurally related compound. ...
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