608 6. ARSENICALS 



REACTIONS OF THE ARSENICALS 



The development of the concept that arsenicals affect biological systems 

 through reaction with SH groups was briefly discussed in the introduction 

 to this chapter. There are no other groups of biological importance with 

 which the trivalent arsenicals readily react, and in this sense these in- 

 hibitors may be said to be quite specific. 



Reactions with Thiols 



The reaction of inorganic trivalent arsenic with sulfides has, of course, 

 been known for a very long time. The first organic thioarsinite to be studied 

 was arsenic trithiolacetic acid: 



S— CH2— COOH 



HOOC— CHj— S— As 



S— CH2— COOH 



in 1904, this being a crystalline substance forming a soluble sodium salt 

 and easily prepared by reacting arsenic trioxide with thiolacetic acid in 

 aqueous solution. Thioarsinites of the organic arsenicals were soon made 

 and tested for activity against microorganisms. Labes (1929 a) obtained 

 the thioarsinite formed by arsenious acid and cysteine (i. e., tricysteinyl- 

 arsine) in crystalline form, and Johnson and Voegtlin (1930) obtained the 

 same product by reacting arsenious chloride with cysteine at room temper- 

 ature. By 1930 there was thus not only good evidence that both inorganic 

 and organic trivalent arsenicals can react with various thiols, but some 

 well-characterized thioarsinites had been prepared in pure form. 



It is important to realize that the 9^-arsonates can also eventually react 

 with thiols. Friedberger (1908) found that p-amino-9:i-arsonate when mixed 

 with thiolacetate becomes highly toxic to mice and is an effective trypano- 

 cide. It was soon shown by Roehl (1909) that this is due to the reduction 

 of the arsonate to the corresponding arsenoxide, which is, of course, active. 

 However, it was noted that if thiolacetate is in excess, some of the arsen- 

 oxide formed reacts to form a dithioarsinite: 



R— AsO(OH)2 + 2 HS— R' ^ R— As=0 + R'— S— S— R' + 2 H^O 



S— R' 



R— As=0 + 2 HS— R' ^ R— As + HjO 



\ 

 S— R' 



The reduction proceeds in acidic but not appreciably in alkaline solutions. 

 If cystine is mixed with an arsenoxide, cysteine is formed and the arsenical 



