Computational Kinetics Study Of Atmospheric Ring-closure And Dehydration Reactions Of 1,4-hydroxycarbonyls In The Gas Phase

Several experimental studies have shown that 1,4-hydroxycarbonyls can undergo sequential reactions involving cyclization followed by dehydration to form dihydrofurans.\footnote{Atkinson, R. et al. Atmos. Environ. 2008, 42, 5859; Ranney, A. P.; Ziemann, P. J. J. Phys. Chem. A 2016, 120, 2561.} As dihydrofurans contain a double bond, they are highly reactive towards OH, O$_{3}$, and NO$_{3}$ in the atmosphere. In this work, we investigate the energetics and kinetics of the cyclization and dehydration reaction steps associated with 4-hydroxybutanal (4-OH-BL), a prototypical 1,4-hydroxycarbonyl molecule using ab initio calculations. The cyclization step transforms 4-OH-BL into 2-hydroxytetrahydrofuran (2-OH-THF), which can subsequently undergo dehydration to form 2,3-dihydrofuran. Since the barriers associated with the cyclization and dehydration steps for 4-OH-BL are respectively 34.8 and 63.0 kcal/mol in the absence of any catalyst, both reaction steps are not feasible under atmospheric conditions. However, the presence of a suitable catalyst can significantly reduce the reaction barriers. Therefore, we investigate the effect of a single molecule of H$_{2}$O, HO$_{2}$ radical, HC(O)OH, HNO$_{3}$, and H$_{2}$SO$_{4}$ as catalysts on the reaction. We find that H$_{2}$SO$_{4}$ lowers the reaction barriers the greatest, with the barrier for the cyclization step being reduced to -13.1 kcal/mol and that for the dehydration step going down to 9.2 kcal/mol, below their respective separated starting reactants. Interestingly, our rate calculations shows that HNO$_{3}$ provides the fastest rate due the combined effects of larger atmospheric concentration and reduced barrier. Thus, our study suggests that with acid catalysis the cyclization reaction step can readily occur for 1,4-hydroxycarbonyls in the gas phase. The 2-OH-THF products, once formed, likely undergo reaction with OH radicals in the atmosphere because the dehydration step involves a large barrier even with acid catalysis. The reaction pathways and rate constant for this reaction in the presence of molecular oxygen ($^{3}$O$_{2}$) were also investigated using computational chemistry over the 200-300K temperature range. The main products found from the 2-OH-THF + OH/$^{3}$O$_{2}$ reactions are succinaldehyde + HO$_{2}$ and 2,3-dihydro-2-furanol + HO$_{2}$

Utility of polymerase chain reaction using two probes for rapid diagnosis of tubercular pleuritis in comparison to conventional methods

We have used polymerase chain reaction (PCR) with IS6110 and a new set of primers from an insertion element like repetitive sequence, (TRC4) to detect Mycobacterium tuberculosis in pleural effusion samples from 50 patients having pleuritis. The results of PCR were compared with the results of conventional methods like smear, culture and adenosine deaminase activity. Thirty six specimens were positive and 14 were negative by PCR. Among the 36 samples, 33 were from patients with clinical evidence of tuberculosis including response to anti-tuberculosis therapy. Only six samples were positive by the gold standard which is culture, and three were positive by smear. The measurement of adenosine deaminase activity classified 19 samples as positives. The overall sensitivity and specificity of PCR was 100 and 85 per cent respectively. PCR using IS6110 and TRC4 primers is a sensitive test as compared to conventional tests for detection of M. tuberculosis from pleural fluid samples of patients with tubercular pleuritis

Evaluation of PCR Using TRC4 and IS6110 Primers in Detection of Tuberculous Meningitis

We have evaluated a new set of primers (TRC4) in comparison with the IS6110 primers commonly used in PCR to detect tuberculous meningitis among children. The levels of concordance between the results of IS6110 PCR and TRC4 PCR with cerebrospinal fluid specimens from patients with clinically confirmed tuberculous meningitis were 80 and 86%, respectively. Results with the two primer sets were concordant for 55 positive and 22 negative specimens (n 5 98). We conclude that the sensitivity of PCR can be increased by using both IS6110 and TRC4 primers

