Partition coefficient experimental measurement

Hiyagon and Ozima (1986) employed a laboratory approach of measuring crystal-melt partition coefficients. They measured noble gas concentration in olivine crystals and basalt melts, which were synthesized at 1370-1300°C under an atmospheric pressure, and also at 1360-1050°C under high pressure (0.2-1.5 GPa), of noble gas mixture. From these experimental results, they obtained ranges for noble gas partition coefficients XHe = 0.07, XNe = 0.006-0.08, KM = 0.05-0.15, KXe = 0.3. These partition coefficients are much larger than the values obtained by Marty and Lussiez (1993) and also these of common incompatible elements such as U (-0.002) or K (0.0002 - 0.008) between olivine and basalt melt (e.g. Henderson, 1982). 

The substituent hydrophobicity constant is a measure of how hydrophobic a substituent is, relative to hydrogen. The value can be obtained as follows. Partition coefficients are measured experimentally for a standard compound with and without a... 

At this point in the chapter, you should be familiar with aU these chemical properties except for the partition coefficient. Experimentally, partition coefficient values (P) are determined by measuring the amount of a given substance in each layer of a partition media between water and n-octanol, the latter oil being chosen historically to resemble how a substance might partition between the lipophilic nature of a lipid bUayer or... 

This argument was explored by Reynard et al. (1999), using values of E and Vg obtained from the experimental partitioning data of Fujimaki (1986). Reynard et al. (1999) used Equation (1) to predict equilibrium REE-apatite partition coefficients at surface temperature and pressure, assuming that the crystal chemistry of bone apatite is broadly similar to that of HAP, and that crystal-melt partition coefficients can be used to estimate crystal-water partitioning. Reynard et al. (1999) then compared the predicted partition coefficients with measured adsorption coefficients for the REE between seawater and HAP derived by Koeppenkastrop and DeCarlo (1992), and concluded that incorporation of REE into bone via a substitution mechanism produces bell shaped REE patterns with relatively little fractionation between La and Lu. Incorporation of REE into bone via an adsorption mechanism, on the other hand, produces significant fractionation between La and Lu (La/Lu = 5). Based on REE patterns found in fossil fish teeth, they concluded that REE uptake in fossil bone was dominated by adsorption mechanisms, but that subsequent recrystallization may superimpose a degree of substitution-related fractionation over the initial, adsorption related REE pattern. It is important to note, however, that these predictions are based on crystal chemistry of hydroxyapatite and fluorapatite, and not dahllite and francolite. Variations in E and Vo will affect relative adsorption and/or partition coefficients, and may alter the predicted partition coefficient ratios (e.g., La/Lu and La/Sm). 

Calculated partition coefficients can also be used gainfully in environmental toxicity studies, where the series of compounds of interest are large and relatively homogeneous. Moreover, the often high lipophilicity of some pollutants makes it difficult to measure their partition coefficients experimentally.208-2 Interesting applications of calculated log P values are apparent in the rapidly growing field of database management and combinatorial libraries. ... 

Mathai and Singh have estimated the permeability coefficient P, using the formula P = kD where k is the partition coefficient and D is the diffusivity. They have used both parallel and series models to calculate P. The experimental values are always greater than measured values. The poor agreement between the experimental and calculated values is attributed to the polar-polar interaction between the epoxy group and nitrile group. 

The quantitative descriptor of lipophilicity, the partition coefficient P, is defined as the ratio of the concentrations of a neutral compound in organic and aqueous phases of a two-compartment system under equilibrium conditions. It is commonly used in its logarithmic form, logP. Whereas 1-octanol serves as the standard organic phase for experimental determination, other solvents are applied to better mimic special permeation conditions such as the cyclohexane-water system for BBB permeation. Measurement of log P is described in Chapters 12 and 13 as well as in Ref [22]. 

However, as stated above, the partition coefficients measured by the shake-flask method or by potenhometric titration can be influenced by the potenhal difference between the two phases, and are therefore apparent values which depend on the experimental condihons (phase volume ratio, nature and concentrahons of all ions in the solutions). In particular, it has been shown that the difference between the apparent and the standard log Pi depends on the phase volume raho and that this relationship itself depends on the lipophilicity of the ion [80]. In theory, the most relevant case for in vivo extrapolation is when V /V 1 as it corresponds to the phase ratio encountered by a drug as it distributes within the body. The measurement of apparent log Pi values does not allow to differentiate between ion-pairing effect and partihoning of the ions due to the Galvani potential difference, and it has been shown that the apparent lipophilicity of a number of quaternary ion drugs is not due to ion-pair partitioning as inihally thought [80]. 

There are surprisingly few microbeam studies of zircon-melt partitioning in natural systems and none in experimental systems. Recently Thomas et al. (2002) have derived zircon-melt partition coefficients from rehomogenised glass inclusions in zircons from an intrusive tonalite, while Hinton et al. (R. Hinton, S. Marshall and R. Macdonald, written comm.) have used an ion-microprobe to measure zircon-melt partition coefficients from a Kenyan peralkaline rhyolite, with an estimated eruption temperature of 700°C (Scaillet and Macdonald 2001). We have used the lanthanide partition coefficients from these two studies to derive best-fit values for and for the large Vlll-co-ordinated site. In total there are 13 individual sets of partition coefficients. All of these yield broadly consistent values of, in the range 0.968-1.018 A, but very variable, in the range 373-1575 GPa. Because Lu is comparable in size to cannot be well... 

