Chemistries of Chemical Warfare Agents
Brian J. Lukey, James A. Romano, Salem Harry in Chemical Warfare Agents, 2019
General Remarks: Tabun was the first compound ever identified as a nerve agent and was discovered by accident in January 1936 by the German chemist Gerhard Schrader. The chemist was experimenting with OPs to create effective insecticides for I.G. Farben (Elberfeld, Germany), a German chemical and pharmaceutical conglomerate. Research demonstrated that in addition to being a potent insecticide, tabun was enormously toxic to humans. A chemical plant for the manufacture of tabun was established in 1939 in Dyhernfurth, Germany (now Brzeg Dolny, Poland), with production beginning in June 1942 (Borkin, 1997) for use in World War II. The plant was captured by Soviet forces near the end of the war, and the Soviet government had the plant dismantled and moved to the Soviet Union soon after.
Battlefield Chemical Inhalation Injury
Jacob Loke in Pathophysiology and Treatment of Inhalation Injuries, 2020
Synonyms for tabun (GA) include gelan, dimethylaminocyanophosphoric acid ethyl ester, ethyl dimethylamidocyanophosphate (MCE), dimethylamidoethoxy phosphoryl cyanide, ethyl phosphorodimethylamide cyanidate, ethyl-M-dimethylphosphoroamido cyanate, ethyl-M, N-dimethylphosphoramidocyanidate, Trilon 83, Substance 83, Le 100, and Taboon A. Its formula is CsHn^OjP; vapor density 5.6; specific gravity 1.08; boiling point 230-245°C (depending on purity). Pure Tabun is both colorless and odorless as a gas. Slight impurities in production may lend a faintly fruity aroma and brown color to the liquid. This odor does not constitute an adequate warning for the presence of toxic levels of the gas. The combustion and hydrolysis of Tabun causes the production of hydrogen cyanide. Calcium hypochlorite should not be used as a decontaminant because it leads to the production of cyanogen chloride.
Anticholinesterases
Kenneth J. Broadley in Autonomic Pharmacology, 2017
Most of the drugs that are now known to inhibit cholinesterases were first described many years before the enzyme was identified and isolated. Physostigmine (eserine) (Table 10.1) was isolated from the Ordeal or Calabar bean in 1864, the pharmacological properties of the seed having already been described some 10 years earlier by Christioson (1855) and by Fraser (1863) and Argyll-Robertson (1863). The first therapeutic use of the pure alkaloid was for the treatment of glaucoma in 1877 (reviewed by Karczmar 1970). Even earlier the synthesis of a highly potent member of the organophosphorus anticholinesterases, tetraethylpyrophosphate (TEPP), was described by deClermont in 1854 (Table 10.2). In 1932, Lange & von Krueger synthesized dimethyl and diethyl phosphorofluoridates and described the persistent choking sensation on their inhalation. German scientists became interested in the potential of this class of agent as insecticides. Commencing in the mid-1930s at Farbenfabriken Bayer, Schrader (1952) performed pioneering work culminating in the synthesis of tabun, one of the most toxic organophosphorus compounds known, and sarin and soman. Schrader synthesized a wide range of compounds in search of improved insecticides. One of the most effective of these early organophosphorus compounds that became a widely used insecticide was parathion. Schrader’s group recognized the potential application of the toxicity of these compounds in chemical warfare, and immediately before and during World War II their efforts were directed towards the synthesis of nerve gases. Tabun and sarin were kept secret for several years. During the war, Germany held large quantities of tabun and sarin, although they were never used during the conflict (Holmstedt 1959).
