O-乙基-S-[2-(二异丙氨基)乙基]甲基硫代磷酸酯 | 50782-69-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: O-乙基-S-[2-(二异丙氨基)乙基]甲基硫代磷酸酯
• 英文名称: O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothiolate
• 英文别名: N-[2-[ethoxy(methyl)phosphoryl]sulfianylethyl]-N-propan-2-ylpropan-2-amine；O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate；Agent VX；O-Ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate；N-[2-[ethoxy(methyl)phosphoryl]sulfanylethyl]-N-propan-2-ylpropan-2-amine
• CAS: 50782-69-9
• 化学式: C₁₁H₂₆NO₂PS
• 分子量: 267.373
• InChiKey: JJIUCEJQJXNMHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  54.8
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

毒理性

• 副作用

其他毒药 - 有机磷

Other Poison - Organophosphate

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 相互作用

两只豚鼠模型被用来研究地西泮、咪达唑仑和东莨菪碱对由神经毒剂塔崩、沙林、梭曼、环沙林、O-乙基 S-(2-(二异丙氨基)乙基)甲基硫代磷酰氧酸（VX）和O-异丁基 S-(2-二乙氨基)乙基)-甲基磷酰硫代酸（VR）诱导的癫痫的 抗惊厥效力。在挑战神经毒剂前30分钟，对用于脑电图记录的动物进行吡啶斯的明溴化物（0.026 mg/kg 肌注）预处理。在模型A中，硫酸阿托品（2.0 mg/kg 肌注）和氯磷定（2-PAM；25.0 mg/kg 肌注）在神经毒剂挑战后1分钟给予，测试的抗惊厥药物在癫痫发作后5分钟给予（肌注）。在模型B中，在神经毒剂挑战后1分钟给予较低剂量的硫酸阿托品（0.1 mg/kg 肌注）和2-PAM，抗惊厥药物在癫痫发作时给予。使用较低剂量的阿托品，所有毒剂的癫痫发生率增加到几乎100%；沙林、环沙林和VX的发作潜伏期缩短；神经毒剂中毒的症状更严重；并且经常出现由环沙林引起的昏迷。东莨菪碱或地西泮的抗惊厥ED50剂量通常在两个模型之间没有差异，而咪达唑仑的抗惊厥ED50值随着较低阿托品剂量的增加而增加了3到17倍。癫痫终止时间并没有系统地受到不同剂量阿托品的影响。在每个模型内，抗惊厥效果的顺序是东莨菪碱 >= 咪达唑仑 > 地西泮。这些发现表明，作为解毒疗法的阿托品剂量可以显著影响神经毒剂毒性和对抗惊厥治疗的反应性。

Two guinea pig models were used to study the anticonvulsant potency of diazepam, midazolam, and scopolamine against seizures induced by the nerve agents tabun, sarin, soman, cyclosarin, O-ethyl S-(2-(diisopropylamino)ethyl)methylphosphonothioate (VX), and O-isobutyl S-(2-diethylamino)ethyl)-methyl phosphonothioate (VR). Animals instrumented for electroencephalogram recording were pretreated with pyridostigmine bromide (0.026 mg/kg im) 30 min before challenge with 2 x LD50 (s.c.) of a nerve agent. In model A, atropine sulfate (2.0 mg/kg im) and pyridine-2-aldoxime methylchloride (2-PAM; 25.0 mg/kg im) were given 1 min after nerve agent challenge, and the tested anticonvulsant was given (im) 5 min after seizure onset. In model B, a lower dose of atropine sulfate (0.1 mg/kg im) was given along with 2-PAM 1 min after nerve agent challenge, and the anticonvulsant was given at seizure onset. With the lower dose of atropine, seizure occurrence increased to virtually 100% for all agents; the time to seizure onset decreased for sarin, cyclosarin, and VX; the signs of nerve agent intoxication were more severe; and coma resulted frequently with cyclosarin. The anticonvulsant ED50 doses for scopolamine or diazepam were, in general, not different between the two models, whereas the anticonvulsant ED50 values of midazolam increased 3- to 17-fold with the lower atropine dose. Seizure termination times were not systematically affected by the different doses of atropine. The order of anticonvulsant effectiveness within each model was scopolamine > or = midazolam > diazepam. The findings indicate that the dose of atropine given as antidotal therapy can significantly influence measures of nerve agent toxicity and responsiveness to anticonvulsant therapy.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

