Methyl Isocyanate Research Articles

Determining the Exposure Routes and Risk Assessment of Isocyanates in Indoor Environments.

Isocyanates are used as raw materials for polyurethane foams, paints, and building materials. The isocyanates can cause acute adverse health effects such as irritation of the respiratory tract, skin, and eyes, and induce asthma and sick house syndrome. However, investigations into the potential sources and risk assessments of indoor isocyanates are limited. Thus, this study aimed to determine the sources and exposure routes of isocyanates and to assess their risk in indoor environments. The results showed that household products, such as infant chairs, mattresses, and polyurethane foam spray, used in indoor environments are potential sources of atmospheric isocyanic acids (ICA). Toluene diisocyanate and methyl isocyanate pose relatively high risks to indoor environments. Total concentrations of isocyanates ranged from 38.2 to 1570ngg-1 in infant chairs, mattresses, and spray polyurethane foams. The indoor products can be indoor sources of ICA because emission rates of ICA from household products were observed in all products (0.0536-1.37ngg-1 d-1). Field observations showed that isocyanate concentrations in house-dust samples ranged from 0.194±0.126 (ethyl isocyanate) to 70.1±67.8 (ICA)ngg-1. Atmospheric isocyanate concentrations ranged from 0.0030±0.020 (propyl isocyanate) to 26.0±14.3 (ICA)ng m-3. An estimation of human exposure demonstrated that air inhalation was the major route of isocyanate exposure. The minimum margin of exposure values of methyl isocyanate and toluene diisocyanate were 523 and 655, respectively, for children, indicating that they may pose a relatively high risk.

Theoretical and experimental study on the pyrolysis of N-methylpyrrolidone

As a widely used organic solvent, N-methylpyrrolidone (NMP) may suffer thermal decomposition during large-scale industrial usage. The complex potential energy surface and corresponding pressure-dependent rate coefficients of NMP and NMP radicals were obtained at a high level of theory. The intermediates and products of NMP pyrolysis within 900–1200 K were identified and measured by synchrotron vacuum ultraviolet photoionization mass spectrometry. Theoretical calculations show that the Keto-enol tautomerization and direct ring-opening channel yielding C2H4, CO, and CH3NCH2 exhibit the highest rate coefficient among NMP unimolecular reactions at low and high temperatures, respectively. However, the fuel decomposition process cannot be exclusively dominated by single low-barrier channel. The ring-opening reaction forming imino aldehyde radical and following decarbonylation reactions are favored channels during the NMP radical decomposition, while the formation of the dihydropyrrolidone via H or CH3 loss competes with them at higher temperatures. Various smaller heterocycle radicals can be produced and act as intermediates for the multi-step isomerization of the ring-opening products with a relatively low energy barrier, changing the position of the functional group and radical site. A variety of nitrogenous and oxygenated species were observed in the experiment, such as ketene, methyl isocyanate, pyrrole, benzene, and different kinds of imines. Among them, C2H4, HCN, and CO are the major products for NMP decomposition. Potential reaction pathways from NMP to the major experimentally observed products were inferred based on the calculated results and existing knowledge on the pyrolysis of nitrogenous and oxygenated compounds. These results shed light on the complex C/H/O/N reaction system. The calculated rate coefficients and extensive mole fractions data could provide good support for the modeling of a detailed reaction mechanism in the future.

Reaction mechanisms for methyl isocyanate (CH3NCO) gas-phase degradation

Methyl isocyanate (MIC) is a toxic chemical found in many commercial, industrial, and agricultural processes, and was the primary chemical involved in the Bhopal, India disaster of 1984. The atmospheric environmental chemical reactivity of MIC is relatively unknown with only proposed reaction channels, mainly involving OH-initiated reactions. The gas-phase degradation reaction pathways of MIC and its primary product, formyl isocyanate (FIC), were investigated with quantum mechanical (QM) calculations to assess the fate of the toxic chemical and its primary transformation products. Transition state energy barriers and reaction energetics were evaluated for thermolysis/pyrolysis-like reactions and bimolecular reactions initiated by relevant radicals (•OH and Cl•) to evaluate the potential energy surfaces and identify the primary reaction pathways and products. Thermolysis/pyrolysis of MIC requires high energy to initiate N-CH3 and C-H bond dissociation and is unlikely to dissociate except under extreme conditions. Bimolecular radical addition and H-abstraction reaction pathways are deemed the most kinetically and thermodynamically favorable mechanisms. The primary transformation products of MIC were identified as FIC, methylcarbamic acid, isocyanic acid (isocyanate radical), and carbon dioxide. The results of this work inform the gas-phase reaction channels of MIC and FIC reactivity and identify transformation products under various reaction conditions.

