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A copper-catalyzed C3 amination of 2H-indazoles with 2H-indazoles and indazol-3(2H)-ones under mild conditions was developed. A series of indazole-containing indazol-3(2H)-one derivatives were produced in moderate to excellent yields. The mechanistic studies suggest that the reactions probably proceed through a radical pathway.
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Conventional plastic foams are usually produced by fossil-fuel-derived polymers, which are difficult to degrade in nature. As an alternative, cellulose is a promising biodegradable polymer that can be used to fabricate greener foams, yet such a process typically relies on methods (e.g., freeze-drying and supercritical-drying) that are hardly scalable and time-consuming. Here, we develop a fast and scalable approach to prepare cellulose-graphite foams via rapidly cross-linking the cellulose fibrils in metal ions-containing solution followed by ambient drying. The prepared foams exhibit low density, high compressive strength, and excellent water stability. Moreover, the cross-linking of the cellulose fibrils can be triggered by various metal ions, indicating good universality. We further use density functional theory to reveal the cross-linking effect of different ions, which shows good agreement with our experimental observation. Our approach presents a sustainable route toward low-cost, environmentally friendly, and scalable foam production for a range of applications.
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Celulosa , Grafito , Iones , Polímeros , AguaRESUMEN
Objective: Total 25(OH)D (t-25[OH]D), a marker traditionally used in the assessment of vitamin D (VitD) in the human body, includes 25(OH)D 2, 25(OH)D 3, and C 3-epimers-25(OH)D 3(C 3-epi). In this study, we analyzed the relationship between serum VitD metabolites and renal impairment in patients with diabetic kidney disease (DKD). Methods: We covered, in the study, 339 subjects, including 114 otherwise healthy controls (HC), 74 type 2 diabetes mellitus (DM) patients with no glomerular filtration dysfunction, and 151 DKD patients. According to the results of combined evaluation of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), the DKD patients were further divided into four subgroups, stage 2 subgroup of patients of DM combined with stage-2 chronic kidney disease (CKD2), stage 3 subgroup of patients of DM combined with CKD3, stage 4 subgroup of patients of DM combined with CKD4, and stage 5 subgroup of patients of DM combined with CKD5. The levels of 25(OH)D 2, 25(OH)D 3, and C 3-epi were measured by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the activity level of 25(OH) 3 (AVitD 3), t-25(OH)D concentration, 25(OH)D 2/25(OH)D 3 ratio, C 3-epi/t-25(OH)D ratio, and C 3-epi/AVitD 3 ratio were calculated. Results: The levels of 25(OH)D 3, t-25(OH)D, and AVitD 3 were lower in the DKD group than those in the DM and HC groups (all P<0.05). C 3-epi/t-25(OH)D ratio and C 3-epi/AVitD 3 ratio were higher in the DKD group than those in the HC group (all P<0.05). The levels of 25(OH)D 3, t-25(OH)D, AVitD 3, and C 3-epi were lower in the stage 5 subgroup than those in the stage 2 and stage 3 subgroups (all P<0.05). The levels of 25(OH)D 3, t-25(OH)D, and C 3-epi were lower in the stage 4 subgroup than those in the stage 3 subgroup (all P<0.05). The 25(OH)D 3, t-25(OH)D, and AVitD 3 levels were lower in the stage 4 subgroup than those in the stage 2 subgroup (all P<0.05). Conclusions: UPLC-MS/MS can be used to perform accurate evaluation of VitD nutritional status in DKD patients. DKD patients have decreased levels of serum t-25(OH)D, 25(OH)D 3, and AVitD 3, all of which progressively decrease along with the rise in CKD staging. The trend of C 3-epi and 25(OH)D 3 changes were not consistent.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Estudios Retrospectivos , Cromatografía Liquida , Diabetes Mellitus Tipo 2/complicaciones , Espectrometría de Masas en Tándem , Vitamina DRESUMEN
BACKGROUND: Fibroblast growth factor receptor (FGFR) signaling influenced tumour occurrence and development. Overexpression of FGFR had been observed in many types of cancers, including colon cancer. FGFR inhibitor is considered to be effective in treating colon cancer patients. METHODS: First, the kinase inhibition rate was determined. MTT, western blotting, colony formation, EdU and comet assays were performed to evaluate the anti-tumour effects of F1-7 in vitro. RNA-seq and bioinformatics analysis were used for further verification. Additionally, a xenograft model was generated to investigate the anti-tumour effect of F1-7. RESULTS: F1-7 can inhibit the proliferation of colon cancer cells in vitro. It could significantly inhibit FGFR phosphorylation and its downstream signaling pathway. Whole-genome RNA-seq analysis found that the changed genes were not only functionally focused on MAPK signaling pathway but also related to cell apoptosis and ferroptosis. Experimental evidence demonstrated that F1-7 can directly increase the level of cellular DNA damage. The occurrence of DNA damage led to cell cycle arrest and inhibition of cell metastasis and cell apoptosis. Mouse model experiments also confirmed that F1-7 could inhibit tumour growth by inhibiting the FGFR pathway. CONCLUSIONS: F1-7 exhibits anti-tumour activity by inhibiting the FGFR pathway. It could be a novel therapeutic agent for targeting colon cancer cells.