目前针对神经毒剂中毒的治疗方法可以提高生存率，但并不能完全防止神经毒剂引起的运动和认知缺陷或神经病理。使用来源于人血浆的丁酰胆碱酯酶（HuBuChE）来中和体内神经毒剂的毒性已被证明既能提高生存率，又能防止神经毒剂暴露后认知功能的下降。最近，一种在转基因山羊奶中表达的、商业生产的重组人丁酰胆碱酯酶（r-HuBuChE ...）的形式已经可用。这种材料在体外试验中与血浆来源的HuBuChE在生物化学上相似。对一种聚乙二醇包被（pegylated）形式的r-HuBuChE在豚鼠中的药代动力学特性进行了确定；该酶迅速生物可用，其半衰期（t1/2）和药代动力学曲线与血浆来源的huBuChE相似。豚鼠在暴露前18小时（sc）注射了140 mg/kg（im）的pegylated r-HuBuChE，然后暴露于5.5xLD50的VX或梭曼。VX和梭曼分三次注射，剂量分别为1.5xLD50、2.0xLD50和2.0xLD50，每次注射间隔2小时。用pegylated r-HuBuChE预处理提供了对多剂量的VX和梭曼致死剂量的100%生存率。豚鼠在暴露后没有显示出神经毒剂毒性的迹象。在神经毒剂暴露后的2周内进行了运动活动、协调和空间记忆获取的评估。在此期间没有可测量的运动或认知功能下降。相比之下，接受1.5xLD50剂量的梭曼或VX挑战并接受标准阿托品、2-PAM和地西泮治疗的动物分别显示出50%和100%的存活率，但表现出明显的运动功能下降，在GD的情况下，空间记忆获取受损。这一领域的进展导致决定选择血浆来源的BuChE和重组形式的BuChE进行高级开发和转向临床试验。...

Currently fielded treatments for nerve agent intoxication promote survival, but do not afford complete protection against either nerve agent-induced motor and cognitive deficits or neuronal pathology. The use of human plasma-derived butyrylcholinesterase (HuBuChE) to neutralize the toxic effects of nerve agents in vivo has been shown to both aid survival and protect against decreased cognitive function after nerve agent exposure. Recently, a commercially produced recombinant form of human butyrylcholinesterase (r-HuBuChE ...) expressed in the milk of transgenic goats has become available. This material is biochemically similar to plasma-derived HuBuChE in in vitro assays. The pharmacokinetic characteristics of a polyethylene glycol coated (pegylated) form of r-HuBuChE were determined in guinea pigs; the enzyme was rapidly bioavailable with a half-life (t1/2) and pharmacokinetic profile that resembled that of plasma-derived huBuChE. Guinea pigs were injected with 140 mg/kg (im) of pegylated r-HuBuChE 18 hr prior to exposure (sc) to 5.5xLD50 VX or soman. VX and soman were administered in a series of three injections of 1.5xLD50, 2.0xLD50, and 2.0xLD50, respectively, with injections separated by 2 hr. Pretreatment with pegylated r-HuBuChE provided 100% survival against multiple lethal doses of VX and soman. Guinea pigs displayed no signs of nerve agent toxicity following exposure. Assessments of motor activity, coordination, and acquisition of spatial memory were performed for 2 weeks following nerve agent exposure. There were no measurable decreases in motor or cognitive function during this period. In contrast, animals receiving 1.5xLD50 challenges of soman or VX and treated with standard atropine, 2-PAM, and diazepam therapy showed 50 and 100% survival, respectively, but exhibited marked decrements in motor function and, in the case of GD, impaired spatial memory acquisition. The advances in this field have resulted in the decision to select both the plasma-derived and the recombinant form of BuChE for advanced development and transition to clinical trials. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

