N‐alkyl‐4‐chloro‐1H‐benzo[c][1,2]thiazine‐3‐carbaldehyde‐2,2‐dioxides—New functional benzothiazine derivatives

A synthesis of N‐alkyl‐4‐chloro‐1H‐benzo[c][1,2]thiazine‐3‐carbaldehyde‐2,2‐dioxides is described. Reactivity of new β‐chloroaldehydes is investigated, a number of novel benzo[c][1,2]thiazine derivatives are synthesized and characterized using ¹H, ¹³C‐NMR, MS and elemental analysis.     

Aromaticity-controlled tautomerism and resonance-assisted hydrogen bonding in heterocyclic enaminone-iminoenol systems

The contribution of aromaticity and intramolecular hydrogen bonding to relative stability, for a set of (1H-azahetero-2-ylidene)-acetaldehyde and 2-azahetero-2-yl-ethanol tautomeric pairs, has been investigated by means of quantum chemical DFT and ab initio methods up to the MP4(SDTQ)/AUG-cc-pVDZ and MP2/AUG-cc-pVTZ levels of theory. It is found that the relative energy of the tautomers is governed by the change in the degree of heterocycle aromaticity upon intramolecular hydrogen transfer. An analysis of geometrical parameters of a hydrogen-bonded system reveals a clear relationship between the aromaticity of the heterocycle, the conjugation in a resonant spacer, and the strengths of the intramolecular hydrogen bonds. This allows the conclusion to be drawn that intramolecular N-H...O and O-H...N hydrogen bonds formed are found to be resonance-assisted and their strength is dependent on the pi-donating/accepting properties of the heterocycle. On the basis of the results of the calculations, a simple model describing the mechanism of resonance assistance of hydrogen bonding has been suggested.     

Stability and rheology of three types of W/O/W multiple emulsions emulsified with lecithin

Three types of multiple emulsions were prepared with lecithin. The morphology, stability, and rheological properties of the three types of W/O/W multiple emulsions were evaluated. The formulation factors, including salts and aliphatic alcohol, were further examined. The three types of multiple emulsions were formed by different emulsifiers. An excellent multiple emulsion occurred with 2?wt% lecithin concentration, stabilized by 0.05?wt% NaCl. All multiple emulsions showed shear-thinning behavior, i.e., the apparent viscosity decreased with the increase of the shear rate. With the high concentration of lecithin, the multiple emulsions exhibited the highest viscosity at low shear rate and had higher storage modulus (G′) and the loss modulus (G″). This study was conducted to reveal that different types of multiple emulsions can be formed with lecithin, and that the stability and rheological properties were different with different types of multiple emulsions.     

Coupling hybridization chain reaction with DNAzyme recycling for enzyme-free and dual amplified sensitive fluorescent detection of methyltransferase activity

Aberrant DNA methylation originated from changes in DNA methyltransferase activity can lead to many genetic diseases and tumor types, and the monitoring of methyltransferase activity is thus of great importance in disease diagnosis and drug screening. In this work, by combing hybridization chain reaction (HCR) and metal ion-dependent DNAzyme recycling, we have developed a convenient enzyme-free signal amplification strategy for highly sensitive detection of DNA adenine methyltransferase (Dam MTase) activity and its inhibitors. The Dam MTase-induced methylation and subsequent cleavage of the methylated hairpin DNA probes by DpnI endonuclease lead to the release of ssDNA triggers for HCR formation of many Mg²⁺-dependent DNAzymes, in which the fluorescently quenched substrate sequences are catalytically and cyclically cleaved by Mg²⁺ to generate remarkably amplified fluorescent signals for highly sensitive detection of Dam MTase at 7.23 × 10⁻⁴ U/mL. In addition, the inhibition of different drugs to Dam MTase activity can also be evaluated with the developed method. With the advantages of simplicity and significant signal amplification over other common methods, the demonstrated biosensing approach thus offers great potential for highly sensitive detection of various methyltransferases and provides a convenient platform for drug screening for therapeutic applications.     

NIR-Sensitized Activated Photoreaction between Cyanines and Oxime Esters: Free-Radical Photopolymerization

Cyanines comprising either a benzo[e]- or benzo[c,d]indolium core facilitate initiation of radical photopolymerization combined with high power NIR-LED prototypes emitting at 805 nm, 860 nm, or 870 nm, while different oxime esters function as radical coinitiators. Radical photopolymerization followed an initiation mechanism based on the participation of excited states, requiring additional thermal energy to overcome an existing intrinsic activation barrier. Heat released by nonradiative deactivation of the sensitizer favored the system, even under conditions where a thermally activated photoinduced electron transfer controls the reaction protocol. The heat generated internally by the NIR sensitizer promotes generation of the initiating reactive radicals. Sensitizers with a barbiturate group at the meso-position preferred to bleach directly, while sensitizers carrying a cyclopentene moiety unexpectedly initiated the photosensitized mechanism.     

