诺维乔克

诺维乔克（俄语：новичок，罗马化：Novichok，直译：新手、新人^[1]^[2]），是苏联（解体后主体为俄罗斯）于1971年至1993年间开发的一系列神经毒剂^{[注 1]}^[4]^[5]。研发诺维乔克之科学家声称这是他们所研发出毒性最强的神经毒剂，有些衍生物的毒性可能为VX的五至八倍^[6]^[7]，有些衍生物质毒性可能为梭曼（甲氟膦酸频那酯）的十倍^[8]。

诺维乔克为苏联FOLIANT计画中的一环^[3]^[9]。据信，其有五种衍生物被用于军事用途上^[10]其中最通用的为诺维乔克5号A-232^[11]。诺维乔克试剂从未被用在战场上^[12]。

英国政府证实，2018年3月在英格兰威尔特郡索尔兹伯里发生的俄罗斯前间谍毒杀案中使用了诺维乔克。来自四间全球禁止化学武器组织的实验室一致确认了此事。^[12]。在此案发生四个月后，于威尔特郡埃姆斯伯里发生的2018埃姆斯伯里毒杀案同样有检验出诺维乔克^[13]。这场毒杀案导致一人死亡^[14]、三人病危及一位员警住院；但俄罗斯政府否认其曾有以诺维乔克的名义制造或是研发任何药剂。^[15]

诺维乔克自1990年代便被大量西方秘密地下组织所知悉^[16]，在2016年，伊朗的化学家合成并分析了五种诺维乔克类试剂，且将其详细的质谱数据添加至禁止化学武器组织的中央分析数据库^[17]^[18]。在这之前，公开的科学数据库中并没有关于诺乔维克质谱特性的详细描述。^[17]^[19]

据称^[谁？]，2017年，在捷克共和国合成了少量的诺维乔克A-230，其目的为对其作进一步分析并协助对抗这些毒性物质^[20]。

维尔·米尔扎亚诺夫（英语：Vil Mirzayanov）是首次提供了这些毒剂相关描述的人^[27]。这些毒剂会散布在气溶胶的超细粉末中，而非气体或蒸气中；且具有十分独特的性质。要么使用不属于禁止化学武器公约管控物质的材料合成，或者是通过条约制度检查无法检测到的办法，来合成一组性质相似的二元试剂（英语：Binary chemical weapon）^[28]。该系列中最有效的化合物——诺维乔克-5和诺维乔克-7——据称比VX强大约五到八倍^[29]。而“诺维乔克”名称是指毒剂的二元形式，最终化合物由其代码号（例如A-232）表示。第一组诺维乔克系列化合物实际上是已知的V系列神经毒剂VR（英语：VR (nerve agent)）的二元试剂^[29]，而后续的诺维乔克试剂则是其他化合物的二元形式，例如A-232和A-234。^[30]

根据1997年1月24日军事情报摘要中美国陆军国家地面情报中心（英语：National Ground Intelligence Center）的机密报告显示^[31]，在“富利安特计划”（Foliant programme）下开发的A-232毒剂、及其乙基类似物A-234，“与VX一样具有剧毒，对梭曼的抑制处理具有抗性，比VX更难检测和更容易合成”。据报吿显示，这些药剂的二元版本使用乙腈和一种“伪装成农药前体”的有机磷酸盐。且A-234的毒性可能为VX的五至八倍^[29]^[32]

米尔扎亚诺夫在其自传中，有提到与西方专家认定结构有所不同的另一种结构的诺维乔克毒剂^[33]。他公开地制作了大量的化合物，这是因为在公开文献中亦有许多毒性较低的同类化合物以新型有机磷杀虫剂的形式提及^[34]，所以这项秘密化学武器研究可以被伪装成是合法的农药研究^[35]。

据报导称，这些毒剂能够通过液体、气溶胶或气体形式投放，其中包括炮弹、炸弹、导弹和喷射方式。^[36]

