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Environmental Analysis, Health and... Sep 2021Methyl isocyanate (MIC), a low molecular weight synthetic aliphatic compound, having an isocyanate group (-NCO), has industrial application. In this study, the effects...
Methyl isocyanate (MIC), a low molecular weight synthetic aliphatic compound, having an isocyanate group (-NCO), has industrial application. In this study, the effects of methyl isocyanate and its mechanism on outer membrane protein of Escherichia coli were observed using experimental and computational methods. In vitro exposure of N-succinimidyl N-methylcarbamate (NSNM) a synthetic analogue of MIC on E. coli to a final concentration of 2 mM was found to affect the growth curve pattern and changes in cell morphology. Molecular docking studies of MIC and NSNM with E. coli outer membrane protein (OmpW, OmpX, OmpF OmpA), and periplasmic domain (PAL) were performed. The in-silico results revealed that outer membrane protein OmpF showed the highest negative binding energy, i.e. ∆G -4.11 kcal/mole and ∆G -3.19 kcal/mole by NSNM and MIC as compared to other proteins. Our study concludes that methyl isocyanate retains lethal toxicity which leads to cell death due to the membrane protein damage of E. coli membrane.
PubMed: 34428861
DOI: 10.5620/eaht.2021020 -
Organic Process Research & Development Dec 2020The cyclic azodicarbonyl 4-methyl-1,2,4-triazoline-3,5-dione (MTAD) is a versatile and powerful reagent used mainly in cycloaddition chemistry. Though known for more...
The cyclic azodicarbonyl 4-methyl-1,2,4-triazoline-3,5-dione (MTAD) is a versatile and powerful reagent used mainly in cycloaddition chemistry. Though known for more than 50 years, its unsafe preparation, as well as purification by sublimation, hampered its widespread applicability on a larger scale. Herein we report a scalable and safe route to MTAD, which avoids the generation of methyl isocyanate. Moreover, we demonstrate that sublimation can be circumvented by the application of judicious oxidation conditions, followed by simple filtration. Overall, up to 25 g of MTAD was prepared in a single batch from commercial starting materials in three steps, with recrystallization serving as the only purification in the sequence. When employed in dearomative methodologies, the MTAD obtained by this protocol displayed synthetic efficiency equivalent to that of MTAD purified by sublimation.
PubMed: 33958851
DOI: 10.1021/acs.oprd.0c00470 -
Hormone Molecular Biology and Clinical... Feb 2021After the global outbreak of coronaviruses caused diseases such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), an outbreak due... (Review)
Review
COVID-19: a review on SARS-CoV-2 origin, epidemiology, virology, clinical manifestations and complications with special emphasis on adverse outcome in Bhopal Gas Tragedy survivor.
After the global outbreak of coronaviruses caused diseases such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), an outbreak due to these viruses occurred in December, 2019 in Wuhan, Hubei Province, China and led to a worldwide spread. Coronavirus 2019 disease (COVID-19) has emerged as a serious global health emergency and spread from a person to another who has the virus. But the scope of an intermediate host is not known. Population at higher risk includes individuals in higher age group (>60 years) or with comorbidities such as diabetes, hypertension, cardiovascular disease and weaker immune system. Many unknown and underestimate risk factors could be responsible for adverse outcomes in COVID-19. These risk factors should be appropriately identified, addressed and necessary actions should be taken to mitigate the effect of COVID-19 pandemic. Bhopal gas tragedy was one of the world's worst industrial chemical leak disaster. The survivors of this incident still suffer from the various complications such as increased rate of cancers, chronic illness like tuberculosis, respiratory diseases, birth defects, nerve injury, growth retardations, gynecological illness and many more. The survivors of Bhopal gas tragedy are at higher risk of developing COVID-19 related adverse outcome. One of the possible explanations can be long term effect of methyl isocyanate (MIC). MIC exposure can lead to possible toxic effect on genetic, epigenetic and non-genetic factors. In this review, we aim to establish the scientific basis for adverse outcome in COVID-19 patients who are also victims of Bhopal gas tragedy.
