Electron ionization mass spectrometry fragmentation routes of Chemical Weapons Convention-related organoarsenic compounds: Electron ionization and density functional theory studies.

RATIONALE: For unambiguous identification of Chemical Weapons Convention (CWC)-related chemicals in environmental and biological samples, access to mass spectra and expertise in spectral interpretation is required. As of today, there is no mass spectrum available for dialkyl alkylarsonodithioites in the literature. Therefore, it is essential to obtain spectral information about these compounds. METHODS: CWC-related organoarsenic compounds were synthesized and analyzed by gas chromatography combined with mass spectrometry (MS), and their retention index (RI) was calculated by Van Den Dool's method. The relationship between RI and density functional theory (DFT)-calculated polarizability (⍺) and molecular weight was also studied. Electron ionization (EI) mode was used to investigate the general fragmentation patterns of the synthesized compounds. A DFT analysis of some major fragment ions was performed in order to confirm the fragmentation pathways. RESULTS: A linear relationship between RI and ⍺ is observed. The mass spectra of compounds 5-7 are affected by alkyl groups on sulfur and arsenic atoms. The molecular ions of compounds 5-7 can be observed in their EI-MS spectra with relatively good abundance. EI-MS studies revealed some interesting fragmentation pathways, such as the formation of arsenic analogue of benzylic and tropylium cations in EI-MS of chemicals 6. CONCLUSIONS: By analyzing the mass spectra and RI values, it is possible to detect CWC-related chemicals in aqueous, blood and urine samples during an on-site or off-site inspection.

Structural characterization of Chemical Weapons Convention-related phosphonoselenoates by electron ionization and electrospray ionization mass spectrometry.

RATIONALE: Organophosphorus compounds with phosphorus atom bonded to one methyl, ethyl or propyl (normal or iso) group are listed in Schedule 2 of the Chemical Weapons Convention (CWC). Selenophosphorus compounds, listed in Schedule 2.B.4, have very limited representation in mass spectral libraries and the open literature. METHODS: Members of a new category of selenophosphorus compounds were prepared via microsynthetic protocols and their fragmentation pathways were investigated using electron ionization (EI) and positive electrospray ionization (ESI) mass spectrometry. The EI and ESI fragmentation pathways were suggested and supported by acquired fragment ions of deuterated analogs and density functional theory calculations. RESULTS: Mass spectrometric investigations showed some interesting fragmentation pathways, such as McLafferty-type, selenono-selenolo rearrangements, intramolecular electrophilic aromatic substitution reaction and α-cleavage. CONCLUSIONS: Efficient microsynthesis was conducted, and EI-MS spectra and ESI-MS/MS spectra of a series of selenophosphorus compounds were collected and studied with the purpose of identifying CWC-related chemicals during on-site inspection and/or off-site analysis.

Novel 1,2,3-Triazole-Based Benzothiazole Derivatives: Efficient Synthesis, DFT, Molecular Docking, and ADMET Studies.

A new series of 1,2,3-triazole derivatives 5a-f based on benzothiazole were synthesized by the 1,3-dipolar cycloaddition reaction of S-propargyl mercaptobenzothiazole and α-halo ester/amide in moderate to good yields (47-75%). The structure of all products was characterized by 1H NMR, 13C NMR, and CHN elemental data. This protocol is easy and green and proceeds under mild and green reaction conditions with available starting materials. The structural and electronic analysis and 1H and 13C chemical shifts of the characterized structure of 5e were also calculated by applying the B3LYP/6-31 + G(d, p) level of density functional theory (DFT) method. In the final section, all the synthesized compounds were evaluated for their anti-inflammatory activity by biochemical COX-2 inhibition, antifungal inhibition with CYP51, anti-tuberculosis target protein ENR, DPRE1, pks13, and Thymidylate kinase by molecular docking studies. The ADMET analysis of the molecules 5a-f revealed that 5d and 5a are the most-promising drug-like molecules out of the six synthesized molecules.

Nitriles with High Gas-Phase Basicity-Part II Transmission of the Push-Pull Effect through Methylenecyclopropene and Cyclopropenimine Scaffolds Intercalated between Different Electron Donor(s) and the Cyano N-Protonation Site.