化学

按照化学武器专家乔纳森·塔克（Jonathan Tucker）的说法，在“富利安特计划”中开发的第一组二元配方是用于制造“第33号物质”（即VR（英语：VR (nerve agent)）毒剂），该毒剂与广为人知的VX非常相似，但不同之处仅在于其分子链上的氮与氧原子上的烷基取代基。而“这类化学武器的代号是诺维乔克。”^[38]

社会上已经报导了诺维乔克的各种各样的潜在结构。其衍生物都具有机磷核心（有时 ${\ce {P=O}}$ 被 ${\ce {P=S}}$ 或 ${\ce {P=Se}}$ 取代），而诺维乔克常被用于描述的是氨基磷酸酯（英语：Phosphoramidate）类或膦酸酯类的神经毒素，而最为通常是氟化的酯（参见单氟磷酸酯（英语：Monofluorophosphate））。诺维乔克的有机基团种类更多，然而其共同的取代基则是光气肟或其类似基团。后者本身就是一种强效化学武器（如荨麻毒素（英语：Nettle agent）），这预计会增加诺维乔克毒剂所可能造成的毒害作用。许多声称诺维乔克类的结构还含有交联剂（英语：Cross-linking agent）基序，后者可以在几个位置与乙酰胆碱酯酶的活性位点发生共价结合，这可能也解释了为什么是毒剂的特征就是酶的快速变性。

一位来自加州大学圣地亚哥分校的化学家——佐兰·拉迪奇（Zoran Radić）将“米尔扎亚诺夫版本的A-232结构”和“乙酰胆碱酯酶的活性位点”之间的抗性进行了计算机对接研究。该模型预测两者具有很高的结合亲和力，且A-232与乙酰胆碱酯酶活性位点中的丝氨酸残基紧密配合形成共价键；其与沙林和梭曼这类已建立数据库的神经毒剂一样，具有相类似结合模式。^[39]

化学结构

有两种有机磷制剂都被归类为诺维乔克毒剂。第一种是有二卤甲醛肟基团的有机磷化合物，其通式如下：其中的 ${\ce {R}}$ 可以是烷基、烷氧基、烷氨基或氟，而 ${\ce {X}}$ 为卤素（氟、氯、溴等），或是像C≡N等拟卤素。这些化合物被广泛地记载在当时的苏联文献中，但不确定是否包括所有的诺维乔克毒剂^[40]^[41]^[42]^[43]^[44]^[45]^[46]^[47]。

米尔扎亚诺夫在其自传中有提到另一种结构的诺维乔克毒剂，其结构如下：

[注 1]
Jonathon B. Tucker writes that approval to commence research into "fourth generation" chemical weapons was given by the Central Committee of the Communist Party and the Soviet Council of Ministers in May 1971. Vil Mirzayanov, the Russian scientist who first alerted the West to the existence of the Novichok agents, states that testing of Novichok-7 was successfully completed in 1993—after the signing of the Chemical Weapons Convention but before Russia ratified the treaty and when it came into force.^[3]^[4]