Comparative evaluation of PCR using IS6110 and a new target in the detection of tuberculous lymphadenitis

We evaluated TRC4 primers using polymerase chain reaction (PCR) which amplify a new target sequence from Mycobacterium tuberculosis genome to diagnose tuberculous lymphadenitis and compared the results with PCR using the widely used IS6110 primers. The PCR results were also compared with conventional methods like smear, culture and histopathology. The sensitivity of PCR using both probes is higher than the conventional methods. Out of 101 samples analysed (49 fresh and 52 fixed specimens), PCR using IS6110 and TRC4 primers was positive in 64 and 70 samples, respectively, whereas results with culture and histopathology methods were positive only in 49 and 58 samples, respectively. The problem of false negativity of IS6110 due to the absence of IS6110 copy in 4 M. tuberculosis isolates was overcome by using TRC4 primers. The results indicate that with improvement in PCR techniques, PCR using both probes, IS6110 and TRC4 can be a rapid and sensitive adjunct to conventional techniques in the diagnosis of tuberculous lymphadenitis

Nucleic acid amplification tests in the diagnosis of tuberculous pleuritis: a systematic review and meta-analysis

BACKGROUND: Conventional tests for tuberculous pleuritis have several limitations. A variety of new, rapid tests such as nucleic acid amplification tests – including polymerase chain reaction – have been evaluated in recent times. We conducted a systematic review to determine the accuracy of nucleic acid amplification (NAA) tests in the diagnosis of tuberculous pleuritis. METHODS: A systematic review and meta-analysis of 38 English and Spanish articles (with 40 studies), identified via searches of six electronic databases, hand searching of selected journals, and contact with authors, experts, and test manufacturers. Sensitivity, specificity, and other measures of accuracy were pooled using random effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. Heterogeneity in study results was formally explored using subgroup analyses. RESULTS: Of the 40 studies included, 26 used in-house ("home-brew") tests, and 14 used commercial tests. Commercial tests had a low overall sensitivity (0.62; 95% confidence interval [CI] 0.43, 0.77), and high specificity (0.98; 95% CI 0.96, 0.98). The positive and negative likelihood ratios for commercial tests were 25.4 (95% CI 16.2, 40.0) and 0.40 (95% CI 0.24, 0.67), respectively. All commercial tests had consistently high specificity estimates; the sensitivity estimates, however, were heterogeneous across studies. With the in-house tests, both sensitivity and specificity estimates were significantly heterogeneous. Clinically meaningful summary estimates could not be determined for in-house tests. CONCLUSIONS: Our results suggest that commercial NAA tests may have a potential role in confirming (ruling in) tuberculous pleuritis. However, these tests have low and variable sensitivity and, therefore, may not be useful in excluding (ruling out) the disease. NAA test results, therefore, cannot replace conventional tests; they need to be interpreted in parallel with clinical findings and results of conventional tests. The accuracy of in-house nucleic acid amplification tests is poorly defined because of heterogeneity in study results. The clinical applicability of in-house NAA tests remains unclear

