One-pot Copper Nanoparticle-catalyzed Synthesis of Imidazo[1,2-α]pyridines Under Solvent-free Conditions

A direct and efficient approach to synthesize imidazo[1,2-α]pyridines through three-component one-pot reaction of 2-aminopyridine,aldehyde and terminal alkyne catalyzed by Cu-nanoparticles under solvent-free conditions has been developed.This method provides a rapid access to substituted imidazo[1,2-α]pyridines with good yields（up to 85％）.     

基于VHTRC的棱柱式高温气冷堆核设计程序验证北大核心CSCD

高温气冷堆是国际公认的固有安全性高的反应堆堆型。针对高温气冷堆包覆颗粒燃料引入的燃料组件的双重非均匀性以及棱柱式堆芯布置的非均匀性和强空间耦合效应,提出基于蒙特卡罗均匀化-确定论输运方法的RMC-SaraGR程序系统作为棱柱式高温气冷堆的核设计程序。基于日本棱柱式高温气冷堆临界实验装置VHTRC基准题,针对此套核设计程序系统开展了均匀化模型研究和初步验证。研究结果表明,基于蒙特卡罗均匀化方法,采用全堆模型、合适的能群结构和分区方式产生组件群常数,并经过超级等效均匀化方法进行等效均匀化修正,可以保证堆芯多群均匀计算具有较高的计算精度。     

Novel inhibitor discovery through virtual screening against multiple protein conformations generated via ligand-directed modeling: a maternal embryonic leucine zipper kinase example

Kinase targets have been demonstrated to undergo major conformational reorganization upon ligand binding. Such protein conformational plasticity remains a significant challenge in structure-based virtual screening methodology and may be approximated by screening against an ensemble of diverse protein conformations. Maternal embryonic leucine zipper kinase (MELK), a member of serine-threonine kinase family, has been recently found to be involved in the tumerogenic state of glioblastoma, breast, ovarian, and colon cancers. We therefore modeled several conformers of MELK utilizing the available chemogenomic and crystallographic data of homologous kinases. We carried out docking pose prediction and virtual screening enrichment studies with these conformers. The performances of the ensembles were evaluated by their ability to reproduce known inhibitor bioactive conformations and to efficiently recover known active compounds early in the virtual screen when seeded with decoy sets. A few of the individual MELK conformers performed satisfactorily in reproducing the native protein-ligand pharmacophoric interactions up to 50% of the cases. By selecting an ensemble of a few representative conformational states, most of the known inhibitor binding poses could be rationalized. For example, a four conformer ensemble is able to recover 95% of the studied actives, especially with imperfect scoring function(s). The virtual screening enrichment varied considerably among different MELK conformers. Enrichment appears to improve by selection of a proper protein conformation. For example, several holo and unliganded active conformations are better to accommodate diverse chemotypes than ATP-bound conformer. These results prove that using an ensemble of diverse conformations could give a better performance. Applying this approach, we were able to screen a commercially available library of half a million compounds against three conformers to discover three novel inhibitors of MELK, one from each template. Among the three compounds validated via experimental enzyme inhibition assays, one is relatively potent (15; K(d) = 0.37 μM), one moderately active (12; K(d) = 3.2 μM), and one weak but very selective (9; K(d) = 18 μM). These novel hits may be utilized to assist in the development of small molecule therapeutic agents useful in diseases caused by deregulated MELK, and perhaps more importantly, the approach demonstrates the advantages of choosing an appropriate ensemble of a few conformers in pursuing compound potency, selectivity, and novel chemotypes over using single target conformation for structure-based drug design in general.     

1,2,6,7-四氢-8H-茚并[5,4-b]呋喃-8-酮的合成新方法

发展了一条1,2,6,7-四氢-8H-茚并[5,4-b]呋喃-8-酮的新合成方法,以价廉、易得的对溴苯酚为原料,在无水碳酸钾作用下与2-溴乙醛缩二乙醇缩合后用多聚磷酸(PPA)环合得5-溴苯并呋喃,该中间体与丙烯酸甲酯在Pd(OAc)2催化下,经Heck偶合反应得3-(苯并呋喃-5-基)丙酸甲酯,在氢氧化钠水溶液中经Raney Ni催化氢化和水解一锅反应得3-(2,3-二氢苯并呋喃-5-基)丙酸,再经二溴代、Friedel-Crafts酰化反应和氢解脱溴,得1,2,6,7-四氢-8H-茚并[5,4-b]呋喃-8-酮,7步反应总收率49.9%.该方法原料易得、反应条件温和、操作简便、产物分离纯化容易,收率良好,适合大规模制备1,2,6,7-四氢-8H-茚并[5,4-b]呋喃-8-酮.     