COVID-19 mortality in 1984 Bhopal gas tragedy survivors: implications for chemically exposed populations.

Leakage of methyl isocyanate from the Union Carbide plant in Bhopal, India, killed thousands and left deleterious trans-generational effects. Gas-exposed populations experience higher rates of lung and metabolic diseases, and immune dysregulation, all associated with adverse outcomes in coronavirus disease 2019 (COVID-19). We used publicly available, official data from government sources to estimate COVID-19-associated crude mortality in populations with and without a history of gas exposure. Overall, there were 1240 deaths among patients hospitalized with known COVID-19 in Bhopal, of which 453 (36.53%) were in gas-exposed individuals, 726 (58.55%) were in gas-unexposed individuals and the exposure status of 61 (4.92%) individuals could not be determined. There were 351 and 375 deaths in gas-unexposed people in the first (April 2020-February 2021) and second (March 2021-July 2021) waves, respectively; in the gas-exposed population, there were 300 and 153 deaths in the two respective waves. The overall annualized crude mortality of COVID-19 was 3.84 (95% CI 3.41 to 4.33) times higher in the gas-exposed population at 83.6 (95% CI 76.1 to 91.7) per 100 000 compared with the gas-unexposed population, at 21.8 (95% CI 20.2 to 23.4) per 100,000. When stratified by age, compared with unexposed people, the gas-exposed individuals experienced 1.88 (95% CI 1.61 to 2.21) and 1.24 (95% CI 1.02 to 1.50) times the mortality rates in the age groups of 35-65 and >65 y, respectively. These findings indicate that gas-exposed individuals are likely to have a higher risk of severe COVID-19 and death and need to be specifically targeted and recognized for preventive and promotive efforts.

Review of Synthesis and Characterization of Cu (I) Complexes

d-block metals show great promise in inorganic catalytic research. Particularly, copper, d9 metal has contributed to catalytic properties of its complexes. A series of copper complexes was synthesized and structurally characterized. The copper (I) complexes of this series were investigated in regard to their reactivity towards dioxygen using stopped-flow techniques. For most complexes no “oxygen adduct” complexes as intermediates could be detected. In this article, some complexes of Cu (I) have been included and the ligands on which work had been done are mentioned below: 1,5-bis(benzimidazole-2-yl)-3-thiapentane Tridentate di-pyrazole -3,6-di-tert-butyl-carbazole (N, N, N-Pincer ligand) Methyl isocyanate N4Cu Tris(pyrazolyl) hydroborate ligand Scorpionate ligand Phenanthroline Tripodal amine ligands Triazole derivatives Keywords: BBES (1,5-bis(benzimidazole-2-yl)-3-thiapentane), MeIN (Methyl isocyanate), CuSCN (copper thiocyanate), PPh3(triphenyl phosphine), PCy3(tricyclohexyl phosphine), TptBuPh (tris[3-(p-tert-butylphenyl)], Tp (tris pyrazolyl hydroborate), Me4-p,3,3 (3,3-dimethylaminopropyl-(2-methylenpyridyl)-amine), Me2-pp3 (3-dimethylaminopropyl-bis(2-methylenpyridyl)-amine)

Effects of explosion suppressants on the dust explosion and pyrolysis characteristics of the fungicide fenaminstrobin

In this study, the explosion and pyrolysis characteristics of fungicide fenaminstrobin dust were studied, and the inhibitory effects of three explosion suppressants, namely, NH4H2PO4, KH2PO4, and KCl, on dust explosion were compared. A combined thermogravimetric (TG)–Fourier transform infrared (FTIR)–mass spectrometry (MS) technique was adopted to analyze the inhibition mechanism. The results showed that the minimum ignition energy (MIE) was 5 mJ, the explosion index (Kst) was 305.7 bar m/s, and the dust explosion hazard was severe. We found that all three compounds (NH4H2PO4, KH2PO4, and KCl) could be used as explosion suppressants. When the addition dose of NH4H2PO4 was 35%, the Kst value dropped by 40.7%, and MIE exceeded 1000 mJ. When the addition of KH2PO4 was 50%, the Kst value dropped by 37.3%, and the MIE increased to 300 mJ. In comparison, NH4H2PO4 showed the best inhibitory effect, while KCl demonstrated the worst inhibitory effect. The pyrolysis of fenaminstrobin produced organic gases, including quinoline, benzonitrile, and methyl isocyanate, and generated large quantities of free radicals. The explosion suppressants could inhibit the explosion through physical pathways (endothermic, coating, and oxygen-diluting processes) and chemical pathways (free-radical capture).

