Hydrophobicity and its Calculation

The earliest successful biological QSAR correlating plant growth regulating activity of X-phenoxyacetic acids utilized Hammett sigma constants for electronic effects and pi-constants for hydrophobicity. Pi (designated by lower case Tt) for the most common substituents was taken as the difference in the 

With the realization that log Poet was a useful and critical tool in understanding bio-molecular interactions, and that the measurement of that parameter for every drug candidate was costly as well as impossible for those yet to be synthesized, a demand was created for a reliable method for calculating it from structure. Given the difficulties in calculating the properties of water itself, it is obvious that log Poet calculations must be, for the most part, empirically based. 

It was also clear that calculation of log Poet for the immense variety of structures that might be considered in computer-assisted drug design (CADD) would be impractical based on the 7i-system, and thus fragmental and whole molecule approaches have dominated these calculations. Since it plays such a pivotal role in the Hammett-Hansch QSAR methodology, the basis for log Poet calculation will be examined in some detail because, even though they lack a firm, theoretical basis, the calculation details can often be as useful in CADD as the bottom line number. 

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