Property-1 -octanol-water partition coefficient correlations

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. 

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... 

The order of the mobilities of alachlor, butylate, and metolachlor in columns of various soils was metolachlor > alachlor > butylate. This correlates directly with the water solubilities and inversely to the adsorption coefficients and octanol/water partition coefficients of these compounds. Diffusion of these compounds in soil thin-layers was as follows butylate > alachlor > metolachlor, which correlates directly with the vapor pressures of these compounds. Significant soil properties affecting diffusion appeared to be bulk density and temperature. Soil moisture is also probably important, but its effect on the diffusion of these compounds was not determined. 

Many groups have discussed the correlation between solubility and molecular properties [14-19], and the octanol/water partition coefficient, the molecular volume and surface area, the boiling point and charge distribution in the molecules are well-documented molecular descriptors that correlate strongly with experimental solubility. 

K generally varies only by factors of three to five for a given solute (12). K typically correlates well with physico-chemical properties of the sorbate, such as aqueous solubility (S) or the octanol-water partition coefficient (K ), again suggesting that hydrophobic interaction predominates. The correlation of Koc with K has led to the definition of linear free-energy relationships (LFER) of the form... 

Kamlet MJ, Abraham MH, Doherty RM, Taft RW (1984) Solubility properties in polymers and biological media. 4. Correlation of octanol/water partition coefficients with solvatochromic parameters. J Am Chem Soc 106 464-466. 

PhC properties most investigated by scientists to date are their water solubility (s, mg/mL), volatility (correlated to the Henry constant H) (pg m atr/pg m wastewater), biodegradability (correlated to pseudo-first-order degradation constant bioi L gSS d ), acid dissociation constant K, distribution and sorption (through the sludge-water distribution coefficient K, expressed in L gSS or the octanol-water partition coefficient Kg ). The main focus has been to find any correlations between these parameters and to determine PhC removal rates during the different treatment steps. Thus, different properties have been quantified for many compounds, and software, such as EPl Suite 4.00 [54], consenting their estimation, is available. 

In view of the predictive properties of the octanol-water partition coefficient, logP, in the description of enzymatic activity [79], this parameter has received much attention. However, as argued in an early but still authoritative review compiled by Carrea and coworkers [80], its usefulness in the correlation of solvent effects on enantioselectivity appears to be limited. The problem is exemplified by the entries in Figure... 

The physicochemical properties that correlate with the biological property are likely to be related to the mechanism by which the chemicals cause the biological activity, and are often referred to as descriptors of the biological activity. Examples of physicochemical properties that often correlate with biological activity and used in the quantification of SARs include octanol-water partition coefficient (logP0/w), dissociation constant (p/<,), and molar refractivity (MR), among others. 

This area is a development in the usage of NDDO models that emphasizes their utility for large-scale problems. Structure-activity relationships (SARs) are widely used in the pharmaceutical industry to understand how the various features of biologically active molecules contribute to their activity. SARs typically take the form of equations, often linear equations, that quantify activity as a function of variables associated with the molecules. The molecular variables could include, for instance, molecular weight, dipole moment, hydrophobic surface area, octanol-water partition coefficient, vapor pressure, various descriptors associated with molecular geometry, etc. For example, Cramer, Famini, and Lowrey (1993) found a strong correlation (r = 0.958) between various computed properties for 44 alkylammonium ions and their ability to act as acetylcholinesterase inhibitors according to the equation... 

Most commonly, correlations are made to chemical constants that are defined by the effect of substituents on a reference reaction. They are usually designated o and are applied to QSARs in the form of Hammett s equation or its various extensions. Alternatively, a descriptor can be a property of a substrate molecule that is available, is readily measurable, and/or can be calculated by independent means, such as octanol/water partition coefficients. Despite their numerous successful applications in QSAR studies, experimentally determined o constants also have some disadvantages. They are available only for a limited set of substituents and are not of very good quality for uncommon functional groups. As an alternative, the use of quantum-chemical parameters may be a solution. 

The parameter is measured using low-solute concentrations less than 0.01 mol/L, where /< , is not affected by solute concentration. Values of Kow are usually measured at room temperature (20 or 25°C). Numerous studies have shown that it is useful to correlate K,r with biological, biochemical, or toxic properties. In recent years, the octanol/water partition coefficient has become a key parameter in studies of the environmental fate of organics,... 

Correlation with Physical and Chemical Properties — The Octanol/Water Partition Coefficient (Kow)and Aqueous Solubility (S)... 

Kaiser, K.L.E., Dixon, D.G., Hodson, PV. (1984) QSAR studies on chlorophenols, chlorobenzenes and para-substituted phenols. In QSAR in Environmental Toxicology. Kaiser, K. L. E., Ed., pp. 189-206, D. Reidel Publishing Co., Dordrecht, The Netherlands. Kamlet, M.J., Doherty, R.M., Carr, P.W., Mackay, D., Abraham, M.H., Taft, R.W. (1988) Linear solvation energy relationship. 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. Kanazawa, J. (1981) Measurement of the bioconcentration factors of pesticides by fresh-water fish and their correlation with physicochemical properties of acute toxicities. Pest. Sci. 12, 417-424. 

An advantage of defining the problem in this manner is that the partition coefficient has become a central property in quantitative structure-activity relationships (QSAR) and a large data base of P values is available in the medicinal chemistry literature (22-24). In particular, if a correlation (Equation 15) between the polymer-water and octanol-water partition coefficients can be established for a series of solutes, it becomes possible to utilize log P (oc-tanol/water) value as a reference point from which to calculate the polymer-water value. 

Bioaccumulation is a partition phenomenon, as the above equations indicate. A common surrogate for partitioning of a chemical between an organism and water is its octanol-water partition coefficient, Kow (sometimes written simply as P), and it will be seen later that this property (in the form of its common logarithm, log Kow) in many cases correlates well with bioaccumulation. 

This equation has been mainly used in correlations of aqueous solubility of compounds, octanol/water partition coefficients and some other partition parameters together with some biological properties [Kamlet et al., 1984 Kamlet et al., 1986a Kam-let et al, 1987a Kamlet et al, 1987c Kamlet et al, 1988c]. 

Kamlet, M.J., Abraham, M.H., Doherty, R.M. and Taft, R.W. (1984). Solubility Properties in Polymers and Biological Media. 4. Correlations of Octanol/Water Partition Coefficients with Solvatochromic Parameters. J.Am.Chem.Soc., 106,464-466. 

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