Synthesis routes of CeO2 nanoparticles dedicated to organophosphorus degradation: a benchmark

Exposure to nerve agents, in military conflicts or terrorist acts, requires efficient decontamination systems. CeO2 nanoparticles appear efficient against organophosphorus compounds, thus we performed a benchmark on the available synthesis routes.

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Nerve Agents’ Surrogates: Invaluable Tools for Development of Acetylcholinesterase Reactivators

Current Organic Chemistry ◽

10.2174/1385272823666190806114017 ◽

2019 ◽

Vol 23 (14) ◽

pp. 1539-1559 ◽

Cited By ~ 3

Author(s):

Samir F. de A. Cavalcante ◽

Alessandro B. C. Simas ◽

Kamil Kuča

Keyword(s):

Organophosphorus Compounds ◽

Nerve Agents ◽

Toxic Chemicals ◽

Restricted Class ◽

Pharmaceutical Substances ◽

Chemical Weapons Convention ◽

Organophosphorus Poisoning ◽

Cholinesterase Reactivators ◽

Terrorist Acts ◽

Acetylcholinesterase Reactivators

The use of nerve agents as warfare and in terrorist acts has drawn much attention from the governments and societies. Such toxic organophosphorus compounds are listed in Chemical Weapons Convention as Schedule 1 chemicals. The discussion about the chemical identity of the elusive Novichok agents, more potent compounds than best known G- and V-Agents, which have been implicated in recent rumorous assassination plots, clearly demonstrating the importance of the matter. Furthermore, accidents with pesticides or misuse thereof have been a pressing issue in many countries. In this context, the continued development of novel cholinesterase reactivators, antidotes for organophosphorus poisoning, a rather restricted class of pharmaceutical substances, is warranted. Testing of novel candidates may require use of actual nerve agents. Nonetheless, only a few laboratories comply with the requirements for storing, possession and manipulation of such toxic chemicals. To overcome such limitations, nerve agents’ surrogates may be a useful alternative, as they undergo the same reaction with cholinesterases, yielding similar adducts, allowing assays with novel antidote candidates, among other applications.

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Shape-selective synthesis of nanoceria for degradation of paraoxon as a chemical warfare simulant

Physical Chemistry Chemical Physics ◽

10.1039/c9cp00179d ◽

2019 ◽

Vol 21 (10) ◽

pp. 5455-5465 ◽

Cited By ~ 11

Author(s):

Isabelle Trenque ◽

Greta Camilla Magnano ◽

Marie Alexandrine Bolzinger ◽

Lucian Roiban ◽

Frédéric Chaput ◽

...

Keyword(s):

Cerium Oxide ◽

Organophosphorus Compounds ◽

Chemical Warfare ◽

Selective Synthesis ◽

Suitable Candidate ◽

Military Conflicts ◽

Shape Selective ◽

Terrorist Acts

Repeated attacks using organophosphorus compounds, in military conflicts or terrorist acts, necessitate developing inexpensive and readily available decontamination systems. Nanosized cerium oxide is a suitable candidate when presents {111} facets.

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Comparative determination of the efficacy of bispyridinium oximes in paraoxon poisoning / Usporedno određivanje učinkovitosti bispiridinijevih oksima pri trovanju paraoksonom

Archives of Industrial Hygiene and Toxicology ◽

10.1515/aiht-2015-66-2623 ◽

2015 ◽

Vol 66 (2) ◽

pp. 129-134 ◽

Cited By ~ 15

Author(s):

Suzana Žunec ◽

Božica Radić ◽

Kamil Kuča ◽

Kamil Musilek ◽

Ana Lucić Vrdoljak

Keyword(s):

Therapeutic Efficacy ◽

Standard Therapy ◽

Organophosphorus Compounds ◽

Nerve Agents ◽

Therapeutic Efficiency ◽

Hi 6 ◽

Comparative Determination

Abstract The inability of standard therapy to provide adequate protection against poisoning by organophosphorus compounds (pesticides and nerve agents) motivated us to search for new, more effective oximes. We investigated the pharmacotoxicological properties of six experimental K-oximes (K027, K033, K048, K074, K075, and K203) in vivo. The therapeutic efficacy of K-oximes (at doses of 5 or 25 % of their LD50) combined with atropine was assessed in paraoxon-poisoned mice and compared with conventionally used oximes HI-6 and TMB-4. The bisoxime K074 was the most toxic (LD50=21.4 mg kg-1) to mice, while monoxime K027 was the least toxic (LD50=672.8 mg kg-1). With the exception of K033, all of the tested K-oximes showed better therapeutic efficiency than HI-6 and TMB-4. K027 and K048 stood out by demonstrating low acute toxicities and ensuring protective indices ranging from 60.0 to 100.0 LD50 of paraoxon. Taking into account that these two oximes showed a similar therapeutic efficacy regardless of the applied doses, our results suggest that K027 and K048 could be antidotes for paraoxon intoxication.

