Octanol/water partition coefficient chemicals

Moriguchi, I., Hirono, S., Liu, Q., Nakagome, I. and Matsushita, Y. (1992) Simple method of calculating octanol/ water partition coefficient. Chemical ei Pharmaceutical Bulletin, 40, 127—130. 

The octanol—water partition coefficient, which is used as an iadicator of the tendency of an organic chemical to accumulate ia living tissue, was low. This iadicates that naphthalene is unlikely to accumulate ia the body. 

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). 

Octanol—Water Partition Coefficient. In environmental calculations, the octanol—water partition coefficient, is related to a chemical s Hpophilicity and... 

The toxicological or cumulative effect of illicit drugs on the ecosystems has not been studied yet. Moreover, their fate and transport in the environment is to a big extent still unknown. Due to their physical-chemical properties (octanol-water partition coefficient, solubility, etc.) some of them, such as cannabinoids, are likely to bioaccumulate in organisms or concentrate in sediments whereas the rest, much more polar compounds, will tend to stay in aqueous environmental matrices. However, continuous exposure of aquatic organisms to low aquatic concentrations of these substances, some of them still biologically active (e.g., cocaine (CO), morphine (MOR) and MDMA) may cause undesirable effects on the biota. 

Octanol-Water Partition Coefficient (Kq )—The equilibrium ratio of the concentrations of a chemical in TT-octanol and water, in dilute solution. 

From an analysis of the key properties of compounds in the World Dmg Index the now well accepted Rule-of-5 has been derived [25, 26]. It was concluded that compounds are most Hkely to have poor absorption when MW>500, calculated octanol-water partition coefficient Clog P>5, number of H-bond donors >5 and number of H-bond acceptors >10. Computation of these properties is now available as a simple but efficient ADME screen in commercial software. The Rule-of-5 should be seen as a qualitative absorption/permeabiHty predictor [43], rather than a quantitative predictor [140]. The Rule-of-5 is not predictive for bioavail-abihty as sometimes mistakenly is assumed. An important factor for bioavailabihty in addition to absorption is liver first-pass effect (metaboHsm). The property distribution in drug-related chemical databases has been studied as another approach to understand drug-likeness [141, 142]. 

Usually aquatic toxicity of chemicals with general narcosis mechanism of action is described by the octanol/water partition coefficient [73]. However, log is a composite descriptor which has components of molecular volume and H-bond acceptor terms. Raevsky and Dearden [74] therefore used molecular polarizabihty (as a volume-related term) and the H-bond acceptor factor instead of log to model aquatic toxicity (log LC50) to the guppy for 90 chemicals with general narcosis mechanisms. This excellent correlation has statistical criteria better than that obtained for the same data using log Pofy, ... 

The following physico-chemical properties of the analyte(s) are important in method development considerations vapor pressure, ultraviolet (UV) absorption spectrum, solubility in water and in solvents, dissociation constant(s), n-octanol/water partition coefficient, stability vs hydrolysis and possible thermal, photo- or chemical degradation. These valuable data enable the analytical chemist to develop the most promising analytical approach, drawing from the literature and from his or her experience with related analytical problems, as exemplified below. Gas chromatography (GC) methods, for example, require a measurable vapor pressure and a certain thermal stability as the analytes move as vaporized molecules within the mobile phase. On the other hand, compounds that have a high vapor pressure will require careful extract concentration by evaporation of volatile solvents. 

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. 

The use of data concerning the physicochemical properties of chemicals (e.g., stability, solubility, pH, octanol-water partition coefficient, and protein binding). 

There is a continuing effort to extend the long-established concept of quantitative-structure-activity-relationships (QSARs) to quantitative-structure-property relationships (QSPRs) to compute all relevant environmental physical-chemical properties (such as aqueous solubility, vapor pressure, octanol-water partition coefficient, Henry s law constant, bioconcentration factor (BCF), sorption coefficient and environmental reaction rate constants from molecular structure). 

Burkhard, L. P, Kuehl, D. W., Veith G. D. (1985c) Evaluation of reversed phase liquid chromatograph/mass spectrometry for estimation of n-octanol/water partition coefficients of organic chemicals. Chemosphere 14, 1551-1560. 

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. 

Wang, L., Zhao, Y., Hong, G. (1992) Predicting aqueous solubihty and octanol/water partition coefficients of organic chemicals from molar volume. Environ. Chem. 11, 55-70. 

Brooke, D.N., Dobbs, A.J., Williams, N. (1986) Octanol/water partition coefficients P measurement, estimation, and interpretation particularly for chemicals with P > 106. Ecotoxicol. Environ. Saf. 11, 251-260. 

Geyer, H.J., Politzki, G., Freitag, D. (1984) Prediction of ecotoxicological behaviour of chemicals relationship between n-octanol/water partition coefficient and bioaccumulation of organic chemicals by alga chlorella. Chemosphere 13(2), 269-284. 

Ritter, S., Hauthal, W.J., Maurer, G. (1995) Octanol/water partition coefficients for environmentally important organic chemicals. Environ. Sci. Pollut. Res. 2, 153-160. 

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