Partition coefficient

3505: 1467:), 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. For cases where a drug reaches its target locations through passive mechanisms (i.e., diffusion through membranes), the ideal distribution coefficient for the drug is typically intermediate in value (neither too lipophilic, nor too hydrophilic); in cases where molecules reach their targets otherwise, no such generalization applies. 275: 1398: 1022: 1761:. 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). 829: 490: 1442:

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. Likewise, hydrophobicity plays a major role in determining where drugs are distributed within the body

1728:

of compounds with experimentally measured partition coefficients. 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

1700:

of designed drug candidates before they are synthesized. As discussed in more detail below, estimates of partition coefficients can be made using a variety of methods, including fragment-based, atom-based, and knowledge-based that rely solely on knowledge of the structure of the chemical. Other

2225: 720: 1475:

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. Partition coefficient can also be used to predict the mobility of

1630:

The pH-metric set of techniques determine lipophilicity pH profiles directly from a single acid-base titration in a two-phase water–organic-solvent system. Hence, a single experiment can be used to measure the logarithms of the partition coefficient (log

1683:

There are many situations where prediction of partition coefficients prior to experimental measurement is useful. For example, tens of thousands of industrially manufactured chemicals are in common use, but only a small fraction have undergone rigorous

1355:

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. Hence, the log

1170: 4526:

Nieto-Draghi C, Fayet G, Creton B, Rozanska X, Rotureau P, de Hemptinne JC, Ungerer P, Rousseau B, Adamo C (December 2015). "A General Guidebook for the Theoretical Prediction of Physicochemical Properties of Chemicals for Regulatory Purposes".

1017:{\displaystyle \log D_{\text{oct/wat}}=\log _{10}\left({\frac {{\big }_{\text{octanol}}^{\text{ionized}}+{\big }_{\text{octanol}}^{\text{un-ionized}}}{{\big }_{\text{water}}^{\text{ionized}}+{\big }_{\text{water}}^{\text{un-ionized}}}}\right).} 1222:. They are sorted by the partition coefficient, smallest to largest (acetamide being hydrophilic, and 2,2',4,4',5-pentachlorobiphenyl lipophilic), and are presented with the temperature at which they were measured (which impacts the values). 822:

is then determined as the logarithm of a ratio—of the sum of the experimentally measured concentrations of the solute's various forms in one solvent, to the sum of such concentrations of its forms in the other solvent; it can be expressed as

504:

of the aqueous phase is adjusted such that the predominant form of the compound in solution is the un-ionized, or its measurement at another pH of interest requires consideration of all species, un-ionized and ionized (see following).

1566:, 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 365: 5270:

Hendriks AJ, van der Linde A, Cornelissen G, Sijm DT (July 2001). "The power of size. 1. Rate constants and equilibrium ratios for accumulation of organic substances related to octanol-water partition ratio and species weight".

2481: 2355: 495:

To a first approximation, the non-polar phase in such experiments is usually dominated by the un-ionized form of the solute, which is electrically neutral, though this may not be true for the aqueous phase. To measure the

2001: 1617:

values, and extrapolation from one chemical class to another—applying a regression equation derived from one chemical class to a second one—may not be reliable, since each chemical classes will have its characteristic

585: 1701:

prediction methods rely on other experimental measurements such as solubility. The methods also differ in accuracy and whether they can be applied to all molecules, or only ones similar to molecules already studied.

1655:, "interfaces between two immiscible electrolyte solutions". The second is droplet experiments. Here a reaction at a triple interface between a conductive solid, droplets of a redox active liquid phase and an 5544:

Klopman G, Zhu H (February 2005). "Recent methodologies for the estimation of n-octanol/water partition coefficients and their use in the prediction of membrane transport properties of drugs". (secondary).

2596: 1986: 1692:

equations, which in turn are based on calculated partition coefficients, can be used to provide toxicity estimates. Calculated partition coefficients are also widely used in drug discovery to optimize

523:

forms of the molecule, such that one must consider partition of all forms, ionized and un-ionized, between the two phases (as well as the interaction of the two equilibria, partition and ionization).

1729:

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.

1550:

In this method the solid particles present into the two immiscible liquids can be easily separated by suspending those solid particles directly into these immiscible or somewhat miscible liquids.

2407: 2281: 2006: 1514:, 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 1502:

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.

259:, represents the concentration of solute A being tested, and "org" and "aq" refer to the organic and aqueous phases respectively. The IUPAC further recommends "partition ratio" for cases where 4847:

Ghose AK, Viswanadhan VN, Wendoloski JJ (1998). "Prediction of Hydrophobic (Lipophilic) Properties of Small Organic Molecules Using Fragmental Methods: An Analysis of AlogP and ClogP Methods".

1709:

Standard approaches of this type, using atomic contributions, have been named by those formulating them with a prefix letter: AlogP, XlogP, MlogP, etc. A conventional method for predicting log

5618:

Mannhold R, Poda GI, Ostermann C, Tetko IV (March 2009). "Calculation of molecular lipophilicity: State-of-the-art and comparison of log P methods on more than 96,000 compounds". (secondary).

1667:

There are attempts to provide partition coefficients for drugs at a single-cell level. This strategy requires methods for the determination of concentrations in individual cells, i.e., with

799:, 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, one essentially always aqueous; as such, it depends on the 4219:

Andrés A, Rosés M, Ràfols C, Bosch E, Espinosa S, Segarra V, Huerta JM (August 2015). "Setup and validation of shake-flask procedures for the determination of partition coefficients (log

5239:"A comparison of log Kow (n-octanol–water partition coefficient) values for non-ionic, anionic, cationic and amphoteric surfactants determined using predictions and experimental methods" 2672:(water solubility) of a substance. The value is greater than one if a substance is more soluble in fat-like solvents such as n-octanol, and less than one if it is more soluble in water. 768: 577: 1745:

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

1651:

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. The first is

1534:

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.

4925:

Molnár L, Keseru GM, Papp A, Gulyás Z, Darvas F (February 2004). "A neural network based prediction of octanol-water partition coefficients using atomic5 fragmental descriptors".

4720:"Atomic Physicochemical Parameters for Three-Dimensional Structure-Directed Quantitative Structure–Activity Relationships I. Partition Coefficients as a Measure of Hydrophobicity" 3685:

Mannhold R, Poda GI, Ostermann C, Tetko IV (March 2009). "Calculation of molecular lipophilicity: State-of-the-art and comparison of log P methods on more than 96,000 compounds".

1542:

A number of methods of measuring distribution coefficients have been developed, including the shake-flask, separating funnel method, reverse-phase HPLC, and pH-metric techniques.

4158:"Transport, Accumulation and Transformation Processes (Ch. 3), Properties of Chemicals and Estimation Methodologies (Ch. 7), and Procedures of Hazard and Risk Assessment (Ch. 8)" 1869: 3340:

Manners CN, Payling DW, Smith DA (March 1988). "Distribution coefficient, a convenient term for the relation of predictable physico-chemical properties to metabolic processes".

1067: 4355:"A new access to Gibbs energies of transfer of ions across liquid|liquid interfaces and a new method to study electrochemical processes at well-defined three-phase junctions" 1713:

through this type of method is to parameterize the distribution coefficient contributions of various atoms to the overall molecular partition coefficient, which produces a

1797:

approaches apply a similarity-matrix-based prediction or an automatic fragmentation scheme into molecular substructures. Furthermore, there exist also approaches using

66:. This ratio is therefore a comparison of the solubilities of the solute in these two liquids. The partition coefficient generally refers to the concentration ratio of 1911: 1463:

targets. 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.,

1200: 4611:

Matter H, Baringhaus KH, Naumann T, Klabunde T, Pirard B (September 2001). "Computational approaches towards the rational design of drug-like compound libraries".

1027:

In the above formula, the superscripts "ionized" each indicate the sum of concentrations of all ionized species in their respective phases. In addition, since log

485:{\displaystyle \log P_{\text{oct/wat}}=\log _{10}\left({\frac {{\big }_{\text{octanol}}^{\text{un-ionized}}}{{\big }_{\text{water}}^{\text{un-ionized}}}}\right).} 1338:

Values for other compounds may be found in a variety of available reviews and monographs. Critical discussions of the challenges of measurement of log

169:

value. A related value, D, does not distinguish between different species, only indicating the concentration ratio of the substance between the two phases.

6383: 1035:

was measured must be specified. In areas such as drug discovery—areas involving partition phenomena in biological systems such as the human body—the log

4415:"Quantitative analysis of biochemical processes in living cells at a single-molecule level: a case of olaparib–PARP1 (DNA repair protein) interactions" 2412: 2286: 278:

An equilibrium of dissolved substance distributed between a hydrophobic phase and a hydrophilic phase is established in special glassware such as this

3729: 263:

can be determined, and "distribution ratio" for the ratio of total analytical concentrations of a solute between phases, regardless of chemical form.

70:

species of compound, whereas the distribution coefficient refers to the concentration ratio of all species of the compound (ionized plus un-ionized).

4413:

Karpińska, Aneta; Pilz, Marta; Buczkowska, Joanna; Żuk, Paweł J.; Kucharska, Karolina; Magiera, Gaweł; Kwapiszewska, Karina; Hołyst, Robert (2021).

2220:{\displaystyle {\begin{aligned}\log D_{\text{acids}}&\cong \log P+\log \left,\\\log D_{\text{bases}}&\cong \log P+\log \left.\end{aligned}}} 715:{\displaystyle \log \ P_{\text{oct/wat}}^{\mathrm {I} }=\log _{10}\left({\frac {{\big }_{\text{octanol}}^{I}}{{\big }_{\text{water}}^{I}}}\right).} 4268:

Valkó K (May 2004). "Application of high-performance liquid chromatography based measurements of lipophilicity to model biological distribution".

5478:

Hill AP, Young RJ (August 2010). "Getting physical in drug discovery: a contemporary perspective on solubility and hydrophobicity". (secondary).

3173:

Comer J, Tam K (2001). "Lipophilicity Profiles: Theory and Measurement". In Testa B, van de Waterbed H, Folkers G, Guy R, Comer J, Tam K (eds.).

5223: 4562:

Judson R, Richard A, Dix DJ, Houck K, Martin M, Kavlock R, Dellarco V, Henry T, Holderman T, Sayre P, Tan S, Carpenter T, Smith E (May 2009).

1639:) of all forms of the molecule over a pH range, e.g., between 2 and 12. The method does, however, require the separate determination of the pK 5793: 2690:

The values listed here are sorted by the partition coefficient. Acetamide is hydrophilic, and 2,2′,4,4′,5-Pentachlorobiphenyl is lipophilic.

4646:

Schuffenhauer A, Ruedisser S, Marzinzik AL, Jahnke W, Blommers M, Selzer P, Jacoby E (2005). "Library design for fragment based screening".

3895:

Kubinyi H (1979). "Lipophilicity and biological activity. Drug transport and drug distribution in model systems and in biological systems".

