A Rhodamine-Based Probe for Detection of Nerve Agents Simulants

In this paper, a rhodamine-based fluorescent and chromogenic probe, N-(Rhodamine B)-lactam-2-aminobenzyl alcohol (RB-AB), was designed to detect nerve agent simulants. We firstly synthesized RB-AB probe by using rhodamine B and 2-aminobenzyl alcohol as main materials. Secondly, the RB-AB probe was applied to evaluate its ability to detect two nerve agent simulants, diethyl chloride phosphate (DCP) and methyl ethyl chloride phosphate (MECP). It was assumed that RB-AB could react with the nerve agent simulants through the benzyl alcohol group and then undergoes structural changes. As a result, the RB-AB detection solution shows fluorescent and color changes during detecting process. The maximum intensity of fluorescence emission increases with the addition of DCP or MECP in a dose-dependent manner. The LOD (limit of detection) of the probe is about 20 ppm for DCP. Moreover, a significant pink color change can be observed in the RB-AB system within a few seconds when detecting DCP or MECP. In conclusion, a rhodamine-based molecule as a fluorescent and chromogenic probe was developed for detecting nerve agent simulants. The RB-AB probe solutions can give rapid and off-on type optical changes including color and fluorescence when reacting with DCP or MECP. We anticipate that RB-AB probe can be used as a helpful tool for visual and fluorescent detection of nerve agents when meeting with terrorist attacks involving with these agents so that effective measures could be promptly taken to cope with the crises.

Assessment of four organophosphorus pesticides as inhibitors of human acetylcholinesterase and butyrylcholinesterase

Toxicity of organophosphorus compounds (OPs) remains a major public health concern due to their widespread use as pesticides and the existence of nerve agents. Their common mechanism of action involves inhibition of enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) which are crucial for neurotransmission. Both chronic and acute poisoning by OPs can leave long-lasting health effects even when the patients are treated with standard medical therapy. Therefore, an increasing urgency exists to find more effective oxime reactivators for compounds which are resistant to reactivation, especially phosphoramidates. Here, we investigated in silico and in vitro interactions and kinetics of inhibition for human cholinesterases with four organophosphate pesticides—ethoprophos, fenamiphos, methamidophos and phosalone. Overall, ethoprophos and fenamiphos displayed higher potency as inhibitors for tested cholinesterases. Our results show that methamidophos-inhibited hAChE was more susceptible to reactivation than hAChE inhibited by fenamiphos by selected oximes. Molecular modelling enabled an evaluation of interactions important for specificity and selectivity of both inhibition and reactivation of cholinesterases. Two newly developed reactivators—bispyridinium triazole oxime 14A and zwitterionic oxime RS194B possess remarkable potential for further development of antidotes directed against pesticides and related phosphoramidate exposures, such as nerve agents tabun or Novichoks.

A Systematic Review on Nerve Chemical Warfare Agents

The recent poisoning of Russian opposition figure and critic Alexei Navalny on August 20th , 2020 with a Soviet-era Novichok nerve agent reminded the world of the use of chemical agents, especially nerve agents to eliminate individual targets or for mass destruction. Nerve agents are a class of organophosphorus compounds. Soman, Sarin, Tabun, Cyclosarin, VX are a few examples of nerve agents. Nerve agents affect a person by disrupting the mechanism by which nerve signals are passed in the body. They inhibit the action of acetylcholinesterase enzyme which is responsible for the breakdown of acetylcholine neurotransmitters leading to accumulation of acetylcholine in the body. Nerve agents have a range of chemical effects on the eye, gastro-intestinal (GI) tract, Central nervous system (CNS), Respiratory system, Cardiovascular system and Neurological system. The management of nerve agent poisoning is done by administering Atropine or Pralidoxime chloride or also by administering anticonvulsants like Benzodiazepines or Diazepam. This review presents all such detailed information on this class of chemical Warfare agents. Keywords: Chemical Warfare Weapon, Nerve Agents, Acetylcholinesterase, Toxicity, Instrumentation

Backbone Conformation Shifts in X-ray Structures of Human Acetylcholinesterase upon Covalent Organophosphate Inhibition

Conformations of Cα backbones in X-ray structures of most organophosphate (OP)-inhibited human acetylcholinesterases (hAChEs) have been previously shown to be similar to that of the native hAChE. One of the exceptions is the structure of the diethylphosphoryl-hAChE conjugate, where stabilization of a large ethoxy group into the acyl pocket (AP) of hAChE-triggered notable loop distortions and consequential dissociation of the hAChE homodimer. Recently, six X-ray structures of hAChE conjugated with large OP nerve agents of the A-type, Novichoks, have been deposited to PDB. In this study we analyzed backbone conformation shifts in those structures, as well as in OP-hAChE conjugates formed by Paraoxon, Soman, Tabun, and VX. A Java-based pairwise alpha carbon comparison tool (PACCT 3) was used for analysis. Surprisingly, despite the snug fit of large substituents on phosphorus, inside Novichok-conjugated hAChEs only minor conformational changes were detected in their backbones. Small magnitudes of observed changes were due to a 1.2–2.4 Å shift of the entire conjugated OP away from the AP. It thus appears that the small AP of AChEs can accommodate, without distortion, substituents of the size of ethoxy or butyryl groups, provided that conjugated OP is “pulled” away from the AP. This observation has practical consequences in the structure-based design of nucleophilic reactivation antidotes as well as in the definition of the AChE specificity that relies on the size of its AP.

Widespread Utilization of Diverse Organophosphate Pollutants by Marine Bacteria

Anthropogenic organophosphates (AOPs), such as phosphotriesters, are used extensively as plasticizers, flame retardants, nerve agents and pesticides. Soil bacteria bearing a phosphotriesterase (PTE) can degrade AOPs, but whether bacteria are capable of utilizing AOPs as a phosphorus source, and how widespread PTEs are in nature, remains unclear. Here, we report the utilization of diverse AOPs by four model marine bacteria and seventeen bacterial isolates from seawater samples. To unravel the details of AOP utilization, two novel PTEs from marine bacteria were isolated and characterized. When expressed in E. coli, these PTEs enabled growth on a pesticide analog as the sole phosphorus source. Utilization of AOPs provides bacteria with a source of phosphorus in depleted environments and offers a new prospect for the bioremediation of a pervasive class of anthropogenic pollutants.