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The density functional theory (DFT) method is applied to investigate the ability of transition metals porphyrins induced in carbon nanocone (TM-PCNC, TM = Ti 2+ , Cr 2+ , Fe 2+ , Co 2+ , Ni 2+ , Cu 2+ , and Zn 2+ ) for identifying and eliminating undesirable SM molecules from the surrounding. The sulfur mustard is effectively adsorbed onto the surface of nanocones through a chemical process. Based on the DFT calculations, the Ti-PCNC displays an appropriate percentage change in energy gap (%ΔE g  = 11.82 and 14.67), thus making it a promising candidate for possessing sensing capabilities towards the sulfur mustard. According to the acquired findings, it can be deduced that the work function of nanocones exhibits minimal alterations after the adsorption of sulfur mustard. This signifies that nanocones may not serve as a suitable work function sensor for sulfur mustard detection. In addition, when the UV-visible spectra of pristine Ti-PCNC are compared with its complexes, it is found that sulfur mustard adsorption does not change the nanocones spectra but increases the number of absorption lines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Large quantities of toxic chemical warfare material, such as mixtures of sulphur mustard (HD) and arsenic-containing chemical warfare agents (As-CWAs) have been submerged in the Baltic Sea region after World War II. Little is known about the possible reactivity between HD and As-CWAs. In this study, we used simple reaction mixtures and ultra-high performance liquid chromatography combined with mass spectrometric techniques to study the reactivity of HD and the half-mustard 2-chloroethyl ethyl sulphide (CEES) with As-CWAs. Altogether 22 novel As-CWA-HD- and As-CWA-CEES-complexes were identified. Eight of the As-CWA-HD-complexes were also detected in environmental samples collected from known CWA dumping sites in the Baltic Sea region. Because the As-CWA-HD- and As-CWA-CEES-complexes have structural moieties of both S-mustards and As-CWAs, they might have toxic properties of both CWA-types. Therefore, their occurrence in the environment is concerning and their potential negative effect on the wellbeing of marine biota and humans should be investigated in the future. This is the first time alkylation of As-CWAs is reported, providing new knowledge on the reactivity of S-mustards. The results increase the understanding of the environmental fate of HD and is valuable for the assessment of the environmental threat of sea-dumped CWAs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The highly blistering sulfur mustard analogue agent T (bis(2-chloroethylthioethyl) ether), also known as O-mustard or oxy-mustard, is a common impurity in military grade sulfur mustard (SM) and a component of mixtures such as "HT" that are still found in old munitions. Together with sesquimustard (Q), it is the most important SM analogue and tightly regulated as a Schedule 1 chemical under the Chemical Weapons Convention. We report the adducts of T with nucleophilic Cys 34 and other residues in human serum albumin (HSA) formed in vitro. A micro liquid chromatography electrospray ionization high-resolution tandem-mass spectrometry method (µLC-ESI MS/HR MS) was developed for the detection and identification of biomarker peptides alkylated by a T-derived hydroxyethylthioethyloxyethylthioethyl (HETEOETE)-moiety (as indicated by an asterisk below). Following proteolysis of T-exposed human plasma with pronase, the dipeptide Cys 34 *Pro and the single amino acid residue His* were produced. The use of proteinase K yielded Cys 34 *ProPhe and the use of pepsin generated ValThrGlu 48 *Phe, AlaGlu 230 *ValSerLysLeu, and LeuGlyMet 329 *Phe. Corresponding peptide-adducts of SM and Q were detected in a common workflow that in principle allowed the estimation of the mustard or mustard composition encountered during exposure. Novel adducts of Q at the Glu 230 and Met 239 residues were detected and are reported accordingly. Based on molecular dynamics simulations, we identified regular interactions of the Cys 34 (-HETEOETE)-moiety with several glutamic acid residues in HSA including Glu 86 , which is not an obvious interaction partner by visual inspection of the HSA crystal structure. The existence of this and other intramolecular cross-links was experimentally proven for the first time., (© 2024. The Author(s).)

Sesquimustard (Q) is a powerful blistering agent that contains additional sulfur atoms. Sulfur mustard causes covalent bonding by alkylating nucleophilic groups of biologically important macromolecules such as lipids, proteins, DNA, or RNA. Most cells maintain relatively high amounts of a unique tripeptide called glutathione (GSH) (γ-glutamyl-cysteinyl glycine), which possesses a free thiol group, to prevent unwanted reactions caused by reactive chemical entities. Moreover, these thiol groups on cysteines (Cys) are the main target for alkylation. Although Q is the most potent vesicant among sulfur mustards, research studies identifying biomarkers of Q are very limited. Therefore, here in this study, we aimed to identify the GSH and Cys conjugates of Q using mass spectrometric methods and to observe the formation of these conjugates in HaCat cell culture following exposure to different doses. We identified four different conjugates of Q, which are bis-glutathionyl ethylthioethylthioethyl conjugate (GSH-ETETE-GSH), hydroxyethylthioethylthioethyl glutathione conjugate (HETETE-GSH), bis-cysteinyl ethylthioethylthioethyl conjugate (Cys-ETETE-Cys), and hydroxyethylthioethylthioethyl cysteine conjugate (HETETE-Cys). The identity of the conjugates was elucidated using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). We also investigated changes in conjugate formation with exposure concentration and time elapsed after exposure in the cell culture. After exposure, GSH conjugates decreased until 1st hour, while Cys conjugates increased until 6th hour. We also observed that conjugate formation depended on the concentration of Q. This is the first study to elucidate the conjugates of Q dependent on GSH conjugation. As biomarkers are essential tools for evaluating exposure to Q, this study contributes to the limited number of studies identifying biomarkers for Q., (© 2024. The Author(s).)

Exposure to mustard gas can cause damage or death to human beings, depending on the concentration and duration. Thus, developing high-performance mustard-gas sensors is highly needed for early warning. Herein, ultrathin WO 3 nanosheet-supported Pd nanoparticles hybrids (WO 3 NSs/Pd) are prepared as chemiresistive sulfur mustard simulant (e.g., 2-chloroethyl ethyl sulfide, 2-CEES) gas sensors. As a result, the optimal WO 3 NSs/Pd-2 (2 wt % of Pd)-based sensor exhibits a high response of 8.5 and a rapid response/recovery time of 9/92 s toward 700 ppb 2-CEES at 260 °C. The detection limit could be as low as 15 ppb with a response of 1.4. Moreover, WO 3 NSs/Pd-2 shows good repeatability, 30-day operating stability, and good selectivity. In WO 3 NSs/Pd-2, ultrathin WO 3 NSs are rich in oxygen vacancies, offer more sites to adsorb oxygen species, and make their size close to or even within the thickness of the so-called electron depletion layer, thus inducing a large resistance change (response). Moreover, strong metal-support interactions (SMSIs) between WO 3 NSs and Pd nanoparticles enhance the catalytic redox reaction performance, thereby achieving a superior sensing performance toward 2-CEES. These findings in this work provide a new approach to optimize the sensing performance of a chemiresistive sensor by constructing SMSIs in ultrathin metal oxides.

Sulfur mustard (SM) is an important chemical warfare agent (CWA) and has been used frequently in various conflicts. It is important to develop a facile, rapid, sensitive and selective detection method for SM. In this work, we constructed a novel fluorescent probe PCS capable of generating active sensing species for rapid and selective detection of SM and its simulant CEES (2-chloroethyl ethyl sulfide). PCS exhibits excellent chemical and photostability and can generate reactive species in situ for rapid (within 90 s, at 60 °C) and selective detection of SM and CEES in solution with high sensitivity (∼nM level). Moreover, PCS could enable the detection of mustards in situ . A test strip with PCS and KOH was prepared and realized the sensitive and selective detection of CEES in the gas phase. In addition, the PCS probe can realize facile and rapid detection of CEES-contaminated surfaces by spraying its sensing system (ethanol solution containing PCS and KOH). The sensing mechanism was well demonstrated through the separation and characterization of the sensing product.

