Methylated and thiolated arsenic species for environmental and health research — A review on synthesis and characterization

Hundreds of millions of people around the world are exposed to elevated concentrations of inorganic and organic arsenic compounds, increasing the risk of a wide range of health effects. Studies of the environmental fate and human health effects of arsenic require authentic arsenic compounds. We summarize here the synthesis and characterization of more than a dozen methylated and thiolated arsenic compounds that are not commercially available. We discuss the methods of synthesis for the following 14 trivalent (III) and pentavalent (V) arsenic compounds: monomethylarsonous acid (MMAIII), dicysteinylmethyldithioarsenite (MMAIII(Cys)2), monomethylarsonic acid (MMAV), monomethylmonothioarsonic acid (MMMTAV) or monothio-MMAV, monomethyldithioarsonic acid (MMDTAV) or dithio-MMAV, monomethyltrithioarsonate (MMTTAV) or trithio-MMAV, dimethylarsinous acid (DMAIII), dimethylarsino-glutathione (DMAIII(SG)), dimethylarsinic acid (DMAV), dimethylmonothioarsinic acid (DMMTAV) or monothio-DMAV, dimethyldithioarsinic acid (DMDTAV) or dithio-DMAV, trimethylarsine oxide (TMAOV), arsenobetaine (AsB), and an arsenicin-A model compound. We have reviewed and compared the available methods, synthesized the arsenic compounds in our laboratories, and provided characterization information. On the basis of reaction yield, ease of synthesis and purification of product, safety considerations, and our experience, we recommend a method for the synthesis of each of these arsenic compounds.