多靶点受体酪氨酸激酶抑制剂ABT-869的有效合成方法

ABT-869是结构新型有效的多靶点受体酪氨酸激酶抑制剂,目前正处在III期临床研究阶段.从商业廉价易得的间氟苯胺出发,以较低的成本经过7步反应以42.3%的总收率实现了多靶点受体酪氨酸激酶抑制剂ABT-869全合成.该工艺在关键步骤Suzuki偶联反应中使用了超声波反应器,极大地缩短反应时间,提高了收率,并且该工艺各步反应中间体不用纯化直接投入下步反应,最终产物只需结晶纯化即可达到大于99%的纯度,无需传统的柱层析分离,更适合于工业生产.     

新型吡唑联吡咯类杂环化合物的合成及杀菌活性

为寻找具有更高生物活性、更环保的新农药杀菌剂,基于杀菌剂氟咯菌腈设计并合成了10个新型吡唑联吡咯类杂环化合物,以吡唑环代替氟咯菌腈上原有的苯环,以期提高其杀菌活性.采用1H NMR,FTIR,单晶X射线衍射、元素分析和熔点测定等测试手段对目标化合物及其中间体的结构进行了表征与确认,并通过挥发法培养得到了6个目标化合物的单晶.还对其中6个化合物进行了生物活性测试,测试结果表明各化合物对水稻纹枯病、黄瓜灰霉病、黄瓜霜霉病均表现出一定的抑菌效果,可作为先导化合物对其结构进行深入的研究,为新农药杀菌剂的开发提供了理论支持.     

Identification and analysis of alkaloids in cortex Phellodendron amurense by high‐performance liquid chromatography with electrospray ionization mass spectrometry coupled with photodiode array detection

Alkaloids from Cortex Phellodendron amurense Rupr. were identified to determine the material basis for the bioactivity of this herb. HPLC–ESI‐MS with photodiode array detection coupled to XCharge C₁₈ column was applied to analyze the alkaloids qualitatively and quantitatively. A total of 37 alkaloids were identified and tentatively characterized from the ethanol extract by online ESI‐MSⁿ fragmentation and UV spectral analysis. A total of ten alkaloids, including four novel natural products, were tentatively identified for the first time in P. amurense. The fragmentation pathways for certain compounds were analyzed. The contents of a pair of isomers (columbamine and jatrorrhizine) and four main alkaloids (phellodendrine, magnoflorine, berberine, and palmatine) were simultaneously quantified using the aforementioned method. Results showed that the newly discovered and known components of P. amurense were helpful in determining the material basis for the bioactivity of the herb. The application of the XCharge C₁₈ column is a suitable and practical method for the isolation of alkaloids in plants.     

Using electrospray laser desorption ionization mass spectrometry to rapidly examine the integrity of proteins stored in various solutions

Electrospray laser desorption ionization mass spectrometry (ELDI/MS) allows the rapid desorption and ionization of proteins from solutions under ambient conditions. In this study, we have demonstrated the use of ELDI/MS to efficiently examine the integrity of the proteins stored in various solutions before they were further used for other biochemical tests. The protein standards were prepared in the solutions containing buffers, organic salts, inorganic salts, strong acid, strong base, and organic solvents, respectively, to simulate those collected from solvent extraction, filtration, dialysis, or chromatographic separation. Other than the deposit of a drop of the sample solution on the metallic sample plate in an ELDI source, no additional sample pretreatment is needed. The sample drop was then irradiated with a pulsed laser; this led to desorption of the analyte molecules, which subsequently entered the ESI plume to undergo post-ionization. Because adjustment of the composition of the sample solution is unnecessary, this technique appears to be useful for rapidly evaluating the integrity of proteins after storage or prior to further biochemical treatment. In addition, when using acid-free and low-organic-solvent ESI solutions for ELDI/MS analysis, the native conformations of the proteins in solution could be detected.

