Concise Strategy Research Articles

A concise strategy for enhancing the performance of bio-based polyurethane aerogels using melamine-modified sodium alginate via Aza-Michael addition reaction

Bio-based waterborne polyurethane (PU) has garnered significant attention as a sustainable alternative petroleum-derived counterpart, offering environmentally friendly alternatives. In this work, a new approach is proposed to fabricate two kinds of composite aerogels of lowly/highly melamine-modified sodium alginate (SAML/SAMH) with methacrylate-terminated PU (SAML-PU and SAMH-PU) through dynamic covalent cross-linking via Aza-Michael addition reactions. We aim to improve the poor compatibility of polysaccharide and PU associated with traditional blending methods and impart the resulting aerogels with good biodegradability, compressive strength, thermal insulation, flame-retardant, and self-healing. Comprehensive characterizations, including Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy collectively demonstrate the successful derivatization of alginate and the effective synthesis of the Aza-Michael addition copolymer involving derivate alginate and PU. Substantial improvements in compressive strength and thermal properties are realized at comparable densities. Higher compressive strength, higher decomposition temperature and lower thermal conductivity are significantly achieved for SAML-PU (0.35 MPa, 410 °C and 0.024 W/m/K at 0.13 g/cm3) and SAMH-PU (0.58 MPa, 427 °C and 0.022 W/m/K at 0.12 g/cm3) compared to pristine PU foams (0.15 MPa, 330 °C and 0.031 W/m/K at 0.15 g/cm3). Additionally, molecular simulations of the Aza-Michael addition reaction and finite element simulations of aerogel thermal-insulation properties are conducted to corroborate experimental results. Notably, the dynamic polymers of SAML-PU and SAMH-PU exhibited excellent self-healing, recycling, biodegradability, and flame-retardant attributes. The elucidated preparation methodology and the exceptional performance and versatile applications of sodium alginate-based PU aerogels suggest a promising trajectory for future research endeavors and industrial implementation.

Attraction behavior induces the aggregation and precipitation of organic dyes: Improving efficiency through co-treatment strategy

Organic dyes harm the environment through bioaccumulation, toxicity, water contamination, and persistence. Organic dyes are commonly charged species, while limited works reported the interaction behavior between the charges. In this study, seven typical organic dyes are selected to investigate the general rules of the aggregation-precipitation behaviors between cationic and anionic organic dyes at molecular scale. The maximum precipitation rates of organic dyes reached 96.0 % when the amount of positive charges of cationic dyes was stoichiometric to the negative charges of anionic dyes. The aggregation process is reversible in ethanol solvent and insensitive to temperature, indicating the aggregation behavior is a physical process. The aggregation behavior of cationic and anionic dyes in water and ethanol solvents was simulated at molecular scale. 94.9 % of water molecules dispersed out of the dye clusters within 20 picoseconds in the simulation, while only 0.8 % of ethanol dispersed under the same conditions. The inter-molecule van der Waals force of the ethanol-solvent system was higher than that of the water-solvent system, resulting in the failure of dyes aggregation in ethanol. This study proposed a concise strategy of mixing cationic and anionic dyes in charge balance to cause aggregation and co-precipitation of dyes to improve removal efficiency.

Imaging Golgi‐Apparatus in Colon Cancer Cells by Small Molecule Hydrazone Fluorophore

Herein, we have designed and synthesised a 2,6‐dihydroxybenzoyl‐hydrazone (compound 3) fluorophore through a concise strategy. Molecular dynamics and quantum chemical simulations revealed that long range charge transfer (CT) to be the underlying mechanism for the emissive property of compound 3. Confocal microscopy and cell viability assays confirmed that within 3h, compound 3 homed into the Golgi‐apparatus of colon cancer cells (HCT‐116) selectively compared to the breast (MCF7), lung (A549), cervical (HeLa) cancer cells and non‐cancerous retinal epithelial pigment cells (RPE‐1) with negligible toxicity. This novel fluorophore has potential to image Golgi‐apparatus in a cancer cell specific manner for diagnosis.

