Preparation and Structure of a New Coagulation Factor XI Catalytic Domain for Drug Discovery

Human blood coagulation factor XI (FXI) is a key enzyme in the amplification phase of blood coagulation cascade,and is recognized as an important target for anti-coagulant deve-lopment in recent years.We designed a new mutant form of FXIa catalytic domain rhFXI 370～607 (N73Q-N113Q-C123S),and report here the facile preparation,protein crystallization,and crystal structure of this protein.We highlight a few unique structural features of FXIa after comparison with the trypsin family serine proteases at sequence and structural levels.This work provides a foundation to develop new small molecular FXIa inhibitors with increased potency and specificity.     

异丙醇羧酸铝催化合成呋喃酚反应研究

选择了异丙醇羧酸铝催化2-(2-甲基烯丙氧基)苯酚合成呋喃酚；探讨异丙醇羧酸铝用量对合成呋喃酚反应的影响.实验结果表明,异丙醇羧酸铝可高效催化2-(2-甲基烯丙氧基)苯酚合成呋喃酚.当催化剂为异丙醇二乙酸铝,用量为2-(2-甲基烯丙氧基)苯酚的2.50％(物质的量比),呋喃酚的收率达到80.8％,高于目前工业上以异丙醇铝为催化剂的78.3％,具有应用价值.     

Synthesis,Characterization and Luminescent Properties of Two Copper(Ⅰ) Complexes Based on 2,2?-Biquinoline and Phosphorous Ligand

Three new copper(Ⅰ) complexes, namely [Cu(DPEphos)(Biq)]CF_3SO_3(1) and [Cu(PPh_3)_2(Biq)]CF_3SO_3(2) and [Cu(PPh_3)_2(Biq)]ClO_4(3)(DPEphos = bis[2-(diphenylphosp hino)phenyl]ether, PPh_3 = triphenylphosphine and Biq = 2,2?-biquinoline), are synthesized and characterized by IR, ~1H NMR, ~(31) P NMR, fluorescence spectra and terahertz time-domain spectroscopy(THz-TDS). Complex 1 crystallizes in triclinic, space group P1 with a = 12.6997(5), b = 13.2813(5), c = 15.3593(6) ?, α = 80.211(3)°, β = 88.752(3)°, γ = 70.113(3)°, V = 2398.85(15) ?~3, C_(55)H_(41.2)CuF_3N_2O_(4.6)P_2S, Mr = 1018.27, Z = 2, Dc = 1.410 g/cm3, F(000) = 1048, μ = 0.628 mm-1, the final R = 0.0450 and w R = 0.1105 for 9419 observed reflections(I 2σ(I)). Complex 2 crystallizes in monoclinic, space group C2/c with a = 19.9961(7), b = 15.9774(5), c = 17.7908(6) ?, β = 119.758(4)°, V = 4982.8(3) ?~3, C_(56.47)H_(47.88)CuF_3N_2O_(4.47)P_2S, Mr = 1040.54, Z = 4, Dc = 1.387 g/cm~3, F(000) = 2154, μ = 0.606 mm-1, the final R = 0.0430 and w R = 0.1218 for 4897 observed reflections(I 2σ(I)). Complex 3 crystallizes in monoclinic, space group C2/c with a = 19.7534(8), b = 15.0797(5), c = 17.8097(7) ?, β = 116.400(5)°, V = 4751.8(3) ?~3, C_(56)H_(45)ClCuN_3O_4P_2, Mr = 984.88, Z = 4, Dc = 1.377 g/cm~3, F(000) = 2040, μ = 0.635 mm-1, the final R = 0.0731 and w R = 0.2180 for 4670 observed reflections(I 2σ(I)). In the emission spectra, shifts of emission peak are derived from ligand-centered(π-π*) transition.     

基于二叉树模型的可转债价值分析——以国君转债为例

针对提高投资收益率的问题,采用二叉树模型对可转债价值进行分析.以国君转债为例,运用二叉树模型计算2019年4月30日—2019年6月11日共30个交易日的可转债理论价格,并与市场实际收市价进行对比.由于可转债有可以提前行权的美式期权特点,可转债价值在多数时间段是处于被高估的状态,并且还受到模型的偏差等因素影响.     

高功率激光器自动准直系统图像处理的可信度评估

自动准直系统是将采集的图像进行特定算法处理获取光束的位置信息,驱动电机调整光斑到指定的位置,其中图像质量对光束定位的精确性影响很大,为尽量避免受严重噪音和光束畸变影响的图像进入图像处理流程而产生准直结果的错误判断,保证自动准直系统图像处理结果的精确性,试图提供一种较为简单的判断依据,采用基于Monte-Carlo模拟方法,建立了远场准直过程中三种主要噪音的干扰评估模型,以测量不确定度作为定量判断处理图像与否的特征参数,将该结果做成统计图表作为判断依据。结果表明,在设定合理测量不确定度阈值的情况下,该特征参数能够较好地排除不良图像,从而提高准直结果的可信度。     

