464 CHEMICAL AGENTS 



agents now in use are general poisons rather than inhibitors of specific 

 enzymes. The same conclusion arises from the finding (319) that sev- 

 eral very different enzymes are inhibited by fungicides and is supported 

 by the usual failure to obtain mutants resistant to organic fungicides 

 (217). 



Structural Modification and Fungitoxicity. The possibility of ob- 

 taining new fungicides or more useful modifications of older materials 

 has motivated considerable research on the relation between structure 

 and activity. Unfortunately, much of this work is of little help in de- 

 termining mode of action, since such essential factors as dissociation of 

 the toxicant, permeability of the cell, and the extent of accumulation 

 are usually unknown. 



Horsfall (174) and Sexton (372) review the general field of structure 

 and activity; some especially important recent work has been published 

 on the 5-triazines (51, 367), derivatives of acetanilide (66), triphenyl- 

 methanes and other dyes (93), substituted pyrazoles (267), unsaturated 

 hydrocarbons (262), ethylene oxide derivatives (329), and nitrophenols 

 (374). 



The phenols have been the most extensively investigated from this 

 aspect. Phenol itself and many of its derivatives have been regarded as 

 structurally non-specific, i.e., as narcotics (29), but activity toward fungi 

 and bacteria is markedly influenced by the number and type of substitu- 

 ents (372, 408). As a rule, alkylation increases activity and, within lim- 

 its, the longer the alkyl side chain the greater the toxicity (29, 141, 377). 

 This follows the rule for homologous series, i.e., there is an optimum 

 chain length for activity against a given organism (372). Halogenation 

 also increases the toxicity of phenols (29, 282, 376), but the position of 

 the halogen is important (29, 375, 408). The nitrophenols have al- 

 ready been mentioned as respiratory inhibitors. 



The bisphenols — not necessarily resembling the phenols in their ac- 

 tion — provide another example of the effect of structure on activity. 

 In general both antifungal and antibacterial activities require that the 

 compound be halogenated, that the linkage between the two rings be 

 ortho to hydroxyl groups, and that the two rings be not too far apart 

 (58, 274). Hexachlorophene, or 2,2'-methylenebis(3,4,6-trichlorophe- 

 nol), illustrates these features: 



CI OH HO CI 