This work extends our earlier quantum chemical studies on the gas-phase basicity of very strong N-bases to two series of nitriles containing the methylenecyclopropene and cyclopropenimine scaffolds with dissymmetrical substitution by one or two electron-donating substituents such as Me, NR2, N=C (NR2)2, and N=P (NR2)3, the last three being strong donors. For a proper prediction of their gas-phase base properties, all potential isomeric phenomena and reasonable potential protonation sites are considered to avoid possible inconsistencies when evaluating the energetic parameters and associated protonation or deprotonation equilibria B + H+ = BH+. More than 250 new isomeric structures for neutral and protonated forms are analyzed. The stable structures are selected and the favored ones identified. The microscopic (kinetic) gas-phase basicity parameters (PA and GB) corresponding to N sites (cyano and imino in the cyclopropenimine or in the substituents) in each isomer are calculated. The macroscopic (thermodynamic) PAs and GBs, referring to the isomeric mixtures of favored isomers, are also estimated. The total (pushing) substituent effects are analyzed for monosubstituted and disubstituted derivatives containing two identical or two different substituents. Electron delocalization is examined in the two π-π conjugated transmitters, the methylenecyclopropene and cyclopropenimine scaffolds. The aromatic character of the three-membered ring is also discussed.

Synthesis and carbonic anhydrase I, II, VII, and IX inhibition studies with a series of benzo[d]thiazole-5- and 6-sulfonamides.

A series of benzo[d]thiazole-5- and 6-sulfonamides has been synthesized and investigated for the inhibition of several human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms, using ethoxzolamide (EZA) as lead molecule. 2-Amino-substituted, 2-acylamino- and halogenated (bromo-and iodo-derivatives at the heterocyclic ring) compounds led to several interesting inhibitors against the cytosolic hCA I, II and VII, as well as the transmembrane, tumor-associated hCA IX isoforms. Several subnanomolar/low nanomolar, isoform-selective sulfonamide inhibitors targeting hCA II, VII and IX were detected. The sharp structure-activity relationship for CA inhibition with this small series of derivatives, with important changes of activity observed even after minor changes in the scaffold or at the 2-amino moiety, make this class of scarcely investigated sulfonamides of particular interest for further investigations.

Fragmentation pathways and structural characterization of organophosphorus compounds related to the Chemical Weapons Convention by electron ionization and electrospray ionization tandem mass spectrometry.

RATIONALE: For unambiguous identification of Chemical Weapons Convention (CWC)-related chemicals in environmental samples, the availability of mass spectra, interpretation skills and rapid microsynthesis of suspected chemicals are essential requirements. For the first time, the electron ionization single quadrupole and electrospray ionization tandem mass spectra of a series of O-alkyl N-[bis(dimethylamino)methylidene]-P-methylphosphonamidates (Scheme 1, cpd 4) were studied for CWC verification purposes. METHODS: O-Alkyl N-[bis(dimethylamino)methylidene]-P-methylphosphonamidates were prepared through a microsynthetic method and were analyzed using electron ionization and electrospray ionization mass spectrometry with gas and liquid chromatography, respectively, as MS-inlet systems. General EI and ESI fragmentation pathways were proposed and discussed, and collision-induced dissociation studies of the protonated derivatives of these compounds were performed to confirm proposed fragment ion structures by analyzing mass spectra of deuterated analogs. RESULTS: Mass spectrometric studies revealed some interesting fragmentation pathways during the ionization process, such as McLafferty rearrangement, hydrogen rearrangement and a previously unknown intramolecular electrophilic aromatic substitution reaction. CONCLUSIONS: The EI and ESI fragmentation routes of the synthesized compounds 4 were investigated with the aim of detecting and identifying CWC-related chemicals during on-site inspection and/or off-site analysis and toxic chemical destruction monitoring. Copyright © 2016 John Wiley & Sons, Ltd.

Determination of lewisite metabolite 2-chlorovinylarsonous acid in urine by use of dispersive derivatization liquid-liquid microextraction followed by gas chromatography-mass spectrometry.