Combined 3D-QSAR, molecular docking, and molecular dynamics study on piperazinyl-glutamate-pyridines/pyrimidines as potent P2Y12 antagonists for inhibition of platelet aggregation

An unusually large data set of 397 piperazinyl-glutamate-pyridines/pyrimidines as potent orally bioavailable P2Y(12) antagonists for inhibition of platelet aggregation was studied for the first time based on the combination of three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, and molecular dynamics (MD) methods. The comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) studies have been performed with a training set of 317 compounds, estimating three superimposition methods. The best CoMFA and CoMSIA models, derived from superimposition I, shows leave-one-out cross-validation correlation coefficients (Q(2)) of 0.571 and 0.592 as well as the conventional correlation coefficients (R(2)(ncv)) of 0.814 and 0.834, respectively. In addition, the satisfactory results, based on the bootstrapping analysis and 10-fold cross-validation, further indicate the highly statistical significance of the optimal models. The external predictive abilities of these models were evaluated using a prediction set of 80 compounds, producing the predicted correlation coefficients (R(2)(pred)) of 0.664 and 0.668, respectively. The key amino acid residues were identified by molecular docking, and the stability and rationality of the derived molecular conformations were also validated by MD simulation. The good concordance between the docking results and CoMFA/CoMSIA contour maps provides helpful clues about the rational modification of molecules in order to design more potent P2Y(12) antagonists. We hope the developed models could provide some instructions for further synthesis of highly potent P2Y(12) antagonists.     

Singly diagonally implicit runge‐kutta method for time‐dependent reaction‐diffusion equation

In this article, an efficient fourth‐order accurate numerical method based on Padé approximation in space and singly diagonally implicit Runge‐Kutta method in time is proposed to solve the time‐dependent one‐dimensional reaction‐diffusion equation. In this scheme, we first approximate the spatial derivative using the second‐order central finite difference then improve it to fourth‐order by applying Padé approximation. A three stage fourth‐order singly diagonally implicit Runge‐Kutta method is then used to solve the resulting system of ordinary differential equations. It is also shown that the scheme is unconditionally stable, and is suitable for stiff problems. Several numerical examples are solved by the scheme and the efficiency and accuracy of the new scheme are compared with two widely used high‐order compact finite difference methods. © 2010 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 27: 1423–1441, 2011     

Expected and unforeseen reactions of 2,3,3-trimethyl-1λ6-isothiazolidine-1,1,4-trione and their spiro derivative

Herein, we present a full account of our studies with respect to the reactivity of insufficiently explored 1λ⁶-isothiazolidine-1,1,4-triones (so-called β-keto-γ-sultams). This heterocyclic system possesses two reaction centers: the EWG-activated methylene group and the carbonyl moiety which were investigated in the course of present study. 2,3,3-Trimethyl-1λ⁶-isothiazolidine-1,1,4-trione and 4-methyl-5λ⁶-thia-4-azaspiro[2.4]heptane-5,5,7-trione were chosen as representatives of the given class of substances. The former is a classical spatially uncomplicated model substance, the latter bearing a spiranic cyclopropane substituent is interesting in terms of evaluation of strain cycle effects. Indeed, the data obtained convey information about the impact of the highly strained substituent on the reaction centers of the ketosultam core. Thus, in addition to less stability of the strained spiranic ketosultam, the reactivity of its carbonyl group is suppressed whereas the activity of the methylene group is enhanced being compared with the nonspiranic substrate. Apart from the difference in the chemical character of the given β-keto-γ-sultams we faced unprecedented products (1,1-dioxo-5-[2-(triphenylphosphonio)acetyl]-2,3-dihydro-1H-1λ⁶-isothiazol-4-olates) formed during the course of the reaction with the Wittig reagent triphenylcarbethoxymethylenephosphorane.     

活性蓄冷器数学模型的研究进展

活性蓄冷器是室温磁制冷机的核心部分,它的性能直接影响整个磁制冷系统。了解其工作机理和热力学特性对制冷机的设计与优化具有重要意义。综述了近年来活性蓄冷器数学模型的研究进展,并对模型进行了比较分析。     

磁制冷研究现状

在能源紧缺、全球气温上升、环境影响日趋严重的背景下,磁制冷作为一项高新绿色制冷技术,其发展前景为各国所看好。文中简要介绍了有关磁制冷样机的研究现状、磁制冷原理、磁制冷循环、磁制冷的关键技术,以及磁制冷的应用,并对磁制冷的趋势作出展望。