LogP

LogP also called Log Kow , is a measurement of the differential Solubilité of chemical compounds in two Solvant S (coefficient of division Octanol/Eau).

LogP is equal to the logarithm of the report/ratio of the concentrations of the substance studied in the octanol and water. LogP = Log (C_oct/C_eau). This value makes it possible to apprehend the character hydrophobic Hydrophile or (lipophilic) of a molecule. Indeed, if LogP is positive and very high, that expresses the fact that the molecule considered is much more soluble in the octanol than in water, which reflects its character Lipophile, and conversely. A value of LogP=0 means that the molecule is distributed in an equal way between the two phases and C_oct=C_eau. The LogD is more refined measurement of the logP taking account of the modification of this one according to the pH of the aqueous phase and the PKa of the studied compound.

Applications

The logP gives an account of the tendency of a molecule to accumulate in the biological membranes of the living organisms. If it is high, the risk of bio-accumulation is important.

Absorption of the drugs

Various statistical studies highlighted the optimal values of logP so that a compound (typically a drug) is absorbed by the human body:

Penetration with the brain: 2,0
oral Absorption: 1,8
sublingual Absorption: 5,5
Absoption percutaneous: 2,6

Anesthetic capacity

The theory of Meyer-Overton which dates from the beginning of the 20th century of the general Anesthésie observes a positive correlation between the effect anesthetic of a molecule and its coefficient of partition, which was then water/olive oil.

Estimate of the logP

Choice of solvent

Although measurement is most frequently done between the octanol and water, other solvents such as the Chloroforme, the Hexane or the propylene glycol diperlargonate are also used. The difference of logP observed between two solvents like the octanol and hexane makes it possible for example to isolate the contribution from the Hydrogen bonds of the studied compound.

Method of the agitated bottle

Most traditional and most reliable of the methods of determination of the logP is the method known as of the " bottle agité".

This method consists in mixing a known quantity of aqueous solution in a known volume of octanol and water, then to measure the distribution of the aqueous solution in each solvent. The most current method to measure this distribution is the spetroscopy UV/Visible.

This method comprises advantages:

most precise Méthode
Précise for the broadest range of aqueous solutions (neutral as charged)
the chemical structure does not need to be known before proceeding.

and of the disadvantages:

the time necessary (30 minutes per sample)
the octanol and water must be premixed and balanced (that takes at least 24 hours)
It is necessary to await solubilization supplements
the concentration ratio/UV/Visible answer must be linear in the range of concentrations of the aqueous solution (Loi of Beer-Lambert)

Determination by HPLC

A faster method of determination of the logP uses the liquid chromatography high efficiency (HPLC).

The logP of an aqueous solution can be given by correlation between its time of retention and that of similar compounds with a known logP.

This method with the advantage of being fast (5-20 minutes by sample), but presents certain disadvantages:

the chemical structure of the aqueous solution must be known before proceeding
Since the logP is usually determined by linear regression, one must know the logP several compounds with a similar structure.
Of the classes of chemical compounds different has different coefficients of correlation, the comparison between the classes is not valid.

Prediction

Simulation programs of logP exist. They function according to different modes.

the method of the fragments

It was shown that the logP of a compound is more or less equal to the sum of the logP of its fragments. ** The fragmentary values logP were statistically given. This method gives mitigated results and a precision from + 0,1 unit does not exceed.

Réseau of neurons

the networks of neurons are usually very good to calculate logP when one has them " entraînés" with similar compounds of known structures and logP.

Other methods

the majority of the programs use a combination of the two methods described above.
Of others uses the charts of Kohonen.

See too

QSAR

External bonds

Calculators of LogP

http://www.molinspiration.com/cgi-bin/properties (interactive logP calculator)
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 calculation and comparison interactives of several methods

Further information

http://www.daylight.com/papers/cp12.html
http://www.vcclab.org/online.html summarized of the interactive tools for calculations of logP
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/

Computer data

http://www-ra.informatik.uni-tuebingen.de/software/joelib/api/joelib/desc/types/LogP.html

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