[1]
What are Novichok nerve agents and did Russia do it?. [2019-02-27]. （原始内容存档于2018-12-20）.
[2]
Oxford Russian Dictionary 3. Oxford University Press. 2000: 265.
[3]
Tucker 2006，第231页
[4]
Mirzayanov, Vil, Dismantling the Soviet/Russian Chemical Weapons Complex: An Insider's View, Global Proliferation of Weapons of Mass Destruction: Hearings Before the Permanent Subcommittee on Investigations of the Committee on Governmental Affairs, 104th Cong., 1995: 393–405
[5]
Tucker 2006，第231–233页
^ 引用错误：没有为名为Birstein的参考文献提供内容
[7]
Albats 1994，第325–328页
[8]
Croddy, Wirtz & Larsen 2001，第201页
[9]
Pitschmann 2014，第1765页
[10]
Tucker 2006，第233页
[11]
Tucker 2006，第253页
[12]
Benjamin Kentish. Poison used on Sergei and Yulia Skripal in Salisbury attack was novichok nerve agent, confirms chemical weapons watchdog. The Independent. 12 April 2018 [2019-02-27]. （原始内容存档于2018-09-06）. 参数|newspaper=与模板{{cite web}}不匹配（建议改用{{cite news}}或|website=） (帮助)
[13]
Wiltshire pair poisoned by Novichok nerve agent. BBC News. 2018-07-04 [2018-07-04]. （原始内容存档于2018-07-04）（英国英语）.
[14]
Novichok: Murder inquiry after Dawn Sturgess dies. [2019-02-27]. （原始内容存档于2019-03-06）.
[15]
Borger, Julian. UK spy poisoning: Russia tells UN it did not make nerve agent used in attack. The Guardian. 15 March 2018 [15 March 2018]. （原始内容存档于2019-02-24）.
[16]
'Unknown' newcomer novichok was long known. NRC. [12 January 2019]. （原始内容存档于2018-06-28）.
[17]
Ryan De Vooght-Johnson. Iranian chemists identify Russian chemical warfare agents. spectroscopyNOW.com. Wiley. 1 January 2017 [18 March 2018]. （原始内容存档于2018-12-13）.
[18]
Hosseini SE, Saeidian H, Amozadeh A, Naseri MT, Babri M. Fragmentation pathways and structural characterization of organophosphorus compounds related to the Chemical Weapons Convention by electron ionization and electrospray ionization tandem mass spectrometry. Rapid Communications in Mass Spectrometry. 5 October 2016, 30 (24): 2585–2593. doi:10.1002/rcm.7757.
[19]
Report of the Scientific Advisory Board on developments in science and technology for the Third Review Conference (PDF) (报告). Organisation for the Prohibition of Chemical Weapons: 3. 27 March 2013 [15 March 2018]. RC-3/WP.1. （原始内容存档 (PDF)于2018-05-20）.
[20]
Земан: в Чехии производился и складировался нервно-паралитический газ "Новичок". [2019-02-27]. （原始内容存档于2018-05-03）.
[21]
Hoenig 2007，第79–80页
[22]
Mirzayanov 2008，第142–145, 179–180页
[23]
Ellison 2008，第37–42页
[24]
Gupta 2015，第339–340页
[25]
Konopski L., Historia broni chemicznej, Warszawa: Bellona, 2009, ISBN 978-83-11-11643-6
[26]
Balali-Mood M, Abdollahim M. (Eds.), Basic and Clinical Toxicology of Organophosphorus Compounds, Springer 2014. ISBN 9781447156253
^ 引用错误：没有为名为Vil的参考文献提供内容
[28]
Hidalgo, Louise. US dismantles chemical weapons. BBC News. 9 August 1999 [20 July 2007]. （原始内容存档于2018-12-20）.
[29]
Peplow, Mark, Nerve agent attack on spy used 'Novichok' poison, Chemical & Engineering News 96 (12), 19 March 2018, 96 (12): 3 [16 March 2018], （原始内容存档于2018-03-15）
[30]
