EFFECTS ON THE KIDNEY 



931 



Such a splitting would occur more rapidly the lower the pH. Certainly this 

 release of Hg++ is not generally responsible for the actions and toxicity of 

 the organic mercurials, and most of the mercurials, such as p-MB, PM, 

 and MM, are quite stable. Hepp (1887) emphasized long ago that alkyl 

 mercurials do not release Hg++ in the body and exert a toxic action much 

 different than Hg++. However, the diuretic mercurials present a different 

 situation and the theory of Hg++ release must be given serious consideration. 

 The possibility that the above reaction might be catalyzed or accelerated by 

 thiols through the formation of mercaptides was presented by Benesch and 

 Benesch (1952) as a result of their polarographic investigations of the reac- 

 tion between mersalyl and dimercaprol. In this scheme, free Hg++ may not 

 be produced directly; instead, a cyclic mercaptide is formed, which could 



OCH, 



I 

 -S-Hg— CHg— CH— R 



hS-Hg— CH2— CH— R 

 OCH, 



-s. 



Hg 



hS 



/ 



CH,= CH — R 



CH,OH 



OCH3 



I + 



R— CH— CHj— Hg 



conceivably be the inhibiting complex in renal transport, although it is also 

 possible that monothiols can act similarly: 



OCH3 

 — S— Hg— CH2— CH— R + H^ 



-S— Hg+ + CH2=CH— R + CH3OH 



since Mudge and Weiner (1958) showed that cysteine increases the split- 

 ting of mersalyl in acid medium. Other acid-stimulated types of splitting 

 would be the simple reactions: 



\\ // 



Hg 



v\ // 



Hg 



R— CH,— Hg + H 



R-CH, - Hg* 



but these usually occur fairly slowly, especially for the alkyl mercurials. 



