“…Few studies have examined Novichok, and they are limited to predictions of reactivity and spectra based on theoretical calculations ,, or reports of the chromatograms and mass spectra of A234 . To the best of our knowledge, there is no information on the LODs, quantitative analyses, and screening methods for Novichok.…”
Novichok A-series compounds, novel nerve agents, pose an increasing threat to citizens worldwide; however, no analytical methods have been reported for detecting their hydrolysis products. Herein, a screening method was developed to detect and identify Novichok A-series degradation products (hydrolysates of A230, A232, A234, A262, and one related compound) and alkyl methylphosphonic acids (RMPAs, conventional nerve agent hydrolysates) using liquid chromatography−tandem mass spectrometry (LC−MS/MS). We identified a suitable derivatization reagent, 4-(4,6dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM), and optimized the reaction conditions. The derivatized esters of Novichok A-series degradation products were stable and easily detected. We used this derivatization to achieve the first analytical method for Novichok hydrolysis products in urine (0.40−4.0 ng/mL). The detection limits of the RMPAs (0.1−0.4 ng/mL) were comparable to those presented in previous reports involving pentafluorobenzylation or direct LC−MS/MS. The applicability of the newly developed method was evaluated by analyzing urine samples from the OPCW Fifth Biomedical Proficiency Test.
“…Few studies have examined Novichok, and they are limited to predictions of reactivity and spectra based on theoretical calculations ,, or reports of the chromatograms and mass spectra of A234 . To the best of our knowledge, there is no information on the LODs, quantitative analyses, and screening methods for Novichok.…”
Novichok A-series compounds, novel nerve agents, pose an increasing threat to citizens worldwide; however, no analytical methods have been reported for detecting their hydrolysis products. Herein, a screening method was developed to detect and identify Novichok A-series degradation products (hydrolysates of A230, A232, A234, A262, and one related compound) and alkyl methylphosphonic acids (RMPAs, conventional nerve agent hydrolysates) using liquid chromatography−tandem mass spectrometry (LC−MS/MS). We identified a suitable derivatization reagent, 4-(4,6dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM), and optimized the reaction conditions. The derivatized esters of Novichok A-series degradation products were stable and easily detected. We used this derivatization to achieve the first analytical method for Novichok hydrolysis products in urine (0.40−4.0 ng/mL). The detection limits of the RMPAs (0.1−0.4 ng/mL) were comparable to those presented in previous reports involving pentafluorobenzylation or direct LC−MS/MS. The applicability of the newly developed method was evaluated by analyzing urine samples from the OPCW Fifth Biomedical Proficiency Test.
“…It is seen that the activation energy calculated by M062X is lower than that of the other two methods (see Table S1 ). Although the first step of the hydrolysis reaction is generally considered the rate-determining step because the energy of transition state on rate-determining step is kinetically the highest energetic number to overcome to go further for overall reaction [48] , it is worth noting that we did not find any correlation between the experimental hydrolysis rate [28] and the calculated activation energy of the hydrolysis reaction of the nerve agents. Fig.…”
Section: Resultsmentioning
confidence: 66%
“…The optimization has been done by using B3LYP/6–311++G(d, p) in the aqueous conditions as the efficiencies of S N 2 reactions are influenced by solvent effects in the H 2 O [46] , [47] . During the hydrolysis with OH ¯ , the P-F and P-S bonds break, in the case of A-, G-series, as well as V-series, respectively [48] . As our concern was not to depict the hydrolysis reaction mechanism of the nerve agents, we have focused only on the activation energy of the first step of the hydrolysis which has been listed in Table S1 .…”
“…The hydrolysis rate confirms the stability of Novichok compounds in the environment or in the organism. An additional group (Otsuka and Miyaguchi 2021 ) used density functional theory to perform theoretical calculations for the hydrolysis reactions of nerve agents, including Novichok compounds. According to data, A-series agents were as resistant to hydrolysis as VX and more resistant to hydrolysis than GB under basic conditions.…”
Section: Toxicity Of Novichoksmentioning
confidence: 99%
“…The activation energy of hydrolysis under basic conditions is lower for compound A-234 compared to that under neutral conditions. Therefore, decontamination will be more effective under basic conditions (Otsuka and Miyaguchi 2021 ).…”
Novichok is the name given to the group of nerve agents created stealthily in the later phases of the Cold War by the Soviet Union. Constitute the fourth generation of chemical warfare agents; like other nerve agents, they are organophosphorus compounds designed to be incurable and undetectable. The mechanism of action is based on the non-competitive and irreversible inhibition of acetylcholinesterase. Due to their enormous toxicity, Novichoks have become attractive targets for terrorists. However, little information is known about the identity of nerve agents. Furthermore, these compounds have never been submitted to the Chemical Weapons Convention. Our article aspires to provide a general overview of Novichoks knowledge. As part of this, we reviewed the available literature data to answer the question, what are Novichoks? In addition to the physical and chemical properties of A-agents, synthesis, mechanism of action, and toxicity of nerve agents were also reviewed. We hope that this review will highlight the tremendous threat posed by nerve agents and will inspire further studies on the interdisciplinary aspects of these compounds.
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