LogP
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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.
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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:
Pros:
- 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)
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.
Pros:
- 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.
Prediction
Computer programs calculate logP several different ways:
- Fragment Method
- 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.
- Other methods
- Many programs utilize combinations of the above two methods. Other methods include Kohonen maps.
See also
External links
LogP calculators
- http://www.daylight.com/daycgi/clogp
- http://www.molinspiration.com/cgi-bin/properties (interactive logP calculator)
- http://www.securebio.umb.edu/daycgi/JMEclogp.pl (applet for CLogP)
- http://intro.bio.umb.edu/111-112/OLLM/111F98/newclogp.html
- http://www.pirika.com/chem/TCPEE/LOGKOW/ourlogKow.htm
- http://www.vcclab.org/lab/alogps (applet for interactive logP calculation and comparison of several methods)
Further information
- http://www.daylight.com/papers/cp12.html
- http://www.vcclab.org/online.html contains list of on-line calculation resources
- http://www.securebio.umb.edu/dayhtml/doc/clogp/
Commercial products
- http://www.acdlabs.com/products/phys_chem_lab/logp/competit1.html
- http://www.organic-chemistry.org/prog/peo/cLogP.html
- http://www.biobyte.com/bb/prod/clogp40.html
- http://www.logp.com/