Efficient Cascade Research Articles

Light-activated carbon dot nanozyme with scandium for a highly efficient and pH-universal bio-nanozyme cascade colorimetric assay.

Nanozyme-based colorimetric assays have attracted much attention due to their cost-effectiveness, high stability, and sensitivity. In particular, the catalytic cascade imparted by the biological enzyme is highly selective. However, developing an efficient, one-pot, and pH-universal bio-nanozyme cascade remains challenging. Considering the tunable activity of the photo-activated nanozyme, we herein demonstrated a pH-universal colorimetric assay based on the Sc3+-boosted photocatalytic oxidation of carbon dots (C-dots). As a strong Lewis acid, Sc3+ shows ultra-fast complexation with OH- over a broad pH range and dramatically decreases the pH of the buffer solutions. In addition to regulating the pH, Sc3+ also binds to the C-dots to produce a persistent and strongly oxidizing intermediate based on photo-induced electron transfer. The proposed Sc3+-boosted photocatalytic system was successfully used in a cascade colorimetric assay with biological enzymes for assessing their activity as well as the detection of enzyme inhibitors at neutral and alkaline pH. Instead of designing new nanozymes for catalytic cascades, this work suggests that introducing promoters can be a convenient strategy in practical applications.

Ultrasensitive electrochemical biosensor for detection of circulating tumor cells based on a highly efficient enzymatic cascade reaction.

There has been great interest in the enzymatic cascade amplification strategy for the electrochemical detection of circulating tumor cells (CTCs). In this work, we designed a highly efficient enzymatic cascade reaction based on a multiwalled carbon nanotubes-chitosan (MWCNTs-CS) composite for detection of CTCs. A high electrochemical effective surface area was obtained for a MWCNTs-CS-modified glassy carbon electrode (GCE) for loading glucose oxidase (GOD), as well as a high loading rate and high electrical activity of the enzyme. As a 'power source', the MWCNTs-CS composites provided a strong driving power for horseradish peroxidase (HRP) on the surface of polystyrene (PS) microspheres, which acted as probes for capturing CTCs and allowed the reaction to proceed with further facilitation of electron transfer. Aptamer, CTCs, and PS microspheres with HRP and anti-epithelial cell adhesion molecule (anti-EpCAM) antibody were assembled on the MWCNTs-CS/GCE to allow for the modulation of enzyme distance at the micrometer level, and thus ultra-long-range signal transmission was made possible. An ultrasensitive response to CTCs was obtained via this proposed sensing strategy, with a linear range from 10 cell mL-1 to 6 × 106 cell mL-1 and a detection limit of 3 cell mL-1. Moreover, this electrochemical sensor possessed the capability to detect CTCs in serum samples with satisfactory accuracy, which indicated great potential for early diagnosis and clinical analysis of cancer.

Aza-dicyclopenta[a,g]naphthalenes: controllable seesaw-like emissive behavior and narrowband AIEgens.

Molecular motions significantly influence the emissive behavior and properties of organic fluorescent molecules. However, achieving controllable emission remains a major challenge for fluorophores. In the case of aggregation-induced emission luminogens (AIEgens), the desired properties of aggregated emission and narrowband spectrum demand molecular motion patterns that inherently oppose each other. A nitrogen-containing dicyclopenta[a,g]naphthalene scaffold was discovered as a controllable luminogenic structure through a highly efficient one-step intermolecular cascade reaction. By carefully balancing molecular motions and introducing additional nitrogen atoms into the skeleton, pyrrole-conjugated dicyclopenta[a,g]naphthalenes with aggregation-caused quenching (ACQ) could be transformed into dual-state emission luminogens (DSEgens). This transformation was achieved by incorporating an additional weak H-bond "lock." Furthermore, the DSEgens could be converted into AIEgens with an exciting narrow full-width-at-half-maximum (FWHM, <50 nm) by methylation. This unprecedented discovery is attributed to the contribution of the weak H-bond "lock," which overcomes the limitations of broad band emission in AIEgens caused by restrictions of intramolecular motion. Specific organelle probes were developed by replacing the methyl group of the onium product with different positioning groups. This study emphasizes the delicate balance of molecular motions in controlling luminescence and demonstrates a successful approach to designing organic luminogens with controllable emission and narrowband AIEgens.