The purpose of this study was to develop a sensitive and simple method, based on dispersive derivatization liquid-liquid microextraction-gas chromatography-mass spectrometry (DDLLME-GC-MS) in scanning and selected-ion-monitoring (SIM) modes, for detection of 2-chlorovinylarsonous acid (CVAA) as a hydrolysis product and urinary metabolite of lewisite in urine samples. Chloroform (65 µL), methanol (500 µL), and ethanedithiol (10 µL) were used as extraction solvent, dispersive solvent, and derivatizing reagent, respectively. Critical conditions of the proposed method were optimized. The nucleophilic reactions of dithiol and monothiol compounds with CVAA were also studied using a competitive method. In view of the high affinity of trivalent arsenic for sulfhydryl groups, the interaction between CVAA and bis(2-chlorovinyl)arsonous acid (BCVAA) and free cysteine (Cys) was also investigated using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). The interference of Cys, present in human urine, with the detection of CVAA was evaluated using dithiol and monothiol chemicals as derivatization agents. The developed method provided a preconcentration factor of 250, and limits of detection of 0.015 and 0.30 µg L(-1) in SIM and scanning modes, respectively. The calibration curves were linear over the concentration range of 1-400 µg L(-1) in full-scan mode. The relative standard deviation (RSD) values were calculated to be 5.5 and 3.2% at concentrations of 20 and 100 µg L(-1), respectively. Collision-induced dissociation studies of the major electron-impact (EI) ions were performed to confirm the proposed fragment structure of CVAA-dithiols derivatives. Results indicated that the developed method for analysis of CVAA is suitable not only for verification of human exposure to lewisite, but also for quantification of CVAA in urine samples.

WITHDRAWN: Green Synthesis and Evaluation of the Biological Activity of New Dihydropyridine Derivatives

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn from the journal Combinatorial Chemistry & High Throughput Screening.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

De novo antioxidant peptide design via machine learning and DFT studies.

Antioxidant peptides (AOPs) are highly valued in food and pharmaceutical industries due to their significant role in human function. This study introduces a novel approach to identifying robust AOPs using a deep generative model based on sequence representation. Through filtration with a deep-learning classification model and subsequent clustering via the Butina cluster algorithm, twelve peptides (GP1-GP12) with potential antioxidant capacity were predicted. Density functional theory (DFT) calculations guided the selection of six peptides for synthesis and biological experiments. Molecular orbital representations revealed that the HOMO for these peptides is primarily localized on the indole segment, underscoring its pivotal role in antioxidant activity. All six synthesized peptides exhibited antioxidant activity in the DPPH assay, while the hydroxyl radical test showed suboptimal results. A hemolysis assay confirmed the non-hemolytic nature of the generated peptides. Additionally, an in silico investigation explored the potential inhibitory interaction between the peptides and the Keap1 protein. Analysis revealed that ligands GP3, GP4, and GP12 induced significant structural changes in proteins, affecting their stability and flexibility. These findings highlight the capability of machine learning approaches in generating novel antioxidant peptides.

Fragmentation pathways of O-alkyl methylphosphonothionocyanidates in the gas phase: toward unambiguous structural characterization of chemicals in the Chemical Weapons Convention framework.

The electron-impact (EI) mass spectra of a series of O-alkyl methylphosphonothionocyanidates were studied for Chemical Weapons Convention (CWC) purposes. General EI fragmentation pathways were constructed and discussed, and collision-induced dissociation studies of the major EI ions were performed to confirm proposed fragment structures by analyzing fragment ions of deuterated analogs and by use of density functional theory (DFT) calculations. Thiono-thiolo rearrangement, McLafferty-type rearrangement, and a previously unknown intramolecular electrophilic aromatic substitution reaction were observed and confirmed. The study also focused on differentiation of isomeric compounds. Retention indices for all compounds, and an electrophilicity index for several compounds, are reported and interpreted.

Gas chromatography-mass spectrometric studies of O-alkyl O-2-(N,N-dialkylamino) ethyl alkylphosphonites(phosphonates) for chemical weapons convention verification.

The electron ionization (EI) mass spectra of a series of O-alkyl O-2-(N,N-dialkylaminolethyl alkylphosphonites(phosphonates), which are precursors of nerve agents, were studied for Chemical Weapons Convention (CWC) verification. General El fragmentation pathways were constructed and discussed. Proposed fragment structures were confirmed through analyzing fragment ions of deuterated analogs and density functional theory (DFT) calculations. The observed fragment ions are due to different fragmentation pathways such as hydrogen and McLafferty+1 rearrangements, alkene, amine and alkoxy elimination by alpha- or beta-cleavage process. Fragment ions distinctly allow unequivocal identification of the interested compounds including those of isomeric compounds. The presence and abundance of fragment ions were found to depend on the size and structure of the alkyl group attached to nitrogen, phosphorus and oxygen atoms.

Magnet-responsive choline carbomer ionogels as a versatile and recyclable catalyst for one-pot synthesis of benzopyran in water.

