Triple Cascade Research Articles

Synthesis of Multi-Substituted 4,5-Dihydrofurans: Microwave Assisted Reaction of β-Ketonitriles, Aldehydes and Pyridinium Phenacyl Salts via [1+1+3] Knoevenagel-Michael-Oxa-Michael Cyclization Triple Cascade Sequence

A microwave assisted protocol for the development of fully substituted dihydrofurans has been explained as a three component triple cascade reaction between pyridinium ylide, phenacyl nitriles and aldehydes. This [1+1+3] annulation protocol produced the dihydrofurans having two stereocentres. A total of 14 molecules have been synthesized with high chemical yields.

Cascade filter system tests for airborne nano‐ and microplastic particle analytics in a laboratory dust chamber

AbstractMeasuring nano‐ and microplastic particle (NMP) loads in air requires suitable analytical filter systems that allow a size‐selective separation of airborne nano‐ and microplastic (NMP) fractions. Previously, various filter materials and setups including nano/micro cascade filtration stacks have been presented (P.‐T. Miclea, 2022). To evaluate these novel filter systems, implementing reliable sampling procedures and instrumentation, as well as sample handling, well‐defined test setups, NMP reference materials, and procedures are of major interest. In this study, a novel triple‐stage silicon (Si) and aluminum oxide (Al2O3) cascade filter system for airborne NMP particles is tested in a laboratory environment. Special focus is put on its ability for size‐selective analytical filtration of airborne NMP particles based on a well‐defined mixture of poly‐ and monodisperse NMP reference materials. For this purpose, a laboratory dust test chamber has been adapted for the dispersion of NMP particles in air as well as the vacuum air extraction through the cascade filter system. A defined NMP test material was fabricated from polydisperse polyethylene (PE) and PE terephthalate, and monodisperse polystyrene, polymethylmethacrylate, spanning a size region from 130 nm to >22 µm. Dispersion and filtration experiments are performed by vacuum extraction under defined temperature, pressure, and humidity conditions on single and triple filtration stages. NMP particle analytics are performed with polydisperse PE particles on a single‐stage filter system with subsequent optical microscopy. Here, the aim is to detect the filtration cutoff for retained particles and transmitted particles referring to initial distribution. A second experiment is run on a triple filtration cascade with mixed poly‐ and monodisperse NMP test material. The different filter stages are equipped with analytical Si and Al2O3 filters with pore sizes of 10 µm, 1 µm, and 100 nm, to test the size selectivity and sealing of the complete cascade setup. The NMP particle size distribution on the individual analytical filter substrates is analyzed by optical and scanning electron microscopy to assess size selectivity performance of the triple‐stage setup. The obtained results in our laboratory NMP dust‐dispersion test chamber demonstrate requirements and limitation of size‐selective NMP cascade filter systems and the involved analytical procedures. Future applications in real indoor and outdoor environments will be discussed.

Ultrasensitive detection of multiple cancer biomarkers by a triple cascade amplification strategy in combination with single particle inductively coupled plasma mass spectrometry.

Aversatile triple cascade amplification strategy was developed for ultrasensitive simultaneous detection of multiple cancer biomarkers using single particle inductively coupled plasma mass spectrometry (spICP-MS). The triple cascade amplification strategy consisted of an enhanced RecJf exonuclease-assisted target recycling amplification module, a hybridization chain reaction amplification module, and a signal amplification module based on DNA-templated multiple metal nanoclusters. In the enhanced RecJf exonuclease-assisted target recycling amplification module, the DNA bases at the 5' ends of aptamers for specific recognition of biomarkers were deliberately replaced by the corresponding RNA bases to enhance amplification efficiency. The signal amplification module based on DNA-templated multiple metal nanoclusters was innovatively used to amplify the signals measured by spICP-MS and at the same time effectively suppress possible background interferences. The proposed spICP-MS platform achieved satisfactory quantitative results for both carcinoembryonic antigen (CEA) and a-fetoprotein (AFP) in human serum samples with accuracy comparable to that of the commercial ELISA kits. Moreover, it has wide dynamic ranges for both CEA (0.01-100ng/mL) and AFP (0.01-200ng/mL). Thelimit of detection for CEA and AFP was 0.6 and 0.5pg/mL, respectively. Compared with conventional biomarkers detection methods, the proposed spICP-MS platform has the advantages of operational simplicity, ultra-highsensitivity, wide dynamic range, and low background. Therefore, it is reasonable to expect that the proposed spICP-MS platform can be further developed to be a promising alternative tool for biomarker detection in fields of clinical diagnosis and biomedical research.

