Sulfur-containing arsenical mistaken for dimethylarsinous acid (DMA(III)) and identified as a natural metabolite in urine: Major implications for studies on assenic metabolism and toxicity

H. R. Hansen, Andrea Raab, Marcel Jaspars, Bruce Forbes Milne, Jorg Feldmann

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

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 (Na2S2O5)/sodium thiosulfate (Na2S2O3) reagent (method A) or by KI, H2SO4, and SO2 (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 C2H7OSAs. The structure was further confirmed by H-1 NMR, and ab initio tautomeric energy calculations showed it to be present as Me2As(=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.

Original languageEnglish
Pages (from-to)1086-1091
Number of pages5
JournalChemical Research in Toxicology
Volume17
DOIs
Publication statusPublished - 2004

Keywords

  • MONOMETHYLARSONOUS ACID
  • THIOREDOXIN REDUCTASE
  • METHYLATED ARSENICALS
  • TRYPANOCIDAL ACTION
  • SPECIATION
  • RATS
  • GLUTATHIONE
  • TRIVALENT
  • MMA(III)
  • PART

Cite this

@article{413be799ad8346dbae6210bf6b69606b,
title = "Sulfur-containing arsenical mistaken for dimethylarsinous acid (DMA(III)) and identified as a natural metabolite in urine: Major implications for studies on assenic metabolism and toxicity",
abstract = "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 (Na2S2O5)/sodium thiosulfate (Na2S2O3) reagent (method A) or by KI, H2SO4, and SO2 (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 C2H7OSAs. The structure was further confirmed by H-1 NMR, and ab initio tautomeric energy calculations showed it to be present as Me2As(=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.",
keywords = "MONOMETHYLARSONOUS ACID, THIOREDOXIN REDUCTASE, METHYLATED ARSENICALS, TRYPANOCIDAL ACTION, SPECIATION, RATS, GLUTATHIONE, TRIVALENT, MMA(III), PART",
author = "Hansen, {H. R.} and Andrea Raab and Marcel Jaspars and Milne, {Bruce Forbes} and Jorg Feldmann",
year = "2004",
doi = "10.1021/tx049978q",
language = "English",
volume = "17",
pages = "1086--1091",
journal = "Chemical Research in Toxicology",
issn = "0893-228X",
publisher = "American Chemical Society",

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TY - JOUR

T1 - Sulfur-containing arsenical mistaken for dimethylarsinous acid (DMA(III)) and identified as a natural metabolite in urine: Major implications for studies on assenic metabolism and toxicity

AU - Hansen, H. R.

AU - Raab, Andrea

AU - Jaspars, Marcel

AU - Milne, Bruce Forbes

AU - Feldmann, Jorg

PY - 2004

Y1 - 2004

N2 - 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 (Na2S2O5)/sodium thiosulfate (Na2S2O3) reagent (method A) or by KI, H2SO4, and SO2 (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 C2H7OSAs. The structure was further confirmed by H-1 NMR, and ab initio tautomeric energy calculations showed it to be present as Me2As(=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.

AB - 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 (Na2S2O5)/sodium thiosulfate (Na2S2O3) reagent (method A) or by KI, H2SO4, and SO2 (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 C2H7OSAs. The structure was further confirmed by H-1 NMR, and ab initio tautomeric energy calculations showed it to be present as Me2As(=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.

KW - MONOMETHYLARSONOUS ACID

KW - THIOREDOXIN REDUCTASE

KW - METHYLATED ARSENICALS

KW - TRYPANOCIDAL ACTION

KW - SPECIATION

KW - RATS

KW - GLUTATHIONE

KW - TRIVALENT

KW - MMA(III)

KW - PART

U2 - 10.1021/tx049978q

DO - 10.1021/tx049978q

M3 - Article

VL - 17

SP - 1086

EP - 1091

JO - Chemical Research in Toxicology

JF - Chemical Research in Toxicology

SN - 0893-228X

ER -