612 6. ARSENICALS 



Peters (1955) has emphasized that the trivalent arsenicals should not 

 all be considered as acting in the same manner. There are, for example, 

 both monosubstituted (arsenoso-) and disubstituted (arsinoso-) compounds, 

 and these have been shown to have different reactivities with different 

 types of thiol. As an outcome of the work on the arsenical war gases, 

 Peters had come to the conclusion that the monosubstituted arsenicals 

 (such as (p-AsO or oxophenarsine) form particularly stable compounds 

 with dithiols where the SH groups are spatially arranged so that a ring 

 can be formed, the most stable ring being a five-membered one. Such 

 cyclic thioarsinites: 



I 1 



HS — C— S— C — 



R— As = + I -^ ^ R— As I + H2O 



HS— C- ^S— C— 



I I 



are more stable than those formed from two molecules of a monothiol: 



H,0 



as may be seen in the tabulation above. The problem of the disubstituted 

 arsenicals had been latent in Peters' mind for many years, inasmuch as 

 he had previously shown that differences in action exist between these 

 and the monosubstituted arsenicals. Furthermore, it is impossible for 

 the disubstituted arsenicals to form ring structures; instead they should 

 react with monothiols: 



R R 



\ \ 



As — OH + HS — R' ^ As — S — R' + H^O 



/ / 



R R 



steric factors should be kept in mind since these may limit the reaction. 

 For example, monosubstituted arsenicals may react with two molecules 

 of a small monothiol, but in the case of bulky thiols, such as proteins, this 

 may be impossible. Disubstituted arsenicals may be able to react with 

 both SH groups of a dithiol but only if the arsenical molecules do not steri- 

 cally interfere with each other. Peters and his collaborators have indeed 

 found enzymes (e. g., isocitrate dehydrogenase and aconitase) which are 

 inhibited by the disubstituted arsenicals but not by the monosubstituted 

 arsenicals, while other enzymes (e. g., the a-keto acid oxidases) are in- 

 hibited more readily by the monosubstituted arsenicals. The problem of 



