Ferric Ion Driven Assembly of Catalase-like Supramolecular Photosensitizing Nanozymes for Combating Hypoxic Tumors

A facile approach to assemble catalase-like photosensitizing nanozymes with a self-oxygen-supplying ability was developed. The process involved Fe³⁺-driven self-assembly of fluorenylmethyloxycarbonyl (Fmoc)-protected amino acids. By adding a zinc(II) phthalocyanine-based photosensitizer (ZnPc) and the hypoxia-inducible factor 1 (HIF-1) inhibitor acriflavine (ACF) during the Fe³⁺-promoted self-assembly of Fmoc-protected cysteine (Fmoc-Cys), the nanovesicles Fmoc-Cys/Fe@Pc and Fmoc-Cys/Fe@Pc/ACF were prepared, which could be disassembled intracellularly. The released Fe³⁺ could catalyze the transformation of H₂O₂ enriched in cancer cells to oxygen efficiently, thereby ameliorating the hypoxic condition and promoting the photosensitizing activity of the released ZnPc. With an additional therapeutic component, Fmoc-Cys/Fe@Pc/ACF exhibited higher in vitro and in vivo photodynamic activities than Fmoc-Cys/Fe@Pc, demonstrating the synergistic effect of ZnPc and ACF.     

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.     

Synthesis,cytotoxicity and apoptosis-inducing activity of novel 1H-benzo[d]imidazole derivatives of dehydroabietic acid

With the expectation of finding new and effective antitumor drugs, a series of novel N-(1H-benzo[d]imidazole-2-yl)-benzamide/benzenesulfonamide derivatives of dehydroabietic acid were synthesized and evaluated for cytotoxic activity against three human cancer cell lines (MCF-7, HeLa, and HepG2 cells) and one human normal hepatocyte cell line (LO2). As a result, a number of derivatives showed moderate to good antitumor activities. Among them, compound 8h exhibited the most potent activities against three cancer cell lines with IC₅₀ values of 0.87 ± 0.18, 9.39 ± 0.72, and 8.31 ± 0.64 μM, respectively, and was less active to normal hepatocyte LO2 cells. Further mechanism studies revealed that compound 8h could arrest the cell cycle of MCF-7 cells at S phase and induce the apoptosis of MCF-7 cells in ROS-mediated mitochondrial pathway.     

Effect of ammonia,ammonia-water,and sulfuric acid on the HO2 + HO2 → H2O2 + 3O2 reaction in troposphere: Competition between stepwise and one-step mechanisms

A detailed theoretical study on the reaction mechanisms for the formations of H₂O₂ + ³O₂ from the self-reaction of HO₂ radicals under the effect of NH₃, H₃N···H₂O, and H₂SO₄ catalysts was performed using the CCSD(T)/CBS//M06-2X/aug-cc-pVTZ method. The rate constant was computed using canonical variational transition state theory (CVT) with small curvature tunneling (SCT). Our results indicate that NH₃-, H₃N···H₂O-, and H₂SO₄-catalyzed reactions could proceed through both one-step and stepwise routes. Calculated rate constants show that the catalyzed routes in the presence of the three catalysts all prefer stepwise pathways. Compared to the catalytic efficiency of H₂O, the efficiencies of NH₃, H₃N···H₂O, and H₂SO₄ are much lower due to their smaller relative concentrations. The present results have provided a definitive example of how basic and acidic catalysts influence the atmospheric reaction of HO₂ + HO₂ → H₂O₂ + ³O₂. These results further encourage one to consider the effects of basic and acidic catalysts on the related atmospheric reactions. Thus, the present investigation should have broad implications in the gas-phase reactions of the atmosphere.     

NIS-promoted multicomponent reaction of 2-aminopyridines with aldehydes and nitromethane for the synthesis of 3-nitroimidazo[1.2-a]pyridines

An efficient synthesis of 3-nitroimidazo[1,2-a]pyridines has been developed via N-iodosuccinimide (NIS)-mediated multicomponents reaction of 2-aminopyridines, aldehydes, and nitromethane under metal-free conditions. This protocol has many advantages such as broad substituent scope, mild and eco-friendly conditions, high step economy, and good yields.     

