氟喹诺酮-3-N-酰胺类衍生物的合成与抗肿瘤活性

为扩展氟喹诺酮由抗菌活性向抗肿瘤活性转化的结构修饰策略,利用药效团生物电子等排及其拼合和骨架迁越药物化学分子构建方法,以酰胺基作为氟喹诺酮C-3位羧基的生物电子等排体,氟喹诺酮骨架为酰胺基的功能修饰基,设计合成了氟喹诺酮-3-N-酰胺类目标化合物。其结构经元素分析和光谱数据确证。体外抗肿瘤实验结果表明,目标化合物对Hep-3B细胞和Capan-1细胞的抗增殖活性均显著强于母体环丙沙星的活性,尤其对Hep-3B细胞的抑制活性最强。因此,用酰胺基来替代C-3羧基有利于提高氟喹诺酮的抗肿瘤活性。     

Polypyridine-Based Helical Amide Foldamer Channels: Rapid Transport of Water and Protons with High Ion Rejection

Synthetic strategies that enable rapid construction of covalent organic nanotubes with an angstrom-scale tubular pore remain scarcely reported. Reported here is a remarkably simple and mild one-pot polymerization protocol, employing POCl₃ as the polymerization agent. This protocol efficiently generates polypyridine amide foldamer-based covalent organic nanotubes with a 2.8 nm length at a yield of 50 %. Trapping single-file water chains in the 2.8 Å tubular cavity, rich in hydrogen-bond donors and acceptors, these tubular polypyridine ensembles rapidly and selectively transport water at a rate of 1.6×10⁹ H₂O⋅S⁻¹⋅channel⁻¹ and protons at a speed as fast as gramicidin A, with a high rejection of ions.     

Atomic-Scale Insight into Exsolution of CoFe Alloy Nanoparticles in La0.4Sr0.6Co0.2Fe0.7Mo0.1O3−δ with Efficient CO2 Electrolysis

In situ exsolution of metal nanoparticles in perovskite under reducing atmosphere is employed to generate a highly active metal–oxide interface for CO₂ electrolysis in a solid oxide electrolysis cell. Atomic-scale insight is provided into the exsolution of CoFe alloy nanoparticles in La_0.4Sr_0.6Co_0.2Fe_0.7Mo_0.1O_3−δ (LSCFM) by in situ scanning transmission electron microscopy (STEM) with energy-dispersive X-ray spectroscopy and DFT calculations. The doped Mo atoms occupy B sites of LSCFM, which increases the segregation energy of Co and Fe ions at B sites and improves the structural stability of LSCFM under a reducing atmosphere. In situ STEM measurements visualized sequential exsolution of Co and Fe ions, formation of CoFe alloy nanoparticles, and reversible exsolution and dissolution of CoFe alloy nanoparticles in LSCFM. The metal–oxide interface improves CO₂ adsorption and activation, showing a higher CO₂ electrolysis performance than the LSCFM counterparts.     

Accelerating Crystallization of Open Organic Materials by Poly(ionic liquid)s

The capability to significantly shorten the synthetic period of a broad spectrum of open organic materials presents an enticing prospect for materials processing and applications. Herein we discovered 1,2,4-triazolium poly(ionic liquid)s (PILs) could serve as a universal additive to accelerate by at least one order of magnitude the growth rate of representative imine-linked crystalline open organics, including organic cages, covalent organic frameworks (COFs), and macrocycles. This phenomenon results from the active C5-protons in poly(1,2,4-triazolium)s that catalyze the formation of imine bonds, and the simultaneous salting-out effect (induced precipitation by decreasing solubility) that PILs exert on these crystallizing species.     

Single Atoms of Iron on MoS2 Nanosheets for N2 Electroreduction into Ammonia

Efforts have been devoted to achieving a highly efficient artificial synthesis of ammonia (NH₃). Reported herein is a novel Fe-MoS₂ catalyst with Fe atomically dispersed onto MoS₂ nanosheets, imitating natural nitrogenase, to boost N₂ electroreduction into NH₃ at room temperature. The Fe-MoS₂ nanosheets exhibited a faradic efficiency of 18.8 % with a yield rate of 8.63 μg mg_cat.⁻¹ h⁻¹ for NH₃ at −0.3 V versus the reversible hydrogen electrode. The mechanism study revealed that the electroreduction of N₂ was promoted and the competing hydrogen evolution reaction was suppressed by decorating the edge sites of S in MoS₂ with the atomically dispersed Fe, resulting in high catalytic performance for the electroreduction of N₂ into NH₃. This work provides new ideas for the design of catalysts for N₂ electroreduction and strengthens the understanding about N₂ activation over Mo-based catalysts.     

