DFT-Spectroscopy Integrated Identification Method on Unknown Terrorist Chemical Mixtures by Incorporating Experimental and Theoretical GC-MS, NMR, IR, and DFT-NMR/IR Data.

In the event of a chemical attack, the rapid identification of unknown chemical agents is critical for an effective emergency response and treatment of victims. However, identifying unknown compounds is difficult, particularly when relying on traditional methods such as gas and liquid chromatography-mass spectrometry (GC-MS, LC-MS). In this study, we developed a density functional theory and spectroscopy integrated identification method (D-SIIM) for the possible detection of unknown or unidentified terrorist materials, specifically chemical warfare agents (CWAs). The D-SIIM uses a combination of GC-MS, nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, and quantum chemical calculation-based NMR/IR predictions to identify potential CWA candidates based on their chemical signatures. Using D-SIIM, we successfully verified the presence of blister and nerve agent simulants in samples by excluding other compounds (ethyl propyl sulfide and methylphosphonic acid), which were predicted to be candidates with high probability by GC-MS. The findings of this study demonstrate that the D-SIIM can detect substances that are likely present in CWA mixtures and can be used to identify unknown terrorist chemicals.

Melittin-Phospholipase A2 Synergism Is Mediated by Liquid-Liquid Miscibility Phase Transition in Giant Unilamellar Vesicles.

The primary constituents of honeybee venom, melittin and phospholipase A2 (PLA2), display toxin synergism in which the PLA2 activity is significantly enhanced by the presence of melittin. It has been shown previously that this is accomplished by the disruption in lipid packing, which allows PLA2 to become processive on the membrane surface. In this work, we show that melittin is capable of driving miscibility phase transition in giant unilamellar vesicles (GUVs) and that it raises the miscibility transition temperature (Tmisc) in a concentration-dependent manner. The induced phase separation enhances the processivity of PLA2, particularly at its boundaries, where a substantial difference in domain thickness creates a membrane discontinuity. The catalytic action of PLA2, in response, induces changes in the membrane, rendering it more conducive to melittin binding. This, in turn, facilitates further lipid phase separation and eventual vesicle lysis. Overall, our results show that melittin has powerful membrane-altering capabilities that activate PLA2 in various membrane contexts. More broadly, they exemplify how this biochemical system actively modulates and capitalizes on the spatial distribution of membrane lipids to efficiently achieve its objectives.

Effect of substituting donors on the hole mobility of hole transporting materials in perovskite solar cells: a DFT study.

Several hole-transporting materials (HTMs) have been designed by incorporating different types of π-conjugation group such as long chain aliphatic alkenes and condensed aromatic rings of benzene and thiophene and their derivatives on both sides between the planar core and donor of a reference HTM. Various electronic, optical, and dynamic properties have been calculated by using DFT, TDDFT, and Marcus theory. In this study, all the designed HTMs show a lower HOMO energy level and match well with the perovskite absorbers. Inserting condensed rings results in better hole mobility compared to aliphatic double bonds. It is found that the charge transfer integral is the dominant factor which mainly influences the hole mobility in our studied HTMs. Other factors such as hole reorganization energy, hole hopping rate, and centroid distance have a minor effect on hole mobility. Thus, this study is expected to provide guidance for the design and synthesis of new HTMs with increased hole mobility.

Real-Time Reaction Monitoring with In Operando Flow NMR and FTIR Spectroscopy: Reaction Mechanism of Benzoxazole Synthesis.

In operando observation of reaction intermediates is crucial for unraveling reaction mechanisms. To address the sensitivity limitations of commercial ReactIR, a flow cell was integrated with a Fourier transform infrared (FTIR) spectrometer yielding a "flow FTIR" device coupled with an NMR spectrometer for the elucidation of reaction mechanisms. The former device detects the low-intensity IR peaks of reaction intermediates by adjusting the path length of the FTIR sample cell, whereas the flow NMR allows the quantitative analysis of reaction species, thus offsetting the limitations of IR spectroscopy resulting from different absorption coefficients of the normal modes. Using the flow NMR and FTIR device, the controversial mechanism of benzoxazole synthesis was conclusively determined by spectroscopic evaluation of the reaction intermediates. This system enabled the accurate acquisition of previously elusive kinetic data, such as the reaction time and rate-determining step. The implementation of reaction flow cells into NMR and FTIR systems could be widely applied to study various reaction mechanisms, including dangerous and harsh reactions, thus avoiding contact with potentially harmful reaction intermediates.

