Organoarsenical agents

Many organoarsenic compounds are prepared by reactions of AsC13 with alkyl group transfer agents such as Grignard reagents, lithium alkyls, or aluminum alkyls. Typical reactions include... 

Other organoarsenicals, most notably lewisite (dichloro[2-chlorovinyl]arsine), were developed in the early twentieth century as chemical warfare agents. Arsenic trioxide was reintroduced into the United States Pharmacopeia in 2000 as an orphan drug for the treatment of relapsed acute promyelocytic leukemia and is finding expanded use in experimental cancer treatment protocols (see Chapter 54). Melarsoprol, another trivalent arsenical, is used in the treatment of advanced African trypanosomiasis (see Chapter 52). 

Although now essentially obsolete for the treatment of human diseases because of their toxicities, organoarsenic compounds were the first synthetic organic pharmaceutical agents and were widely used in the early 1900s. The first pharmaceutical application was that of atoxyl (the sodium salt of 4-aminophenylarsinic acid), which was used to treat sleeping sickness. The synthesis of Salvarsan by Dr. Paul Ehrlich in 1907 was a development that may be considered the beginning of modem chemotherapy (chemical treatment of disease). Salvarsan was widely used for the treatment of syphilis. Toxic effects of Salvarsan included jaundice and encephalitis (brain inflammation). 

Discuss the historical aspects of organometallic compound toxicity, including organoarsenicals used as pharmaceutical agents, gasoline antiknock additives, and compounds used in applications such as catalysis and chemical synthesis. 

Stewart, D.L., E.J. Sass, L.K. Fritz and L.B. Sasser. 1989. Toxicology studies on lewisite and sulfur mustard agents Mutagenicity of lewisite in the Salmonella histidine reversion assay. Final Report, Pacific Northwest Laboratory Report, PNL-6872, Richland, WA. Trammell, G.L. 1992. Toxicodynamics of organoarsenic chemical warfare agents. In Somani, S.M., Ed. Chemical Warfare Agents. Academic Press, Inc. New York, pp.255-270. 

The toxicity of arsenic has been put into practical use in medicine. Ehrlich in 1909 developed Salvarsan, the trade name for arsphenamine (1), which was the first modem chemotherapeutic agent effective in the treatment of syphilis, which was eventually phased out by better organoarsenicals and latter by penicillin. Some specialist arsenical dmgs are still the treatment of choice for amoebic infections like glycobiarsol (2). ... 

Trammell, G.L. (1992). Toxicodynamics of organoarsenic chemical warfare agents. In Chemical Warfare Agents (Somani, S.M., ed.), pp. 255-210. Academic Press, New York. 

A small amount of organoarsenicals is used for animal feed additives. Four arsenic compounds are now used in animal husbandry (5 8) in the USA. The heterocycle 10,10 -oxybisphenoxarsine (9) is manufactured and marketed as an antimicrobial agent which is particularly useful in conjunction with plastics. These organoarsenicals are shown in Figure 2. 

Chemical analysis of organoarsenic based chemical warfare agents in the environment... 

Henriksson, J., Johannisson, A., Bergqvist, P.A., Norrgren, L., 1996. The toxicity of organoarsenic-based warfare agents in vitro and in vivo studies. Arch. Environ. Contam. Toxicol. 30, 213-219. 

Pitten, F.A., Muller. G Konig, P., Schmidt, D., Thuow, K Kramer, A., 1999. Risk assessment of a former military ba.se contaminated with organoarsenic-based warfare agents. Uptake of arsenic by terrestrial plants. Sci. Total Environ. 226, 237-245. 

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