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| <!--This article is in Commonwealth English-->
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| In the [[physical sciences]], a '''partition'''- or '''distribution-coefficient''' is the ratio of [[concentration]]s of a [[chemical compound|compound]] in a mixture of two [[immiscible]] [[phase (matter)|phases]] at [[partition equilibrium|equilibrium]]. These coefficients are a measure of the difference in [[solubility]] of the compound in these two phases.
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| In the [[chemistry|chemical]] and [[pharmaceutical sciences]], the two phases are often restricted to mean two immiscible [[solvent]]s. In this context, a partition coefficient is the ratio of concentrations of a compound in the two phases of a mixture of two immiscible liquids at equilibrium.<ref name="Leo">{{cite journal |author=Leo A, Hansch C, and Elkins D|title=Partition coefficients and their uses |journal=Chem Rev |volume=71 |issue=6 |pages=525–616 |year=1971 |doi=10.1021/cr60274a001}}</ref> Normally one of the solvents chosen is [[water]] while the second is [[hydrophobic]] such as [[1-octanol]].<ref name="Sangster">{{cite book |last=Sangster |first=James |title=Octanol-Water Partition Coefficients: Fundamentals and Physical Chemistry, Vol. 2 of Wiley Series in Solution Chemistry |publisher=John Wiley & Sons Ltd. |year=1997 |location=Chichester |pages=178 pages |isbn=978-0-471-97397-3}}</ref> Hence both the partition and distribution coefficient are measures of how [[hydrophilic]] ("water-loving") or [[hydrophobic]] ("water-fearing") a chemical substance is. In medical practice, partition coefficients are useful for example in estimating [[distribution (pharmacology)|distribution]] of drugs within the body. Hydrophobic drugs with high octanol/water partition coefficients are preferentially distributed to hydrophobic compartments such as [[lipid bilayers]] of cells while hydrophilic drugs (low octanol/water partition coefficients) preferentially are found in hydrophilic compartments such as [[Blood plasma|blood serum]].
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| If one of the solvents is a gas and the other a liquid, the "gas/liquid partition coefficient" is the same as the dimensionless form of the [[Henry's law]] constant. For example, the [[blood/gas partition coefficient]] of a [[general anesthetic]] measures how easily the anesthetic passes from gas to blood. Partition coefficients can also be used when one or both solvents is a [[solid]] (see [[solid solution]]).
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| The phrase "partition coefficient" is now considered obsolete by [[IUPAC]], and "partition constant", "partition ratio", or "distribution ratio" are all more appropriate terms that should be used.<ref name="isbn0-86542-684-8">{{cite book | author = Wilkinson, Andrew M.; McNaught, Alan D. | authorlink = | editor = | others = | title = Compendium of Chemical Terminology: IUPAC Recommendations | edition = | language = | publisher = Blackwell Science | location = Oxford | year = 1997 | origyear = | pages = | quote = | isbn = 0-86542-684-8 | oclc = | doi = 10.1351/goldbook | url = | accessdate = | chapter = Partition Coefficient | chapterurl = http://goldbook.iupac.org/P04437.html }}</ref>
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| ==Partition coefficient and log P==
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| The '''partition coefficient''' is a ratio of concentrations of un-[[Ionization|ionized]] compound between the two solutions. To measure the '''partition coefficient''' of ionizable solutes, the [[pH]] of the aqueous phase is adjusted such that the predominant form of the compound is un-ionized. The [[logarithm]] of the ratio of the [[concentration]]s of the un-ionized [[solution|solute]] in the solvents is called '''log ''P''''': The log P value is also known as a measure of [[lipophilicity]].
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| :* <math>\log\ P_{\rm oct/wat} = \log\Bigg(\frac{\big[\rm{solute}\big]_{\rm octanol}}{\big[\rm{solute}\big]_{\rm water}^{\rm un-ionized}}\Bigg)</math>
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| ==Distribution coefficient and log D==
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| The '''distribution coefficient''' 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. For measurements of '''distribution coefficient''', the pH of the aqueous phase is [[Buffer solution|buffered]] to a specific value such that the pH is not significantly perturbed by the introduction of the compound. The logarithm of the ratio of the sum of concentrations of the solute's various forms in one solvent, to the sum of the concentrations of its forms in the other solvent is called '''log D''':
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| :* <math>\log\ D_{\rm oct/wat} = \log\Bigg(\frac{\big[\rm{solute}\big]_{\rm octanol}}{\big[\rm{solute}\big]_{\rm water}^{\rm ionized}+\big[\rm{solute}\big]_{\rm water}^{\rm neutral}}\Bigg)</math>
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| In addition, log D is pH dependent, hence one must specify the pH at which the log D was measured. Of particular interest is the log D at pH = 7.4 (the physiological pH of blood serum).