Correction: Analysis of 1-aminoisoquinoline using the signal amplification by reversible exchange hyperpolarization technique.

Correction for 'Analysis of 1-aminoisoquinoline using the signal amplification by reversible exchange hyperpolarization technique' by Hye Jin Jeong et al., Analyst, 2020, 145, 6478-6484. DOI: .

Optimization of signal amplification by reversible exchange for polarization of tridentate chelating bis[(2-pyridyl)alkyl]amine.

Signal amplification by reversible exchange (SABRE) is an effective NMR hyperpolarization technique for signal enhancement using para-hydrogen on iridium catalysts. To date, monodentate chelating nitrogen analogs have been predominantly used as substrates for SABRE because of the limited chelating sites of the Ir-catalyst with different molecular orientations. Herein, for the first time, the use of a tridentate chelating ligand (BPEA) containing pyridine moieties and a secondary amine as a SABRE substrate is demonstrated. For the optimization of the tridentate chelating ligand, alkyl chain lengths were varied with the optimization of the external magnetic field and concentrations of three different ligands. Because many chemically multidentate complexes present in nature have scarcely been studied as SABRE substrates, this optimized tridentate chelating ligand structure with the SABRE catalyst and its polarization transfer from para-hydrogen will broaden the scope of hyperpolarizable substrates and help in the investigation of chelating structures for future applications.

Organic Reaction Monitoring of a Glycine Derivative Using Signal Amplification by Reversible Exchange-Hyperpolarized Benchtop Nuclear Magnetic Resonance Spectroscopy.

Currently, signal amplification by reversible exchange (SABRE) using para-hydrogen is an attractive method of hyperpolarization for overcoming the sensitivity problems of nuclear magnetic resonance (NMR) spectroscopy. Additionally, SABRE, using the spin order of para-hydrogen, can be applied in reaction monitoring processes for organic chemistry reactions where a small amount of reactant exists. The organic reaction monitoring system created by integrating SABRE and benchtop NMR is the ideal combination for monitoring a reaction and identifying the small amounts of materials in the middle of the reaction. We used a laboratory-built setup, prepared materials by synthesis, and showed that the products obtained by esterification of glycine were also active in SABRE. The products, which were synthesized esterified glycine with nicotinoyl chloride hydrochloride, were observed with a reaction monitoring system. The maximum SABRE enhancement among them (approximately 147-fold) validated the use of this method. This study is the first example of the monitoring of this organic reaction by SABRE and benchtop NMR. It will open new possibilities for applying this system to many other organic reactions and also provide more fruitful future applications such as drug discovery and mechanism study.

Analysis of 1-aminoisoquinoline using the signal amplification by reversible exchange hyperpolarization technique.

Signal amplification by reversible exchange (SABRE), a parahydrogen-based hyperpolarization technique, is valuable in detecting low concentrations of chemical compounds, which facilitates the understanding of their functions at the molecular level as well as their applicability in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). SABRE of 1-aminoisoquinoline (1-AIQ) is significant because isoquinoline derivatives are the fundamental structures in compounds with notable biological activity and are basic organic building blocks. Through this study, we explain how SABRE is applied to hyperpolarize 1-AIQ for diverse solvent systems such as deuterated and non-deuterated solvents. We observed the amplification of individual protons of 1-AIQ at various magnetic fields. Further, we describe the polarization transfer mechanism of 1-AIQ compared to pyridine using density functional theory (DFT) calculations. This hyperpolarization technique, including the polarization transfer mechanism investigation on 1-AIQ, will provide a firm basis for the future application of the hyperpolarization study on various bio-friendly materials.

Hyperpolarization of Nitrile Compounds Using Signal Amplification by Reversible Exchange.

Signal Amplification by Reversible Exchange (SABRE), a hyperpolarization technique, has been harnessed as a powerful tool to achieve useful hyperpolarized materials by polarization transfer from parahydrogen. In this study, we systemically applied SABRE to a series of nitrile compounds, which have been rarely investigated. By performing SABRE in various magnetic fields and concentrations on nitrile compounds, we unveiled its hyperpolarization properties to maximize the spin polarization and its transfer to the next spins. Through this sequential study, we obtained a ~130-fold enhancement for several nitrile compounds, which is the highest number ever reported for the nitrile compounds. Our study revealed that the spin polarization on hydrogens decreases with longer distances from the nitrile group, and its maximum polarization is found to be approximately 70 G with 5 µL of substrates in all structures. Interestingly, more branched structures in the ligand showed less effective polarization transfer mechanisms than the structural isomers of butyronitrile and isobutyronitrile. These first systematic SABRE studies on a series of nitrile compounds will provide new opportunities for further research on the hyperpolarization of various useful nitrile materials.