Identification of O-arylated huperzinines as novel cholinergic anti-inflammatory pathway agonists against gout arthritis

Lycodine alkaloids are important natural products with diverse biological effects. In this manuscript, we set out the first structural optimization of the 2-pyridone moiety of Lycodine alkaloid via selective O-arylation under metal-free conditions and obtained a series of potent bioactive molecules against monosodium urate (MSU)-induced IL-1β production. Further investigations demonstrated that these natural product derivatives could activate the neuro-immunomodulatory cholinergic anti-inflammatory pathway (CAP) to block the initial phase of NLRP3 inflammasome activation. Compared with the clinical drugs hydrocortisone and indomethacin, as well as commercially available CAP agonists GTS-21 and pnu282987, 3k and 3q possessed greater potency against MSU-induced IL-1β production. Meanwhile, these molecules possessed less cytotoxicity against promonocytic THP-1 macrophages when compared with colchicine. This work reports a concise strategy for direct modification of 2-pyridone moiety from natural Lycodine alkaloids, and provides novel frameworks for discovering CAP activators and drugs for gout arthritis.

On-demand bactericidal and self-adaptive antifouling hydrogels for self-healing and lubricant coatings of catheters

Catheter-related infections are one of the most common nosocomial infections with increasing morbidity and mortality, and robust antibacterial or antifouling catheter coatings remain great challenges for long-term implantation. Herein, multifunctional hydrogel coatings were developed to provide persistent and self-adaptive antifouling and antibacterial effects with self-healing and lubricant capabilities. Polyvinyl alcohol (PVA) with β-cyclodextrin (β-CD) grafts (PVA-Cd) and 4-arm polyethylene glycol (PEG) with adamantane and quaternary ammonium compound (QAC) terminals (QA-PEG-Ad) were crosslinked through host-guest recognitions between adamantane and β-CD moieties to acquire PVEQ coatings. In response to bacterial infections, QACs exhibit reversible transformation between zwitterions (pH 7.4) and cationic lactones (pH 5.5) to generate on-demand bactericidal effect. Highly hydrophilic PEG/PVA backbones and zwitterionic QACs build a lubricate surface and decrease the friction coefficient 10 times compared with that of bare catheters. The antifouling hydrated layer significantly inhibits blood protein adsorption and platelet activation and reveals negligible hemolysis and cytotoxicity. The dynamic host-guest crosslinking achieves full self-healing of cracks in PVEQ hydrogels, and the mechanical profiles were recovered to over 90 % after rejuvenating the broken hydrogels, exhibiting a long-term stability after mechanical stretching, twisting, knotting and compression. After subcutaneous implantation and local bacterial infection, the retrieved PVEQ-coated catheters display no tissue adhesion and 3 log folds lower bacterial number than that of bare catheters. PVEQ coatings effectively prevent the repeated bacterial infections and there are few inflammatory reactions in the surrounding tissue, while substantial lymphoid infiltration and inflammatory cell aggregation occur in muscle tissues around the bare catheter. Thus, this study demonstrates a catheter coating strategy by on-demand bactericidal, self-adaptive antifouling, self-healing and lubricant hydrogels to address medical devices-related infections. Statement of significanceIt is estimated over two billion peripheral intravenous catheters are annually used in hospitals around the world, and catheter-associated infection has become a great clinical challenge with rapidly rising morbidity and mortality. Surface coating is considered a promising approach, but substantial challenges remain in the development of coatings that simultaneously satisfy both anti-fouling and antibacterial attributes. Even more, few attempts have been made to design mechanically robust coatings and reversible antibacterial or antifouling capabilities, which are critical for long-term medical implants. To address these challenges, we propose a concise strategy to develop hydrogel coatings from commercially available poly(ethylene glycol) and polyvinyl alcohol. In addition to self-healing and lubricant capabilities, the reversible conversion between zwitterionic and cationic lactones of quaternary ammonium compounds enables on-demand bactericidal and self-adaptive antifouling effects.

Backbone-Enabled and Ester Groups Switched δ-C(sp2)-H Amination/Fluorination: Cyclic Dipeptides Synthesis.

An efficient and concise strategy for the synthesis of cyclic dipeptides via Pd-catalyzed site-selective δ-C(sp2)-H amination/fluorination and N-to-C cyclization is disclosed. The backbone amides within the dipeptides serves as endogenous directing groups, while the desired products were switched by the C-terminal ester group. This chemistry presents a novel and robust alternative to construct cyclodipeptide fragments.