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| For un-ionizable compounds, log P = log D at any pH.
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| ==Applications==
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| ===Pharmacology===
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| A drug's distribution coefficient strongly affects how easily the drug can reach its intended target in the body, how strong an effect it will have once it reaches its target, and how long it will remain in the body in an active form.
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| LogP is one criterion used in [[medicinal chemistry]] to assess the [[druglikeness]] of a given molecule, and used to calculate [[lipophilic efficiency]], a function of potency and LogP that evaluate the quality of research compounds.<ref>{{Cite journal | title = Role of Physicochemical Properties and Ligand Lipophilicity Efficiency in Addressing Drug Safety Risks| author = Edwards MP, Price DA | doi = 10.1016/S0065-7743(10)45023-X | year = 2010 | journal = Annual Reports in Medicinal Chemistry | pages = 381–391| volume = 45 | series = Annual Reports in Medicinal Chemistry | isbn = 978-0-12-380902-5}}</ref><ref name="pmid17971784">{{cite journal | author = Leeson PD, Springthorpe B | title = The influence of drug-like concepts on decision-making in medicinal chemistry | journal = Nat Rev Drug Discov | volume = 6 | issue = 11 | pages = 881–90 |date=November 2007 | pmid = 17971784 | doi = 10.1038/nrd2445 | url = }}</ref> For a given compound [[lipophilic efficiency]] is defined as the [[IC50|pIC<sub>50</sub>]] (or [[EC50|pEC<sub>50</sub>]]) of interest minus the LogP of the compound.
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| ====Pharmacokinetics====
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| In the context of [[pharmacokinetics]] (what the body does to a drug), the distribution coefficient has a strong influence on [[ADME]] properties of the drug. Hence the hydrophobicity of a compound (as measured by its distribution coefficient) is a major determinant of how [[Druglikeness|drug-like]] it is. More specifically, for a drug to be orally absorbed, it normally must first pass through [[lipid bilayer]]s in the intestinal [[epithelium]] (a process known as [[transcellular]] transport). For efficient transport, the drug must be hydrophobic enough to partition into the lipid bilayer, but not so hydrophobic, that once it is in the bilayer, it will not partition out again.<ref name="Kubinyi">{{cite journal |author=Kubinyi H |title=Nonlinear dependence of biological activity on hydrophobic character: the bilinear model|journal= Farmaco [Sci] |volume=34 |issue=3 |pages=248–76 |year= 1979 |pmid= 43264 }}</ref> Likewise, hydrophobicity plays a major role in determining where drugs are distributed within the body after absorption and as a consequence in how rapidly they are metabolized and excreted.
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| ====Pharmacodynamics====
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| In the context of [[pharmacodynamics]] (what a drug does to the body), the [[hydrophobic effect]] is the major driving force for the binding of drugs to their [[receptor (biochemistry)|receptor]] targets.<ref name="Eisenberg">{{cite journal |author=Eisenberg D, McLachlan AD|title=Solvation energy in protein folding and binding|journal= Nature |volume= 319 |issue= 6050 |pages= 199–203 |year= 1986 |pmid= 3945310 | doi = 10.1038/319199a0|bibcode = 1986Natur.319..199E }}</ref><ref name="Miyamoto">{{cite journal |author=Miyamoto S, Kollman PA |title=What determines the strength of noncovalent association of ligands to proteins in aqueous solution?|journal= Proc Natl Acad Sci USA |volume= 90|issue= 18 |pages= 8402–6 |year= 1993 |pmid= 8378312 | doi = 10.1073/pnas.90.18.8402 |pmc=47364|bibcode = 1993PNAS...90.8402M }}</ref> On the other hand, hydrophobic drugs tend to be more toxic because they, in general, are retained longer, have a wider distribution within the body (e.g., [[intracellular]]), are somewhat less selective in their binding to proteins, and finally are often extensively metabolized. In some cases the metabolites may be chemically reactive. Hence it is advisable to make the drug as hydrophilic as possible while it still retains adequate binding affinity to the therapeutic protein target.<ref name="Pliska">{{cite book |last = Pliska |first = Vladimir |coauthors = Testa B, Van De Waterbeemd H |title = Lipophilicity in Drug Action and Toxicology |publisher = John Wiley & Sons Ltd. |year = 1996 |location = New York |pages = 439 pages |isbn = 978-3-527-29383-4}}</ref> Therefore the ideal distribution coefficient for a drug is usually intermediate (not too hydrophobic nor too hydrophilic).
