Synthesis of Benzofuran-Fused Oxepines through Cs₂CO₃‑Promoted [4 + 3] Annulation of Aurones with Crotonate-Derived Sulfonium Salts

Benzofuran-fused derivatives display important and reliable therapeutic properties. Herein, we describe the synthesis of benzofuran-fused oxepines using aurones and crotonate-derived sulfonium salts via a [4 + 3] annulation reaction in the presence of Cs2CO3. This reaction proceeds under mild and operationally simple conditions. The synthetic utility of this approach was highlighted by several transformations, including the efficient synthesis of a novel tetracyclic fused benzofuran derivative

Formation of Nitroanthracene and Anthraquinone from the Heterogeneous Reaction Between NO₂ and Anthracene Adsorbed on NaCl Particles

Oxidative derivatives of polycyclic aromatic hydrocarbons (PAHs), that is, nitro-PAHs and quinones, are classed as hazardous semivolatile organic compounds but their formation mechanism from the heterogeneous reactions of PAHs adsorbed on atmospheric particles is not well understood. The heterogeneous reaction of NO₂ with anthracene adsorbed on NaCl particles under different relative humidity (RH 0–60%) was investigated under dark conditions at 298 K. The formation of the major products, 9,10-anthraquinone (9,10-AQ) and 9-nitroanthracene (9-NANT), were determined to be second-order reactions with respect to NO₂ concentration. The rate of formation of 9,10-AQ under low RH (0–20%) increased as the RH increased but decreased when the RH was further increased in high RH (40–60%). In contrast, the rate of formation of 9-NANT across the whole RH range (0–60%) decreased significantly with increasing RH. Two different reaction pathways are discussed for the formation of 9,10-AQ and 9-NANT, respectively, and both are considered to be coupled to the predominant reaction of NO₂ with the NaCl substrate. These results suggest that relative humidity, which controls the amount of surface adsorbed water on NaCl particles, plays an important role in the heterogeneous reaction of NO₂ with adsorbed PAHs

Automated Fragmentation QM/MM Calculation of Amide Proton Chemical Shifts in Proteins with Explicit Solvent Model

We have performed a density functional theory (DFT) calculation of the amide proton NMR chemical shift in proteins using a recently developed automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach. Systematic investigation was carried out to examine the influence of explicit solvent molecules, cooperative hydrogen bonding effects, density functionals, size of the basis sets, and the local geometry of proteins on calculated chemical shifts. Our result demonstrates that the predicted amide proton (¹H_N) NMR chemical shift in explicit solvent shows remarkable improvement over that calculated with the implicit solvation model. The cooperative hydrogen bonding effect is also shown to improve the accuracy of ¹H_N chemical shifts. Furthermore, we found that the OPBE exchange-correlation functional is the best density functional for the prediction of protein ¹H_N chemical shifts among a selective set of DFT methods (namely, B3LYP, B3PW91, M062X, M06L, mPW1PW91, OB98, OPBE), and the locally dense basis set of 6-311++G**/4-31G* is shown to be sufficient for ¹H_N chemical shift calculation. By taking ensemble averaging into account, ¹H_N chemical shifts calculated by the AF-QM/MM approach can be used to validate the performance of various force fields. Our study underscores that the electronic polarization of protein is of critical importance to stabilizing hydrogen bonding, and the AF-QM/MM method is able to describe the local chemical environment in proteins more accurately than most widely used empirical models

Kinetic Study of Gas-Phase Reactions of OH and NO₃ Radicals and O₃ with iso-Butyl and <i>tert</i>-Butyl Vinyl Ethers

Using a relative rate technique, kinetic studies on the gas-phase reactions of OH radicals, ozone, and NO₃ radicals with iso-butyl vinyl ether (iBVE) and <i>tert</i>-butyl vinyl ether (<i>t</i>BVE) have been performed in a 405 L Duran glass chamber at (298 ± 3) K and atmospheric pressure (750 ± 10 Torr) in synthetic air using in situ FTIR spectroscopy to monitor the reactants. The following rate coefficients (in units of cm³ molecule^–1 s^–1) have been obtained: (1.08 ± 0.23) × 10^–10 and (1.25 ± 0.32) × 10^–10 for the reactions of OH with iBVE and <i>t</i>BVE, respectively; (2.85 ± 0.62) × 10^–16 and (5.30 ± 1.07) × 10^–16 for the ozonolysis of iBVE and <i>t</i>BVE, respectively; and (1.99 ± 0.56) × 10^–12 and (4.81 ± 1.01) × 10^–12 for the reactions of NO₃ with iBVE and <i>t</i>BVE, respectively. The rate coefficients for the NO₃ reactions are first-time determinations. The measured rate coefficients are compared with estimates using current structure activity relationship (SAR) methods and the effects of the alkoxy group on the gas-phase reactivity of the alkyl vinyl ethers toward the oxidants are compared and discussed. In addition, estimates of the tropospheric lifetimes of iBVE and <i>t</i>BVE with respect to their reactions with OH, ozone, and NO₃ for typical OH radical, ozone, and NO₃ radical concentrations are made, and their relevance for the environmental fate of compounds is considered