Crip Life Amidst Debilitation: Medicalization, Survival, and the Bhopal Gas Leak

In a textbook horror-story of global capitalism, on December 3, 1984, the U.S owned Union Carbide pesticide factory spewed forty tons of lethal toxic methyl isocyanate (MIC) on the city of Bhopal in India. Nearly 10,000 people died and 30,000 people were disabled overnight. Continued exposure to MIC at the factory site has disabled many more in the decades since. Yet, few disability scholars have considered the histories of the survivors of the leak as a key site of crip politics. Drawing on work by Nirmala Erevelles, Jina Kim, Jasbir Puar, and Alison Kafer, this paper explores how the long history of debilitation, disablement, and survivorship since the Bhopal Gas Leak provides essential ground for re-zoning disability studies in the Global South. Braiding the theory of debility with the methodology of critical disability studies, this article posits that it is insufficient to say that the most marginalized in the Global South experience debility. Rather, it is also necessary to focus on their modes of survival in the face of the constant material and intellectual reproduction of said debilitation. The article demonstrates how poor lower-caste and Muslim workers and city-dwellers in Bhopal were subject to the debilitating logics of transnational corporate negotiations, racialized environmental de-regulation, and governmental profit-seeking in the years leading up to the leak. Through crip readings of medical research published between 1985 and 2000, I argue that this debility has been compounded through knowledge production which did not pay heed to the ways in which its victims contended with their vulnerability. In contrast to these sources, this article further examines testimonies and organizational pamphlets to contend that survivors in Bhopal offer their own model of disability justice and crip survival in the face of debilitation. In an era of vibrant disability rights organizing in the United States, the survivors of the leak emerged in global media primarily as victims of a tragedy caught in an endless cycle of injustice. Moving past the stance of pity often deployed in discussions of Bhopal, I highlight efforts of survivance that center disabled futurity, even as these activists use a different vocabulary and thereby strive to channel attention and resources to the myriad forms of crip survival in postcolonial India.

Perioperative exposure to volatile organic compounds in neonates undergoing cardiac surgery

ObjectiveVolatile organic compounds (VOCs) are used in the sterilization and manufacture of medical equipment. These compounds have high vapor pressures with low water solubility and are emitted as gases from solids or liquids. They can be mutagenic, neurotoxic, genotoxic, and/or carcinogenic. Safe limits of exposure are not known for neonates. This study examined determinants of exposure in newborns undergoing cardiac surgery. MethodsTwenty metabolites of 16 VOCs (eg, xylene, cyanide, acrolein, acrylonitrile, N, N-dimethylformamide, 1,3-butadiene, styrene, and benzene) were measured as metabolites in daily urine samples collected from 10 neonates undergoing cardiac operations (n = 150 samples). Metabolites were quantified using reversed-phase ultra-high performance liquid chromatography and electrospray ionization tandem mass spectrometry. Repeated measures analysis of covariance was performed for each metabolite to examine associations with use of medical devices. ResultsAt least 3 metabolites were detected in every sample. The median number of metabolites detected in each sample was 14 (range, 3-15). In a model controlling for other factors, the use of extracorporeal membrane oxygenation was associated with significantly (P ≤ .05) greater metabolite levels of acrolein, acrylonitrile, ethylene oxide, propylene oxide, styrene, and ethylbenzene. Patients breathing ambient air had greater levels of metabolites of acrolein, xylene, N,N-dimethylformamide, methyl isocyanate, cyanide, 1,3-butadiene (all P ≤ .05). ConclusionsExposure to volatile organic compounds is pervasive in newborns undergoing cardiac surgery. Sources of exposure likely include medical devices and inhalation from the air in the intensive care unit. The contribution of VOC exposure during cardiac surgery in newborns to adverse outcomes warrants further evaluation.