1749:

values have been determined in a statistical method analogous to the atomic methods (least-squares fitting to a training set). In addition,

6085: 1426:

properties of the drug. Hence the hydrophobicity of a compound (as measured by its distribution coefficient) is a major determinant of how

1798: 3007: 3527:

Brodsky J, Ballschmiter K (1988). "Reversed phase liquid chromatography of PCBs as a basis for calculation of water solubility and

5424:

Comer J, Tam K (2001). "Lipophilicity Profiles: Theory and Measurement". In Testa B, van de Waterbed HM, Folkers G, Guy R (eds.).

128:

measures how easily the anesthetic passes from gas to blood. Partition coefficients can also be defined when one of the phases is

113:

of cells. Conversely, hydrophilic drugs (low octanol/water partition coefficients) are found primarily in aqueous regions such as

3833:

Bodor N, Buchwald P (April 1999). "Recent advances in the brain targeting of neuropharmaceuticals by chemical delivery systems".

2534: 1923: 5896: 4386: 1583: 120:

If one of the solvents is a gas and the other a liquid, a gas/liquid partition coefficient can be determined. For example, the

5742: 5723: 5704: 5675: 5608: 5468: 5449: 5199: 4985: 4173: 4041: 3817: 3741: 3666: 3584: 3231: 3190: 3148: 3108: 3076: 3047: 3019: 2990: 2965: 2906: 1668: 725:

To distinguish between this and the standard, un-ionized, partition coefficient, the un-ionized is often assigned the symbol

3757:

Leeson PD, Springthorpe B (November 2007). "The influence of drug-like concepts on decision-making in medicinal chemistry".

3296:

Scherrer RA, Howard SM (January 1977). "Use of distribution coefficients in quantitative structure-activity relationships".

815:

to a specific value such that the pH is not significantly perturbed by the introduction of the compound. The value of each

136:

and the second is a solid metal, or when both phases are solids. The partitioning of a substance into a solid results in a

2363: 2237: 1635:) giving the distribution of molecules that are primarily neutral in charge, as well as the distribution coefficient (log 5686: 4305:"Water-oil partition profiling of ionized drug molecules using cyclic voltammetry and a 96-well microfilter plate system" 2835: 2618: 1485: 106: 5038:

Pinsuwan S, Li A, Yalkowsky SH (May 1995). "Correlation of Octanol/Water Solubility Ratios and Partition Coefficients".

4414: 6130: 5786: 5161: 5101: 5022: 3400:

Wolfenden R (January 1978). "Interaction of the peptide bond with solvent water: a vapor phase analysis". (primary).

811:

for non-ionizable compounds at any pH. For measurements of distribution coefficients, the pH of the aqueous phase is

188:

recommends that the title term no longer be used, rather, that it be replaced with more specific terms. For example,

3868:

Kubinyi H (March 1979). "Nonlinear dependence of biological activity on hydrophobic character: the bilinear model".

6078: 5987: 4384:

Bond AM, Marken F (1994). "Mechanistic aspects of the electron and ion transport processes across the electrode".

2488: 1422:(how the body absorbs, metabolizes, and excretes a drug), the distribution coefficient has a strong influence on 735: 544: 121: 579:, is defined in the same manner as for the un-ionized form. For instance, for an octanol–water partition, it is 6449: 6220: 4304: 2648:. It is also frequently referred to by the symbol P, especially in the English literature. It is also known as 1494:

is used to predict and model the migration of dissolved hydrophobic organic compounds in soil and groundwater.

4719: 4468:"Cellular Uptake of Bevacizumab in Cervical and Breast Cancer Cells Revealed by Single-Molecule Spectroscopy" 1659:

solution have been used to determine the energy required to transfer a charged species across the interface.

286:

is determined. Here, the green substance has a greater solubility in the lower layer than in the upper layer.

5102:"A review of methods for the calculation of solution free energies and the modelling of systems in solution" 6454: 6373: 6045: 5949: 5779: 1605:

An advantage of this method is that it is fast (5–20 minutes per sample). However, since the value of log

1165:{\displaystyle \log D_{\text{oct/wat}}=\log _{10}\left(\sum _{I=0}^{M}f^{I}P_{\text{oct/wat}}^{I}\right),} 6444: 6303: 6071: 5858: 1833: 102: 5428:

Pharmacokinetic Optimization in Drug Research: Biological, Physicochemical, and Computational Strategies

3175:

Pharmacokinetic Optimization in Drug Research: Biological, Physicochemical, and Computational Strategies

2981:

Shargel L, Susanna WP, Yu AB (2012). "Chapter 10: Physiological Drug Distribution and Protein Binding".

6358: 5965: 5762:. Overview of the many logP and other physical property calculators available commercially and on-line. 5737:. (secondary). Wiley Series in Solution Chemistry. Vol. 2. Chichester: John Wiley & Sons Ltd. 3575:, Leo A (1979). "Chapter 5: Calculation of Octanol-Water Partition Coefficients from Fragments, etc.". 2960:. Wiley Series in Solution Chemistry. Vol. 2. Chichester: John Wiley & Sons Ltd. p. 178. 2847: 1992: 1519: 1372:

in evaluating the quality of research compounds, where the efficiency for a compound is defined as its

3802:

Role of Physicochemical Properties and Ligand Lipophilicity Efficiency in Addressing Drug Safety Risks

2899:

Handbook of Essential Pharmacokinetics, Pharmacodynamics and Drug Metabolism for Industrial Scientists

147:, etc.) or estimated by calculation based on a variety of methods (fragment-based, atom-based, etc.). 6250: 5873: 5841: 5185: 3975:"What determines the strength of noncovalent association of ligands to proteins in aqueous solution?" 3252:

Pagliara A, Carrupt PA, Caron G, Gaillard P, Testa B (1997). "Lipophilicity Profiles of Ampholytes".

1782: 1738: 1693: 4085: 6235: 6170: 6014: 6009: 5970: 520: 309: 159: 1675:. Partition coefficient at a single-cell level provides information on cellular uptake mechanism. 6190: 4772:"Computation of octanol-water partition coefficients by guiding an additive model with knowledge" 4354: 2873: 2864: – Generalisation describing the distribution of a solute between two non miscible solvents. 1460: 155: 78: 5765: 1430:

it is. More specifically, for a drug to be orally absorbed, it normally must first pass through

6288: 6283: 6140: 6033: 5923: 5696: 5690: 5655: 3211: 1778: 1774: 1373: 274: 101:("water-fearing") a chemical substance is. Partition coefficients are useful in estimating the 5667: 3223: 3096: 1210:-th form (of the solute) in the aqueous phase, and other variables are defined as previously. 6368: 6021: 5999: 5944: 5851: 5831: 5433: 4682: 3474:

Whitehead KE, Geankoplis CJ (1955). "Separation of Formic and Sulfuric Acids by Extraction".

2894: 2853: 2850: – Rule of thumb to predict if a chemical compound is likely to be an orally active drug 2602: 1369: 770:

expression for ionized solutes becomes simply an extension of this, into the range of values

63: 20: 5659: 5574:

Leo A, Hansch C, and Elkins D (1971). "Partition coefficients and their uses". (secondary).

5425: 3215: 3064: 6102: 6094: 5908: 5891: 5802: 5516: 5507:

Kah M, Brown CD (August 2008). "LogD: lipophilicity for ionisable compounds". (secondary).

5116: 4856: 3986: 3931: 3616: 1889: 1178: 256: 3439: 2687:

typically range between -3 (very hydrophilic) and +10 (extremely lipophilic/hydrophobic).

2524:, of an organic compound is known or predicted in both water and 1-octanol, then log 1443:

after absorption and, as a consequence, in how rapidly they are metabolized and excreted.

8: 6215: 6185: 6004: 5982: 5868: 5826: 5695:. (secondary) (1st ed.). Baltimore, MD: Lippincott Williams & Wilkins. pp. 4164:. Dordrecht: Kluwer Acad. Publ. pp. 37–102, and 239–338, esp. 39ff, 240ff, 306, and 2812: 2778: 2664:, being a type of partition coefficient, serves as a measure of the relationship between 1567: 1361: 5520: 5120: 4860: 3990: 3935: 3620: 3042:(8th ed.). Amsterdam: Elsevier/Butterworth-Heinemann. pp. 93–120, esp. 106ff. 5992: 5883: 5816: 5643: 5340: 5315: 5296: 5217: 5014: 4907: 4771: 4752: 4588: 4563: 4505: 4492: 4467: 4445: 4335: 3955: 3782: 3710: 3551: 3069:

An Introduction to Aspects of Thermodynamics and Kinetics Relevant to Materials Science

1456: 1342:

and related computation of its estimated values (see below) appear in several reviews.

1219: 143:

Partition coefficients can be measured experimentally in various ways (by shake-flask,

125: 5528: 4370: 3846: 3809: 6459: 6393: 6352: 6255: 6038: 5918: 5846: 5836: 5738: 5719: 5700: 5671: 5660: 5635: 5604: 5562: 5532: 5495: 5464: 5445: 5426: 5412: 5345: 5288: 5205: 5195: 5167: 5157: 5134: 5082: 5018: 4981: 4942: 4899: 4791: 4697: 4663: 4628: 4593: 4544: 4509: 4497: 4449: 4437: 4399: 4327: 4285: 4250: 4169: 4142: 4037: 4014: 4009: 3974: 3947: 3922:

Eisenberg D, McLachlan AD (1986). "Solvation energy in protein folding and binding".

3904: 3877: 3850: 3813: 3786: 3774: 3737: 3702: 3662: 3580: 3417: 3357: 3313: 3269: 3227: 3216: 3186: 3144: 3104: 3072: 3043: 3015: 2986: 2961: 2902: 2796: 1721: 1610: 1313: 1300: 1061:), thus covering both un-ionized and ionized species. For example, in octanol–water: 324: 279: 260: 55: 27: 5597: 5300: 5237:

Hodges G, Eadsforth C, Bossuyt B, Bouvy A, Enrici MH, Geurts M, et al. (2019).

3959: 3655: 3555: 3506:"Octanol–Water Partition Coefficients and Aqueous Solubilities of Organic Compounds" 3459: 1789:

values when used with compounds that have similar chemical structures and known log

6328: 6323: 6155: 6115: 5977: 5863: 5666:. (secondary) (2nd ed.). Boca Raton: CRC Press/Taylor & Francis. pp. 5647: 5627: 5583: 5554: 5524: 5487: 5437: 5404: 5392: 5335: 5327: 5280: 5250: 5124: 5074: 5047: 5010: 4973: 4934: 4911: 4891: 4864: 4827: 4783: 4756: 4742: 4734: 4655: 4620: 4583: 4575: 4536: 4487: 4479: 4429: 4395: 4366: 4339: 4319: 4277: 4240: 4232: 4201: 4138: 4107: 4066: 4004: 3994: 3939: 3842: 3805: 3766: 3714: 3694: 3624: 3543: 3483: 3454: 3409: 3349: 3305: 3261: 3178: 3136: 3014:(2nd ed.). Philadelphia, Pa.: Lippincott Williams & Wilkins. p. 243. 2938: 2861: 2502: 1754: 1750: 1714: 1452: 1419: 1175:

which sums the individual partition coefficients (not their logarithms), and where

151: 3601: 6313: 6298: 6230: 6195: 6180: 6175: 6160: 6125: 5939: 5491: 5408: 5001:

Fraczkiewicz R (2013). "In Silico Prediction of Ionization". In Reedijk J (ed.).

