CHELATION 483 



tested as fungitoxicants (174), but it is presumed that the active group- 

 ing is the same in all. 



The important reactions of the dithiocarbamates from the standpoint 

 of mode of action may be summarized (127): 



TMTD 



Oxidation 



Reduction 



metals 



CS 2 + (CH 3 ) 2 NH <- - DMDT ;± Metal complexes (8) 



Hydrolysis 



TMTM 



(Symbols are taken from Figure 11; TMTM = tetramethylthiuram 

 monosulfide.) 



The primary problems of mode of action in this series are set for us 

 by (1) the bimodal response curve and (2) the effect of metals on toxic- 

 ity. Although it has been considered possible that carbon disulfide, 

 formed under acid conditions (234) or enzymatically (191, 192, 384) 

 from DMDT, is the active toxicant, both this and other decomposition 

 products are of too low inherent toxicity to account for DMDT action 

 (322, 432). 



The best available working hypothesis for the action of DMDT is 

 rather similar to that just discussed for oxine. It is proposed (127, 196) 

 that the first peak in the dose-response curve mirrors the formation of 

 a toxic 1:1 complex of DMDT with copper present in the medium. It 

 is suggested on the basis of work with yeast that this water-soluble 

 charged 1:1 complex exerts its effect at or just beneath the cell mem- 

 brane (127); this suggestion, supported by indirect evidence, avoids the 

 problem of explaining penetration of a charged complex. At higher 

 DMDT concentrations the insoluble and non-toxic 1:2 copper complex 

 (2 moles DMDT per copper atom) forms and accounts for the trough 

 in the dose-response curve. At still higher concentrations of DMDT, 

 either the free anion becomes toxic (196) or some other toxic complex, 

 e.g., with zinc, is formed (127). The first of these possibilities seems 

 more probable; free dithiocarbamate inhibits enzymes in vitro (319). 



It is to be noted that this hypothesis explains the first peak of the 

 bimodal response curve as a function of copper in the system; in a me- 

 dium low in copper and other metals there should be only a single peak 

 in the curve. This is borne out by visual estimates of mycelial growth 

 (196) but has not yet been shown by the more precise spore germination 

 technique. 