Construction of a copper hydroxystannate functionalized graphene oxide for rigid polyvinyl chloride foam toward improved fire safety

AbstractA copper hydroxystannate (CHS) functionalized graphene oxide (GO) (CHS@GO) was feasibly prepared through an in‐situ method, and well characterized by TEM, XRD, FTIR and XPS. Rigid poly vinyl chloride (RPVC) foams containing CHS@GO were prepared by utilizing methyl hexahydrophthalic anhydride and isocyanate as coupling agents, azodiisobutyronitrile and azodicarbonamide as blowing agents. The fire safety, mechanical properties and thermal decomposition behavior of the RPVC foams were studied. The RPVC foam containing 2 wt% CHS@GO (RPVC/2CHS@GO) achieved a limiting oxygen index (LOI) of 35.5% and a V0 rating in the UL‐94 tests. The cone calorimetric tests (CCT) results demonstrated the peak heat release rate (pHRR) and total heat release (THR) of RPVC/2CHS@GO were reduced by 40.6% and 36.8%, respectively, compared with those of pure RPVC foam (pure RPVC). The compressive strength and flexural strength of RPVC/2CHS@GO were increased by 47.3% and 34.6%, respectively, in contrast with those of Pure RPVC. The thermogravimetry results showed that CHS@GO endowed the RPVC foams with improved char residue.

Exposure Risks and Potential Control Measures for a Fire Behavior Lab Training Structure: Part B—Chemical Gas Concentrations

Firefighters’ or instructors’ exposure to airborne chemicals during live-fire training may depend on fuels being burned, fuel orientation and participants’ location within the structure. This study was designed to evaluate the impact of different control measures on exposure risk to combustion byproducts during fire dynamics training where fuel packages are mounted at or near the ceiling. These measures included substitution of training fuels (low density wood fiberboard, oriented strand board (OSB), pallets, particle board, plywood) and adoption of engineering controls such as changing the location of the instructor and students using the structure. Experiments were conducted for two different training durations: the typical six ventilation cycle (six-cycle) and a shorter three ventilation cycle (three-cycle) with a subset of training fuels. In Part A of this series, we characterized the fire dynamics within the structure, including the ability of each fuel to provide an environment that achieves the training objectives. Here, in Part B, airborne chemical concentrations are reported at the location where fire instructors would typically be operating. We hypothesized that utilizing a training fuel package with solid wood pallets would result in lower concentrations of airborne contaminants at the rear instructor location than wood-based sheet products containing additional resins and/or waxes. In the six-cycle experiments (at the rear instructor location), OSB-fueled fires produced the highest median concentrations of benzene and 1,3 butadiene, plywood-fueled fires produced the highest total polycyclic aromatic hydrocarbon (PAH) concentrations, particle board-fueled fires produced the highest methyl isocyanate concentrations, and pallet-fueled fires produced the highest hydrogen chloride concentrations. All fuels other than particle board produced similarly high levels of formaldehyde at the rear instructor location. The OSB fuel package created the most consistent fire dynamics over six-cycles, while fiberboard resulted in consistent fire dynamics only for the first three cycles. In the follow-on three-cycle experiment, PAH, benzene, and aldehyde concentrations were similar for the OSB and fiberboard-fueled fires. Air sampling did not identify any clear differences between training fires from burning solid wood pallets and those that incorporate wood-based sheet products for this commonly employed fuel arrangement with fuels mounted high in the compartment. However, it was found that exposure can be reduced by moving firefighters and instructors lower in the compartment and/or by moving the instructor in charge of ventilation from the rear of the structure (where highest concentrations were consistently measured) to an outside position.

MIC accident: lesson may guide for evaluation of genotoxic potential of the industrial chemicals for prevention of industrial accidents.

Most of the individual and/or amalgamated compounds present in the atmospheric air are not known for their toxicologic potential and impact on human health. The toxicologic strength of methyl isocyanate (MIC) gas was unknown till its accidental leakagethat instantly claimed thousands of lives. Cytogenetic study showed increased chromosome aberrations (CA) and sister chromatid exchanges (SCEs) and delayed cell replication index (RI) in a multicentre genetic screeningprogram on gas victimsimmediate post-disaster. A surveillance study after 30 years displayed reduction in CA compared to the initial status in survivors of the severely and moderately exposed strata. Altogether, cytogenetic damage was significantly predominant in the severely exposed population. Stable and replicable aberrations and chromatid exchanges were detected in both studies, which collectively indicate genetic instability. The variation in individual cytogenetic spectrum from similar exposure status could be the result of inter-individual response to the external factors over 30 years post-disaster. The spectrum of CA detected after 30 years might be the cumulative effect of occupational, environmental and life-style factors at a background of one episode of acute MIC exposure. Had MIC's toxicologic potential was known before, fatality and health effects could have been averted. In vitro assessment of toxicity of tin showed a positive correlation with dose and age of exposure, which was aggravated by smoking. Age has shown a significant effect on CA in the general population. The present report recommends evaluation of toxicity prior to use, and reduction of pollution at source for a maintaining a sustainable environmental context.