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Neoplasias del Colon , Inhibidores de Proteínas Quinasas , Animales , Muerte Celular , Línea Celular Tumoral , Proliferación Celular , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Daño del ADN , Humanos , Ratones , Inhibidores de Proteínas Quinasas/farmacología , Receptores de Factores de Crecimiento de Fibroblastos/genéticaRESUMEN
The huge consumption of single-use plastic straws has brought a long-lasting environmental problem. Paper straws, the current replacement for plastic straws, suffer from drawbacks, such as a high cost of the water-proof wax layer and poor water stability due to the easy delamination of the wax layer. It is therefore crucial to find a high-performing alternative to mitigate the environmental problems brought by plastic straws. In this paper, all natural, degradable, cellulose-lignin reinforced composite straws, inspired by the reinforcement principle of cellulose and lignin in natural wood are developed. The cellulose-lignin reinforced composite straw is fabricated by rolling up a wet film made of homogeneously mixed cellulose microfibers, cellulose nanofibers, and lignin powders, which is then baked in oven at 150 °C. When baked, lignin melts and infiltrates the micro-nanocellulose network, acting as a polyphenolic binder to improve the mechanical strength and hydrophobicity performance of the resulting straw. The obtained straws demonstrate several advantageous properties over paper straws, including 1) excellent mechanical performance, 2) high hydrostability, and 3) low cost. Moreover, the natural degradability of the cellulose-lignin reinforced composite straws makes them promising candidates to replace plastic straws and suggests possible substitutes for other petroleum-based plastics.
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Lignina , Nanofibras , Celulosa , Interacciones Hidrofóbicas e Hidrofílicas , MaderaRESUMEN
We report the synthesis, characterization, and reactivity of [(NHC)PdCl2(aniline)] complexes. These well-defined, air- and moisture-stable catalysts are highly active in the Suzuki-Miyaura cross-coupling of amides by N-C(O) activation as well as in the Suzuki-Miyaura cross-coupling of esters, aryl chlorides, and Buchwald-Hartwig amination. Most crucially, this study introduces broadly available anilines as stabilizing ligands for well-defined Pd(II)-NHC catalysts. The availability of various aniline scaffolds, including structural and electronic diversity, has a significant potential in fine-tuning of challenging cross-couplings by Pd-NHCs. The parent catalyst in this class, [Pd(IPr)(AN)Cl2], has been commercialized in collaboration with Millipore Sigma, offering broad access for reaction screening and optimization.
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3D printing of lignocellulosic biomass (cellulose, hemicellulose, and lignin) has attracted increasing attention by using this abundant, sustainable, and ecofriendly material. While cellulose can be easily tailored into a highly viscous ink for 3D printing, after solvent evaporation, the final printed structures become highly porous, fragile, and easily fall apart in water due to its hydrophilic nature. Lignin, another crucial component of natural lignocellulose, has not yet been reported for ink printing due to its unfavorable rheological behavior. Herein, a low-cost direct ink printing strategy is developed to fabricate lignin-based 3D structures with lignin no further refined and a more compact microstructure as well as different functionalities compared with printed cellulose. By using a soft triblock copolymer as the crosslinking agent, the rheology of lignin-based inks can be adjusted from soft to rigid, and even enables vertical printing which requires stiff and self-supporting features. The lignin-based inks contain less water (≈40 wt%) and exhibit a much denser, stiffer structure, resulting in a wet tensile strength of ≈30 MPa, compared to only ≈0.6 MPa for printed cellulose. In addition, the unique macromolecular structure of lignin also demonstrates significantly improved stability in water and under heat, as well as UV-blocking performance.