Single Biosensor for Simultaneous Quantification of Glucose and pH in a Rat Brain of Diabetic Model Using Both Current and Potential Outputs

Glucose and pH are two important indicators of diabetes mellitus. However, their dynamic changes at the same time in brain are still not clear, mainly due to a lack of a single biosensor capable of simultaneous quantification of two species in a live rat brain. In this work, a selective and sensitive ratiometric electrochemical biosensor was developed for simultaneously quantifying glucose and pH using both current and potential outputs in a rat brain of diabetic model. Here, glucose oxidase was first employed as a specific recognition element for both glucose and pH because the active center (FAD) could undergo a 2H⁺/2e^– process. Moreover, an insensitive molecule toward pH and glucose was used as an inner-reference element to provide a built-in correction to improve the accuracy. The ratio between the oxidation peak current density of glucose and that of ABTS gradually increased with increasing concentration of glucose, and showed a good linearity in the range of 0.3–8.2 mM. Meanwhile, the midpotential difference between glucose oxidase and 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) positively shifted with pH decreasing, leading to accurate determination of pH in the linear range of 5.67–7.65. Thus, combined with the unique properties of carbon fiber microelectrode, including easy to insert and good biocompatibility, the developed single biosensor was successfully applied to detect pH and glucose at the same time in hippocampus, striatum, and cortex in a live rat brain of diabetic model

Coupling effect of high-temperature and microbial community on the removal of antibiotics and antibiotic resistance genes in sludge hyper-temperature aerobic bio-drying system

Antibiotic residues and antibiotic resistance genes (ARGs) in sludge pose high risks to human health and the ecological environment. Hyper-temperature aerobic bio-drying system (HTAB) has the potential for higher degradation efficiency of antibiotics and ARGs due to high-temperature and rapid organic matter degradation. This study firstly reports two sludge HTAB processes, hyperthermophilic aerobic bio-drying (HAB) and electro-assisted heating bio-drying (EHAB), for the removal efficiency of four types of antibiotics, quinolones, tetracyclines, macrolides, and sulfonamide antibiotics, and ARGs, as well as the relationship between antibiotics and ARGs. The microbial communities of the two HTAB processes showed significant differences compared to the conventional bio-drying process (CAB). Compared to the CAB, the HTAB significantly improved the removal efficiency of antibiotics and ARGs and shortened the half-life of antibiotics. In the two HTAB processes, the total antibiotic removal of the HAB and EHAB processes was 78.11 and 74.15%, respectively. Compared with the EHAB process, the HAB process had higher removal for all four types of antibiotics, especially significantly improving the removal efficiency of tetracyclines. Compared to the CAB, both HTAB processes significantly enhanced the removal efficiency of ARGs and mobile genetic elements (MGEs). In the two HTAB processes, the HAB showed a higher removal efficiency of ARGs and MGEs compared to the EHAB. The relevant mechanisms indicated that temperature and changes in microbial communities jointly affected the removal efficiency of antibiotics and ARGs.</p

Synergy of phosphate and hyperthermophilic bio-drying reduces pollution of sludge bio-drying: Reducing ammonia emissions and heavy metal migration risk