有机磷化合物，如神经毒剂，通过在酶的活性部位磷酸化，几乎不可逆地抑制胆碱酯酶。目前用于治疗急性神经毒剂中毒的解毒治疗包括联合使用抗胆碱能药物（通常是阿托品）和乙酰胆碱酯酶（AChE，EC 3.1.1.7）复活剂（HI-6，奥比多西姆，普瑞多西姆），从化学角度看，这些复活剂是吡啶或双吡啶醛肟类化合物的衍生物（通常称为"肟"）。肟类化合物对抗由于AChE抑制导致的乙酰胆碱增加。在人体环境中，这些化合物是强大的亲核试剂，能够破坏AChE与神经毒剂分子之间的键。这个过程导致酶功能的恢复——即其复活。肟在复活过程中的有效性取决于其化学结构以及抑制AChE的神经毒剂。由于这个事实，选择合适的复活剂在治疗中毒时非常重要。这项工作比较了VX和俄罗斯VX在大鼠、猪和人脑中的体外抑制效力差异，随后我们测试了用HI-6、奥比多西姆、普瑞多西姆、三甲多西姆和甲氧西姆复活被这些毒剂抑制的大鼠脑胆碱酯酶。结果显示，VX和俄罗斯VX抑制的胆碱酯酶复活过程没有显著差异。复活过程的相似性是由神经毒剂的相似化学结构造成的；并且HI-6似乎是最有效的复活剂测试，这证实了HI-6是目前对由神经毒剂抑制的AChE最有效的复活剂...

Organophosphorus compounds such as nerve agents inhibit, practically irreversibly, cholinesterases by their phosphorylation in the active site of these enzymes. Current antidotal treatment used in the case of acute nerve agent intoxications consists of combined administration of anticholinergic drug (usually atropine) and acetylcholinesterase (AChE, EC 3.1.1.7) reactivator (HI-6, obidoxime, pralidoxime), which from a chemical view is a derivative from the group of pyridinium or bispyridinium aldoximes (commonly called "oxime"). Oximes counteract acetylcholine increase, resulting from AChE inhibition. In the human body environment these compounds are powerful nucleophiles and are able to break down the bond between AChE and nerve agent molecule. This process leads to renewal of enzyme functionality -- to its reactivation. The usefulness of oxime in the reactivation process depends on its chemical structure and on the nerve agent whereby AChE is inhibited. Due to this fact, selection of suitable reactivator in the treatment of intoxications is very important. This work compared differences in the in vitro inhibition potency of VX and Russian VX on rat, pig and human brain, and subsequently we have tested reactivation of rat brain cholinesterase inhibited by these agents using oxime HI-6, obidoxime, pralidoxime, trimedoxime and methoxime. The results showed that no major differences in the reactivation process of both VX and Russian VX-inhibited cholinesterase. The similarity in reactivation was caused by analogous chemical structure of either nerve agent; and that oxime HI-6 seems to be the most effective reactivator tested, which confirms that HI-6 is currently the most potent reactivator of AChE inhibited by nerve agents...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

当前工作旨在评估从人血清中纯化得到的丁酰胆碱酯酶（HuBChE）预防梭曼和VX对恒河猴引起的毒性的能力。然后评估数据在不同物种之间的一致性，作为将数据外推到人类的基础。在静脉注射后，酶在猴子体内的平均驻留时间为34小时。静脉注射后，HuBChE在血液中的生物利用度很高（>80%）。在摩尔比大约为HuBChE:OP 1.2的情况下，可以预防静脉注射2.1倍LD50 VX的毒性，而比例为0.62就足以保护猴子免受静脉注射3.3倍LD50梭曼的毒性，无需额外的暴露后治疗。在梭曼引起的空间辨别任务表现中的行为缺陷也得到了显著的防护。多个物种的结果一致性为预测HuBChE对人类神经毒剂毒性的清除化学计量学和预防程度提供了可靠的预测。