While over the past ten years, our ability to measure U-series disequilibria and interpret this data has improved significantly it is important to note that many questions still remain. In particular, because of uncertainties in the partition coefficients, fully quantitative constraints can only be obtained when more experimental data, as a function of P and T as well as source composition, become available. Furthermore, the robustness of the various melting models that are used to interpret the data needs to be established and 2D and 3D models need to be developed. However, full testing of these models will only be possible when more comprehensive data sets including all the geochemical parameters are available for more locations and settings. 

In whole tissue or cell monolayer experiments, transcellular membrane resistance (Rm = Pm1) lumps mucosal to serosal compartment elements in series with aqueous resistance (R = P ). The operational definition of Lm depends on the experimental procedure for solute transport measurement (see Section VII), but its magnitude can be considered relatively constant within any given experimental system. Since the Kp range dwarfs the range of Dm, solute differences in partition coefficient dominate solute differences in transcellular membrane transport. The lumped precellular resistance and lumped membrane resistance add in series to define an effective resistance to solute transport ... 

The advantage of using the time lag method is that the partition coefficient K can be determined simultaneously. However, the accuracy of this approach may be limited if the membrane swells. With D determined by Eq. (12) and the steady-state permeation rate measured experimentally, K can be calculated by Eq. (10). In the case of a variable D(c ), equations have been derived for the time lag [6,7], However, this requires that the functional dependence of D on Ci be known. Details of this approach have been discussed by Meares [7], The characteristics of systems in which permeation occurs only by diffusion can be summarized as follows ... 

The presence of a transporter can be assessed by comparing basolateral-to-apical with apical-to-basolateral transport of substrates in polarized cell monolayers. If P-gp is present, then basolateral-to-apical transport is enhanced and apical-to baso-lateral transport is reduced. Transport experiments are in general performed with radioactively labeled compounds. Several studies have been performed with Caco-2 cell lines (e.g. Ref. [85]). Since Caco-2 cells express a number of different transporters, the effects measured are most probably specific for the ensemble of transporters rather than for P-gp alone. P-gp-specific transport has been assayed across confluent cell layers formed by polarized kidney epithelial cells transfected with the MDR1 gene [86], Figure 20.11 shows experimental data obtained with these cell lines. A rank order for transport called substrate quality was determined for a number of compounds [86]. The substrate quality is a qualitative estimate, but nevertheless allows an investigation of the role of the air/water (or lipid/water) partition coefficient, log Kaw, for transport as seen in Fig. 20.11(A). For most of the compounds, a linear correlation is observed between substrate quality and log Kaw- However, four compounds are not transported at all despite their distinct lipophilicity. A plot of the substrate quality as a function of the potential of a... 

Physical and Chemical Properties. Most of the important physical-chemical properties of acrylonitrile have been determined (see Chapter 3). However, the partitioning of acrylonitrile between the air and water has been evaluated by using an estimated value for a Henry s law constant. This general approach assumes that the concentration of the chemical in water is low. Because acrylonitrile is relatively soluble in water, this approach may not be accurate. Experimental measurement of the partition coefficient for acrylonitrile at water-air interfaces would be useful in refining models on the behavior of acrylonitrile in the environment. 

In the multimedia models used in this series of volumes, an air-water partition coefficient KAW or Henry s law constant (H) is required and is calculated from the ratio of the pure substance vapor pressure and aqueous solubility. This method is widely used for hydrophobic chemicals but is inappropriate for water-miscible chemicals for which no solubility can be measured. Examples are the lower alcohols, acids, amines and ketones. There are reported calculated or pseudo-solubilities that have been derived from QSPR correlations with molecular descriptors for alcohols, aldehydes and amines (by Leahy 1986 Kamlet et al. 1987, 1988 and Nirmalakhandan and Speece 1988a,b). The obvious option is to input the H or KAW directly. If the chemical s activity coefficient y in water is known, then H can be estimated as vwyP[>where vw is the molar volume of water and Pf is the liquid vapor pressure. Since H can be regarded as P[IC[, where Cjs is the solubility, it is apparent that (l/vwy) is a pseudo-solubility. Correlations and measurements of y are available in the physical-chemical literature. For example, if y is 5.0, the pseudo-solubility is 11100 mol/m3 since the molar volume of water vw is 18 x 10-6 m3/mol or 18 cm3/mol. Chemicals with y less than about 20 are usually miscible in water. If the liquid vapor pressure in this case is 1000 Pa, H will be 1000/11100 or 0.090 Pa m3/mol and KAW will be H/RT or 3.6 x 10 5 at 25°C. Alternatively, if H or KAW is known, C[ can be calculated. It is possible to apply existing models to hydrophilic chemicals if this pseudo-solubility is calculated from the activity coefficient or from a known H (i.e., Cjs, P[/H or P[ or KAW RT). This approach is used here. In the fugacity model illustrations all pseudo-solubilities are so designated and should not be regarded as real, experimentally accessible quantities. 

Octanol/water partition coefficients, Pow, which measure the relative solubilities of solutes in octanol and in water, are widely used as descriptors in quantitative structure-activity relationships (QSAR), for example in pharmacological and toxicological applications.49 Since experimental values of these are not always available, a number of procedures for predicting them have been proposed (see references in Brinck et al.).50... 

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