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| ===Consumer Products===
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| Many other industries take into account distribution coefficients for example in the formulation of make-up, topical ointments, dyes, hair colors and many other consumer products.
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| ===Agrochemicals===
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| Hydrophobic insecticides and herbicides tend to be more active. Hydrophobic agrochemicals in general have longer half lives and therefore display increased risk of adverse environmental impact.
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| ===Metallurgy=== | |
| In [[metallurgy]], the partition coefficient is an important factor in determining how different impurities are distributed between molten and solidified metal. It is a critical parameter for purification using [[zone melting]], and determines how effective an impurity can be removed using [[directional solidification]], described by the [[Scheil equation]].
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| ===Environmental===
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| The hydrophobicity of a compound can give scientists an indication of how easily a compound might be taken up in groundwater to pollute waterways, and its toxicity to animals and aquatic life.<ref name="Cronin">{{cite journal |author= Cronin D, Mark T |title=The Role of Hydrophobicity in Toxicity Prediction|journal=Current Computer - Aided Drug Design |volume=2 |issue=4 |pages=405–413 |year= 2006| doi = 10.2174/157340906778992346}}</ref> Distribution coefficients may be measured or predicted for compounds currently causing problems or with foresight to gauge the structural modifications necessary to make a compound environmentally more friendly in the research phase.
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| In the field of [[hydrogeology]], the octanol water partition coefficient, or K<sub>ow</sub>, is used to predict and model the migration of dissolved hydrophobic organic compounds in soil and groundwater.
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| ==Measurement==
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| ===Shake flask (or tube) method===
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| [[Image:Separatory funnel.jpg|thumb|Two phase system, hydrophobic (top) and hydrophilic (bottom) for measuring the partition coefficient of compounds.]]
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| 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. 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:
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| Pros:
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| :* Most accurate method
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| :* Accurate for broadest range of solutes (neutral and charged compounds applicable)
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| :* Chemical structure does not have to be known beforehand.
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| Cons:
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| :* Time consuming (>30 minutes per sample)
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| :* Octanol and water must be premixed and equilibrated (takes at least 24 hours to equilibrate)
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| :* Complete solubility must be attained, and it can be difficult to detect small amounts of undissolved material.
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| :* The concentration vs. UV-Vis response must be linear over the solute's concentration range. ''(See [[Beer-Lambert law]])''
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| :* If the compound is extremely lipophilic or hydrophilic, the concentration in one of the phases will be exceedingly small, and thus difficult to quantify.
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| :* Relative to chromatographic methods, large amounts of material are required.
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| As an alternative to [[UV/VIS spectroscopy]] other methods can be used to measure the distribution, one of the best is to use a [[carrier free]] [[radiotracer]]. In this method (which is well suited for the study of the extraction of [[metals]]) a known amount of a [[radioactive]] material is added to one of the phases. The two phases are then brought into contact and mixed until [[chemical equilibrium|equilibrium]] has been reached. Then the two phases are separated before the radioactivity in each phase is measured. Using an energy dispersive detector (such as a high purity [[germanium]] detector) allows the use of several different radioactive metals at once, whereas the simpler gamma ray detectors only allow one radioactive element to be used in the sample.
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| If the volume of both of the phases are the same then the math is very simple.
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| For a hypothetical solute (''S'')
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| ''D'' or ''P'' = radioactivity of the organic phase / radioactivity of the aqueous phase
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| ''D'' or ''P'' = [S<sub>organic</sub>]/[S<sub>aqueous</sub>]
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| In such an experiment using a carrier free radioisotope the solvent loading is very small, hence the results are different from those obtained when the concentration of the solute is very high. A disadvantage of the carrier free radioisotope experiment is that the solute can adsorb to the surfaces of the glass (or plastic) equipment or at the interface between the two phases. To guard against this the mass balance should be calculated.