Detecting low concentrations of unsaturated C-C bonds by parahydrogen-induced polarization using an efficient home-built parahydrogen generator.

Parahydrogen is a potentially significant source of hyperpolarization. However, a heat exchanger at an ultralow temperature, which is normally sustained wastefully using liquid nitrogen, is essential for the generation of hyperpolarized parahydrogen. In order to cut down on the use of liquid nitrogen, we employed a cryogenic storage dewar as the key component of our home-built parahydrogen generator, which lasted over 20 days with a single filling. Small concentrations of an unsaturated compound in a mixture were identified by hydrogenation in a principle-based experiment involving the use of hyperpolarization and phase difference. Less than 1 µl of styrene in 1 ml of chloroform was identified in a single scan with a 43 MHz benchtop nuclear magnetic resonance (NMR) spectrometer following hydrogenation with 50% parahydrogen. This method can potentially undergo a significant development through the use of high-field NMR techniques, higher parahydrogen concentrations, and increased scan times for data collection, among others. Because hydrogenation with parahydrogen induces a phase reversal during attachment to unsaturated CC bonds, it may be possible to detect many other unsaturated bonds in organic molecules. All in all, this study not only broadens the research on parahydrogen-based unsaturated-bond detection, but also facilitates the use of hyperpolarization by a broader range of researchers through the introduction of a long-lasting home-built parahydrogen generator.

Real-Time Reaction Monitoring of Azide-Alkyne Cycloadditions Using Benchtop NMR-Based Signal Amplification by Reversible Exchange (SABRE).

Rufinamide, possessing a triazole ring, is a new antiepileptic drug (AED) relatively well-absorbed in the lower dose range (10 mg/kg per day) and is currently being used in antiepileptic medications. Triazole derivatives can interact with various enzymes and receptors in biological systems via diverse non-covalent interactions, thus inducing versatile biological effects. Strain-promoted azide-alkyne cycloaddition (SPAAC) is a significant method for obtaining triazoles, even under physiological conditions, in the absence of a copper catalyst. To confirm the progress of chemical reactions under biological conditions, research on reaction monitoring at low concentrations is essential. This promising strategy is gaining acceptance for applications in fields such as drug development and nanoscience. We investigated the optimum Ir catalyst and magnetic field for achieving maximum proton hyperpolarization transfer in triazole derivatives. These reactions were analyzed using signal amplification by reversible exchange (SABRE) to overcome the limitations of low sensitivity in nuclear magnetic resonance spectroscopy, when monitoring copper-free click reactions in real time. Finally, a more versatile copper-catalyzed click reaction was monitored in real time, using a 60 MHz benchtop NMR system, in order to analyze the reaction mechanism.

Water-Compatible and Recyclable Heterogeneous SABRE Catalyst for NMR Signal Amplification.

A water-compatible and recyclable catalyst for nuclear magnetic resonance (NMR) hyperpolarization via signal amplification by reversible exchange (SABRE) was developed. The [Ir(COD)(IMes)Cl] catalyst was attached to a polymeric resin of bis(2-pyridyl)amine (heterogeneous SABRE catalyst, HET-SABRE catalyst), and it amplified the 1H NMR signal of pyridine up to (-) 4455-fold (43.2%) at 1.4 T in methanol and (-) 50-fold (0.5%) in water. These are the highest amplification factors ever reported among HET-SABRE catalysts and for the first time in aqueous media. Moreover, the HET-SABRE catalyst demonstrated recyclability by retaining its activity in water after more than three uses. This newly designed polymeric resin-based heterogeneous catalyst shows great promise for NMR signal amplification for biomedical NMR and MRI applications in the future.

Hyperpolarization study on remdesivir with its biological reaction monitoring via signal amplification by reversible exchange.