Topics: Aged; Aged, 80 and over; Bhopal Accidental Release; COVID-19; China; Comorbidity; Disaster Victims; Disasters; Humans; India; Middle Aged; Pandemics; SARS-CoV-2; Survivors
PubMed: 33600673
DOI: 10.1515/hmbci-2020-0070 -
Environmental Science and Pollution... Apr 2021Methylcarbamoyl mercapturic acid (MCAMA, N-acetyl-S-(N-methylcarbamoyl)-L-cysteine) is a urinary metabolite of N,N-dimethylformamide and methyl isocyanate, which are...
Characterization of US population levels of urinary methylcarbamoyl mercapturic acid, a metabolite of N,N-dimethylformamide and methyl isocyanate, in the National Health and Nutrition Examination Survey (NHANES) 2005-2006 and 2011-2016.
Methylcarbamoyl mercapturic acid (MCAMA, N-acetyl-S-(N-methylcarbamoyl)-L-cysteine) is a urinary metabolite of N,N-dimethylformamide and methyl isocyanate, which are volatile organic compounds that are harmful to humans. N,N-dimethylformamide exposure causes liver damage, and methyl isocyanate inhalation damages the lining of the respiratory tract, which can increase risk of chronic obstructive pulmonary disease and asthma. This study characterizes urinary MCAMA levels in the US population and explores associations of MCAMA concentrations with select demographic and environmental factors. We used liquid chromatography tandem mass spectrometry to measure MCAMA in urine collected from study participants ≥ 12 years old (N = 8272) as part of the National Health and Nutrition Examination Survey 2005-2006 and 2011-2016. We produced multiple regression models with MCAMA concentrations as the dependent variable and sex, age, fasting time, race/ethnicity, diet, and cigarette smoking as independent variables. Cigarette smokers and nonsmokers had median urinary MCAMA concentrations of 517 μg/g creatinine and 127 μg/g creatinine, respectively. Sample-weighted multiple regression analysis showed that MCAMA was positively associated with serum cotinine (p < 0.0001). Compared to non-exposed participants (serum cotinine ≤ 0.015 ng/mL), presumptive exposure to second-hand tobacco smoke (serum cotinine > 0.015-≤ 10 ng/mL and 0 cigarettes smoked per day) was associated with 20% higher MCAMA (p < 0.0001). Additionally, smoking 1-10 cigarettes per day was associated with 261% higher MCAMA (p < 0.0001), smoking 11-20 cigarettes per day was associated with 357% higher MCAMA (p < 0.0001), and smoking > 20 cigarettes per day was associated with 416% higher MCAMA (p < 0.0001). These findings underscore the strong association of tobacco smoke exposure with urinary MCAMA biomarker levels.
Topics: Acetylcysteine; Biomarkers; Child; Cotinine; Dimethylformamide; Humans; Isocyanates; Nutrition Surveys; Tobacco Smoke Pollution
PubMed: 33398732
DOI: 10.1007/s11356-020-12135-7 -
Carbohydrate Polymers Jan 2021We report a facile chemical method to convert the hydroxyl groups of hydroxypropyl cellulose (HPC) into carbamates. It was achieved by the reaction of HPC with N-methyl...
We report a facile chemical method to convert the hydroxyl groups of hydroxypropyl cellulose (HPC) into carbamates. It was achieved by the reaction of HPC with N-methyl carbamoylimidazole, which is a safe and easy to handle replacement for the particularly hazardous reagent methyl isocyanate. Using a series of HPC with a range of molar substitution of hydroxypropyl groups, we synthesized HPC methylcarbamates showing lower critical solution temperature (LCST) in the range between 94 and 15 °C. A linear dependence of LCST versus methylcarbamate degree of substitution is observed. The lower the initial hydroxypropyl content of HPC, the greater the effect of methylcarbamate on the LCST. Surface tension study showed that methylcarbamate modification has an insignificant effect on the hydrophilic-hydrophobic balance of the macromolecules below LCST unless the molecular substitution of hydroxypropyl groups is so low (0.8) that the native cellulose OH groups can react with N-methyl carbamoylimidazole.