Visible light-induced cascade N-alkylation/amidation reaction of quinazolin-4(3H)-ones and related N-heterocycles.

An efficient and visible light-promoted cascade N-alkylation/amidation of quinazolin-4(3H)-ones with benzyl halides and allyl halides has been described for the first time to provide a convenient access to quinazoline-2,4(1H,3H)-diones. This cascade N-alkylation/amidation reaction shows good functional group tolerance and could also be applied to N-heterocycles such as benzo[d]thiazoles, benzo[d]imidazoles, and quinazolines. Control experiments show that K2CO3 plays an important role in this transformation.

Investigations into oxidation induced ring opening of terarylenes containing π-extended thieno[b]thiophene units

Four terarylenes having thieno[b]thiophene moieties with highly efficient intermolecular cascade ring opening reactivities have been synthesized.

Applying green chemistry principles to iron catalysis: mild and selective domino synthesis of pyrroles from nitroarenes.

An efficient and general cascade synthesis of pyrroles from nitroarenes using an acid-tolerant homogeneous iron catalyst is presented. Initial (transfer) hydrogenation using the commercially available iron-Tetraphos catalyst is followed by acid catalysed Paal-Knorr condensation. Both formic acid and molecular hydrogen can be used as green reductants in this process. Particularly, under transfer hydrogenation conditions, the homogeneous catalyst shows remarkable reactivity at low temperatures, high functional group tolerance and excellent chemoselectivity transforming a wide variety of substrates. Compared to classical heterogeneous catalysts, this system presents complementing reactivity, showing none of the typical side reactions such as dehalogenation, debenzylation, arene or olefin hydrogenation. It thereby enhances the chemical toolbox in terms of orthogonal reactivity. The methodology was successfully applied to the late-stage modification of multi-functional drug(-like) molecules as well as to the one-pot synthesis of the bioactive agent BM-635.

Palladium-catalyzed cascade cyclization of allenamide with 2-iodoanilines to access functionalized indoloquinolines.

A novel and efficient palladium-catalyzed cascade cyclization to indoloquinoline derivatives in one pot has been developed by using allenamide derivatives and 2-iodoanilines as the key building blocks. The process involved two cyclizations: intramolecular cyclization/π-allylic substitution and intramolecular 6-endo Heck cyclization. Furthermore, dihydrobenzofuro[2,3-b]quinoline derivatives could also be achieved via this strategy using allenyl ethers instead of allenamides. The readily available substrates, mild conditions, high efficiency and step economy make this strategy a promising method in the synthesis of polycyclic motifs.

Efficient cascade conversion of starch to gluconic acid by a chemoenzymatic system with co-immobilized Au nanoparticles and enzymes

A chemoenzymatic cascade system (GA&amp;GOx@Au–SiO2) was fabricated by immobilizing Au nanoparticles onto silica (SiO2) followed by the co-immobilization of glucoamylase (GA) and glucose oxidase (GOx) for the production of gluconic acid from starch.

Polymerization boosting cascade energy transfer based on opened glucopyranosyl β-cyclodextrin.

An injectable polysaccharide supramolecular hydrogel was successfully fabricated from opened D-glucopyranosyl β-cyclodextrin with four aldehyde groups (ACD) cross-linked with biomacromolecule chitosan (CS), which was not only beneficial to the clustering-triggered emission of CS with high quantum yield (32.25%), but also could co-assemble with a first stage acceptor triphenylamine derivative (TPA) and encapsulate Cyanine 5 (Cy5) or Nile blue (NiB) achieving supramolecular cascade energy transfer from the cross-linked polymer to the dyes, leading to fluorescence emission at 673 nm or 680 nm, and could be further applied in cell imaging.

Rapid access to pyrrolo[3,4-c]quinoline-1,3-diones: An improved synthetic protocol using a precursor prepared by Pfitzinger reaction

An efficient pTSA-mediated cyclization cascade reaction of Pfitzinger's ester and benzoyl hydrazines has been developed providing a simple procedure for synthesis of pyrrolo [3,4-c]quinoline-1,3-dione derivatives. Unlike traditional synthetic protocol, this method avoids an additional step of conversion of quinoline-3,4-dicarboxylic acids to an anhydride, allowing direct reaction of ester derivative with hydrazine nucleophiles.

