472 CHEMICAL AGENTS 



reaches the site of action. The contrast between ionized salts and 

 unionized lipid-soluble organic compounds is especially marked. 



2. Toxicity of the metals is affected by hydrogen ion and divalent 

 cations and by the presence of natural substances — proteins, amino 

 acids, hydroxy acids, etc. — which bind metal ions. 



3. Metals are accumulated by spores in large amounts from dilute 

 solutions. 



4. If metal ions cross a permeability barrier slowly, it is possible that 

 accumulation occurs by an adsorption process and is followed by a 

 slower entrance of the ion or a complex of it into the protoplast. Ion 

 antagonism, according to this hypothesis, is exerted in the adsorption 

 phase. For the present, however, it must be admitted that this mecha- 

 nism is speculative. 



5. Although the primary effect of metals is probably on enzymes in 

 the interior of the cell, effects on the permeability barrier itself cannot 

 be excluded entirely. 



6. Heavy metals inactivate enzymes. Combination with essential 

 sulfhydryl groups is the favored explanation, but it is likely that other 

 inactivation reactions, involving the formation of electrostatic or co- 

 ordinate bonds, also contribute to enzyme inhibition. 



8. THE ACTION OF SULFUR 



The most important organic sulfur fungicides are the dithiocarba- 

 mates, considered later as chelating agents. Many other organic sulfur 

 compounds — dithiazolidines (12), thiourea (80, 112), mercaptobenzo- 

 thiazole (100), xanthates (82), arylthioalkanecarboxylic acids (102), 

 phenothiazone (131), 3-pyridinethiol (394), benzothiazoles (142), com- 

 pounds with the N-trichloromethylthio grouping (201), substituted thio- 

 cyanates (215, 444), thiobisphenols (328), and such antibiotics as acti- 

 thiazic acid and gliotoxin — are more or less fungitoxic. However, there 

 is no reason to suppose that sulfur is necessarily directly involved in the 

 reaction of all these diverse compounds with cellular constituents. In 

 some organic molecules, the presence or absence of sulfur has no influ- 

 ence on toxicity (37, 82); in others it has (102). Some of the sulfur 

 compounds probably act primarily as chelating agents (11, 174). In 

 others sulfur may exert an effect by modifying the reactivity of nearby 

 functional groups or by affecting solubility. 



Inorganic sulfur, like copper, has been in use as a fungicide since the 

 beginning of serious efforts to control plant disease. The various forms 

 used, including liquid lime sulfur, all act ultimately as elemental sulfur. 

 Sulfur is, of course, virtually water-insoluble, and a great deal of effort 



