Octanol, partition coefficient

The ending caine stems from cocaine, the first clinically employed local anaesthetic. Procaine and tetracaine are ester-linked substances, the others are amides. Amide bonded local anaesthetics usually contain two i s in their name, ester-bonded only one. In the structure drawings, the lipophilic portion of the molecule is depicted at the left, the amine at the right. The asterisk marks the chiral centre of the stereoisomeric drugs. Lipid solubility is given as the logarithm of the water octanol partition coefficient, log(P). 

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. 

At the opposite extreme is the example of amiodarone. The log octanol partition coefficient is 7.8 [162], whereas the membrane constant is reported as 6.0 [429], surprisingly, almost two orders of magnitude smaller (8 = —1.8). 

In this model, one can argue that a peptide must have both an affinity for the interface (favorable n-octanol partition coefficient) and small desolvation energy (favorable A log PC) in order to efficiently cross a cell membrane. On the other hand, this model also predicts that a peptide with a large n-octanol/water partition coefficient and large desolvation energy, due to a significant number of polar groups, should adsorb and remain at the membrane interface. Both of these predicted events have been observed in the laboratory. 

Fig. 15.9. Correlation between observed retention indices and octanol partition coefficients [66],...

Thus, water-octanol partition coefficients (logP0ct) were shown to follow equation 7 ... 

Marple, L., Berridge, B., and Throop, L. Measurement of the water-octanol partition coefficient of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Environ. Sci. Technol, 20(4) 397-399,1986. 

The correlation between partition coefficient and chromatographic retention has been examined by many workers in an attempt to predict log F, the logarithm of water-octanol partition coefficient used in establishing structure-function relationships, from retention data or vice versa. The data (92, 203, 215) seem to imply changes in log k are linear in changes in log P but that log k changes more slowly. Some literature data suggest that the retention is directly proportional to the partition coefficient. This apparent equality disappears, however, if the data are recalculated to identical experimental conditions. 

Fio. 38. Plot of the algorithm of the retention factor, k, and log P, the water-/i>octanol partition coefficient of eight amino acids. The chromatographic data were obtained on 3 ftm LiChrosorb kP-8, 230 x 4.6 mm i.d. eluierit 0.1 M aqueous phosphate buffer, pH 6.7, T 70 C. Eluites Trp, tryptophan Phe, phenylalanine Leu, leudne Val. valine Tyr, tyrosine Lys, lysine Ala, alanine Gly, glycine. Reprinted with permission from Molnar and Horvith QOS). 

The octanol/water partition coefficient (log P) indicates the hydrophobiaty of a substrate. Fligher hydrophobicity of a chemical compound will decrease its aqueous solubility. Because hydroxyl radicals have reaction rates that are most likely diffusion controlled, the reaction rates of hydrophobic compounds in aqueous systems, such as Fenton s reaction, will be negatively affected. Figure 6.22 shows the effect of the octanol/partition coefficient on the oxidation rates of 2-chlorophenol, 2,4-dichlorophenol, 2,4,6-trichlorophe-nol, and pentachlorophenol. Pentachlorophenol has the lowest aqueous solubility and correspondingly its reaction rates are significantly affected. 

Marple L, Berridge B, Throop L. 1986a. Measurement of the water-octanol partition coefficient of... 

FIGURE 3.18 Water-octanol partition coefficients measured and calculated by CLOGP. [Graph reconstructed from data by Yang et al., J. Pharm. Sci., 91, 517 (2001).]... 

Octanol Partition Coefficients Using Theoretical Descriptors Derived from Molecular Surface Area and the Electrostatic Potential. 

Isnard, P., Lambert, S. (1988) Estimating bioconcentration factors from octanol partition coefficient and aqueous solubility. Chemo-sphere 17, 21-34. 

Haeberlein, M. and Brinck, T. (1997). Prediction of Water-Octanol Partition Coefficients Using Theoretical Descriptors Derived from the Molecular Surface Area and the Electrostatic Potential. J.Chem.Soc. Perkin Trans.2,289-294. 

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