Transient receptor potential (TRP) channels are important in the sensing of pain and other stimuli. They may be triggered by electrophilic agonists after covalent modification of certain cysteine residues. Sulfur mustard (SM) is a banned chemical warfare agent and its reactivity is also based on an electrophilic intermediate. The activation of human TRP ankyrin 1 (hTRPA1) channels by SM has already been documented, however, the mechanism of action is not known in detail. The aim of this work was to purify hTRPA1 channel from overexpressing HEK293 cells for identification of SM-induced alkylation sites. To confirm hTRPA1 isolation, Western blot analysis was performed showing a characteristic double band at 125 kDa. Immunomagnetic separation was carried out using either an anti-His-tag or an anti-hTRPA1 antibody to isolate hTRPA1 from lysates of transfected HEK293 cells. The identity of the channel was confirmed by micro liquid chromatography-electrospray ionization high-resolution tandem-mass spectrometry. Following SM exposure, hTRPA1 channel modifications were found at Cys 462 and Cys 665 , as well as at Asp 339 and Glu 341 described herein for the first time. Since Cys 665 is a well-known target of hTRPA1 agonists and is involved in hTRPA1 activation, SM-induced modifications of cysteine, as well as aspartic acid and glutamic acid residues may play a role in hTRPA1 activation. Considering hTRPA1 as a target of other SM-related chemical warfare agents, analogous adducts may be predicted and identified applying the analytical approach described herein., (© 2022. The Author(s).)

The continuing threats of military conflicts and terrorism may involve the misuse of chemical weapons. The present study aims to use environmental samples to find evidence of the release of such agents at an incident scene. A novel approach was developed for identifying protein adducts in plants. Basil ( Ocimum basilicum ), bay laurel leaf ( Laurus nobilis ) and stinging nettle ( Urtica dioica ) were exposed to 2.5 to 150 mg m -3 sulfur mustard, 2.5 to 250 mg m -3 sarin, and 0.5 to 25 g m -3 chlorine gas. The vapors of the selected chemicals were generated under controlled conditions in a dedicated set-up. After sample preparation and digestion, the samples were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) and liquid chromatography high resolution tandem mass spectrometry (LC-HRMS/MS), respectively. In the case of chlorine exposure, it was found that 3-chloro- and 3,5-dichlorotyrosine adducts were formed. As a result of sarin exposure, the o -isopropyl methylphosphonic acid adduct to tyrosine could be analyzed, and after sulfur mustard exposure the N1- and N3-HETE-histidine adducts were identified. The lowest vapor exposure levels for which these plant adducts could be detected, were 2.5 mg m -3 for sarin, 50 mg m -3 for chlorine and 12.5 mg m -3 for sulfur mustard. Additionally, protein adducts following a liquid exposure of only 2 nmol Novichock A-234, 0.4 nmol sarin and 0.2 nmol sulfur mustard could still be observed. For both vapor and liquid exposure, the amount of adduct formed increased with the level of exposure. In all cases synthetic reference standards were used for unambiguous identification. The window of opportunity for investigation of agent exposure through the analysis of plant material was found to be remarkably long. Even three months after the actual exposure, the biomarkers could still be detected in the living plants, as well as in dried leaves. An important benefit of the current method is that a relatively simple and generic sample work-up procedure can be applied for all agents studied. In conclusion, the presented work clearly demonstrates the possibility of analyzing chemical warfare agent biomarkers in plants, which is useful for forensic reconstructions, including the investigation into alleged use in conflict areas.

The peroxide-based decontaminants had attracted great attention for degradation of chemical warfare agents (CWAs) because of their high performance, non-corrosive and environmental-friendly merits. Hydrogen peroxide can be activated by some organic activators to enhance the oxidation ability. In this work, a novel formula based on sodium percarbonate (SPC) complexed with 1-acetylguanidine (ACG) was investigated for decontamination of sulfur mustard (HD) and VX as CWAs. In the experimental results, the active species acetyl peroxide imide acid in the formula aqueous solution was detected in situ by Raman and 13 C NMR spectroscopy. The optimized conditions of the decontamination formula (SPC/ACG) were suggested that, the molar ratio of active oxygen and activator ([O]/[ACG]) was 1:1 while the pH value of the formula aqueous solution was about 9. To achieve the decontamination percentage over 99%, the molar ratio of active oxygen to CWA ((O)/(CWA)) needed to be at least 3 for HD and 7 for VX. Meanwhile, the degradation products detected by gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS) and ion chromatography (IC) indicated that the oxidation and elimination reactions should have occurred on HD molecule, while the degradation of VX mainly originate from the nucleophilic substitution and oxidation reactions.

Plasmonic nanostructures have attracted increasing interest in the fields of photochemistry and photocatalysis for their ability to enhance reactivity and tune reaction selectivity, a benefit of their strong interactions with light and their multiple energy decay mechanisms. Here we introduce the use of earth-abundant plasmonic aluminum nanoparticles as a promising renewable detoxifier of the sulfur mustard simulant 2-chloroethylethylsulfide through gas phase photodecomposition. Analysis of the decomposition products indicates that C-S bond breaking is facilitated under illumination, while C-Cl breaking and HCl elimination are favored under thermocatalytic (dark) conditions. This difference in reaction pathways illuminates the potential of plasmonic nanoparticles to tailor reaction selectivity toward less hazardous products in the detoxification of chemical warfare agents. Moreover, the photocatalytic activity of the Al nanoparticles can be regenerated almost completely after the reaction concludes through a simple surface treatment.

The rapid, discriminative, and portable detection of highly toxic chemical warfare agents is extremely important for response to public security emergencies but remains a challenge. One plausible solution involves the integration of porous molecular traps onto a photoelectrochemical (PEC) sensor. Here, a fast and facile protocol is developed to fabricate sub-1 nm AgNPs encapsulated hydrogen-bonded organic framework (HOF) nanocomposite materials through an in situ photoreduction and subsequent encapsulation process. Compared to traditional semiconductors and selected metal-organic frameworks (MOF) materials, these AgNPs@HOFs show significantly enhanced photocurrent. Most importantly, the portable PEC device based on AgNPs@HOF-101 can selectively recognize 13 different mustard gas simulants, including 2-chloroethyl ethyl sulfide (CEES), based on synergistic size-exclusion and specific recognition. The extremely low detection limit for CEES (15.8 nmol L -1 ), reusability (at least 30 cycles), and long-term working stability (at least 30 d) of the portable PEC device warrant its use as a chemical warfare agents (CWAs) sensor in practical field settings. More broadly, this work indicates that integrating porous molecular traps onto PEC sensors offers a promising strategy to further develop portable devices for CWAs detection with both ultrahigh sensitivity and selectivity., (© 2022 Wiley-VCH GmbH.)

In the recent past, the blister agent sulfur mustard (SM) deployed by the terroristic group Islamic State has caused a huge number of civilian and military casualties in armed conflicts in the Middle East. The vaporized or aerolized agent might be inhaled and have direct contact to skin and hair. Reaction products of SM with plasma proteins (adducts) represent well-established systemic targets for the bioanalytical verification of exposure. The SM-derived hydroxyethylthioethyl (HETE)-moiety is attached to nucleophilic amino acid side chains and allows unambiguous adduct detection. For shipping of common blood and plasma samples, extensive packaging rules are to be followed as these matrices are considered as potentially infectious material. In contrast, hair is considered as non-infectious thus making its handling and transportation much less complicated. Therefore, we addressed this matrix to develop a procedure for bioanalytical verification. Following optimized lysis of SM-treated human scalp hair and pepsin-catalyzed proteolysis of adducts of keratin type I and II, microbore liquid chromatography-electrospray ionization high-resolution tandem-mass spectrometry (µLC-ESI MS/HR MS) was used to detect three alkylated keratin-derived biomarker peptides: AE(-HETE)IRSDL, FKTIE(-HETE)EL, and LE(-HETE)TKLQF simultaneously. All bear the HETE-moiety bound to a glutamic acid residue. Protein adducts were stable for at least 14 weeks at ambient temperature and contact to air, and were not affected by washing the hair with shampoo. The biomarker peptides were also obtained from beard, armpit, abdominal, and pubic hair. This is the first report introducing stable local peptide adduct biomarkers from hair, that is easily accessible by a non-invasive sampling process., (© 2022. The Author(s).)