Iron-Catalyzed Radical Relay Enabling the Modular Synthesis of Fused Pyridines from Alkyne-Tethered Oximes and Alkenes

We have rationally designed a new class of alkyne-tethered oximes and applied them in an unprecedented iron-catalyzed radical relay protocol for the rapid assembly of a wide array of structurally new and interesting fused pyridines. This method shows broad substrate scope and good functional-group tolerance and enabled the synthesis of several biologically active molecules. Furthermore, the fused pyridines could be diversely functionalized through various simple transformations, such as cyclization, C−H alkylation, and a click reaction. DFT calculation studies indicate that the reactions involve cascade 1,5-hydrogen atom transfer, 5-exo-dig radical addition, and cyclization processes. Moreover, preliminary biological investigations suggest that some of the fused pyridines exhibit good anti-inflammatory activity by restoring the imbalance of inflammatory homeostasis of macrophages in a lipopolysaccharide-induced model.     

Stereoselectivity and nonmigratory insertion mechanism of dimethylacetylene dicarboxylate into metallocene-hydride of Cp2M(L)H [Cp = η5-C5H5; M = Nb,V; L = CO,P (OMe)3]: A DFT study

The insertion of an alkyne into transition metal–hydrogen bonds is a key elementary step in catalytic polymerization and hydrogenation processes. It was found that a (Z)- or (E)-type alkyenyl complex can be formed through trans/cis stereospecific processes. In this work, the reaction mechanism of Cp₂M(L)H [Cp = η⁵-C₅H₅; M = Nb, V; L = CO, P (OMe)₃] with dimethylacetylene dicarboxylate (DMAD), and the factors influencing the stereoselectivity have been investigated based on density functional theory calculations. The calculated results show that all of the reactions are exothermic. For L = CO, the Z-isomer product forms first even at low temperatures because of the low Gibbs free energy barrier (ΔG^#). Then the Z-pro converts to E-pro , while for L = P (OMe)₃, the exclusive product is the E-isomer. For different metal centers, the reaction mechanisms of the Cp₂M(CO)H + DMAD (M = Nb and V) reaction are similar, while their products are different at room temperature. For M = Nb, because the energy barrier of the isomerization from Z-pro to E-pro is low and the relative free energies of Z-pro and E-pro are almost equal, both Z-pro and E-pro can be obtained. While for the Cp₂V(CO)H + DMAD reaction, only the Z-pro can be obtained under mild conditions, E-pro can be obtained only at high temperatures. For the Cp₂M(CO)H+DMAD(M=V and Nb) reactions, the formation of E-isomer products proceeds via two five-membered ring transition states. The calculated results provide an reasonable explanation for the experimental results and predict a new insertion reaction.     

In Situ Metal-Assisted Ligand Modification Induces Mn4 Cluster-to-Cluster Transformation: A Crystallography,Mass Spectrometry,and DFT Study

Dehydration of (S,S)-1,2-bis(1H-benzo[d]imidazol-2-yl)ethane-1,2-diol (H₄L) to (Z)-1,2-bis(1H-benzo[d]imidazol-2-yl)ethenol) (H₃L′) was found to be metal-assisted, occurs under solvothermal conditions (H₂O/CH₃OH), and leads to [Mn^II₄(H₃L)₄Cl₂]Cl₂ ⋅ 5 H₂O ⋅ 5 CH₃OH ( Mn₄L₄ ) and [Mn^II₄(H₂L′)₆(μ₃-OH)]Cl ⋅ 4 CH₃OH ⋅ H₂O ( Mn₄L′₆ ), respectively. Their structures were determined by single-crystal XRD. Extensive ESI-MS studies on solutions and solids of the reaction led to the proposal consisting of an initial stepwise assembly of Mn₄L₄ from the reactants via [MnL] and [Mn₂L₂] below 80 °C, and then disassembly to [MnL] and [MnL₂] followed by ligand modification before reassembly to Mn₄L′₆ via [MnL′], [MnL′₂], and [Mn₂L′₃] with increasing solvothermal temperature up to 140 °C. Identification of intermediates [Mn₄L_xL′_6−x] (x=5, 4, 3, 2, 1) in the process further suggested an assembly/disassembly/in situ reaction/reassembly transformation mechanism. These results not only reveal that multiple phase transformations are possible even though they were not realized in the crystalline state, but also help to better understand the complex transformation process between coordination clusters during “black-box” reactions.     

液相色谱手性拆分机理的热力学方法研究

手性识别是分子识别的一个重要组成部分。液相色谱手性拆分机理研究有助于色谱条件的优化和新型手性固定相的设计,也有助于理解手性识别机制。本文就线性色谱与非线性色谱条件下手性拆分过程对应热力学参数的推求方法进行了评述,阐述了相关热力学参数的涵义及其在色谱保留及手性拆分机理探讨中的应用,并展望了该领域的研究前景。