Base-Mediated Cascade Lactonization/1,3-Dipolar Cycloaddition Pathway for the One-Pot Assembly of Coumarin-Functionalized Pyrrolo[2,1-a]isoquinolines.

An elegant and highly concise strategy for the construction of coumarin-functionalized pyrrolo[2,1-a]isoquinolines from available propargylamines and isoquinolinium N-ylides has been disclosed. In this reaction, isoquinolinium N-ylides acted as a C2 synthon to form a coumarin ring as well as a 1,3-dipole to construct a pyrrole ring in a single pot. This cascade process involves 1,4-conjugate addition/lactonization/1,3-dipolar cycloaddition to construct four chemical bonds (one C-O bond and three C-C bonds) and two new heterocyclic skeletons. Additionally, most of these compounds showed good fluorescence properties and exhibited high molar extinction coefficient and large Stokes shifts.

Assembly-Induced Dynamic Structural Color in a Host-Guest System for Time-Dependent Anticounterfeiting and Double-Lock Encryption.

Manipulation of periodic micro/nanostructures in polymer film is of great importance for academics and industrial applications in anticounterfeiting. However, with the increasing demand on information security, materials with time-dependent features are urgently required, especially the material where the same information can appear more than once on the time scale. Here, one concise strategy to realize time-dependent anticounterfeiting and "double-lock" information encryption based on a host-guest system is proposed, with one photoresponsive azopolymer as the host and one liquid-crystalline molecule as the guest. The system exhibits a tunable mass transport in pre-designed periodic micro/nanostructures by tailoring the process of cis-to-trans recovery of azo groups and assembly of mesogenic trans-isomers, resulting in a dynamic structural color in film. Taking advantage of this extraordinary feature, time-dependent dynamic anticounterfeiting has been achieved. More importantly, the time of each state's appearance in the whole process can be modulated by changing the host-guest ratio. Combining the manipulatable process of mass transport with the unique decoding method, the stored information in film can be decrypted correctly. This work provides an unprecedented dynamic approach for advanced anticounterfeiting technology with a higher level of security and high-end applications in information encryption.

Assembly‐Induced Dynamic Structural Color in a Host‐Guest System for Time‐Dependent Anticounterfeiting and Double‐Lock Encryption

AbstractManipulation of periodic micro/nanostructures in polymer film is of great importance for academics and industrial applications in anticounterfeiting. However, with the increasing demand on information security, materials with time‐dependent features are urgently required, especially the material where the same information can appear more than once on the time scale. Here, one concise strategy to realize time‐dependent anticounterfeiting and “double‐lock” information encryption based on a host‐guest system is proposed, with one photoresponsive azopolymer as the host and one liquid‐crystalline molecule as the guest. The system exhibits a tunable mass transport in pre‐designed periodic micro/nanostructures by tailoring the process of cis‐to‐trans recovery of azo groups and assembly of mesogenic trans‐isomers, resulting in a dynamic structural color in film. Taking advantage of this extraordinary feature, time‐dependent dynamic anticounterfeiting has been achieved. More importantly, the time of each state's appearance in the whole process can be modulated by changing the host‐guest ratio. Combining the manipulatable process of mass transport with the unique decoding method, the stored information in film can be decrypted correctly. This work provides an unprecedented dynamic approach for advanced anticounterfeiting technology with a higher level of security and high‐end applications in information encryption.

Construct Phenylethanoid Glycosides Harnessing Biosynthetic Networks, Protein Engineering and One‐Pot Multienzyme Cascades