Spider Silk-Improved Quartz-Enhanced Conductance Spectroscopy for Medical Mask Humidity Sensing

Spider silk is one of the hottest biomaterials researched currently, due to its excellent mechanical properties. This work reports a novel humidity sensing platform based on a spider silk-modified quartz tuning fork (SSM-QTF). Since spider silk is a kind of natural moisture-sensitive material, it does not demand additional sensitization. Quartz-enhanced conductance spectroscopy (QECS) was combined with the SSM-QTF to access humidity sensing sensitively. The results indicate that the resonance frequency of the SSM-QTF decreased monotonously with the ambient humidity. The detection sensitivity of the proposed SSM-QTF sensor was 12.7 ppm at 1 min. The SSM-QTF sensor showed good linearity of ~0.99. Using this sensor, we successfully measured the humidity of disposable medical masks for different periods of wearing time. The results showed that even a 20 min wearing time can lead to a >70% humidity in the mask enclosed space. It is suggested that a disposable medical mask should be changed <2 h.     

Expanding new chemistry of aza-boracyclophanes with unique dipolar structures,AIE and redox-active open-shell characteristics

π-Conjugated macrocycles involving electron-deficient boron species have received increasing attention due to their intriguing tunable optoelectronic properties. However, most of the reported B(sp²)-doped macrocycles are difficult to modify due to the synthetic challenge, which limits their further applications. Motivated by the research of non-strained hexameric bora- and aza-cyclophanes, we describe a new class of analogues MC-BN5 and MC-ABN5 that contain charge-reversed triarylborane (Ar₃B) units and oligomeric triarylamines (Ar₃N) in the cyclics. As predicted by DFT computations, the unique orientation of the donor–acceptor systems leads to an increased dipole moment compared with highly symmetric macrocycles (M1, M2 and M3), which was experimentally represented by a significant solvatochromic effect with large Stokes shifts up to 12 318 cm⁻¹. Such a ring-structured design also allows the easy peripheral modification of aza-boracyclophanes with tetraphenylethenyl (TPE) groups, giving rise to a change in the luminescence mechanism from aggregation-caused quenching (ACQ) in MC-BN5 to aggregation-induced emission (AIE) in MC-ABN5. The open-shell characteristics have been chemically enabled and were characterized by UV-Vis-NIR spectroscopy and electron paramagnetic resonance (EPR) for MC-BN5. The present study not only showed new electronic properties, but also could expand the research of B/N doped macrocycles into the future scope of supramolecular chemistry, as demonstrated in the accessible functionalization of ring systems.

We have achieved the synthesis of new B/N doped macrocycles by stitching oligoarylamine pentamers using arylborane acceptor segments. They exhibit open-shell radical species and AIE under ambient conditions.     

铁改性的HMS分子筛催化苯酚羟基化反应合成二酚

邻苯二酚和对苯二酚是重要的精细化工中间体,在各个行业中具有广泛的应用。苯酚与过氧化氢反应合成苯二酚是一条反应条件温和、环境友好的合成路线,该合成路线的关键是催化剂的选择和反应条件的优化。本文以铁改性的HMS分子筛为催化剂,研究了金属负载量、催化剂使用量、反应温度、反应时间等因素对催化性能的影响,优化了反应条件。以水为溶剂,n(Fe)∶n(Si)=0.04,n(苯酚)∶n(H2O2)=2∶1,反应温度50℃,催化剂用量0.1g,反应4h,苯酚的转化率达45.5%,苯二酚选择性为94.9%。N2吸附-脱附结果表明,Fe/HMS具有良好的介孔结构,铁进入HMS材料的骨架中,并且催化剂具有良好的稳定性,循环使用后骨架保持完整。     

Study on kinetics of the pyrolysis process of aluminum sulfate

Abstract

Using high aluminum gangue as a raw material, aluminum sulfate 18 hydrate was made by the sulfuric acid leaching method under certain conditions. The product was characterized using X-ray diffraction (XRD) analysis of the phases, x-ray-fluorescence (XRF) analysis of the aluminum and sulfur content and thermogravimetric analysis of the crystallized water [Al₂(SO₄)₃·18H₂O]. Change characteristics of the crystal form and morphology during pyrolysis of octadecahydrate aluminum sulfate were studied by thermogravimetric Analysis (TGA), differential scanning calorimetry (DSC), differential thermogravimetry (DTG), XRD and scanning electron microscope (SEM). The theoretical basis for the preparation of metallurgical alumina from octadecahydrate aluminum sulfate was provided. According to the characteristics of the crystal structure change, the pyrolysis process of octadecahydrate aluminum sulfate can be separated into three stages. The first stage (dehydration stage 87–250?°C) had a weight loss rate of 40.5% and a loss of 15 water molecules; the weight loss rate of the second stage (dehydration stage 280–414?°C) was 8.1% with three water molecules lost; the weight loss rate of the third stage (decomposition stage 770–900?°C) was 36.1%, where three SO₃ molecules were lost. The pyrolysis products were mainly Al₂O₃. The activation energies of the three reaction stages were calculated using the Coats-Redfern method as 90.02?kJ/mol, 205.74?kJ/mol and 284.40?kJ/mol, respectively.