Novichok: a murderous nerve agent attack in the UK
Published in Clinical Toxicology, 2018
J. Allister Vale, Timothy C. Marrs, Robert L. Maynard
Nerve agents (predominantly tabun) were employed by Iraq in the Iran–Iraq war in 1984–1988 and against that country’s own Kurdish population in 1988 in the Al-Anfal Campaign. Terrorists released nerve agents in Japan on 11 occasions in 1994–1995: sarin, for example, was used in Matsumoto in 27 June 1994 and in the Tokyo subway attack 20 March 1995 [10,11]. Sarin was also released in Ghouta, Syria in August 2013 when 1400 people were killed. In April 2017, sarin was used again in an attack on Khan Sheikhoun, in northern Syria, that killed more than 80 civilians. VX was used as a weapon of assassination in Osaka on 2 December 1994 [12] and on 13 February 2017 when Kim Jong-nam, the estranged half-brother of the North Korean ruler, Kim Jong-un, was killed at Kuala Lumpur International airport after his face was smeared with the agent.
Synthesis, in vitro screening and molecular docking of isoquinolinium-5-carbaldoximes as acetylcholinesterase and butyrylcholinesterase reactivators
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
David Malinak, Rafael Dolezal, Vendula Hepnarova, Miroslava Hozova, Rudolf Andrys, Petr Bzonek, Veronika Racakova, Jan Korabecny, Lukas Gorecki, Eva Mezeiova, Miroslav Psotka, Daniel Jun, Kamil Kuca, Kamil Musilek
For BChE, compounds 17–18 (inhibition of hBChE over 100 µM) and 30–32 (inhibition of hBChE over 1000 µM) were selected and tested for reactivation potential against sarin, VX or paraoxon inhibited hBChE and compared to obidoxime (Table 3). The obidoxime was found to have some reactivation ability for sarin and VX, but markedly lower for paraoxon. Apparently, some novel compounds (17–18) showed markedly improved reactivation than obidoxime for sarin (17), VX (17–18) and paraoxon (17) when tested at 100 µM. This finding seems to be important since obidoxime formerly resulted as the best reactivator of hBChE inhibited by tabun23, although its reactivation was found not appropriate for constructing a pseudo-catalytic scavenger. More interestingly, these symmetrical isoquinolinium carbaldoximes with three or four-member linkers were found better hBChE reactivators than obidoxime at 10 µM for sarin and VX. On the other hand, the isoquinolinium carbaldoximes with pyridinium amide moiety (30–32) which were poor BChE inhibitors were endowed with minimal reactivation for all tested OPs.
Phosgene oxime: a highly toxic urticant and emerging chemical threat
Published in Toxicology Mechanisms and Methods, 2021
Satyendra K. Singh, Joshua A. Klein, Holly N. Wright, Neera Tewari-Singh
Among the weapons of mass destruction (WMD), chemical substances whose toxic properties can be utilized to kill, incapacitate, or cause devastating injuries to human beings, are known as chemical weapons. Chemical weapons have been synthesized, stockpiled, and used in warfare as chemical warfare agents (CWAs) or in acts of terrorism on the civilian population (Dacre and Goldman 1996; Ganesan et al. 2010). The main categories of CWAs include: (i) nerve agents (G-agents are sarin, cyclosarin, tabun, and soman; V-agents include VE, VG, VM, VR and VX), (ii) vesicating agents (blistering agents nitrogen mustard and sulfur mustard, arsenical agents like lewisite, and urticant phosgene oxime), (iii) choking agents or asphyxiants (phosgene, chlorine, chloropicrin etc), (iv) riot control agents (tear gases; chloroacetophenone, chlorobenzylidenemalononitrile, dibenzoxazepine, diphenylaminoarsine), (v) blood agents (cyanide), and (vi) toxic industrial chemicals/toxic industrial materials (TICs/TIMs; chlorine, bromine, hydrogen sulfide, methyl isocyanate, etc.) (Watson and Griffin 1992; Saladi et al. 2006; Geraci 2008; Dickinson and Love 2017; Goswami et al. 2018). The first well-documented report on the use of CWAs was in April 1915, when the German Army used thousands of cylinders of chlorine gas in the Battle of Ypres during World War I (WWI) (Ganesan et al. 2010). Toxic chemicals including chlorine, sulfur mustard (mustard gas; SM), phosgene, and nerve agents like sarin have been used in various conflicts since WWI, including the Iran-Iraq war in the 1980s (Ganesan et al. 2010).
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