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| It should be the case that:
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| radioactivity of the organic phase + radioactivity of the aqueous phase = initial radioactivity of the phase bearing the radiotracer
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| For nonradioactive metals, it is possible in some cases to use [[ICP-MS]] or [[ICP-AES]]. Sadly ICP methods often suffer from many interferences that do not apply to [[gamma spectroscopy]] hence the use of radio-tracers (counted by gamma ray spectroscopy) is often more straightforward.
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| ===HPLC determination===
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| A faster method of log ''P'' determination makes use of [[High-performance liquid chromatography#High performance liquid chromatography .28HPLC.29|high-performance liquid chromatography]]. The log ''P'' of a solute can be determined by [[correlation|correlating]] its [[retention time]] with similar compounds with known log ''P'' values.<ref name="pmid15214672">{{cite journal | author = Valkó K | title = Application of high-performance liquid chromatography based measurements of lipophilicity to model biological distribution | journal = Journal of Chromatography A | volume = 1037 | issue = 1–2 | pages = 299–310 | year = 2004 | pmid = 15214672 | doi = 10.1016/j.chroma.2003.10.084 }}</ref>
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| Pros:
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| :* Fast method of determination (5-20 minutes per sample)
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| Cons:
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| :* The solute's [[chemical structure]] must be known beforehand.
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| :* Since the value of log ''P'' is determined by [[linear regression]], several compounds with similar structures must have known log ''P'' values.
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| :* Different chemical classes will have different [[parameter|regression parameters]], hence extrapolations to other chemical classes (applying a regression equation derived from one chemical class to a second chemical class) are not reliable.
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| ===Electrochemical methods===
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| In the recent past some experiments using polarized liquid interfaces have been used to examine the thermodynamics and kinetics of the transfer of charged species from one phase to another. Two main methods exist.
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| *[[ITIES]], '''I'''nterfaces between '''t'''wo '''i'''mmiscible '''e'''lectrolyte '''s'''olutions,<ref name="pmid12948031">{{cite journal | author = Ulmeanu SM, Jensen H, Bouchard G, Carrupt PA, Girault HH | title = Water-oil partition profiling of ionized drug molecules using cyclic voltammetry and a 96-well microfilter plate system | journal = Pharm. Res. | volume = 20 | issue = 8 | pages = 1317–22 | year = 2003 | pmid = 12948031 | doi = 10.1023/A:1025025804196 }}</ref> which, for example, has been used at [[Ecole Polytechnique Fédérale de Lausanne]].
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| * Droplet experiments, which have been used by Alan Bond, Frank Marken, and the team at the Ecole Polytechnique Fédérale de Lausanne. Here a reaction at a triple interface between a conductive solid, droplets of a redox active liquid phase and an electrolyte solution have been used to determine the energy required to transfer a charged species across the interface.<ref name="Bond_1994">{{cite journal | author = Bond AM, Marken F | title = Mechanistic aspects of the electron and ion transport processes across the electrode | journal = [[Journal of Electroanalytical Chemistry]] | volume = 372 | issue = 1–2 | pages = 125–135 | year = 1994| doi = 10.1016/0022-0728(93)03257-P }}</ref>
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| ==Prediction==
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| [[Quantitative structure-property relationship]] (QSPR) algorithms calculate a log ''P'' in several different ways: | |
| * Atomic based prediction (atomic contribution; AlogP, XlogP,<ref>{{cite journal|last=Cheng|first=Tiejun|coauthors=Yuan Zhao; Xun Li; Fu Lin; Yong Xu; Xinglong Zhang; Yan Li; Renxiao Wang; Luhua Lai|title=Computation of Octanol−Water Partition Coefficients by Guiding an Additive Model with Knowledge|journal=Journal of Chemical Information and Modeling|year=2007|volume=47|issue=6|pages=2140–2148|doi=10.1021/ci700257y|pmid=17985865|url=http://www.sioc-ccbg.ac.cn/?p=42&software=xlogp3}}</ref> MlogP, etc.)