关于可控组装的一些思考（一）——从催化到催组装

分子组装的范畴和复杂性远歹乇于合成反应,但是它们有着相同目标,即高选择性和高效率地创造新物质和制备新功能材料．因此,我们尝试将合成中广泛应用的催化概念拓展至组装研究,提出用于调控和加速组装过程的催组装（cassemblysis）的新思路．为此,我们将迄今泛用的自组装、助组装等术语重新进行规范和分类,即所有的分子组装可分为自组装和助组装．绝大多数组装属于助组装,这可进一步分为催组装、共组装和外场助组装3大类．催组装中的催组剂（cassemblyst）类似于合成中的催化剂,可在不改变总吉布斯自由能变化的条件下加速组装过程,催组装因此有望成为在分子以上层次高选择性且高效率地创造新物质的最佳途径．一些催组装体系在组装之后还会进一步进行化学耦联反应,由此显著提高产物的稳定性,组装与耦联总过程可称为催组联（catassemblysis）．我们分别在小分子和生物大分子两个层次上,分析说明了迄今已被不自觉使用的催组装和催组联的一些典型事例,提出了光电催组装的设想,比较了与催组装关联的纳米粒子组装体系,探讨了与催组装相关的简要模型和机理．本：炙强调,在开展可控组装研究中,不仅要设计与合成各种新组装基元,而且要注重构建催组剂和催组联剂,发展催组装的实验和理论方法学,揭示催组剂作用于组装基元的机理,将有望推动可控组装在创造新物质和制备新功能材料方面发挥更大作用．     

蛋黄-壳结构Fe3O4@SiO2@PMO磁性微球的制备及对漆酶的固定化

以蛋黄-壳结构的Fe₃O₄@SiO₂@PMO磁性微球作为载体, 采用交联法对漆酶进行固定, 考察了戊二醛浓度等对固定效果的影响, 并对固定后漆酶的活性进行了研究. 结果表明, 蛋黄-壳结构的磁性微球负载漆酶仅需6 h, 磁性微球对漆酶的固载量高达475 mg/g. 固定后漆酶的稳定性显著提高, 在pH=2.5~4.5的强酸性条件下, 固定后漆酶酶活仍可保持70%以上, 即使温度升高至60 ℃, 固定后漆酶的相对酶活仍保持65%以上. 这说明漆酶经所合成的材料固定后, 其耐酸和耐热能力都明显优于游离漆酶. 包覆的Fe₃O₄粒子使得材料很容易经磁铁分离法回收, 固定后漆酶经磁分离循环使用10次后仍然能保留85%的酶活, 具有良好的可操作性和稳定性, 有效降低了漆酶的使用成本.     

新型咪唑-查尔酮衍生物的设计、合成及抗宫颈癌和顺铂耐药活性研究

摘要 目的 以甘草查尔酮母核为先导化合物骨架,设计、合成一系列新型咪唑-查尔酮衍生物并进行抗宫颈癌活性研究。方法 在查尔酮骨架的B环引入4种咪唑环,在A环分别引入甲氧基、氨基、羟基等活性基团;采用Claisen-Schmidt反应合成系列新型咪唑-查尔酮衍生物,其结构经1H-NMR、13C-NMR和HRMS进行表征。通过MTT、Transwell、流式细胞仪和分子对接实验方法,初步探索目标化合物的抗宫颈癌活性及作用机制。结果 大部分化合物具有一定的抗宫颈癌活性,其中2i较为显著,且对正常细胞的毒性较小。此外,化合物2i能够显著抑制HeLa和HeLa/DDP细胞的迁移和侵袭能力,能够诱导其凋亡,并阻滞HeLa和HeLa/DDP细胞于G2/M期;分子对接模拟显示2i与查尔酮母核和原配体秋水仙碱相比,2i与微管蛋白秋水仙碱结合位点具有较好的结合能力,并能够产生氢键相互作用力。结论 化合物2i具有较显著的抗宫颈癌和抗宫颈癌顺铂耐药活性作用,这可能与其抑制了微管蛋白靶点有关。     

Optics for the lattice of the compact storage ring for a Compton X-ray source

We present two types of optics for the lattice of a compact storage ring for a Compton X-ray source. The optics design for different operation modes of the storage ring are discussed in detail. For the pulse mode optics, an IBS-suppression scheme is applied to optimize the optics for lower IBS emittance growth rate; as for the steady mode, the method to control momentum compact factor is adopted [Gladkikh P, Phys. Rev. ST Accel. Beams 8, 050702] to obtain stability of the electron beam.     

Optics for the lattice of the compact storage ring for a Compton X-ray source

We present two types of optics for the lattice of a compact storage ring for a Compton X-ray source. The optics design for different operation modes of the storage ring are discussed in detail. For the pulse mode optics, an IBS-suppression scheme is applied to optimize the optics for lower IBS emittance growth rate; as for the steady mode, the method to control momentum compact factor is adopted [Gladkikh P, Phys. Rev. ST Accel. Beams 8, 050702] to