A comprehensive kinetic study of the combustion mechanismof methyl isocyanate

A detailed mechanism for the combustion of methyl isocyanate is proposed for the first time. Electronic structures were calculated at the CCSD(T)/cc-VTQ∞Z//B2PLYP-D3/6-311++G(3df,2pd) level of theory to investigate potential energy profiles and used in reaction rate theories to compute rate coefficients. The mechanism contains 130 reactions and was merged with the reaction base proposed by Glarborg et al.[1] for light hydrocarbons and nitrogen-containing species. Experimental data related to the pyrolysis of methyl isocyanate were simulated in a closed reactor and a good agreement was observed for all the species profiles reported. Similarly, the auto-ignition temperature (Tign) of methyl isocyanate was calculated based on the standard ASTME659-78 test, and led to a value close to the experimental value. Flow rate and sensitivity analysis were performed under pyrolysis and combustion conditions in order to highlight the main reaction pathways.

Decomposition of N,O-dimethylcarbamate to methyl isocyanate: A DFT study

The non-catalytic and catalyzed by phenol and zinc methoxide decomposition of N,O-dimethylcarbamate to methyl isocyanate and methanol was studied by B3LYP/6–311++G(df,p) and PBE0/6–311++G(df,p) methods. Non-catalytic transformation has a large activation barrier and is therefore not feasible. Catalysis with phenol slightly reduces the activation barrier. The non-catalytic and phenol-catalyzed reactions are single-step. Zinc methoxide-catalyzed reaction proceeds through two stages. The greatest decrease in the activation barrier is observed in the case of zinc methoxide-catalyzed reaction.

Amides inventory towards the G+0.693−0.027 molecular cloud

ABSTRACT Interstellar amides have attracted significant attentions as they are potential precursors for a wide variety of organics essential to life. However, our current understanding of their formation in space is heavily based on observations in star-forming regions and hence the chemical networks lack the constraints on their early origin. In this work, unbiased sensitive spectral surveys with IRAM 30 m and Yebes 40 m telescopes are used to systematically study a number of amides towards a quiescent Galactic centre molecular cloud, G+0.693−0.027. We report the first detection of acetamide (CH3C(O)NH2) and trans-N-methylformamide (CH3NHCHO) towards this cloud. In addition, with the wider frequency coverage of the survey, we revisited the detection of formamide (NH2CHO) and urea (carbamide; NH2C(O)NH2), which had been reported previously towards G+0.693−0.027. Our results are compared with those present in the literature including recent laboratory experiments and chemical models. We find constant abundance ratios independently of the evolutionary stages, suggesting that amides related chemistry is triggered in early evolutionary stages of molecular cloud and remain unaffected by the warm-up phase during the star formation process. Although a correlation between more complex amides and NH2CHO have been suggested, alternative formation routes involving other precursors such as acetaldehyde (CH3CHO), methyl isocyanate (CH3NCO), and methylamine (CH3NH2) may also contribute to the production of amides. Observations of amides together with these species towards a larger sample of sources can help to constrain the amide chemistry in the interstellar medium.

Effect on Antioxidants and Chromosomal Aberrations in the Offspring of Methyl Isocyanate Exposed Population of Bhopal

