Optimization of 1,2,5‐Thiadiazole Carbamates as Potent and Selective ABHD6 Inhibitors

At present, inhibitors of α/β‐hydrolase domain 6 (ABHD6) are viewed as a promising approach to treat inflammation and metabolic disorders. This article describes the development of 1,2,5‐thiadiazole carbamates as ABHD6 inhibitors. Altogether, 34 compounds were synthesized, and their inhibitory activity was tested using lysates of HEK293 cells transiently expressing human ABHD6 (hABHD6). Among the compound series, 4‐morpholino‐1,2,5‐thiadiazol‐3‐yl cyclooctyl(methyl)carbamate (JZP‐430) potently and irreversibly inhibited hABHD6 (IC₅₀=44 nM ) and showed ～230‐fold selectivity over fatty acid amide hydrolase (FAAH) and lysosomal acid lipase (LAL), the main off‐targets of related compounds. Additionally, activity‐based protein profiling indicated that JZP‐430 displays good selectivity among the serine hydrolases of the mouse brain membrane proteome. JZP‐430 has been identified as a highly selective, irreversible inhibitor of hABHD6, which may provide a novel approach in the treatment of obesity and type II diabetes.     

MW-GAC-H2O2降解水中微量硝基苯的动力学研究

采用MW-GAC-H2O2工艺(微波-活性炭颗粒-过氧化氢)降解水中微量硝基苯,研究了硝基苯初始质量浓度、pH、HCO3-和腐植酸对MW/GAC/H2O2降解硝基苯的动力学行为的影响。结果表明,硝基苯初始质量浓度越大,硝基苯降解速率越小;初始溶液pH为8时,硝基苯的降解速率最高;投加适量HCO3(-100～200mg/L)、腐植酸均可促进系统降解硝基苯。在硝基苯初始质量浓度为200μg/L、微波功率为300W、GAC和H2O2投加量分别为4g/L和10mg/L的试验条件下反应21min,MW-GAC-H2O2工艺降解硝基苯的速率为0.052 1 min-1,反应过程遵循1级反应动力学方程。     

Flavin‐grafted poly(vinyl alcohol): Preparation and properties

An NAD(P)H oxidase‐like activity was found in semisynthetic flavoadducts, prepared from an aldehyde derivative of riboflavin and commercial poly(vinylalcohol) (PVA), previously grafted with aminopropyl side chains. Both water‐soluble and water‐insoluble beaded preparations were obtained. The products showed a noticeable NAD(P)H oxidase‐like activity, converting the nucleotide substrate to its oxidized counterpart NAD(P)⁺ at the expense of molecular oxygen, the latter being reduced to hydrogen peroxide. In contrast to some “true” β‐NAD(P)H oxidases, the PVA adducts do not require the presence of additional flavin adenine dinucleotide (FAD) to work; some properties of the flavoadducts were studied that make these flavoadducts good candidates for technological applications. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2471–2477, 2002     

Design and synthesis of porous polymeric materials and their applications in gas capture and storage: a review

The design and synthesis of porous organic materials that have increasing physical and chemical characteristics have been discussed. For example, a variety of porous organic polymers, metal–organic frameworks, conjugated microporous polymers, and polymers of intrinsic microporosity have been designed and synthesized using simple and efficient procedures. Such materials have unique gas adsorption properties and can be used in gases separation and storage. In addition, they have high surface area, porosity, and selectivity towards carbon dioxide compared to other gases such as nitrogen and methane.     