Kobliha, Halámek E. Z. POTENCIÁLNÍ BOJOVÉ CHEMICKÉ LÁTKY (PDF). Chemicke Listy. 2011, 105 (5): 323–333 [2019-02-28]. （原始内容存档 (PDF)于2018-03-17）.
[31]
Pike, John. Russia dodges chemical arms ban By Bill Gertz THE WASHINGTON TIMES Tuesday. www.globalsecurity.org. [2019-02-28]. （原始内容存档于2018-04-23）.
[32]
Spy poisoning: Putin most likely behind attack – Johnson, BBC News, 16 March 2018 [16 March 2018], （原始内容存档于2018-11-29）
[33]
Vásárhelyi, Györgyi; Földi, László. History of Russia's chemical weapons (PDF). AARMS. 2007, 6 (1): 135–146 [2019-02-28]. （原始内容 (PDF)存档于2018-03-14）.
[34]
Sokolov VB, Martynov IV. Effect of Alkyl Substituents in Phosphorylated Oximes. Zhurnal Obshchei Khimii. 1987; 57(12):2720–2723.
[35]
Vil S Mirzayanov. State Secrets. An Insider's Chronicle of the Russian Chemical Weapons Program. (2009) pp142-145, 179-180. ISBN 978-1-4327-2566-2
^ 引用错误：没有为名为Croddy的参考文献提供内容
[37]
Emil Halámek and Zbynek Kobliha. Potential Chemical Warfare Agents. Chemicke Listy. May 2011.
[38]
Peplow, Mark. Nerve agent attack on spy used 'Novichok' poison. Chemical & Engineering News. 19 March 2018, 96 (12): 3 [28 March 2018]. （原始内容存档于2018-03-15）.
[39]
Stone, R. U.K. attack shines spotlight on deadly nerve agent developed by Soviet scientists. Science. 19 March 2018 [28 March 2018]. doi:10.1126/science.aat6324. （原始内容存档于2018-03-25）.
[40]
Kruglyak Yu L, Malekin SI, Martynov IV. Phosphorylated oximes. XII. Reactions of 2-halophospholanes with dichlorofluoronitrosomethane. Zhurnal Obshchei Khimii. 1972; 42(4):811-14.
[41]
Raevskii OA, Chapysheva NV, Ivanov AN, Sokolov VB, Martynov IV. Effect of Alkyl Substituents in Phosphorylated Oximes. Zhurnal Obshchei Khimii. 1987; 57(12):2720-2723
[42]
Raevskii OA, Grigor'ev V Yu, Solov'ev VP, Ivanov AN, Sokolov VB, Martynov IV. Electron-Donor Functions of Ethyl Methylchloroformimino Methylphosphonate. Zhurnal Obshchei Khimii. 1987; 57(9):2073-2078
[43]
Makhaeva GF, Filonenko IV, Yankovskaya VL, Fomicheva SB, Malygin VV. Comparative studies of O,O-dialkyl-O-chloromethylchloroformimino phosphates: interaction with neuropathy target esterase and acetylcholinesterase. Neurotoxicology. 1998 Aug-Oct;19(4-5):623-8. PMID 9745921
[44]
Raevskiĭ OA, Chistiakov VV, Agabekian RS, Sapegin AM, Zefirov NS. Formation of models of the interaction between organophosphate compound structure and their ability to inhibit cholinesterase. Bioorganicheskaia Khimiia. 1990 Nov;16(11):1509-22. PMID 2096825
[45]
Ivanov IuIa, Sokolov VB, Epishina TA, Martynov IV. O-substituted alkylchloroformoximes as substrates and inhibitors of cholinesterases. Doklady Akademii Nauk SSSR. 1990;310(5):1253-5. PMID 2354654
[46]
Malygin VV, Sokolov VB, Richardson RJ, Makhaeva GF. Quantitative structure-activity relationships predict the delayed neurotoxicity potential of a series of O-alkyl-O-methylchloroformimino phenylphosphonates. Journal of Toxicology and Environmental Health Part A. 2003 Apr 11;66(7):611-25. PMID 12746136
[47]
Steven L. Hoenig. Compendium of Chemical Warfare Agents. Springer New York, 2007. ISBN 978-0-387-34626-7