4281: 4157: 2841: 2476:{\displaystyle \log D_{\text{bases}}\cong \log P-\mathrm {p} K_{a}+\mathrm {pH} } 2350:{\displaystyle \log D_{\text{acids}}\cong \log P+\mathrm {p} K_{a}-\mathrm {pH} } 1802: 1794: 1523: 812: 4540: 4483: 6363: 6318: 6308: 6225: 6120: 6110: 6050: 5441: 5154:

Octanol-water partition coefficients : fundamentals and physical chemistry

5078: 5065:

Wang J, Hou T (June 2011). "Recent advances on aqueous solubility prediction".

4938: 4466:

Karpinska, Aneta; Magiera, Gaweł; Kwapiszewska, Karina; Hołyst, Robert (2023).

4236: 4111: 4070: 3979:

Proceedings of the National Academy of Sciences of the United States of America

3182: 1758: 1672: 1595: 336: 137: 110: 5255: 5238: 5209: 4977: 4895: 4323: 4057:

Cronin D, Mark T (2006). "The Role of Hydrophobicity in Toxicity Prediction".

3353: 6438: 6408: 6245: 6205: 6150: 5903: 5558: 5393:"Determination of liquid-liquid partition coefficients by separation methods" 5331: 4683:"Lipophilicity--methods of determination and its role in medicinal chemistry" 4659: 4624: 4205: 3646: 3572: 2926: 2763: 2665: 1883: 1718: 1477: 1464: 1439: 1431: 1287: 1203: 332: 301: 51: 5171: 4192:

Dearden JC, Bresnan GM (1988). "The Measurement of Partition Coefficients".

3999: 1218:

The values for the octanol-water system in the following table are from the

6265: 6260: 5639: 5566: 5536: 5499: 5416: 5349: 5292: 5284: 5189: 5138: 5086: 5007:

Reference Module in Chemistry, Molecular Sciences and Chemical Engineering

4946: 4903: 4795: 4701: 4667: 4632: 4597: 4548: 4501: 4441: 4331: 4289: 4254: 4093:) for the Modelling of Transport Processes of Radionuclides in Groundwater" 3854: 3778: 3706: 3273: 1725: 1697: 1688:

evaluation. Hence there is a need to prioritize the remainder for testing.

1515: 1481: 1427: 1365: 308:

between the two solvents (a biphase of liquid phases), specifically for un-

114: 5316:"Octanol-Water Partition Coefficient Measurement by a Simple H NMR Method" 5100:

Skyner RE, McDonagh JL, Groom CR, van Mourik T, Mitchell JB (March 2015).

5003:

Reference Module in Chemistry, Molecular Sciences and Chemical Engineering

4738: 4018: 3951: 3361: 6418: 6333: 5735:

Octanol-Water Partition Coefficients: Fundamentals and Physical Chemistry

4882:

Liao Q, Yao J, Yuan S (August 2006). "SVM approach for predicting LogP".

4770:

Cheng T, Zhao Y, Li X, Lin F, Xu Y, Zhang X, Li Y, Wang R, Lai L (2007).

4747: 3804:. Annual Reports in Medicinal Chemistry. Vol. 45. pp. 381–391. 3421: 2958:

Octanol–Water Partition Coefficients: Fundamentals and Physical Chemistry

2870: – Electrochemical interface that is either polarisable or polarised 2748: 1770: 1656: 1591: 1274: 348: 340: 98: 94: 86: 5587: 5051: 4579: 4303:

Ulmeanu SM, Jensen H, Bouchard G, Carrupt PA, Girault HH (August 2003).

3908: 3881: 3487: 3413: 3317: 3309: 3128: 2942: 6413: 6403: 6398: 6275: 5913: 5461:

Substituent Constants for Correlation Analysis in Chemistry and Biology

5129: 4832: 4815: 4433: 4245: 3577:

Substituent Constants for Correlation Analysis in Chemistry and Biology

3547: 3440:"The partition of organic compounds. between higher alcohols and water" 2669: 1685: 1511: 1435: 67: 59: 5771: 5631: 4868: 4787: 3698: 3265: 3012:

Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy

6423: 6378: 6293: 6063: 5821: 4645: 3943: 3628: 3222:(2nd ed.). Boca Raton: CRC Press/Taylor & Francis. pp. 3140: 2718: 2624: 1619: 1248: 344: 313: 90: 74: 5759: 5368:

Dortmund Data Bank Software & Separation Technology (DDBST) GmbH

5269: 3770: 3375: 1397: 6240: 4960:

Perrin DD, Dempsey B, Serjeant EP (1981). "Chapter 3: Methods of pK

2733: 1261: 85:. Most commonly, one of the solvents is water, while the second is 4816:"Simple method of calculating octanol/water partition coefficient" 4465: 3602:"Octanol–Water Partition Coefficients of Simple Organic Compounds" 3131:. In Miloslav N, Jirát J, Košata B, Jenkins A, McNaught A (eds.). 1518:, and determines how effectively an impurity can be removed using 1364:

in pre-clinical drug discovery, for example, in the assessment of

181:

remains the predominantly used term in the scientific literature.

6343: 6145: 6135: 2230:

Further approximations for when the compound is largely ionized:

356: 82: 3342:

Xenobiotica; the Fate of Foreign Compounds in Biological Systems

1613:, several compounds with similar structures must have known log 4814:

Moriguchi I, Hirono S, Liu Q, Nakagome I, Matsushita Y (1992).

4610: 4525: 3438:

Collander R, Lindholm M, Haug CM, Stene J, Sörensen NA (1951).

3005: 305: 5768:, a simple LogP estimater used by PubChem (release 2021.05.07) 5658:(2010). "Chapter 4: The Hydrophobic Properties of Molecules". 3214:(2010). "Chapter 4: The Hydrophobic Properties of Molecules". 2838: – Measure of solubility of general anaesthetics in blood 6165: 5599:

Exploring QSAR, Hydrophobic, Electronic, and Steric Constants

5099: 3657:

Exploring QSAR, Hydrophobic, Electronic, and Steric Constants

2867: 2631: 1785:. This method is usually very successful for calculating log 1652: 1459:

is the major driving force for the binding of drugs to their

185: 133: 129: 5191:

Multimedia environmental models : the fugacity approach

4302: 3251: 2985:(6th ed.). New York: McGraw-Hill Medical. p. 211. 2929:, Elkins D (1971). "Partition coefficients and their uses". 1917:

into non-polar phase can be neglected, can be formulated as

1039:

at the physiologic pH = 7.4 is of particular interest.

541:) the logarithm of the corresponding partition coefficient, 5236: 4352: 4036:. New York: John Wiley & Sons Ltd. pp. 439 pages. 2901:. New York: Kluwer Academic/Plenum Publishers. p. 44. 2591:{\displaystyle \log P=\log S_{\text{o}}-\log S_{\text{w}}.} 1981:{\displaystyle \log D\cong \log P+\log \left(f^{0}\right).} 1717:. This parametric model can be estimated using constrained 1689: 1423: 1384: 1377: 144: 5617: 5603:. (secondary). Washington, DC: American Chemical Society. 4846: 4813: 4412: 4031: 3684: 3437: 3083:

Solid–solid equilibria equivalent to the solid–liquid case

3038:

Stallman RE, Ngan AH (2014). "Chapter 3: Solidification".

3006:

Golan DE, Tashjian AH, Armstrong EJ, Armstrong AP (2008).

1360:

of a molecule is one criterion used in decision-making by

4564:"The toxicity data landscape for environmental chemicals" 3133:

Compendium of Chemical Terminology: IUPAC Recommendations

1991:

The following approximate expressions are valid only for

527:

is used to indicate the number of ionized forms; for the

5718:. (secondary) (1st ed.). New York: Pergamon Press. 5363: 3503: 3033: 3031: 177:

Despite formal recommendation to the contrary, the term

5067:

Combinatorial Chemistry & High Throughput Screening

4613:

Combinatorial Chemistry & High Throughput Screening

4353:

Scholz F, Komorsky-Lovrić Š, Lovrić M (February 2000).

800: 501: 323:. When one of the solvents is water and the other is a 4924: 4218: 2612: 1368:

of drug candidates. Likewise, it is used to calculate

105:

of drugs within the body. Hydrophobic drugs with high

5009:. Vol. 5. Amsterdam, the Netherlands: Elsevier. 4959: 4680: 4561: 3028: 2537: 2415: 2366: 2289: 2240: 2004: 1926: 1892: 1836: 1213: 1181: 1070: 832: 780: 738: 588: 547: 368: 282:

that allows shaking and sampling, from which the log

6384:

List of boiling and freezing information of solvents

5463:. (secondary). New York: John Wiley & Sons Ltd. 4521: 4519: 2402:{\displaystyle \mathrm {p} K_{a}-\mathrm {pH} >1} 2276:{\displaystyle \mathrm {pH} -\mathrm {p} K_{a}>1} 1741:

and is termed cLogP. It has been shown that the log

109:

are mainly distributed to hydrophobic areas such as

5716:

Partition Coefficient: Determination and Estimation

5573: 5194:. J. Mark Parnis (Third ed.). Boca Raton, FL. 5037: 3526: 3504:Wasik SP, Tewari YB, Miller MM, Martire DE (1981). 3473: 3339: 3122: 3120: 351:respectively; for example, in a biphasic system of 16:

