The organophosphorus /anticholinergic/ anti-ChE agents are hydrolyzed in the body by two families of enzymes known as the carboxylesterases and the paraoxonases (A-esterases). The enzymes are found in plasma and liver and scavenge or hydrolyze a large numberof organophosphorus compounds by cleaving the phosphoester, anhydride, PF, or PCN bonds.
Toxicology: Effects: Nerve agents are the most toxic of the known chemical agents. Liquids or vapors from these agents are hazardous and can cause death within minutes after exposure. Nerve agents disrupt the function of the nervous system by interfering with the enzyme acetylcholinesterase. The major effects will be on skeletal muscles, certain organs, and the central nervous system. These compounds are similar to, but much more deadly than, agricultural organophosphate pesticides. Pathways: "G" series nerve agents are hazardous through inhalation, skin and eye exposure, ingestion, and abraded skin (e.g., breaks in the skin or penetration of skin by debris). /"G" Series Nerve Agents/
These experiments were performed on a rat model. The rats were divided into eight groups and consequently exposed to either a saline solution (control), atropine or a combination of atropine and tabun. The reactivation efficacy of the oximes was estimated on the rats exposed to tabun, atropine and a reactivator of AChE. The oximes HI-6, obidoxime, trimedoxime, K203 and KR-22836 were used as representative compounds of commonly available and new AChE reactivators. Besides the positive effect of the administered reactivators on blood AChE activity, the sizable modulation of low molecular weight antioxidant (LMWA) levels was also determined. The LMWA levels in the the animals treated with the oxime reactivators were decreased in comparison with the animals treated by atropine alone. It was found that the levels of LMWA returned to the level found in the control animals when either trimedoxime, K203 or KR-22836 were administered. ...
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 effected 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.
...readily absobed by passive diffusion, across the lungs and gastrointestinal tract, with peak blood concentrations occurring within minutes to several hours. Dermal and mucous membrane absorption tends to be slightly slower.../Organophosphate compounds/
水解酯三甲基-1,2,2 丙基和异丙基甲基磷酰氟（soman 和 sarin 相关），du N,N-二甲基磷酰胺氰化物 d'ethyle (tabum) et du (diethyl nitro-4 phenyl) 磷酸 dans dessolutions aqueuses micelliaires de chlorure de (palmityl trimethyl) 铵, en d'acide iodosyl-«2»benzoique
Chiral Separation of G-type Chemical Warfare Nerve Agents via Analytical Supercritical Fluid Chromatography
作者：Shane A. Kasten、Steven Zulli、Jonathan L. Jones、Thomas Dephillipo、Douglas M. Cerasoli
DOI：10.1002/chir.22368
日期：2014.12
Chemicalwarfare nerve agents (CWNAs) are extremely toxic organophosphorus compounds that contain a chiral phosphorus center. Undirected synthesis of G‐type CWNAs produces stereoisomers of tabun, sarin, soman, and cyclosarin (GA, GB, GD, and GF, respectively). Analytical‐scale methods were developed using a supercritical fluid chromatography (SFC) system in tandem with a mass spectrometer for the separation
elimination of O-cyclohexyl methylphosphonate to afford a nitrile. Reaction of the hydroxamicacid with GA depends on whether the nitrogen atom of the hydroxamicacid bears a substituent or not. The unsubstituted hydroxamicacid affords a stable phosphate ester lacking the cyanide and the dimethylamino group of GA. If the hydroxamicacid is methylated, the initially formed phosphorylated product undergoes a number
Degradation of Paraoxon and the Chemical Warfare Agents VX, Tabun, and Soman by the Metal–Organic Frameworks UiO-66-NH<sub>2</sub>, MOF-808, NU-1000, and PCN-777
作者：Martijn C. de Koning、Marco van Grol、Troy Breijaert
DOI：10.1021/acs.inorgchem.7b01809
日期：2017.10.2
and the chemicalwarfareagents tabun, VX, and soman, in N-ethylmorpholine buffer (pH 10) as well as in pure water. All MOFs showed excellent ability to degrade the agents under basic conditions. It was further disclosed that tabun is degraded by different mechanisms depending on the conditions. The presence of an amine, either as part of the MOF structure (UiO-66-NH2) or in the agent itself (VX, tabun)
Trace level detection and identification of tabun in aqueous media by derivatization and liquid chromatography tandem mass spectrometry analysis
作者：Moran Madmon、Avi Weissberg
DOI：10.1016/j.ijms.2020.116393
日期：2020.10
detection and identification of the G-nerve agent tabun (GA) was developed. 2-[(Dimethylamino)methyl]phenol (2-DMAMP), which was recently developed for the derivatization of GB, GD and GF, was also found to be efficient for the derivatization of GA. The optimized derivatization procedure in an aqueous medium was the addition of 2-DMAMP followed by 5 min of stirring at ambient temperature and subsequent
摘要 开发了一种用于检测和鉴定G神经毒剂塔崩（GA）的高灵敏度方法。2-[(二甲基氨基)甲基]苯酚 (2-DMAMP)，最近开发用于衍生 GB、GD 和 GF，也被发现对 GA 的衍生化是有效的。在水性介质中优化的衍生化程序是添加 2-DMAMP，然后在环境温度下搅拌 5 分钟，然后进行 LC-ESI(+)-MS/MS 分析。衍生的 GA 比完整的 GA 更稳定，检测灵敏度高近两个数量级。其 ESI-MS/MS 谱图显示 m/z 242 和 m/z 214 处的两个主要产物离子。开发的方法比任何其他基于 LC-MS 或 GC-MS 的方法更灵敏，并清楚地展示了“冻结时钟”用于确定水性介质中的活性 GA，饮用水中的检测限 (LOD) 为 10 pg/mL。衍生化反应效率通过土壤、沥青、布料、胶木和油毡的水提取物加 GA 进行评估，发现与饮用水相似。该方法还被发现可用于提高 GA 家族其他成员
Analogues with Fluorescent Leaving Groups for Screening and Selection of Enzymes That Efficiently Hydrolyze Organophosphorus Nerve Agents
作者：Luis Briseño-Roa、Jim Hill、Stuart Notman、David Sellers、Andy P. Smith、Christopher M. Timperley、Janet Wetherell、Nichola H. Williams、Gareth R. Williams、Alan R. Fersht、Andrew D. Griffiths
DOI：10.1021/jm050518j
日期：2006.1.1
and dimefox, and the nerveagentsDFP, tabun, sarin, cyclosarin, soman, VX, and Russian-VX. Data from inhibition of acetylcholinesterase, in vivo toxicity tests of a representative analogue (cyclosarin), and kinetic studies with phosphotriesterase (PTE) from Pseudomonas diminuta, and a mammalian serum paraoxonase (PON1), confirmed that the analogues mimic the parent nerveagents effectively. They are
