“Novichok” refers to a new group of nerve agents called the A-series agents. Their existence came to light in 2018 after incidents in the UK and again in 2020 in Russia. They are unique organophosphorus-based compounds developed during the Cold War in a program called Foliant in the USSR. This review is based on original chemical entities from Mirzayanov's memoirs published in 2008. Due to classified research, a considerable debate arose about their structures, and hence, various structural moieties were speculated. For this reason, the scientific literature is highly incomplete and, in some cases, contradictory. This review critically assesses the information published to date on this class of compounds. The scope of this work is to summarize all the available and relevant information, including the physicochemical properties, chemical synthesis, mechanism of action, toxicity, pharmacokinetics, and medical countermeasures used to date. The environmental stability of A-series agents, the lack of environmentally safe decontamination, their high toxicity, and the scarcity of information on post-contamination treatment pose a challenge for managing possible incidents.

A-series agent A-234 belongs to a new generation of nerve agents. The poisoning of a former Russian spy Sergei Skripal and his daughter in Salisbury, England, in March 2018 led to the inclusion of A-234 and other A-series agents into the Chemical Weapons Convention. Even though five years have already passed, there is still very little information on its chemical properties, biological activities, and treatment options with established antidotes. In this article, we first assessed A-234 stability in neutral pH for subsequent experiments. Then, we determined its inhibitory potential towards human recombinant acetylcholinesterase (HssAChE; EC 3.1.1.7) and butyrylcholinesterase (HssBChE; EC 3.1.1.8), the ability of HI-6, obidoxime, pralidoxime, methoxime, and trimedoxime to reactivate inhibited cholinesterases (ChEs), its toxicity in rats and therapeutic effects of different antidotal approaches. Finally, we utilized molecular dynamics to explain our findings. The results of spontaneous A-234 hydrolysis showed a slow process with a reaction rate displaying a triphasic course during the first 72 h (the residual concentration 86.2%). A-234 was found to be a potent inhibitor of both human ChEs (HssAChE IC₅₀ = 0.101 ± 0.003 µM and HssBChE IC₅₀ = 0.036 ± 0.002 µM), whereas the five marketed oximes have negligible reactivation ability toward A-234-inhibited HssAChE and HssBChE. The acute toxicity of A-234 is comparable to that of VX and in the context of therapy, atropine and diazepam effectively mitigate A-234 lethality. Even though oxime administration may induce minor improvements, selected oximes (HI-6 and methoxime) do not reactivate ChEs in vivo. Molecular dynamics implies that all marketed oximes are weak nucleophiles, which may explain the failure to reactivate the A-234 phosphorus-serine oxygen bond characterized by low partial charge, in particular, HI-6 and trimedoxime oxime oxygen may not be able to effectively approach the A-234 phosphorus, while pralidoxime displayed low interaction energy. This study is the first to provide essential experimental preclinical data on the A-234 compound.

Nitrogen mustards are blistering chemical warfare agents which are considered to be persistent contaminants highly resistant to decontamination. The paper describes the development and optimization of a method for the extraction of nitrogen mustards bis(2-chloroethyl)ethylamine (HN-1), bis(2-chloroethyl)methylamine (HN-2), and tris(2-chloroethyl)amine (HN-3) from sand samples with subsequent identification by gas chromatography–mass spectrometry (GC-MS) in a military deployable laboratory. Common solvents which have been used for various methods in field analysis and are available in deployable laboratories were tested as the extraction reagents—dichloromethane, dichloroethane, hexane, heptane, ethyl acetate, methanol, and acetone. Calibration curves for the determination of nitrogen mustards were created. Methods for the extraction from the sand matrix were developed and optimized. The extraction efficiencies of the tested solvents were compared. Limits of detection of nitrogen mustards in sand samples were determined for all tested extractants. For quantitative purposes, the internal standardization method was used. The extraction efficiencies for the studied solvents varied in the range from 10.8 to 86.4%. The most effective extraction reagents for HN-1, HN-2, and HN-3 extraction were dichloromethane and acetone. Acetone was determined to be the most practical extraction reagent of nitrogen mustards in sand after the consideration of various criteria.

Nitrogen mustards are dangerous and available blistering chemical warfare agents. In the presented study, six derivatization methods are compared for the analysis of degradation products of the most important blistering nitrogen mustards (ethyl diethanolamine, methyl diethanolamine and triethanolamine) by gas chromatography coupled with mass spectrometry. Five silylation methods (using BSTFA and BSA) and one trifluoroacetylation method (using TFAA) were tested. The derivatization reactions were performed in acetonitrile. As the method with optimal results, trifluoroacetylation by TFAA was selected. Analytes reacted with the corresponding reagent rapidly, quantitatively, with stable kinetics and at room temperature. Calibration curves for quantitative analysis of ethanolamines after TFAA derivatization were created. Correspond-ing detection limits varied between 9?10-3 and 7?10-5 mmol?dm-3 for the tested analytes. The developed method was applied for the analysis of ethanolamines after extraction from sand using acetonitrile. Limits of detection were 11.4 to 12.3 ?g of the analyte in 1 g of sand. It is encouraged to use the developed method in military deployable laboratories designated for rapid identification of chemical warfare agents and corresponding degradation products.

Effective sampling is a key step in the process of proving the use of chemical weapons. An alternative to collecting the respective sample is to perform a wipe of surface contamination. This work deals with the optimization of the wiping process of the surfaces of selected matrices contaminated with bis(2-chloroethyl)sulfide and tris(2-chloroethyl)amine. Optimization of the procedure was carried out in terms of the choice of wiping material, wetting solvent and extraction of the wiped contaminant. Furthermore, the time decrease of surface contamination was monitored. The effect of transport on the change in the observed recovery value was investigated and the measurement deviations of the wipe method were discussed. The resulting values of observed recovery were negatively influenced by the volatility of the analyte, the porosity of the matrix and the time that passed since the contamination. Viscose was evaluated as the most effective wipe material. Low relative standard deviations (≤7 %) were achieved with this material. The optimal wetting solvent was dichloromethane. There was no degradation of contaminants on the surface of the matrices, so the fate was only affected by evaporation and penetration into the material.