An efficient synthesis of 6-benzyl-2-arylthieno[2,3-d]pyrimidin-4(3H)-ones catalyzed by HCl involving a Friedel-Crafts alkylation reaction

Aldehyde could undergo not only the subsequent condensation and cyclization with 2-aminothiophene-3-carboxamide to build a pyrimidine ring, but also a Friedel-Crafts alkylation reaction with thiophene moiety to give unexpected 6-benzyl-2-arylthieno[2,3-d]pyrimidin-4(3H)- ones in good yields catalyzed by concentrated HCl.     

Self-Assembly of Highly Stable Zirconium(IV) Coordination Cages with Aggregation Induced Emission Molecular Rotors for Live-Cell Imaging

The self-assembly of highly stable zirconium(IV)-based coordination cages with aggregation induced emission (AIE) molecular rotors for in vitro bio-imaging is reported. The two coordination cages, NUS-100 and NUS-101, are assembled from the highly stable trinuclear zirconium vertices and two flexible carboxyl-decorated tetraphenylethylene (TPE) spacers. Extensive experimental and theoretical results show that the emissive intensity of the coordination cages can be controlled by restricting the dynamics of AIE-active molecular rotors though multiple external stimuli. Because the two coordination cages have excellent chemical stability in aqueous solutions (pH stability: 2–10) and impressive AIE characteristics contributed by the molecular rotors, they can be employed as novel biological fluorescent probes for in vitro live-cell imaging.     

Formation and Fate of Formaldehyde in Methanol-to-Hydrocarbon Reaction: In Situ Synchrotron Radiation Photoionization Mass Spectrometry Study

HCHO has been confirmed as an active intermediate in the methanol-to-hydrocarbon (MTH) reaction, and is critical for interpreting the mechanisms of coke formation. Here, HCHO was detected and quantified during the MTH process over HSAPO-34 and HZSM-5 by in situ synchrotron radiation photoionization mass spectrometry. Compared with conventional methods, excellent time-resolved profiles were obtained to study the formation and fate of HCHO, and other products during the induction, steady-state reaction, and deactivation periods. Similar formation trends of HCHO and methane, and their close correlation in yields suggest that they are derived from disproportionation of methanol at acidic sites. In the presence of Y₂O₃, the amount of HCHO changes, affecting the hydrogen-transfer processes of olefins into aromatics and aromatics into cokes. The yield of HCHO affects the aromatic-based cycle and the formation of ethylene, indicating that ethylene is mainly formed from the aromatic-based cycle.     

Rationally Designed Three-Layered Cu2S@Carbon@MoS2 Hierarchical Nanoboxes for Efficient Sodium Storage

Hybrid materials, integrating the merits of individual components, are ideal structures for efficient sodium storage. However, the construction of hybrid structures with decent physical/electrochemical properties is still challenging. Now, the elaborate design and synthesis of hierarchical nanoboxes composed of three-layered Cu₂S@carbon@MoS₂ as anode materials for sodium-ion batteries is reported. Through a facile multistep template-engaged strategy, ultrathin MoS₂ nanosheets are grown on nitrogen-doped carbon-coated Cu₂S nanoboxes to realize the Cu₂S@carbon@MoS₂ configuration. The design shortens the diffusion path of electrons/Na⁺ ions, accommodates the volume change of electrodes during cycling, enhances the electric conductivity of the hybrids, and offers abundant active sites for sodium uptake. By virtue of these advantages, these three-layered Cu₂S@carbon@MoS₂ hierarchical nanoboxes show excellent electrochemical properties in terms of decent rate capability and stable cycle life.     

Efficient Screening for Ternary Molecular Ionic Cocrystals Using a Complementary Mechanosynthesis and Computational Structure Prediction Approach

The discovery of molecular ionic cocrystals (ICCs) of active pharmaceutical ingredients (APIs) widens the opportunities for optimizing the physicochemical properties of APIs whilst facilitating the delivery of multiple therapeutic agents. However, ICCs are often observed serendipitously in crystallization screens and the factors dictating their crystallization are poorly understood. We demonstrate here that mechanochemical ball milling is a versatile technique for the reproducible synthesis of ternary molecular ICCs in less than 30 min of grinding with or without solvent. Computational crystal structure prediction (CSP) calculations have been performed on ternary molecular ICCs for the first time and the observed crystal structures of all the ICCs were correctly predicted. Periodic dispersion-corrected DFT calculations revealed that all the ICCs are thermodynamically stable (mean stabilization energy=−2 kJ mol⁻¹) relative to the crystallization of a physical mixture of the binary salt and acid. The results suggest that a combined mechanosynthesis and CSP approach could be used to target the synthesis of higher-order molecular ICCs with functional properties.