Octanol/water partition parameter

Both 3- and 4-substituted TFMS series members exhibit at least some dependence on tt, the octanol/water partitioning parameter. As judged by the magnitudes of the tr and tt2 parameter coefficients, one must conclude that the herbicidal activity of the 4-substituted sulfonanilides in general depends much more strongly on partitioning events than does the activity of 3-substituted series members both in the presence and absence of surfactant. 

An overview of some basic mathematical techniques for data correlation is to be found herein together with background on several types of physical property correlating techniques and a road map for the use of selected methods. Methods are presented for the correlation of observed experimental data to physical properties such as critical properties, normal boiling point, molar volume, vapor pressure, heats of vaporization and fusion, heat capacity, surface tension, viscosity, thermal conductivity, acentric factor, flammability limits, enthalpy of formation, Gibbs energy, entropy, activity coefficients, Henry s constant, octanol—water partition coefficients, diffusion coefficients, virial coefficients, chemical reactivity, and toxicological parameters. 

Many additional consistency tests can be derived from phase equiUbrium constraints. From thermodynamics, the activity coefficient is known to be the fundamental basis of many properties and parameters of engineering interest. Therefore, data for such quantities as Henry s constant, octanol—water partition coefficient, aqueous solubiUty, and solubiUty of water in chemicals are related to solution activity coefficients and other properties through fundamental equiUbrium relationships (10,23,24). Accurate, consistent data should be expected to satisfy these and other thermodynamic requirements. Furthermore, equiUbrium models may permit a missing property value to be calculated from those values that are known (2). 

A sampling of appHcations of Kamlet-Taft LSERs include the following. (/) The Solvatochromic Parameters for Activity Coefficient Estimation (SPACE) method for infinite dilution activity coefficients where improved predictions over UNIEAC for a database of 1879 critically evaluated experimental data points has been claimed (263). (2) Observation of inverse linear relationship between log 1-octanol—water partition coefficient and Hquid... 

Several Hansch-Leo n substituent parameters denved from octanol-water partition coefficients (P), = log p (ce sX) - log P (C H ), are hsted m Table 9... 

Swann R, Laskowski D, McCAll P, et al. 1983. A rapid method for the estimation of the environmental parameters octanol/water partition coefficient, soil sorption constant, water to air ratio, and water solubility. Residue Rev 85 18-28. 

The importance of lipophilicity to bitterness has been well established, both directly and indirectly. The importance of partitioning effects in bitterness perception has been stressed by Rubin and coworkers, and Gardner demonstrated that the threshold concentration of bitter amino acids and peptides correlates very well with molecular connectivity (which is generally regarded as a steric parameter, but is correlated with the octanol-water partition coefficient ). Studies on the surface pressure in monolayers of lipids from bovine, circumvallate papillae also indicated that there is a very good correlation between the concentration of a bitter compound that is necessary in order to give an increase in the surface pressure with the taste threshold in humans. These results and the observations of others suggested that the ability of bitter compounds to penetrate cell membranes is an important factor in bitterness perception. 

Polar surface area (PSA) - defined simply as the part of a molecular surface that is polar - is probably, together with the octanol-water partition coefficient, one of the most important parameters used to characterize the transport properties of drugs. PSA has been shown to provide very good correlations with intestinal... 

To further analyze the relationships within descriptor space we performed a principle component analysis of the whole data matrix. Descriptors have been normalized before the analysis to have a mean of 0 and standard deviation of 1. The first two principal components explain 78% of variance within the data. The resultant loadings, which characterize contributions of the original descriptors to these principal components, are shown on Fig. 5.8. On the plot we can see that PSA, Hhed and Uhba are indeed closely grouped together. Calculated octanol-water partition coefficient CLOGP is located in the opposite corner of the property space. This analysis also demonstrates that CLOGP and PSA are the two parameters with... 

At any rate, due to its wide popularity and the vast availability of literature and in-house data, whether computed or experimentally determined, octanol-water partition or distribution data remain by far the most utilized single parameter for ADME, QSPR and QSAR predictions. 