... The present work was designed to assess the ability of butyrylcholinesterase, purified from human serum (HuBChE), to prevent the toxicity induced by soman and VX in rhesus monkeys. The consistency of the data across species was then evaluated as the basis for the extrapolation of the data to humans. The average mean residence time of the enzyme in the circulation of monkeys following an intravenous loading was 34 hr. High bioavailability of HuBChE in blood (>80%) was demonstrated after intramuscular injection. A molar ratio of HuBChE:OP approximately 1.2 protected against an i.v. bolus injection of 2.1 x LD50 VX, while a ratio of 0.62 was sufficient to protect monkeys against an i.v. dose of 3.3 x LD50 of soman, with no additional postexposure therapy. A remarkable protection was also seen against soman-induced behavioral deficits detected in the performance of a spatial discrimination task. The consistency of the results across several species offers a reliable prediction of both the stoichiometry of the scavenging and the extent of prophylaxis with HuBChE against nerve agent toxicity in humans.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

这项研究的目的是评估一种新型防护霜配方在减少神经毒剂（VX）2xLD(50)液体挑战的经皮毒性方面的有效性……在体外和体内使用家猪。在（内耳皮肤）暴露部位涂抹防护霜可以消除死亡，减少胆碱酯酶抑制，并防止任何生理或生化中毒迹象。相比之下，未经处理的动物暴露于VX后表现出严重的中毒迹象，几乎完全的乙酰胆碱酯酶抑制，通常在（3小时）暴露期间内死亡（5/6动物）。涂抹防护霜显著减少了VX污染的皮肤面积。暂时得出的结论是，扩散主要是一种表面现象（可能是通过毒剂通过微隆起或毛发毛囊之间的毛细血管运动介导），而角质层的横向扩散几乎没有贡献。体外和体内皮肤吸收测量之间存在差异，归因于体外缺乏系统性清除。然而，两种模型都表明皮肤内有大量的VX储备……

The purpose of this study was to evaluate the efficacy of a novel barrier cream formulation at reducing the percutaneous toxicity of a 2xLD(50) liquid challenge of nerve agent (VX) ... in vitro and in vivo using the domestic pig. Pretreatment of the (inner ear skin) exposure site with barrier cream eliminated mortality, reduced cholinesterase inhibition and prevented any physiological or biochemical signs of intoxication. In contrast, untreated animals exposed to VX exhibited severe signs of intoxication, near total AChE inhibition and generally died within the (3 hr) exposure period (5/6 animals). Application of the barrier cream caused a significant decrease in the area of skin contaminated by VX. It was tentatively concluded that spreading was predominantly a surface phenomena (possibly mediated by capillary movement of the agent through the microrelief or between hair follicles) with little or no contribution from lateral diffusion within the stratum corneum. There was a disparity between the in vitro and in vivo skin absorption measurements that was ascribed to the absence of systemic clearance in vitro. However, both models indicated a substantial reservoir of VX within the skin ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

为了获得 (+/-)-VX 的基本毒物动力学信息，即在100%生物利用度条件下的情况，测量了无毛豚鼠在相当于1倍和2倍 LD50 的静脉注射剂量下的血药水平。导出的药时曲线下面积（AUCs）表明毒物动力学与剂量之间有合理的线性关系。此外，还研究了在绒猴灵长类动物中，以相当于无毛豚鼠1倍 LD50 的绝对静脉注射剂量，这导致了与无毛豚鼠中2倍 LD50 观察到的 (+/-)-VX 血液水平大约相同的水平。最后，通过经皮途径在相当于1倍 LD50 (pc) 的剂量下测量了无毛豚鼠中 (+/-)-VX 的毒物动力学。在 (+/-)-VX 的渗透速率和血液中乙酰胆碱酯酶（AChE）抑制的同步进展方面，个体动物之间观察到了大的变异。血液中 (+/-)-VX 的水平在6小时的时间段内逐渐增加。经过7小时的渗透期，总AUC相当于静脉给药的2.5%的生物利用度。与G-剂 C(+/-)P(+/-)-梭曼和 (+/-)-沙林相比，两个对映体 (+/-)-VX 的立体专一性并不是一个显著的现象。似乎 (+/-)-VX 在体内的持久性远大于这两种G-剂。这种持久性可能会削弱预先使用碳酰胺对抗经皮中毒的效果，尤其是由于 (+/-)-VX 逐渐取代碳酰胺上的AChE，而传统的使用肟类治疗中毒的效果则受到肟类相对于毒剂的短暂持久性的阻碍。