A novel cascade latent heat thermal energy storage system consisting of erythritol and paraffin wax for deep recovery of medium-temperature industrial waste heat

Recovering medium-temperature (e.g., 150–180 °C) industrial waste heat through latent heat thermal energy storage (LHTES) can effectively attenuate the consumption of fossil fuels. However, the LHTES system containing a single medium-temperature phase change material (PCM), e.g., erythritol, cannot absorb the part of heat below the PCM's melting point (∼118 °C) during the charging process. Meanwhile, a single low-temperature PCM, e.g., paraffin wax, is unable to supply a significant amount of heat at temperatures higher than its melting point upon discharging. Therefore, a cascade LHTES system combining one erythritol unit and two paraffin wax units (melting point of ∼60 °C) was proposed to deeply recover the waste heat during charging and increase the heat supply temperature during discharging. Through prototype testing, the performance of such a cascade system was examined under various working conditions. It was shown that the cascade system could improve the efficiency of the waste heat recovery from 15.8% to 63.4% under the charging condition of 100 L/h and 160 °C, as compared to a single-stage erythritol-based system. The average heat supply temperature of the cascade system was also increased from 37 °C (at a constant flow rate) to 53.6 °C via an active discharging strategy (by tuning the flow rate). This highly efficient cascade LHTES system has great potential for recovery of medium-temperature waste heat towards a decarbonized future of space heating for buildings.

Screening and identification of 3-aryl-quinolin-2-one derivatives as antiviral agents against influenza A.

Quinolin-2-one represents an important and valuable chemical motif that possesses a wide variety of biological activities; however, the anti-influenza activities of quinolin-2-one-containing compounds were rarely reported. Herein, we describe the screening and identification of 3-aryl-quinolin-2-one derivatives as a novel class of antiviral agents. The 3-aryl-quinolinone derivatives were synthesized via an efficient copper-catalyzed reaction cascade that we previously developed. Using this synthetic method, preliminary structure-activity relationships of this scaffold against the influenza A virus infection were systematically explored. The most potent compound 34 displayed IC50 values of 2.14 and 4.88 μM against the replication of H3N2 (A/HK/8/68) and H1N1 (A/WSN/33) strains, respectively, without apparent cytotoxicity on MDCK cells. We further demonstrated that 27 and 34 potently inhibited the plaque formation of the IAV, rendering this scaffold attractive for pursuing novel anti-influenza agents.

Synthesis of 2‐(Oxindol‐3‐yl)acetamides via Visible‐light‐mediated Oxidative Carbamoylation of N‐arylacrylamides

AbstractUnder metal free condition, an efficient and mild cascade reaction of N‐arylacrylamides with hydrazinecarboxamides is disclosed. Catalyzed by Rose Bengal, it undergoes oxidative dehydrazination, radical addition, and subsequent 5‐exo‐trig cyclization in the presence of visible light. A series of 2‐(oxindol‐3‐yl)acetamides are obtained in moderate to excellent yields, which could be utilized as precursors in the synthesis of bioactive pyrrolidinoindolines.

A Double Hemin Bonded G-Quadruplex Embedded in Metal-Organic Frameworks for Biomimetic Cascade Reaction.

Biocatalytic transformations in living cells, such as enzymatic cascades, function effectively in spatially confined microenvironments. However, mimicking enzyme catalytic cascade processes is challenging. Herein, we report a new dual-Hemin-G-quadruplex (dHemin-G4) DNAzyme with high catalytic activity over noncovalent G4/Hemin and monocovalent counterparts (G4-Hemin and Hemin-G4) by covalently linking hemin to both ends of an intramolecular G4. We use MAF-7, a hydrophilic metal-organic framework (MOF), as the protecting scaffold to integrate a biocatalytic cascade consisting of dHemin-G4 DNAzyme and glucose oxidase (GOx), by a simple and mild method with a single-step encapsulation of both enzymes. Such a MAF-7-confined cascade system shows superior activity over not only traditional G4/Hemin but also other MOFs (ZIF-8 and ZIF-90), which was mainly attributed to high-payload enzyme packaging. Notably, the introduction of hydrophilic G4 allows to avoid the accumulation of hydrophobic hemin on the surface of MAF-7, which decreases cascade biocatalytic activity. Furthermore, MAF-7 as protective coatings endowed the enzyme with excellent recyclability and good operational stability in harsh environments, including elevated temperature, urea, protease, and organic solvents, extending its practical application in biocatalysis. In addition, the incorporated enzymes can be replaced on demand to broaden the scope of catalytic substrates. Taking advantages of these features, the feasibility of dHemin-G4/GOx@MAF-7 systems for biosensing was demonstrated. This study is conducive to devise efficient and stable enzyme catalytic cascades to facilitate applications in biosensing and industrial processes.

