Octanol partition

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. 

The homologous series of (/ -methyibenzyl)alkylamines [387] indicates an interesting 8/log P ct plot, shown in Fig. 5.5. The slope factor of the smaller members of the series, —1.02, is larger than that of the phenol series. The value being near 1 indicates that log m is invariant with the octanol partition constant—the... 

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. 

Clearly, the ability to cross membranes, as represented by octanol partitioning, correlates with the extent of reabsorption, with reabsorption only occurring at log Dy 4 values above 0. 

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). 

RBR is the relative biological response, tt is defined as log Pg - log P where P is generally the water-octanol partition coefficent for the parent molecule and P is the partition coefficient for the molecule containing substituent S. The a s are standard Hammett or Taft substituent constants (26, 27). 

This important piece of work had four main facets first, it showed that structure could be quantitatively related to biological activity secondly, it introduced the concept of activity being described by more than one parameter thirdly, the two-stage variation of activity wim the water-octanol partition coefficioit, denot by logP, was quantified using a quadratic equation and fourthly, it introduced the concept of the... 

Air-particle partition coefficient and air-octanol partition constant gKl3p = a ogKl30 +b 11... 

Figure 6.2 Experimentally determined air- dry octanol partition constants versus calculated (Eq. 6-11) air- wet octanol partition constants. Data from Hamer and Mackay (1995), Gruber et al. (1997), Hamer and Bidleman (1998a,b), Abraham et al. (2001).

Figure 6.7 Plot of the decadic logarithms of the air-olive oil partition coefficients versus the air-octanol partition constants for various sets of structurally related apolar, monopolar, and bipolar compounds. Note that olive oil is a mixture of compounds that may vary in composition. Therefore, we refer to A" a oUve oi] as the air-olive oil partition coefficient (and not constant, see Box 3.2). Adapted from Goss and Schwarzenbach (2001). The a and b values for the LFERs (Eq. 6-12) are alkanes (a - 1.15, b = 0.16), alkyl aromatic compounds (a = 1.08, b = 0.22), ethers (a = 0.97, 6 = 0.01), esters (a = 0.88, b = -0,14), ketones (a = 1.21, b = 1.06), alcohols (a = 0.98, b = 1.07).

Furthermore, air-organic solvent partition constants, in particular the air-octanol partition constant, are widely used to evaluate and/or predict the partitioning of organic compounds between air and natural organic phases. Such organic phases are present, for example, in aerosols or soils (Chapters 9 and 11) or as part of biological systems (Chapter 10). 

For estimating the air-olive oil partition coefficient, calculate first the air-octanol partition constant from the air-water (Kisw) and octanol-water (Ki0Vi) partition constants given in Appendix C (Eq. 6-11) ... 

Within a given class of apolar or weakly polar compounds (e.g., alkanes, chlorobenzenes, alkylbenzenes, PCBs), the variation in the air-octanol partition constants (Kiao) is much larger than the variation in the air-water partition constants (Kiaw). For example, the Kim values of the chlorinated benzenes vary between 10 3 5 (chlorobenzene) and 10-7 (hexachlorobenzene, see Hamer and Mackay, 1995), whereas their A, aw values are all within the same order of magnitude (Appendix C). Try to explain these findings. 

Table 10.4 LFERs Relating Air-Plant Partition Coefficients, K,ap, and Air-Octanol Partition Constants, Kiao, of PCBs for Various Herbs and Grasses at 25°C.(A, aP values are in kg dry weight-L"1.)a...

Air-Octanol Partition Constants (Kiao), Average Enthalpies of Air-Pasture Transfer (Aap//,), and Average Concentrations in Pasture (Cjp) and Air (Cja) of Three PCB Congeners... 

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