Octanol-water partition coefficent

Quantitative structure-activity relationships for fathead minnow Pimephales promelas) LC50 data were developed. As others have observed, log toxicity and log octanol/water partition coefficent (log P) are linearly related for alcohols (n = 20), alkyl ketones (n = 14), alkyl esters (n = 16), and alkyl nitriles (n = 8). When the sums of Taft sigma constants for the substituents of the most anionic carbon in each chemical structure were included in the regression of log LC50 versus log P, the coefficient of determination (r ) improved from 0.84 (for log P only) to 0.92 for alcohols, from 0.82 to 0.92 for ketones, from 0.77 to 0.91 for esters, and from 0.15 to 0.94 for nitriles. The r for the sum of Taft sigma constants versus LC50 for each class was less than 0.17. When the sum of a, was used instead of Taft sigma constants similar results were obtained. 

In developing some of the relationships, it is helpful to use a four-quadrant diagram in which each quadrant represents a species in a lipid or water phase. The diagram below shows a typical distribution of an acid, AH, between two phases where ion partitioning is assumed to be negligible. The partition coefficent, P, is the ratio of the concentration of AH in the octanol to the concentration of AH in the aqueous phase. The distribution coefficient, D, is the ratio of the concentration in the octanol to that of all forms in the water. This is also called the apparent partition coefficient. 

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). 

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