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Tinta , Lignina , Celulosa , Hidrogeles , Impresión TridimensionalRESUMEN
Carbon-black-supported nanoparticles (CNPs) have attracted considerable attention for their intriguing catalytic properties and promising applications. The traditional liquid synthesis of CNPs commonly involves demanding operation conditions and complex pre- or post-treatments, which are time consuming and energy inefficient. Herein, a rapid, scalable, and universal strategy is reported to synthesize highly dispersed metal nanoparticles embedded in a carbon matrix via microwave irradiation of carbon black with preloaded precursors. By optimizing the amount of carbon black, the microwave absorption is dramatically improved while the thermal dissipation is effectively controlled, leading to a rapid temperature increase in carbon black, ramping to 1270 K in just 6 s. The whole synthesis process requires no capping agents or surfactants, nor tedious pre- or post-treatments of carbon black, showing tremendous potential for mass production. As a proof of concept, the synthesis of ultrafine Ru nanoparticles (≈2.57 nm) uniformly embedded in carbon black using this microwave heating technique is demonstrated, which displays remarkable electrocatalytic performance when used as the cathode in a Li-O2 battery. This microwave heating method can be extended to the synthesis of other nanoparticles, thereby providing a general methodology for the mass production of carbon-supported catalytic nanoparticles.
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The activation and overexpression of fibroblast growth factor receptors (FGFRs) are highly correlated with a variety of cancers. Most small molecule inhibitors of FGFRs selectively target FGFR1-3, but not FGFR4. Hence, designing highly selective inhibitors towards FGFR4 remains a great challenge because FGFR4 and FGFR1 have a high sequence identity. Recently, two small molecule inhibitors of FGFRs, ponatinib and AZD4547, have attracted huge attention. Ponatinib, a type II inhibitor, has high affinity towards FGFR1/4 isoforms, but AZD4547, a type I inhibitor of FGFR1, displays much reduced inhibition toward FGFR4. In this study, conventional molecular dynamics (MD) simulations, molecular mechanics/generalized Born surface area (MM/GBSA) free energy calculations and umbrella sampling (US) simulations were carried out to reveal the principle of the binding preference of ponatinib and AZD4547 towards FGFR4/FGFR1. The results provided by MM/GBSA illustrate that ponatinib has similar binding affinities to FGFR4 and FGFR1, while AZD4547 has much stronger binding affinity to FGFR1 than to FGFR4. A comparison of the individual energy terms suggests that the selectivity of AZD4547 towards FGFR1 versus FGFR4 is primarily controlled by the variation of the van der Waals interactions. The US simulations reveal that the PMF profile of FGFR1/AZD4547 has more peaks and valleys compared with that of FGFR4/AZD4547, suggesting that the dissociation process of AZD4547 from FGFR1 are easily trapped into local minima. Moreover, it is observed that FGFR1/AZD4547 has much higher PMF depth than FGFR4/AZD4547, implying that it is more difficult for AZD4547 to escape from FGFR1 than from FGFR4. The physical principles provided by this study extend our understanding of the binding mechanisms and provide valuable guidance for the rational design of FGFR isoform selective inhibitors.
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Simulación de Dinámica Molecular , Inhibidores de Proteínas Quinasas/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/química , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/química , Benzamidas/química , Benzamidas/metabolismo , Imidazoles/química , Imidazoles/metabolismo , Modelos Químicos , Piperazinas/química , Piperazinas/metabolismo , Unión Proteica , Isoformas de Proteínas , Inhibidores de Proteínas Quinasas/química , Pirazoles/química , Pirazoles/metabolismo , Piridazinas/química , Piridazinas/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/metabolismoRESUMEN
Exploiting new solvents on efficiently dissolving cellulose is imperative to promote the utilization of cellulosic resources. The process of cellulose dissolution typically necessitates extreme conditions, such as high-temperature treatment, utilization of potent acidic or basic solvents, or the catalytic action of Lewis acids. As a result, the structure of the cellulose is invariably compromised, subsequently obstructing the creation of high-performance materials. In this study, we address this challenge through a simple process, introducing polyethylene glycol (PEG) as glycosidic bond protecting agent, to preserve the polymerization degree of cellulose during its room-temperature dissolution in ZnCl2-phosporic acid eutectic solvent. The PEG units preferentially coordinate with Zn2+ to weaken the hydrolysis of glycosidic bond of cellulose through ether bond competition. The polymerization degree of regenerated cellulose is thus greatly improved, reaching up to seven times that of unprotected cellulose. Overall, this study offers an easy and cost-effective approach to develop cellulose solvents and provides a significant drive towards the fabrication of practical materials through cellulose dissolution.
