Science China Chemistry最新文献

Alicyclic nitrogen heterocycles, such as enantioenriched polycyclic fused [1,2-a]indoline derivatives, are widespread in natural products, agrochemicals and pharmaceutical agents. Existing methods predominantly rely on the recent emerging Heck-type catalytic asymmetric dearomatization (CADA) protocol, wherein noble palladium catalysts commonly necessitate the form aryl-Pd species-triggered these transformations. In contrast, a more sustainable base metal catalysis paradigm through alkyl metal species disrupting the aromaticity, that is, the utilization of challenging asymmetric Csp³–Csp³ bond formation entry to such important chiral densely functionalized polycyclic molecular scaffolds, remains an elusive task. Herein, we report the first copper-catalyzed dearomative borylative cyclization of indoles under mild reaction conditions, affording an array of valuable Bpin-containing pyrrolo-fused [1,2-a]indolines bearing four consecutive stereogenic centers with excellent enantio- and diastereoselectivity. The synthetic potential was documented via an array of useful transformations. Density functional theory (DFT) calculation studies elucidated the origin of the chemo-, regio-, enantio- and diastereoselectivities of this conversion.

Endoplasmic reticulum (ER) viscosity has emerged as a new potential biomarker for hepatic fibrosis (HF). Herein, we report the first ER-targeting viscosity-responsive near-infrared (NIR) fluorescent probe HBT-PP for investigations of HF pathogenesis. The twisted intramolecular charge transfer (TICT) and the excited state intramolecular proton transfer (ESIPT) are combined to endow HBT-PP with the selective response towards viscosity (∼62-fold) and a super large stokes shift (∼320 nm). HBT-PP mainly targets organelle ER and is able to image the drug- or alcohol-induced viscosity elevation in living cells. Significantly, HBT-PP was successfully applied to visualize the gender difference in HF and the protective role of estrogen in restraining HF progression. Of note, after 10 min of stain with HBT-PP, HF lesions showed a stage-based response, indicating the potential of this probe in fast and early diagnosis of HF. These results clearly demonstrated the promising application of HBT-PP as a new tool for exploring ER viscosity-involved physiological and pathological processes.

Potassium ions (K⁺) doped graphitic carbon nitride (g-C₃N₄) was prepared by a thermal etching method using potassium hydroxide (KOH) as an ion source. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) results showed that the generation of the cyano group was detected while introducing K⁺. Under simulated sunlight irradiation, the sample with a K⁺ doping amount of 10% showed the highest hydrogen peroxide (H₂O₂) generation rate of 2,140.2 µmol h⁻¹ g⁻¹. The apparent quantum yield (AQY) at 400 nm and the solar-to-chemical conversion (SCC) are 4.35% and 1.23%, respectively. K⁺ acted as a bridge between g-C₃N₄ layers, which enhanced charge transfer efficiency. Meanwhile, the cyano group enhanced the adsorption capacity of protons (H⁺) and promoted the yield of H₂O₂. The catalyst exhibited excellent photocatalytic stability based on four-cycle experiments. In addition, a mechanism study showed that superoxide radicals (·O₂⁻) were the most important active species in the reaction system. Photocatalytic production of H₂O₂ was achieved through consecutive single-electron steps. This study deepens the understanding of the oxygen reduction reaction process and opens up a new venue for improving H₂O₂ generation.

Despite great achievements obtained for polymer-based room-temperature phosphorescence (RTP) materials, the limited efficiencies of persistent RTP still hinder their development. Herein, a simple and universal strategy of using the dual-functional additive of Cs⁺ was presented, which could simultaneously enhance the efficiency (Φ_p) and maintain the long lifetime (τ_p) of RTP in existing polymer-based systems with various phosphors and polymers. Among them, the commercial emitter (TpB)-doped polyvinyl alcohol (PVA)/Cs₂CO₃ system possessed an extremely high Φ_p up to 75.5% and still maintained a long τ_p of 2.13 s, by introducing the heavy-atom effect and an extra network of ionic bonding through the Cs⁺ additive. Additionally, the temperature resistance of RTP in TpB@PVA/Cs⁺ film could also be improved to 85 °C. More satisfactorily, the efficiency of Förster resonance energy transfer (FRET) from RTP to near-infrared (NIR) was also remarkably enhanced in the multi-component systems. This work provides a simple and universal strategy for developing polymer systems with high RTP performance.

Supramolecular polymer networks (SPNs) have garnered significant research interest due to their dynamic properties. However, while current developments primarily focus on managing supramolecular crosslinks, the role of polymer backbones—equally crucial to SPN properties—has not yet been sufficiently explored. Herein, we utilize mechanically interlocked [an]daisy chain as backbone to prepare a class of SPNs, where the force-induced motion of successive mechanical bonds toughens and reinforces the networks. In specific, the [an]daisy chain backbones connect with polynorbornene chains through quadruple H-bonding in the SPN networks. Compared to the control with non-slidable backbone, The representative SPN-2 exhibits a robust feature in tensile tests with high maximum stress (14.7 vs. 7.89 MPa) and toughness (83.8 vs. 48.6 MJ/m³). Moreover, it also has superior performance in energy dissipation benefitting from the [an]daisy chain backbones as well as supramolecular crosslinks. Additionally, the SPN-2 displayed exceptional self-healing and reprocessing capabilities due to their dynamic quadrable H-bonding crosslinkers. These findings demonstrate the untapped potential of [an]daisy chain as a polymer skeleton to develop SPNs and open the door to design mechanically robust supramolecular materials with diverse smart functions.