Thermal Decomposition of 2‑Pentanol: A Shock Tube Study and RRKM Calculations

A single pulse shock tube was used to study the thermal decomposition of 2-pentanol in the temperatures between 1110 and 1325 K. Three major decomposition products are methane, ethylene, and propylene. The minor products detected in lower concentration are ethane, acetylene, acetaldehyde, 1-pentene, and 2-pentene. The rate coefficient for the overall decomposition of 2-pentanol was found to be <i>k</i>_total^exp(1110–1325 K) = (4.01 ± 0.51) × 10⁹ exp­(−(36.2 ± 4.7)/<i>RT</i>) s^–1, where the activation energies are given in kcal mol^–1. To simulate reactant and product distribution over the experimentally studied temperatures between 1110 and 1325 K, a reaction scheme was constructed with 34 species and 39 reactions. In addition to this, the temperature and pressure dependent rate coefficients were computed for various unimolecular dissociation pathways using RRKM theory. The high pressure limit rate coefficient for overall decomposition of 2-pentanol was obtained to be <i>k</i>_total^theory(500–2500 K) = (9.67 ± 1.11) × 10¹⁴ exp­(−(67.7 ± 2.9)/<i>RT</i>) s^–1. The calculated high pressure rate coefficients and experimentally measured rate constants are in good agreement with each other. The reaction is primarily governed by the unimolecular elimination of water

Organic Acid Formation from the Atmospheric Oxidation of Gem Diols: Reaction Mechanism, Energetics, and Rates

Computational chemistry is used to investigate the gas phase reaction of several gem diols in the presence of OH radical and molecular oxygen (³O₂) as would occur in the Earth’s troposphere. Four gem diols, represented generically as R–HC­(OH)₂, with R being either −H, −CH₃, −HC­(O), and −CH₃C­(O) are investigated. We find that after the abstraction of the hydrogen atom from the C–H moiety of the diol by atmospheric OH, molecular oxygen quickly adds onto the resulting radicals leading to the formation of a geminal diol peroxy adduct (R–C­(OO)­(OH)₂), which is the key intermediate in the oxidation process. Unimolecular reaction of this R–C­(OO)­(OH)₂ radical adduct, occurs via a proton-coupled electron transfer (PCET) mechanism and leads to the formation of an organic acid and a HO₂ radical. Further, the barrier for the unimolecular reaction step decreases along the R substitution series: −H, −CH₃, −HC­(O), −CH₃C­(O); this trend most likely arises from increased internal hydrogen bonding along the series. The reaction where the R group is CH₃C­(O), associated with methylglyoxal diol, has the lowest barrier with its transition state being ∼4.3 kcal/mol above the potential energy well of the corresponding CH₃C­(O)-C­(OO)­(OH)₂ peroxy adduct. The rate constants for the four diol oxidation reactions were investigated using the MESMER master equation solver kinetics code over the temperature range between 200 and 300 K. The calculations suggest that once formed, gem diol radicals react rapidly with O₂ in the atmosphere to produce organic acids and HO₂ with an effective gas phase bimolecular rate constant of ∼1 × 10^–11 cm³/molecule s at 300 K

A Computational Study Investigating the Energetics and Kinetics of the HNCO + (CH₃)₂NH Reaction Catalyzed by a Single Water Molecule

High-level ab initio calculations are used to explore the energetics and kinetics for the formation of 1,1-dimethyl urea via the reaction of isocyanic acid (HNCO) with dimethyl amine (DMA) catalyzed by a single water molecule. Compared to the uncatalyzed HNCO + DMA reaction, the presence of a water molecule lowers the reaction barrier, defined here as the energy difference between the separated HNCO + DMA + H₂O reactants and the transition state (TS), by ∼26 kcal/mol. In addition to the HNCO + DMA + H₂O reaction, the energetics of the analogous reactions involving, respectively, ammonia and methyl amine were also investigated. Comparing the barriers for these three amine addition reactions, which can be represented as HNCO + R-NH-R′ + H₂O with R and R′ being either −CH₃ or −H, we find that the reaction barrier decreases with the degree of methylation on the amine nitrogen atom. The effective rate constants for the bimolecular reaction pathways HNCO··H₂O + DMA and HNCO··DMA + H₂O were calculated using canonical variational TS theory coupled with both small curvature and zero-curvature tunneling corrections over the 200–300 K temperature range. For comparison, we also calculated the rate constant for the HNCO + OH reaction. Our results suggest that the HNCO + H₂O + DMA reaction can make a non-negligible contribution to the gas-phase removal of atmospheric HNCO under conditions where the HNCO and water concentrations are high and the temperature is low