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Excessive activation of FGF19/fibroblast growth factor receptor 4 (FGFR4) signaling is associated with poor survival of patients with hepatocellular carcinoma (HCC). FGFR4 inhibitors show promise for HCC treatment. F30, an indazole derivative designed through computer-aided drug design targeting FGFR4, demonstrated anti-HCC activity as described in our previous studies. However, the precise molecular mechanisms underlying F30's anticancer effects remain largely unexplored. We report here that F30 could effectively induce ferroptosis in HCC cells. The concentrations of cellular ferrous iron, the peroxidation of cell membranes and the homeostasis of reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG) were dysregulated by F30, thereby affecting cellular redox status. Induction of ferroptosis in HCC by F30 was inhibited by specific ferroptosis inhibitor ferrostatin-1. F30 upregulates various ferroptosis-related genes, including the heme oxygenase enzymes 1 (HMOX1), a key mediator of redox regulation. Surprisingly, F30-induced ferroptosis in HCC is dependent on HMOX1. The dysregulation of cellular ferrous iron concentrations and cell membrane peroxidation was rescued when knocking down HMOX1 with specific small interfering RNA. These findings shed light on the molecular mechanisms underlying FGFR4-targeting F30's anti-HCC effects and suggest that FGFR4 inactivation could be beneficial for HCC treatment involving ferroptosis.
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Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/metabolismo , Línea Celular Tumoral , Proliferación Celular , Hierro , Hemo-Oxigenasa 1RESUMEN
Imidazolium salts bearing TEMPO groups react with commercially available copper powder affording Cu-NHC complexes. The in situ generated Cu-NHC-TEMPO complexes are quite efficient catalysts for aerobic oxidation of primary alcohols into aldehydes. The catalyst is easily available, and various primary alcohols were selectively converted to aldehydes in excellent yields.
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Alcoholes/química , Aldehídos/síntesis química , Cobre/química , Óxidos N-Cíclicos/química , Compuestos Heterocíclicos/química , Metano/análogos & derivados , Compuestos Organometálicos/química , Aldehídos/química , Catálisis , Metano/química , Estructura Molecular , Oxidación-ReducciónRESUMEN
We have developed an efficient and green strategy for the synthesis of C2-amino indolin-3-ones and C2-acyloxy indolin-3-ones via KI-catalyzed C(sp3)-H amination and acyloxylation of indolin-3-ones using air as the oxidant. The reaction provides straightforward access to 2-substituted indolin-3-ones by the direct functionalization of indolin-3-ones at the C2 position under mild conditions. Moreover, the conditions enable direct functionalization of a range of complex pharmaceuticals, providing attractive products for medicinal chemistry programs.
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Iron-catalyzed direct C-N bond formation between azoles and amides is described. The oxidative coupling reactions of sp(3) C-H bonds adjacent to a nitrogen atom in amides and sulfonamides with the N-H bond in azoles proceeded smoothly in the presence of FeCl(2) and di-tert-butyl peroxide (DTBP).
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Amidas/química , Azoles/química , Compuestos Ferrosos/química , Nitrógeno/química , Alquilación , Catálisis , Estructura MolecularRESUMEN
An in-depth understanding of the electronic structures of catalytically active centers and their surrounding vicinity is key to clarifying the structure-activity relationship, and thus enabling the design and development of novel metal-free carbon-based materials with desired catalytic performance. In this study, boron atoms are introduced into phosphorus-doped nanoporous carbon via an efficient strategy, so that the resulting material delivers better catalytic performance. The doped B atoms alter the electronic structures of active sites and cause the adjacent C atoms to act as additional active sites that catalyze the reaction. The B/P co-doped nanoporous carbon shows remarkable catalytic performance for benzyl alcohol oxidation, achieving high yield (over 91% within 2 h) and selectivity (95%), as well as low activation energy (32.2 kJ mol-1 ). Moreover, both the conversion and selectivity remain above 90% after five reaction cycles. Density functional theory calculations indicate that the introduction of B to P-doped nanoporous carbon significantly increases the electron density at the Fermi level and that the oxidation of benzyl alcohol occurs via a different reaction pathway with a very low energy barrier. These findings provide important insights into the relationship between catalytic performance and electronic structure for the design of dual-doped metal-free carbon catalysts.
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Iron-catalyzed direct C-N bond formation between imidazoles and benzylic hydrocarbons is described. The reaction utilizes an inexpensive iron catalyst-oxidant system that is suitable for the coupling of a range of benzylic C-H bonds with various imidazoles.
