Search

One of the most important types of chemical weapons is nerve agents. In recent years, a group of the newest, most unknown, and at the same time the most common nerve agents known as Novichok has been used in terrorist attacks. It is necessary to become more familiar with the basic and clinical chemical and pharmacologic features of this group of nerve agents for all the employees of the medical group. In this article, while reviewing the history of development and production, chemical structure, mechanism of action, toxicokinetic, and toxicology of these agents, the latest information regarding the methods of diagnosis and treatment of poisoning with these agents was also reviewed. Contrary to early information, it appears that Novichok poisoning is similar to other organophosphate agents and can be managed with prompt and appropriate treatment. Considering the existence of global threats in the field of terrorist incidents with these agents, the medical team must be familiar with these poisons to diagnose and treat the victims optimally. [ABSTRACT FROM AUTHOR]

The present study was intended to develop suitable methods for unambiguous identification and determination of ethyl (1-(diethylamino)ethylidene) phosphoramidofluoridate (known as A234-Novichok) biomarkers in urine and plasma samples. Multiple biomarkers were investigated for the first time, to verify intoxication by the A234-Novichok agent, using sensitive and accurate techniques including gas and liquid chromatography-tandem mass spectrometry (GC–MS/MS and LC–MS/MS). Like other nerve agents, in biological matrices, the A234-Novichok agent reacts with several proteins to form related adducts. Considering this, two different protein adduct biomarkers in blood samples were analyzed, and the regenerated A234 was determined. Two-dimensional chromatography and solid-phase extraction techniques were employed for blood sample preparation. Limits of detection for butyrylcholinesterase (BChE) adduct, the regenerated A234, and albumin covalent adduct were determined and reported as 1, 1, and 10 ng mL−1, while the related calibration curves were linear within the range of 2–100, 2–100, and 15–100 ng mL−1, respectively. The detection limit and linear range for the intact agent in the urine sample were determined as 0.1 and 1–100 ng mL−1, respectively. Since A234 and some other Novichok chemicals have been added to the Schedule 1 of the Chemical Weapons Convention (CWC), Annex on Chemicals, after UK incidents, the analytical methods developed in this work might be used for verification purposes, as well as OPCW Biomedical Proficiency Tests. [ABSTRACT FROM AUTHOR]

Thiophosphinoylation of N-methyl p-substituted benzohydroxamic acids using disulfanes (method A) or diphenylphosphinothioyl chloride (method B) provides only one conformer of the respective O-phosphothioyl derivative (X-ray and NMR analysis). Undergoing the P-transamidoxylation reaction is an evidence of the reversibility of thiophosphinoylation. Only those products containing strong EWG substituents in the aroyl residue or bulky substituents at the phosphorus atom possess E conformation. DFT calculations confirmed the energetic domination of each isomer. The Z-isomers are distorted amides having both high degree of nitrogen pyramidalization (38–55°) and amide twist (12–30°). In solution they exist in a defined conformation that is evidenced by the presence of a sharp signal of N-methyl protons at low temperature. They do not isomerize in solutions. Some of them slowly undergo the N-O bond scission above 100 °C. Both isomers are not as sensitive to neutral hydrolysis as twisted amides can be and are inert toward amines. The rate of alkaline hydrolysis can be correlated with pKa of hydroxamic acid. Because of their outstanding oxyphilicity, these compounds can be defined as nerve agent surrogates and safer alternatives of phosphorus fluorides for serine-active enzyme inhibition studies. [ABSTRACT FROM AUTHOR]