Background: The use and storage of chemical weapons in war was banned. However, chemical weapons continue to be used in wars. Therefore, in this study, we tried to identify the chemical agents used by defining the characteristics of chemical attacks., Method: We designed our study using the international dataset that can be accessed from www.start.umd.edu/gtd/. Chemical attacks between 1970 and 2020 were recorded in terms of decade, type of attack, success, suicidal purpose, property damage, number of deaths and injuries, and agents used., Results: A total of 347 attacks were reported. The highest number of attacks was 162 (46.7 percent), which occurred between 2010 and 2020. Among the chemical agents used, acidic substances (39, 11.2 percent), chlorine gas (32, 9.2 percent), and tearing agents (24, 6.9 percent) were found to be the most common. When the distribution of the five most common chemical agents by years was examined, it was found that the use of chlorine gas gradually increased in the last three decades. In the last decade, it was found that the use of mustard gas increased, whereas cyanide was not used., Conclusion: In the last decade, we found that chemical attacks have increased more, especially chlorine and mustard gas were predominantly used.

Sulfur mustard (SM, bis[2-chloroethyl]-sulfide) is a banned chemical warfare agent deployed in the violent conflict in the Middle East poisoning humans and animals. For legal reasons, bioanalytical methods are mandatory proving exposure to SM. Reaction products (adducts) of SM with endogenous proteins, for example, serum albumin (SA), are valuable long-lived targets for analysis. Whereas nearly all methods known so far focus on human proteins, we address for the first time neat chicken SA and avian serum from chicken, duck, and ostrich. After proteolysis, protein precipitation, evaporation of the supernatant, and re-dissolution analysis were performed by micro-liquid chromatography-electrospray ionization tandem-mass spectrometry in the selected reaction monitoring mode, μLC-ESI MS/MS (SRM), for detection of the hydroxyethylthioethyl product ion [HETE] + at m/z 105.0. After in vitro incubation with SM and pronase-catalyzed proteolysis, the alkylated amino acids Glu(-HETE) and His(-HETE) were detected. Both borne the SM-characteristic HETE-moiety bound to their side chain. The eightfold deuterated SM analog (d8-SM) was also applied to support adduct identification. Proteolysis conditions were optimized with respect to pH (8.0), temperature (50°C), and time to maximize the yield of Glu(-HETE) (30 min) and His(-HETE) (180 min). Amino acid adducts were stable in the autosampler for at least 24 h. Protein-adducts were stable in serum at -30°C for at least 33 days and for three freeze-and-thaw cycles. At the body temperature of chicken (+40°C), Glu(-HETE) was degraded in serum (period of half-change 3 days), whereas His(-HETE) remained stable. The presented method broadens the toolbox of procedures to document poisoning with SM., (© 2022 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

Background: Due to the increasing chemical and biological threats posed by terrorist attacks, there is a need to design and prepare nanofibers (NFs) with the ability to neutralize CWAs. For this purpose polyacrylonitrile NFs and polyoxomolybdate [Mo 154 ] (abbreviated as PAN NFs/[Mo 154 ]) as a heterogeneous catalyst was prepared by electrospinning method with a diameter of about 100nm., Objective: The PAN NFs/[Mo 154 ] catalyze the selective aerobic oxidation of sulfur mustard stimulants, such as 2-chloroethyl ethyl sulfide (2-CEES) and 2-chloroethyl phenyl sulfide (2-CEPS) under green and "ambient" conditions (25 °C, 1atm O 2 ) in the presence of ethanol with high efficiency and selectivity. 2-CEES was selected as a model reaction to optimize the parameters of the reaction., Methods: The progress of the reaction was evaluated after different times using GC-FID, GCMS and TLC. The reaction product was also confirmed by 1 H-NMR spectroscopy., Results: The aerobic oxidation results of 2-CEES showed that PAN NFs/[Mo 154 ] have a conversion of 98% to produce only a nontoxic product, 2-CEESO with the selectivity of 100% after 45min. The results were performed using [Mo 154 ] without any PAN NFs for comparison whereas [Mo 154 ] converts only 52% of 2-CEES under identical conditions., Conclusion: Heterogeneous PAN NFs/[Mo 154 ] catalyst was reused after washing with solvent up to 5 steps without leaching of [Mo 154 ] from PAN NFs and without any loss in efficiency due to the morphology of NFs. In addition to the recovery of PAN NFs/[Mo 154 ] in different cycles, the use of FT-IR, UV-Vis and TEM techniques confirms the stability and morphology of PAN NFs/[Mo 154 ] after the fifth cycle, 2-CEES oxidation. According to our information, this report is the first use of PAN NFs enriched with [Mo 154 ] for aerobic oxidation of sulfur mustard simulants., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Although great potential hazards and threats still occur from sulfur mustard, there are no specific medicine or therapy for the intoxication of sulfur mustard. Herein, we have demonstrated a supramolecular approach for the detoxification of the sulfur mustard simulant CEES ( 4 ) in vitro and in vivo by carboxylatopillar[5]arene potassium salts (CP[5]AK 1 ) efficiently based on host-guest interactions. The encapsulation of CEES ( 4 ) by the cavity of the pillar[5]arene 2 is driven by C-H···π interactions between CEES ( 4 ) and the electron-rich cavity of pillar[5]arene 2 , which was investigated by 1 H NMR titration, density functional theory studies, and the independent gradient model studies. CEES ( 4 ) is degradated to the reactive sulfonium salts quickly in aqueous media, resulting in the alkylation of DNA and proteins. The sulfonium salts can be encapsulated by CP[5]AK 1 efficiently, which accelerates the degradation of the sulfonium salts about 14 times. The cell and animal experiments indicated that the bioactivities of the sulfonium salts are inhibited with the formation of stable host-guest complexes, and CP[5]AK 1 has a good therapeutic effect on the damages caused by CEES ( 4 ) at either pre- or post-treatments. Due to the low cytotoxicity and good therapeutic effect, the anionic pillar[5]arenes are expected to be developed as specific antidotes against sulfur mustard (HD).

Sulfur mustard reacts with blood proteins, such as hemoglobin, to form stable adducts that can be used as long-lived biomarkers of exposure. These adducts can be analyzed by liquid chromatography coupled to tandem mass-spectrometry (LC-MS/MS) after an enzymatic digestion step. The objective of this study was to develop trypsin-based immobilized enzyme reactors (IMERs) in order to obtain a faster digestion of hemoglobin than the conventional in-solution digestion. Trypsin IMERs were synthetized by grafting the enzyme on a CNBr-Sepharose gel and the influence of several parameters on the digestion yields, such as the transfer volume between the injection loop and the IMER, the temperature and the digestion time was studied. The repeatability of the digestion on three laboratory-made IMERs was demonstrated for pure hemoglobin and hemoglobin previously exposed to different concentrations of sulfur mustard (RSD inferior to 13% and 21% respectively) and was better than that obtained for in-solution digestions (RSD inferior to 28% and up to 53% respectively). A preferential adduction of sulfur mustard on the histidine residues of hemoglobin was confirmed, for both in-solution and IMER digestion results. On a quantitative point of view, the performances of in-solution and IMER digestions were similar, with the theoretical possibility to detect peptides resulting from the in vitro incubation of hemoglobin in pure water with sulfur mustard at 7.5 ng⋅mL -1 . However, digestion on IMER proved to be more repeatable and 32 times faster than in-solution digestion, and a given IMER could be reused at least 60 times., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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 2 , as a chlorine carrier which can be easily coated on textile fibers. A chlorine bleaching converted the amine groups located on the MOF linker to active N-chlorine structures. The fibrous composite exhibited rapid biocidal activity against both Gram-negative bacteria ( E. coli ) and Gram-positive bacteria ( S. aureus ) with up to a 7 log reduction within 5 min for each strain as well as a 5 log reduction of SARS-CoV-2 within 15 min. Moreover, the active chlorine loaded MOF/fiber composite selectively and rapidly degraded sulfur mustard and its chemical simulant 2-chloroethyl ethyl sulfide (CEES) with half-lives less than 3 minutes. The versatile MOF-based fibrous composite designed here has the potential to serve as protective cloth against both biological and chemical threats.

