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We have carried out a two-layer our own n-layered integrated molecular orbital and molecular mechanics (MM) study on the mechanism of ethanol to propene on H-ZSM-5 and H-FAU zeolites. The entire me...

NLRP3 inflammasome is a vital player in macrophages pyroptosis, which is a type of proinflammatory cell-death and takes part in the pathogenesis of atherosclerosis. In this study, we used apoE−/− mice and ox-LDL induced THP-1 derived macrophages to explore the mechanisms of MCC950, a selective NLRP3 inhibitor in treating atherosclerosis. For the in vivo study, MCC950 was intraperitoneal injected to 8-week-old apoE−/− mice fed with high-fat diet for 12 weeks. For the in vitro study, THP-1 derived macrophages were treated with ox-LDL and MCC950 for 48 h. MCC950 administration reduced plaque areas and macrophages contents, but did not improve the serum lipid profiles in aortic root of apoE−/− mice. MCC950 inhibited the activation of NLRP3/ASC/Caspase-1/GSDMD-N axis, and alleviated macrophages pyroptosis and the production of IL-1β and IL-18 both in aorta and in cell lysates. However, MCC950 did not affect the expression of TLR4 or the mRNA levels of NLRP3 inflammasome and its downstream proteins, suggesting that MCC950 had no effects on the priming of NLRP3 inflammasome activation in macrophages. The anti-atherosclerotic mechanisms of MCC950 on attenuating macrophages inflammation and pyroptosis involved in inhibiting the assembly and activation of NLRP3 inflammasome, rather than interrupting its priming.

We have carried out a two-layer our own n-layered integrated molecular orbital and molecular mechanics (ONIOM) study on the hydrodesulfurization (HDS) mechanism of three hydrogenated thiophene derivatives over Cu-Mo modified FAU zeolite. The thiophene is hydrogenated relatively easily to 2,3-dihydrothiophene (2,3-DHT), 2,5-dihydrothiophene (2,5-DHT) and tetrahydrothiophene (THT) due to low free energy barriers. Hydrogenolysis desulfurization (HYD) and direct desulfurization (DDS) are discussed. Ring-opening, hydrogen transfer and C−S bond cleavage steps of thiophene derivatives are involved in the HYD process. The rate-determining steps are the hydrogen transfer step for 2,5-DHT and C−S bond cracking step for 2,3-DHT and THT. The concerted DDS pathway is probably more favorable than the HYD pathway in the desulfurization of 2,5-DHT. The hydrogenation of thiophene to 2,5-DHT, 2,3-DHT and THT and their HDS process are entropy-decreased; the formation of sulfur vacancy is entropy-increased. The difference charge density (DCD) analysis reveals that for the ring-opening process, the electrons are migrated from the organic chain to the Cu-Mo catalytic center. The reduced density gradient (RDG) plots indicate that both a steric hindrance and a weak van der Waals attractive interaction exist between organic fragment and catalytic center for all transition states (TSs). The localized orbital locator (LOL) maps for all TSs suggest that there are strong covalent interactions between the atoms in the forming chemical bonds and weak van der Waals interactions between the atoms in the breaking chemical bonds.

MCC950 has been proposed as a specific small molecule inhibitor that can selectively block NLRP3 inflammasome activation. However, the exact mechanism of its action is still ambiguous. Accumulating investigations imply that chloride efflux-dependent ASC speck oligomerization and potassium efflux-dependent activation of caspase-1 are the two relatively independent, but indispensable events for NLRP3 inflammasome activation. Previous studies suggested that influence of MCC950 on potassium efflux and its consequent events such as interaction between NEK7 and NLRP3 are limited. However, inhibiting chloride intracellular channel-dependent chloride efflux leads to a modification of inflammatory response, which is similar to the function of MCC950. Based on these findings, we shed new insights on the understanding of MCC950 that its function might correlate with chloride efflux, chloride intracellular channels, or other targets that act upstream of chloride efflux.

