610 6. ARSENICALS 



and Eo — AsCl react rapidly with thiols, and this might point to the 

 R — As(0H)2 form as the reactive one. It is unlikely that an intermediate 

 of the type R — As(0H)2 — S- — R' is involved, since Parker and Kharasch 

 (1959) have shown that such unstable compounds are hydrolyzed to yield 

 the corresponding arsonic acid. One would also like to know more about 

 the relative rates at which various arsenicals react with different thiols. 

 Aldridge and Cremer (1955) reacted three arsenicals with glutathione and 

 dimercaprol, and determined the extent of the reaction by measuring the 

 increase in the time for reduction of 2,6-dichlorophenolindophenol by the 

 thiol (Table 6-2). It is seen that all the arsenicals react with dimercaprol 

 faster than with glutathione; indeed, arsenite does not react with gluta- 

 thione at all, a fact confirmed by Drummond and Stern (1960), who observed 

 no mercaptide formation even at 100 mM arsenite. It is also interesting 

 that di-9^-AsCl is the most reactive of the three, at least with the monothiol. 

 Stocken and Thompson (1946 b) reacted lewisite with a variety of thiols 

 and then determined how rapidly the resulting thioarsinites hydrolyze 

 by measuring the rate of porphyrindin reduction (see accompanying 

 tabulation), and these results well demonstrate the markedly greater sta- 



bility of the compounds formed with the dithiols. The fairly rapid splitting 

 of the monothioarsinites and the protein complexes indicate that most 

 enzyme inhibitions by the arsenicals should be readily reversible if secondary 

 changes in the protein have not occurred. 