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Catalytic Degradation of Nerve Agents

Catalysts ◽

10.3390/catal10080881 ◽

2020 ◽

Vol 10 (8) ◽

pp. 881

Author(s):

Agatino Zammataro ◽

Rossella Santonocito ◽

Andrea Pappalardo ◽

Giuseppe Trusso Sfrazzetto

Keyword(s):

World War Ii ◽

Acute Toxicity ◽

Organophosphorus Compounds ◽

Organophosphorus Pesticides ◽

Lethal Effect ◽

Nerve Agents ◽

Catalytic Degradation ◽

World War ◽

Degradation Reactions ◽

Chemical Hydrolysis

Nerve agents (NAs) are a group of highly toxic organophosphorus compounds developed before World War II. They are related to organophosphorus pesticides, although they have much higher human acute toxicity than commonly used pesticides. After the detection of the presence of NAs, the critical step is the fast decontamination of the environment in order to avoid the lethal effect of these organophosphorus compounds on exposed humans. This review collects the catalytic degradation reactions of NAs, in particular focusing our attention on chemical hydrolysis. These reactions are catalyzed by different catalyst categories (metal-based, polymeric, heterogeneous, enzymatic and MOFs), all of them described in this review.

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The Possibilities of Working Capacity Maintenance at Organophosphorous Compounds Intoxication

Journal of NBC Protection Corps ◽

10.35825/2587-5728-2019-3-4-311-318 ◽

2019 ◽

Vol 3 (4) ◽

pp. 311-318

Keyword(s):

Oral Administration ◽

Organophosphorus Compounds ◽

Working Capacity ◽

Industrial Accidents ◽

Experimental Animals ◽

Single Oral Administration ◽

Combined Use ◽

The World ◽

Organophosphorous Compounds ◽

Terrorist Acts

Th e experience of modern local armed confl icts and the monitoring of terrorist activity in the world indicate the possibility of the aff ection of people by organophosphorus compounds (OPs) in combat and as a result of industrial accidents and terrorist acts. It can be predicted that in case of timely use of PPE by the personnel, in addition to lethal and severe aff ections, up to 30 ± 5% of them will be mild forms of intoxication. It is shown in the article, that the actoprotectors with diff erent mechanism of action (hypoxene, octodrine and meldonium) increase the endurance of experimental animals with mild poisoning of OPs in case of single oral administration. Moreover, the degree of inhibition of peripheral blood acetylcholinesterase of all animals treated with model OPs did not diff er between groups and ranged from 8 to 24%. As a result of the experiments on animals, the preparations were distributed in the following order: meldonium <octodrine <hypoxene. Joint oral administration of the test substances was not accompanied by a potentiation of the actoprotective eff ect. It is established, that the combined use of the studied actoprotectors is comparable with the isolated administration of meldonium, has no advantages over the use of octodrine and surpasses hypoxene in rate of onset of the eff ect, but is inferior to it in severity and duration. Th ese facts indicate the viability of use of the studied actoprotectors to prevent a decrease in combat readiness in case of the threat of the aff ection by OPs (hypoxene), for its urgent increase in case of mild aff ection (octodrine) and for the complex treatment of poisoning due to organophosphates (OPs) (meldonium, hypoxene)

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Enzymatic Degradation of Organophosphorus Pesticides and Nerve Agents by EC: 3.1.8.2

Catalysts ◽

10.3390/catal10121365 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1365

Author(s):

Marek Matula ◽

Tomas Kucera ◽

Ondrej Soukup ◽

Jaroslav Pejchal

Keyword(s):