Density functional theory calculations were carried out to study the reaction mechanism of the Rh(iii)-catalyzed regioselective C-H cyanation of indole and indoline with N-cyano-N-phenyl-para-methylbenzenesulfonamide (NCTS). This mechanism involves four major steps: C-H activation, cyano group insertion, β-N elimination, and regeneration of active species. How different indole and indoline substrates affect the regioselectivity of C-H bond cyanation has been examined and analyzed in detail. Our calculation results indicate that the regioselectivity of C-H bond cyanation of indole depends on the nucleophilicity of carbon atoms in C-Rh(iii) bonds to the cyano group. For indoline, it can be attributed to the different hybridization platforms of the C-H bond activation.

Copper-mediated radical cyclization of naphthalenyl iododifluoromethyl ketones with olefins was successfully developed to generate a series of unprecedented gem-difluorodihydrophenanthrenones, especially 2,2-difluoro-3,4-dihydrophenanthren-1(2H)-one derivatives. This strategy features the use of cheap copper powder and excellent regioselectivity and diastereoselectivity, thus providing a facile approach for application in drug discovery and development. Preliminary mechanistic studies indicate the involvement of difluorinated radical intermediates. Density functional theory (DFT) calculation was performed to provide further evidence for regioselectivity.

We have presented a two-layer ONIOM study on the unimolecular and bimolecular hydrodesulfurization (HDS) mechanisms of thiophene catalyzed by H-Beta, H-MCM-22, H-ZSM-5, and H-FAU zeolites. The rate...

The GeO2 modified high-concentration Er3+/Yb3+ co-doped phosphate glasses with composition 64P2O5–2ZnO–13BaCO3–13K2CO3–8Al2O3–0.5Er2O3–12Yb2O3–xGeO2 mol% (PEYG, x=0, 2.5, 5, 7.5, and 10) were successfully prepared by the melt-quenching method. The structure and spectroscopic properties were revealed by analyzing refractive index, expansion coefficient, glass transition temperature, absorption and emission spectra, and laser properties. We studied the relationship between GeO2 doping content and spectroscopic properties, finding that GeO2 could enhance 1535 nm emission of the PEYG glasses. The PEYG modified with 5 mol% GeO2 showed the best spectroscopic properties. The study provided a good guidance for the design of high gain laser glasses and fibers.

As a novel solid-phase extraction material, zinc oxide crystal whiskers were used to extract flavonoid compounds and showed good extraction abilities. X-ray diffraction, scanning electron microscopy with energy dispersive X-ray spectroscopy and surface area/pore volume characterized the sorbent. The zinc oxide was packed into a solid-phase extraction micro-column and its extraction ability was evaluated by four model flavonoid compounds. The sample loading and elution parameters were optimized and the zinc oxide based analytical method for flavonoids was established. It showed that the method has wide linearities from 1 to 150μg/L and low limits of detection at 0.25μg/L. The relative standard deviations of a single column repeatability and column to column reproducibility were less than 6.8% and 10.6%. Several real samples were analyzed by the established method and satisfactory results were obtained. The interactions between flavonoids and zinc oxide were calculated and proved to be from the Van der Waals' forces between the 4p and 5d orbitals from zinc atom and the neighboring π orbitals from flavonoid phenyl groups. Moreover, the zinc oxide crystal whiskers showed good stability and could be reused more than 50 times under the operation conditions. This work proves that the zinc oxide crystal whiskers are a good candidate for flavonoids enrichment.

The contributions of the poly(methylbenzene) (polyMB) and alkene cycles to the methanol to propene (MTP) process in H-FAU zeolite have been investigated by a two-layer ONIOM (our own n-layered integrated molecular orbital and molecular mechanics) method, which is important to understand the nature of formation of propene in zeolite with large pore sizes. The calculated results demonstrate that the different pathways in the polyMB cycle occur in the following order of reactivity: methyl-transfer pathway > spiro pathway > direct internal H-shift > paring pathway. The polyMB cycle is more competitive than the alkene cycle for the MTP process in H-FAU, which is different from the previous results on H-ZSM-5. Introduction of Li+ and Ag+ cations into FAU zeolite does not reduce the free energy barriers of the methylation steps involved in polyMB and alkene cycles, indicating that the experimental efforts to improve propene selectivity probably should focus on the physical effect of Li+ and Ag+ cations. For the ...