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Benceno/química , Imidazoles/química , Hierro/química , Catálisis , Espectroscopía de Resonancia Magnética , Oxidación-Reducción , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Transparent wood is considered a promising structural and light management material for energy-efficient engineering applications. However, the solution-based delignification process that is used to fabricate transparent wood generally consumes large amounts of chemicals and energy. Here, we report a method to produce optically transparent wood by modifying the wood's lignin structure using a solar-assisted chemical brushing approach. This method preserves most of the lignin to act as a binder, providing a robust wood scaffold for polymer infiltration while greatly reducing the chemical and energy consumption as well as processing time. The obtained transparent wood (~1 mm in thickness) demonstrates a high transmittance (>90%), high haze (>60%), and excellent light-guiding effect over visible wavelength. Furthermore, we can achieve diverse patterns directly on wood surfaces using this approach, which endows transparent wood with excellent patternability. Combining its efficient, patternable, and scalable production, this transparent wood is a promising candidate for applications in energy-efficient buildings.
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Abundant and renewable cellulose is a potential candidate for petroleum-derived synthetic polymers. However, the efficient dissolution of this material is problematic because of the high cost, severe reaction condition (e.g., high temperature) and environmentally unfriendly (e.g., toxic reagents, and solvent recyclability). Herein, to realize the room temperature dissolution of cellulose with an inexpensive and eco-friendly solvent, we design a novel low-cost deep eutectic solvent that is composed of zinc chloride, water and phosphoric acid for the efficient dissolution of cellulose. This solvent is featured as having both the superior hydrogen bonding acidity and the hydrogen bonding basicity, and thus can act as a hydrogen bond molecular scissors to cleave the hydrogen bonds within cellulose. In this process, microcrystalline cellulose can be easily dissolved in the solvent at room temperature with a dissolution ratio up to 15 wt%. The dissolved cellulose can also be recovered without any derivatization. The universality, recyclability and pilot production of dissolving cellulose using this solvent are also demonstrated. This work provides a new strategy for the design of novel deep eutectic solvent capable of disrupting the hydrogen bonds of cellulose under mild conditions.
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Disolventes Eutécticos Profundos , Temperatura , Celulosa , Enlace de Hidrógeno , Solubilidad , Agua/químicaRESUMEN
Many efforts have been dedicated to exploring nanofluidic systems for various applications including water purification and energy generation. However, creating robust nanofluidic materials with tunable channel orientations and numerous nanochannels or nanopores on a large scale remains challenging. Here, we demonstrate a scalable and cost-effective method to fabricate a robust and highly conductive nanofluidic wood hydrogel membrane in which ions can transport across the membrane. The ionically conductive balsa wood hydrogel membrane is fabricated by infiltrating poly(vinyl alcohol) (PVA)/acrylic acid (AA) hydrogel into the inherent bimodal porous wood structure. The balsa wood hydrogel membrane demonstrates a 3 times higher strength (52.7 MPa) and 2 orders of magnitude higher ionic conductivity compared to those of natural balsa both in the radial direction (coded as R direction) and along the longitudinal direction (coded as L direction). The ionic conductivity of the balsa wood hydrogel membrane is 1.29 mS cm-1 along the L direction and nearly 1 mS cm-1 along the R direction at low salt concentrations (up to 10 mM). In addition, the surface-charge-governed ion transport also renders the balsa wood hydrogel membrane able to harvest electrical energy from salinity gradients. A current density of up to 17.65 µA m-2 and an output power density of 0.56 mW m-2 are obtained under a 1000-fold salt concentration gradient, which can be further improved to 2.7 mW m-2 by increasing the AA content from 25 wt % to 50 wt %. These findings make contributions to develop energy-harvesting systems and other nanofluidic devices from sustainable wood materials.
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Hidrogeles , Nanoporos , Hidrogeles/química , Madera , Iones/química , Conductividad EléctricaRESUMEN
Phosphorus-doped carbon materials are promising alternatives to noble metal-based catalysts for the highly selective oxidation of benzyl alcohol to benzaldehyde, but it is challenging to achieve high loadings of high-activity P dopants in metal-free catalysts. Here, the preparation of high-loading and well-dispersed P atoms confined to the surfaces of cellulose-derived carbon via a dissolving-doping strategy is reported. In this method, cellulose is dissolved in phosphoric acid to generate a cellulose-phosphoric supramolecular collosol, which is then directly carbonized. The as-prepared carbon possesses a high specific surface area of 1491 cm3 g-1 and a high P content of 8.8 wt%. The P-doped nanoporous carbon shows a superior catalytic activity and cyclic stability toward benzyl alcohol oxidation, with a high turnover frequency of 3.5 × 10-3 mol g-1 h-1 and a low activation energy of 35.6 kJ mol-1 . Experimental results and theoretical calculations demonstrate that the graphitic C3 PO species is the leading catalytic active center in this material. This study provides a novel strategy to prepare P dopants in nanoporous carbon materials with excellent catalytic performance.