Octanol/water partitioning system partition coefficient characterization

A CRO may also allow for the in-house introduction of specialized lipophilic scales by transferring routine measurements. While the octanol-water scale is widely applied, it may be advantageous to utilize alternative scales for specific QSAR models. Solvent systems such as alkane or chloroform and biomimetic stationary phases on HPLC columns have both been advocated. Seydel [65] recently reviewed the suitabihty of various systems to describe partitioning into membranes. Through several examples, he concludes that drug-membrane interaction as it relates to transport, distribution and efficacy cannot be well characterized by partition coefficients in bulk solvents alone, including octanol. However, octanol-water partition coefficients will persist in valuable databases and decades of QSAR studies. 

The partition coefficient Kq of an organic compound in the 1-octanol/water system is used to assess the bioaccumulation potential and the distribution pattern of drugs and pollutants. The partition coefficient of imidazole and ILs strongly depends on the hydrogen bond formed by these molecules and is less than one due to the high solubility in water. The low value of the 1-octanol/water partition coefficient is required for new substances, solvents, insecticides to avoid bioaccumulation. Kqw is an extremely important quantity because it is the basis of correlations to calculate bioaccumulation, toxicity, and sorption to soils and sediments. Computing the activity of a chemical in human, fish, or animal lipid, which is where pollutants that are hydrophobic will appear, is a difficult task. Thus, it is simpler to measure the 1-octanol/water partition coefficient. This parameter is used as the primary parameter characterizing hydrophobisity. 

In general, there is a positive correlation between hydrophobicity of solvents and nontoxicity for biocatalysts. The log P value was demonstrated to be a suitable parameter for characterization of solvent hydrophobicity (Table 1). Log P is the logarithm of the partition coefficient of a solvent in a water-l-octanol two-phase system [11,12,41,77]. Solvents with log P > A are very hydrophobic and generally nontoxic for biocatalysts. 

Chmelfk, J. Hudecek, J. Putyera, K. Makovicka, J. Kalous, V. Chmelikova, J., Characterization of the hydrophobic properties of amino acids on the basis of their partition and distribution coefficients in the 1-octanol-water system, Collect. Czech. Chem. Commum. 56, 2030-2040 (1991). 

The plots of log k vs. log P w and the plots of log k (v) vs. log k (z) were studied for seven cephalosporins. A linear relationship was obtained in micellar solution and in microemulsion solution (Tables 3 and 4). The results obtained indicate that the capacity factor determined by EKC could be used both as parameter to characterize the partition behavior of drugs in ME and MC and as hydrophobic parameter instead of log Pow. k appears to be an evident parameter, and it shows a better diversification than P w. In the 1-octanol/water system, we did not found high values of the partition coefficients. In contrast, the ME systems used provide a better characterization of the drugs according to their hydrophilic/lipophilic properties. 

Different balance between intermolecular forces can be accessible via partition coefficients measured in solvents systems other than the traditional 1-octanol/water. Therefore there was a growing interest in the partition processes in several solvent/ water systems [64, 65] and in particular the critical quartet of solvents which was designed to merge the main information about a solute concerning its partition and transport. Only a few studies have been performed to characterize the lipophilicity profile of new chemical entities in different solvent/water systems and consequently the number of methods attempting to model such partitioning systems is limited. 

Most environmental toxins share the properties of being lipid soluble and persistent to metabolism or breakdown, biotic as well as abiotic. Lipophilicity is commonly characterized by the partition coefficient between octanol and water (Kow) and generally the bioavailability or tendency to be absorbed by biotic systems increases with increasing Kow. At very high Kow, however, the uptake might be hindered by the large molecular size or the substance might get stuck in lipophilic structures such as plasma membranes. The ideal value of Kow for absorption is around unity (Walker et al., 2001). 

In 1962, Hansch, Maloney and Fujita [Hansch, Maloney et al, 1962] published their study on the structure-activity relationships of plant growth regulators and their dependency on Hammett constants and hydrophobidty. Using the octanol/water system, a whole series of partition coefficients was measured and, thus, a new hydrophobic scale was introduced for describing the inclination of molecules to move through environments characterized by different degrees of hydrophilicity such as blood and cellular membranes. The delineation of Hansch models led to explosive development in QSAR analysis and related approaches [Hansch and Leo, 1995]. This approach known with the name of Hansch analysis became and it still is a basic tool for QSAR modeling. 

A useful list of 5800 partition coefficients is given by Hansch, Leo and Elkins (1971). They are presented as log P values in the system octanol/water or, if determined in another system, they are transposed to octanol/water values. The book Substituent Constants for Correlation Analysis (Hansch and Leo, 1979) has two very useful tables. Table VI-1, headed Well-characterized Aromatic Substituents contains the following information for 166 groups ... 

The range of most convenient hydrophobicity of organic compounds for reversed-phase (RP) HPLC separation may be estimated approximately as —1 < log P < + 5 (log P is the logarithm of the partition coefficient of the compound being characterized in the standard solvent system 1-octanol/water). Highly hydrophUic substances with log P < —1 need a special choice of analysis conditions, e.g., introduction of ion-pair additives into the eluents. Another approach is their conversion to more hydrophobic derivatives by the modification of functional groups with active hydrogen atoms. 

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