trans-2-chlorovinyldichloroarsine | 50361-05-2

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: trans-2-chlorovinyldichloroarsine
• 英文别名: trans-dichloro(2-chlorovinyl) arsine；β-Chlorovinyldichloroarsine；dichloro(2-chlorovinyl)arsine；2-chlorovinyldichloroarsine；β-lewisite；Lewisite-1；Lewisite；dichloro-[(E)-2-chloroethenyl]arsane
• CAS: 50361-05-2
• 化学式: C₂H₂AsCl₃
• 分子量: 207.318
• InChiKey: GIKLTQKNOXNBNY-OWOJBTEDSA-N

物化性质

• 沸点：
  185.6°C (estimate)
• 物理描述：
  When pure, a colorless oily liquid solidifying at -13°C. Impurities cause colors ranging from brown to violet. Faint odor of geranium. Irritating to the eyes and mucous membranes at concentrations below the threshold of odor. Very toxic; used as a war gas. Produces severe vesication (blistering) even through rubber (Merck); absorbed through the skin to produce seven systemic effects. Antidote: dimercaprol (British Anti-Lewisite). Prolonged exposure of container to fire or intense heat may result in violent rupturing and rocketing of container.
• 颜色/状态：
  Colorless liquid when pure; impurities lead to colors ranging from violet to brown.
• 气味：
  Faint odor of geranium
• 熔点：
  0.1 °C
• 闪点：
  None (EPA, 1998)
• 溶解度：
  0.00 M
• 密度：
  1.888 at 20 °C/4 °C
• 蒸汽密度：
  7.1 (EPA, 1998) (Relative to Air)
• 蒸汽压力：
  0.58 mm Hg at 25 °C
• 分解：
  When heated to decomposition it emits toxic fumes of /hydrogen chloride and Arsenic/.
• 气味阈值：
  1.40X10-2 mg/L (purity of sample: not specified)
• 保留指数：
  1083

计算性质

• 辛醇/水分配系数(LogP)：
  2.24
• 重原子数：
  6
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

ADMET

代谢

人们认为，刘易斯剂进入完整皮肤的水性介质后，会迅速水解为稳定、水溶性、但剧毒的衍生物2-氯乙烯砷氧化物（刘易斯剂氧化物）和盐酸。……刘易斯剂氧化物可能是刘易斯剂在组织中的主要代谢物和主要细胞毒性形式。还认为，高度活性的三价砷形式是所有砷化合物，包括刘易斯剂，对生物体系产生明显毒性的原因。

It is assumed that upon entry of Lewisite into the aqueous medium of the intact skin it is rapidly hydrolyzed to a stable, water-soluble, but highly toxic derivative 2-chlorovinylarsine oxide (Lewisite oxide) and hydrochloric acid. ... Lewisite oxide may be the principal metabolite and major cytotoxic form of Lewisite within tissues. It is also believed that the trivalent form of arsenic, which is highly reactive in biological systems, is responsible for the overt toxicity of all arsenicals, including Lewisite, to living systems.

来源:Hazardous Substances Data Bank (HSDB)

代谢

砷主要通过吸入或摄入进入人体，其次是皮肤接触。进入人体后，砷会在全身分布，根据需要被还原成亚砷酸盐，然后通过亚砷酸盐甲基转移酶被甲基化成单甲基砷（MMA）和二甲基硅酸（DMA）。砷及其代谢物主要通过尿液排出体外。已知砷能诱导金属结合蛋白金属硫蛋白，金属硫蛋白通过结合砷和其他金属，使它们生物学上失活，并作为抗氧化剂，从而减少砷和其他金属的有毒效果。

Arsenic is absorbed mainly by inhalation or ingestion, as to a lesser extent, dermal exposure. It is then distributed throughout the body, where it is reduced into arsenite if necessary, then methylated into monomethylarsenic (MMA) and dimethylarsenic acid (DMA) by arsenite methyltransferase. Arsenic and its metabolites are primarily excreted in the urine. Arsenic is known to induce the metal-binding protein metallothionein, which decreases the toxic effects of arsenic and other metals by binding them and making them biologically inactive, as well as acting as an antioxidant. (L20)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

