Partition coefficient derivatives

FIGURE 9 Linear correlation of octanol-water, PCL-water, and poly-dimethylsiloxane (PDMS)-water partition coefficients derived for a series of 10 solutes. (From Ref. 58.)... 

Fig. 11.6. (r-dependence of various partition coefficients (derived from... 

Renberg, L., Sundstrom, G. (1979) Prediction of bioconcentration potential of organic compounds using partition coefficients derived from reversed phase thin layer chromatography. Chemosphere 7, 449 459. 

Usefulness of partition coefficients derives from the empirical observation (Figure 5-3) that they may be related to the molecular weight of a solute. Although these observations have been analyzed extensively it must be conceded that as yet they cannot be totally accounted theoretically. When a plot such as that in Figure 5-3 is used to make an estimate of molecular weight, it is advisable to use only the linear region of the plot and to include standard proteins which have molecular weights above and below that of the unknown. 

An appreciation of the mechanisms of trace element-bone interaction can be gained by comparing uptake of REE in bone with experimental and analytical studies of high temperature apatite-melt REE partitioning behavior. Apatite-melt partition coefficients derived from experimental studies, when plotted against ion radius, show parabolic traces with maxima around Nd-Sm (Fig. 3). These REE ions have radii closest to Ca, and indicate that REE are held in Ca sites in the lattice. Blundy and Wood (1994) developed a predictive model for calculation of equilibrium partition coefficients of trace elements between crystals and melt in igneous systems. In this model, the partitioning behavior of isovalent cations between a mineral and liquid at a particular pressure, temperature, and composition of interest can be explained by a version of the Brice (1975) equation, in which the size and elasticity of the crystal lattice sites play a critical role ... 

Figure 3. Apatite-melt partition coefficients derived from high temperature experimental and natural systems (A-C) and estimates of partitioning between ichthyoliths and bottom water (D), together with the best fit of Equation (1) (Blundy and Wood 1994) to this data. Values taken from ...

Figure 3.22 Representative isotherms for the sorption of volatile organic compounds in plant cuticular matrix at 25°C. Plant matrix-air partition coefficients derived from slopes of the isotherms. [Reproduced with permission from B. Welke, K. Ettlinger, and M. Riederer, Environ. Sci. Technol. 32, 1099 (1998). Copyright 1998, American Chemical Society.]...

The investigations cited above were all laboratory studies. In this paper, partition coefficients derived from field measurements in the St. Clair, Detroit and Niagara Rivers are reported. These coefficients will be correlated with octanol-water partition coefficients and compared to empirically-derived equations. 

Thus one must rely on macroscopic theories and empirical adjustments for the determination of potentials of mean force. Such empirical adjustments use free energy data as solubilities, partition coefficients, virial coefficients, phase diagrams, etc., while the frictional terms are derived from diffusion coefficients and macroscopic theories for hydrodynamic interactions. In this whole field of enquiry progress is slow and much work (and thought ) will be needed in the future. 

The derivation of a QSAR equation involves a number of distinct stages. First, it is obviousl necessary to synthesise the compormds and determine their biological activities. Whe planning which compormds to synthesise, it is important to cover the range of propertie that may affect the activity. This means applying the data-checking and -manipulation prc cedures discussed earlier. For example, it would be unwise to make a series of coinpound with almost identical partition coefficients if this is believed to be an important property. 

In contrast to SDS, CTAB and C12E7, CufDSjz micelles catalyse the Diels-Alder reaction between 1 and 2 with enzyme-like efficiency, leading to rate enhancements up to 1.8-10 compared to the reaction in acetonitrile. This results primarily from the essentially complete complexation off to the copper ions at the micellar surface. Comparison of the partition coefficients of 2 over the water phase and the micellar pseudophase, as derived from kinetic analysis using the pseudophase model, reveals a higher affinity of 2 for Cu(DS)2 than for SDS and CTAB. The inhibitory effect resulting from spatial separation of la-g and 2 is likely to be at least less pronoimced for Cu(DS)2 than for the other surfactants. 

This distinction between Kd and D is important. The partition coefficient is an equilibrium constant and has a fixed value for the solute s partitioning between the two phases. The value of the distribution ratio, however, changes with solution conditions if the relative amounts of forms A and B change. If we know the equilibrium reactions taking place within each phase and between the phases, we can derive an algebraic relationship between Kd and D. 

These partition coefficient data were derived from the log P values reported therein. 

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). 