Sensitive detection of T4 polynucleotide kinase activity based on coupled exonuclease reaction and nicking enzyme-assisted fluorescence signal amplification

As a prominent member of the 5′-kinase family, T4 polynucleotide kinase (PNK) plays an important role in gene function regulations, and the study of PNK activity and its potential inhibitors is significant for research related to the DNA phosphorylation process. Here, we proposed a novel strategy for the detection of PNK activity and its inhibition, which combines exonuclease enzyme reaction and nicking enzyme-assisted fluorescence signal amplification. Through recycling cleavage of DNA fluorescence probe for signal amplification, a highly sensitive PNK sensing platform is developed, and a very low detection limit of 0.05 mU/mL is achieved, which is better than or comparable to that of the previously reported PNK assays. The present approach adopts a simple separation-free procedure in which the enzyme assay is conducted in homogeneous solutions. Additionally, the inhibitory effects of several known kinase inhibitors on PNK have been successfully detected. Since the proposed assay exhibits the advantages of high sensitivity and simplicity, it holds great potential in providing a promising platform for convenient and highly sensitive detection of PNK activity and its inhibitors.

Integration of [(Co(bpy)3]2+ Electron Mediator with Heterogeneous Photocatalysts for CO2 Conversion

An efficient chemical system for electron generation and transfer is constructed by the integration of an electron mediator ([Co(bpy)₃]²⁺; bpy=2,2′‐bipyridine) with semiconductor photocatalysts. The introduction of [Co(bpy)₃]²⁺ remarkably enhances the photocatalytic activity of pristine semiconductor photocatalysts for heterogeneous CO₂ conversion; this is attributable to the acceleration of charge separation. Of particular interest is that the excellent photocatalytic activity of heterogeneous catalysts can be developed as a universal photocatalytic CO₂ reduction system. The present findings clearly demonstrate that the integration of an electron mediator with semiconductors is a feasible process for the design and development of efficient photochemical systems for CO₂ conversion.     

空心NiCo2S4纳米球助催化剂担载ZnIn2S4纳米片用于可见光催化制氢

纳米片与空心球上之间的合理界面调控是开发高效太阳能制氢光催化剂的潜在策略。在各类光催化材料中,金属硫化物由于具有相对较窄的带隙和优越的可见光响应能力而被广泛研究。ZnIn₂S₄是一种层状的三元过渡金属半导体光催化剂,其带隙可控(约2.4 eV)。在众多金属硫化物光催化剂中,ZnIn₂S₄引起了广泛兴趣。然而,单纯的ZnIn₂S₄光催化活性仍然相对较差,主要是因为光生载流子的复合率较高、迁移速率较慢。在半导体光催化剂上负载助催化剂是提升光催化剂性能的一种有效方法,因为它不仅可以加速光生电子和空穴的分离,而且还可以降低质子还原反应的活化能。作为一种三元过渡金属硫化物,NiCo₂S₄表现出较高的导电性、较低的电负性、丰富的氧化还原特性以及优越的电催化活性。这些特性表明,NiCo₂S₄可以作为光催化制氢的助催化剂,以加速电荷分离和转移。此外,NiCo₂S₄和ZnIn₂S₄都属于三元尖晶石的晶体结构,这可能有助于构建具有紧密界面接触的NiCo₂S₄/ZnIn₂S₄复合物,从而提高光催化性能。本文中,将超薄ZnIn₂S₄纳米片原位生长到非贵金属助催化剂NiCo₂S₄空心球上,形成具有强耦合界面和可见光吸收的NiCo₂S₄@ZnIn₂S₄分级空心异质结构光催化剂。最优NiCo₂S₄@ZnIn₂S₄复合样品(NiCo₂S₄含量：ca. 3.1%)的析氢速率高达78 μmol·h^-1,约是纳米片组装ZnIn₂S₄光催化剂析氢速率的9倍、约是1% (w, 质量分数)Pt/ZnIn₂S₄样品析氢速率的3倍。此外,该复合光催化剂在反应中表现出良好的稳定性。荧光和电化学测试结果表明,NiCo₂S₄空心球是一种有效的助催化剂,可促进光生载流子的分离和传输,并降低析氢反应的活化能。最后,提出了NiCo₂S₄@ZnIn₂S₄光催化析氢的可能反应机理。在NiCo₂S₄@ZnIn₂S₄复合光催化剂中,具有高导电性的NiCo₂S₄助催化剂可快速接受ZnIn₂S₄上的光生电子,用以还原质子生成氢气,而电子牺牲剂TEOA捕获光生空穴,进而完成光催化氧化还原循环。该研究有望为基于纳米片为次级结构的分级空心异质结光催化剂的设计合成及其光催化制氢研究提供一定的指导。     