[5] [注 1]
Jonathon B. Tucker writes that approval to commence research into "fourth generation" chemical weapons was given by the Central Committee of the Communist Party and the Soviet Council of Ministers in May 1971. Vil Mirzayanov, the Russian scientist who first alerted the West to the existence of the Novichok agents, states that testing of Novichok-7 was successfully completed in 1993—after the signing of the Chemical Weapons Convention but before Russia ratified the treaty and when it came into force.^[3]^[4]

[1] [1]
What are Novichok nerve agents and did Russia do it?. [2019-02-27]. （原始内容存档于2018-12-20）.

[2] [2]
Oxford Russian Dictionary 3. Oxford University Press. 2000: 265.

[auto-3] [3]
Tucker 2006，第231页

[Cong-4] [4]
Mirzayanov, Vil, Dismantling the Soviet/Russian Chemical Weapons Complex: An Insider's View, Global Proliferation of Weapons of Mass Destruction: Hearings Before the Permanent Subcommittee on Investigations of the Committee on Governmental Affairs, 104th Cong., 1995: 393–405

[6] [5]
Tucker 2006，第231–233页

[Birstein-7] 引用错误：没有为名为Birstein的参考文献提供内容

[Albats-8] [7]
Albats 1994，第325–328页

[9] [8]
Croddy, Wirtz & Larsen 2001，第201页

[10] [9]
Pitschmann 2014，第1765页

[11] [10]
Tucker 2006，第233页

[12] [11]
Tucker 2006，第253页

[:0-13] [12]
Benjamin Kentish. Poison used on Sergei and Yulia Skripal in Salisbury attack was novichok nerve agent, confirms chemical weapons watchdog. The Independent. 12 April 2018 [2019-02-27]. （原始内容存档于2018-09-06）. 参数|newspaper=与模板{{cite web}}不匹配（建议改用{{cite news}}或|website=） (帮助)

[14] [13]
Wiltshire pair poisoned by Novichok nerve agent. BBC News. 2018-07-04 [2018-07-04]. （原始内容存档于2018-07-04）（英国英语）.

[15] [14]
Novichok: Murder inquiry after Dawn Sturgess dies. [2019-02-27]. （原始内容存档于2019-03-06）.

[Borger-16] [15]
Borger, Julian. UK spy poisoning: Russia tells UN it did not make nerve agent used in attack. The Guardian. 15 March 2018 [15 March 2018]. （原始内容存档于2019-02-24）.

[17] [16]
'Unknown' newcomer novichok was long known. NRC. [12 January 2019]. （原始内容存档于2018-06-28）.

[spectroscopynow-20170101-18] [17]
Ryan De Vooght-Johnson. Iranian chemists identify Russian chemical warfare agents. spectroscopyNOW.com. Wiley. 1 January 2017 [18 March 2018]. （原始内容存档于2018-12-13）.

[rcms-20161005-19] [18]
Hosseini SE, Saeidian H, Amozadeh A, Naseri MT, Babri M. Fragmentation pathways and structural characterization of organophosphorus compounds related to the Chemical Weapons Convention by electron ionization and electrospray ionization tandem mass spectrometry. Rapid Communications in Mass Spectrometry. 5 October 2016, 30 (24): 2585–2593. doi:10.1002/rcm.7757.

[opcw-20130327-20] [19]
Report of the Scientific Advisory Board on developments in science and technology for the Third Review Conference (PDF) (报告). Organisation for the Prohibition of Chemical Weapons: 3. 27 March 2013 [15 March 2018]. RC-3/WP.1. （原始内容存档 (PDF)于2018-05-20）.

[21] [20]
Земан: в Чехии производился и складировался нервно-паралитический газ "Новичок". [2019-02-27]. （原始内容存档于2018-05-03）.

[22] [21]
Hoenig 2007，第79–80页

[23] [22]
Mirzayanov 2008，第142–145, 179–180页

[24] [23]
Ellison 2008，第37–42页

[gupta339-340-25] [24]
Gupta 2015，第339–340页

[26] [25]
Konopski L., Historia broni chemicznej, Warszawa: Bellona, 2009, ISBN 978-83-11-11643-6

[27] [26]
Balali-Mood M, Abdollahim M. (Eds.), Basic and Clinical Toxicology of Organophosphorus Compounds, Springer 2014. ISBN 9781447156253

[Vil-28] 引用错误：没有为名为Vil的参考文献提供内容

[Hidalgo-29] [28]
Hidalgo, Louise. US dismantles chemical weapons. BBC News. 9 August 1999 [20 July 2007]. （原始内容存档于2018-12-20）.

[peplow-30] [29]
Peplow, Mark, Nerve agent attack on spy used 'Novichok' poison, Chemical & Engineering News 96 (12), 19 March 2018, 96 (12): 3 [16 March 2018], （原始内容存档于2018-03-15）

[31] [30]
Kobliha, Halámek E. Z. POTENCIÁLNÍ BOJOVÉ CHEMICKÉ LÁTKY (PDF). Chemicke Listy. 2011, 105 (5): 323–333 [2019-02-28]. （原始内容存档 (PDF)于2018-03-17）.

[32] [31]
Pike, John. Russia dodges chemical arms ban By Bill Gertz THE WASHINGTON TIMES Tuesday. www.globalsecurity.org. [2019-02-28]. （原始内容存档于2018-04-23）.