Ionogels are gaining popularity as a potential replacement for volatile organic solvents in various processes, such as catalysts, electrochemistry, spectroscopy, and medicinal chemistry, due to their low toxicity, high thermal stability, and good solubility. Magnet-responsive ion gels with high magnetic susceptibility are promising and can be used as catalysts, sensors, and MRI contrast agents. Herein, we fabricated simple and novel magnet choline carbomer ionogels using a precipitation-deposition method with carbomers and choline hydroxide. The morphology and structure of the resulting ionogels were analyzed using various characterization techniques, including FTIR, EDX, TGA, and SEM spectroscopy. These magnet ionogels were effective catalysts for a one-pot, three-component synthesis of benzopyran derivatives, providing mild reaction conditions, environmental friendliness, and good to excellent (78-96%) yields within a short reaction time (1-2 h). Additionally, the magnet ionogels were easily recyclable, and they could be reused up to five times without catalytic deactivation.

Design and optimization various formulations of PEGylated niosomal nanoparticles loaded with phytochemical agents: potential anti-cancer effects against human lung cancer cells.

BACKGROUND: Phytochemicals and their derivatives are good options to improve treatment efficiency in cancer patients. Artemisinin (ART) and metformin (MET) are widely used phytochemicals to treat various types of cancers. However, their application because of their dose-dependent side effects, and poor bioavailability brings several challenges. Niosome is a novel nanocarrier that is the best choice to encapsulate both lipophilic and hydrophilic drugs. In this study, we synthesized and characterized various formulations of PEGylated (polyethylene glycol) niosomal nanoparticles co-loaded with ART-MET and evaluated their anticancer effect on A549 lung cancer cells. METHODS: Various formulations of PEGylated noisome were prepared by the thin-film hydration method and characterized in size, morphology, release pattern, and physicochemical structure. The cytotoxic effect of the free ART-MET and optimized PEGylated niosomal nanoparticles loaded with ART-MET on A549 cells were evaluated by MTT assay. Furthermore, the Real-time PCR (RT-PCR) technique used to evaluate apoptotic and anti-apoptotic gene expression. RESULTS: The size, encapsulation efficiency (EE), and polydispersity index (PDI) of the optimized nanoparticles are 256 nm, 95%, and 0.202, respectively. Additionally, due to the PEGylation hydrophilic character, there is a major consideration of the high impact of PEGylation on reducing niosome size. According to the results of the MTT assay, free ART-MET and ART-MET-loaded niosomal nanoparticles showed dose-dependent toxicity and inhibits the growth of A549 lung cancer cells. Furthermore, the RT-PCR results indicated that ART-MET-loaded niosomal nanoparticles have a higher anti-proliferative effect by inhibiting anti-apoptotic and inducing apoptotic gene expression in A549 lung cancer cells. CONCLUSIONS: Our study revealed that the simultaneous use of ART and MET in the optimized PEGylated niosomal nanoparticles delivery system could be an appropriate approach to improve the effectiveness of lung cancer treatment.

Novel edaravone-based azo dyes: efficient synthesis, characterization, antibacterial activity, DFT calculations and comprehensive investigation of the solvent effect on the absorption spectra.

The present study deals with designing and synthesizing novel dyes using the drug combination of edaravone and azo compounds which can be used as an indicator for anions and cations. The desired product synthesis was accomplished via a two-step process involving diazotizing the aromatic amines followed by the resultant salts coupling with edaravone. The resulting dyes were obtained with high yields under mild conditions. The structures of the dyes were identified with UV-vis, FT-IR, 1H NMR and 13C NMR spectra and CHN analysis. To investigate the solvatochromism effect, the interaction of different solvents with the selected dyes was evaluated using several parameters including the dielectric constant, refractive index, hydrogen bond donating ability, hydrogen bond accepting ability and dipolarity/polarizability scale. To achieve deep understanding about the stability and geometrical characteristics of the azo-hydrazo tautomers of the synthesized dyes and their UV-visible spectra prediction, some DFT calculations were also carried out on the synthesized dyes. The antibacterial activities of some synthesized compounds were also evaluated using the disk diffusion method. The results revealed different activity of the selected synthesized dyes for antibacterial tests against selected Gram positive and Gram negative bacteria.

Anion recognition by urea metal-organic frameworks: remarkable sensitivity for arsenate and fluoride ions.