Ratio of concentrations in a mixture at equilibrium

5596: 5390: 4155: 3921: 3756: 3654: 2590: 2475: 2401: 2349: 2275: 2219: 1980: 1905: 1863: 1194: 1164: 1016: 762: 714: 571: 484: 339:. The defined precedent is for the lipophilic and 266: 5713: 5662:Quantitative Drug Design: A critical introduction 4809: 4807: 4805: 4516: 3593: 3218:Quantitative Drug Design: A critical introduction 3126: 3071:(3rd ed.). Amsterdam: Elsevier. p. 98. 2497:, which in turn can be used to estimate log 1914: 6436: 5594: 3680: 3678: 3644: 3117: 2980: 2895:"4.2.4: Partition and Distribution Coefficients" 519:, is derived for cases where there are dominant 4187: 4185: 3972: 3609:Journal of Physical and Chemical Reference Data 3335: 3333: 3331: 3329: 3327: 3206: 3204: 3202: 2983:Applied Biopharmaceutics & Pharmacokinetics 2924: 1529: 93:. Hence the partition coefficient measures how 4972:. London: Chapman & Hall. pp. 21–26. 4802: 4769: 4191: 4125:Noble A (July 1993). "Partition coefficients ( 4083: 4077: 3295: 3247: 3245: 3243: 1558:The classical and most reliable method of log 1405:axis) as a function of partition coefficient ( 6079: 5787: 5432:. (secondary). Weinheim: Wiley-VCH. pp. 5313: 4713: 4711: 4194:Quantitative Structure-Activity Relationships 4162:Risk Assessment of Chemicals: An Introduction 4032:Pliska V, Testa B, Van De Waterbed H (1996). 3888: 3861: 3832: 3727: 3675: 3661:. Washington, DC: American Chemical Society. 3168: 3166: 3164: 3162: 3160: 3101:Pharmaceutics: The Science of Medicine Design 3008:"Chapter 15: General Anesthetic Pharmacology" 988: 975: 954: 941: 921: 908: 887: 874: 686: 673: 653: 640: 456: 443: 423: 410: 5307: 5093: 5058: 5000: 4927:Bioorganic & Medicinal Chemistry Letters 4918: 4875: 4776:Journal of Chemical Information and Modeling 4717: 4639: 4604: 4555: 4461: 4459: 4296: 4261: 4182: 3826: 3799: 3750: 3433: 3431: 3324: 3199: 3037: 1827:For cases where the molecule is un-ionized: 5692:Introduction to the Pharmaceutical Sciences 4881: 4225:European Journal of Pharmaceutical Sciences 4212: 4034:Lipophilicity in Drug Action and Toxicology 3736:. (secondary). John Wiley & Sons, Inc. 3291: 3289: 3287: 3285: 3283: 3240: 3088: 3065:"Chapter 3: Free Energy and Phase Diagrams" 1808: 1545: 763:{\displaystyle \log P_{\text{oct/wat}}^{I}} 572:{\displaystyle \log P_{\text{oct/wat}}^{I}} 132:, for instance, when one phase is a molten 6086: 6072: 5794: 5780: 5543: 5222:: CS1 maint: location missing publisher ( 5040:Journal of Chemical & Engineering Data 4840: 4708: 4383: 4056: 3730:"Chapter 2.2: Pharmacokinetic Phase: ADME" 3157: 1042:It is often convenient to express the log 498:partition coefficient of ionizable solutes 300:, is defined as a particular ratio of the 5687:"Chapter 3: Solubility and Lipophilicity" 5477: 5458: 5339: 5254: 5128: 4831: 4746: 4587: 4491: 4456: 4377: 4244: 4156:van Leeuwin CJ, Hermens JL, eds. (2012). 4008: 3998: 3973:Miyamoto S, Kollman PA (September 1993). 3915: 3571: 3567: 3565: 3467: 3458: 3428: 3399: 3393: 3177:. Weinheim: Wiley-VCH. pp. 275–304. 1031:is pH-dependent, the pH at which the log 5732: 5506: 5423: 5151: 4994: 4681:Rutkowska E, Pajak K, Jóźwiak K (2013). 3966: 3734:Retrometabolic Drug Design and Targeting 3599: 3499: 3497: 3280: 3172: 2955: 1497: 1470: 1401:Drug permeability in brain capillaries ( 1396: 359:(hereafter simply "octanol") and water: 273: 5801: 5714:Pearlman RS, Dunn WJ, Block JH (1986). 5064: 3894: 3867: 3640: 3638: 3579:. New York: John Wiley & Sons Ltd. 3520: 3094: 3062: 2949: 1662: 6437: 6093: 5684: 5654: 5314:Cumming H, Rücker C (September 2017). 5273:Environmental Toxicology and Chemistry 5184: 4970:Prediction for Organic Acids and Bases 4953: 4387:Journal of Electroanalytical Chemistry 4050: 4025: 3562: 3376:"Octanol–Water Partition Coefficients" 3210: 1598:with similar compounds with known log 1584:high-performance liquid chromatography 6067: 5775: 5391:Berthod A, Carda-Broch S (May 2004). 4648:Current Topics in Medicinal Chemistry 4267: 4124: 3494: 2920: 2918: 2856: – Parameter used in drug design 2601:There are a variety of approaches to 1669:Fluorescence correlation spectroscopy 1455:(how the drug affects the body), the 512:for ionizable compounds, abbreviated 150:If a substance is present as several 5595:Leo A, Hoekman DH, Hansch C (1995). 3635: 2892: 2639:-octanol-water partition coefficient 194: 107:octanol-water partition coefficients 5547:Mini Reviews in Medicinal Chemistry 5109:Physical Chemistry Chemical Physics 2619:Octanol-water partition coefficient 2613:Octanol-water partition coefficient 2508: 1874:For other cases, estimation of log 1864:{\displaystyle \log D\cong \log P.} 1553: 1486:octanol–water partition coefficient 1446: 1413: 162:, each species is assigned its own 13: 5620:Journal of Pharmaceutical Sciences 5383: 5015:10.1016/B978-0-12-409547-2.02610-X 4727:Journal of Computational Chemistry 4100:Current Computer-Aided Drug Design 4059:Current Computer-Aided Drug Design 3687:Journal of Pharmaceutical Sciences 3127:Wilkinson AM, McNaught AD (1997). 2915: 2844: – Interdisciplinary science 2623:The partition coefficient between 2469: 2466: 2448: 2389: 2386: 2368: 2343: 2340: 2322: 2253: 2245: 2242: 2197: 2194: 2176: 2083: 2072: 1764: 1646: 1214:Example partition coefficient data 609: 14: 6471: 5753: 5529:10.1016/j.chemosphere.2008.04.074 4568:Environmental Health Perspectives 4129:-octanol—water) for pesticides". 3099:. In Denton P, Rostron C (eds.). 3097:"Hydrophobicity and Partitioning" 2675: 1913:, in the case where partition of 1732: 1590:of a solute can be determined by 781:Distribution coefficient and log 3870:Il Farmaco; Edizione Scientifica 1737:The most common of these uses a 1480:in groundwater. In the field of 1050:, defined above (which includes 343:phase types to always be in the 5356: 5263: 5230: 5178: 5145: 5031: 4849:Journal of Physical Chemistry A 4763: 4674: 4406: 4359:Electrochemistry Communications 4346: 4149: 4118: 3793: 3721: 3460:10.3891/acta.chem.scand.05-0774 3368: 2836:Blood–gas partition coefficient 1350: 1345: 1326:2,2',4,4',5-Pentachlorobiphenyl 172: 154:in the partition system due to 122:blood/gas partition coefficient 3835:Advanced Drug Delivery Reviews 3759:Nature Reviews. Drug Discovery 3298:Journal of Medicinal Chemistry 3056: 2999: 2974: 2886: 2653:-octanol-water partition ratio 2505:have frequently been applied. 1537: 803:of the aqueous phase, and log 267:Partition coefficient and log 261:transfer activity coefficients 1: 5243:Environmental Sciences Europe 4718:Ghose AK, Crippen GM (1986). 4371:10.1016/S1388-2481(99)00156-3 3847:10.1016/S0169-409X(98)00090-8 3810:10.1016/S0065-7743(10)45023-X 3800:Edwards MP, Price DA (2010). 3135:. Oxford: Blackwell Science. 2880: 1704: 1678: 1573: 1505: 6374:Inorganic nonaqueous solvent 5492:10.1016/j.drudis.2010.05.016 5409:10.1016/j.chroma.2004.01.001 4400:10.1016/0022-0728(93)03257-P 4282:10.1016/j.chroma.2003.10.084 4143:10.1016/0021-9673(93)80072-G 3728:Bodor N, Buchwald P (2012). 1625: 1530:Consumer product development 7: 5397:Journal of Chromatography A 4690:Acta Poloniae Pharmaceutica 4541:10.1021/acs.chemrev.5b00215 4484:10.1021/acs.jpclett.2c03590 4270:Journal of Chromatography A 4131:Journal of Chromatography A 3103:. OUP Oxford. p. 129. 2828: 1753:are included to account of 1643:value(s) of the substance. 1582:determination makes use of 1202:indicates the pH-dependent 238: 10: 6476: 6359:Acid dissociation constant 5442:10.1002/9783906390437.ch17 5364:"Dortmund Data Bank (DDB)" 5079:10.2174/138620711795508331 4939:10.1016/j.bmcl.2003.12.024 4237:10.1016/j.ejps.2015.05.008 4223:) from low drug amounts". 4112:10.2174/157340906778992346 4071:10.2174/157340906778992346 3649:(1995). "Octanol log 3534:for polychlorobiphenyls". 