... In order to obtain basic information on the toxicokinetics of (+/-)-VX, i.e., under conditions of 100% bioavailability, the blood levels of this agent were measured in hairless guinea pigs at iv doses corresponding with 1 and 2 x LD50. The derived AUCs indicate a reasonable linearity of the toxicokinetics with dose. Also, the toxicokinetics in marmoset primates was studied at an absolute iv dose corresponding with 1 x LD50 in the hairless guinea pig which led to approximately the same levels of (+/-)-VX in blood as observed at 2 x LD50 in the hairless guinea pig. Finally, the toxicokinetics of (+/-)-VX were measured in hairless guinea pigs via the ... percutaneous route at a dose corresponding with 1 x LD50 (pc). Large variations were observed between individual animals in the rate of penetration of (+/-)-VX and in concomitant progression of AChE inhibition in blood of these animals. Blood levels of (+/-)-VX increased gradually over a 6-hr period of time. After a 7-hr penetration period, the total AUC corresponded with 2.5% bioavailability relative to iv administration. In contrast with the G-agents C(+/-)P(+/-)-soman and (+/-)-sarin, stereospecificity in the sequestration of the two enantiomers of (+/-)-VX is not a prominent phenomenon. It appears that (+/-)-VX is substantially more persistent in vivo than the two G-agents. This persistence may undermine the efficacy of pretreatment with carbamates of percutaneous intoxication in particular due to gradual replacement of carbamate on AChE by (+/-)-VX, whereas classical treatment of intoxication with oximes is hampered by the short persistence of oximes relative to the agent.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

当前研究的目的是通过使用猪、人类和豚鼠的皮肤来测量和比较体外对VX的皮肤吸收动力学，以突显出任何潜在的种间皮肤渗透性差异。当未稀释的VX直接应用于皮肤时，豚鼠皮肤的渗透性大约是人类皮肤的7倍。猪和人类皮肤的渗透性没有显著差异。当用异丙醇稀释的VX应用于皮肤时，豚鼠皮肤的渗透性大约是人类皮肤的4倍。猪和人类皮肤的渗透性没有显著差异。由此数据可以推断，经皮肤磨削的腹部猪皮是人类皮肤吸收VX的合适模型。

... The purpose of the present study was to measure and compare the skin absorption kinetics of VX in vitro using pig, human and guinea pig skin to highlight any potential species differences in skin permeability. When undiluted VX was applied directly to the skin, the permeability of guinea pig skin was approximately 7-fold greater than human skin. There was no significant difference in the permeability of pig and human skin. When VX diluted with isopropyl alcohol was applied to the skin, the permeability of guinea pig skin was approximately 4-fold greater than human skin. There was no significant difference in the permeability of pig and human skin. From this data it may be inferred that dermatomed, abdominal pig skin is an appropriate model for the human skin absorption of VX.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

1960年11月，对液体VX通过皮肤的渗透进行了研究，研究对象是服务志愿者。将带有放射性标记的VX滴在三个位置之一：背部、前臂或手心。除了手心之外，所选区域都用电动剃须刀剃毛，并在皮肤上固定一个环。前臂和手心的环是由聚乙烯制成，内径为2.5厘米；背部的环是由黄铜制成，直径为7厘米。在环内皮肤上滴上2-4微克的VX。在环的顶部贴上尼龙薄膜。将装置和VX留在原位6-10小时，在此期间使用盖革计数器进行测量。然后移除装置并对皮肤进行消毒，首先用粘性胶带剥离，然后用异丙醇和肥皂水清洗。...根据志愿者的记录，有16名男性参与了这项研究。...观察到的胆碱酯酶抑制率很小，从1.9%到3.9%不等。经过短暂的延迟后，VX通过前臂和背部的渗透是“规律且迅速”的：平均而言，在8小时内，有8%的VX剂量通过背部皮肤渗透，15%通过前臂皮肤渗透。