钻井液用无机盐类抑制剂评价方法适应性探究

针对钻井液用抑制剂性能评价过程中出现实验结论异常的现象,通过泥页岩线性膨胀量实验、岩心浸泡实验、热滚回收实验、岩心滴染扫描电镜观察实验等多种方法,探讨了多种包括无机盐、硅酸盐、聚乙烯醇等在内的抑制剂抑制性评价方法的适应性问题。结果表明,低浓度的氯化钾与氯化钠不适用于采用人工岩心浸泡实验和线性膨胀量实验进行评价;线性膨胀量实验要求抑制剂质量分数在0.3%以上且实验时间不少于6 h才能得到相对准确的实验结论;基浆粘度对泥页岩热滚回收实验具有明显的影响,基浆粘度越高初始热滚回收率越高。为此,在进行抑制剂效果评价时应充分重视评价方法、抑制剂浓度、实验持续时间、基浆粘度等多种因素的影响,寻求针对性评价手段以避免得到错误的实验结论。     

Structure-Based Design,Docking and Binding Free Energy Calculations of A366 Derivatives as Spindlin1 Inhibitors

The chromatin reader protein Spindlin1 plays an important role in epigenetic regulation, through which it has been linked to several types of malignant tumors. In the current work, we report on the development of novel analogs of the previously published lead inhibitor A366. In an effort to improve the activity and explore the structure–activity relationship (SAR), a series of 21 derivatives was synthesized, tested in vitro, and investigated by means of molecular modeling tools. Docking studies and molecular dynamics (MD) simulations were performed to analyze and rationalize the structural differences responsible for the Spindlin1 activity. The analysis of MD simulations shed light on the important interactions. Our study highlighted the main structural features that are required for Spindlin1 inhibitory activity, which include a positively charged pyrrolidine moiety embedded into the aromatic cage connected via a propyloxy linker to the 2-aminoindole core. Of the latter, the amidine group anchor the compounds into the pocket through salt bridge interactions with Asp184. Different protocols were tested to identify a fast in silico method that could help to discriminate between active and inactive compounds within the A366 series. Rescoring the docking poses with MM-GBSA calculations was successful in this regard. Because A366 is known to be a G9a inhibitor, the most active developed Spindlin1 inhibitors were also tested over G9a and GLP to verify the selectivity profile of the A366 analogs. This resulted in the discovery of diverse selective compounds, among which 1s and 1t showed Spindlin1 activity in the nanomolar range and selectivity over G9a and GLP. Finally, future design hypotheses were suggested based on our findings.     

Development of nanosilica-based catalyst for syngas production via CO2 reforming of CH4: A review

The alarming global warming issue has sparked interest in researchers to mitigate greenhouse gas emissions via CO₂ reforming of CH₄ (CRM). Regrettably, the main drawback of CRM is catalyst deactivation because of coking and metal sintering. Therefore, exceptional resistance towards coking and sintering is crucial to formulate viable CRM catalysts. This article reviewed the latest development of nanosilica-based catalysts (mesoporous nanosilica, dendritic fibrous nanosilica, green nanosilica, and core@shell nanosilica) for CRM application. The physicochemical properties of nanosilica supports could be modulated by synthesis methods to improve their resistance towards coking and sintering. Furthermore, this review compiled the influence of catalytic properties of nanosilica supported catalysts, such as active metal dispersion, crystallite size, acid-basic properties, oxygen mobility, reducibility, porosity, and morphology on CRM. To conclude, nanosilica supports with strong metal-support interaction, homogeneous metal dispersion, appropriate crystallite size, and moderate acidity/basicity, exhibited satisfactory catalytic activity, thermal stability, and resistance towards coking and sintering. The fundamental study and depth understanding on this catalysis field is of worth in configuring robust catalysts for future industrial applications success of CRM reaction with superb activity and carbon resistance for CRM.     

High-Performance Bimetallic Catalysts for Low-Temperature Carbon Dioxide Reforming of Methane

Catalytic dry reforming of methane (DRM) is a promising way for renewable syngas production due to the utilization of both CO₂ and CH₄ greenhouse gases. Current approaches were made to improve the catalytic activity and coke resistance by introducing a second metal into the Ni-based catalytic system. This bimetallic catalytic system showed a significant improvement in coke resistance due to the synergistic effect of both metals towards the reaction. This review summarizes recent developments in bimetallic catalysts in DRM which focused on the evaluation of catalysts, deactivation studies, and reaction mechanisms of developed bimetallic catalysts.