Lipophilicity distribution coefficient

Lipophilicity represents the affinity of a molecule or a moiety for a lipophilic (= fat-loving) environment and is commonly measured by the partition coefficient, (where aaa represent a generic biphasic system, e.g. oct indicates the standard octanol-water). P is valid for a single electrical species, to be specified (P for neutral forms and P for ionized species). The distribution coefficient, expressed as is a pH-dependent descriptor (Eq. 3) for ionizable solutes and results from the weighted contributions of all electrical forms present at this pH ... 

Of course, the shape of the lipophilicity profiles becomes much more complicated for molecules with multiple ionized forms. Nevertheless, the partition coefficients may be calculated from the distribution coefficient using the general equation [113] ... 

However, recent studies on the variation of the distribution coefficient of ionizable drugs as a function of pH (pH-lipophilicity profiles) shows that the partitioning of charged species cannot be neglected [143]. In other words, the general relationship between distribution and partition coefficients [Eq. (15)] cannot be simplified. 

Note that the distribution coefficient depends only on pH, pKa values, and P (not on concentration of sample species). Equation (4.7) is applicable to all lipophilicity calculations. Special cases, such as eq. 4.9, have been tabulated [275],... 

The un-ionized form is assumed to be sufficiently lipophilic to traverse membranes in the pH-partition hypothesis. If it were not, no transfer could be predicted, irrespective of pH. The lipophilicity of compounds is experimentally determined as the partition coefficient (log P) or distribution coefficient (log D) [16]. The partition coefficient is the ratio of concentrations of the neutral species between aqueous and nonpolar phases, while the distribution coefficient is the ratio of all species between aqueous and nonpolar phases [17,18],... 

The lipophilicity of a substance, that is, the tendency of a substance to become dissolved in a lipid, is often measured by the tendency of a substance to become dissolved in a nonpolar solvent, for example, by the n-octanol-water distribution coefficient. The lipophilicity of a substance is inversely proportional to its water solubility. 

Distribution Coefficients for Selected 3-Hydroxy-4-pyridinones and their Iron(III) Complexes, Arranged in Order of Increasing Lipophilicity... 

Sorption of pharmaceuticals onto the surface of particulate matter or their distribution between two phases (water and either sludge, sediment or soil) depends on many factors, the most important being liquid phase pH and redox potential, the stereochemical structure and chemical nature of both the pharmaceutical compound and the sorbent, the lipophilicity of the sorbed molecules (excellent sorption at log Kov > 4, low sorption at log < 2.4), the sludge-water distribution coefficient Kd Kd > 2 L g SS good sorption, < 0.3 L g SS low sorption), the extent of neutral and ioiuc species present in the wastewater and the characteristics of the suspended particles. Moreover, the presence of humic and fulvic substances may alter the surface properties of the sludge, as well as the number of sites available for sorption and reactions, thereby enhancing or suppressing sorption of PhCs [38, 55, 61]. 

The partition coefficient (log P) describes the intrinsic lipophilicitY of the collection of functional groups and carbon skeleton, which combine to make up the structure of the compound, in the absence of dissociation or ionization. Methods to measure partition and distribution coefficients have been described [3,4]. 

H. Schott, Hydrophilic-lipophilic balance and distribution coefficients of nonionic surfactants, J. Pharm. Sci. 60 (1971) 648-649. 

Hansch and Toshio Fujita, a postdoctoral researcher in Hansch s group, designed a parameter, ttr, to estimate the lipophilicity of an R-group.3 Hansch s parameter relies on partition coefficients to measure lipophilicity. Partition coefficients, P, are equilibrium constants describing the degree to which a molecule distributes into a biphasic mixture of two immiscible solvents. Hansch used 1-octanol and water as the model solvents because these were known to simulate the lipid membrane-cytosol interface. The partition coefficient of a molecule is defined as the ratio of a molecule s concentration in an octanol layer to its concentration in an aqueous layer (Equation 12.12). 

The increase in extraction efficiency, evaluated by the distribution coefficients DM, is often considered to be the result of an increase in the overall lipophilicity of a system. Synergism has been studied systematically using four types of extractant combinations 1) chelating extractant/neutral extractant 2) acidic extractant/neutral extractant 3) two neutral extractants 4) two chelating extractants, with the observed synergistic effect generally decreasing from class 1 to 4. [49]... 

Figure 5 Illustration of the lock-in mechanism for estradiol-CDS. Octanol-water log partition (log P) and distribution coefficients (log D) are shown to illustrate the significant changes in partition properties. The lipophilic CDS (5) (log P > 4) can easily cross the blood-brain barrier (BBB), but the hydrophilic intermediate (6) (log D < 0) is no longer able to come out providing a sustained release of the active estradiol (7). 

Unger, S.H., Chiang, G.H. (1981) Octanol-physiological buffer distribution coefficients of lipophilic amines by reversed-phase high-performance liquid chromatography and their correlation with biological activity. J. Med. Chem. 24(3), 262-270. 

The partition coefScient is defined as the ratio of the concentration of a solute in the organic phase to its concentration in the water phase. This definition applies to the same neutral microspecies. However, many small molecules of pharmaceutical, agricultural and environmental interest may assume different protomeric and tautomeric forms, which increases the complexity of the above (simple) definition. Indeed, many small molecules contain moieties that ionize in water, thus contributing to a decrease in lipophilicity. The distribution coefficient, log D y, measures the pH-dependent distribution of drug in octa-nol-water phases at pH xy. 

Lipophilicity is frequently used in QSAR analysis and expressed as the partition coefficient P (or by its decimal logarithm, log P) between a nonaqueous and aqueous phase. Another parameter, which takes into account the equilibrium of an ionizable compound at a stated pH value, is the distribution coefficient (Z>), which depends on the P of the single species and on the pAT values of the chosen compound. P and D have been evaluated for different N-substituted l,2-benzisothiazol-3-one derivatives using the partition between -octanol and water. Selected data are reported in Table 9 <1996FES493, 2002EJM553>. 

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