Sulfur mustard (SM, bis[2-chloroethyl]-sulfide) is a banned chemical warfare agent that was frequently used in recent years and led to numerous poisoned victims who developed painful erythema and blisters. Post-exposure analysis of SM incorporation can be performed by the detection of human serum albumin (HSA)-derived peptides. HSA alkylated by SM contains a hydroxyethylthioethyl (HETE)-moiety bound to the cysteine residue C 34 yielding the dipeptide biomarker C(-HETE)P after pronase-catalyzed proteolysis. We herein present a novel procedure for the selective precolumn nicotinylation of its N-terminus using 1-nicotinoyloxy-succinimide. The reaction was carried out for 2 h at ambient temperature with a yield of 81%. The derivative NA-C(-HETE)P was analyzed by micro liquid chromatography-electrospray ionization tandem-mass spectrometry working in the selected reaction monitoring mode (μLC-ESI MS/MS SRM). The derivative was shown to be stable in the autosampler at 15°C for at least 24 h. The single protonated precursor ion (m/z 428.1) was subjected to collision-induced dissociation yielding product ions at m/z 116.1, m/z 137.0, and m/z 105.0 used for selective monitoring without any plasma-derived interferences. NA-C(-HETE)P showed a mass spectrometric response superior to the non-derivatized dipeptide thus yielding larger peak areas (factor 1.3 ± 0.2). The lower limit of identification corresponded to 80 nM SM spiked to plasma in vitro. The presented procedure was applied to real case plasma samples from 2015 collected in the Middle East confirming SM poisoning., (© 2021 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

The primary aim of this study was to identify biomarkers of exposure to some so-called Schedule 1 sulfur mustard (HD) analogues, in order to facilitate and expedite their retrospective analysis in case of alleged use of such compounds. Since these HD analogues can be regarded as model compounds for possible impurities of HD formed during synthesis processes, the secondary aim was to explore to which extent these biomarkers can be used for chemical provenancing of HD in case biomedical samples are available. While the use of chemical attribution signatures (CAS) for neat chemicals or for environmental samples has been addressed quite frequently, the use of CAS for investigating impurities in biomedical samples has been addressed only scarcely. Human plasma was exposed to each of the five HD analogues. After pronase or proteinase K digestion of precipitated protein and sample work-up, the histidine (His) and tripeptide (CPF) adducts to proteins were analyzed, respectively. Adducts of the analogues could still be unambiguously identified next to the main HD adducts in processed plasma samples after exposure to HD mixed with each of the analogues, at a 1% level relative to HD. In conclusion, we have identified plasma protein adducts of a number of HD analogues, which can be used as biomarkers to assess an exposure to these Schedule 1 chemicals. We have shown that adducts of these analogues can still be analyzed after work-up of plasma samples which had been exposed to these analogues in a mixture with HD, supporting the hypothesis that biomedical sample analysis might be useful for chemical provenancing.

Sulfur mustard is a highly reactive chemical warfare agent that causes severe damages to the victims exposed by alkylating multiple biomolecules such as proteins. Resulting alkylated products can be used as biomarkers of exposure to this chemical agent. A liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method was thus developed to detect alkylated peptides after the tryptic digestion of hemoglobin (50 mg.mL -1 ) incubated with sulfur mustard at different concentrations (0.25, 0.5, 1, 10 and 100 µg.mL -1 ). Five new alkylation sites were accurately identified on the protein (α-His 72 , α-His 87 , α-His 89 , β-His 2 and β-Val 98 ) and fifteen adducted peptides were detected, among which eight of them resulted from the alkylation of four peptides, each presenting two potential sites of adduction that could be discriminated by the method specificity. Similarly, it was possible to discriminate the three potential adduction sites of the peptide α-T9. Moreover, the method allowed the quantification of all the alkylated peptides with a satisfying repeatability, with RSD ranging from 0.5 to 9.3% for an exposure of hemoglobin to sulfur mustard at 100 µg.mL -1 . The analysis of hemoglobin incubated with different concentrations of sulfur mustard levels led to a linear response for all the alkylated peptides with the studied concentrations (0.25, 0.5, 1, 10 and 100 µg.mL -1 ). A variation of the alkylation rate was also observed between the different peptides studied, with a preferential adduction of sulfur mustard on the histidine residues but also on the N-terminal valine residues of both globin chains and on the Val 98 residue of globin β. Furthermore, the presented method proved to be sensitive, with a theoretical possibility to detect alkylated peptides resulting from in vitro incubation of hemoglobin in deionized water with sulfur mustard at 2.63 ng.mL -1 . After further development, this method could potentially be used for the analysis of blood samples in vivo exposed to sulfur mustard., (Copyright © 2020 Elsevier B.V. All rights reserved.)

At present, there is a real threat of chemical warfare agents being used in terrorist acts and military clashes. Sulfur and nitrogen mustards are blister agents with high lethality and rapid disruption of armed forces. These highly poisonous substances are hydrolyzed to the characteristic marker compounds when released into the environment. Analysis of environmental objects allows to establish the fact of alleged use of chemical warfare agents and to reveal their type. However, water and soil samples are not always reliable for retrospective analysis. The resulting chemical warfare agent markers may be washed out from the application site over time by groundwaters or atmospheric condensations. This study shows the potential for using plants as a convenient material for retrospective analysis. Garden cress (Lepidium sativum) was chosen as a model plant for this purpose, since it can be easily and quickly grown hydroponically. The plants were cultivated in the environment of the selected markers to study an accumulation of these compounds by the plants. An effective and fast method of homogenization with subsequent ultrasonic extraction was applied. The extracts were analyzed using a specially developed and validated HPLC-MS/MS approach. Separation of the hydrophilic markers was carried out on a reversed-phase column with a polar endcapping. Sensitive mass spectrometric detection was performed in the multiple reaction monitoring mode. Achieved limits of detection for most markers were in the range of 2-40 ng mL -1 . It was discovered from the research that after the removal of markers from the growing medium the plants are able to store and concentrate these markers for at least 5 weeks, ensuring a high retrospectivity of the analysis. The obtained results indicate the perspective of using plants as additional objects of analysis during the investigation of incidents related to the use of chemical warfare agents. However, more complex plants and models should be studied in the future., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Sulfur-(SM) and nitrogen (NM)-based mustards are the mutagenic incapacitating compounds which are widely used in vesicating the chemical warfare and cause toxicity in many organs, especially skin. SM, as a potent vesicating agent, contributes to the destruction of skin in dermis and epidermis layers. The progression of the lesion depends on the concentration of SM and the duration of exposure. Body responses start with pruritus, erythema, edema and xerosis, which lead to the accumulation of immune cells in the target sites and recruitment of mast cells and paracrine-mediated activity. Pro-inflammatory effectors are accumulated in the epidermis, hair follicles, and sebaceous glands resulting in the destruction of the basement membrane beneath the epidermis. There is still no satisfactory countermeasure against SM-induced lesions in clinical therapy, and the symptomatic or supportive treatments are routine management approaches., Objective: The current review highlights the recent progression of herbal medicines application in SM-induced injuries through the illustrative examples and also demonstrates their efficacies, properties and mechanism of actions as therapeutic agents., Conclusion: Phytochemicals and herbal extracts with anti-bacterial, anti-inflammatory and antioxidant properties have been recently shown to hold therapeutic promise against the SM-induced cutaneous complications. The present review discusses the possible application of herbal medicines in the healing of SM-induced injuries., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

