Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2

Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL^pro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide ( 2 b ), which is known to bind into the S3 and S4 pockets of the SARS-CoV PL^pro. Moreover, we report the discovery of isoindolines as a new class of potent PL^pro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PL^pro are valuable starting points for the development of new pan-coronaviral inhibitors.     

片状变燃速发射药燃烧性能的数值计算

为研究包覆方式对片状发射药燃烧性能的影响,建立了不同包覆方式下多层片状发射药的物理模型,并推导了形状函数和燃气生成猛度表达式,利用Matlab软件对不同的宽厚比、长厚比及多层结构的片状发射药进行了数值计算;制备了不同长厚比的片状变燃速发射药,并进行了密闭爆发器实验。结果表明,四面包覆和全包覆可以很好地消除临界宽厚比对片状发射药燃烧性能的影响;与两面包覆的片状发射药相比,四面包覆和全包覆的片状发射药能够延缓内层药减面燃烧的时间,其燃气生成猛度的阶跃程度分别提高了1.17%和1.23%,呈现出良好的燃烧渐增性。     

Metal Complexes as Antiviral Agents for SARS-CoV-2

The severe acute respiratory syndrome – coronavirus 2 (SARS-CoV-2), the infectious agent responsible for COVID-19 – has caused more than 2.5 million deaths worldwide and triggered a global pandemic. Even with successful vaccines being delivered, there is an urgent need for novel treatments to combat SARS-CoV-2, and other emerging viral diseases. While several organic small molecule drug candidates are in development, some effort has also been devoted towards the application of metal complexes as potential antiviral agents against SARS-CoV-2. Herein, the metal complexes that have been reported to show antiviral activity against SARS-CoV-2 or one of its target proteins are described and their proposed mechanisms of action are discussed.     

Subcellular Localisation of a Quinoline-Containing Fluorescent Cyclometallated IrIII Complex in Plasmodium falciparum

A fluorescent analogue of a previously synthesised N,N-chelated Ir^III complex was prepared by coordination of the organic ligand to an extrinsic bis(2-phenylpyridine)iridium(III) fluorophore. This cyclometallated Ir^III complex in itself displays good, micromolar activity against the chloroquine-sensitive NF54 strain of Plasmodium falciparum. Live-cell confocal microscopy found negligible localisation of the fluorescent complex within the digestive vacuole of the parasite. This eliminated the haem detoxification pathway as a potential mechanism of action. Similarly, no localisation of the complex within the parasitic nucleus was found, thus suggesting that this complex probably does not interfere with the DNA replication process. A substantial saturation of fluorescence from the complex was found near phospholipid structures such as the plasma and nuclear membranes but not in neutral lipid bodies. This indicates that an association with these membranes, or organelles such as the endoplasmic reticulum or branched mitochondrion, could be essential to the efficacies of these types of antimalarial compounds.     

无机盐对新疆油田三元复合驱界面性能影响研究

界面性能对复合驱提高采收率有重大的影响,界面张力越低,洗油效率越高;Zeta电位越高,油水乳状液越稳定。研究了各类无机盐对新疆油田复合驱界面性能的影响。结果显示,Zeta电位的绝对值随着无机盐浓度的增高而增大;无机碱中,碳酸根离子降低界面张力效果最好,氢氧根次之,碳酸氢根最差;阳离子中,钾离子降低界面张力效果最好,其次是钠离子,镁离子会略微提高界面张力,钙离子则会大幅度提高界面张力;阴离子中,与硫酸根相比,氯离子能更好地降低界面张力。通过以上研究,确定了Q站污水处理站外排水更适合三元复合驱配液。     

机械活化-湿化学合成LiMn2O4的组成、结构与表征

以MnO2和LiOH·H2O为原料,采用机械活化与湿化学集成的方法,在水溶液中直接合成了结晶态的尖晶石锂锰氧化物.当锂含量介于3.78%～4.35%之间时,所得锂锰氧化物为纳米级球形粉末,以尖晶石结构为主,含极少量的Mn3O4杂相;在300～800℃温度范围内热处理后,Mn3O4杂相消失,尖晶石结构更趋完善.所合成的含锂5.80%的高锂样品则以LiMnO2层状结构为主,含少量Mn3O4杂相,其SEM形貌为片状;在300～700℃下热处理8 h后,层状LiMnO2转变成尖晶石LiMn2O4,Mn3O4杂相峰明显减弱并随热处理温度的升高而消失;当温度升高至700～800℃时,开始出现缺锂的Li1-xMn2O4相.结果表明:该法制备锂锰氧化物可实现锂、锰、氧在原子级水平的均匀混合,所得产物的热稳定性能良好,其化学计量组成与结构易于调整和控制.     

Run(n=2～7)金属团簇与氧反应的DFT研究

采用密度泛函理论的广义梯度近似(DFT／GGA)，对Run簇(n=2～7)与氧相互作用的几何结构与电子结构及吸附能之间的关系进行讨论。对氧原子及氧分子在Run金属簇上的吸附研究表明：电荷主要是从Ru的5s、4d轨道向O的2p轨道迁移，并使得金属．金属之间的键减弱。比较特殊的是当氧分子在桥位吸附时，Ru与吸附的O2会发生化学反应，并且由于Ru金属轨道的电子向O2的反键πg轨道转移，导致Ru-O之间的键的生成以及O-O之间的键发生断裂。同时，作者也观察到Ru．Ru之间的化学键发生断裂，形成具有原子活性的自由Ru原子，这可以部分解释一旦氧化物种形成，经过一诱导期后，氧化反应会加速进行的实验事实。     

静电纺丝技术制备无机物纳米纤维的最新研究进展

静电纺丝技术近年来在制备纳米纤维领域得到了广泛的应用,被认为是最简单有效的方法之一,已经用这种方法成功地制备了不同的纳米纤维.本文对静电纺丝法做了较全面的总结,对机理和改进方法进行了介绍,对影响因素做了细致的分析,还对无机纳米纤维的应用做了简单的展望.