Forming electrostatic nanocomplexes (ENCs) with counter-ions can improve the delivery efficiency of chemotherapy drugs. However, water-soluble chemotherapy drugs like mitoxantrone (MTO), have limited affinity for counter-ions, posing challenges in the creation of stable ENCs. Herein, MTO was connected to fatty alcohols of varying chain lengths (C8, C12, C16) via disulfide bonds, forming hydrophobic prodrugs. We found that conjugating MTO to fatty alcohols significantly improved its affinity for the counter-ion sodium cholesterol sulfate (SCS). Among the designed prodrugs, conjugated to fatty alcohols with longer carbon chain lengths exhibited heightened affinity for SCS, resulting in the formation of more stable ENCs. However, extending the carbon chain also slowed the rate of drug release. Overall, compared with MTO solution, these ENCs demonstrated comparable therapeutic efficacy while causing minimal damage to healthy tissues, especially for MTO-SS-C16 ENCs. Our research provides new insights for constructing stable and safe ENCs for hydrophilic drugs like MTO.

The development of a nucleophilic fluorination protocol using hydrofluoric acid as the fluoride source represents a long-sought goal in the field of organofluorine chemistry. We report herein the realization of such a reaction that employed alkyl-substituted sulfonium ylides as the substrates. The key to the success of the protocol was attributed to two factors: First, as a Brønsted base, the ylide was able to be protonated by HFaq, thus serving as a phase-transfer shuttle generated in situ to bring F⁻ from aqueous phase to the organic phase promoting desolvation of fluoride ion. Second, after protonation, a sulfonium salt, a good leaving group, was generated and subsequent attacked by the fluoride to afford the alkyl fluoride. Mechanistic investigation indicates that the reaction occurs via an S_N1 pathway. Because of the nature of the cationic intermediate in the reaction, two attractive rearrangement-fluorination approaches including 1,2-aryl migration fluorination and ring-expansion fluorination were disclosed.

Fe-N-C is hailed as the most promising candidate for replacing costly platinum-based catalysts for proton-exchange membrane fuel cells (PEMFCs) owing to their impressive catalytic activity and low cost. However, the durability of Fe-N-C catalysts remains a major challenge, primarily due to an insufficient understanding of their degradation mechanisms. In this study, we monitor the real-time changes in the electrode during the oxygen reduction reaction (ORR), shedding light on the potential-dependent degradation mechanisms inherent to Fe-N-C catalysts. Utilizing in-situ differential electrochemical mass spectroscopy, we identify three distinct potential regions with varying degrees of performance loss, notably observing carbon corrosion signals at low potentials. Theoretical calculations and fluorescence probe experiments corroborate that degradation mechanisms at high potentials are primarily driven by strong oxidative potentials that overcome the carbon oxidation energy barrier, whereas the degradation at low potentials is predominantly caused by the high concentrations of reactive oxygen species (ROS) generated during the ORR. The potential-dependent carbon corrosion consequently leads to a similar dependence of demetallation of active sites on the working potential. This study offers a comprehensive understanding of the intrinsic interrelations among various degradation mechanisms, thus paving the way for enhancing the durability of Fe-N-C catalysts in PEMFC applications.

Although supramolecular chirality tuning is prosperous in systems with small molecular building blocks, these systems lack structural strength and have limited practical applications. Conversely, polymer systems do not exhibit these drawbacks but suffer from topological chain entanglement, which often leads to large dynamic obstacles and therefore limits the tunability of supramolecular chirality. Herein, we report that by manipulating stoichiometry and employing light to alter the H-bond crosslinking between a photoexcitation-induced aggregatable molecule and high molecular weight poly(L-lactic acids), supramolecular chirality tuning of the polymer gel systems can be achieved in different ways through a cooperative self-assembly. Specifically, the Cotton effects of the examined systems can be negatively tuned by varying their stoichiometry, while positive tuning can be realized by photoirradiation. After deexcitation, negative Cotton effect tuning occurs again spontaneously in some cases. Such supramolecular chirality tuning is accompanied by rheological property tuning, demonstrating that our strategy can overcome polymer chain entanglement limitations. The proposed strategy inspires further works on the precise control of polymer chirality and, hence, development of asymmetric materials with changeable optical activity and modulus.

Transcription factors (TFs) play vital roles in regulating gene expressions. Dysregulated or mutated TFs are implicated in a wide array of diseases, highlighting their potential as drug targets. However, TFs are considered undruggable by conventional inhibitor-based modalities. The recently emerged proteolysis targeting chimeras (PROTACs) have exhibited great potential in tackling TFs. In particular, DNA-ligand chimeras that arm E3 ligase-recruiting ligands to TF-binding double-strand DNA represent a promising strategy for the targeted proteolysis of TFs. Here, we report a DNAzyme-inducible PROTAC (DzTAC) that selectively degrades NF-κB in a zinc ion-dependent manner. We further applied zinc-imidazolate metal-organic framework-90 (ZIF-90) to encapsulate DzTAC (ZIF-90@DzTAC), facilitating its delivery into cancer cells while self-supplying Zn²⁺ via adenosine triphosphate (ATP)-triggered ZIF-90 dissociation. Moreover, ZIF-90@DzTAC can enhance the treatment efficacy of doxorubicin-based chemotherapy in tumor-bearing mice. The developed DzTAC provides specific modulation over TF activity and opens an avenue for more functional nucleic acid-based control over targeted protein degradation.