While linkers with various conformations pose challenges in the design and prediction of metal-organic framework (MOF) structures, they ultimately provide great opportunities for the discovery of novel structures thereby enriching structural diversity. Tetratopic carboxylate linkers, for example, have been widely used in the formation of Zr-based MOFs due to the ability to target diverse topologies, providing a promising platform to explore their mechanisms of formation. However, it remains a challenge to control the resulting structures when considering the complex assembly of linkers with unpredicted conformations and diverse Zr 6 node connectivities. Herein, we systematically explore how solvents and modulators employed during synthesis influence the resulting topologies of Zr-MOFs, choosing H 4 TCPB-Br 2 (1,4-dibromo-2,3,5,6-tetrakis(4-carboxyphenyl)benzene) as a representative tetratopic carboxylate linker. By modulating the reaction conditions, the conformations of the linker and the connectivities of the Zr 6 node can be simultaneously tuned, resulting in four types of structures: a new topology (NU-500), she (NU-600), scu (NU-906), and csq (NU-1008). Importantly, we have synthesized the first 5-connected Zr 6 node to date with the (4,4,4,5)-connected framework, NU-500. We subsequently performed detailed structural analyses to uncover the relationship between the structures and topologies of these MOFs and demonstrated the crucial role that the flexible linker played to access varied structures by different degrees of linker deformation. Due to a variety of pore structures ranging from micropores to hierarchical micropores and mesopores, the resulting MOFs show drastically different behaviors for the adsorption of n -hexane and dynamic adsorption of 2-chloroethyl ethyl sulfide (CEES) under dry and humid conditions.

Due to the unpredictable nature of a battlefield environment, in the simultaneous degradation of sulfur mustard and nerve agents it is preferable to use just one decontaminant. Herein, the new composite HPVMo@MOF-808 (HPVMo = H 5 PV 2 Mo 10 O 40 ) was deliberately synthesized via a simple impregnation method and thoroughly characterized. The results showed that the decontamination rate of the composites (30-40 mg) with optimal HPVMo loadings for HD (4 μL) and GD (4 μL) under ambient conditions was 97.2% (within 120 min) and 90.8% (within 30 min), respectively. Due to the combinational/synergistic effect of MOF-808 and encapsulated homogeneously dispersed HPVMo, the composite can very efficiently oxidize HD to nontoxic products in a single system, while retaining the inherent excellence of MOF-808 in hydrolytically degrading GD. The decontamination process was found to follow first-order reaction kinetics, and the rate constant and half-life of the composite for HD and GD were 0.0231 min -1 , 30.13 min and 0.0795 min -1 , 8.72 min, respectively. In addition, experimental results in guinea pigs and Kunming mice used as animal models showed that the composite provided effective skin protection against HD and GD, showing great potential for application in skin decontamination and protection.

Human scalp hair is a biological matrix that can trap chemical vapours from explosives (TNT), drugs (THC) and chemical weapons (yperite). The external contamination of human's hair following exposure to organophosphorus (OP) nerve agent was simulated by model compounds: triethyl phosphate (TEP) and diisopropyl fluorophosphate (DFP). In this work were exposed strands of hair to vapours of TEP and DFP (3 and 7 ppm v ) to model sorption kinetics. Sorption isotherms were also investigated at several contamination levels (80-3000 mg min.m -3 ). OP nerve agent simulants were extracted from hair by soaking in DCM. Raw extracts were analysed in GC-MS/MS to quantify each simulant content in hair. Results were fitted by applying isotherm or kinetic equations. The best model was found to be bimodal first-order, suggesting the co-existence of two different mechanisms of sorption. The best equation to describe OP vapours incorporation on hair was Freundlich model. Thus hair can be used as a passive sensor able to trap chemical G-agents and can also offer valuable information regarding both individual contamination and proof of exposure to chemical weapons., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Bis(2-chloroethyl)ethylamine (HN-1) and Bis(2-chloroethyl)methylamine (HN-2) are two classifications under the blistering agents, which are taken as target nitrogen mustard gas in the current research. α-arsenene nanosheets in its puckered configuration, are employed as a prime material to detect the above mentioned gas molecules. The chemo-sensing nature of the base material towards the target gas is ascertained with the assistance of electronic and surface assimilating attributes with the help of density functional theory technique. Initially, the geometric firmness of the base material is ensured with formation energy, which was computed to be -4.262 eV/atom, and we studied the electronic properties like the density of states spectrum, band structure, and electron density. Furthermore, surface assimilating attributes like Bader charge transfer, adsorption energy, average energy gap variation are estimated at atomistic levels using ATK-VNL package. The adsorption of nitrogen mustard gas molecules on α-arsenene nanosheets shows physisorption type of binding. The average energy gap variation of α-arsenene nanosheets upon adsorption of nitrogen mustard gas molecules ranges from 1.33 to 4.1%. Hence, the results suggest that α-arsenene nanosheets can be used as a chemical nanosensor for nitrogen mustard gas., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Sulfur mustard is one of the most harmful chemical warfare agents and can induce skin, eye, and lung injuries. However, it is hard for medical stuff to diagnose sulfur mustard poisoning early because of the incubation period after sulfur mustard exposure. Detecting intact sulfur mustard in vivo might be an effective approach for the early diagnosis of sulfur mustard poisoning. A series of fluorescent probes for intact sulfur mustard detection were developed in this study. All of the developed probes could react with sulfur mustard selectivity. Among these probes, SiNIR-SM exhibited an extremely good response rate and a high off/on contrast. To the best of our knowledge, SiNIR-SM is the first near-infrared fluorescent probe for the sulfur mustard detection. Both SiNIR-SM and OxSM-1 were successfully applied to image sulfur mustard in living cells. Using SiNIR-SM, we found that sulfur mustard accumulates in the mitochondria of living cells. This result could provide a new insight for the treatment of sulfur mustard injuries. We also found that SiNIR-SM is suitable for the early diagnostic imaging of sulfur mustard poisoning in SKH-1 mice via the detection of intact sulfur mustard.

Nanohybrid membranes based on the Keggin-type polyoxometalate (POM) H 5 PV 2 Mo 10 O 40 and aminosilane-modified silicate (Ormosil and Ormosil(NR 4 + Cl - )) hybrids were synthesized as a new barrier to protect against simulants of chemical and biological toxicant. The 31 P NMR and XPS results indicated that POM was bound to the Ormosil and Ormosil(NR 4 + Cl - ) hybrids after impregnation. The antibacterial effects of the hybrids and hybrid-impregnated fabrics against Gram-negative and Gram-positive bacteria were investigated with zone of inhibition, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and plate-counting method. The MIC/MBC values of Ormosil(NR 4 + Cl - )/POM and Ormosil/POM against bacteria were 0.267/2.67 and 2.67/26.7, respectively, and the percentage reduction of bacteria was approximately 100% after 20 laundry cycles of their fabrics. The reaction products and mechanisms of the adsorptive degradation of 2-chloroethylethylsulfide (CEES) by hybrids were investigated with 13 C NMR. The results of this study showed that POM-doped Ormosil systems are capable of destroying bacteria and CEES., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A pyrene-containing salicylic acid derivative ( 4 ) was found to be low in fluorescence, but its derivative pyrene-containing methyl salicylate ( 3 ) was found to be highly fluorescent in aqueous solution. This derivative has been tested in solution and found to be superior in the fluorogenic assay of pharmaceutical compounds, detection of chemical warfare agents, a preliminary toxicology test, mutagenicity of medicinal compounds, and other chemical analyses, including trimethylsilyl diazomethane; alkyl bromides and iodides; a sulfur mustard mimic 2-chloroethyl ethyl sulfide; and anticancer drugs, busulfan and pipobroman. The salicylic acid derivative ( 4 ) was applied as a fluorogenic probe for the detection of alkylating agents by esterification and generating fluorescence at 475 nm in solutions at low concentrations.