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| :A conventional method for predicting log ''P'' is to parameterize the contributions of various atoms to the over-all molecular partition coefficient, which produces a [[parametric model]]. This parametric model can be estimated using constrained [[Least squares|least-squares]] [[estimation theory|estimation]], using a [[training set]] of compounds with experimentally measured partition coefficients.<ref name="Ghose_1986">{{cite journal | author = Ghose AK, Crippen GM | title=Atomic Physicochemical Parameters for Three-Dimensional Structure-Directed Quantitative Structure-Activity Relationships I. Partition Coefficients as a Measure of Hydrophobicity | journal= Journal of Computational Chemistry | volume= 7 | issue= 4 | pages = 565–577 | year= 1986| doi = 10.1002/jcc.540070419}}</ref><ref name="Ghose_1998">{{cite journal |author=Ghose AK, Viswanadhan VN, Wendoloski, JJ |title=Prediction of Hydrophobic (Lipophilic) Properties of Small Organic Molecules Using Fragmental Methods: An Analysis of AlogP and ClogP Methods | journal = Journal of Physical Chemistry A |volume=102 |issue=21 |pages=3762–3772 |year= 1998 |doi=10.1021/jp980230o }}</ref><ref name="Moriguchi">{{cite journal |author=Moriguchi I, Hirono S, Liu Q, Nakagome I, Matsushita Y |title=Simple method of calculating octanol/water partition coefficient|journal= Chem Pharm Bull |volume=40 |issue=1 |pages=127–130 |year= 1992 }}</ref> In order to get reasonable correlations, the most common elements contained in drugs (hydrogen, carbon, oxygen, sulfur, nitrogen, and halogens) are divided into several different atom types depending on the environment of the atom within the molecule. While this method is generally the least accurate, the advantage is that it is the most general, being able to provide at least a rough estimate for a wide variety of molecules.
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| * Fragment based prediction ([[Group contribution method|group contribution]]; ClogP, etc.)
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| :It has been shown that the log ''P'' of a compound can be determined by the sum of its non-overlapping molecular fragments (defined as one or more atoms covalently bound to each other within the molecule). Fragmentary log ''P'' values have been determined in a statistical method analogous to the atomic methods (least squares fitting to a training set). In addition, [[Hammett equation|Hammett type corrections]] are included to account of [[Inductive effect|electronic]] and [[steric effects]]. This method in general gives better results than atomic based methods, but cannot be used to predict partition coefficients for molecules containing unusual functional groups for which the method has not yet been parameterized (most likely because of the lack of experimental data for molecules containing such functional groups).<ref name="Hansch">{{cite book |last = Hansch |first = Corwin |coauthors = Leo A| title = Substituent Constants for Correlation Analysis in Chemistry and Biology |publisher = John Wiley & Sons Ltd. |year = 1979 |location = New York |pages = 178 pages |isbn = 978-0-471-05062-9}}</ref><ref name="Leo2">{{cite book |last = Leo |first = Albert |coauthors = Hoekman DH, Hansch C| title = Exploring QSAR, Hydrophobic, Electronic, and Steric Constants |publisher = American Chemical Society |year = 1995 |location = Washington, DC |isbn = 978-0-8412-3060-6}}</ref>
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| * Data mining prediction
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| : A typical [[data mining]] based prediction uses [[support vector machine]]s,<ref name="pmid17031534">{{cite journal | author = Liao Q, Yao J, Yuan S | title = SVM approach for predicting LogP | journal = Mol. Divers. | volume = 10 | issue = 3 | pages = 301–9 | year = 2006 | pmid = 17031534 | doi = 10.1007/s11030-006-9036-2 }}</ref> [[Decision tree learning|decision trees]], or [[neural networks]].<ref name="pmid15012980">{{cite journal | author = Molnár L, Keseru GM, Papp A, Gulyás Z, Darvas F | title = A neural network based prediction of octanol-water partition coefficients using atomic5 fragmental descriptors | journal = Bioorg. Med. Chem. Lett. | volume = 14 | issue = 4 | pages = 851–3 | year = 2004 | pmid = 15012980 | doi = 10.1016/j.bmcl.2003.12.024 }}</ref> This method is usually very successful for calculating log ''P'' values when used with compounds that have similar chemical structures and known log ''P'' values.
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| * Molecule mining prediction
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| : [[Molecule mining]] approaches apply a similarity matrix based prediction or an automatic fragmentation scheme into molecular substructures. Furthermore there exist also approaches using [[Maximum common subgraph isomorphism problem|maximum common subgraph]] searches or [[Molecule mining|molecule kernel]]s.