Topics: Carbamates; Cellulose; Hydrophobic and Hydrophilic Interactions; Phase Transition; Polymers; Solutions; Temperature
PubMed: 33152849
DOI: 10.1016/j.carbpol.2020.117015 -
Ciencia & Saude Coletiva Oct 2020There is credible evidence that the 1984-Bhopal-methyl isocyanate (MIC)-gas-exposed long-term survivors and their offspring born post-exposure are susceptible to...
There is credible evidence that the 1984-Bhopal-methyl isocyanate (MIC)-gas-exposed long-term survivors and their offspring born post-exposure are susceptible to infectious/communicable and non-communicable diseases. Bhopal's COVID-19 fatality rate suggests that the MIC-gas tragedy survivors are at higher risk, owing to a weakened immune system and co-morbidities. This situation emboldened us to ponder over what we know, what we don't, and what we should know about their susceptibility to COVID-19. This article aims at answering these three questions that emerge in the minds of public health officials concerning prevention strategies against COVID-19 and health promotion in the Bhopal MIC-affected population (BMAP). Our views and opinions presented in this article will draw attention to prevent and reduce the consequences of COVID-19 in BMAP. From the perspective of COVID-19 prophylaxis, the high-risk individuals from BMAP with co-morbidities need to be identified through a door-to-door visit to the severely gas-affected regions and advised to maintain good respiratory hygiene, regular intake of immune-boosting diet, and follow healthy lifestyle practices.
Topics: Betacoronavirus; COVID-19; Communicable Disease Control; Coronavirus Infections; Disasters; Disease Susceptibility; Environmental Exposure; Humans; Immunocompromised Host; India; Isocyanates; Pandemics; Pneumonia, Viral; SARS-CoV-2; Self Care; Survivors; Vulnerable Populations
PubMed: 33027359
DOI: 10.1590/1413-812320202510.2.28682020 -
The Journal of Chemical Physics Aug 2020The vacuum-ultraviolet threshold photoelectron spectrum of methyl isocyanate CHNCO has been recorded from 10.4 eV to 12 eV using synchrotron radiation and a coincidence...
The vacuum-ultraviolet threshold photoelectron spectrum of methyl isocyanate CHNCO has been recorded from 10.4 eV to 12 eV using synchrotron radiation and a coincidence technique allowing for a mass-discrimination of the photoelectron signal. A significant improvement is achieved over previous investigations as this experimental setup leads to a much more resolved spectrum. Ten sharp peaks and a broad feature spanning 1.2 eV were recorded. This spectrum consists of X̃A←X̃ A and ÃA←X̃ A ionizing transitions. For the former, the adiabatic ionization energy was determined experimentally to be 10.596(6) eV; for the latter, its value was estimated to be 10.759(50) eV. Seven sharp peaks could be assigned to vibrational modes of the cation X̃A and neutral X̃ A ground electronic states involving only the NCO group atoms. Theoretical modeling of the threshold photoelectron spectrum has proven difficult as methyl isocyanate is a non-rigid molecule displaying large amplitude internal rotation of the methyl group and ∠CNC bending mode, leading to the quasi-symmetry. With the help of ab initio calculations, a theoretical model in which these two large amplitude motions are included in addition to the five small amplitude vibrational modes involving NCO group atoms is proposed. Comparison with the experimental spectrum shows that the broad feature and the strongest peak line positions are well accounted for; their intensities are also fairly well reproduced after adjusting a few parameters.
PubMed: 32828110
DOI: 10.1063/5.0017753 -
The Journal of Physical Chemistry. A Aug 2020The reaction of CHNC with OH radicals was studied in smog chamber experiments employing PTR-ToF-MS and long-path FTIR detection. The rate coefficient was determined to...
