Abstract
When the relative hydrogen-bonding effect of drugs on phases involved in the binding at the site of biological action differs from that in the 1-octanol-H2O partitioning phases used as the reference to estimate the hydrophobicity, a parameter (or parameters) which represents the "extra" hydrogen-bonding effect on the biological activity is required in the Hansch-type correlations. As a first approximation, the effect is analyzed in terms of the ratio of hydrogen-bonding association constants and the ratio of molarities of hydrogen-bonding species constituting the biological and organic phases. Sometimes, the association constants in both phases are so similar that they are not important in determining the extra hydrogen-bonding effect. The net result is that the effect is expressible by an indicator variable term the slope of which corresponds to the molarity ratio. The variable only applies to substituents having appreciable association capability in correlating a certain biological action exhibited by a series of congeners.
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