发疱剂影响身体的外部和内部部分。发疱剂会引起炎症、水疱和组织的普遍破坏。蒸气对身体湿润区域的影响更大。眼睛特别容易受到发疱剂的伤害。吸入发疱剂会导致肺膜肿胀并充满液体（肺水肿）。由于缺氧，可能导致死亡。砷基发疱剂也是全身性药剂，容易通过皮肤影响到包括血细胞和肝脏的易感组织。砷基发疱剂还充当催吐剂...并产生剧烈的打喷嚏和反流。应将砷基发疱剂视为致癌物质。发疱剂通过吸入、皮肤和眼睛接触、摄入以及擦伤的皮肤（例如，皮肤破裂或碎片穿透皮肤）具有危害。液态药剂比它们的蒸气危险得多。/发疱剂 - 砷基/

Vesicants affect both exterior and interior parts of the body. Vesicants cause inflammation, blisters, and general destruction of tissues. Vapors have a greater impact on moist areas of the body. Eyes are especially susceptible to vesicants. Inhalation of vesicants can cause lung membranes to swell and become filled with liquid (pulmonary edema). Death may result from lack of oxygen. Arsenical vesicants are also systemic agents and readily pass through the skin to affect susceptible tissue including blood cells and the liver. Arsenical vesicants also act as vomiting agents ... and produce violent sneezing and regurgitation. Arsenical vesicants should be considered carcinogenic. Vesicants are hazardous through inhalation, skin and eye exposure, ingestion, and abraded skin (e.g., breaks in the skin or penetration of skin by debris). Liquid agents are much more hazardous than their vapors. /Vesicants - Arsenic Based/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

砒霜及其代谢物通过多种机制干扰ATP的产生。在柠檬酸循环层面，砒霜抑制了丙酮酸脱氢酶，并通过与磷酸竞争解耦了氧化磷酸化，从而抑制了与能量相关的NAD+还原、线粒体呼吸和ATP合成。过氧化氢的产生也增加了，这可能会形成活性氧物种和氧化应激。砒霜的致癌性受到砒霜与微管蛋白结合的影响，导致非整倍体、多倍体和有丝分裂停滞。其他砒霜蛋白靶点的结合也可能导致DNA修复酶活性改变、DNA甲基化模式改变和细胞增殖。

Arsenic and its metabolites disrupt ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress. Arsenic's carginogenicity is influenced by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. The binding of other arsenic protein targets may also cause altered DNA repair enzyme activity, altered DNA methylation patterns and cell proliferation. (T1, A17)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

3, 其对人类致癌性无法分类。

3, not classifiable as to its carcinogenicity to humans. (L135)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

砒霜中毒可能导致多系统器官衰竭而死亡，可能是由于坏死细胞死亡，而非凋亡。砒霜也是一种已知的致癌物，特别是在皮肤癌、肝癌、膀胱癌和肺癌中。

Arsenic poisoning can lead to death from multi-system organ failure, probably from necrotic cell death, not apoptosis. Arsenic is also a known carcinogen, esepcially in skin, liver, bladder and lung cancers. (T1, L20)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服（L2）；吸入（L2）；皮肤（L2）

Oral (L2) ; inhalation (L2) ; dermal (L2)

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

路易斯毒剂接触皮肤后迅速渗透。它强烈地与蛋白质和硫醇结合，其局部和全身毒性机制可能通过这种结合介导。它会在体内含有硫醇的组织中浓缩（例如，皮肤和头发）。

Lewisite penetrates skin rapidly on contact. It binds avidly to proteins and thiols, and the mechanism of its local and systemic toxicity is likely mediated through this binding. It is concentrated in the thiol-containing tissues throughout the body (e.g., skin and hair).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

路易斯剂通过皮肤吸收；皮肤上只要有2毫升就可能致命。

Lewisite is absorbed through skin; as little as 2 mL on the skin can cause death.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

路易斯毒剂会迅速通过皮肤和粘膜被吸收。

Lewisite is rapidly absorbed through the skin and mucous membranes.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在兔子中，以等毒性致死剂量给药时，砒霜的砷组织水平远高于路易氏剂。有一个显著的例外，即肺部，肺部的组织水平路易氏剂略高。考虑到路易氏剂的静脉致死剂量，基于砷含量，远低于砒霜，路易氏剂的砷明显优先分布到肺部。