We present the forensic analyses of plasma samples of human victims exposed to sulfur mustard (SM) in a crisis region in the Middle East in 2015. A few hours after exposure, poisoned persons showed typical signs and symptoms of percutaneous SM exposure including erythema and later on blisters and hardly healing skin wounds. Blood samples were collected 15 days after poisoning to be analyzed for the presence of long-lived protein-adduct biomarkers to verify SM poisoning. We applied a novel bioanalytical toolbox targeting four human serum albumin-derived biomarkers that were made accessible after plasma proteolysis. These adducts contained the SM-specific hydroxyethylthioethyl moiety either bound to the thiol group of a cysteine residue (C 34 *) or to the side-chain carboxylic group of a glutamic acid residue (E 230 *). Peptide biomarkers were produced from plasma of the victims using proteinase K (C 34 *PF), pronase (C 34 *P) and pepsin (AE 230 *VSKL and LQQC 34 *PFEDHVKL) for enzymatic protein cleavage. Separation and detection were carried out by selective micro-liquid chromatography-electrospray ionization high-resolution tandem mass spectrometry (µLC-ESI MS/HR MS). In addition to this site-specific adduct detection, a general approach after alkaline hydrolysis of the plasma protein fraction was applied. Liberated thiodiglycol (TDG) was derivatized with heptafluorobutyric anhydride and detected by gas chromatography-electron ionization mass spectrometry (GC-EI MS). The different bioanalytical methods yielded congruent results confirming SM poisoning for all patients who showed clinical signs and symptoms. This is the first time that real cases of SM poisoning were confirmed and presented by such a broad compilation of protein-derived biomarkers.

In this work, we fabricate two types of hierarchical microspheres, i.e., one coassembled from two fluorene-based oligomers (1 and 2) and one self-assembled from a fluorene-based oligomer (1), for ultrasensitive and selective detection of trace sulfur mustard (SM) vapor. On the basis of distinct fluorescence responses of 1-2 coassembled and individual 1 hierarchical microspheres that originate from differential noncovalent interactions between analytes and these sensors, SM vapor can be ultrasensitively detected (30 ppb) and easily discriminated from various sulfides and other potential interferents. Our work that utilizes differential noncovalent interactions to give sensitive and selective fluorescence response patterns represents a new detection approach for SM and other hazardous chemicals.

Herein, we demonstrate a nanocomposite material Eu/ZnO/pPy for enhanced performance in photoelectrocatalytic degradation of chemical warfare agent sulphur mustard (SM) at ambient conditions which is growing concern of the Scientific Community amidst the current climate of terrorism. Eu/ZnO/pPy was electrochemically prepared on Au electrode at ambient conditions and was used for electrocatalytic reductive elimination of chloride from SM and results indicated one electron involvement process for the cleavage of the carbon-chloride bond. Surface morphology of Eu/pPy, ZnO/pPy and Eu/ZnO/pPy composites were characterized by SEM and confirmed the formation of the nanoparticles and nanorods on the modified electrode which leads to provide more surface area for the reductive elimination reaction. The elemental composition, functional groups and phase of materials on the modified electrode were deduced using EDX, Raman spectroscopy and XRD, respectively. Eu/ZnO/pPy/Au electrode was utilized for the photoelectrocatalytic degradation of SM as it exhibit excellent electrocatalytic activity and degradation products were analyzed by GC-MS. In the reductive elimination of SM, the following parameters were deduced (i) heterogeneous rate constant (0.127 s -1 ), (ii) transfer coefficient (0.32) and (iii) number of electron involved (1.0). The enhanced photoelectrocatalytic capability of this nanocomposite could serve as a novel and promising catalyst in defence and environmental applications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Sulfur mustard (SM) is the most utilized chemical warfare agent in modern history and has caused more casualties than all other chemical weapons combined. SM still poses a threat to civilians globally because of existing stockpiles and ease of production. Exposure to SM causes irritation to the eyes and blistering of skin and respiratory tract. These clinical signs of exposure to SM can take 6-24 h to appear. Therefore, analyzing biomarkers of SM from biological specimens collected from suspected victims is necessary for diagnosis during this latent period. Here, we report a rapid, simple, and direct quantitative analytical method for an important and early SM biomarker, sulfur mustard oxide (SMO). The method includes addition of a stable isotope labeled internal standard, SMO extraction directly into dichloromethane (DCM), rapid drying and reconstitution of the extract, and direct analysis of SMO using gas chromatography-chemical ionization-mass spectrometry. The limit of detection of the method was 0.1 μM, with a linear range from 0.5 to 100 μM. Method selectivity, matrix effect, recovery, and short-term stability were also evaluated. Furthermore, the applicability of the method was tested by analyzing samples from inhalation exposure studies performed in swine. The method was able to detect SMO from 100% of the exposed swine (N = 9), with no interferences present in the plasma of the same swine prior to exposure. The method presented here is the first of its kind to allow for easy and rapid diagnosis of SM poisoning (sample analysis <15 min), especially important during the asymptomatic latency period., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The threat of chemical warfare agents (CWA) compels research into novel self-decontaminating materials (SDM) for the continued safety of first-responders, civilians, and active service personnel. The capacity to actively detoxify, as opposed to merely sequester, offending agents under typical environmental conditions defines the added value of SDMs in comparison to traditional adsorptive materials. Porous polymers, synthesized via the high internal phase emulsion (HIPE) templating, provide a facile fabrication method for materials with permeable open cellular structures that may serve in air filtration applications. PolyHIPEs comprising polydicyclopentadiene (polyDCPD) networks form stable hydroperoxide species following activation in air under ambient conditions. The hydroperoxide-containing polyDCPD materials react quickly with CWA simulants, Demeton-S and 2-chloroethyl ethyl sulfide, forming oxidation products as confirmed via gas chromatography mass spectrometry. The simplicity of the detoxification chemistry paired with the porous foam form factor presents an exciting opportunity for the development of self-decontaminating filter media., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this study, SPE method using a carbon aerogel(CA)-based sorbent was developed and evaluated for the simultaneous extraction of sulfur mustard (HD) degradation products from environmental water samples. Applied CAs proved to be very promising materials for use as SPE sorbents, due to their high porosity, very low density and a large specific surface area. 10 degradation products of HD, both aliphatic and cyclic (thiodiglycol (TDG), TDG sulfoxide, TDG sulfone, 3,5-dithia-1,7-heptanediol, 3,6-dithia-1,8-octanediol, 1,4-thioxane, 1,3-dithiolane, 1,4-dithiane, 1,2,5-trithiepane, and 1,4,5-oxadithiepane) were extracted on a CA-based SPE cartridge. The concentrations of target analytes in the eluate were determined by HPLC-DAD and CE-DAD. Several parameters affecting the extraction efficiency, including the kind and volume of the eluting solvent, sample loading flow rate, volume and ionic strength as well as the reusability of the cartridge, were investigated and optimized to achieve the best performance for the analytes. A series of quantitative parameters such as linear range, coefficient of determination, LOD, LOQ and precision were examined under the optimized conditions. High sensitivity (LODs 0.17-0.50 μM) and high precision (intraday RSD = 2.0-7.7% and interday RSD = 2.7-9.9%) for all the analytes were achieved. The performance of the CA-based sorbent was compared with that of commonly used SPE sorbents. Applied for the analysis of spiked pore water samples collected from the Bornholm Basin, one of the largest chemical warfare dumping sites in the Baltic Sea, the proposed method allowed high SPE recoveries of all the analytes ranging from 83.5 to 99.7% to be obtained., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The vesicant sulfur mustard (SM) is a banned chemical warfare agent. Although, SM has been used in combat since WWI, there is no causal therapy currently available. Accordingly, development and investigation of antidotes and scavengers targeting SM are of high clinical relevance. N-acetylcysteine (NAC) was shown to mitigate symptoms of SM intoxications in vitro and in vivo. However, it is still unclear whether the beneficial effects of NAC are only due to physiological processes or also due to chemical scavenging of SM. Therefore, in this study, we examined the scavenging potential of NAC toward SM. Co-incubations of SM and different NAC concentrations in human serum were performed to monitor diverse adducts (covalent reaction products) of human serum albumin (HSA), NAC, and SM. After proteolytic cleavage of HSA with proteinase K the alkylated tripeptide hydroxyethylthioethyl-CysProPhe (HETE-CPF) and the disulfide bridged tripeptide NAC-CPF were detected. Samples were analyzed by microbore liquid chromatography-electrospray ionization-high-resolution tandem-mass spectrometry (μLC-ESI MS/HR MS). Furthermore, degradation kinetics of SM in phosphate buffered saline were measured in the presence and absence of NAC. Although NAC-CPF was identified and characterized for the first time by mass spectrometry and reaction products of NAC and SM were detected and identified by MS/HR MS, analyses clearly documented minor reactivity not significantly contributing to reduction of SM concentrations. Therefore, we conclude that chemical scavenging of SM by NAC does not play the key role in NAC therapy of SM poisoning., (Copyright © 2017 John Wiley & Sons, Ltd.)

