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Metal–organic framework (MOF) derived carbon-based nanocatalysts have received great attention in environmental remediation application. However, the aggregation and poor separation characteristics...

The BCR-ABL fusion oncoprotein causes chronic myeloid leukemia or acute lymphoblastic leukemia in Ph+ patients because the ABL kinase is constitutively activated. However, current clinical treatment with ABL inhibitors is seriously limited by drug resistance and adverse effects. Although the emerging proteolysis-targeting chimeras (PROTACs) have been introduced to degrade BCR-ABL, most of them showed limited activity and could not overcome the common drug-resistant mutants, especially for T315I mutant. Herein, we systematically designed a set of unique PROTACs by globally targeting all the three binding sites of BCR-ABL, including dasatinib-, ponatinib-, and asciminib-based PROTACs. Our ponatinib-based PROTACs showed practical activity as dasatinib-based PROTACs, while no reported ponatinib-based PROTACs could degrade BCR-ABL before. As a proof of concept, some additional dasatinib-based PROTACs were then designed to degrade T315I mutant too. We provided a global PROTAC toolbox for degrading both wild-type and T315I-mutated BCR-ABL from each binding site. More importantly, these PROTACs showed better selectivity and less adverse effects than the inhibitors, indicating that PROTACs had great potential for overcoming clinical drug resistance and safety issues.

Selective removal of organic pollutants from surface water with high efficiency is crucial in water purification. Here, yolk-shell Co/C nanoreactors (YSCCNs) are facilely synthesized via pyrolysis of controllably etched ZIF-67 by tannic acid, and their degradation performance on multiple pollutants is demonstrated. To present the structure-performance relationship between the designed nanocatalyst and the selective removal of organic pollutants, bisphenol A (BPA) was selected as the targeted pollutant with coexistence of humus acid (HA). For comparison, solid and hollow ZIF-67 derived Co/C nanoparticles denoted as SCCNs and HCCNs, were also tested. The results show that YSCCNs exhibit enhanced BPA degradation rate of 0.32 min-1, which is 23.1% and 45.4% higher than that of HCCNs and SCCNs in HA (10 ppm) system. The essential improvement can be ascribed to the synergetic effects from shell layer (size-exclusion) and core/shell (confinement effect). The degradation mechanism and pathway are further confirmed by radical quenching experiments and liquid chromatography-mass spectrograph (LC-MS), respectively. In addition, some influential factors, including reaction temperature, pH value, and peroxymonosulfate (PMS) dosage are investigated in detail. This work provides a possible way to selectively remove target contaminant from multiple pollutants in complex water system.

[Image: see text] PROTACs-induced targeted protein degradation has emerged as a novel therapeutic strategy in drug development and attracted the favor of academic institutions, large pharmaceutical enterprises (e.g., AstraZeneca, Bayer, Novartis, Amgen, Pfizer, GlaxoSmithKline, Merck, and Boehringer Ingelheim, etc.), and biotechnology companies. PROTACs opened a new chapter for novel drug development. However, any new technology will face many new problems and challenges. Perspectives on the potential opportunities and challenges of PROTACs will contribute to the research and development of new protein degradation drugs and degrader tools.

A structure-hopping strategy was applied to discover a series of novel 4-aminoquinoline-3-carboxamide derivatives as potent, reversible BTK inhibitors. Compared to the previously described cinnoline scaffold compounds, the 4-aminoquinoline analogues showed significantly improved drug-like properties, especially in their aqueous solubility. The most potent compound

The performance of thin film nanocomposite (TFN) membrane is significantly determined by the inherent structure and composition of the incorporated nanofillers. In this work, hydrophilic hollow nanocubes (HHNs) derived from zeolitic imidazolate framework 8 (ZIF-8) were incorporated into the polyamide layer via an interfacial polymerization approach. The HHNs with abundant hydroxyl groups on the surface were obtained by etching solid ZIF-8 using tannic acid. Benefiting from the hydrophilicity, hollow structure, and negative charge of HHNs, the outstanding nanofiltration performance of the composite membrane was achieved. With the assistance of HHNs, the permeance and Na2SO4 rejection of the TFN membrane increased up to 19.4 ± 0.6 L/(m2·h·bar) and 95.2 ± 1.4%, corresponding to an improvement of 190% of the permeance and 2.0% of the rejection compared to the pristine thin film composite membrane. Comparatively, the performance of TFN membranes prepared with solid ZIF-8 only shows 116% improvements of the permeance with slightly increased salt rejection. More importantly, the antifouling property of the TFN-4H membrane was also elevated. The flux recovery ratios of the TFN-4H membrane are 93.2 and 84.7% corresponding to humic acid and bovine serum albumin solutions, respectively. The results indicate that the nanofiltration performance of the composite membrane was significantly enhanced with the incorporation of HHNs.