Bhopal gas tragedy was one of the worst industrial disasters that produced short-term as well as long-term health effects in the exposed population. The present study is an attempt to know about the genomic damage as well as the level of antioxidant caused by Methyl Isocyanate in the offspring of the exposed population and to know about the frequency of chromosomal aberrations in them. Offspring’s of the Methyl Isocyanate Exposed individuals living in the vicinity of 1.5 km from the Union Carbide’s pesticide plant were selected randomly from the study. Equal number of age (20 years – 50 years), sex (male / female) and locality matched non-exposed individuals were also enrolled as controls. All the subjects were non smokers and not employed at any type of chemical industry or a radiation department. Cytogenetic analysis was performed by standard protocol of lymphocyte culture as per as Moorhead et al. Chromosomal aberrations were observed. The antioxidant level of Vitamin E and Blood Glutathione was also recorded. Student’s t-test was performed to test the significance difference between means of chromosomal aberrations. The means were considered to be statistically significant at 1% level of probability. It was observed that the level of antioxidants (both Vitamin E by Jargar et al. and Blood Glutathione by Beutler et al.) was highly significant in the MIC Exposed and MIC Exposed F2 Generation Population as compared to MIC Non-Exposed Population. But, significant difference between MIC Exposed and MIC Exposed F2 Generation Population was observed. The mean percentage of normal metaphase in the Exposed group was significantly higher (p < 0.0001) as compared to Non-Exposed. Besides this, chromosomal aberrations (dicentrics and double minutes) were recorded at mitotic metaphase and were statistically elevated in the MIC Exposed Population. The present study indicates that the genomic instability still persists at a higher intensity among the Bhopal Gas Survivors. The higher incidence of chromosomal aberrations may act as the intermediate processes in the pathway of the progression of any genetic disorders and cancers. Hence, our study suggests that the Exposed Populations and their Offspring’s is more vulnerable and gas affected.
 Keywords: Chromosomal aberrations, Methyl isocyanate, Bhopal gas tragedy, Long-term genotoxicity, Exposed Population

Ethics of Chemistry

Abstract Imagine yourself a chemist confronted with the use of chemical weapons during World War IO. Or a citizen living in Bhopal, India, perhaps having negotiated the siting of the plant in your city as a politician or an employee bringing home a good wage working at Union Carbide’s methyl isocyanate plant. Or perhaps you are a student in 2023 needing to make informed choices about climate engineering or the rapid full-scale extraction of rare-earth materials to mitigate the climate crisis. What is the right thing to do in each of these scenarios? How can the study of the moral values, norms, judgments, and virtues relevant to chemistry equip students to deeply reflect about the practice of chemistry and guide them to make informed and responsible choices about their behaviour as professionals?

Modelling studies of the diffusivity and intersolubility of semi volatile organic compounds in water

Semi-volatile organic compounds (SVOCs) are hazardous contaminants found in several products - ranging from personal care products to plastic products and the environment. Their chemical migration into food substances, raising environmental and health concerns, has been well documented. The dispersion/diffusion and solubility of SVOCs in food simulants is an indicator of their migration from food packaging materials. Here, we employed molecular dynamics simulations to investigate molecular mass transfer/diffusivity and intersolubility of three (S)VOCs from various sources into water. The simulation results illustrated that the molecular weight of SVOCs affects their dispersion and solubility in water. SVOC molecules are also much easier to diffuse into water at higher temperatures and longer time periods. The intersolubility of SVOCs in water according to the Flory-Huggins parameter (χ) and Hildebrand solubility parameter (δ) occurs in the following order: methyl isocyanate > caprolactam > naphthalene. The solubility of SVOCs increases with temperature, as evident by the decreasing δSVOCs and χsvocs. These results will play a key role in expanding the knowledge base of chemical migration of small molecules into food simulants.

Novel Inhibitors of Acetyl- and Butyrylcholinesterase Derived from Benzohydrazides: Synthesis, Evaluation and Docking Study.

On the basis of previous reports, novel 2-benzoylhydrazine-1-carboxamides were designed as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Inhibitors of these enzymes have many clinical applications. 2-(Substituted benzoyl)hydrazine-1-carboxamides decorated with N-methyl or tridecyl were prepared with three methods from commercially available or self-prepared hydrazides and isocyanates. For methyl derivatives, N-succinimidyl N-methylcarbamate was used or methyl isocyanate was prepared via Curtius rearrangement. Tridecyl isocyanate was synthesized again via Curtius rearrangement or from triphosgene and tridecylamine. The compounds were evaluated for the inhibition of AChE and BChE using Ellman's spectrophotometric method. Most of the derivatives showed the dual inhibition of both enzymes with IC50 values of 44-100 µM for AChE and from 22 µM for BChE. In general, the carboxamides inhibited AChE more strongly. A large number of the compounds showed better or quite comparable inhibition of cholinesterases in vitro than that of the drug rivastigmine. Molecular docking was performed to investigate the possible conformation of the compounds and their interactions with target enzymes. In both AChE and BChE, the compounds occupied the enzyme active cavity, and, especially in the case of BChE, the compounds were placed in close proximity to the catalytic triad.