AbstractPhenylethanoid glycosides (PhGs) exhibit a multitude of structural variations linked to diverse pharmacological activities. Assembling various PhGs via multienzyme cascades represents a concise strategy over traditional synthetic methods. However, the challenge lies in identifying a comprehensive set of catalytic enzymes. This study explores biosynthetic PhG reconstruction from natural precursors, aiming to replicate and amplify their structural diversity. We discovered 12 catalytic enzymes, including four novel 6′‐OH glycosyltransferases and three new polyphenol oxidases, revealing the intricate network in PhG biosynthesis. Subsequently, the crystal structure of CmGT3 (2.62 Å) was obtained, guiding the identification of conserved residue 144# as a critical determinant for sugar donor specificity. Engineering this residue in PhG glycosyltransferases (FsGT61, CmGT3, and FsGT6) altered their sugar donor recognition. Finally, a one‐pot multienzyme cascade was established, where the combined action of glycosyltransferases and acyltransferases boosted conversion rates by up to 12.6‐fold. This cascade facilitated the reconstruction of 26 PhGs with conversion rates ranging from 5–100 %, and 20 additional PhGs detectable by mass spectrometry. PhGs with extra glycosyl and hydroxyl modules demonstrated notable liver cell protection. This work not only provides catalytic tools for PhG biosynthesis, but also serves as a proof‐of‐concept for cell‐free enzymatic construction of diverse natural products.

Construct Phenylethanoid Glycosides Harnessing Biosynthetic Networks, Protein Engineering and One-Pot Multienzyme Cascades.

Phenylethanoid glycosides (PhGs) exhibit a multitude of structural variations linked to diverse pharmacological activities. Assembling various PhGs via multienzyme cascades represents a concise strategy over traditional synthetic methods. However, the challenge lies in identifying a comprehensive set of catalytic enzymes. This study explores biosynthetic PhG reconstruction from natural precursors, aiming to replicate and amplify their structural diversity. We discovered 12 catalytic enzymes, including four novel 6'-OH glycosyltransferases and three new polyphenol oxidases, revealing the intricate network in PhG biosynthesis. Subsequently, the crystal structure of CmGT3 (2.62 Å) was obtained, guiding the identification of conserved residue 144# as a critical determinant for sugar donor specificity. Engineering this residue in PhG glycosyltransferases (FsGT61, CmGT3, and FsGT6) altered their sugar donor recognition. Finally, a one-pot multienzyme cascade was established, where the combined action of glycosyltransferases and acyltransferases boosted conversion rates by up to 12.6-fold. This cascade facilitated the reconstruction of 26 PhGs with conversion rates ranging from 5-100 %, and 20 additional PhGs detectable by mass spectrometry. PhGs with extra glycosyl and hydroxyl modules demonstrated notable liver cell protection. This work not only provides catalytic tools for PhG biosynthesis, but also serves as a proof-of-concept for cell-free enzymatic construction of diverse natural products.

Rapid Access to Tigliane, Ingenane, and Rhamnofolane Diterpenes from a Lathyrane Precursor via Biomimetic Skeleton Transformation Strategy.

Bioinspired skeleton transformation of a tricyclic lathyrane-type Euphorbia diterpene was conducted to efficiently construct a tetracyclic tigliane diterpene on a gram scale via a key aldol condensation. The tigliane diterpene was then respectively converted into naturally rare ingenane and rhamnofolane diterpenes through a semipinacol rearrangement and a visible-light-promoted regioselective cyclopropane ring-opening reaction. This work provides a concise strategy for high-efficiency access to diverse polycyclic Euphorbia diterpene skeletons from abundant lathyrane-type natural products and paves the way for biological activity investigation of naturally rare molecules.

Catalytic NIR chemiluminescence sensor with enhanced persistence and intensity for in vivo imaging

Chemiluminescence (CL) is a self-illumination phenomenon that involves the emission of light from chemical reactions, and it provides favorable spatial and temporal information on biological processes. However, it is still a great challenge to construct effective CL sensors that equip strong CL intensity, long emission wavelength, and persistent luminescence for deep tissue imaging. Here, we report a liposome encapsulated polymer dots (Pdots)-based system using catalytic CL substrates (L-012) as energy donor and fluorescent polymers and dyes (NIR 695) as energy acceptors for efficient Near-infrared (NIR) CL in vivo imaging. Thanks to the modulation of paired donor and acceptor distance and the slow diffusion of biomarker by liposome, the Pdots show a NIR emission wavelength (λ em, max = 720 nm), long CL duration (>24 h), and a high chemiluminescence resonance energy transfer efficiency (46.5 %). Furthermore, the liposome encapsulated Pdots possess excellent biocompatibility, sensitive response to H2O2, and persistent whole-body NIR CL imaging in the drug-induced inflammation and the peritoneal metastatic tumor mouse model. In a word, this NIR-II CL nanoplatform with long-lasting emission and high spatial-temporal resolution will be a concise strategy in deep tissue imaging and clinical diagnostics.