Developing novel coating materials for fast and sensitive solid-phase microextraction (SPME) is highly desired but few are achieved. In this work, a new material of metal-organic framework (MOF)-derived hollow carbon nanocubes (HCNCs) was prepared as a fiber coating material for SPME. The HCNC-coated fiber (denoted as HCNCs-F) exhibited a better enrichment performance than solid carbon nanocube (SCNC)-coated fiber (denoted as SCNCs-F) and commercial fibers based on the abundant active sites of the hollow structure, hydrophobic interactions, and π-π interactions. Moreover, because of the reduced mass-transport lengths of the hollow mesoporous structure, the HCNCs-F demonstrated a faster mass transfer compared with the SCNCs-F. The HCNCs-F was used to determine the six hydrophobic polycyclic aromatic hydrocarbons (PAHs) with wide linear ranges (10-2000 ng L-1 for naphthalene and 5-2000 ng L-1 for the other five analytes), good reproducibility (relative standard deviation < 8.8%), and low detection limits (0.03-0.70 ng L-1). Finally, the HCNCs-F was successfully applied for the determination of PAHs from the real water samples. It can be concluded from the results that MOF-derived hollow carbon materials are promising candidates for the fast SPME and can be used for practical applications in analytical chemistry.

Teixobactin, targeting lipid II, represents a new class of antibiotics with novel structures and has excellent activity against Gram-positive pathogens. We developed a new convergent method to synthesize a series of teixobactin analogues and explored structure-activity relationships. We obtained equipotent and simplified teixobactin analogues, replacing the l- allo-enduracididine with lysine, substituting oxygen to nitrogen on threonine, and adding a phenyl group on the d-phenylalanine. On the basis of the antibacterial activities that resulted from corresponding modifications of the d-phenylalanine, we propose a hydrophobic interaction between lipid II and the N-terminal of teixobactin analogues, which we map out with our analogue 35. Finally, a representative analogue from our series showed high efficiency in a mouse model of Streptococcus pneumoniae septicemia.

N-doped hollow carbon spheres (N-HCSs) are promising candidates as electrode material for supercapacitor application. In this work, we report a facile one-step synthesis of discrete and highly dispersible N-HCSs with dopamine (DA) as a carbon precursor and TEOS as a structure-assistant agent in a mixture containing water, ethanol, and ammonia. The architectures of resultant N-HCSs, including yolk-shell hollow carbon spheres (YS-HCSs), single-shell hollow carbon spheres (SS-HCSs), and double-shells hollow carbon spheres (DS-HCSs), can be efficiently controlled through the adjustment of the amount of ammonia. To explain the relation and formation mechanism of these hollow carbon structures, the samples during the different synthetic steps, including polymer/silica spheres, carbon/silica spheres and silica spheres by combustion in air, were characterized by TEM. Electrochemical measurements performed on YS-HCSs, SS-HCSs, and DS-HCSs showed high capacitance with 215, 280, and 381 F g(-1), respectively. Moreover, all the nitrogen-doped hollow carbon nanospheres showed a good cycling stability 97.0% capacitive retention after 3000 cycles. Notably, the highest capacitance of DS-HCSs up to 381 F g(-1) is higher than the capacitance reported so far for many carbon-based materials, which may be attributed to the high surface area, hollow structure, nitrogen functionalization, and double-shell architecture. These kinds of N-doped hollow-structured carbon spheres may show promising prospects as advanced energy storage materials and catalyst supports.

Yolk-shell nanoparticles (YSNs) with active metal cores have shown promising applications in nanoreactors with excellent catalytic performance. In this work, Fe(0)@SiO2 YSNs were synthesized by a sequential "two-solvents" impregnation-reduction approach. Specifically, FeSO4 aqueous solution was introduced into the preformed hollow mesoporous silica spheres (HMSS), dispersed in n-hexane, via a "two-solvent" impregnation way. Subsequently, aqueous solution of sodium borohydride (NaBH4) was introduced into the cavity of HMSS by the same way, leading to the formation of Fe core inside the HMSS through the reaction between Fe(2+) and NaBH4. The resulting Fe(0)@SiO2 YSNs possess distinctive structures, including active cores, accessible mesoporous channels, protective shells, and hollow cavities. To present the catalytic performance of YSNs nanoreactors, Fenton-like catalytic oxidation of phenol was chosen as the model catalysis reaction. In addition to the Fe(0)@SiO2 YSNs, two other materials were also applied to the catalytic system for comparison, including Fe@SiO2 composites with iron nanoparticles sticking on the outer shells of HMSS (Fe@SiO2-DI) and bare iron nanoparticles without HMSS (bare Fe(0)), respectively. The catalytic results show that Fe(0)@SiO2 YSNs exhibit higher catalytic rate toward phenol removal at 2-fold and 4-fold as compared to that of Fe@SiO2-DI and bare Fe(0), indicating the outstanding catalytic property of YSNs nanoreactors. To further clarify the relationship between catalytic properties and structural characteristics, the adsorption experiments of the three samples were also performed in the absence of H2O2. Other than catalytic results, Fe(0)@SiO2 YSNs show slightly higher adsorption efficiency than the other two samples, indicating the accessibility of nanoreactors. This result demonstrates that the removal of phenol in the oxidation system of Fe(0)@SiO2 YSNs may have contributed to the structure-enhanced effect of YSNs as nanoreactors.

An efficient single-step approach toward the synthesis of 2-alkylquinolines is described. Through a Lewis acid mediated [3 + 3] annulation reaction between 3-ethoxycyclobutanones and aromatic amines, a variety of multisubstituted 2-alkylquinoline derivatives were prepared regioselectively at room temperature.