3183:10.1002/9783906390437.ch17 3040:Modern Physical Metallurgy 2616: 1993:monoprotic acids and bases 1520:directional solidification 81:, both phases usually are 18: 6342: 6274: 6204: 6101: 5958: 5932: 5882: 5874:Thermodynamic equilibrium 5809: 5256:10.1186/s12302-018-0176-7 4978:10.1007/978-94-009-5883-8 4896:10.1007/s11030-006-9036-2 4086:"Partition Coefficients ( 4084:Heuel-Fabianek B (2006). 3354:10.3109/00498258809041669 1739:group contribution method 1390:, minus its value of log 1376:, via measured values of 6027:Distribution coefficient 5971:Hammett acidity function 5950:Liquid–liquid extraction 5859:Le Chatelier's principle 5559:10.2174/1389557053402765 5459:Hansch C, Leo A (1979). 5332:10.1021/acsomega.7b01102 4660:10.2174/1568026054637700 4625:10.2174/1386207013330896 4206:10.1002/qsar.19880070304 3536:Fresenius' Z. Anal. Chem 1886:of the un-ionized form, 1878:at a given pH, from log 1751:Hammett-type corrections 1546:Separating-funnel method 790:distribution coefficient 732:, such that the indexed 42:distribution coefficient 19:Not to be confused with 6324:Solubility table (data) 6191:Apparent molar property 4324:10.1023/A:1025025804196 4312:Pharmaceutical Research 4000:10.1073/pnas.90.18.8402 3129:"Partition Coefficient" 2874:Ionic partition diagram 2848:Lipinski's rule of five 1799:maximum common subgraph 1775:support-vector machines 1773:-based prediction uses 1578:A faster method of log 79:pharmaceutical sciences 6289:Total dissolved solids 6284:Solubility equilibrium 6209:and related quantities 5988:Coordination complexes 5924:Thermodynamic activity 5285:10.1002/etc.5620200703 3897:Arzneimittel-Forschung 2592: 2503:Hammett type equations 2477: 2403: 2351: 2277: 2221: 1982: 1907: 1865: 1410: 1196: 1166: 1128: 1018: 764: 716: 573: 486: 331:value is a measure of 287: 6450:Equilibrium chemistry 6389:Partition coefficient 6369:Polar aprotic solvent 6000:Dissociation constant 5945:Equilibrium unfolding 5832:Equilibrium chemistry 5156:. Chichester: Wiley. 4739:10.1002/jcc.540070419 2854:Lipophilic efficiency 2668:(fat solubility) and 2593: 2478: 2404: 2352: 2278: 2222: 1983: 1908: 1906:{\displaystyle f^{0}} 1866: 1620:regression parameters 1562:determination is the 1498:Agrochemical research 1471:Environmental science 1400: 1370:lipophilic efficiency 1197: 1195:{\displaystyle f^{I}} 1167: 1108: 1019: 765: 717: 574: 510:partition coefficient 487: 316:of the ratio is thus 292:partition coefficient 277: 179:partition coefficient 32:partition coefficient 21:distribution constant 6304:Enthalpy of solution 6231:Volume concentration 6226:Number concentration 5909:Predominance diagram 5892:Equilibrium constant 5480:Drug Discovery Today 2603:predict solubilities 2535: 2528:can be estimated as 2413: 2364: 2287: 2238: 2002: 1924: 1890: 1834: 1663:Single-cell approach 1438:(a process known as 1179: 1068: 830: 736: 586: 545: 366: 257:equilibrium constant 97:("water-loving") or 58:in a mixture of two 6455:Medicinal chemistry 6216:Molar concentration 6186:Dilution (equation) 5983:Binding selectivity 5959:Specific equilibria 5869:Reversible reaction 5827:Dynamic equilibrium 5803:Chemical equilibria 5733:Sangster J (1997). 5588:10.1021/cr60274a001 5521:2008Chmsp..72.1401K 5152:Sangster J (1997). 5121:2015PCCP...17.6174S 5052:10.1021/je00019a019 4884:Molecular Diversity 4861:1998JPCA..102.3762G 4580:10.1289/ehp.0800168 4472:J. Phys. Chem. Lett 3991:1993PNAS...90.8402M 3936:1986Natur.319..199E 3645:Leo A, Hoekman DH, 3621:1989JPCRD..18.1111S 3600:Sangster J (1989). 3488:10.1021/ie50550a029 3414:10.1021/bi00594a030 3310:10.1021/jm00211a010 3063:Machlin ES (2007). 2956:Sangster J (1997). 2943:10.1021/cr60274a001 2813:Pentachlorobiphenyl 2694: 2520:If the solubility, 1694:screening libraries 1568:UV/VIS spectroscopy 1522:, described by the 1153: 1003: 969: 936: 902: 759: 701: 668: 614: 568: 471: 438: 6445:Physical chemistry 6256:Isotopic abundance 6221:Mass concentration 6095:Chemical solutions 5993:Macrocyclic effect 5817:Chemical stability 5685:Pandit NK (2007). 5130:10.1039/c5cp00288e 4833:10.1248/cpb.40.127 4434:10.1039/D1AN01769A 3548:10.1007/BF00481899 3095:McAuley W (2013). 2693: 2588: 2473: 2399: 2347: 2273: 2217: 2215: 1978: 1903: 1861: 1564:shake-flask method 1457:hydrophobic effect 1451:In the context of 1434:in the intestinal 1418:In the context of 1411: 1362:medicinal chemists 1220:Dortmund Data Bank 1192: 1162: 1139: 1014: 985: 951: 918: 884: 760: 745: 712: 683: 650: 598: 569: 554: 482: 453: 420: 288: 190:partition constant 126:general anesthetic 50:) is the ratio of 6432: 6431: 6061: 6060: 6039:Common-ion effect 5966:Acid dissociation 5919:Reaction quotient 5837:Equilibrium stage 5744:978-0-471-97397-3 5725:978-0-08-033649-7 5706:978-0-7817-4478-2 5677:978-1-4200-7099-6 5632:10.1002/jps.21494 5610:978-0-8412-3060-6 5486:(15–16): 648–55. 5470:978-0-471-05062-9 5451:978-3-906390-22-2 5201:978-1-000-09499-2 4987:978-0-412-22190-3 4869:10.1021/jp980230o 4855:(21): 3762–3772. 4820:Chem. Pharm. Bull 4788:10.1021/ci700257y 4535:(24): 13093–164. 4428:(23): 7131–7143. 4175:978-0-7923-3740-9 4043:978-3-527-29383-4 3930:(6050): 199–203. 3819:978-0-12-380902-5 3743:978-1-118-40776-9 3699:10.1002/jps.21494 3668:978-0-8412-3060-6 3586:978-0-471-05062-9 3482:(10): 2114–2122. 3266:10.1021/cr9601019 3233:978-1-4200-7099-6 3192:978-3-906390-22-2 3150:978-0-86542-684-9 3110:978-0-19-965531-1 3078:978-0-08-054968-2 3049:978-0-08-098204-5 3021:978-0-7817-8355-2 2992:978-0-07-160393-5 2967:978-0-471-97397-3 2908:978-1-4757-8693-4 2826: 2825: 2797:Hexamethylbenzene 2582: 2563: 2429: 2303: 2204: 2126: 2100: 2022: 1611:linear regression 1609:is determined by 1336: 1335: 1314:Hexamethylbenzene 1301:p-Dichlorobenzene 1146: 1084: 1005: 1001: 996: 983: 967: 962: 949: 934: 929: 916: 900: 895: 882: 846: 752: 703: 694: 681: 661: 648: 605: 597: 561: 473: 469: 464: 451: 436: 431: 418: 382: 325:non-polar solvent 312:solutes, and the 280:separatory funnel 246: 245: 184:In contrast, the 28:physical sciences 6467: 6329:Solubility chart 6156:Phase separation 6116:Aqueous solution 6088: 6081: 6074: 6065: 6064: 5978:Binding constant 5864:Phase separation 5796: 5789: 5782: 5773: 5772: 5748: 5729: 5710: 5681: 5665: 5651: 5614: 5602: 5591: 5570: 5540: 5503: 5474: 5455: 5431: 5420: 5378: 5377: 5375: 5374: 5360: 5354: 5353: 5343: 5326:(9): 6244–6249. 5311: 5305: 5304: 5267: 5261: 5260: 5258: 5234: 5228: 5227: 5221: 5213: 5182: 5176: 5175: 5149: 5143: 5142: 5132: 5106: 5097: 5091: 5090: 5062: 5056: 5055: 5035: 5029: 5028: 4998: 4992: 4991: 4957: 4951: 4950: 4922: 4916: 4915: 4879: 4873: 4872: 4844: 4838: 4837: 4835: 4811: 4800: 4799: 4767: 4761: 4760: 4750: 4724: 4715: 4706: 4705: 4687: 4678: 4672: 4671: 4643: 4637: 4636: 4608: 4602: 4601: 4591: 4559: 4553: 4552: 4529:Chemical Reviews 4523: 4514: 4513: 4495: 4478:(5): 1272–1278. 4463: 4454: 4453: 4419: 4410: 4404: 4403: 4394:(1–2): 125–135. 4381: 4375: 4374: 4350: 4344: 4343: 4309: 4300: 4294: 4293: 4276:(1–2): 299–310. 4265: 4259: 4258: 4248: 4216: 4210: 4209: 4189: 4180: 4179: 4153: 4147: 4146: 4122: 4116: 4115: 4097: 4081: 4075: 4074: 4054: 4048: 4047: 4029: 4023: 4022: 4012: 4002: 3970: 3964: 3963: 3944:10.1038/319199a0 3919: 3913: 3912: 3892: 3886: 3885: 3865: 3859: 3858: 3841:(2–3): 229–254. 3830: 3824: 3823: 3797: 3791: 3790: 3754: 3748: 3747: 3725: 3719: 3718: 3682: 3673: 3672: 3660: 3642: 3633: 3632: 3629:10.1063/1.555833 3615:(3): 1111–1227. 3606: 3597: 3591: 3590: 3569: 3560: 3559: 3542:(3–4): 295–301. 3524: 3518: 3517: 3501: 3492: 3491: 3471: 3465: 3464: 3462: 3447:Acta Chem. Scand 3444: 3435: 3426: 3425: 3397: 3391: 3390: 3388: 3386: 3372: 3366: 3365: 3337: 3322: 3321: 3293: 3278: 3277: 3260:(8): 3385–3400. 