Structure, spectroscopic signatures, and formation of hydroxy-azirine: a potential interstellar prebiotic molecule

ABSTRACT Hydroxy-azirine (C2H3NO) is a -OH derivative of azirine (C2H3N), molecule that has been the subject of several unfruitful searches in space. Hydroxy-azirine is an isomer of the detected prebiotic species methyl isocyanate, CH3NCO, and glycolonitrile, HOCH2CN, as well as the yet undetected imine acetaldehyde, NHCHCHO. However, the lack of preliminary spectroscopic data on hydroxy-azirine has prevented its astronomical search. The aim of this study is to provide high-level theoretical spectroscopic signatures of the most stable hydroxy-azirine isomers to enable their eventual interstellar search. A total of 12 isomers have been characterized for hydroxy-azirine and their isomerization processes have been analysed at the CCSD(T)-F12/cc-pVTZ-F12 level. The most stable structures are 3-hydroxy-2H-azirine (I) and 2-hydroxy-2H-azirine (II) in their syn- and anti-configurations, which are suggested as the most relevant candidates for laboratory and interstellar detection. To ease their identification by means of rotational spectroscopy, we report a set of the required spectroscopic parameters using state-of-the-art composite and coupled-cluster approaches. For astronomical purposes, we provide a complete line list for I-syn and I-antihydroxy-azirine up to 50 GHz, which takes the hyperfine structure into account, and will be essential to hunt for these interstellar candidates experimentally. In addition, anharmonic vibrational frequencies and intensities are reported to predict a trustworthy vibrational spectra and to estimate the vibrational partition function. Finally, we analyse the possibility of formation of hydroxy-azirine from the reaction of azirine with the hydroxyl radical in the gas-phase and on the surface of ices, finding for the latter a feasible formation route under interstellar conditions.

Millimeter wave spectrum and search for vinyl isocyanate toward Sgr B2(N) with ALMA

Context. The interstellar detections of isocyanic acid (HNCO), methyl isocyanate (CH3NCO), and very recently also ethyl isocyanate (C2H5NCO) invite the question of whether or not vinyl isocyanate (C2H3NCO) can be detected in the interstellar medium. There are only low-frequency spectroscopic data (<40 GHz) available for this species in the literature, which makes predictions at higher frequencies rather uncertain, which in turn hampers searches for this molecule in space using millimeter (mm) wave astronomy. Aims. The aim of the present study is on one hand to extend the laboratory rotational spectrum of vinyl isocyanate to the mm wave region and on the other to search, for the first time, for its presence in the high-mass star-forming region Sgr B2, where other isocyanates and a plethora of complex organic molecules are observed. Methods. We recorded the pure rotational spectrum of vinyl isocyanate in the frequency regions 127.5–218 and 285–330 GHz using the Prague mm wave spectrometer. The spectral analysis was supported by high-level quantum-chemical calculations. On the astronomy side, we assumed local thermodynamic equilibrium to compute synthetic spectra of vinyl isocyanate and to search for it in the ReMoCA survey performed with the Atacama Large Millimeter/submillimeter Array (ALMA) toward the high-mass star-forming protocluster Sgr B2(N). Additionally, we searched for the related molecule ethyl isocyanate in the same source. Results. Accurate values for the rotational and centrifugal distortion constants are reported for the ground vibrational states of trans and cis vinyl isocyanate from the analysis of more than 1000 transitions. We report nondetections of vinyl and ethyl isocyanate toward the main hot core of Sgr B2(N). We find that vinyl and ethyl isocyanate are at least 11 and 3 times less abundant than methyl isocyanate in this source, respectively. Conclusions. Although the precise formation mechanism of interstellar methyl isocyanate itself remains uncertain, we infer from existing astrochemical models that our observational upper limit for the CH3NCO:C2H5NCO ratio in Sgr B2(N) is consistent with ethyl isocyanate being formed on dust grains via the abstraction or photodissociation of an H atom from methyl isocyanate, followed by the addition of a methyl radical. The dominance of such a process for ethyl isocyanate production, combined with the absence of an analogous mechanism for vinyl isocyanate, would indicate that the ratio C2H3NCO:C2H5NCO should be less than unity. Even though vinyl isocyanate was not detected toward Sgr B2(N), the results of this work represent a significant improvement on previous low-frequency studies and will help the astronomical community to continue searching for this species in the Universe.