A chromatographic model for the biophase

Octanol/water partition coefficients, as we have seen, have been useful predictors of biological activity. In spite of this it has been suggested that bulk liquid phases may not be the most appropriate models for a stmctured biophase such as a biological membrane, and chromatographic stationary phases have been proposed as an alternative because of the stmcmring of the membranous hydrophobic chains. 

The large number of methods used to calculate log P values have been elegantly reviewed by Leo. The method proposed in 1964 by Fujita, Iwasa and Hansch used values for the parent molecule and values for substituents gathered by analysis of thousands of values of log P for homologous and other series. In this method of substituents log P is considered to be an additive-constitutive free-energy-related property, where one can define Ft for substituent X as the difference between the log P values for the parent solute and the compound with the substituent  

The fragmental method developed by Rekker and Mannhold uses the contributions of simple fragments. This may be illustrated by the example  

PEI being a proximity effect, an adjusting fraction for polar fragments in nonpolar surroundings. So 

A method based on the surface areas of molecules has also been proposed to obtain measures of logP in a manner analogous to the calculation of solubility. Computer programs for calculation of log P are also in use and are described in detail, in Leo s 1993 review. 

---