C Hansch, RM Muir, T Fujita, PP Maloney, E Geiger, M Streich. The correlation of biological activity of plant growth regulators and chloromycetm derivatives with Hammett constants and partition coefficients. J Am Chem Soc 85 2817-2824, 1963. 

T Fujita, J Iwasa, C Hansch. A new substituent constant, 7i, derived from partition coefficients. J Am Chem Soc 86 5175-5180, 1964. 

General anaesthetics have been in use for the last 100 years, yet their mechanism of action are still not yet clearly defined. For many years it was thought that general anaesthetics exerted their effects by dissolving in cell membranes and perturbing the lipid environment in a non-specific manner. This theory derived from the observation that for a number of drugs which induced anaesthesia, their potency correlated with their oil-water partition coefficients. This Meyer-Oveiton correlation was accepted for a number of years, however in the last 15-20 years evidence has shown that a more likely theory is that of specific interactions of anaesthetics with proteins, particularly those within the CNS that mediate neurotransmission [1]. 

It is also necessary to select the initiator according to the particular monomer(s) and the substrate. Factors to consider in this context, aside from initiator half-lives and decomposition rates, are the partition coefficient ot the initiator between the monomer and polyolefin phases and the reactivity of the monomer vs the polyolefin towards the initiator-derived radicals. 

After phase separation, two sets of equations such as those in Table A-1 describe the polymerization but now the interphase transport terms I, must be included which couples the two sets of equations. We assume that an equilibrium partitioning of the monomers is always maintained. Under these conditions, it is possible, following some work of Kilkson (17) on a simpler interfacial nylon polymerization, to express the transfer rates I in terms of the monomer partition coefficients, and the iJolume fraction X. We assume that no interphase transport of any polymer occurs. Thus, from this coupled set of eighteen equations, we can compute the overall conversions in each phase vs. time. We can then go back to the statistical derived equations in Table 1 and predict the average values of the distribution. The overall average values are the sums of those in each phase. 

The BUSES model provides an estimate of the organic carbon/water partition coefficient (Koc) based on the octanol/water partition coefficient (Kow)- From these data, it is evident that the methyltins are less likely to partition onto organic carbon (in sediments, soils, biota) than are the butyl- and octyltin compormds due to then-lower partition coefficients and higher water solubilities. The 7/oc value can then be used to derive sohds/water partition coefficients in suspended matter, in sediment, and in soil using values of 10%, 5%, and 2% for organie carbon, representing typical organic carbon contents of suspended matter, sediment, and soil, respeetively. 

As most organotins decompose, boiling points of 250 °C were assumed in the absence of a "true boiling point. The values for Henry s law constant and organic carbon/water partition coefficient were all derived from EUSES unless otherwise indicated. The chlorides were chosen as soluble salts in this table toxicity is independent of salt (see section 8), and soluble salts maximize likely environmental exposure, giving worst case in modelling environmental fate. 

When a two- or higher-phase system is used with two or more phases permeable to the solute of interest and when interactions between the phases is possible, it would be necessary to apply the principle of local mass equilibrium [427] in order to derive a single effective diffusion coefficient that will be used in a one-equation model for the transport. Extensive justification of the principle of local thermdl equilibrium has been presented by Whitaker [425,432]. If the transport is in series rather than in parallel, assuming local equilibrium with equilibrium partition coefficients equal to unity, the effective diffusion coefficient is... 

Further supporting evidence for the importance of lipophilicity in bitter response is provided by the taste of isohumulone (118), the principal, bitter-tasting component of beer, and some of its derivatives. Isohumulone can exist in both cis and trans forms. Clarke and Hilderbrand reported that the cis form, having a partition coefficient of 0.78, is more bitter than... 

In view of these potentials for major reductions in preservative efficacy, considerable effort has gone into attempts to devise equations in which one might substitute variously derived system parameters such as partition coefficients, surfactant and polymer binding constants and oil water ratios in order to obtain estimates of residual preservative levels in aqueous phases. Although some modestly successful predictions have been obtained for very simple laboratory systems, they have proved of limited practical value as data for many of the required parameters are unavailable for technical grade ingredients or for the more complex commercial systems. 

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]. 

Livingstone, D. J., Ford, M. G., Huuskonen, J. J., Salt, D. W. Simultaneous prediction of aqueous solubility and octanol/water partition coefficient based on descriptors derived from molecular structure. J. Comput.-Aided Mol. Des. 2001, 15, 741-752. 

Haeberlein, M., Brinck, T. Prediction of water-octanol partition coefficients using theoretical descriptors derived from the molecular surface area and the electrostatic potential. J. Chem. Soc. 

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