3254:Chemical Reviews 3249: 3238: 3237: 3221: 3208: 3197: 3196: 3170: 3155: 3154: 3141:10.1351/goldbook 3124: 3115: 3114: 3092: 3086: 3085: 3060: 3054: 3053: 3035: 3026: 3025: 3003: 2997: 2996: 2978: 2972: 2971: 2953: 2947: 2946: 2922: 2913: 2912: 2890: 2862:Distribution law 2782:-Dichlorobenzene 2695: 2692: 2634:is known as the 2597: 2595: 2594: 2589: 2584: 2583: 2580: 2565: 2564: 2561: 2482: 2480: 2479: 2474: 2472: 2461: 2460: 2451: 2431: 2430: 2427: 2408: 2406: 2405: 2400: 2392: 2381: 2380: 2371: 2356: 2354: 2353: 2348: 2346: 2335: 2334: 2325: 2305: 2304: 2301: 2282: 2280: 2279: 2274: 2266: 2265: 2256: 2248: 2226: 2224: 2223: 2218: 2216: 2209: 2205: 2203: 2202: 2201: 2200: 2189: 2188: 2179: 2159: 2128: 2127: 2124: 2105: 2101: 2099: 2098: 2097: 2096: 2095: 2086: 2075: 2055: 2024: 2023: 2020: 1987: 1985: 1984: 1979: 1974: 1970: 1969: 1912: 1910: 1909: 1904: 1902: 1901: 1870: 1868: 1867: 1862: 1803:molecule kernels 1715:parametric model 1671:or quantitative 1554:Shake flask-type 1453:pharmacodynamics 1447:Pharmacodynamics 1420:pharmacokinetics 1414:Pharmacokinetics 1225: 1224: 1209: 1201: 1199: 1198: 1193: 1191: 1190: 1171: 1169: 1168: 1163: 1158: 1154: 1152: 1147: 1144: 1138: 1137: 1127: 1122: 1099: 1098: 1086: 1085: 1082: 1060: 1023: 1021: 1020: 1015: 1010: 1006: 1004: 1002: 999: 997: 994: 992: 991: 984: 981: 979: 978: 968: 965: 963: 960: 958: 957: 950: 947: 945: 944: 937: 935: 932: 930: 927: 925: 924: 917: 914: 912: 911: 901: 898: 896: 893: 891: 890: 883: 880: 878: 877: 870: 861: 860: 848: 847: 844: 776: 769: 767: 766: 761: 758: 753: 750: 721: 719: 718: 713: 708: 704: 702: 700: 695: 692: 690: 689: 682: 679: 677: 676: 669: 667: 662: 659: 657: 656: 649: 646: 644: 643: 636: 627: 626: 613: 612: 606: 603: 595: 578: 576: 575: 570: 567: 562: 559: 540: 530: 508:A corresponding 491: 489: 488: 483: 478: 474: 472: 470: 467: 465: 462: 460: 459: 452: 449: 447: 446: 439: 437: 434: 432: 429: 427: 426: 419: 416: 414: 413: 406: 397: 396: 384: 383: 380: 240: 230: 229: 227: 226: 221: 218: 195: 152:chemical species 6475: 6474: 6470: 6469: 6468: 6466: 6465: 6464: 6435: 6434: 6433: 6428: 6338: 6299:Solvation shell 6270: 6208: 6200: 6196:Miscibility gap 6181:Serial dilution 6176:Supersaturation 6126:Buffer solution 6097: 6092: 6062: 6057: 6010:Self-ionization 5954: 5940:Buffer solution 5928: 5878: 5805: 5800: 5756: 5751: 5745: 5726: 5707: 5678: 5611: 5471: 5452: 5395:. (secondary). 5386: 5384:Further reading 5381: 5372: 5370: 5362: 5361: 5357: 5312: 5308: 5279:(7): 1399–420. 5268: 5264: 5235: 5231: 5215: 5214: 5202: 5183: 5179: 5164: 5150: 5146: 5104: 5098: 5094: 5063: 5059: 5036: 5032: 5025: 4999: 4995: 4988: 4969: 4963: 4958: 4954: 4923: 4919: 4880: 4876: 4845: 4841: 4812: 4803: 4768: 4764: 4722: 4716: 4709: 4685: 4679: 4675: 4644: 4640: 4609: 4605: 4560: 4556: 4524: 4517: 4464: 4457: 4417: 4411: 4407: 4382: 4378: 4351: 4347: 4307: 4301: 4297: 4266: 4262: 4217: 4213: 4190: 4183: 4176: 4154: 4150: 4123: 4119: 4095: 4092: 4082: 4078: 4055: 4051: 4044: 4030: 4026: 3971: 3967: 3920: 3916: 3893: 3889: 3866: 3862: 3831: 3827: 3820: 3798: 3794: 3771:10.1038/nrd2445 3755: 3751: 3744: 3726: 3722: 3683: 3676: 3669: 3643: 3636: 3604: 3598: 3594: 3587: 3570: 3563: 3533: 3525: 3521: 3502: 3495: 3472: 3468: 3442: 3436: 3429: 3398: 3394: 3384: 3382: 3374: 3373: 3369: 3338: 3325: 3294: 3281: 3250: 3241: 3234: 3209: 3200: 3193: 3171: 3158: 3151: 3125: 3118: 3111: 3093: 3089: 3079: 3061: 3057: 3050: 3036: 3029: 3022: 3004: 3000: 2993: 2979: 2975: 2968: 2954: 2950: 2923: 2916: 2909: 2893:Kwon Y (2001). 2891: 2887: 2883: 2878: 2842:Cheminformatics 2831: 2707: 2686: 2680:Values for log 2678: 2663: 2647: 2621: 2615: 2579: 2575: 2560: 2556: 2536: 2533: 2532: 2518: 2495: 2489:prediction of p 2465: 2456: 2452: 2447: 2426: 2422: 2414: 2411: 2410: 2385: 2376: 2372: 2367: 2365: 2362: 2361: 2360:for bases with 2339: 2330: 2326: 2321: 2300: 2296: 2288: 2285: 2284: 2261: 2257: 2252: 2241: 2239: 2236: 2235: 2234:for acids with 2214: 2213: 2193: 2184: 2180: 2175: 2174: 2170: 2163: 2158: 2154: 2129: 2123: 2119: 2110: 2109: 2091: 2087: 2082: 2071: 2070: 2066: 2059: 2054: 2050: 2025: 2019: 2015: 2005: 2003: 2000: 1999: 1965: 1961: 1957: 1925: 1922: 1921: 1897: 1893: 1891: 1888: 1887: 1835: 1832: 1831: 1825: 1823: 1795:Molecule mining 1783:neural networks 1767: 1765:Knowledge-based 1735: 1707: 1696:and to predict 1681: 1665: 1649: 1647:Electrochemical 1642: 1628: 1576: 1556: 1548: 1540: 1532: 1524:Scheil equation 1508: 1500: 1493: 1473: 1449: 1416: 1388: 1381: 1353: 1348: 1237: 1216: 1207: 1186: 1182: 1180: 1177: 1176: 1148: 1143: 1133: 1129: 1123: 1112: 1107: 1103: 1094: 1090: 1081: 1077: 1069: 1066: 1065: 1055: 998: 993: 987: 986: 980: 974: 973: 964: 959: 953: 952: 946: 940: 939: 938: 931: 926: 920: 919: 913: 907: 906: 897: 892: 886: 885: 879: 873: 872: 871: 869: 865: 856: 852: 843: 839: 831: 828: 827: 786: 771: 754: 749: 737: 734: 733: 696: 691: 685: 684: 678: 672: 671: 670: 663: 658: 652: 651: 645: 639: 638: 637: 635: 631: 622: 618: 608: 607: 602: 587: 584: 583: 563: 558: 546: 543: 542: 532: 528: 466: 461: 455: 454: 448: 442: 441: 440: 433: 428: 422: 421: 415: 409: 408: 407: 405: 401: 392: 388: 379: 375: 367: 364: 363: 327:, then the log 272: 255:is the process 254: 225: 222: 219: 217: 214: 213: 211: 209: 205: 198: 175: 168: 24: 17: 12: 11: 5: 6473: 6463: 6462: 6457: 6452: 6447: 6430: 6429: 6427: 6426: 6421: 6416: 6411: 6406: 6401: 6396: 6391: 6386: 6381: 6376: 6371: 6366: 6364:Protic solvent 6361: 6356: 6348: 6346: 6340: 6339: 6337: 6336: 6331: 6326: 6321: 6316: 6311: 6309:Lattice energy 6306: 6301: 6296: 6291: 6286: 6280: 6278: 6272: 6271: 6269: 6268: 6263: 6258: 6253: 6248: 6243: 6238: 6233: 6228: 6223: 6218: 6212: 6210: 6202: 6201: 6199: 6198: 6193: 6188: 6183: 6178: 6173: 6168: 6163: 6161:Eutectic point 6158: 6153: 6148: 6143: 6138: 6133: 6128: 6123: 6121:Solid solution 6118: 6113: 6111:Ideal solution 6107: 6105: 6099: 6098: 6091: 6090: 6083: 6076: 6068: 6059: 6058: 6056: 6055: 6054: 6053: 6043: 6042: 6041: 6031: 6030: 6029: 6019: 6018: 6017: 6007: 6002: 5997: 5996: 5995: 5985: 5980: 5975: 5974: 5973: 5962: 5960: 5956: 5955: 5953: 5952: 5947: 5942: 5936: 5934: 5930: 5929: 5927: 5926: 5921: 5916: 5911: 5906: 5901: 5900: 5899: 5888: 5886: 5880: 5879: 5877: 5876: 5871: 5866: 5861: 5856: 5855: 5854: 5849: 5839: 5834: 5829: 5824: 5819: 5813: 5811: 5807: 5806: 5799: 5798: 5791: 5784: 5776: 5770: 5769: 5763: 5755: 5754:External links 5752: 5750: 5749: 5743: 5730: 5724: 5711: 5705: 5682: 5676: 5652: 5615: 5609: 5592: 5582:(6): 525–616. 5571: 5541: 5515:(10): 1401–8. 5504: 5475: 5469: 5456: 5450: 5421: 5387: 5385: 5382: 5380: 5379: 5355: 5306: 5262: 5229: 5200: 5177: 5162: 5144: 5115:(9): 6174–91. 5092: 5057: 5046:(3): 623–626. 5030: 5023: 4993: 4986: 4967: 4961: 4952: 4917: 4874: 4839: 4826:(1): 127–130. 4801: 4762: 4733:(4): 565–577. 4707: 4673: 4638: 4603: 4554: 4515: 4455: 4405: 4376: 4365:(2): 112–118. 4345: 4318:(8): 1317–22. 4295: 4260: 4211: 4200:(3): 133–144. 4181: 4174: 4148: 4117: 4106:(4): 405–413. 4090: 4076: 4065:(4): 405–413. 4049: 4042: 4024: 3985:(18): 8402–6. 3965: 3914: 3903:(8): 1067–80. 3887: 3860: 3825: 3818: 3792: 3765:(11): 881–90. 3749: 3742: 3720: 3674: 3667: 3634: 3592: 3585: 3561: 3531: 3519: 3516:(2406): S1–56. 3510:NBS Techn. Rep 3493: 3476:Ind. Eng. Chem 3466: 3427: 3392: 3367: 3323: 3279: 3239: 3232: 3198: 3191: 3156: 3149: 3116: 3109: 3087: 3077: 3055: 3048: 3027: 3020: 2998: 2991: 2973: 2966: 2948: 2937:(6): 525–616. 