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| * Estimation of log ''D'' (at a given pH) from log ''P'' and p''K''<sub>a</sub>:<ref name="Scherrer">{{cite journal |author=Scherrer RA, Howard SM |title=Use of distribution coefficients in quantitative structure-activity relationships |journal=J Med Chem |volume=20 |issue=1 |pages=53–8 |year=1977 |pmid= 13215 |doi=10.1021/jm00211a010}}</ref>
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| ** exact expressions:
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| *: <math>log\ D_{acids} = log\ P + log\Bigg[\frac{1}{(1+10^{pH-pK_a})}\Bigg]</math>
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| *: <math>log\ D_{bases} = log\ P + log\Bigg[\frac{1}{(1+10^{pK_a-pH})}\Bigg]</math>
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| ** approximations for when the compound is largely ionized:
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| *: <math>\mathrm{for\ acids\ with\ } \big(pH - pK_a\big) > 1,\ log\ D_{acids} \cong log\ P + pK_a - pH</math>
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| *: <math>\mathrm{for\ bases\ with\ } \big(pK_a - pH\big) > 1,\ log\ D_{bases} \cong log\ P - pK_a + pH</math>
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| ** approximation when the compound is largely un-ionized:
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| *: <math>log\ D \cong log\ P</math>
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| * Prediction of p''K''<sub>a</sub>
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| *:For prediction of p''K''<sub>a</sub>, which in turn can be used to estimate log ''D'', [[Hammett equation|Hammett type equations]] have frequently been applied.<ref name="Perrin">{{cite book |last = Perrin |first = DD |coauthors = Dempsey B, Serjeant EP | title = pKa Prediction for Organic Acids and Bases |publisher = Chapman & Hall |year = 1981 |location = London |isbn = 0-412-22190-X }}</ref> See<ref name="CMC2_2007">{{cite conference | last = Fraczkiewicz | first = R | title = In Silico Prediction of Ionization | booktitle = Comprehensive Medicinal Chemistry II | editor = Testa B and van de Waterbeemd H, eds. | volume = vol. 5 | publisher = Elsevier | location = Amsterdam, The Netherlands | year = 2007 }}</ref> for a recent review of newer methods.
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| == Some octanol-water partition coefficient data ==
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| The given values<ref>[[Dortmund Data Bank]]</ref> are sorted by the partition coefficient.
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| Acetamide is hydrophilic and 2,2',4,4',5-pentachlorobiphenyl is lipophilic.
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| {| cellpadding="4" rules="all" style="margin: 1em 0em; background: #ffffff; border: 2px solid #aaa;"
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| |- align="center" bgcolor="#f0f0f0"
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| !Component
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| !log P<sub>OW</sub>
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| !T (°C)
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| ||[[Acetamide]]<ref name="Wolfenden">{{cite journal |author=Wolfenden R|title=Interaction of the peptide bond with solvent water: a vapor phase analysis|journal= Biochemistry |volume=17 |issue=1 |pages=201–4 |year= 1978 |pmid= 618544 |doi=10.1021/bi00594a030}}</ref>||-1.16||25
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| ||[[Methanol]]<ref name="Collander">{{cite journal |author=Collander R| title=The partition of organic compounds. between higher alcohols and water|journal= Acta Chem Scand |volume=5 |issue= |pages=774–780 |year= 1951| doi=10.3891/acta.chem.scand.05-0774 |last2=Lindholm |first2=Martta |last3=Haug |first3=Carl Monthei |last4=Stene |first4=JöRgine |last5=Sörensen |first5=Nils Andreas }}</ref>||-0.82||19
| |
| |-
| |
| ||[[Formic acid]]<ref name="Whitehead">{{cite journal |author=Whitehead KE, Geankoplis CJ| title=Separation of Formic and Sulfuric Acids by Extraction|journal= Ind Eng Chem |volume=47 |issue=10 |pages=2114–2122 |year= 1955 |doi=10.1021/ie50550a029}}</ref>||-0.41||25
| |
| |-
| |
| ||[[Diethyl ether]]<ref name="Collander"/>||0.83||20
| |
| |-
| |