... In rabbits, at doses of equal lethal toxicity, tissue levels of arsenic were much higher with sodium arsenite than with lewisite. There was a notable exception, namely the lungs, where tissue levels were slightly higher with lewisite. Bearing in mind that the intravenous lethal dose of lewisite is , on an arsenic content basis, much lower than that of sodium arsenite, the arsenic of lewisite clearly preferentially distributes to the lung.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  trans-2-chlorovinyldichloroarsine 生成 chloro-bis-(2-chloro-vinyl)-arsine
  参考文献：
  名称：

  Hewett, Journal of the Chemical Society, 1948, p. 1204

  摘要：

  DOI：
• 作为产物：
  描述：

  2-氯乙烯基砷酸 在 盐酸 、 二氧化硫 、 水 、 碘 作用下， 生成 trans-2-chlorovinyldichloroarsine
  参考文献：
  名称：

  Hewett, Journal of the Chemical Society, 1948, p. 1204

  摘要：

  DOI：

文献信息

• Reaction of Lewisite-1 with Alcohols, Diols, and Thiols in Water—A Simple Method of Derivatization of Thiodiglycol
  作者：Mieczysław S. Sokołowski、Leszek Konopski

  DOI：10.1080/10426500701429197

  日期：2008.9.5

  Reaction of 2-chlorovinyldichloroarsine (Lewisite-1) with alcohols, thiols, diols, and hydroxy thiols in water at 40°C has been examined. The expected derivatization products, dialkyl 2-chlorovinylarsonites or corresponding arsonodithiolites, were obtained with alcohols and thiols, whereas reactions with bifunctional diols and hydroxythiols produced analogous cyclic esters. All derivatives may be easily

  研究了 2-氯乙烯基二氯胂（Lewisite-1）与醇、硫醇、二醇和羟基硫醇在 40°C 下在水中的反应。用醇和硫醇获得预期的衍生产物，二烷基 2-氯乙烯基亚拉森酯或相应的 arsonodithiolites，而与双官能二醇和羟基硫醇的反应产生类似的环酯。使用气相色谱法可以很容易地检测所有衍生物。发现该反应可用于将双（2-羟乙基）硫化物（硫二甘醇）（一种硫芥子分解产物）轻松转化为稳定的八元环状亚砷酸盐衍生物。用二氯甲烷萃取后，可以使用 GC/MS 轻松且选择性地检测水基质中 100 ppb 硫代二甘醇含量的衍生物，从而避免繁琐的水蒸发和硅烷化过程。
• Two-dimensional NMR studies of arsenical-sulfhydryl adducts
  作者：Richard J. O'Connor、Evelyn L. McGown、Kilian Dill、Susan F. Hallowell

  DOI：10.1002/mrc.1260270713

  日期：1989.7

  dimercaptopropanesulfonic acid. These two disulfhydryl compounds were compared with BAL by studying the structures of their adducts with two organic arsenicals, phenyldichloroarsine and trans‐2‐chlorovinylarsine oxide. The 1:1 adducts were synthesized and characterized by one‐ and two‐dimensional NMR spectroscopy. 1H and 13C spectral data and resonance assignments, verified by spin simulation, are presented

  英国抗路易斯（2,3-二巯基丙醇）（BAL）长期以来被用作砷解毒剂，但其治疗效果受到其固有毒性的限制。BAL 的两种毒性较低的潜在替代品是二巯基琥珀酸和二巯基丙磺酸。通过研究它们与两种有机砷化合物苯基二氯胂和反式 2-氯乙烯胂氧化物的加合物的结构，将这两种二巯基化合物与 BAL 进行了比较。合成了 1:1 加合物，并通过一维和二维 NMR 光谱对其进行了表征。1H 和 13C 光谱数据和共振分配，通过自旋模拟验证，提供了加合物。都是五元杂原子环系统，具有不同的溶解性。当可检测到立体异构体时，反异构体与顺异构体的比例会发生变化，
• Knunjanz; Pil'skaja, Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1955, p. 472,476; engl.Ausg.S.417,420
  作者：Knunjanz、Pil'skaja

  DOI：——

  日期：——
• 5. Hydrolyses and derivatives of some vesicant arsenicals
  作者：William A. Waters、J. Howarth Williams

  DOI：10.1039/jr9500000018

  日期：——
• Das-Gupta, Journal of the Indian Chemical Society, 1937, vol. 14, p. 231,235
  作者：Das-Gupta

  DOI：——

  日期：——

表征谱图