Stretchable stiffness-tuning of liquid metal elastomer triggered by homocrystal seeds

The hybrid structure of liquid metal units and organic elastomer has huge potential in achieving stretchable and reversible stiffness regulation, while such tuning is often restrained by high energy consumption for liquid metal solidification. Here, we conceive to solve the above challenge through introducing the fully leveraging interaction between supercooled liquid metal and homocrystal seeds within silicone elastomer. It is disclosed that the supercooled liquid metal-elastomer can maintain an extremely stable soft state until the supercooling is eliminated by modulating the mechanical force and elastomer deformation. This circumvents the utilization of intricate refrigeration equipment and offers a highly efficient and concise strategy for stiffness regulation. Moreover, conceptual experiments were performed to demonstrate the practical values of this technology through designing and testing the new shape memory materials, temperature-sensitive switches, and controlled circuits. The solidification mechanisms of supercooled Ga triggered by homocrystal seeds were interpreted. Overall, the present finding has generalized purposes and holds promise to significantly extend the theoretical and technological categories of classical stiffness tunable materials.

Stereoselective synthesis of 2-deoxy-α-C-glycosides from glycals

2-Deoxy-α-C-Glycosides are a significant class of carbohydrates found in numerous bioactive molecules and medicines. Developing a concise strategy for the assembly of these α-configured C-glycosides is crucial in the field of carbohydrate chemistry. However, current methods are restricted to the utilization of glycosyl radical precursors, which are required for pre-syntheses. Herein, we present a novel approach for the synthesis of 2-deoxy-α-C-glycosides using a nickel-catalyzed stereoselective coupling reaction with commercially available glycals. Notably, this method circumvents the preparation for diverse glycosyl radical precursors. The developed protocol exhibits a broad substrate scope and remarkable stereoselectivity under mild reaction conditions. Furthermore, the raw materials required for this process are readily accessible, eliminating the necessity for pre-functionalization modifications of the glycosyl substrates and ensuring high atomic economy.

Synergistic modulation of oxygen vacancies and heterojunction structure in Pd@CN@TiO2 promotes efficient photocatalytic Suzuki–Miyaura CC coupling reactions

This paper reports a concise strategy for the controlled preparation of Pd@g‐C3N4/TiO2 photocatalysts rich in oxygen vacancies. The scheme forms black TiO2 with oxygen vacancies on a carbon nitride material by in‐situ growth and heat treatment, and then utilizes solvothermal reduction to load metallic palladium into the material. The composites were structurally analyzed using Fourier transform infrared (FT‐IR), X‐ray photoelectron spectroscopy (XPS), X‐ray diffraction analysis (XRD), transmission electron microscopy (TEM), electron paramagnetic resonance (EPR), scanning electron microscopy (SEM), elemental mapping, diffuse reflectance spectroscopy (DRS), and inductively coupled plasma (ICP) analysis. The results show that the oxygen vacancies in the black TiO2 materials prepared by the method reported in this paper can effectively improve the separation efficiency of the photogenerated electron–hole pairs and prolong the lifetime of the charge carriers by inhibiting charge recombination. In addition, the heterojunction structure formed between TiO2 and g‐C3N4 materials also enhances the photocatalytic performance of the materials to some extent. After a simple optimization of the conditions, the Pd@g‐C3N4/TiO2 photocatalyst could promote the Suzuki–Miyaura CC coupling reactions under mild conditions (room temperature, 30 W LED lamp, λ = 455 nm), and good biaryl yields were obtained (optimum yield = 99%). It is very noteworthy that the photogenerated electrons and holes generated by the photoexcited catalyst were confirmed to be the main active species in the photocatalytic process of the catalyst by radical trapping assay and EPR test. The Pd@g‐C3N4/TiO2 material reported in this paper has excellent photocatalytic activity and stability in use, which provides a new reference scheme for wider green synthesis and catalysis.

A general photocatalytic strategy for the synthesis of β-hydroxy acid derivatives from alkenes

We report a general and concise strategy to realize the photo-induced difunctionalization of alkenes for the synthesis of β-hydroxy acid derivatives. The reaction proceeds through an alkoxycarbonyl radical-induced process, and...