The log octanol-water partition coefficient (log Pq/w) probably is the most frequently used physicochemical parameter in medicinal chemistry [101 104]. Octanol, with a polar head and a flexible, nonpolar tail, has hydrogen-bonding capabilities and amphilicity similar to... 

The pKa of a molecule, a charge-state-related parameter, is a descriptor of an acid-base equilibrium reaction [34,35]. Lipophilicity, often represented by the octanol-water partition coefficient Kp is a descriptor of a two-phase distribution equilibrium reaction [36]. So is solubility [37-39]. These three parameters are thermodynamic constants. On the other hand, permeability Pe is a rate coefficient, a kinetics parameter, most often posed in a first-order distribution reaction [40-42]. 

The procedure takes as input parameters the measured (or calculated) pKa and the measured (or calculated) octanol-water partition coefficient, log P. The latter parameter is used to estimate the intrinsic solubility So, using the Hansch-type expression [38], log So = 1.17 — 1.38 log P, or an improved version for ionizable molecules of moderate lipophilicity (Fig. 6.6) ... 

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. 

Nevertheless, Absolv gave us five additional parameters to work with. What is more, we used ALOGP, the predicted octanol/water partition coefficient also calculated by Absolv. We combined these descriptors with CLOGP, CMR and those from HYBOT. Forward step-wise regression gave Eq. (7) ... 

Hawker, D. W. (1990a) Vapor pressures and Henry s law constants of polychlorinated biphenyls. Environ. Sci. Technol. 23, 1250-1253. Hawker, D. W. (1990b) Description of fish bioconcentration factors in terms of solvatochromic parameters. Chemosphere 20, 267-477. Hawker, D. W., Connell, D. W. (1988) Octanol-water partition coefficients of polychlorinated biphenyl congeners. Environ. Sci. Technol. 22, 382-387. 

Kamlet, M. J., Doherty, R. M., Carr, P. W., Mackay, D., Abraham, M. H., Taft, R. W. (1988) Linear solvation energy relationships. 44. Parameter estimation rules that allow accurate prediction of octanol/water partition coefficients and other solubility and toxicity properties of polychlorinated biphenyls and polycyclic aromatic hydrocarbons. Environ. Sci. Technol. 22, 503-509. 

Sutton. C., Calder, J.A. (1975) Solubility of alkylbenzenes in distilled water and seawater at 25°C. J. Chem Eng. Data 20, 320-322. Swann, R.L., Laskowski, D.A., McCall, P.J., Vender Kuy, K., Dishburger, J.J. (1983) A rapid method for the estimation of the environmental parameters octanol/water partition coefficient, soil sorption constant, water to air ratio, and water solubility. Res. Rev. 85, 17-28. 

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. 

The physical properties of -hexane (see Table 3-2) that affect its transport and partitioning in the environment are water solubility of 9.5 mg/L log Kow (octanol/water partition coefficient), estimated as 3.29 Henry s law constant, 1.69 atm-m3 mol vapor pressure, 150 mm Hg at 25 °C and log Koc in the range of 2.90 to 3.61. As with many alkanes, experimental methods for the estimation of the Koc parameter are lacking, so that estimates must be made based on theoretical considerations (Montgomery 1991). 

Basak, S. C., Gute, B. D., and Grunwald, G. D. A comparative study of topological and geometrical parameters in estimating normal boiling point and octanol-water partition coefficient. J. Chem. Inf. Comput. Sci. 1996, 36, 1054—1060. 

The correlation (or lack of correlation) of other physiochemical characteristics has not yet been established. For instance, are all surfactants irritants Can one classify severity by the size of the molecule Can octanol water partition coefficients predict irritation potential does a propensity to partition out of the ocular fluid mean that a compound presents more of an irritation hazard than one which is more water soluble Theoretically, these data should reflect the ability of a compound to penetrate the eye and cause an irreversible lesion. However, until definitive data are available, physical and chemical parameters will probably have limited utility in an overall assessment of irritation. 

Physical and Chemical Properties. As reported in Section 3.2, the relevant physical and chemical properties of cyanide compounds are known. Certain physical parameters such as octanol/water partition coefficient and soil partition coefficient that are used generally for covalently bound organic compounds to predict environmental fate and transport are neither available nor useful for most of the ionic cyanide compounds. 

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