Our experiments indicate hyperpolarized proton signals in the entire structure of remdesivir are obtained due to a long-distance polarization transfer by para-hydrogen. SABRE-based biological real-time reaction monitoring, by using a protein enzyme under mild conditions is carried out. It represents the first successful para-hydrogen based hyperpolarization application in biological reaction monitoring.

Effective degradation of sulfur mustard simulant using novel sulfur-doped mesoporous zinc oxide under ambient conditions.

Sulfur doped metal oxides were synthesized using a two-step precipitation method. When reacted against neat 2-CEES (2-chloroethyl-ethyl sulfide, a mustard gas simulant) under ambient conditions, sulfur doped mesoporous zinc oxide (MS-Zn) showed higher catalytic activity than the other metal oxides with 92.7% overall conversion in 24 h for a 2.5 µL neat 2-CEES droplet added on top of 2 × 2 cm large 400 mg catalyst layer. The reaction proceeded mainly by hydrolysis and further solvolysis reaction also occurred depending on the extracting solvents. Cyclic sulfonium ion intermediate reaction was thought to be involved in this reaction, and metal oxide surfaces were thought to facilitate the formation of sulfonium ions from adsorbed 2-CEES. All other by-products were also found to form via sulfonium ions, reconfirming the well-known importance of this intermediate species for the degradation reaction to proceed. The sulfur content for MS-Zn was varied and tested for degradation of neat 2-CEES. This modification showed that there is an optimal amount of sulfur content for the peak catalytic activity of MS-Zn for 2-CEES degradation. Adsorption energy of a 2-CEES molecule was calculated on model sulfur doped and non doped zinc oxide surfaces and the different adsorption energy levels were correlated with the catalytic activity of sulfur doped zinc oxide.

Decomposition of the Simulant 2-Chloroethyl Ethyl Sulfide Blister Agent under Ambient Conditions Using Metal-Organic Frameworks.

Metal organic frameworks (MOFs) have been suggested as promising materials for application in the degradation of chemical warfare agents, with the majority of studies to date focusing on nerve agents. One of the most prominent MOFs used in the detoxification of nerve agents is UiO-66, which is of interest as a future nerve agent decontaminant. However, blister agents, which constitute one of the most toxic and highly reactive categories of chemical agents, are yet to be examined as gas-phase decontamination targets using MOF structures. In this study, a novel type of UiO-66 with a smaller particle size, namely, UiO-66S, was used as a decontaminant for the blister agent simulant, 2-chloroethyl ethyl sulfide (2-CEES). The gas-phase chemical adsorption and decomposition of 2-CEES were demonstrated for the first time, with an estimated t1/2 of 1.34 h. This value is the highest reported value for an MOF in gas-phase reaction conditions. The obtained nontoxic degradation products were identified, and the reaction mechanism was studied using density functional theory calculations. Furthermore, the synthesized UiO-66S catalyst also exhibits superior catalytic ability toward nerve agent simulants (diisopropyl fluorophosphate).The results of the study provide a firm basis for the use of UiO-66S as a future decontaminant for both nerve and blister agents.

Signal amplification by reversible exchange for COVID-19 antiviral drug candidates.

Several drug candidates have been proposed and tested as the latest clinical treatment for coronavirus pneumonia (COVID-19). Chloroquine, hydroxychloroquine, ritonavir/lopinavir, and favipiravir are under trials for the treatment of this disease. The hyperpolarization technique has the ability to further provide a better understanding of the roles of these drugs at the molecular scale and in different applications in the field of nuclear magnetic resonance/magnetic resonance imaging. This technique may provide new opportunities in diagnosis and research of COVID-19. Signal amplification by reversible exchange-based hyperpolarization studies on large-sized drug candidates were carried out. We observed hyperpolarized proton signals from whole structures, due to the unprecedented long-distance polarization transfer by para-hydrogen. We also found that the optimal magnetic field for the maximum polarization transfer yield was dependent on the molecular structure. We can expect further research on the hyperpolarization of other important large molecules, isotope labeling, as well as polarization transfer on nuclei with a long spin relaxation time. A clinical perspective of these features on drug molecules can broaden the application of hyperpolarization techniques for therapeutic studies.

Molecular phylogenetics and biogeography of the Neocellia Series of Anopheles mosquitoes in the Oriental Region.

