U.K. attack puts nerve agent in the spotlight

Abstract

Researchers race to understand deadly compound developed by Soviet scientists.

Reversal of Tabun Toxicity Enabled by a Triazole‐Annulated Oxime Library—Reactivators of Acetylcholinesterase

“…[17] Recently,anew set of highly toxic phosphoramidates were broughtt ol ight through an attempted homicide, with ac ompound in the Novichok series bearing af luoride leaving group. [18] The triazole compounds synthesized here and screened in terms of reactivation of the tabun conjugate, in relation to other methylphosphonate and alkyl phosphorate conjugates, suggest that they could serve as lead countermeasures for tabun and other phosphoramidate exposure. The lead reactivators contain an aldoximes ubstituted ortho-t ot he methylpyridiniumn itrogen or a2 -methylimidazole aldoxime moiety.O ur study hasi ncluded reactivation measurements of AChE inhibited by common nerve agents, VX, sarin and cyclosarin, and pesticides forming at oxicant analogous to paraoxon, along with initial assessments of their toxicityi nc ell culture and mice.…”

“…Recently, a new set of highly toxic phosphoramidates were brought to light through an attempted homicide, with a compound in the Novichok series bearing a fluoride leaving group . The triazole compounds synthesized here and screened in terms of reactivation of the tabun conjugate, in relation to other methylphosphonate and alkyl phosphorate conjugates, suggest that they could serve as lead countermeasures for tabun and other phosphoramidate exposure.…”

“…Multidimensional and hydrogen bonding constraints in the AChE active center gorge conjugated with methylphosphonates, phosphorates and phosphoramidates, mitigate against the likelihood of finding a single reactivator most efficient for tabun, sarin, VX, cyclosarin, paraoxon and their congeners. Nevertheless, our findings offer a valuable and comprehensive platform for further development of antidotes and scavengers against tabun and related phosphoramidate exposures, such as the Novichok series of compounds used in poisoning in Salisbury, England in the Spring of 2018 …”

“…Nevertheless, our findings offer av aluable and comprehensive platform for furtherd evelopment of antidotes and scavengers against tabun and related phosphoramidate exposures, such as the Novichok series of compounds used in poisoningi nS alisbury, Englandi nt he Spring of 2018. [18] Experimental Section Chemistry.T he majority of oximes were synthesized by Cu I -catalyzed azide-alkyne cycloaddition to form the anti-triazole using al ibrary of small molecule building blocks, as shown in Figure 1. 1 H and 13 CNMR spectra were recorded on aV arian INOVA-400 spectrometer in CDCl 3 (7.26 ppm for 1 H, 77.00 ppm 13 C), [D 6 ]DMSO (2.50 ppm for 1 H, 39.43 ppm for 13 C) as standards.…”

Supramolecular Detection of a Nerve Agent Simulant by Fluorescent Zn–Salen Oligomer Receptors

“…Although use, synthesis, and storage of chemical warfare agents (CWAs) are forbidden for security reasons, OP compounds, such as Sarin, Soman, and the more recent Novichock [3] are still used as weapons to injure or kill people, as demonstrated by some recent international events [4,5]. …”