Chemical warfare agents have been used to incapacitate, injure or kill people, in a context of war or terrorist attack. It has previously been shown that hair could trap the sulphur mustard simulants methyl salicylate and 2-chloroethyl ethyl sulphide. In order to investigate simulants persistency in hair after intense vapour exposure, their desorption kinetics were studied by using two complementary methods: hair residual content measurement and desorbed vapour monitoring. Results showed that both simulants were detected in air and could be recovered from hair 2 h after the end of exposure. Longer experiments with methyl salicylate showed that it could still be recovered from hair after 24 h. Our data were fitted with several kinetic models and best correlation was obtained with a bimodal first-order equation, suggesting a 2-step desorption kinetics model: initial fast regime followed by a slower desorption. 2-chloroethyl ethyl sulphide was also detected in the immediate environment after hair exposure for 2 h, and hair simulant content decreased by more than 80%. Our results showed that hair ability to release formerly trapped chemical toxics could lead to health hazard. Their persistency however confirmed the potentiality of hair analysis as a tool for chemical exposure assessment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Divinyl sulfone (DVS) is an important oxidative metabolic product of sulfur mustard (SM) in vitro and in vivo. Although DVS is not a classical blister agent, its high reactivity and toxicity induced by vinyl groups can also cause blisters like SM upon contact with the skin, eyes, and respiratory organs. The purpose of this paper was to identify whether DVS could covalently bind to DNA bases to form new DNA adducts in cells in vitro. A series of adducts were synthesized and characterized using purine, nucleoside, or DNA, separately, as starting materials. The covalent site, pattern, and relative reactivity of adduct formation were identified and discussed in detail. The results showed that five high abundance site-specific DNA adducts, including two monoadducts and three cross-linked adducts, were obtained when DNA was used as a substrate. When HaCaT cells were exposed to 30 μM of DVS, four new DNA adducts containing monoadducts and cross-linked adducts were found and identified in cells, including N3-A monoadduct, N7-G monoadduct, N7G-N7G bis-adduct, and N3A-N7G cross-linked adduct. Among them, the abundance of N3-A monoadduct was 10 times higher than that of the other three adducts. DNA adduct formation with DVS showed significant differences from that observed with SM. The observation of these new DNA adduct in vitro cells revealed that DNA damage could be also induced by DVS.

The evaporation, degradation, and decontamination of sulfur mustard on environmental matrices including sand, concrete, and asphalt are described. A specially designed wind tunnel and thermal desorber in combination with gas chromatograph (GC) produced profiles of vapor concentration obtained from samples of the chemical agent deposited as a drop on the surfaces of the matrices. The matrices were exposed to the chemical agent at room temperature, and the degradation reactions were monitored and characterized. A vapor emission test was also performed after a decontamination process. The results showed that on sand, the drop of agent spread laterally while evaporating. On concrete, the drop of the agent was absorbed immediately into the matrix while spreading and evaporating. However, the asphalt surface conserved the agent and slowly released parts of the agent over an extended period of time. The degradation reactions of the agent followed pseudo first order behavior on the matrices. Trace amounts of the residual agent present at the surface were also released as vapor after decontamination, posing a threat to the exposed individual and environment.

The fast and effective neutralization of the mustard-gas simulant 2-chloroethyl ethyl sulfide (CEES) using a simple and portable continuous flow device is reported. Neutralization takes place through a fully selective sulfoxidation by a stable source of hydrogen peroxide (alcoholic solution of urea-H 2 O 2 adduct/MeSO 3 H freshly prepared). The reaction progress can be monitored with an in-line benchtop NMR spectrometer, allowing a real-time adjustment of reaction conditions. Inherent features of millireactors, that is, perfect control of mixing, heat and reaction time, allowed the neutralization of 25 g of pure CEES within 46 minutes in a 21.5 mL millireactor (t R =3.9 minutes). This device, which relies on affordable and nontoxic reagents, fits into a suitcase, and can be deployed by police/military forces directly on the attack site., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this study, novel, fast, and simple methods based on RP-HPLC and MEKC with DAD are developed and validated for the qualitative and quantitative determination of five cyclic sulfur mustard (HD) degradation products (1,4-thioxane, 1,3-dithiolane, 1,4-dithiane, 1,2,5-trithiepane, and 1,4,5-oxadithiepane) in water samples. The HPLC method employs a C18 column and an isocratic water-ACN (55:45, v/v) mobile phase. This method enables separation of all five cyclic compounds within 8 min. With the CE method, the baseline separation of five compounds was achieved in less than 11 min by applying a simple BGE composed of a 10 mM borate buffer and 90 mM SDS (pH 9.15). Both methods showed good linear correlation (R 2 > 0.9904). The detection limits were in the range of 0.08-0.1 μM for the HPLC method and 10-20 μM for MEKC. The precision tests resulted in RSDs for migration times and peak areas less than 0.9 and 5.5%, respectively, for the HPLC method, and less than 1.1 and 7.7% for the MEKC method, respectively. The developed methods were successfully applied to the analysis of five cyclic HD degradation products in water samples. With the HPLC method, the LODs were lowered using the SPE for sample purification and concentration., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Sulfur mustard (SM), a chemical warfare agent, causes DNA alkylation, which is believed to be the main cause of its toxicity. SM DNA adducts are commonly used to verify exposure to this vesicant. However, the required analytical state-of-the-art mass-spectrometry methods are complex, use delicate instruments, are not mobile, and require laboratory infrastructure that is most likely not available in conflict zones. Attempts have thus been made to develop rapid detection methods that can be used in the field. The analysis of SM DNA adducts (HETE-G) by immunodetection is a convenient and suitable method. For a diagnostic assessment, HETE-G levels must be determined in relation to the total DNA in the sample. Total DNA can be easily visualized by the use of fluorescent DNA dyes. This study examines whether SM and related compounds affect total DNA staining, an issue that has not been investigated before. After pure DNA was extracted from human keratinocytes (HaCaT cells), DNA was exposed to different S- and N-alkylating agents. Our experiments revealed a significant, dose-dependent decrease in the fluorescence signal of fluorescent dye-stained DNA after exposure to alkylating agents. After mass spectrometry and additional fluorescence measurements ruled out covalent modifications of ethidium bromide (EthBr) by SM, we assumed that DNA crosslinks caused DNA condensation and thereby impaired access of the fluorescent dyes to the DNA. DNA digestion by restriction enzymes restored fluorescence, a fact that strengthened our hypothesis. However, monofunctional agents, which are unable to crosslink DNA, also decreased the fluorescence signal. In subsequent experiments, we demonstrated that protons produced during DNA alkylation caused a pH decrease that was found responsible for the reduction in fluorescence. The use of an appropriate buffer system eliminated the adverse effect of alkylating agents on DNA staining with fluorescent dyes. An appropriate buffer system is thus crucial for DNA quantification with fluorescent dyes in the presence of alkylating compounds., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

