Experimental partition coefficients

Although experimental partition coefficients are the values of reference, drug design often necessitates log evaluations before the compound has been synthesized. Consequently, various methods have been developed to predict lipophilicity [188], and they generally apply only to neutral compounds in the water-OCT system. 

In summary, a key aspect to the utility of U-series isotopes in the study of arc lavas is that whereas Th and Pa are observed and predicted to behave as relatively immobile high field strength elements (HFSE), Ra and (under oxidizing conditions) U behave like large ion lithophile elements (LILE) and are significantly mobilized in aqueous fluids. Fluid-wedge interaction will only serve to increase these fractionations. Just how robust the experimental partition coefficients are remains to be established by future experiments. 

Fig. 19. Experimental partition coefficients and those predicted by size exclusion theory (Eq. (4), shown as a solid line) for vitamin B12 (a relatively large, hydrophilic solute) in 10 x 4 PNIPAAm gel. Although size exclusion theory consistently underestimates the value of K, the sharp drop predicted at the transition temperature is observed. Error bars (standard deviation of three samples) not shown are smaller than the symbol. The dotted line is to guide the eye. Reprinted from the Journal of Controlled Release (1992) 18 1, by permission of the publishers, Elsevier Science Publishers BV [70]...

Angus J.G., Rayner B.J. and Robson M. (1979) Reliability of experimental partition coefficients in carbonate systems evidence for inhomogeneous distribution of impurity cations. Chem. Geol. 27, 181-205. 

Model Parent Compound Series. Experimental partition coefficient data for a variety of substituted benzenes and seven other related parent compound series (phenoxyacetic acid, phenylacetic acid, benzoic acid, benzyl alcohol, phenol, aniline, nitrobenzene) were reported in 1964 by Fujita et al. (II). The ir values (see Equation 3) derived for individual substituents in each of the above-mentioned parent compound series have since been frequently used (with varying degrees of success) by many investigators to approximate tt values for the corresponding substituents in other related parent compounds for which no experimental partitioning data are available. For example, Hansch and Deutsch (26), in a correlation study of structure—activity relationships in cholinesterase inhibitors, used tr values derived for aromatic ring substituents (X) in the phenoxyacetic acid series... 

Several models for estimating soil sorption coefficients take advantage of the correlation between Koc and other experimental partition coefficients, specially Kow For example, Kqc values have been estimated from experimental octanol-water partition coefficients by... 

The single constant Wilson equation was fitted to experimental partition coefficient data for ethanol for the ternary systems benzene-water-ethanol (9) and n-hexane-water-ethanol (12). The partition coefficient was calculated from equation (12) using the Wilson equation to compute the activity coefficients. The constants, Xy, were chosen to give a best fit in the least squares. sense to the experimental partition coefficients. Table II shows the resulting constants. 

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... 

As a fittther test of the veracity of the derived we compare in Table HI the experimental partition coefficients of cyclohexane and methylcyclohexane with the calculated from the mean solvent activity... 

The partition-coefficient data for benzene and toluene solutes with squedane + dinonyl phthalate solvents provide em opportunity to test this, the putative with DNP being reported (39) to be 0.Z76 t 0.026 and 0.261 t 0.030 dm mol , respectively, at 30°C. [a corroborative value of 0.2Z 0.10 dm mol has also been obtained by NMR for the former (49).1 Accordingly, we compue in Table V below the experimental partition coefficients of these solutes with the calculated with equation 22 and the given in Table... 

Fig. 1. Experimental partition coefficients of penicillin G and those predicted using...

Table 4 Selected Rmw and ipo lipophilicity parameteis and the values of experimental partition coefficients and partition coefficients calculated by using different theoretical methods.

Lipophilicity is first and foremost an experimental property of chemical compounds hence experimental partition coefficients remain the values of reference. This statement has lost some of its strength, however, for at least two important reasons. First, many technical difficulties await the experimental worker measuring partition coefficients. As a result, the accuracy of innumerable data in the literature is unreliable or outright suspect the frequently modest agreement of independent log P measurements of the same compound is another serious concern. And second, drug designers often need log P data before the compound is even synthesized. 

Oremusova, J., Greksakova, O. Determination of the critical micelle concentration, hydrodynamic micelle radius and experimental partition coefficient of (-)-N-dode-cyl-N-methylephedrinium bromide. Tenside Surfactants Deterg. 2003,40(2), 90-95. Akhter, M.S., Alawi, S.M. A comparison of micelle formation of ionic surfactants in formamide, in N-methylformamide and in N,N-dimethylformamide. Colloids Surf. A 2003, 279(1-3), 281-290. 

---