A two-layer ONIOM study has been carried out to investigate the unimolecular and bimolecular cracking mechanisms of thiophene catalyzed by acidic and metal cation-exchanged (Li + , Na + , K + , Cu + , and Ag + ) beta zeolites. The unimolecular cracking reactions of 3,4-dimethylthiophene (3,4-DMT) and benzothiophene (BT) catalyzed by acidic beta zeolite are also calculated. It was found that the rate-determining steps in these two mechanisms are both C S bond cracking. Furthermore, the activation energy of C S bond cracking in bimolecular mechanism is lower than that in unimolecular mechanism, indicating that the bimolecular cracking process is more favorable. In addition, although the activation energies of C S bond cleavage of 3,4-DMT and BT over H-beta zeolite are relatively lower than thiophene, the practical process would be difficult to occur due to still high energy barriers. A close analysis of activation energies over cation-exchanged zeolites suggests that the metal cations do not reduce and contrarily increase their difficulty of thiophene cracking reactions.

This paper presents diffusion data of N2, O2, H2S and SO2 in MFI and 4A zeolites obtained by molecular dynamics simulations, especially its dependence on temperature and loading. At high loadings and temperatures, the order of self-diffusivity of guests in two zeolites is O2 > N2 > H2S>SO2. The diffusion behaviour is different in different zeolites at lower loadings, reflecting different influences from straight channels (MFI) and α-cages (4A). Furthermore, with increasing loading, the self-diffusivity of guest molecules decreases in MFI but generally increases in 4A. The centre of mass (COM) probability densities and diffusion trajectories of guests give insight into molecular-level diffusion process. The simulation results reveal that with increasing loading, the diffusion mechanism would change from the inter-pore to intra-pore diffusion in MFI. However, in 4A, the intra-pore diffusion is predominant at low and high loadings, but inter-pore diffusion is more important at moderate loadings.

Using force field parameters developed and validated for zeolitic imidazolate frameworks (ZIFs) and carbon dioxide (CO2) independently from adsorption data, we predicted CO2/ZIFs adsorption isotherms using the Grand Canonic Monte Carlo (GCMC) method. The results are in sharp contradiction: the calculated adsorption data agree well with the experimental data for SOD-type ZIF-8, but are more than 100% higher than the experimental data for GME-type ZIFs. Using non-equilibrium molecular dynamics simulations and potential of mean force (PMF) calculations, we reveal that the discrepancies are due to the kinetic blockage which is significant for ZIF-68 but negligible for ZIF-8. This study demonstrates that a force field developed independently from the adsorption data can be used to predict the adsorptions accurately; and the kinetic factor must be considered if the bottlenecks exist in the adsorption paths due to geometric and energetic features of adsorbate and adsorbent. It could be very misleading if the force field parameters are adjusted by fitting the GCMC simulation data to experimental data without considering the kinetic factors.

A solid-phase extraction (SPE) method for the efficient analysis of trace phenolic acids (PAs, caffeic acid, ferulic acid, protocatechuic acid, cinnamic acid) in urine was established. In this work, a graphene oxide (GO) coating was grafted onto pure silica to be investigated as SPE material. The prepared GO surface had a layered and wrinkled structure that was rough and well organized, which could provide more open adsorption sites. Owing to its hydrophilicity and polarity, GO showed higher extraction efficiency toward PAs than reduced GO did, in agreement with the theoretical calculation results performed by Gaussian 09 software. The adsorption mechanism of PAs on GO@Sil was also investigated through static state and kinetic state adsorption experiments, which showed a monolayer surface adsorption. Extraction capacity of the as-prepared material was optimized using the response surface methodology. Under the optimized conditions, the as-established method provided wide linearity range (2–50 μg L−1 for protocatechuic acid and 1–50 μg L−1 for caffeic acid, ferulic acid, and cinnamic acid) and low limits of detection (0.25–1 μg L−1). Finally, the established method was applied for the analysis of urine from two healthy volunteers. The results indicate that the prepared material is a practical, cost-effective medium for the extraction and determination of phenolic acids in complex matrices.

