STRUCTURE AND ACTIVITY 



457 



Figure 7. The general form of 

 the relation between pH and the 

 toxicity of a weak acid. Redrawn 

 from Simon and Beevers (381), by 

 permission of the American Asso- 

 ciation for the Advancement of 

 Science. 



pH (scale of units) 



effect of structural changes on toxicity, indicates that the acridines act 

 at the surface and that they compete with other cations. Competition 

 between toxicant ions and other cations is considered elsewhere, in 

 connection with the action of copper. It should only be mentioned 

 here that this competition, insofar as hydrogen ion is involved, repre- 

 sents still another effect of pH on fungitoxicity. 



Finally, as suggested by Burchfield and Storrs (50), the internal pH 

 of the cell could affect fungicidal action by its influence upon the 

 ionization of cellular compounds which react with the toxicant. Thus, 

 reaction of amino groups with 2,4-dichloro-6-(o-chloroanilino)-s-triazine 

 probably occurs only if they are unionized, but sulfhydryl groups react 

 only if ionized. 



6. STRUCTURE AND ACTIVITY 



Structurally Non-Specific Inhibitors. Specific chemical structure as 

 a determinant of toxicity may be approached by considering first the 

 structurally non-specific poisons, the narcotics. These are compounds, 

 the effect of which is freely reversible, e.g., hydrocarbons, chlorinated 

 hydrocarbons, aliphatic alcohols, and phenols. The data on these are, 

 with few exceptions, derived from studies on animal systems. 



Probably no compound is absolutely without structural specificity. 

 The structurally non-specific inhibitors are, however, characterized by 

 a relatively low specificity, in the sense that changes in structure cause 

 no apparent change in the mode of action. Historically, the concept 

 of structural non-specificity arose from consideration of the effect of 

 homologous series; in general, toxicity on a molar basis rises with 



