Partition coefficients experimental determination

Moreover, A log P was proposed as a molecular descriptor for modeling hydrogen bonding capacity it corresponds to the difference between the partition coefficient experimentally determined in octanol/water (log Pow) and partition coefficients determined in other systems, such as octanol/water-heptane/water (logPaijj) systems and octanol/water-chloroform/water (log PCH3C1) systems [El Tayar, Tsai et al, 1991b Winiwarter, Ax et al., 2003]. 

Male Fischer 344/N rats were exposed via the nose only for 6 h to concentrations of vinylidene fluoride ranging from 27 to 16 000 ppm [71-42 000 mg/m. Tidal volume (mean, 1.51 mL/brcath) and respiratory frequency (mean, 132 breaths/min) were not influenced by exposure concentration. Steady-state blood levels of vinylidene fluoride increased linearly with increasing exposure concentration up to 16 000 ppm. Vinylidene fluoride tissue/air partition coefficients were determined experimentally to be 0.07, 0.18, 0.8,10, and 0.29 for water, blood, liver, fat and muscle, respectively. Previously published detenninations (Filser Bolt, 1979) for the maximum velocity of metabolism in mg/li/kg) and Michaelis Menten constant (K in mg/L) are 0.07 and 0.13, respectively. Time to reach steady-state blood levels of vinylidene fluoride was less than 15 min for all concentrations. After cessation of exposure, blood levels of vinylidene fluoride decreased to 10% of steady-state levels within 1 h. Simulation of the metabolism of vinylidene fluoride mdicated that although blood levels of vinylidene fluoride increased linearly with increasing exposure concentration, the amount of vinylidene fluoride metabolized per 6-h exposure period approached a maximum at about 2000 ppm [5240 mg/m vinylidene fluoride (Medinsky et al., 1988). 

Figure 6.8 shows the plot of Mt vs. t for Equation (6.36). As time approaches infinite, the graph gives a straight line, which is a representation of Equation (6.37) for the time lag. The time intercept is calculated from Equation (6.38). This intercept and the slope [ = 4n ab(b - a)KCj ], which is the steady-state release rate, are used to determine the diffusion and partition coefficients experimentally. Mathematical expressions, which include the amount of the drug diffused from freshly prepared and stored geometrical membranes (sheet and cylinder) at steady state are presented in Table 6.2. 

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... 

In QSAR studies the lipophilic character of a compound is usually expressed in terms of the logarithm of the octanol/water partition coefficient (i.e., log P). Experimentally, the octanol/water partition coefficient is determined by the shake-flask method. Unfortunately, it is often difficult to obtain precise values for the octanol/water partition coefficient because solute impurities will affect the measured distribution coefficient. For example, reported log P values for benzene (1-5) vary from 1.56 to as high as 2.34. 

Describe how the octanokwater partition coefficient, is determined experimentally. If the concentration of benzene is 3.7 ppm in water, what is its concentration in octanol, assuming standard laboratory conditions (Hint See Table 2.2 for log value for benzene.)... 

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]. 

The pH-metric technique used to determine partition coefficients was first used in the 1950s in solvent extraction of metal complexes [280-282], but it is in pharmaceutical research that it is most widely used thanks to the recent development of a fully automated and computer-controlled apparatus [125,283]. The potentiometric approach has been validated in various solvent systems [284-287], and it has become a relevant and expanding experimental technique to obtain lipophilicity descriptors [257,287-289]. 

Ilmenite. There are currently no experimentally-determined ilmenite-melt partition coefficients. We must rely instead on phenocryst-groundmass data analyzed by PIXE (Stimac and Hickmott 1994 Ewart and Griffin 1994). Like magnetite, ilmenite is characterised by two relatively small sites, and is therefore unlikely to take up appreciable amounts of lanthanides or large alkaline earths. We will confine ourselves again to U, Th and Pa. 

Barth MG, Foley SF, Horn 1 (2002) Partial melting in Archean subduction zones constraints from experimentally determined trace element partition coefficients between eclogitic minerals and tonahtic melts under upper mantle conditions. Precamb Res 113 323-340... 

Jenner GA, Foley SF, Jackson SE, Green TH, Fryer BJ, Longerich HP (1994) Determination of partition coefficients for trace elements in high pressnre-temperature experimental ran products by laser ablation microprobe-inductively conpled plasma-mass spectrometry (LAM-ICP-MS). Geochim Cosmochim Acta 58 5099-5103... 

Both dynamic melting and equilibrium transport melting require that the porosity when two nuclides are fractionated from one another is similar to the size of the larger of the partition coefficients for the two nuclides. Given the low values of the experimental determinations of Du and Dxh, the porosities required to explain the observational data in these models are generally less than 0.5% and often times closer to 0.1%. Such low porosity estimates have been criticized based on physical grounds given the low estimated mantle permeability derived from the extent of melt connection observed in experiments (Paul 2001). 

Table 2. Experimentally determined mineral/melt partition coefficients (x 10 ) for U, Th, and Ba in clinopyroxene and garnet and calculated bulk partition coefficients (xlO ) for a garnet peridotite source.

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