铜基串联催化剂电催化CO2还原的研究进展

化石燃料的燃烧和其他人类活动排放了大量的CO₂气体,引发了诸多环境问题。电催化CO₂还原反应(CO₂RR)可以储存间歇可再生能源,实现人为闭合碳循环,被认为是获得高附加值化学品和燃料的有效途径。电催化CO₂RR涉及多个电子-质子转移步骤,其中^*CO通常被认为是关键中间体。铜由于对^*CO具有合适的吸附能,已被广泛证明是唯一能够有效地将CO₂还原为碳氢化合物和含氧化合物的金属催化剂。然而,纯Cu稳定性差、产品选择性低、过电位高,阻碍了工业级多碳产品的生产。构筑Cu基串联催化剂是提高CO₂RR性能的一种有前途的策略。本文首先介绍电催化CO₂RR的反应路线和串联机理。然后,系统地总结铜基串联催化剂对电催化CO₂RR的最新研究进展。最后,提出合理设计和可控合成新型电催化CO₂RR串联催化剂面临的挑战和机遇。     

基于MXenes的功能纤维的制备及其在智能可穿戴领域的应用

在电子信息和物联网技术的推动下,人类对可穿戴电子器件和智能织物的需求愈发突出,功能纤维作为智能可穿戴设备的重要载体,近年来获得快速发展。功能纤维的性能很大程度上取决于纤维的基础构筑单元。过渡金属碳/氮化物(MXenes)作为一种新兴的二维材料,凭借其高电导率、优异的可加工性能、可调节的表面特性以及出色的机械强度等优点,受到了极大的关注,也逐渐成为构筑功能纤维的重要单元。本文将主要综述MXenes的湿化学、熔融盐、无氟试剂刻蚀等方法和力学、电学、光学和化学稳定性等性能,阐述基于该材料制备的功能纤维在传感、储能以及其他智能领域的应用,最后讨论了基于MXenes材料的功能纤维的未来应用前景和技术挑战。     

Development of a method to screen and isolate xanthine oxidase inhibitors from black bean in a single step: Hyphenation of semipreparative liquid chromatography and stepwise flow rate countercurrent chromatography

Black bean, in which isoflavones are the main active constituent, also contains saponins and monoterpenes. Soybean isoflavone is a secondary metabolite that is formed during the growth of soybean; it exhibits antioxidant and cardiovascular activities and traces estrogen-like effects. In this study, black bean isoflavones were extracted with n-butanol, and ultrafiltration–liquid chromatography–mass spectrometry was used to screen their activity. Subsequently, the inhibitors were isolated and purified using semipreparative liquid chromatography and stepwise flow rate countercurrent chromatography. Thereafter, five active compounds were identified using mass spectrometry and nuclear magnetic resonance experiments. Finally, the inhibition types of the xanthine oxidase inhibitors were determined using enzymatic kinetic studies. The IC₅₀ values of daidzin, glycitein-7-O-glucoside, genistin, daidzein, and genistein were determined to be 35.08, 56.22, 30.76, 68.79, and 95.37 μg/mL, respectively. Daidzin, genistin, and daidzein exhibited reversible inhibition, whereas glycitein-7-O-glucoside and genistein presented irreversible inhibition. This novel approach, which was based on ultrafiltration–liquid chromatography–mass spectrometry and stepwise flow rate countercurrent chromatography, is a powerful method for screening and isolating xanthine oxidase inhibitors from complex matrices. The study of enzyme inhibition types is helpful for understanding the underlying inhibition mechanism. Therefore, a beneficial platform was developed for the large-scale production of bioactive and nutraceutical ingredients.