H E A V Y METALS 



465 



Replacement of the methylene bridging group by sulfur yields active 

 materials (328), and still other linkages are compatible with activity 

 (73, 295). Bisphenols have proved especially effective in the protection 

 of textiles from fungal decay (386) and against fungi pathogenic to 

 animals (58). The mode of action is not known; hexachlorophene is 

 inhibitory at high dilution to several respiratory enzymes (135, 136). 

 In considering the effect of substitution on fungitoxicity, data can- 

 not be evaluated properly on the basis solely of the usual two-dimen- 

 sional visualization of an organic molecule. Some of the often neg- 

 lected factors may be listed very briefly: 



1. A substituent may alter the reactivity of nearby groups or of as 

 large a component as an entire ring. Substituents may be electron-at- 

 tracting or electron-repelling, may encourage or discourage hydrogen 

 bonding and chelation. 



2. A change in structure may either reduce or facilitate stabilization 

 by resonance. 



3. The addition of substituents may change the pK a . This is espe- 

 cially marked in the phenols (29); phenol itself has a pK a of 10.0, p-ni- 

 trophenol of 7.2, 2,4-dinitrophenol of 4.0 (383). Thus, at pH 7 phenol 

 is less than 1 per cent ionized and 2,4-dinitrophenol is over 99 per cent 

 ionized. 



4. The oxidation-reduction potential of, for example, the naphtho- 

 quinones may be either raised or lowered by substituent groups. 



5. The shape of the molecule, considered three-dimensionally, may 

 be altered by substitution; this has been especially thoroughly explored 

 in the acridines, the antibacterial action of which requires a minimum 

 planar area (6). 



6. Alterations in a molecule may make it more or less susceptible to 

 biochemical attack by enzymes of the test organism, as suggested by 

 Owens (319) for substituted phenols. 



7. Lastly, as previously discussed, changes in the physical properties 

 of a compound may render it more or less able to enter the cell or to 

 accumulate at its site of action. 



7. THE ACTION OF HEAVY METALS 



The major share of our information on the fungistatic activity of 

 the heavy metals comes from studies on copper, the active ingredient, 

 at least until the advent of organic fungicides, of some of the most 

 important plant and textile protectants. Mercury compounds have 

 been used less for fungi but more as bacteriostatic agents. Silver 

 is of little practical importance because of its cost, although it is an 



