788 6. ARSENICALS 



As long ago as 1815 poisoning in Germany had been ascribed to certain 

 wallpapers containing arsenical pigments and many fatalities were reported. 

 A garlic odor was noted under these circumstances and was associated 

 with some toxic volatile compound, but it was not until 1874 that Selmi 

 suggested that molds might be responsible, and not until 1891 that Gosio 

 began his important studies which showed that certain fungi in culture 

 can release toxic substances from arsenite — since called "Gosio gas" — 

 and attempted to determine its nature (Gosio, 1893 a, b). He worked mainly 

 with Penicillium (Scopulariopsis) brevicaule but showed that some species 

 of Aspergillus and Mucor could also catalyze the reaction. Gosio believed 

 the volatile substance to be some sort of alkyl arsine and Challenger et al. 

 (1933) at Leeds finally identified it definitely as trimethylarsine. An excel- 

 lent review of this subject was written by Challenger (1945). 



The mechanism of this methylation by bread molds has been difficult 

 to unravel. The arsenicals were first thought to react with acetate but 

 little evidence for this was obtained; then formaldehyde was considered 

 as a possible donor but the data would not support this either; finally, it 

 was decided that there is a transfer of a methyl group from some donor 

 such as creatine or betaine, reduction of the arsenical occurring simulta- 

 neously. This type of methylation is probably not fundamentally different 

 from many transmethylations now known to occur, and similar enzyme 

 systems may be involved. Some fungi act on both arsenite and organic 

 arsenicals, some not on arsenite, and very few attack the phenylarsenoxides 

 (Bird et al., 1948). It is interesting that no ethylation occurs, even when 

 the proper donors are added, nor does dealkylation take place with the 

 formation of arsine or inorganic arsenite. Trichophyton rubrmn has recently 

 been shown to produce arsines from arsenate but not from arsenite (Zussman 

 et al., 1961). We know nothing about whether such methylations can occur 

 in animals. The presence of a garlic-like odor on persons poisoned by arsenic 

 indicates a volatile product, and unknown volatile substances have been 

 detected in animal tissues (Clements et al., 1951). 



THIOARSENITES 



The biochemical and pharmacological properties of the conjugates be- 

 tween arsenicals and thiols will be considered briefly. One would expect 

 the effects of the thioarsenites upon injection into animals or application 

 to isolated systems to depend mainly on the rate and degree to which they 

 are dissociated into the free arsenicals. If an infinitely stable thioarsenite 

 were used, no action should be observed unless the complex itself posses- 

 ses some activity unrelated to combination with SH groups. Complexes 

 with less and less stability should exert progressively more rapid and greater 

 effects. The stability of the thioarsenite in solution may be of some impor- 