| ||[[p-Dichlorobenzene]]<ref name="Wasik">{{cite journal |author=Wasik SP, Tewari YB, Miller MM, Martire DE| title=Octanol - Water Partition Coefficients and Aqueous Solubilities of Organic Compounds|journal= NBS Techn Rep |volume=81 |issue= 2406|pages=S1–56 |year= 1981 }}</ref>||3.37||25
| |
| |-
| |
| ||[[Hexamethylbenzene]]<ref name="Wasik"/>||4.61||25
| |
| |-
| |
| ||[[2,2',4,4',5-Pentachlorobiphenyl]]<ref name="Brodsky">{{cite journal |author=Brodsky J, Ballschmiter K | title=Reversed phase liquid chromatography of PCBs as a basis for calculation of water solubility and K<sub>ow</sub> for polychlorobiphenyls|journal= Fresenius Z Anal Chem |volume=331 |issue= 3–4|pages=295–301 |year= 1988 | doi=10.1007/BF00481899 }}</ref>||6.41||Ambient
| |
| |}
| |
| | |
| Values for other compounds may be found in Sangster Research Laboratories' database.<ref name="url_LOGKOW">{{cite web | url = http://logkow.cisti.nrc.ca/logkow/ | title = LOGKOW: A databank of evaluated octanol-water partition coefficients (LogP) | author = Sangster J | authorlink = | coauthors = | date = | format = | work = | publisher = Sangster Research Laboratories | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2010-04-04 }}</ref>
| |
| | |
| ==Limitations==
| |
| {{unref-section|date=January 2014}}
| |
| Log P is not an accurate determinant of [[lipophilicity]] for [[ionization|ionizable]] compounds because it only correctly describes the partition coefficient of neutral (uncharged) molecules. Taking the example of [[drug discovery]] we see how the limitations of log P can affect research. Since the majority of [[drug]]s (approximately 80%) are ionizable, log P is not an appropriate predictor of a compound's behaviour in the changing [[pH]] environments of the body. The [[distribution coefficient]] (Log D) is the correct descriptor for ionizable systems.
| |
| Alternatively, use may be made of the ''apparent partition coefficient'', which is defined as follows: (true partition coefficient) x (fraction of the drug that is ''unionised''). Clearly, if the drug is 100% un-ionized then P<sub>apparent</sub> = P<sub>true</sub>.
| |
| | |
| ==See also==
| |
| * [[Blood–gas partition coefficient]]
| |
| * [[Cheminformatics]]
| |
| ** [[ADME]]
| |
| ** [[Lipinski Rule of 5]]
| |
| ** [[Druglikeness]]
| |
| ** [[Lipophilic Efficiency]]
| |
| ** [[QSAR]]
| |
| * [[Distribution law]]
| |
| * [[ITIES]]
| |
| * [[Ionic partition diagram]]
| |
| * [[Chemicalize.org]]:[[Chemicalize.org#List_of_the_predicted_structure_based_properties|List of predicted structure based properties]]
| |
| | |
| ==References==
| |
| {{Reflist|2}}
| |
| | |
| == External links ==
| |
| | |
| There are many logP calculators or predictors available both commercially and for free.
| |
| | |
| * [[Chemistry Development Kit]]
| |
| * [[JOELib]]
| |
| * [http://biobyte.com/bb/prod/bioloom.html BioByte ClogP/Bio-Loom]
| |
| * [http://www.acdlabs.com/logp ACD/LogP DB] a commercial application that calculates LogP values and includes the largest commercially available database of experimental logP values with calculation of Rule-of-5 parameters
| |
| * [http://www.acdlabs.com/freelogp ACD/LogP Freeware] Download the free logP calculator
| |
| * [[Simulations Plus]] - [http://www.simulations-plus.com/Definitions.aspx?lID=59&pID=13 S+logP] an application for calculating logP with high accuracy
| |
| * [http://www.vcclab.org/lab/alogps ALOGPS] Free online calculations and comparison of 10 logP methods
| |
| * [http://www.organic-chemistry.org/prog/peo/ Molecular Property Explorer]
| |
| * [http://www.chemaxon.com/demosite/marvin/index.html Free online logP calculations] using [[ChemAxon]]'s Marvin and Calculator Plugins - requires Java]
| |
| * [http://www.molinspiration.com/cgi-bin/properties miLogP] free logP and [[Rule of Five]] calculator by [[Molinspiration]]
| |
| * [http://www.vcclab.org/online.html an overview of on-line WWW resources for logP and other PhysProp calculations]
| |
| * [http://preadmet.bmdrc.org PreADMET] Web-based logP/logS and ADME/Tox prediction program
| |
| * [http://www.sioc-ccbg.ac.cn/?p=42&software=xlogp3 XLOGP3] an online and standalone logP calculator (including rule-of-5). Free for academy.
| |
| | |
| | |
| {{Chemical equilibria}}
| |
| {{chemical solutions}}
| |
| | |
| [[Category:Equilibrium chemistry]]
| |
| [[Category:Medicinal chemistry]]
| |
| [[Category:Solvents]]
| |
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