An efficient chemoenzymatic cascade strategy for transforming biomass into furfurylamine with lobster shell-based chemocatalyst and mutated ω-transaminase biocatalyst in methyl isobutyl ketone-water

To date, an efficient process for manufacturing valuable furan compounds from available renewable resources has gained great attention via a chemoenzymatic route. In this study, a sulfonated tin-loaded heterogeneous catalyst CLUST-Sn-LS using lobster shell as biobased carrier was prepared to convert corncob (75.0 g/L) into furfural (122.5 mM) at 170 °C for 30 min in methyl isobutyl ketone (MIBK)–H2O biphasic system (2:1, v/v). To improve furfurylamine yield, a novel recombinant E. coli TFTS harboring robust mutant Aspergillus terreus ω-transaminase [hydrophilic threonine (T) at position 130 was site-directed mutated to hydrophobic phenylalanine (F)] was constructed to transform 300–500 mM furfural into furfurylamine (90.1–93.6 % yield) at 30 °C and pH 7.5 in MIBK-H2O. Corncob was converted to furfurylamine in MIBK-H2O with a high productivity of 0.461 g furfurylamine/(g xylan). This constructed chemoenzymatic method coupling bio-based chemocatalyst CLUST-Sn-LS and mutant ω-transaminase biocatalyst in a biphasic system could efficiently convert lignocellulose into furfurylamine.

Bismuth(III)-catalyzed cascade condensation of alkynyl alcohols with terminal alkynes: A facile construction of propargyl cyclic ethers

Herein, we report a Bi(OTf)3-catalyzed cascade condensation between alkynols (particularly pent-4-yn-1-ols and hex-5-yn-1-ols) and terminal alkynes (aryl alkynes) to facile access to diverse propargyl cyclic ethers (2‑alkynyl tetrahydrofurans and 2‑alkynyl tetrahydropyrans). This simple and efficient cascade transformation proceeds through initial intramolecular hydroalkoxylation of alkynols to give corresponding cyclic enol ethers (via exo-dig or endo-dig mode of ring-closure) followed by hydroalkynylation. Cost-effective, naturally abundant, green Lewis acid catalysis, ambient reaction conditions, short reaction times, good substrate scope, and high yields are salient features of this strategy.

Biomimetic multienzyme nanocomplex for efficient cascade reactions

In nature, living cells form multienzyme complex by spatializing enzymes in confined compartments to enable cascade reactions. As these reactions are highly efficient and crucial to cellular metabolism, it is important to understand their catalytic behaviors. Herein, we report a living cell-inspired design of nanoscale multienzyme complex (nanocomplex), in which different enzymes are densely packed with intact conformations as the cellular multienzyme complex does, allowing sufficient transportation of intermedia and creating efficient cascade reactions. Benefit from the similarity between the proposed nanocomplex and cellular multienzyme complex, the systematic study of the effect of enzyme ratios and quantity to the nanocomplex reaction efficiency can inspire the investigation of the basic rules of cellular catalytic behaviors. In addition, the nanocomplex can also contribute to boosting the detection sensitivity of multienzyme-based biosensing due to its unsurpassed efficiency. Using the nanocomplex fabricated with methoxy polyethylene glycol (mPEG), glucose oxidase (GOx) and horseradish peroxidase (HRP), glucose in untreated urine, plasma and saliva samples can be detected with a remarkable detection limit of 1.6 µM and a detection time of just 30 s, surpass the current glucose detection approaches. Remarkably, the proposed sensor can also perform glucose detection with preserved cascade activity under high temperature, acid environment, or after long-time storage. Overall, this work can potentially provide a general understanding of multienzyme catalytic behaviors and a promising platform of ultrasensitive biosensing for disease diagnosis and prognosis.