Shear Stress‐Triggered Theranostic Nanoparticles for Piezoelectric‐Fenton‐Photodynamic Thrombolysis and Endogenous Thrombus Imaging

AbstractThrombus therapy is challenged by potential bleeding risk of thrombolytic agents, and external irradiation is usually needed in thrombus imaging. Herein, highly efficient theranostic platforms are designed for piezoelectric‐Fenton‐photodynamic thrombolysis and endogenous thrombus imaging in response to the elevated shear stress at the thrombus site. Piezoelectric tetragonal barium titanate (tBT) nanoparticles (NPs) are coated with Fe3+‐coordinated metal‐organic frameworks (MOFs), followed by inoculation of chlorin e6‐luminol conjugates and heparin absorption to obtain theranostic tBT@MOFCL/Hep NPs. Shear stress‐induced piezopotential on NPs accelerates Fe3+/Fe2+ transformation to deplete MOF layers, activates Fenton reaction and produces reactive oxidative species (ROS) for non‐pharmacological thrombolysis. In the meantime, the site‐specific ROS generation oxidizes luminol and the chemiluminescent resonance energy transfer with chlorin e6 generates red fluorescence for thrombus imaging without using external light irradiation. After intravenous injection into a carotid artery thrombosis model, the heparin‐mediated thrombus targeting yields 6.5‐fold higher luminescent intensity at the thrombus site. Thrombi in the carotid arteries are almost completely dissolved with integration of piezoelectric dynamic therapy, piezopotential‐enhanced Fenton reaction, and chemiluminescence‐excited photodynamic therapy, while causing no haematologic and histopathologic abnormality. This study demonstrates a concise strategy to generate shear stress‐responsive built‐in piezoelectric potentials, site‐specific non‐pharmacological thrombolysis, self‐illuminating, and stenosis degree‐adaptable thrombus imaging.

Small-Molecule Endoplasmic Reticulum Stress Inducer Triggers Apoptosis in Cancer Cells.

Endoplasmic reticulum (ER) is highly critical for the sub-cellular protein synthesis, post-translational modifications and myriads of signalling pathways to maintain cellular homeostasis. Consequently, dysregulation in the ER functions leads to the ER stress in different pathological situations including cancer. Hence, exploring small molecules to induce ER stress emerged as one of the unorthodox strategies for future cancer therapeutics. However, development of ER targeted novel small molecules remains elusive due to the dearth of ER targeting moieties. Herein we have synthesized a small library of 3-methoxy-pyrrole-enamine through a concise strategy. Screening of this library in cervical (HeLa), colon (HCT-116), breast (MCF7) and lung cancer (A549) cells identified a novel small molecule which localized into the ER of the HeLa cervical cancer cells within 3 h, induced ER stress through the increased expression of ER stress markers (CHOP, IRE1α, PERK, BiP and Cas-12) and triggered the programmed cell death (apoptosis) leading to remarkable HeLa cell killing. This novel small molecule can be explored further as a tool to understand the chemical biology of ER towards the development of ER targeted cancer therapeutics.

Chimeric Small Molecules for Detouring Drugs into Mitochondria to Engender Apoptosis in Cancer Cells.

Mitochondrion has appeared as one of the important targets for anti-cancer therapy. Subsequently, small molecule anti-cancer drugs are directed to the mitochondria for improved therapeutic efficacy. However, simultaneous imaging and impairing mitochondria by a single probe remained a major challenge. To address this, herein Chimeric Small Molecules (CSMs) encompassing drugs, fluorophore and mitochondria homing moiety were designed and synthesized through a concise strategy. Screening of the CSMs in a panel of cancer cell lines (HeLa, MCF7, A549, and HCT-116) revealed that one of the CSMs comprising Indomethacin V exhibited remarkable cervical cancer cell (HeLa) killing (IC50 =0.97 μM). This lead CSM homed into the mitochondria of HeLa cells within 1 h followed by mitochondrial damage and reactive oxygen species (ROS) generation. This novel Indomethacin V-based CSM-mediated mitochondrial damage induced programmed cell death (apoptosis). We anticipate these CSMs can be used as tools to understand the drug effects in organelle chemical biology in diseased states.