After application of sulfur mustard to the soil surface, its possible fate via evaporation, degradation following absorption, and vapor emission after decontamination was studied. We used a laboratory-sized wind tunnel, thermal desorber, gas chromatograph-mass spectrometry (GC-MS), and 13 C nuclear magnetic resonance ( 13 C NMR) for systematic analysis. When a drop of neat HD was deposited on the soil surface, it evaporated slowly while being absorbed immediately into the matrix. The initial evaporation or drying rates of the HD drop were found to be power-dependent on temperature and initial drop volume. Moreover, drops of neat HD, ranging in size from 1 to 6 μL, applied to soil, evaporated at different rates, with the smaller drops evaporating relatively quicker. HD absorbed into soil remained for a month, degrading eventually to nontoxic thiodiglycol via hydrolysis through the formation of sulfonium ions. Finally, a vapor emission test was performed for HD contaminant after a decontamination process, the results of which suggest potential risk from the release of trace chemical quantities of HD into the environment., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Corneal injuries resulting from ocular exposure to sulfur mustard (SM) vapor are the most prevalent chemical warfare injury. Ocular exposures exhibit three distinct, dose-dependent clinical trajectories: complete injury resolution, immediate transition to a chronic injury, or apparent recovery followed by the subsequent development of persistent ocular manifestations. These latter two trajectories include a constellation of corneal symptoms that are collectively known as mustard gas keratopathy (MGK). The etiology of MGK is not understood. Here, we synthesize recent findings from in vivo rabbit SM vapor studies, suggesting that tissue-specific damage during the acute injury can decrement the regenerative capacities of corneal endothelium and limbal stem cells, thereby predisposing the cornea to the chronic or delayed forms of MGK. This hypothesis not only provides a mechanism to explain the acute and MGK injuries but also identifies novel therapeutic modalities to mitigate or eliminate the acute and long-term consequences of ocular exposure to SM vapor., (Published 2016. This article is a U.S. Government work and is in the public domain in the USA.)

Sulfur mustard (SM; bis-(2-chlororethyl) sulfide) is a highly reactive, potent warfare agent that has recently reemerged as a major threat to military and civilians. Exposure to SM is often fatal, primarily due to pulmonary injuries and complications caused by its inhalation. Profound inflammation, hypercoagulation, and oxidative stress are the hallmarks that define SM-induced pulmonary toxicities. Despite advances, effective therapies are still limited. This current review focuses on inflammatory and coagulation pathways that influence the airway pathophysiology of SM poisoning and highlights the complexity of developing an effective therapeutic target., (© 2016 New York Academy of Sciences.)

Exposure to the vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) causes severe skin injury with delayed blistering. Depending upon the dose and time of their exposure, edema and erythema develop into blisters, ulceration, necrosis, desquamation, and pigmentation changes, which persist weeks and even years after exposure. Research advances have generated data that have started to explain the probable mechanism of action of vesicant-induced skin toxicity; however, despite these advances, effective and targeted therapies are still deficient. This review highlights studies on two SM analogs, 2-chloroethyl ethyl sulfide (CEES) and NM, and CEES- and NM-induced skin injury mouse models that have substantially added to the knowledge on the complex pathways involved in mustard vesicating agent-induced skin injury. Furthermore, employing these mouse models, studies under the National Institutes of Health Countermeasures Against Chemical Threats program have identified the flavanone silibinin as a novel therapeutic intervention with the potential to be developed as an effective countermeasure against skin injury following exposure to mustard vesicating agents., (© 2016 New York Academy of Sciences.)

Sulfur mustard (SM) is a chemical warfare agent that causes painful blisters and chemically modifies endogenous biomacromolecules by alkylation to hydroxyethylthioethyl (HETE) adducts representing valuable long-term markers for post-exposure analysis. The albumin adduct formed in human plasma in vitro (HETE bound to the side chain of cysteine 34) was isolated and cleaved by current lots of pronase primarily generating the internal modified dipeptide (HETE-cysteine-proline, HETE-CP) instead of the formerly reported HETE-CPF tripeptide. The analyte was detected by liquid chromatography-electrospray ionization tandem-mass spectrometry (LC-ESI-MS-MS). In principle, HETE-CP undergoes a dynamic on-column equilibrium of cis-trans isomerism thus requiring separation at 50°C to obtain one narrow peak. Accordingly, we developed both a novel longer lasting but more sensitive microbore (1 mm i.d., flow 30 µL/min, cycle time 60 min, LOD 50 nM) and a faster, less sensitive narrowbore (2.1 mm i.d., 200 µL/min, cycle time 16 min, LOD 100 nM, both on Atlantis T3 material at 50°C) LC-ESI-MS-MS method suitable for verification analysis. The corresponding tri- and tetrapeptide, Q(HETE)-CPF were monitored simultaneously. HETE-CP peak areas were directly proportional to SM concentrations added to plasma in vitro (0.05-100 µM). Albumin adducts formed by deuterated SM (d8-SM) served as internal standard., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Sulfur mustard binds to reactive cysteine residues, forming a stable sulfur-hydroxyethylthioethyl [SHETE]adduct that can be used as a long-term biomarker of sulfur mustard exposure in humans. The digestion of sulfur mustard-exposed blood samples with proteinase K following total protein precipitation with acetone produces the tripeptide biomarker [S-HETE]-Cys-Pro-Phe. The adducted tripeptide is purified by solid phase extraction, separated by ultra high pressure liquid chromatography, and detected by isotope dilution tandem mass spectrometry. This approach was thoroughly validated and characterized in our laboratory. The average interday relative standard deviation was ≤ 9.49%, and the range of accuracy was between 96.1 and 109% over a concentration range of 3.00 to 250. ng/mL with a calculated limit of detection of1.74 ng/mL. A full 96-well plate can be processed and analyzed in 8 h, which is 5 times faster than our previous 96-well plate method and only requires 50 μL of serum, plasma, or whole blood. Extensive ruggedness and stability studies and matrix comparisons were conducted to create a robust, easily transferrable method. As a result, a simple and high-throughput method has been developed and validated for the quantitation of sulfur mustard blood protein adducts in low volume blood specimens which should be readily adaptable for quantifying human exposures to other alkylating agents.

A new isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of sulfur mustard (SM) has been developed using a direct chemical derivatization method by nucleophile potassium thioacetate (PTA) in aqueous solution. The reaction conditions for derivatization, such as reaction temperature, time, solvent and concentration of PTA, were optimized for high performance. Reversed phase liquid chromatography was suitable for analysis of such a PTA derivatized SM in complex environmental samples. Compared with other conventional gas chromatography or gas chromatography-mass spectrometry methods for direct detection on SM, better sensitivity and selectivity were achieved by this direct derivatization and LC-MS/MS method, where SM can be detected as low as 0.05 ng/mL in acetonitrile. The linear range was from 0.1 to 1000 ng/mL. The relative standard deviation (RSD) of the intra-day precision was less than 11.8%, and RSD of the inter-day precision was less than 12.3%. The whole procedure for both derivatization and analysis was quick and simple, and the total time was less than 1h. This established method has been successfully employed for determination of spiking samples both in water and soil. A detection limit of 0.1 ng/mL was achieved for river water, while the SM in soil sample could be detected at 0.1 ng/g., (Copyright © 2014 Elsevier B.V. All rights reserved.)