Catalytic Activity ◽

Organophosphorus Compounds ◽

Organophosphorus Pesticides ◽

Chemical Warfare Agents ◽

Enzyme Commission Number ◽

Nerve Agents ◽

Organophosphorus Acid Anhydrolase ◽

Warfare Agents ◽

Heavy Burden ◽

Medical Countermeasures

The organophosphorus substances, including pesticides and nerve agents (NAs), represent highly toxic compounds. Standard decontamination procedures place a heavy burden on the environment. Given their continued utilization or existence, considerable efforts are being made to develop environmentally friendly methods of decontamination and medical countermeasures against their intoxication. Enzymes can offer both environmental and medical applications. One of the most promising enzymes cleaving organophosphorus compounds is the enzyme with enzyme commission number (EC): 3.1.8.2, called diisopropyl fluorophosphatase (DFPase) or organophosphorus acid anhydrolase from Loligo Vulgaris or Alteromonas sp. JD6.5, respectively. Structure, mechanisms of action and substrate profiles are described for both enzymes. Wild-type (WT) enzymes have a catalytic activity against organophosphorus compounds, including G-type nerve agents. Their stereochemical preference aims their activity towards less toxic enantiomers of the chiral phosphorus center found in most chemical warfare agents. Site-direct mutagenesis has systematically improved the active site of the enzyme. These efforts have resulted in the improvement of catalytic activity and have led to the identification of variants that are more effective at detoxifying both G-type and V-type nerve agents. Some of these variants have become part of commercially available decontamination mixtures.

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Nanoscavenger provides long-term prophylactic protection against nerve agents in rodents

Science Translational Medicine ◽

10.1126/scitranslmed.aau7091 ◽

2019 ◽

Vol 11 (473) ◽

pp. eaau7091 ◽

Cited By ~ 19

Author(s):

Peng Zhang ◽

Erik J. Liu ◽

Caroline Tsao ◽

Shane A. Kasten ◽

Michael V. Boeri ◽

...

Keyword(s):

Organophosphorus Compounds ◽

Pharmacokinetic Profile ◽

Nerve Agents ◽

Nerve Agent ◽

Prophylactic Administration ◽

Guinea Pig Model ◽

Effective Drugs ◽

Scavenging Efficiency

Nerve agents are a class of organophosphorus compounds (OPs) that blocks communication between nerves and organs. Because of their acute neurotoxicity, it is extremely difficult to rescue the victims after exposure. Numerous efforts have been devoted to search for an effective prophylactic nerve agent bioscavenger to prevent the deleterious effects of these compounds. However, low scavenging efficiency, unfavorable pharmacokinetics, and immunological problems have hampered the development of effective drugs. Here, we report the development and testing of a nanoparticle-based nerve agent bioscavenger (nanoscavenger) that showed long-term protection against OP intoxication in rodents. The nanoscavenger, which catalytically breaks down toxic OP compounds, showed a good pharmacokinetic profile and negligible immune response in a rat model of OP intoxication. In vivo administration of the nanoscavenger before or after OP exposure in animal models demonstrated protective and therapeutic efficacy. In a guinea pig model, a single prophylactic administration of the nanoscavenger effectively prevented lethality after multiple sarin exposures over a 1-week period. Our results suggest that the prophylactic administration of the nanoscavenger might be effective in preventing the toxic effects of OP exposure in humans.

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Gene-Delivered Butyrylcholinesterase Is Prophylactic against the Toxicity of Chemical Warfare Nerve Agents and Organophosphorus Compounds

Journal of Pharmacology and Experimental Therapeutics ◽

10.1124/jpet.110.175646 ◽

2010 ◽

Vol 337 (1) ◽

pp. 92-101 ◽

Cited By ~ 32

Author(s):

Kalpana Parikh ◽

Ellen G. Duysen ◽

Benjamin Snow ◽

Neil S. Jensen ◽

Veeraswamy Manne ◽

...

Keyword(s):

Organophosphorus Compounds ◽

Nerve Agents ◽

Chemical Warfare

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Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.12.23 ◽

2016 ◽

Vol 12 ◽

pp. 204-228 ◽

Cited By ~ 27

Author(s):

Sophie Letort ◽

Sébastien Balieu ◽

William Erb ◽

Géraldine Gouhier ◽

François Estour

Keyword(s):

Organophosphorus Compound ◽

Organophosphorus Compounds ◽

Organophosphorus Pesticides ◽

Nerve Agents ◽

Cyclic Structure ◽

Biological Target

The aim of this review is to provide an update on the current use of cyclodextrins against organophosphorus compound intoxications. Organophosphorus pesticides and nerve agents play a determinant role in the inhibition of cholinesterases. The cyclic structure of cyclodextrins and their toroidal shape are perfectly suitable to design new chemical scavengers able to trap and hydrolyze the organophosphorus compounds before they reach their biological target.

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