Functionalized metal-organic frameworks (F-MOFs) are known as a promising chemical sensors since they have specific merits like fixed functionalized ligands projecting into the pores which can be utilized to enhance sensitivity and selectivity. Due to the important role of anions in biological process and environmental systems, there is an increasing interest in synthesis and design of new receptors for anions. Urea groups can operate as a hydrogen bond donating site with hydrogen bond acceptor molecules. Strong and directional hydrogen-bonding between the positive urea groups and anions could reduce vibrational quenching and enhance the fluorescence intensity. In this study, two luminescent porous urea decorated MOFs have been successfully assembled and structurally characterized. Luminescence studies of these MOFs toward anions revealed that these F-MOFs exhibit high sensitivity and selectivity toward H2AsO4- and F- anions as two major ground water pollutants. Moreover, the proposed materials have been applied for the removal of arsenate and nitrate in contaminant well water samples. Graphical abstract.

Preparation and characterization of polycaprolactone nanocapsules containing pretilachlor as a herbicide nanocarrier.

Polycaprolactone nanocapsules (PCL) containing pretilachlor were prepared, and Fourier transform infrared spectroscopy, atomic force microscopy, and transmission electron microscopy were used for their structural and morphological investigations. The results revealed that the nanocapsules had irregular shape and their particles size was in the range of 70-200 nm. The encapsulation efficiency of pretilachlor was measured as 99.5 ± 1.3% using high-performance liquid chromatography analysis. The physicochemical stability studies over 60 days showed that the nanocapsules were stable in the suspension without any aggregation. The herbicide activity was examined in a pre-emergence manner using barnyard grass as a target plant and rice as a non-target plant. The nanoformulation had no negative effect on rice plant. However, its effect on barnyard grass was significant. The cytotoxicity analysis indicated that the nanocapsulated herbicide is less toxic rather than the commercial formulation. Therefore, encapsulation of pretilachlor in PCL nanocapsules can be used effectively to construct environmentally friendly PCL-herbicide systems in agriculture.

Immobilized copper nanoparticles on nitrogen-rich porous activated carbon from egg white biomass: a robust hydrophilic-hydrophobic balance catalyst for click reaction.

Biomass conversion to carbonaceous materials and their use in various applications, such as capacitors, catalyst supports, and adsorbents, have attracted considerable attention from the viewpoint of green chemistry. In this regard, chicken egg white is one of the most important biomass, which can act as an in situ nitrogen doping source. In this paper, nitrogen-rich porous carbon material was synthesized from egg white biomass via pyrolysis at 600 °C under nitrogen atmosphere, followed by chemical activation with KOH at 500 °C. The results showed that the as-synthesized porous carbon material has a high content of nitrogen and high surface area, on which nitrogen can tune the surface hydrophobicity-hydrophilicity through interaction with water molecules. Then, the copper nanoparticles were immobilized on the surface of nitrogen-rich activated carbon by a chemical reduction method. Nanocatalyst structure was characterized by elemental analysis, TEM, AFM, Raman, FT-IR, porosimetry and atomic adsorption techniques. Finally, catalytic activity was evaluated for the one-pot synthesis of triazole in aqueous medium. The nanocatalyst offers some advantages such as excellent activity, low loading of catalyst, good yields of products and short reaction times.

Investigation of sarin(Se) reactivity against human plasma proteins using liquid chromatography-tandem mass spectrometry.

Electron ionization mass spectrum of sarin(Se) was interpreted in compare of sarin MS spectrum. Inhibition of butyrylcholinesterase of human plasma by sarin and sarin(Se) was determined spectrophotometrically using modified Ellman method. It appeared that after incubation with sarin and sarin(Se), cholinesterase inhibition were 93% and 83%, respectively. Sarin, sarin(Se), and sarin(Se)-d7 were spiked into a vial containing human plasma, and albumin adduct metabolites were identified using liquid chromatography-tandem mass spectrometry. The experiments show that these agents are attached to tyrosine on albumin in human blood. Corresponding deuterated adducts were used to confirm the proposed mechanisms for the formation of the fragments in mass spectrometry experiments.

Characterization of isomeric VX nerve agent adducts on albumin in human plasma using liquid chromatography-tandem mass spectrometry.

This study includes the characterization of isomeric VX organophosphorus adducts on albumin in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). VX or its structural isomers were spiked into a vial containing plasma in order to obtain phosphorylated albumin. After pronase and trypsin digestion, the resulting solutions were analyzed to confirm adduct formation with the amino acid tyrosine on the albumin in human plasma. The LC-MS/MS experiments show that VX and its isomers can be attached to tyrosine on the albumin in human blood. Mass spectrometric studies revealed some interesting fragmentation pathways during the ionization process, such as ethylene, formic acid and ammonia elimination and an intermolecular electrophilic aromatic substitution reaction. The proposed mechanisms for the formation of the fragments were confirmed through the analysis of fragments of deuterated adducts.