The reaction of CHNC with OH radicals was studied in smog chamber experiments employing PTR-ToF-MS and long-path FTIR detection. The rate coefficient was determined to be = (7.9 ± 0.6) × 10 cm molecule s at 298 ± 3 K and 1013 ± 10 hPa; methyl isocyanate was the sole observed product of the reaction. The experimental results are supported by CCSD(T*)-F12a/aug-cc-pVTZ//M06-2X/aug-cc-pVTZ quantum chemistry calculations showing the reaction to proceed primarily via electrophilic addition to the isocyanide carbon atom. On the basis of the quantum chemical data, the kinetics of the OH reaction was simulated using a master equation model revealing the rate coefficient to be nearly independent of pressure at tropospheric conditions and having a negative temperature dependence with = 4.2 × 10 cm molecule s at 298 K. Additional quantum chemistry calculations on the CHNC reactions with O and NO show that these reactions are of little importance under atmospheric conditions. The atmospheric fate of methyl isocyanide is discussed.
PubMed: 32663395
DOI: 10.1021/acs.jpca.0c05127 -
Risk Analysis : An Official Publication... Sep 2020Model averaging for dichotomous dose-response estimation is preferred to estimate the benchmark dose (BMD) from a single model, but challenges remain regarding...
Model averaging for dichotomous dose-response estimation is preferred to estimate the benchmark dose (BMD) from a single model, but challenges remain regarding implementing these methods for general analyses before model averaging is feasible to use in many risk assessment applications, and there is little work on Bayesian methods that include informative prior information for both the models and the parameters of the constituent models. This article introduces a novel approach that addresses many of the challenges seen while providing a fully Bayesian framework. Furthermore, in contrast to methods that use Monte Carlo Markov Chain, we approximate the posterior density using maximum a posteriori estimation. The approximation allows for an accurate and reproducible estimate while maintaining the speed of maximum likelihood, which is crucial in many applications such as processing massive high throughput data sets. We assess this method by applying it to empirical laboratory dose-response data and measuring the coverage of confidence limits for the BMD. We compare the coverage of this method to that of other approaches using the same set of models. Through the simulation study, the method is shown to be markedly superior to the traditional approach of selecting a single preferred model (e.g., from the U.S. EPA BMD software) for the analysis of dichotomous data and is comparable or superior to the other approaches.
Topics: Bayes Theorem; Dose-Response Relationship, Drug; Isocyanates; Nitrosamines; Risk Assessment; Uncertainty
PubMed: 32602232
DOI: 10.1111/risa.13537 -
RSC Advances Apr 2020Isocyanurates are cyclic trimers of isocyanate molecules. They are generally known as highly thermostable compounds. However, it is interesting how the thermal...
Isocyanurates are cyclic trimers of isocyanate molecules. They are generally known as highly thermostable compounds. However, it is interesting how the thermal stabilities of the isocyanurate molecules will be altered depending on the substituents of their three nitrogen atoms. We performed computational investigations on the thermochemical behaviors of isocyanurate molecules with various alkyl and phenyl substituents. The cyclotrimerization processes of isocyanates are highly exothermic. Our best estimate of the enthalpy change for the cyclotrimerization of methyl isocyanate into trimethyl isocyanurate was -66.4 kcal mol. Additional negative cyclotrimerization enthalpy changes were observed for -alkyl-substituted isocyanates. This trend was enhanced with an extension of -alkyl chains. Conversely, low negative cyclotrimerization enthalpy changes were shown for secondary and tertiary alkyl-substituted isocyanates. The -alkyl-substituted isocyanurates were shown to be stabilized due to attractive dispersion interactions between the substituents. Meanwhile, the branched alkyl-substituted isocyanurates were destabilized due to the deformation of their isocyanurate rings. For various alkyl-substituted isocyanates, the sum of the deformation energy of the isocyanurate ring and the intramolecular inter-substituent nonbonding interaction energies was found to be linearly correlated with their cyclotrimerization energies. The cyclotrimerization energy for phenyl isocyanate was shown to have significantly deviated from the linear relationship observed for the alkyl-substituted isocyanurates. This is probably attributable to a remarkable change in the orbital resonance interactions during the cyclotrimerization of phenyl isocyanate to triphenyl isocyanurate.
PubMed: 35493671
DOI: 10.1039/d0ra02463e