Hyperthermophilic bio-drying has stronger organic matter degradation and drying ability than the conventional bio-drying. However, ammonia emissions during the hyperthermophilic bio-drying are significantly higher than those during the conventional bio-drying process due to the higher temperature and pH value. Phosphate has been reported to reduce ammonia emissions during composting. Meanwhile, both the degradation of organic matter and the addition of phosphate buffer can promote the formation of EPS. EPS exhibits strong passivation and adsorption properties for heavy metals and organic pollutants, thus positively impacting the control of pollution in bio-drying products. Furthermore, the formation of EPS and the risk of the migration of heavy metals during hyperthermophilic bio-drying have not been reported. According to the results, compared to conventional bio-drying, the hyperthermophilic bio-drying significantly increased the yield of EPS and generated more active groups, reducing the migration risk of Cu, Zn, Cr, Pb, Cd, As, and Ni. The comprehensive potential ecological risk was reduced by 29.71%, which was higher than the reduction achieved by conventional bio-drying (13.81%). The addition of phosphate significantly reduced the ammonia emissions from the hyperthermophilic bio-drying and retained more nitrogen. Meanwhile, it promoted the formation of EPS and the enrichment of active groups, further reducing the migration risk of heavy metals. Moreover, the addition of phosphate buffer further reduced the comprehensive potential ecological risk of the products obtained from.</p

Table_1_Automated Fragmentation QM/MM Calculation of NMR Chemical Shifts for Protein-Ligand Complexes.PDF

<p>In this study, the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) method was applied for NMR chemical shift calculations of protein-ligand complexes. In the AF-QM/MM approach, the protein binding pocket is automatically divided into capped fragments (within ~200 atoms) for density functional theory (DFT) calculations of NMR chemical shifts. Meanwhile, the solvent effect was also included using the Poission-Boltzmann (PB) model, which properly accounts for the electrostatic polarization effect from the solvent for protein-ligand complexes. The NMR chemical shifts of neocarzinostatin (NCS)-chromophore binding complex calculated by AF-QM/MM accurately reproduce the large-sized system results. The ¹H chemical shift perturbations (CSP) between apo-NCS and holo-NCS predicted by AF-QM/MM are also in excellent agreement with experimental results. Furthermore, the DFT calculated chemical shifts of the chromophore and residues in the NCS binding pocket can be utilized as molecular probes to identify the correct ligand binding conformation. By combining the CSP of the atoms in the binding pocket with the Glide scoring function, the new scoring function can accurately distinguish the native ligand pose from decoy structures. Therefore, the AF-QM/MM approach provides an accurate and efficient platform for protein-ligand binding structure prediction based on NMR derived information.</p

A New Quantum Calibrated Force Field for Zinc–Protein Complex

A quantum calibrated polarizable-charge transfer force field (QPCT) has been proposed to accurately describe the interaction dynamics of zinc–protein complexes. The parameters of the QPCT force field were calibrated by quantum chemistry calculation and capture the polarization and charge transfer effect. QPCTs are validated by molecular dynamic simulation of the hydration shell of the zinc ion, five proteins containing the most common zinc-binding sites (ZnCys2His2, ZnCys3His1, ZnCys4, Zn2Cys6), as well as protein–ligand binding energy in zinc protein MMP3. The calculated results show excellent agreement with the experimental measurement and with results from QM/MM simulation, demonstrating that QPCT is accurate enough to maintain the correct structural integrity of the zinc binding pocket and provide accurate interaction dynamics of the zinc–residue complex. The current approach can also be extended to the study of interaction dynamics of other metal-containing proteins by recalibrating the corresponding parameters to the specific complexes

Development of an Effective Polarizable Bond Method for Biomolecular Simulation

An effective polarizable bond (EPB) model has been developed for computer simulation of proteins. In this partial polarizable approach, all polar groups of amino acids are treated as polarizable, and the relevant polarizable parameters were determined by fitting to quantum calculated electrostatic properties of these polar groups. Extensive numerical tests on a diverse set of proteins (including 1IEP, 1MWE, 1NLJ, 4COX, 1PGB, 1K4C, 1MHN, 1UBQ, 1IGD) showed that this EPB model is robust in MD simulation and can correctly describe the structure and dynamics of proteins (both soluble and membrane proteins). Comparison of the computed hydrogen bond properties and dynamics of proteins with experimental data and with results obtained from the nonpolarizable force field clearly demonstrated that EPB can produce results in much better agreement with experiment. The averaged deviation of the simulated backbone N–H order parameter of the B3 immunoglobobulin-binding domain of streptococcal protein G from experimental observation is 0.0811 and 0.0332 for Amber99SB and EPB, respectively. This new model inherited the effective character of the classic force field and the fluctuating feature of previous polarizable models. Different from other polarizable models, the polarization cost energy is implicitly included in the present method. As a result, the present method avoids the problem of over polarization and is numerically stable and efficient for dynamics simulation. Finally, compared to the traditional fixed AMBER charge model, the present method only adds about 5% additional computational time and is therefore highly efficient for practical applications