Molecular studies of population divergence and speciation across the Oriental Region are sparse, despite the region's high biodiversity and extensive Pliocene and Pleistocene environmental change. A molecular phylogenetic study of the Neocellia Series of Anopheles mosquitoes was undertaken to identify patterns of diversification across the Oriental Region and to infer the role of Pleistocene and Pliocene climatic change. A robust phylogeny was constructed using CO2 and ND5 mitochondrial genes and ITS2 and D3 nuclear ribosomal markers. Bayesian analysis of mitochondrial genes was used to date divergence events. The repeated contraction and expansion of forest habitat resulting from Pleistocene climatic fluctuations appears to have had a substantial impact on intraspecific diversification, but has not driven speciation within this group. Primarily early to mid Pliocene speciation was detected within the Annularis Group, whereas speciation within the Maculatus and Jamesii Groups occurred during the mid and late Pliocene. Both allopatric divergence driven by late Pliocene environmental changes and ecological adaptation, involving altitudinal replacement and seasonality, are likely to have influenced speciation in the Maculatus Group.

Mitochondrial pseudogenes in the nuclear genome of Aedes aegypti mosquitoes: implications for past and future population genetic studies.

BACKGROUND: Mitochondrial DNA (mtDNA) is widely used in population genetic and phylogenetic studies in animals. However, such studies can generate misleading results if the species concerned contain nuclear copies of mtDNA (Numts) as these may amplify in addition to, or even instead of, the authentic target mtDNA. The aim of this study was to determine if Numts are present in Aedes aegypti mosquitoes, to characterise any Numts detected, and to assess the utility of using mtDNA for population genetics studies in this species. RESULTS: BLAST searches revealed large numbers of Numts in the Ae. aegypti nuclear genome on 146 supercontigs. Although the majority are short (80% < 300 bp), some Numts are almost full length mtDNA copies. These long Numts are not due to misassembly of the nuclear genome sequence as the Numt-nuclear genome junctions could be recovered by amplification and sequencing. Numt evolution appears to be a complex process in Ae. aegypti with ongoing genomic integration, fragmentation and mutation and the secondary movement of Numts within the nuclear genome.The PCR amplification of the putative mtDNA nicotinamide adenine dinucleotide dehydrogenase subunit 4 (ND4) gene from 166 Southeast Asian Ae. aegypti mosquitoes generated a network with two highly divergent lineages (clade 1 and clade 2). Approximately 15% of the ND4 sequences were a composite of those from each clade indicating Numt amplification in addition to, or instead of, mtDNA. Clade 1 was shown to be composed at least partially of Numts by the removal of clade 1-specific bases from composite sequences following enrichment of the mtDNA. It is possible that all the clade 1 sequences in the network were Numts since the clade 2 sequences correspond to the known mitochondrial genome sequence and since all the individuals that produced clade 1 sequences were also found to contain clade 2 mtDNA-like sequences using clade 2-specific primers. However, either or both sets of clade sequences could have Numts since the BLAST searches revealed two long Numts that match clade 2 and one long Numt that matches clade 1. The substantial numbers of mutations in cloned ND4 PCR products also suggest there are both recently-derived clade 1 and clade 2 Numt sequences. CONCLUSION: We conclude that Numts are prevalent in Ae. aegypti and that it is difficult to distinguish mtDNA sequences due to the presence of recently formed Numts. Given this, future population genetic or phylogenetic studies in Ae. aegypti should use nuclear, rather than mtDNA, markers.

SQUID-based ultralow-field MRI of a hyperpolarized material using signal amplification by reversible exchange.

The signal amplification by reversible exchange (SABRE) technique is a very promising method for increasing magnetic resonance (MR) signals. SABRE can play a particularly large role in studies with a low or ultralow magnetic field because they suffer from a low signal-to-noise ratio. In this work, we conducted real-time superconducting quantum interference device (SQUID)-based nuclear magnetic resonance (NMR)/magnetic resonance imaging (MRI) studies in a microtesla-range magnetic field using the SABRE technique after designing a bubble-separated phantom. A maximum enhancement of 2658 for 1H was obtained for pyridine in the SABRE-NMR experiment. A clear SABRE-enhanced MR image of the bubble-separated phantom, in which the para-hydrogen gas was bubbling at only the margin, was successfully obtained at 34.3 µT. The results show that SABRE can be successfully incorporated into an ultralow-field MRI system, which enables new SQUID-based MRI applications. SABRE can shorten the MRI operation time by more than 6 orders of magnitude and establish a firm basis for future low-field MRI applications.