High Capacity Adsorption and Degradation of a Nerve Agent Simulant and a Pesticide by a Nickel Pyrazolate Metal-Organic Framework.

The development of materials that enable the efficient removal of toxic compounds is important for the improvement of current protective materials or decontamination technologies. Current materials rely either on agent removal by adsorption or by effecting (catalytic) degradation. Ideally, both of these mechanisms are combined in a single material in order to target a more broad spectrum of toxic agents and to improve the performance of the materials.

Molecular modeling of Mannich phenols as reactivators of human acetylcholinesterase inhibited by A-series nerve agents.

The A-series is the most recent generation of chemical warfare nerve agents (CWA) which act directly on the inhibition of the human acetylcholinesterase (HssAChE) enzyme. These compounds lack accurate experimental data on their physicochemical properties, and there is no evidence that traditional antidotes effectively reactivate HssAChE inhibited by them. In the search for potential antidotes, we employed virtual screening, molecular docking, and molecular dynamics (MD) simulations for the theoretical assessment of the performance of a library of Mannich phenols as potential reactivators of HssAChE inhibited by the Novichok agents A-230, A-232, and A-234, in comparison with the commercial oximes pralidoxime (2-PAM), asoxime (HI-6), trimedoxime (TMB-4), and obidoxime.

Effective Degradation of Novichok Nerve Agents by the Zirconium Metal-Organic Framework MOF-808.

Novichoks are a novel class of nerve agents (also referred to as the A-series) that were employed in several poisonings over the last few years. This calls for the development of novel countermeasures that can be applied in protective concepts (e.g.

Utilizing Zirconium MOF-functionalized Fiber Substrates Prepared by Molecular Layer Deposition for Toxic Gas Capture and Chemical Warfare Agent Degradation.

Metal-organic frameworks (MOFs) are a class of porous organic-inorganic solids extensively explored for numerous applications owing to their catalytic activity and high surface area. In this work MOF thin films deposited in a one-step, molecular layer deposition (MLD), an all-gas-phase process, on glass wool fibers are characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and their capabilities towards toxic industrial chemical (TIC) capture and chemical warfare agents (CWA) degradation are investigated. It is shown that despite low volume of the active material used, MOFs thin films are capable of removal of harmful gaseous chemicals from air stream and CWA from neutral aqueous environment.

Immobilized Regenerable Active Chlorine within a Zirconium-Based MOF Textile Composite to Eliminate Biological and Chemical Threats.

The most recent global health crisis caused by the SARS-CoV-2 outbreak and the alarming use of chemical warfare agents highlight the necessity to produce efficient protective clothing and masks against biohazard and chemical threats. However, the development of a multifunctional protective textile is still behind to supply adequate protection for the public. To tackle this challenge, we designed multifunctional and regenerable N-chlorine based biocidal and detoxifying textiles using a robust zirconium metal-organic framework (MOF), UiO-66-NH, as a chlorine carrier which can be easily coated on textile fibers.

Enzymatic Decontamination of G-Type, V-Type and Novichok Nerve Agents.

Organophosphorus nerve agents (OPNAs) are highly toxic compounds inhibiting cholinergic enzymes in the central and autonomic nervous systems and neuromuscular junctions, causing severe intoxications in humans. Medical countermeasures and efficient decontamination solutions are needed to counteract the toxicity of a wide spectrum of harmful OPNAs including G, V and Novichok agents. Here, we describe the use of engineered OPNA-degrading enzymes for the degradation of various toxic agents including insecticides, a series of OPNA surrogates, as well as real chemical warfare agents (cyclosarin, sarin, soman, tabun, VX, A230, A232, A234).

Synthesis and in vitro evaluation of novel non-oximes for the reactivation of nerve agent inhibited human acetylcholinesterase.