2914: 2907: 2884: 2882: 2879: 2877: 2876: 2871: 2865: 2859: 2858: 2857: 2851: 2839: 2832: 2830: 2827: 2824: 2823: 2821: 2818: 2815: 2808: 2807: 2805: 2802: 2799: 2793: 2792: 2790: 2787: 2784: 2775: 2774: 2772: 2769: 2766: 2760: 2759: 2757: 2754: 2751: 2745: 2744: 2742: 2739: 2736: 2730: 2729: 2727: 2724: 2721: 2715: 2714: 2711: 2708: 2705: 2699: 2684: 2677: 2676:Example values 2674: 2670:hydrophilicity 2661: 2645: 2617:Main article: 2614: 2611: 2599: 2598: 2587: 2578: 2574: 2571: 2568: 2559: 2555: 2552: 2549: 2546: 2543: 2540: 2517: 2507: 2493: 2485: 2484: 2471: 2468: 2464: 2459: 2455: 2450: 2446: 2443: 2440: 2437: 2434: 2425: 2421: 2418: 2398: 2395: 2391: 2388: 2384: 2379: 2375: 2370: 2358: 2345: 2342: 2338: 2333: 2329: 2324: 2320: 2317: 2314: 2311: 2308: 2299: 2295: 2292: 2272: 2269: 2264: 2260: 2255: 2251: 2247: 2244: 2228: 2227: 2212: 2208: 2199: 2196: 2192: 2187: 2183: 2178: 2173: 2169: 2166: 2162: 2157: 2153: 2150: 2147: 2144: 2141: 2138: 2135: 2132: 2130: 2122: 2118: 2115: 2112: 2111: 2108: 2104: 2094: 2090: 2085: 2081: 2078: 2074: 2069: 2065: 2062: 2058: 2053: 2049: 2046: 2043: 2040: 2037: 2034: 2031: 2028: 2026: 2018: 2014: 2011: 2008: 2007: 1989: 1988: 1977: 1973: 1968: 1964: 1960: 1956: 1953: 1950: 1947: 1944: 1941: 1938: 1935: 1932: 1929: 1900: 1896: 1882:and the known 1872: 1871: 1860: 1857: 1854: 1851: 1848: 1845: 1842: 1839: 1824: 1821: 1807: 1779:decision trees 1766: 1763: 1759:steric effects 1734: 1733:Fragment-based 1731: 1706: 1703: 1680: 1677: 1673:Image analysis 1664: 1661: 1648: 1645: 1640: 1627: 1624: 1596:retention time 1575: 1572: 1555: 1552: 1547: 1544: 1539: 1536: 1531: 1528: 1507: 1504: 1499: 1496: 1491: 1472: 1469: 1448: 1445: 1432:lipid bilayers 1415: 1412: 1386: 1379: 1352: 1349: 1347: 1344: 1334: 1333: 1330: 1327: 1323: 1322: 1319: 1316: 1310: 1309: 1306: 1303: 1297: 1296: 1293: 1290: 1284: 1283: 1280: 1277: 1271: 1270: 1267: 1264: 1258: 1257: 1254: 1251: 1245: 1244: 1238: 1235: 1229: 1215: 1212: 1189: 1185: 1173: 1172: 1161: 1157: 1151: 1142: 1136: 1132: 1126: 1121: 1118: 1115: 1111: 1106: 1102: 1097: 1093: 1089: 1080: 1076: 1073: 1025: 1024: 1013: 1009: 990: 977: 972: 956: 943: 923: 910: 905: 889: 876: 868: 864: 859: 855: 851: 842: 838: 835: 785: 779: 757: 748: 744: 741: 723: 722: 711: 707: 699: 688: 675: 666: 655: 642: 634: 630: 625: 621: 617: 611: 601: 594: 591: 566: 557: 553: 550: 536:= 1, 2, ... , 493: 492: 481: 477: 458: 445: 425: 412: 404: 400: 395: 391: 387: 378: 374: 371: 337:hydrophobicity 302:concentrations 294:, abbreviated 271: 265: 252: 244: 243: 234: 232: 223: 215: 207: 203: 174: 171: 166: 138:solid solution 111:lipid bilayers 52:concentrations 15: 9: 6: 4: 3: 2: 6472: 6461: 6458: 6456: 6453: 6451: 6448: 6446: 6443: 6442: 6440: 6425: 6422: 6420: 6417: 6415: 6412: 6410: 6407: 6405: 6402: 6400: 6397: 6395: 6392: 6390: 6387: 6385: 6382: 6380: 6377: 6375: 6372: 6370: 6367: 6365: 6362: 6360: 6357: 6354: 6350: 6349: 6347: 6345: 6341: 6335: 6332: 6330: 6327: 6325: 6322: 6320: 6317: 6315: 6312: 6310: 6307: 6305: 6302: 6300: 6297: 6295: 6292: 6290: 6287: 6285: 6282: 6281: 6279: 6277: 6273: 6267: 6264: 6262: 6259: 6257: 6254: 6252: 6251:Mass fraction 6249: 6247: 6246:Mole fraction 6244: 6242: 6239: 6237: 6234: 6232: 6229: 6227: 6224: 6222: 6219: 6217: 6214: 6213: 6211: 6207: 6206:Concentration 6203: 6197: 6194: 6192: 6189: 6187: 6184: 6182: 6179: 6177: 6174: 6172: 6169: 6167: 6164: 6162: 6159: 6157: 6154: 6152: 6151:Phase diagram 6149: 6147: 6144: 6142: 6139: 6137: 6134: 6132: 6131:Flory–Huggins 6129: 6127: 6124: 6122: 6119: 6117: 6114: 6112: 6109: 6108: 6106: 6104: 6100: 6096: 6089: 6084: 6082: 6077: 6075: 6070: 6069: 6066: 6052: 6049: 6048: 6047: 6044: 6040: 6037: 6036: 6035: 6032: 6028: 6025: 6024: 6023: 6020: 6016: 6013: 6012: 6011: 6008: 6006: 6003: 6001: 5998: 5994: 5991: 5990: 5989: 5986: 5984: 5981: 5979: 5976: 5972: 5969: 5968: 5967: 5964: 5963: 5961: 5957: 5951: 5948: 5946: 5943: 5941: 5938: 5937: 5935: 5931: 5925: 5922: 5920: 5917: 5915: 5912: 5910: 5907: 5905: 5904:Phase diagram 5902: 5898: 5897:determination 5895: 5894: 5893: 5890: 5889: 5887: 5885: 5881: 5875: 5872: 5870: 5867: 5865: 5862: 5860: 5857: 5853: 5850: 5848: 5845: 5844: 5843: 5840: 5838: 5835: 5833: 5830: 5828: 5825: 5823: 5820: 5818: 5815: 5814: 5812: 5808: 5804: 5797: 5792: 5790: 5785: 5783: 5778: 5777: 5774: 5767: 5764: 5761: 5758: 5757: 5746: 5740: 5736: 5731: 5727: 5721: 5717: 5712: 5708: 5702: 5698: 5694: 5693: 5688: 5683: 5679: 5673: 5669: 5664: 5663: 5657: 5653: 5649: 5645: 5641: 5637: 5633: 5629: 5626:(3): 861–93. 5625: 5621: 5616: 5612: 5606: 5601: 5600: 5593: 5589: 5585: 5581: 5577: 5572: 5568: 5564: 5560: 5556: 5553:(2): 127–33. 5552: 5548: 5542: 5538: 5534: 5530: 5526: 5522: 5518: 5514: 5510: 5505: 5501: 5497: 5493: 5489: 5485: 5481: 5476: 5472: 5466: 5462: 5457: 5453: 5447: 5443: 5439: 5435: 5430: 5429: 5422: 5418: 5414: 5410: 5406: 5403:(1–2): 3–14. 5402: 5398: 5394: 5389: 5388: 5369: 5365: 5359: 5351: 5347: 5342: 5337: 5333: 5329: 5325: 5321: 5317: 5310: 5302: 5298: 5294: 5290: 5286: 5282: 5278: 5274: 5266: 5257: 5252: 5248: 5244: 5240: 5233: 5225: 5219: 5211: 5207: 5203: 5197: 5193: 5192: 5187: 5181: 5173: 5169: 5165: 5163:0-471-97397-1 5159: 5155: 5148: 5140: 5136: 5131: 5126: 5122: 5118: 5114: 5110: 5103: 5096: 5088: 5084: 5080: 5076: 5073:(5): 328–38. 5072: 5068: 5061: 5053: 5049: 5045: 5041: 5034: 5026: 5024:9780124095472 5020: 5016: 5012: 5008: 5004: 4997: 4989: 4983: 4979: 4975: 4971: 4964:Prediction". 4956: 4948: 4944: 4940: 4936: 4932: 4928: 4921: 4913: 4909: 4905: 4901: 4897: 4893: 4889: 4885: 4878: 4870: 4866: 4862: 4858: 4854: 4850: 4843: 4834: 4829: 4825: 4821: 4817: 4810: 4808: 4806: 4797: 4793: 4789: 4785: 4782:(6): 2140–8. 4781: 4777: 4773: 4766: 4758: 4754: 4749: 4748:2027.42/38274 4744: 4740: 4736: 4732: 4728: 4721: 4714: 4712: 4703: 4699: 4695: 4691: 4684: 4677: 4669: 4665: 4661: 4657: 4654:(8): 751–62. 4653: 4649: 4642: 4634: 4630: 4626: 4622: 4619:(6): 453–75. 4618: 4614: 4607: 4599: 4595: 4590: 4585: 4581: 4577: 4574:(5): 685–95. 4573: 4569: 4565: 4558: 4550: 4546: 4542: 4538: 4534: 4530: 4522: 4520: 4511: 4507: 4503: 4499: 4494: 4489: 4485: 4481: 4477: 4473: 4469: 4462: 4460: 4451: 4447: 4443: 4439: 4435: 4431: 4427: 4423: 4416: 4409: 4401: 4397: 4393: 4389: 4388: 4380: 4372: 4368: 4364: 4360: 4356: 4349: 4341: 4337: 4333: 4329: 4325: 4321: 4317: 4313: 4306: 4299: 4291: 4287: 4283: 4279: 4275: 4271: 4264: 4256: 4252: 4247: 4242: 4238: 4234: 4230: 4226: 4222: 4215: 4207: 4203: 4199: 4195: 4188: 4186: 4177: 4171: 4167: 4163: 4159: 4152: 4144: 4140: 4137:(1–2): 3–14. 4136: 4132: 4128: 4121: 4113: 4109: 4105: 4101: 4094: 4089: 4080: 4072: 4068: 4064: 4060: 4053: 4045: 4039: 4035: 4028: 4020: 4016: 4011: 4006: 4001: 3996: 3992: 3988: 3984: 3980: 3976: 3969: 3961: 3957: 3953: 3949: 3945: 3941: 3937: 3933: 3929: 3925: 3918: 3910: 3906: 3902: 3898: 3891: 3883: 3879: 3876:(3): 248–76. 3875: 3871: 3864: 3856: 3852: 3848: 3844: 3840: 3836: 3829: 3821: 3815: 3811: 3807: 3803: 3796: 3788: 3784: 3780: 3776: 3772: 3768: 3764: 3760: 3753: 3745: 3739: 3735: 3731: 3724: 3716: 3712: 3708: 3704: 3700: 3696: 3693:(3): 861–93. 3692: 3688: 3681: 3679: 3670: 3664: 3659: 3658: 3652: 3648: 3641: 3639: 3630: 3626: 3622: 3618: 3614: 3610: 3603: 3596: 3588: 3582: 3578: 3574: 3568: 3566: 3557: 3553: 3549: 3545: 3541: 3537: 3530: 3523: 3515: 3511: 3507: 3500: 3498: 3489: 3485: 3481: 3477: 3470: 3461: 3456: 3452: 3448: 3441: 3434: 3432: 3423: 3419: 3415: 3411: 3407: 3403: 3396: 3381: 3377: 3371: 3363: 3359: 3355: 3351: 3348:(3): 331–50. 