Glucose‐Responsive Enzymatic Cascade Microreactors in Gas‐Shearing Microfluidics Microcapsules

AbstractEnzymatic cascade reactions are essential for metabolic pathway and biological signal transduction in living cells. More and more attention has been paid to artificial microreactors, which mimic these efficient, methodical, and selective biological cascade catalytic systems in cells. Natural hydrogels such as alginate and chitosan are thought of as suitable materials for matching the chemical, physical, and mechanical properties with extracellular matrix. Inspired by the structures of eukaryotic cells, alginate/chitosan multicompartment microcapsules for enzymatic cascade reaction are developed using an oil‐free gas‐shearing method. Multiple enzymes as biocatalysts are encapsulated in the particles to resemble complex physiological reactions. Biocatalysts, including glucose oxidase and peroxidase in alginate Janus core as a model, sense the external hyperglycemic environment, resulting in insulin release following chitosan shell protonation. The microcapsules show an excellent recyclability, room‐temperature long‐term and anti‐proteolysis stability. The microreactor approach leads to the development of a multi‐enzymatic cascade reaction system and provides an ideal carbohydrate platform to further understand the biomimetic metabolic function of organelles and organs.

Observation of Phonon Cascades in Cu-Doped Colloidal Quantum Wells.

Electronic doping has endowed colloidal quantum wells (CQWs) with unique optical and electronic properties, holding great potential for future optoelectronic device concepts. Unfortunately, how photogenerated hot carriers interact with phonons in these doped CQWs still remains an open question. Here, through investigating the emission properties, we have observed an efficient phonon cascade process (i.e., up to 27 longitudinal optical phonon replicas are revealed in the broad Cu emission band at room temperature) and identified a giant Huang-Rhys factor (S ≈ 12.4, more than 1 order of magnitude larger than reported values of other inorganic semiconductor nanomaterials) in Cu-doped CQWs. We argue that such an ultrastrong electron-phonon coupling in Cu-doped CQWs is due to the dopant-induced lattice distortion and the dopant-enhanced density of states. These findings break the widely accepted consensus that electron-phonon coupling is typically weak in quantum-confined systems, which are crucial for optoelectronic applications of doped electronic nanomaterials.

Amorphous NiB@IrOx nanozymes trigger efficient apoptosis-ferroptosis hybrid therapy

The apoptosis-ferroptosis hybrid therapy opens up a new avenue for tumor eradication. Constructing efficient self-cascade platform is highly desired to enhance its therapeutic effect. Herein, we report on the synthesis of novel nanozyme consist of amorphous NiB alloy completely coated with an ultrathin layer of IrOx shell (A-NiB@C-IrOx). These core-shell nanoparticles exhibited peroxidase (POD)-, catalase (CAT)- and glutathione oxidase (GSH-OXD)-like properties for inducing self-cascade catalysis. Specifically, the amorphous IrOx shell with abundant active sites can effectively convert intratumor hydrogen peroxide (H2O2) to cytotoxic reactive oxygen species (ROS) and oxygen (O2). In presence of O2, amorphous NiB core and ultrathin IrOx shell collectively catalyze the oxidation of GSH to generate H2O2, which is subsequently converted to ROS and O2 by IrOx component. Thus, these enzymatic activities endow A-NiB@C-IrOx nanozymes with the ability of unceasing generation of ROS and O2 and depletion of GSH. In vitro and in vivo studies demonstrate a high therapeutic efficiency of A-NiB@C-IrOx nanozymes via apoptosis-ferroptosis combination therapy. Statement of significanceApoptosis-ferroptosis hybrid therapy opens up new avenues for eradicating tumor cells. However, its actual therapeutic effect is still unsatisfied. Current efforts on this hybrid therapy focus on developing efficient self-cascade nanozymes to improve the efficiency of both ROS generation and GSH depletion. In this study, we constructed amorphous NiB alloy with a completed thin layer of IrOx shell (denoted as A-NiB@C-IrOx) for apoptosis-ferroptosis combination therapy. As expected, A-NiB@C-IrOx can trigger efficient cascade catalytic reactions to continuously generate ROS and consume GSH, finally inducing augmented apoptosis-ferroptosis combination therapy.