Since several decades oximes have been used as part of treatment of nerve agent intoxication with the aim to restore the biological function of the enzyme acetylcholinesterase after its covalent inhibition by organophosphorus compounds such as pesticides and nerve agents. Recent findings have illustrated that, besides oximes, certain Mannich phenols can reactivate the inhibited enzyme very effectively, and may therefore represent an attractive complementary class of reactivators. In this paper we further probe the effect of structural variation on the in vitro efficacy of Mannich phenol based reactivators.

Decontamination of Toxic Industrial Chemicals and Fentanyl by Application of the RSDL® Kit.

Purpose: This study investigated the decontamination effectiveness of selected toxic industrial chemicals using RSDL® (Reactive Skin Decontamination Lotion Kit; Emergent BioSolutions Inc.; https://www.rsdl.

Contact transfer risk from fentanyl-contaminated RSDL® Kit.

The RSDL® (Reactive Skin Decontamination Lotion) Kit contains a lotion-impregnated sponge extensively studied for the removal or neutralization of chemical warfare agents from skin. Pilot investigation of efficacy with industrial threat compounds noted that synthetic opioid fentanyl citrate was removed by the RSDL Kit but not chemically inactivated by the lotion. This implies that after use the RSDL Kit will contain intact fentanyl, which may pose a dermal health hazard if the fentanyl is then transferred to skin after use without proper handling.

Interactions between acetylcholinesterase, toxic organophosphorus compounds and a short series of structurally related non-oxime reactivators: Analysis of reactivation and inhibition kinetics in vitro.

Poisoning by organophosphorus compounds (OP) is characterized by inhibition of the key enzyme acetylcholinesterase (AChE) and potentially fatal outcomes in humans. Insufficient efficacy of the standard therapy with atropine and AChE reactivators (oximes) against certain OP initiated synthesis of novel non-oxime reactivators basing on the common structure 4-amino-2-((diethylamino)methyl)phenol (ADOC). Recently, we reported of a pyrrolidine-bearing ADOC analogue (3 l) with a remarkable ability to reactivate OP-inhibited AChE.

Discovery of a potent non-oxime reactivator of nerve agent inhibited human acetylcholinesterase.

Organophosphorous (OP) compounds (such as nerve agents) inhibit the enzyme acetylcholinesterase (AChE) by covalent phosphylation of a key serine residue in the active site of the enzyme resulting in severe symptoms and ultimately death. OP intoxications are currently treated by administration of certain oxime compounds. The presently fielded oximes reactivate OP-inhibited AChE by liberating the phosphylated serine.

Application of the Ugi Multicomponent Reaction in the Synthesis of Reactivators of Nerve Agent Inhibited Acetylcholinesterase.

Recently, a new class of reactivators of chemical warfare agent inhibited acetylcholinesterase (AChE) with promising in vitro potential was developed by the covalent linkage of an oxime nucleophile and a peripheral site ligand. However, the complexity of these molecular structures thwarts their accessibility. We report the compatibility of various oxime-based compounds with the use of the Ugi multicomponent reaction in which four readily accessible building blocks are mixed together to form a product that links a reactivating unit and a potential peripheral site ligand.

Nanometric MIL-125-NH₂ Metal-Organic Framework as a Potential Nerve Agent Antidote Carrier.

The three-dimensional (3D) microporous titanium aminoterephthalate MIL-125-NH₂ (MIL: Material of Institut Lavoisier) was successfully isolated as monodispersed nanoparticles, which are compatible with intravenous administration, by using a simple, safe and low-cost synthetic approach (100 °C/32 h under atmospheric pressure) so that for the first time it could be considered for encapsulation and the release of drugs. The nerve agent antidote 2-[(hydroxyimino)methyl]-1-methyl-pyridinium chloride (2-PAM or pralidoxime) was effectively encapsulated into the pores of MIL-125-NH₂ as a result of the interactions between 2-PAM and the pore walls being mediated by π-stacking and hydrogen bonds, as deduced from infrared spectroscopy and Monte Carlo simulation studies. Finally, colloidal solutions of MIL-125-NH₂ nanoparticles exhibited remarkable stability in different organic media, aqueous solutions at different pH and under relevant physiological conditions over time (24 h).