Background/Aims: The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) is a basic leucine zipper transcription factor that plays essential roles in tumor progression. Although decreased or absent C/EBPα expression in many cancers suggests a possible role for C/EBPα as a tumor suppressor, the functions of C/EBPα in lung adenocarcinoma remain unclear. Methods: Here, C/EBPα expression levels in 26 lung adenocarcinoma and para-carcinoma tissue samples were detected by qRT-PCR and immunohistochemistry. Cell transwell assays, wound healing assay and three-dimensional spheroid invasion assay were performed to assess the effects of C/EBPα on migration and invasion in lung adenocarcinoma cells in vitro . Western blotting was applied to analyze the potential mechanisms. Results: C/EBPα was found to be decreased in lung adenocarcinoma tissues compared to para-carcinoma tissues. Overexpression of C/EBPα significantly inhibited the migration and invasion of lung adenocarcinoma cells. In addition, C/EBPα overexpression suppressed the epithelial–mesenchymal transition (EMT) that was characterized by a gain of epithelial and loss of mesenchymal markers. Further study showed that C/EBPα suppressed the transcription of β-catenin and downregulated the levels of its downstream targets. Conclusion: Our data suggest that C/EBPα inhibits lung adenocarcinoma cell invasion and migration by suppressing β-catenin-mediated EMT in vitro . Thus, C/EBPα may be helpful as a potential target for treatment of lung adenocarcinoma.

Two-layer ONIOM calculations have been carried out to study methanol to propene (MTP) conversion reactions catalyzed by H-beta zeolite. On the basis of the so-called side-chain hydrocarbon pool (HCP) mechanism, this work proposes the complete catalytic cycle pathway for the MTP reaction. The cycle starts from the methylation of pentamethylbenzene (PMB), which leads to the formation of hexamethylbenzenium ion (hexaMB+). Subsequent steps involving deprotonation, methylation, an internal H-shift, and a unimolecular CH3-shift are required to produce propene and ethene. The calculated activation barriers and reaction energy data indicate that propene is the more favored product, rather than ethene, from both kinetic and thermodynamic perspectives, which is consistent with experimental observations. In addition, the calculations suggest that the activation barriers of the reaction steps decrease in the order: internal H-shift > methylation > unimolecular CH3-shift ≥ deprotonation. In the methylation step, methylation of the exocyclic double bond is easier than methylation of the ring carbons on the aromatic benzene derivative.

The crystal structure of 1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-6-ethyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile was obtained and determined by X-ray crystallography. The reaction mechanism of 5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrile with unsaturated carbonyl compounds was further proposed.

Equilibrium and non-equilibrium molecular dynamics and Monte Carlo simulation techniques were applied to predict various thermodynamic, transport and vapor–liquid equilibrium properties of binary mixtures of ethylene glycol and water (EG–W) based on OPLS-AA and SPC/E force fields. The properties predicted include density, vaporization enthalpy, enthalpy of mixing, heat capacities, diffusion coefficients, shear viscosities, thermal conductivities, vapor–liquid coexistence isotherms and isobaric curves, and saturation vapor pressures. Good agreements with experimental data were obtained for most of these properties. Errors are mostly related to inaccuracy found in predictions of pure fluids; a correction to prediction of pure substance can systematically improve prediction for the mixture. This work suggests that OPLS-AA and SPC/E force fields using the common combining rules are transferable for predicting multiple physical properties of EG–W mixtures.

We propose to incorporate a lithium tetrazolide group into porous materials for enhancing hydrogen storage capacity. The lithium tetrazolide group is much more stable and polarized than the models made by doping aromatic groups with lithium atoms. More importantly, each of the lithium tetrazolide provides 14 binding sites for hydrogen molecules with modest interaction energies. The advantage of multiple binding sites with modest binding energies is partially demonstrated by constructing a new porous aromatics framework (PAF-4) with the lithium tetrazolide moieties and predicting its hydrogen uptake using first-principles GCMC simulations. The predicted hydrogen uptake reaches 4.9 wt % at 233 K and 10 MPa, which exceeds the 2010 DOE target of 4.5 wt %.