3347: 3343: 3336: 3334: 3332: 3330: 3328: 3319: 3315: 3311: 3307: 3303: 3299: 3292: 3290: 3288: 3286: 3284: 3275: 3271: 3267: 3263: 3259: 3255: 3248: 3246: 3244: 3235: 3229: 3225: 3220: 3219: 3213: 3207: 3205: 3203: 3194: 3188: 3184: 3180: 3176: 3169: 3167: 3165: 3163: 3161: 3152: 3146: 3142: 3138: 3134: 3130: 3123: 3121: 3112: 3106: 3102: 3098: 3091: 3084: 3080: 3074: 3070: 3066: 3059: 3051: 3045: 3041: 3034: 3032: 3023: 3017: 3013: 3009: 3002: 2994: 2988: 2984: 2977: 2969: 2963: 2959: 2952: 2944: 2940: 2936: 2932: 2928: 2921: 2919: 2910: 2904: 2900: 2896: 2889: 2885: 2875: 2872: 2869: 2866: 2863: 2860: 2855: 2852: 2849: 2846: 2845: 2843: 2840: 2837: 2834: 2833: 2822: 2819: 2816: 2814: 2810: 2809: 2806: 2803: 2800: 2798: 2795: 2794: 2791: 2788: 2785: 2783: 2781: 2777: 2776: 2773: 2770: 2767: 2765: 2764:Diethyl ether 2762: 2761: 2758: 2755: 2752: 2750: 2747: 2746: 2743: 2740: 2737: 2735: 2732: 2731: 2728: 2725: 2722: 2720: 2717: 2716: 2712: 2709: 2704: 2700: 2697: 2696: 2691: 2688: 2683: 2673: 2671: 2667: 2666:lipophilicity 2660: 2656: 2654: 2652: 2644: 2640: 2638: 2633: 2629: 2627: 2620: 2610: 2608: 2605:, and so log 2604: 2585: 2576: 2572: 2569: 2566: 2557: 2553: 2550: 2547: 2544: 2541: 2538: 2531: 2530: 2529: 2527: 2523: 2516: 2512: 2506: 2504: 2500: 2496: 2492: 2462: 2457: 2453: 2444: 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Retrieved 3379: 3370: 3345: 3341: 3301: 3297: 3257: 3253: 3217: 3174: 3132: 3100: 3090: 3082: 3068: 3058: 3039: 3011: 3001: 2982: 2976: 2957: 2951: 2934: 2930: 2898: 2888: 2811:2,2′,4,4′,5- 2779: 2702: 2689: 2681: 2679: 2658: 2657: 2650: 2649: 2642: 2636: 2635: 2625: 2622: 2606: 2600: 2525: 2521: 2519: 2514: 2510: 2498: 2490: 2486: 2229: 1990: 1879: 1875: 1873: 1826: 1818: 1814: 1810: 1801:searches or 1790: 1786: 1768: 1746: 1742: 1736: 1726:training set 1710: 1708: 1698:druglikeness 1682: 1666: 1650: 1636: 1632: 1629: 1614: 1606: 1604: 1599: 1587: 1579: 1577: 1563: 1559: 1557: 1549: 1541: 1533: 1516:zone melting 1509: 1501: 1488: 1482:hydrogeology 1474: 1450: 1417: 1406: 1402: 1391: 1366:druglikeness 1357: 1354: 1351:Pharmacology 1346:Applications 1339: 1337: 1240: 1232: 1217: 1174: 1056: 1051: 1047: 1046:in terms of 1043: 1041: 1036: 1032: 1028: 1026: 818: 816: 808: 804: 795: 793: 789: 787: 782: 772: 728: 726: 724: 537: 533: 524: 515: 513: 509: 507: 497: 494: 352: 328: 319: 317: 296: 295: 291: 289: 283: 268: 249: 247: 236: 200: 189: 183: 178: 176: 173:Nomenclature 163: 160:dissociation 149: 142: 119: 103:distribution 72: 62:solvents at 46: 45: 41: 36: 35: 31: 25: 6419:Lyonium ion 6334:Miscibility 6319:Henry's law 6051:Henry's law 5842:Free energy 5509:Chemosphere 4696:(1): 3–18. 4246:2445/143737 3453:: 774–780. 3304:(1): 53–8. 2804:25 °C 2789:25 °C 2771:20 °C 2756:25 °C 2749:Formic acid 2741:19 °C 2726:25 °C 1771:data-mining 1657:electrolyte 1592:correlating 1538:Measurement 1275:Formic acid 349:denominator 341:hydrophilic 156:association 115:blood serum 99:hydrophobic 95:hydrophilic 87:hydrophobic 64:equilibrium 6439:Categories 6414:Amphiphile 6409:Lipophilic 6404:Hydrophile 6399:Hydrophobe 6276:Solubility 6171:Saturation 6141:Suspension 6034:Solubility 6005:Hydrolysis 5914:Phase rule 5760:vcclab.org 5373:2020-05-20 5210:1182869019 4231:: 181–91. 2881:References 2713:Reference 2698:Substance 1769:A typical 1755:electronic 1724:, using a 1722:estimation 1705:Atom-based 1679:Prediction 1586:. The log 1574:HPLC-based 1512:metallurgy 1506:Metallurgy 1436:epithelium 1228:Component 1000:un-ionized 933:un-ionized 531:-th form ( 468:un-ionized 435:un-ionized 89:, such as 68:un-ionized 60:immiscible 6424:Lyate ion 6379:Solvation 6294:Solvation 6236:Normality 6022:Partition 5852:Helmholtz 5822:Chelation 5656:Martin YC 5320:ACS Omega 5218:cite book 4510:256415374 4450:240110114 3787:205476574 3380:ddbst.com 3212:Martin YC 2931:Chem. Rev 2719:Acetamide 2573:⁡ 2567:− 2554:⁡ 2542:⁡ 2513:from log 2445:− 2439:⁡ 2433:≅ 2420:⁡ 2383:− 2337:− 2313:⁡ 2307:≅ 2294:⁡ 2250:− 2191:− 2152:⁡ 2140:⁡ 2134:≅ 2117:⁡ 2080:− 2048:⁡ 2036:⁡ 2030:≅ 2013:⁡ 1955:⁡ 1943:⁡ 1937:≅ 1931:⁡ 1853:⁡ 1847:≅ 1841:⁡ 1813:from log 1626:pH-metric 1428:drug-like 1249:Acetamide 1110:∑ 1101:⁡ 1075:⁡ 1054:as state 863:⁡ 837:⁡ 743:⁡ 629:⁡ 593:⁡ 552:⁡ 399:⁡ 373:⁡ 345:numerator 314:logarithm 91:1-octanol 6460:Solvents 6394:Polarity 6353:Category 6241:Molality 6103:Solution 6015:of water 5810:Concepts 5640:18683876 5576:Chem Rev 5567:15720283 5537:18565570 5500:20570751 5417:15214657 5350:31457869 5301:25971836 5293:11434281 5188:(2021). 5186:Mackay D 5172:36430034 5139:25660403 5087:21470182 4947:15012980 4904:17031534 4796:17985865 4702:23610954 4668:16101415 4633:11562252 4598:19479008 4549:26624238 4502:36719904 4442:34726203 4332:12948031 4290:15214672 4255:25968358 3960:21867582 3855:10837718 3779:17971784 3707:18683876 3647:Hansch C 3573:Hansch C 3556:91775126 3385:19 March 3274:11851494 2927:Hansch C 2829:See also 2820:Ambient 2734:Methanol 2628:-Octanol 1793:values. 1602:values. 1461:receptor 1332:Ambient 1262:Methanol 813:buffered 83:solvents 75:chemical 56:compound 6344:Solvent 6146:Colloid 6136:Mixture 5648:9595034 5517:Bibcode 5341:6644330 5117:Bibcode 4912:1196330 4857:Bibcode 4757:4272062 4589:2685828 4493:9923738 4422:Analyst 4340:9917932 4019:8378312 3987:Bibcode 3952:3945310 3932:Bibcode 3715:9595034 3617:Bibcode 3362:3289270 2925:Leo A, 2753:−0.413 2738:−0.824 2723:−1.155 1374:potency 1206:of the 1145:oct/wat 1083:oct/wat 966:ionized 928:octanol 899:ionized 894:octanol 845:oct/wat 751:oct/wat 660:octanol 604:oct/wat 560:oct/wat 521:ionized 430:octanol 381:oct/wat 357:octanol 310:ionized 228:⁠ 212:⁠ 73:In the 26:In the 5884:Models 5766:XLOGP3 5741: 5722: 5703: 5674: 5646: 5638: 5607: 5565: 5535: 5498: 5467: 5448: 5436:–304. 5415: 5348: 5338: 5299: 5291: 5208: 5198: 5170: 5160: 5137: 5085: 5021: 4984: 4945: 4910: 4902: 4794: 4755: 4700: 4666: 4631: 4596: 4586: 4547: 4508: 4500: 4490: 4448: 4440: 4338: 4330: 4288: 4253: 4172: 4166:passim 4040: 4017: 4007: 3958: 3950: 3924:Nature 3907: 3880: 3853: 3816: 3785: 3777: 3740: 3713: 3705: 3665: 3583: 3554: 3422:618544 3420: 3360: 3316: 3272: 3230: 3189: 3147: 3107: 3075: 3046: 3018: 2989: 2964: 2905: 2817:6.410 2801:4.610 2786:3.370 2768:0.833 1484:, the 982:solute 948:solute 915:solute 881:solute 807:= log 775:> 0 680:solute 647:solute 596: 500:, the 450:solute 417:solute 306:solute 248:where 6166:Alloy 5847:Gibbs 5697:34–37 5670:–73. 5644:S2CID 5297:S2CID 5249:(1). 5105:(PDF) 4908:S2CID 4753:S2CID 4723:(PDF) 4686:(PDF) 4506:S2CID 4446:S2CID 4418:(PDF) 4336:S2CID 4308:(PDF) 4096:(PDF) 4010:47364 3956:S2CID 3909:40579 3882:43264 3783:S2CID 3711:S2CID 3605:(PDF) 3552:S2CID 3443:(PDF) 3318:13215 3226:–73. 2868:ITIES 2641:, or 2632:water 2428:bases 2302:acids 2125:bases 2021:acids 1817:and p 1781:, or 1653:ITIES 1409:axis) 1279:−0.41 1266:−0.81 1253:−1.16 1243:(°C) 995:water 961:water 693:water 463:water 304:of a 186:IUPAC 134:metal 130:solid 124:of a 54:of a 40:) or 5739:ISBN 5720:ISBN 5701:ISBN 5672:ISBN 5636:PMID 5605:ISBN 5563:PMID 5533:PMID 5496:PMID 5465:ISBN 5446:ISBN 5413:PMID 5401:1037 5346:PMID 5289:PMID 5224:link 5206:OCLC 5196:ISBN 5168:OCLC 5158:ISBN 5135:PMID 5083:PMID 5019:ISBN 4982:ISBN 4943:PMID 4900:PMID 4792:PMID 4698:PMID 4664:PMID 4629:PMID 4594:PMID 4545:PMID 4498:PMID 4438:PMID 4328:PMID 4286:PMID 4274:1037 4251:PMID 4170:ISBN 4038:ISBN 4015:PMID 3948:PMID 3905:PMID 3878:PMID 3851:PMID 3814:ISBN 3775:PMID 3738:ISBN 3703:PMID 3663:ISBN 3581:ISBN 3418:PMID 3387:2016 3358:PMID 3314:PMID 3270:PMID 3228:ISBN 3187:ISBN 3145:ISBN 3105:ISBN 3073:ISBN 3044:ISBN 3016:ISBN 2987:ISBN 2962:ISBN 2903:ISBN 2701:log 2630:and 2509:Log 2487:For 2394:> 2268:> 1809:Log 1757:and 1690:QSAR 1594:its 1424:ADME 1329:6.41 1318:4.61 1305:3.37 1292:0.83 1231:log 817:log 794:log 788:The 727:log 514:log 347:and 318:log 290:The 145:HPLC 77:and 30:, a 5628:doi 5584:doi 5555:doi 5525:doi 5488:doi 5438:doi 5434:275 5405:doi 5336:PMC 5328:doi 5281:doi 5251:doi 5125:doi 5075:doi 5048:doi 5011:doi 4974:doi 4935:doi 4892:doi 4865:doi 4853:102 4828:doi 4784:doi 4743:hdl 4735:doi 4656:doi 4621:doi 4584:PMC 4576:doi 4572:117 4537:doi 4533:115 4488:PMC 4480:doi 4430:doi 4426:146 4396:doi 4392:372 4367:doi 4320:doi 4278:doi 4241:hdl 4233:doi 4202:doi 4139:doi 4135:642 4108:doi 4067:doi 4005:PMC 3995:doi 3940:doi 3928:319 3843:doi 3806:doi 3767:doi 3695:doi 3653:". 3625:doi 3544:doi 3540:331 3484:doi 3455:doi 3410:doi 3350:doi 3306:doi 3262:doi 3179:doi 3137:doi 2939:doi 2570:log 2551:log 2539:log 2436:log 2417:log 2310:log 2291:log 2149:log 2137:log 2114:log 2045:log 2033:log 2010:log 1952:log 1940:log 1928:log 1850:log 1838:log 1510:In 1385:pEC 1383:or 1378:pIC 1321:25 1308:25 1295:20 1282:25 1269:19 1256:25 1092:log 1072:log 1059:= 0 854:log 834:log 740:log 620:log 590:log 549:log 390:log 370:log 335:or 216:org 158:or 6441:: 5699:. 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