Dimethylthioarsenicals as Arsenic Metabolites and Their Chemical Preparations

Abstract

Two unidentified arsenic metabolites were detected in the liver of rats on a gel filtration column by HPLC inductively coupled argon plasma mass spectrometry after an injection of dimethylarsinic (DMA^V), dimethylarsinous (DMA^III), monomethylarsonic (MMA^V), or monomethylarsonous (MMA^III) acid. The same arsenicals were also produced in vitro by incubation of DMA^III in the liver supernatant but not by DMA^V. The two arsenic metabolites eluted at the same retention times as those of the two arsenicals prepared by reaction of DMA^V with either thiosulfate plus disulfite or hydrogen sulfide or sodium sulfide plus sulfuric acid. The faster and slower eluting products on a gel filtration column were assigned as dimethyldithioarsinic acid (dimethylarsinodithioic acid) (DMTA^V) and dimethylthioarsinous acid (DMTA^III) from mass spectrometric data at m/z = 170 and 138 by electrospray ionization mass spectrometry with negative and positive ion modes, respectively. They were prepared selectively by reacting DMA^V with hydrogen sulfide or sodium sulfide plus sulfuric acid under different reaction conditions. DMA^III but not DMA^V was transformed to DMTA^III and DMTA^V in the presence of sodium sulfide in vitro, suggesting that DMA^V is reduced to DMA^III with hydrogen sulfide, thiolated to DMTA^III, and then further thiolated oxidatively to DMTA^V. Metabolically, it is assumed that DMA^III is transformed to DMTA^III in the presence of sulfide ions, and then, DMTA^III is oxidatively thiolated to DMTA^V. As the chemical species produced by reduction with the Reay and Asher method are DMTA^III and DMTA^V, and different from DMA^III, the studies carried out with DMA^III with the Reay and Asher method have to be reexamined.