Studies of the penetration of liquid VX through skin were conducted with Service volunteers in November 1960 ... . Drops of radioactively-tagged VX were placed on the skin in one of three locations: the back, the forearm, or the palm of the hand. The chosen area, excepting the palm, was shaved with an electric razor and a ring was attached to the skin. The rings used on the forearm and the palm were made of polythene with an internal diameter of 2.5 cm; those on the back were made of brass measuring 7 cm in diameter. VX was placed on the skin inside the ring in drops of 2 - 4 ug. Nylon film was stuck over the top of the ring. The assembly and VX were left in place for 6-10 hours, during which time a Geiger counter was used to take measurements. The assembly was then removed and the skin decontaminated, first by stripping with adhesive tape and then by washing with isopropanol and soapy water. ... According to the volunteer records, 16 men took part in this study. ... ChE depressions observed were small, varying from 1.9% to 3.9%. After a brief delay the penetration of VX through the forearm and the back was "regular and rapid": on average, 8% of the VX dose penetrated through back skin and 15% through forearm skin in 8 hours.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 储存条件：
  库房应保持低温、通风和干燥，采用密闭储存，并与其他食品原料分开存放。

反应信息

• 作为反应物：
  描述：

  O-乙基-S-[2-(二异丙氨基)乙基]甲基硫代磷酸酯 在 (cyclen)zinc(II) perchlorate 、 重水 作用下， 生成
  参考文献：
  名称：

  31 P编辑的扩散有序1 H NMR光谱用于光谱分离和鉴定与化学武器剂及其降解产物有关的有机磷化合物

  摘要：

  有机磷化合物代表一类大分子，包括农药，阻燃剂，生物学相关分子和化学武器试剂（CWA）。有机磷分子的检测和鉴定，特别是在农药和化学废水中，是各个组织对国际条约进行核实的关键。为此，可以为传统分析提供额外支持的新颖分析方法对于明确鉴定这些化合物非常重要。我们开发了一种NMR方法，可通过31 P– 1选择性地编辑有机磷化合物H异核单量子相关性（HSQC），并通过1 H扩散有序光谱法（DOSY）：1 H– 31 P HSQC-DOSY ，基于各个物种的自扩散性，提供了另一种类似于色谱的分离。该技术首先使用CWA VX（O-乙基S- [2-（二异丙基氨基）乙基]甲基硫代磷酸酯）通过传统的二维DOSY光谱进行验证。然后，我们将该技术扩展为VX降解产物的复杂混合物，并确定暴露于锌-周期有机金属均相催化剂后产生的所有主要含磷副产物。

  DOI：

  10.1021/ac302788x
• 作为试剂：
  描述：

  6-(4-(hydroxycarbamoyl)-1H-1,2,3-triazol-1-yl)-6-deoxy-1-O-methyl-α-D-glucopyranose 、 三羟甲基氨基甲烷盐酸盐 在 O-乙基-S-[2-(二异丙氨基)乙基]甲基硫代磷酸酯 作用下， 以 aq. buffer 为溶剂， 生成
  参考文献：
  名称：

  神经毒性有机磷化合物与肟或异羟肟酸反应的途径

  摘要：

  为了获得对最近证明的含有肟或异羟肟酸残基取代基的 β-环糊精衍生物的解毒能力的机理洞察，用环沙林 (GF)、塔崩 (GA) 和 O-乙基 S-处理具有相同取代基的类似葡萄糖衍生物[2-(二异丙基氨基)乙基]甲基硫代膦酸酯(VX)在(Tris)-HCl缓冲液(0.1 m，pH 7.40)中，不同的反应途径通过31P NMR光谱和质谱进行了研究。与之前的报道一致，肟被 GF 膦酰化，然后消除 O-环己基甲基膦酸酯以提供腈。异羟肟酸与GA的反应取决于异羟肟酸的氮原子是否带有取代基。未取代的异羟肟酸提供了不含氰化物和 GA 的二甲氨基的稳定磷酸酯。如果异羟肟酸被甲基化，最初形成的磷酸化产物会经历许多转变，包括异羟肟酸的 C-N 键断裂。异羟肟酸与 VX 的反应涉及洛森重排。因此，这些研究表明，所有研究的亲核试剂在所选条件下与神经毒剂反应时都会发生不可逆的修饰，这表明以肟或异羟肟酸为取代基的环糊精不

