1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 DOI: 10.1002/minf.201800106 After Salisbury Nerve Agents Revisited Lars Carlsen [a] This paper is dedicated to Prof. Paola Gramatica on the occasion of her retirement. Abstract: In March 2018 the term Novichok (HoSYhok) became publically known following an attempted murder of a former Russian spy in Salisbury, UK. Novichok is the name of a group of nerve agents secretly produced by Russia in the later stages of the Cold War. These compounds were never declared under the Chemical Weapons Con- vention and very little is known about the actual identity and characteristics of these compounds. Structures of some of the Novichoks have been reported by a former Russian chemist, Vil Mirzayanov, previously working at the Russian State Scientific Research Institute of Organic Chemistry and Technology (GOSNIIOKhT). It was in this context claimed that at least two compounds of the Novichok family, known as Novichok-5 and Novichok-7 were 5–8 times more potent than the hitherto most toxic nerve agent, VX. The present study elucidates, applying a series of QSAR models toxicity, skin permeation, pharmacokinetic aspects as well as the environmental fate of a series of Novichoks. Virtually the results from the different studies related to human health point in the same direction, i. e., the Novichoks are significantly less toxic than VX and the skin permeation much lower and less efficient than observed for VX. Hence, the claim by Mirzayanov could not be substantiated. Keywords: Nerve agents · Novichok · QSAR · Toxicology · Skin permeation · Hydrolysis 1 Introduction On March 4, 2018 the former Russian GRU spy, Sergey Skripal and his daughter Yulia were found unconscious in Salisbury, UK. Based on analyses carried out by the British “Defence Science and Technology Laboratory” in Porton Down it was concluded that the Skripals were poisoned by a nerve agent of the so-called Novichok group. [1] Novichok (HoSYhok) is the name of a group of nerve agents developed and produced by Russia in the last stage of the Cold War. [2] It is in this connection worthwhile to mention that neither the precursors nor the actual Novichok compounds are currently covered by the Chemical Weap- ons Convention (CWC). Apparently the compounds deliber- ately were synthesized in order to maintain a stock of chemical weapons without ‘interference’ from the Organ- ization for the Prohibition of Chemical Weapons (OPCW) according the Vil Mirzayanov. [3] The findings of the Porton Down laboratory [4] was later confirmed by OPCW. [5] How- ever, the actual identity of the Novichok agent was neither by the British authorities nor by the OPCW disclosed. The incident, regarded as attempted murder obviously gave rise to a variety of questions and due to the lack of concrete information conspiracy theories were cuing up. [6] On June 30, 2018 a further incident of Novichok poisoning took place in Amesbury, close to Salisbury. An apparently unoffending British couple were found poisoned with the same compound as the Skripals. [7] Both Sergey Skripal and his daughter, after prolonged hospitalization survived the attack, whereas the British woman poisoned in Amesbury depart this life on July 8, 2018. [8] It is not an objective with the present paper to contribute to the speculations concerning the possible perpetrator(s). Thus, due to the virtually complete lack of experimental data for substances from the Novichok family, [3,5] the present study aims, based on theoretical considerations to elucidate the health effects and the environmental behavior of the compounds in order possibly to answer the question why did the Skripals not die following expose to such high potent agents; just compare to the killing of Kim Jong-nam on February 13, 2017 in Kuala Lumpur International Airport, where he was attacked by the highly toxic VX, 1, and died shortly after. [9] 2 Methods 2.1 The Novichok Family Novichok (in Russian HoSYhok = newbie or newcomer) is the name for a group of compounds that are closely related [a] Prof. L. Carlsen Awareness Center Linkøpingvej 35, Trekroner, DK-4000 Roskilde, Denmark E-mail: LC@AwarenessCenter.dk Full Paper www.molinf.com © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Mol. Inf. 2019, 38, 1800106 (1 of 8) 1800106