[33] [32]
Spy poisoning: Putin most likely behind attack – Johnson, BBC News, 16 March 2018 [16 March 2018], （原始内容存档于2018-11-29）

[34] [33]
Vásárhelyi, Györgyi; Földi, László. History of Russia's chemical weapons (PDF). AARMS. 2007, 6 (1): 135–146 [2019-02-28]. （原始内容 (PDF)存档于2018-03-14）.

[35] [34]
Sokolov VB, Martynov IV. Effect of Alkyl Substituents in Phosphorylated Oximes. Zhurnal Obshchei Khimii. 1987; 57(12):2720–2723.

[36] [35]
Vil S Mirzayanov. State Secrets. An Insider's Chronicle of the Russian Chemical Weapons Program. (2009) pp142-145, 179-180. ISBN 978-1-4327-2566-2

[Croddy-37] 引用错误：没有为名为Croddy的参考文献提供内容

[38] [37]
Emil Halámek and Zbynek Kobliha. Potential Chemical Warfare Agents. Chemicke Listy. May 2011.

[39] [38]
Peplow, Mark. Nerve agent attack on spy used 'Novichok' poison. Chemical & Engineering News. 19 March 2018, 96 (12): 3 [28 March 2018]. （原始内容存档于2018-03-15）.

[40] [39]
Stone, R. U.K. attack shines spotlight on deadly nerve agent developed by Soviet scientists. Science. 19 March 2018 [28 March 2018]. doi:10.1126/science.aat6324. （原始内容存档于2018-03-25）.

[41] [40]
Kruglyak Yu L, Malekin SI, Martynov IV. Phosphorylated oximes. XII. Reactions of 2-halophospholanes with dichlorofluoronitrosomethane. Zhurnal Obshchei Khimii. 1972; 42(4):811-14.

[42] [41]
Raevskii OA, Chapysheva NV, Ivanov AN, Sokolov VB, Martynov IV. Effect of Alkyl Substituents in Phosphorylated Oximes. Zhurnal Obshchei Khimii. 1987; 57(12):2720-2723

[43] [42]
Raevskii OA, Grigor'ev V Yu, Solov'ev VP, Ivanov AN, Sokolov VB, Martynov IV. Electron-Donor Functions of Ethyl Methylchloroformimino Methylphosphonate. Zhurnal Obshchei Khimii. 1987; 57(9):2073-2078

[44] [43]
Makhaeva GF, Filonenko IV, Yankovskaya VL, Fomicheva SB, Malygin VV. Comparative studies of O,O-dialkyl-O-chloromethylchloroformimino phosphates: interaction with neuropathy target esterase and acetylcholinesterase. Neurotoxicology. 1998 Aug-Oct;19(4-5):623-8. PMID 9745921

[45] [44]
Raevskiĭ OA, Chistiakov VV, Agabekian RS, Sapegin AM, Zefirov NS. Formation of models of the interaction between organophosphate compound structure and their ability to inhibit cholinesterase. Bioorganicheskaia Khimiia. 1990 Nov;16(11):1509-22. PMID 2096825

[46] [45]
Ivanov IuIa, Sokolov VB, Epishina TA, Martynov IV. O-substituted alkylchloroformoximes as substrates and inhibitors of cholinesterases. Doklady Akademii Nauk SSSR. 1990;310(5):1253-5. PMID 2354654

[47] [46]
Malygin VV, Sokolov VB, Richardson RJ, Makhaeva GF. Quantitative structure-activity relationships predict the delayed neurotoxicity potential of a series of O-alkyl-O-methylchloroformimino phenylphosphonates. Journal of Toxicology and Environmental Health Part A. 2003 Apr 11;66(7):611-25. PMID 12746136

[48] [47]
Steven L. Hoenig. Compendium of Chemical Warfare Agents. Springer New York, 2007. ISBN 978-0-387-34626-7

[1]

[2]

[注 1]

[4]

[5]

[6]

[7]

[8]

[3]

[9]

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诺维乔克

化学

化学结构

Wikiwand in your browser!

诺维乔克

化学

化学结构

Wikiwand in your browser!

历史

性质与描述

注释

参考资料