  DOI：

  10.1002/ejoc.201601053

文献信息

• Synthesis of macroscopic monolithic metal–organic gels for ultra-fast destruction of chemical warfare agents
  作者：Chuan Zhou、Shouxin Zhang、Hongjie Pan、Guang Yang、Lingyun Wang、Cheng-an Tao、Heguo Li

  DOI：10.1039/d1ra01703a

  日期：——

  for the destruction of CWAs. We found that the UiO-66-NH2 xerogel with a larger pore size and a higher surface area than the UiO-66-NH2 powder possessed better degradability of 2-chloroethyl ethyl sulfide (2-CEES), which is a sulfur mustard simulant. These UiO-66-X xerogels exhibit outstanding performance for decomposing CWAs. The half-lives of vesicant agent sulfur mustard (HD) and nerve agent O-ethyl

  源自化学战剂 (CWA) 的潜在威胁促进了先进材料的发展，以加强对平民和军事人员的保护。Zr 基金属有机骨架（Zr-MOFs）最近已被证明是分解 CWAs 的优良催化剂，但将 Zr-MOFs 的微晶粉末整合到整体中的挑战仍然存在。在此，我们报告了用于破坏 CWA 的分级多孔单片 UiO-66-X 干凝胶。我们发现UiO-66-NH 2干凝胶比UiO-66-NH 2具有更大的孔径和更高的表面积。粉末对硫芥模拟物2-氯乙基乙基硫醚（2-CEES）具有更好的降解性。这些 UiO-66-X 干凝胶在分解 CWA 方面表现出出色的性能。发泡剂硫芥 (HD) 和神经毒剂O-乙基S- [2-(二异丙基氨基)乙基] 甲基硫代磷酸酯 (VX)的半衰期分别短至 14.4 分钟和 1.5 分钟。据我们所知，这项工作是关于用于超快分解 CWA 的宏观整体 UiO-66-X 干凝胶的第一份报告。
• Facile Hydrolysis-Based Chemical Destruction of the Warfare Agents VX, GB, and HD by Alumina-Supported Fluoride Reagents
  作者：E. Gershonov、I. Columbus、Y. Zafrani

  DOI：10.1021/jo8019972

  日期：2009.1.2

  A facile solvent-free hydrolysis (chemical destruction) of the warfare agents VX (O-ethyl S-2-(diisopropylamino)ethyl methylphosphonothioate), GB (O-isopropyl methylphosphonofluoridate or sarin), and HD (2,2′-dichloroethyl sulfide or sulfur mustard) upon reaction with various solid-supported fluoride reagents is described. These solid reagents include different alumina-based powders such as KF/Al2O3

  简便的无溶剂水解剂（战争破坏剂VX（O-乙基S -2-（二异丙氨基氨基）乙基甲基硫代磷酸酯），GB（O-异丙基甲基氟代磷酸酯或沙林）和HD（2,2'-二氯乙基硫醚）描述了在与各种固体负载的氟化物试剂反应后产生的硫芥末或硫芥末）。这些固体试剂包括不同的氧化铝基粉末，例如KF / Al 2 O 3，AgF / KF / Al 2 O 3和KF / Al 2 O 3，它们富含所谓的配位不饱和氟化物离子（我们称其为ECUF- KF / Al 2 O 3）。当吸附在这些吸附剂上时，神经毒剂VX迅速水解（t 1/2范围在0.1-6.3 h之间）水解成相应的无毒膦酸主要成分EMPA（> 90％）和相对毒性的脱乙基VX（< 10％）。后者的副产物进一步水解为无毒的MPA产物（t 1/2范围为2.2-161 h）。发现反应速率和产物分布强烈地取决于KF / Al 2 O 3基质中氟离子的性质及其含水量。所研
• Group 13 chelates in nerve gas agent and pesticide dealkylation
  作者：Amitabha Mitra、David A. Atwood、Jeffrey Struss、Daniel J. Williams、Bradley J. McKinney、William R. Creasy、David J. McGarvey、H. Dupont Durst、Roderick Fry

