Sulfur-containing arsenical mistaken for dimethylarsinous acid [DMA(III)] and identified as a natural metabolite in urine: major implications for studies on arsenic metabolism and toxicity.
It is vital that methylated trivalent arsenicals [MA(III) and DMA(III)] are described and characterized unequivocally due to their high toxicity. Two different ways of generating the methylated trivalent arsenicals have been practiced-reduction of the methylated pentavalent arsenical either by the sodium-metabisulfite (Na(2)S(2)O(5))/sodium thiosulfate (Na(2)S(2)O(3)) reagent (method A) or by KI, H(2)SO(4), and SO(2) (method B). The shared identity between the products of the two synthetic methods has never been questioned or proven. Here, we characterize and identify the arsenic species formed when reducing DMA(V) by method A or B. Dimethylarsinous acid [DMA(III)] was formed when reducing DMA(V) by method B, but DMA(III) was not the main product of the reaction by method A. The product was revealed by HPLC-ICP-MS coupled simultaneously to HPLC-ES-MS and ES-Q-TOF-MS to have the molecular formula C(2)H(7)OSAs. The structure was further confirmed by (1)H NMR, and ab initio tautomeric energy calculations showed it to be present as Me(2)As(=S)OH (dimethylarsinothioic acid). Dimethylarsinothioic acid was also identified as a metabolite in urine and in wool extract from sheep naturally consuming large amounts of arsenosugars (35 mg of As daily) through their major food source, seaweed.
Department of Chemistry, College of Physical Sciences, University of Aberdeen, Meston Walk, Old Aberdeen AB24 3UE, United Kingdom.
Helle R
HR
Hansen
Andrea
A
Raab
Marcel
M
Jaspars
Bruce F
BF
Milne
Jörg
J
Feldmann
D000818:Animals; D020261:Arsenic Poisoning / Q000652:urine; D001152:Arsenicals / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000652:urine*; D002101:Cacodylic Acid / Q000031:analogs & derivatives* / Q000032:analysis* / Q000378:metabolism / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D012756:Sheep; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods / Q000592:standards; D013457:Sulfur Compounds / Q000737:chemistry* / Q000378:metabolism / Q000652:urine; D014935:Wool / Q000737:chemistry
D001152:Arsenicals; D013457:Sulfur Compounds; C472511:dimethylarsinous acid; D002101:Cacodylic Acid