靶向抑制DNA拓扑异构酶的抗肿瘤药物研究

DNA拓扑异构酶是真核细胞和原核细胞中的一种基本酶,广泛存在于细胞核中,对DNA的转录、复制以及基因表达过程中的DNA拓扑结构的改变起着重要的作用。研究发现DNA拓扑异构酶在肿瘤组织中高度表达,许多抗肿瘤药物的作用机制与抑制拓扑异构酶有关,目前拓扑异构酶已成为筛选抗肿瘤药物的重要靶点。     

静电纺丝素/胶原/聚合物复合纤维的制备及其力学性能的研究

目前,将天然高分子蛋白和聚合物共混利用静电纺丝法制作各种组织工程支架材料倍受关注。基于这种研究背景,在本文中利用静电纺丝技术,制备了丝素(SF)/胶原(COL)/聚左旋乳酸(PLLA)和SF/COL/聚左旋乳酸-己内酯(PLCL)两种共混复合纤维膜,通过扫描电镜(SEM)对纤维形态结构分析,发现复合纤维形貌良好,直径较为均一。同时改变纺丝液中高分子蛋白的比例,复合纤维的直径也随之减小。此外,对复合纤维进行了力学性能测试,发现随着聚合物含量的增加,复合纤维膜的力学性能得以改善,SF/COL/PLCL组复合纤维的拉伸性能明显优于SF/COL/PLLA组。     

茶叶中乙酰甲胺磷及甲胺磷对映体的气相色谱法分离与测定

建立了乙酰甲胺磷、甲胺磷对映体在茶叶基质中的手性拆分与定量方法。比较了2种手性柱对乙酰甲胺磷及甲胺磷对映体的分离效果,并对分离效果较优的BGB-176手性柱进行色谱条件优化。茶叶样品经改良QuEChERS法处理后,气相色谱测定,外标法定量。在0.04,0.08,0.4 mg/kg 3个加标水平下,甲胺磷、乙酰甲胺磷的回收率分别为58.3%~66.4%和50.8%~57.6%,相对标准偏差(n=5)均小于7%。方法检出限为0.003~0.01 mg/kg。该方法简便、可靠,满足分析要求。通过实际样品的检测,发现乙酰甲胺磷、甲胺磷对映体在茶树上存在一定的降解差异。     

石墨烯负载的金属氧化物纳米颗粒的可控制备及催化性能

采用直接浸渍法、过氧化氢均相氧化沉积法和氨水催化水解法制备了石墨烯负载的铁、钴、镍金属氧化物纳米颗粒.研究了三种沉积方法对颗粒尺寸分布的影响;采用透射电子显微镜、傅里叶变换红外光谱、X射线衍射和X射线光电子能谱表征了催化剂的形貌与结构.用过氧化氢均相氧化沉淀法可制得粒径分布最均匀的纳米颗粒.过氧化氢的氧化作用可使石墨烯表面的氧化基团含量最大化,为纳米颗粒提供了足够的吸附与成核点.氨水加速了金属离子的水解与成核,导致纳米颗粒的粒径增大与不均.以苯甲醇氧化为探针反应考察了催化剂的性能.催化剂的活性按以下顺序逐渐下降:过氧化氢辅助沉积法>直接浸渍法>氨水催化水解法,与纳米颗粒尺寸增长趋势一致.纳米催化剂颗粒尺寸与其活性的良好关联性显示,发展石墨烯负载尺寸可控的纳米催化剂的方法具有重要意义.     

A New Near-Infrared Neutral pH Fluorescent Probe for Monitoring Minor pH Changes and its Application in Imaging of HepG2 Cells

A new near-neutral pH near-infrared (NIR) fluorescent probe utilizing a fluorophore–receptor molecular framework that can modulate the fluorescence emission intensity through a fast photoinduced electron transfer process was developed. Our strategy was to choose tricarbocyanine (Cy), a NIR fluorescent dye with high extinction coefficients, as a fluorophore, and N-methylpiperazine (MP) as a receptor. The pH titration indicated that MP-Cy can monitor the minor physiological pH fluctuations with a pKa of ～7.10 near physiological pH, which is valuable for intracellular pH researches. The probe responds linearly and rapidly to minor pH fluctuations within the range of 3.05–7.10 and exhibits strong dependence on pH changes. As expected, the real-time imaging of cellular pH and the detection of pH in situ was achieved successfully in living HepG2 cells by this probe. It is shown that the probe effectively avoids the influence of autofluorescence and native cellular species in biological systems and meanwhile exhibits high sensitivity, good photostability, and excellent cell membrane permeability.     

