Hydrophobicity octanol-water partition coefficient

Figure 5.5 Comparing liposome-water to octanol-water partition coefficients of a series of uncharged substituted benzylalkylamines [387]. The membrane partitioning of the smaller members of the series (n — 0 3) is thought to be dominated by electrostatic and H-bonding effects (enthalpy-driven), whereas the partitioning of the larger members is thought to be directed by hydrophobic forces (entropy-driven) [387]. [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

Winters and Lee134 describe a physically based model for adsorption kinetics for hydrophobic organic chemicals to and from suspended sediment and soil particles. The model requires determination of a single effective dififusivity parameter, which is predictable from compound solution diffusivity, the octanol-water partition coefficient, and the adsorbent organic content, density, and porosity. 

Second, P-gp differs from other transporters in that it recognizes its substrates when dissolved in the lipid membrane [52], and not when dissolved in aqueous solution. The site of recognition and binding has been shown to be located in the membrane leaflet facing the cytosol [53, 54], This implies that the membrane concentration of the substrate, Csm, determines activation [57]. Since the nature of a molecular interaction is strongly influenced by the solvent, the lipid membrane must be taken into account as the solvent for the SAR analysis of P-gp. Under certain conditions, the effect of additional solvents or excipients (used to apply hydrophobic substrates or inhibitors) on the lipid membrane and/or on the transporter must also be considered. Lipophilicity of substrates has long been known to play an important role in P-gp-substrate interactions nevertheless, the correlation of the octanol/water partition coefficients with the concentration of half-maximum... 

The octanol-water partition coefficient KqW provides a direct estimate of hydrophobicity or of partitioning tendency from water to organic media such as lipids, waxes and natural organic matter such as humin or humic acid. It is invaluable as a method of estimating KoC, the organic carbon-water partition coefficient, the usual correlation invoked being that of Karickhoff (1981)... 

The octanol-water partition coefficient Kow is widely used as a descriptor of hydrophobicity. Variation in /fow is primarily attributable to variation in activity coefficient in the aqueous phase (Miller et al. 1985) thus, the same correlations used for solubility in water are applicable to /fow. Most widely used is the Hansch-Leo compilation of data (Leo et al. 1971, Hansch and Leo 1979) and related predictive methods. Examples of Kow correlations are ... 

Bruggeman, W. A., van der Steen, J., Hutzinger, O. (1982) Reversed-phase thin-layer chromatography of polynuclear aromatic hydrocarbons and chlorinated biphenyls. Relationship with hydrophobicity as measured by aqueous solubility and octanol-water partition coefficient. J. Chromatogr. 238, 335-346. 

De Bruijn, J., Busser, G., Seinen, W., Hermens, J. (1989) Determination of octanol/water partition coefficient for hydrophobic organic chemicals with the slow-stirring method. Environ. Toxicol. Chem. 8, 499-512. 

De Bruijn, J., Hermens, J. (1990) Relationships between octanol/water partition coefficients and total molecular surface area and total molecular volume of hydrophobic organic chemicals. Quant. Struct.-Act. Relat. 9, 11-21. 

Doucette, W. J., Andren, A. W. (1987) Correlation of octanol/water partition coefficients and total molecular surface area for highly hydrophobic aromatic compounds. Environ. Sci. Technol. 21, 521-524. 

Wasik, S. P., Miller, M. M., Tewari, Y. B., May, W. E., Sonnefeld, W. J., DeVoe, H., Zoller, W. H. (1983) Determination of the vapor pressure, aqueous solubihty, and octanol/water partition coefficient of hydrophobic substances by coupled generator column/ liquid chromatographic methods. Res. Rev. 85, 29 42. 

DeVoe, H., Miller, M.M., Wasik, S.P. (1981) Generator columns and high pressure liquid chromatography for determining aqueous solubilities and octanol-water partition coefficients of hydrophobic substances. J. Res. Natl. Bur. Std. 86, 361. 

Doucette, W.J., Andren, A.W. (1988) Estimation of octanol/water partition coefficients Evaluation of six methods for highly hydrophobic aromatic hydrocarbons. Chemosphere 17, 345-359. 

Fisk, A.T., R.J. Norstrom, C.D. Cymbalisty, and D.C.G. Muir. 1998. Dietary accumulation and depuration of hydrophobic organochlorines bioaccumulation parameters and their relationship with the octanol/water partition coefficient. Environ. Toxicol. Chem. 17 951-961. 

Log P is the hydrophobicity (log octanol-water partition coefficient) calculated according to the Ghose-Crippen algorithm.201 dpifA of the carboxylic acid corresponding to the W-acyloxyl substituent. 

The octanol-water partition coefficient, Kow, is the most widely used descriptor of hydrophobicity in quantitative structure activity relationships (QSAR), which are used to describe sorption to organic matter, soil, and sediments [15], bioaccumulation [104], and toxicity [105 107J. Octanol is an amphiphilic bulk solvent with a molar volume of 0.12 dm3 mol when saturated with water. In the octanol-water system, octanol contains 2.3 mol dm 3 of water (one molecule of water per four molecules of octanol) and water is saturated with 4.5 x 10-3 mol dm 3 octanol. Octanol is more suitable than any other solvent system (for) mimicking biological membranes and organic matter properties, because it contains an aliphatic alkyl chain for pure van der Waals interactions plus the alcohol group, which can act as a hydrogen donor and acceptor. 

The octanol-water partition coefficient appears to correlate better with biological activity than partition coefficients in other solvent-water mixtures as, for example, hexane water, because the amphiphilic nature of octanol can accommodate a greater variety of more or less hydrophobic molecules. 

The most notable correlation found for the organic carbon partition coefficient (Koc) of hydrophobic chemicals is that obtained with the octanol/water partition coefficient (Kow). Recently, a single correlation has been proposed for all these compounds based on previous data (log(Koc/Kow) versus logAow) the specific approximation proposed was Koc = 0.35 Kow, but this could vary by a factor of 2.5 in either direction [39]. 

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