  DOI：10.1039/b717041f

  日期：——

  Schiff base boron and aluminium bromides have been used to cleave organophosphate nerve agents and pesticides and their simulants: salben(tBu)[BBr2]2 was very effective in cleaving the VX simulants EMPPT and DEPPT and nerve agent VX; salen(tBu)AlBr was effective in cleaving the nerve agents VX and Soman and the pesticideDiazinon.

  席夫碱硼和铝溴化物已被用于裂解有机磷神经毒剂和农药及其模拟物：salben(tBu)[BBr2]2在裂解VX模拟物EMPPT和DEPPT以及神经毒剂VX方面非常有效；salen(tBu)AlBr在裂解神经毒剂VX和梭曼以及农药Diazinon方面有效。
• Reaction of Nerve Agents with Phosphate Buffer at pH 7
  作者：William R. Creasy、Roderick A. Fry、David J. McGarvey

  DOI：10.1021/jp3024809

  日期：2012.7.12

  31P NMR. Phosphate causes faster reaction to the corresponding alkyl methylphosphonic acids, and produces a mixed phosphate/phosphonate compound as an intermediate reaction product. GB has the fastest reaction rate, with a bimolecular rate constant of 4.6 × 10–3 M–1s–1[PO43-]. The molar product branching ratio of GB acid to the pyro product (isopropyl methylphosphonate phosphate anhydride) is 1:1.4, independent

  化学武器神经毒剂，包括异丙基甲基膦酰氟（GB或Sarin），频哪醇甲基膦酰氟（GD或Soman）和S-（2-二异丙基氨基乙基）O-乙基甲基膦酰硫（VX），在中等pH值的水溶液中反应缓慢。相对于蒸馏水或醋酸盐缓冲液，pH值为7的磷酸盐缓冲液中神经药的反应性增加。使用31 P NMR研究反应。磷酸盐导致与相应的烷基甲基膦酸的反应更快，并产生混合的磷酸盐/膦酸酯化合物作为中间反应产物。GB具有最快的反应速率，双分子速率常数为4.6×10 –3 M –1 s –1 [PO4 3- ]。GB酸与焦油产物（异丙基甲基膦酸酯磷酸酐）的摩尔产物支化比为1：1.4，与磷酸盐浓度无关，焦油产物继续反应得很慢，形成GB酸。焦烧产物在31 P NMR光谱中有两个双峰。GD的反应速率比GB慢，速率常数为1.26×10 –3 M –1 s –1 [PO 4 3- ]。VX的速率要慢得多，速率常数为1.39×10 –5
• Oxidative detoxification of phosphonothiolates
  作者：Yu Chu Yang、Linda L. Szafraniec、William T. Beaudry、Dennis K. Rohrbaugh

  DOI：10.1021/ja00174a025

  日期：1990.8

  The chemical nerve agent O-ethyl S-[2-(diisopropylamino) ethyl] methylphosphonothiolate (VX) is an unusually selective oxidation substrate. Relative to the thiolo sulfur, the amino nitrogen was a more reactive oxidation site. The oxidation of VX and a phosphonothiolate derivative by a broad range of peroxygen compounds was examined in organic, polar organic, and aqueous solvents

  化学神经毒剂 O-乙基 S-[2-(二异丙基氨基) 乙基] 甲基硫代膦酸酯 (VX) 是一种不寻常的选择性氧化底物。相对于硫醇硫，氨基氮是更具反应性的氧化位点。在有机、极性有机和水性溶剂中，研究了多种过氧化合物对 VX 和硫代膦酸酯衍生物的氧化

表征谱图