纤连蛋白在石墨烯修饰二氧化钛表面吸附的计算机模拟

采用全原子分子动力学模拟方法研究了纤连蛋白(FN)在金红石表面、23%石墨烯覆盖率的金红石表面、92%石墨烯覆盖率的金红石表面、石墨表面的吸附行为.模拟结果表明:FN在金红石表面吸附不稳定.通过石墨烯修饰二氧化钛表面可降低金红石表面的亲水性;当表面含有石墨烯层时,FN都将稳定地吸附在表面上.在23%石墨烯覆盖率的金红石表面上,FN的特异性识别位点朝向溶液而有利于整合素识别.DSSP分析结果显示在40 ns的分子动力学模拟过程中,FN的七个β-折叠结构在所有体系中均没有发生太大变化.由于有石墨烯层存在,表面附近水分子层密度减小.FN的表面吸附能随着表面石墨烯覆盖率的增加而增大.石墨烯修饰能加强二氧化钛表面对蛋白质的吸附.本工作可以为移植体修饰生物材料设计与开发提供参考.     

Machine-Driven Chemoenzymatic Synthesis of Glycopeptide

Historically, researchers have put considerable effort into developing automation systems to prepare natural biopolymers such as peptides and oligonucleotides. The availability of such mature systems has significantly advanced the development of natural science. Over the past twenty years, breakthroughs in automated synthesis of oligosaccharides have also been achieved. A machine-driven platform for glycopeptide synthesis by a reconstructed peptide synthesizer is described. The designed platform is based on the use of an amine-functionalized silica resin to facilitate the chemical synthesis of peptides in organic solvent as well as the enzymatic synthesis of glycan epitopes in the aqueous phase in a single reaction vessel. Both syntheses were performed by a peptide synthesizer in a semiautomated manner.     

Electrochemical Phase Evolution of Metal-Based Pre-Catalysts for High-Rate Polysulfide Conversion

In situ evolution of electrocatalysts is of paramount importance in defining catalytic reactions. Catalysts for aprotic electrochemistry such as lithium–sulfur (Li-S) batteries are the cornerstone to enhance intrinsically sluggish reaction kinetics but the true active phases are often controversial. Herein, we reveal the electrochemical phase evolution of metal-based pre-catalysts (Co₄N) in working Li-S batteries that renders highly active electrocatalysts (CoS_x). Electrochemical cycling induces the transformation from single-crystalline Co₄N to polycrystalline CoS_x that are rich in active sites. This transformation propels all-phase polysulfide-involving reactions. Consequently, Co₄N enables stable operation of high-rate (10 C, 16.7 mA cm⁻²) and electrolyte-starved (4.7 μL mg_S⁻¹) Li-S batteries. The general concept of electrochemically induced sulfurization is verified by thermodynamic energetics for most of low-valence metal compounds.     

Molten-Salt-Assisted Synthesis of Bismuth Nanosheets for Long-term Continuous Electrocatalytic Conversion of CO2 to Formate

Two-dimensional (2D) monometallic pnictogens (antimony or Sb, and bismuth or Bi) nanosheets demonstrate potential in a variety of fields, including quantum devices, catalysis, biomedicine and energy, because of their unique physical, chemical, electronic and optical properties. However, the development of general and high-efficiency preparative routes toward high-quality pnictogen nanosheets is challenging. A general method involving a molten-salt-assisted aluminothermic reduction process is reported for the synthesis of Sb and Bi nanosheets in high yields (>90 %). Electrocatalytic CO₂ reduction was investigated on the Bi nanosheets, and high catalytic selectively to formate was demonstrated with a considerable current density at a low overpotential and an impressive stability. Bi nanosheets continuously convert CO₂ into formate in a flow cell operating for one month, with a yield rate of 787.5 mmol cm⁻² h⁻¹. Theoretical results suggest that the edge sites of Bi are far more active than the terrace sites.     

An Endo-Selective Epoxide-Opening Cascade for the Fast Assembly of the Polycyclic Core Structure of Marine Ladder Polyethers

The rapid synthesis of marine ladder polyethers from polyepoxide precursors (in analogy with the biosynthetic pathway hypothesized by Nakanishi) is hampered by the fact that the exo-selective epoxide-opening cyclization cascade that gives THF-type polyethers is preferred over the endo-selective cascade that gives the desired products. We found that perfluoro-tert-butanol (PFTB) cooperating with 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM]BF₄) can promote endo-selective epoxide-opening cyclization reactions of trisubstituted epoxy alcohols. Starting from readily accessible homochiral polyepoxy alcohols with a methyl group at all the endo-cyclization sites, we were able to construct polyethers up to five consecutive fused 6-, 7-, and/or 8-membered rings in one step. Notably, molecules with the 7/7/6/6 and 7/7/6/7/6 polyether frameworks of hemibrevetoxin B and brevenal, respectively, could be synthesized in 40 % and 17 % chemical yields.