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.     

Cross-Module Enoylreduction in the Azalomycin F Polyketide Synthase

The colinearity of canonical modular polyketide synthases, which creates a direct link between multienzyme structure and the chemical structure of the biosynthetic end-product, has become a cornerstone of knowledge-based genome mining. Herein, we report genetic and enzymatic evidence for the remarkable role of an enoylreductase in the polyketide synthase for azalomycin F biosynthesis. This internal enoylreductase domain, previously identified as acting only in the second of two chain extension cycles on an initial iterative module, is shown to also catalyze enoylreduction in trans within the next module. The mechanism for this rare deviation from colinearity appears to involve direct cross-modular interaction of the reductase with the longer acyl chain, rather than back transfer of the substrate into the iterative module, suggesting an additional and surprising plasticity in natural PKS assembly-line catalysis.     

A Green and Wide-Scope Approach for Chiroptical Sensing of Organic Molecules through Biomimetic Recognition in Water

Optical chirality sensing has attracted a lot of interest due to its potential in high-throughput screening in chirality analysis. A molecular sensor is required to convert the chirality of analytes into optical signals. Although many molecular sensors have been reported, sensors with wide substrate scope remain to be developed. Herein, we report that the amide naphthotube-based chirality sensors have an unprecedented wide scope for chiroptical sensing of organic molecules. The substrates include, but are not limited to common organic products in asymmetric catalysis, chiral molecules with inert groups or remote functional groups from their chiral centers, natural products and their derivatives, and chiral drugs. The effective chirality sensing is based on biomimetic recognition in water and on effective chirality transfer through guest-induced formation of a chiral conformation of the sensors. Furthermore, the sensors can be used in real-time monitoring on reaction kinetics in water and in determining absolute configurations and ee values of the products in asymmetric catalysis.     

Research on gamma-ray irradiation-assisted synthesis of cross-linked polystyrene via bulk polymerization

Journal of Radioanalytical and Nuclear Chemistry - Controlling heat accumulation is one of the major challenges for block materials synthesizing via bulk polymerization. In the paper, cross-linked...     

A novel signal-on fluorescent aptasensor for ochratoxin A detection based on RecJf exonuclease-induced signal amplification

This article describes a simple and homogeneous fluorescent aptasensor for the detection of ochratoxin A (OTA). With its high specificity and simplicity; RecJ_f exonuclease is used to cleave DNA strand of the FAM-aptamer/OTA complex and realize target recycling signal amplification. In order to avoid the loss of reaction system, magnetic beads (MBs) are added only once at the last experimental step. This proposed fluorescent aptasensor showed the higher sensitivity in the range of 0.1–100 ng/mL with LOD of 0.056 ng/mL, and the good selectivity against other interfering toxins. The feasibility of the prepared aptasensor was studied by detecting OTA in spiked liquor and cereal samples. The obtained average recoveries ranged from 92% to 115%. This study provides a promising application with convenience and rapidness in the aptasensor fabrication for food safety analysis.     

The inhibition profiles of 4'-acylpyrrole–5-fluoroindolin-2-ones with a C-3' side chain for VEGFR2, PDGFR-β, and FGFR-1 protein kinases

In this study, we reported the inhibition profiles of 4′-acylpyrrole–5-fluoroindolin-2-one 3 with a C-3′ side chain for VEGFR2, PDGFR-β, and FGFR-1 protein kinases. The pyrrole-fused cyclohexanone moiety provided 3 with the best potency to inhibit the three kinases, and the C-3′ side chains contributed to the different inhibition profiles of 3 . Compound 3b with a C-3′ 2-carboxylethyl side chain showed good potency for the three kinase (IC₅₀: 25–260 nM), and compound 3g with a N,N-dialkyl-2-carbamoylethyl side chain was more active for VEGFR2 (IC₅₀: 59 nM) and PDGFR-β (IC₅₀: 16 nM) than FGFR-1 (IC₅₀: 1.7 μM). The C-3′ 3-(dialkylamino)propyl side chain accomplished 3h – j as selective PDGFR-β inhibitors (IC₅₀: 7.8–13 nM). Compound 3b was further investigated and found potent to inhibit VEGF- and FGF-dependent cell proliferation with moderate in vivo anticancer activity. Results from docking simulations revealed that the interactions of 3b with VEGFR2 and FGFR-1 which could account for the different inhibition profiles of 3 .     