Degradation of Paraoxon and the Chemical Warfare Agents VX, Tabun, and Soman by the Metal-Organic Frameworks UiO-66-NH, MOF-808, NU-1000, and PCN-777.

In recent years, Zr-based metal-organic frameworks (MOFs) have been developed that facilitate catalytic degradation of toxic organophosphate agents, such as chemical warfare agents (CWAs). Because of strict regulations, experiments using live agents are not possible for most laboratories and, as a result, simulants are used in the majority of cases. Reports that employ real CWAs are scarce and do not cover the whole spectrum of agents.

Docking and molecular dynamics studies of peripheral site ligand-oximes as reactivators of sarin-inhibited human acetylcholinesterase.

In the present work, we performed docking and molecular dynamics simulations studies on two groups of long-tailored oximes designed as peripheral site binders of acetylcholinesterase (AChE) and potential penetrators on the blood brain barrier. Our studies permitted to determine how the tails anchor in the peripheral site of sarin-inhibited human AChE, and which aminoacids are important to their stabilization. Also the energy values obtained in the docking studies corroborated quite well with the experimental results obtained before for these oximes.

A step toward the reactivation of aged cholinesterases--crystal structure of ligands binding to aged human butyrylcholinesterase.

Organophosphorus nerve agents irreversibly inhibit cholinesterases. Phosphylation of the catalytic serine can be reversed by the mean of powerful nucleophiles like oximes. But the phosphyl adduct can undergo a rapid spontaneous reaction leading to an aged enzyme, i.

Different virucidal activities of hyperbranched quaternary ammonium coatings on poliovirus and influenza virus.

Virucidal activity of immobilized quaternary ammonium compounds (IQACs) coated onto glass and plastic surfaces was tested against enveloped influenza A (H1N1) virus and nonenveloped poliovirus Sabin1. The IQACs tested were virucidal against the influenza virus within 2 min, but no virucidal effect against poliovirus was found in 6 h.

Peripheral site ligand conjugation to a non-quaternary oxime enhances reactivation of nerve agent-inhibited human acetylcholinesterase.

Commonly employed pyridinium-oxime (charged) reactivators of nerve agent inhibited acetylcholinesterase (AChE) do not readily pass the blood brain barrier (BBB) because of the presence of charge(s). Conversely, non-ionic oxime reactivators often suffer from a lack of reactivating potency due to a low affinity for the active site of AChE. It was therefore hypothesized that an extra contribution in affinity may be achieved by covalently connecting a peripheral site ligand (PSL) to a non-ionic reactivator, which may result in a higher reactivation potency of the total construct.

Respiratory allergy to trimellitic anhydride in rats: concentration-response relationships during elicitation.

The present study investigated whether airway responses of sensitized rats to trimellitic anhydride (TMA) were concentration dependent and whether these were related to irritation by TMA. Groups of BN and Wistar rats were sensitized by two dermal applications of TMA (50% w/v, followed by 25% w/v in vehicle). Controls received vehicle (acetone-olive oil 4:1, v/v).

Synthesis and in vitro evaluation of PNA-peptide-DETA conjugates as potential cell penetrating artificial ribonucleases.

We report the synthesis of novel artificial ribonucleases with potentially improved cellular uptake. The design of trifunctional conjugates 1a and 1b is based on the specific RNA-recognizing properties of PNA, the RNA-cleaving abilities of diethylenetriamine (DETA), and the peptide (KFF)(3)K for potential uptake into E. coli.

Synthetic developments towards PNA-peptide conjugates.

Since the discovery of peptide nucleic acids (PNAs) as DNA mimics in the early 1990s, a tremendous effort has been directed to their application as antisense and antigene probes. With the aim of further enhancing their properties, PNAs have been conjugated to a variety of effector molecules. Among these, small peptide fragments, often derived from functional proteins, are able to convey their specific properties to the conjugate.