Gamble Bryan M, Gallagher Patricia A, Shoemaker Jody A, Parks Amy N, Freeman David M, Schwegel Carol A, Creed John T
United States Environmental Protection Agency, Office of Research and Development, National Exposure Research Laboratory, Microbiological and Chemical Exposure Assessment Research Division, Cincinnati, OH 45268, USA.
Analyst. 2003 Dec;128(12):1458-61. doi: 10.1039/b306931a. Epub 2003 Nov 5.
This paper evaluates the chemical stability of four arsenosugars using tetramethylammonium hydroxide (TMAOH) as an extraction solvent. This solvent was chosen because of the near quantitative removal of these arsenicals from difficult to extract seafood (oysters and shellfish). Four arsenosugars (3-[5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropylene glycol--As(328), 3-5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropanesulfonic acid--As(392), 3-[5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropyl hydrogen sulfate--As(408), and 3-[5'-deoxy-5'-(dimethylarsinoyl)-beta-ribofuranosyloxy]-2-hydroxypropyl-2,3-hydroxypropyl phosphate--As(482)) were evaluated. The stability of these four arsenosugars were studied independently in a solution of 2.5% TMAOH at 60 degrees C over a period of up to 8 h. Two arsenosugars, As(328) and As(392), were found to be relatively stable in this solution for up to 8 h. However, As(408) and As(482) formed detectable quantities of dimethylarsinic acid (DMAA) and As(328) within 0.5 and 2 h, respectively. It was found that 97% of As(408) degrades after 8 h of treatment producing 3.4 times as much DMAA as As(328). This is contrary to As(482), which produces 13 times as much As(328) as DMAA and only 37% of the As(482) was converted by the 8 h treatment at 60 degrees C. These degradation products led to the investigation of weaker TMAOH extraction solvents. Three different concentrations (2.5%, 0.83% and 0.25%) were used to determine the effect of TMAOH concentration on the degradation rate of As(408). By reducing the TMAOH concentration to 0.83%, the conversion of the arsenosugar to As(328) and DMAA is nearly eliminated (less than 5% loss). Arsenosugars, As(408) and As(482), were also studied in 253 mM NaOH to verify the degradation products. The NaOH experiments were conducted to investigate a possible hydroxide based reaction mechanism. Similar degradation plots were found for each arsenosugar when compared to the 2.5% TMAOH data. A mechanism has been proposed for the formation of As(328) from As(408) and As(482) in base via an SN2 reaction (hydroxide attack) at the side chain carbon adjacent to the inorganic ester. The formation of DMAA is observed in all arsenosugars after prolonged exposure. This probably occurs via an SN2 attack at the arsenic atom.
本文以氢氧化四甲铵（TMAOH）作为萃取溶剂，评估了四种砷糖的化学稳定性。选择这种溶剂是因为它能将近乎定量地从难以萃取的海产品（牡蛎和贝类）中去除这些砷化物。对四种砷糖（3-[5'-脱氧-5'-(二甲基亚砷酰基)-β-呋喃核糖氧基]-2-羟基丙二醇——As(328)、3-5'-脱氧-5'-(二甲基亚砷酰基)-β-呋喃核糖氧基]-2-羟基丙烷磺酸——As(392)、3-[5'-脱氧-5'-(二甲基亚砷酰基)-β-呋喃核糖氧基]-2-羟基丙基硫酸氢酯——As(408)和3-[5'-脱氧-5'-(二甲基亚砷酰基)-β-呋喃核糖氧基]-2-羟基丙基-2,3-羟基丙基磷酸酯——As(482)）进行了评估。在60℃下，将这四种砷糖分别置于2.5%的TMAOH溶液中，长达8小时，研究它们的稳定性。发现两种砷糖As(328)和As(392)在该溶液中长达8小时相对稳定。然而，As(408)和As(482)分别在0.5小时和2小时内形成了可检测量的二甲基次砷酸（DMAA）和As(328)。结果发现，处理8小时后，97%的As(408)降解，产生的DMAA是As(328)的3.4倍。这与As(482)相反，As(482)产生的As(328)是DMAA的13倍，在60℃下处理8小时后，只有37%的As(482)发生了转化。这些降解产物促使人们对较弱的TMAOH萃取溶剂进行研究。使用三种不同浓度（2.5%、0.83%和0.25%）来确定TMAOH浓度对As(408)降解速率的影响。通过将TMAOH浓度降至0.83%，砷糖向As(328)和DMAA的转化几乎被消除（损失小于%）。还在253 mM的NaOH中研究了砷糖As(408)和As(482)，以验证降解产物。进行NaOH实验是为了研究可能的基于氢氧化物的反应机理。与2.5% TMAOH的数据相比，每种砷糖都得到了类似的降解曲线。有人提出了一种机制，即As(408)和As(482)在碱中通过与无机酯相邻的侧链碳上的SN2反应（氢氧化物攻击）形成As(328)。长时间暴露后，在所有砷糖中都观察到了DMAA的形成。这可能是通过对砷原子的SN2攻击发生的。