Deciphering an Abnormal Layered-Tunnel Heterostructure Induced by Chemical Substitution for the Sodium Oxide Cathode

Demands for large-scale energy storage systems have driven the development of layered transition-metal oxide cathodes for room-temperature rechargeable sodium ion batteries (SIBs). Now, an abnormal layered-tunnel heterostructure Na_0.44Co_0.1Mn_0.9O₂ cathode material induced by chemical element substitution is reported. By virtue of beneficial synergistic effects, this layered-tunnel electrode shows outstanding electrochemical performance in sodium half-cell system and excellent compatibility with hard carbon anode in sodium full-cell system. The underlying formation process, charge compensation mechanism, phase transition, and sodium-ion storage electrochemistry are clearly articulated and confirmed through combined analyses of in situ high-energy X-ray diffraction and ex situ X-ray absorption spectroscopy as well as operando X-ray diffraction. This crystal structure engineering regulation strategy offers a future outlook into advanced cathode materials for SIBs.     

Carbene-Catalyzed Enantioselective Aromatic N-Nucleophilic Addition of Heteroarenes to Ketones

The aromatic nitrogen atoms of heteroarylaldehydes are activated by carbene catalysts to react with ketone electrophiles. Multi-functionalized cyclic N,O-acetal products are afforded in good to excellent yields and optical purities. Our reaction involves the formation of an unprecedented aza-fulvene-type acylazolium intermediate. A broad range of N-heteroaromatic aldehydes and electron-deficient ketone substrates works effectively in this transformation. Several of the chiral N,O-acetal products afforded through this protocol exhibit excellent antibacterial activities against Ralstonia solanacearum (Rs) and are valuable in the development of novel agrichemicals for plant protection.     

Synthesis and biological evaluation of new mono naphthalimide platinum(IV) derivatives as antitumor agents with dual DNA damage mechanism

Naphthalimide has emerged as an interesting DNA intercalator and possessed attracting antitumor properties. In this context, naphthalimide group was linked to platinum(IV) core to construct a series of new mono naphthalimide platinum(IV) derivatives. The title compounds exert effective antitumor activities to the tested tumor cells lines in vitro, especially the one with propionyl chain displays comparable or even better bioactivities than platinum(II) reference drugs cisplatin and oxaliplatin. Moreover, the mono naphthalimide platinum(IV) derivative displays comparable tumor growth inhibitory competence against CT26 xenograft tumors in BALB/c mice in vivo without severe toxic effects in contrast to oxaliplatin. A dual DNA damage mechanism was proven for the title complex. Both naphthalimide ligand and the liberated platinum(II) moiety could generate DNA lesions to tumor cells synergistically and active the apoptotic pathway by up-regulating the expression of caspase 9 and caspase 3. Meanwhile, the conversion of platinum(II) drug into tetravalent form by incorporating naphthalimide moiety increases the uptake of platinum in whole cells and DNA remarkably. All these facts might be the factors for the title platinum(IV) complexes to overcome platinum(II) drug resistance. Additionally, the mono naphthalimide platinum(IV) complex could interact with human serum albumin by hydrogen bond and van der Waals force which would further influence their storage, transport and bioactivities.     

Polyhydroxy Fullerene-loaded ZIF-8 Nanocomposites for Better Photodynamic Therapy

Photodynamic therapy (PDT) has been received broad attentions as a cancer treatment, and fullerenes are potential photosensitizer owing to their unique electronic structures. However, fullerenes show insolubility in water for the special structure, which will induce aggregation to hinder the production of reactive oxygen species (ROS). Furthermore, the size of fullerenes is not conducive to reach the tumors through the enhanced permeability and retention (EPR) effect. Herein, a polyhydroxy fullerene-loaded metal-organic framework is designed and prepared to address the mentioned problems encountering with fullerenes as photosensitizers. The nanocomposite PHF@ZIF-8, which is synthesized by a simple one-pot method, displays great biocompatibility and outstanding photodynamic performance under the 448 nm laser irradiation. This work provides strong evidence for PHF@ZIF-8 as a promising photosensitizer candidate.