Octanol-water partition coefficient determination

Berthod, A., Menges, R.A., Armstrong, D.W. (1992) Direct octanol-water partition coefficient determination using co-current... 

Gluck, S.J., Martin, E.J. (1990) Extended octanol-water partition coefficient determination by dual-mode centrifugal partition chromatography. J. Liq. Chromatogr. 13, 3559-3570. 

V. Lee, "Synthesis of (14C)Methylsi anes and Their Octanol-Water Partition Coefficient Determinations," M.S. thesis, San Jose State College, San Jose, Cal., 1967. 

Water solubility determined by the generator column method by van Haelst et al. [244]. n-Octanol/water partition coefficients determined by Van Haelst et al. using the slow stirring method [245]. 

Methods and Error in Octanol-Water Partition Coefficient Determinations... 

A. Berthod, R.A. Meng and D.W. Armstrong, Direct Octanol Water Partition Coefficient Determination using Cocurrent Chromatography, J. Liq. Chromatogr., 15 2769 (1992). 

An important factor in determining the course of uptake, transport, and distribution of xenobiotics is their polarity. Compounds of low polarity tend to be lipophilic and of low water solubility. Compounds of high polarity tend to be hydrophilic and of low fat solubility. The balance between the lipophilicity and hydrophilicity of any compound is indicated by its octanol-water partition coefficient (K J, a value determined when equilibrium is reached between the two adjoining phases ... 

Paschke, A., Manz, M., Schtiurmann, G. Application of different RP-HPLC methods for the determination of the octanol/water partition coefficient of selected tetrachlorobenzyltoluenes. Chemosphere 2001, 45, 721-728. 

Ostergaard, J., Hansen, S. H., Larsen, C., Schou, C., Heegaard, N. H. Determination of octanol-water partition coefficients for carbonate esters and other small organic molecules by microemulsion electrokinetic chromatography. Electrophoresis 2003, 24, 1038-1045. 

Avdeef, A. pH-metric logP. Part 1. Difference plots for determining ion-pair octanol-water partition coefficients of multiprotic substances. Quant. Struct.-Aaiv. Relat. 1992, 11, 510-517. 

Takacs-Novak, K., Avdeef, A., Box, K. J., Podanyi, B., Szasz, G. Determination of protonation macro- and microconstants and octanol/water partition coefficient of the antiinflammatory drug niflumic add. J. Pharm. Biomed. Anal. 1994, 12, 1369-1377. 

Krikorian SE, Chom TA, King JW. 1987. Determination of octanol/water partition coefficients of certain organophosphorus compounds using high-performance liquid chromatography. Quant Struct-Act Relat 6(2) 65-69. 

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 binding constants of a number of compounds were measured using dialysis, solubility and sorption techniques. The solubility technique was used for compounds which were not radiolabeled. All data was collected at pH = 8.3. The binding constants were then compared to the octanol/water partition coefficients for the compounds and the molar solubilities of the compounds. The data is presented in Table II. The Kow values were taken from the literature.18 22-2 The solubility values were determined in this research with the exception of DDT and Lindane, which were taken from the literature. A plot of log Kc vs. log Kow is presented in Figure 5. The slope of this line is 0.71, the intercept is 0.75 and the value of the correlation coefficient is 0.9258. The regression is highly significant... 

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. 

Physical Properties. Octanol/water partition coefficients were determined following the method described by A. Leo, et al.,... 

Indirect determination of octanol-water partition coefficients by microemulsion electrokinetic chromatography, J. Chromatogr. A. 1996, 744(1-2), 141-146. 

McFarland et al. recently [1] published the results of studies carried out on 22 crystalline compounds. Their water solubilities were determined using pSOL [21], an automated instrument employing the pH-metric method described by Avdeef and coworkers [22]. This technique assures that it is the thermodynamic equilibrium solubility that is measured. While only ionizable compounds can be determined by this method, their solubilities are expressed as the molarity of the unionized molecular species, the intrinsic solubility, SQ. This avoids confusion about a compound s overall solubility dependence on pH. Thus, S0, is analogous to P, the octanol/water partition coefficient in both situations, the ionized species are implicitly factored out. In order to use pSOL, one must have knowledge of the various pKas involved therefore, in principle, one can compute the total solubility of a compound over an entire pH range. However, the intrinsic solubility will be our focus here. There was one zwitterionic compound in this dataset. To obtain best results, this compound was formulated as the zwitterion rather than the neutral form in the HYBOT [23] calculations. 

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 logarithm of the 1 -octanol - water partition coefficient, denoted log Kq j or log P, indicates the distribution of the compound between the organic and the water phase. For highly lipophilic compounds, the log P is determined via reversed-phase thin-layer chromatography, giving the so-called log P tlc value1. 

A wide variety of solubilities (in units of g/m3 or the equivalent mg/L) have been reported. Experimental data have the method of determination indicated. In other compilations of data the reported value has merely been quoted from another secondary source. In some cases the value has been calculated. The abbreviations are generally self-explanatory and usually include two entries, the method of equilibration followed by the method of determination. From these values a single value is selected for inclusion in the summary data table. Vapor pressures and octanol-water partition coefficients are selected similarly. 

Boublik, T., Fried, V., Hala, E. (1984) The Vapor Pressure of Pure Substances, 2nd revised Edition, Elsevier, Amsterdam, The Netherlands. Bowman, B. T., Sans, W. W. (1983) Determination of octanol-water partitioning coefficient (KqW) of 61 organophosphorus and carbamate insecticides and their relationship to respective water solubility (S) values. J. Environ. Sci. Health B18, 667-683. Bradley, R. S., Cleasby, T. G. (1953) The vapour pressure and lattice energy of some aromatic ring compounds. J. Chem. Soc. 1953, 1690-1692. 

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. 

Rapaport, R. A., Eisenreich, S. J. (1984) Chromatographic determination of octanol-water partition coefficients (K, )W s) for 58 polychlorinated biphenyl congeners. Environ. Sci. Technol. 18, 163-170. 

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. 

Griffin, S., Grant Willie, S., Markham, J. (1999) Determination of octanol-water partition coefficient for terpenoids using reversed-phase high performance liquid chromatography. J. Chromatog. A, 864, 221-228. 

---