Two-layer ONIOM calculations were carried out to study initial reactions of catalytic cracking of 1-butene to produce propene and ethene on HZSM-5 and HFAU zeolites. Direct cracking and dimerization cracking mechanisms were evaluated. The calculated data indicate that the dimerization cracking is more favorable than the direct cracking based on both kinetic and thermodynamic considerations. HZSM-5 is catalytically more effective than HFAU for the cracking reactions. ONIOM energy analysis shows that the effectiveness of zeolite is due to long-range van der Waals interaction energies that stabilize all reaction intermediates, and short-range interaction between the zeolite and the reacting species that reduce the activation energies. For the dimerization process, stepwise and concerted mechanisms are similar in energy changes. Generally speaking, dimerizations appear to be exothermic reactions with modest activation energies. The activation energies for isomerization, β-scission, and deprotonation are lower...

A two-layer ONIOM study on the hydrodesulfurization mechanism of thiophene in H-FAU and M-FAU (M = Li(+), Na(+), and K(+)) has been carried out. The calculated results reveal that in H-FAU, for a unimolecular mechanism, the rate-determining step is hydrogenation of alkoxide intermediate. The assistance of H2O and H2S molecules does not reduce the difficulty of the C-S bond cracking step more effectively. A bimolecular hydrodesulfurization mechanism is more favorable due to the lower activation barriers. The rate-determining step is the formation of 2-methylthiophene, not the C-S bond cracking of thiophene. Moreover, the ring opening of thiophene is much easier to occur than the desulfurization step. A careful analysis of energetics indicates that H2S, propene, and methyl thiophene are the major products for the hydrodesulfurization process of thiophene over H-FAU zeolite, in good agreement with experimental findings. In M-FAU zeolites, both unimolecular and bimolecular cracking processes are difficult to occur because of the high energy barriers. Compared to the case on H-FAU, the metal cations on M-FAU increase the difficulty of occurrence of bimolecular polymerization and subsequent C-S bond cracking steps. Graphical abstract Hydrodesulfurization process of thiophene can take place in H-FAU zeolite. Two different mechanisms, unimolecular and bimolecular ones, have been proposed and evaluated in detail. The bimolecular mechanism is more favorable due to lower activation barrier as described in the picture above. Our calculated data indicate that H2S, propene, and methylthiophene are the major products, in good agreement with experimental observations. The effect of metal cations on the reaction mechanism is also investigated in this work.

An all-atom force field is developed for metal organic frameworks Zn4O(RCO2)6 by fitting to quantum mechanics data. Molecular simulations are conducted to validate the force field by calculating thermal expansion coefficients, crystal bulk and Young’s moduli, power spectra, self-diffusion coefficients, and activation energies of self-diffusions for benzene and n-hexane. The calculated results are in good agreement with available experimental data. The proposed force field is suitable for simulations of adsorption or diffusion of organic molecules with flexible frameworks.

Highly stable salt functional groups consisting of lithium cation and aromatic anions (C n H n N5-n -Li) are studied for hydrogen storage using ab initio calculations, force field development, and grand canonical Monte Carlo simulations. Second-order Moller-Plesset perturbation theory with the resolution of identity approximation calculations are calibrated at the CCSD(T)/complete basis set (CBS) level of theory. The calibrations on different types of binding sites are different, but can be used to correct the van der Waals interactions systematically. The anion and salt functional groups provide multiple binding sites. With increased number of nitrogen atoms in the aromatic anion, the number of binding sites increases but the average binding energy decreases. Among the functional groups considered, CHN4-Li exhibits the largest number of binding sites (14) and a weak average binding energy of 5.7 kJ mol(-1) with CCSD(T)/CBS correction. The calculated adsorption isotherms demonstrate that the introduction of the functional group significantly enhances hydrogen uptake despite relatively weak average binding energy. Therefore, it is concluded that searching for functional groups with the larger number of binding sites is another key factor for enhancing the hydrogen storage capacity, given that other conditions such as free volume and surface area are fixed.

The first setup of pulse radiolysis system in China with the time resolution of 2μs has been built up recently in Beijing Radiation Center. The experimental apparatus is described briefly. The observation of transient absorption of Br-2 and I-2 radicals in aqueous solution using this system is introduced.