A triple cascade gas turbine waste heat recovery system based on supercritical CO2 Brayton cycle: Thermal analysis and optimization

• A new triple cascade gas turbine waste heat recovery system based on supercritical CO 2 Brayton cycle. • Evaluated the performance of an integrated system combining a gas turbine and a triple cascade cycle. • Analyze and optimize the system's thermodynamic and economic performance. A new triple cascade waste heat recovery system coupled with a supercritical CO 2 power cycle and transcritical CO 2 regenerative cycle is proposed for the high temperature exhaust waste heat generated during the operation of gas turbine, and thermodynamic and economic models are established to analyze the performance of the system, with the following performance indicators: the net output power is 5.67MW, the thermal efficiency is 24.94%, the exergy efficiency is 46.08%, the total investment cost rate is 126.06$/h, and the per unit energy cost is 6.31$/GJ. The thermal performance of the integrated system consisting of the gas turbine unit and the proposed triple cascade waste heat recovery system is evaluated, and the results show that the integrated system effectively utilizes the waste heat compared with the gas turbine unit alone, while the net output power of the integrated system is 22.17 MW and the thermal efficiency is 47.7%. Each component's exergy and cost analysis is performed. The heat exchanger accounts for a large percentage of the exergy destruction, and the investment cost rate of the turbine, compressor and other work-making components is high, indicating the direction of system optimization. The sensitivity analysis of the system's key parameters was carried out through the control variables method to reveal the influence of individual setting parameters on the system performance. Based on the research range of the set parameters, the system is optimized with multiple objectives, and the net output power, exergy efficiency and per unit energy cost are selected as the objective functions. The optimization results show that the combination of exergy efficiency and per unit energy cost resulted in better economic performance, with exergy efficiency of 50.37% and per unit energy cost of 4.66$/GJ. Comparing the system with the other two configurations proves the superiority of the proposed system.

Colorimetric aptasensor for the sensitive detection of ochratoxin A based on a triple cascade amplification strategy

Ochratoxin A(OTA), a highly toxic mycotoxin commonly found in food, poses a serious threat to health even at low concentrations. Developing a sensitive, accurate, simple, and cost-effective detection method is of great significance for food safety and quality control. Herein, a triple cascade amplification strategy was used to construct the colorimetric assay for the detection of OTA, where the amplification process consists of an entropy-driven DNA circuit (EDC), a catalytic hairpin assembly (CHA), and Mg2+-assisted DNAzyme catalysis (MNAzyme). Through the specific binding of ochratoxin A (OTA) and its aptamer, an initiator strand is released to initiate upstream EDC and then produce a new trigger unit that motivates downstream CHA to generate MNAzyme, which further cleaves the substrate strand to induce the formation of G-quadruplex/hemin DNAzyme as a signal readout. The aptasensor was shown to detect OTA, with a low detection limit of 8.7 fM and good selectivity. The developed method could be used as a highly colorimetric aptasensor for the detection of OTA in spiked rice samples.

Biocatalysis tips another domino: A single-enzyme Enders triple cascade reaction

Multi-enzyme cascades are increasingly popular, but single-enzyme cascades, which avoid issues of catalyst compatibility, are still rare. A new article by Melchiorre and co-workers in Angewandte Chemie describes the design and engineering of an enzyme capable of catalyzing the Enders triple cascade reaction, resulting in four new stereocenters. Multi-enzyme cascades are increasingly popular, but single-enzyme cascades, which avoid issues of catalyst compatibility, are still rare. A new article by Melchiorre and co-workers in Angewandte Chemie describes the design and engineering of an enzyme capable of catalyzing the Enders triple cascade reaction, resulting in four new stereocenters.

Enantioselective Biocascade Catalysis with a Single Multifunctional Enzyme.

Asymmetric catalytic cascade processes offer direct access to complex chiral molecules from simple substrates and in a single step. In biocatalysis, cascades are generally designed by combining multiple enzymes, each catalyzing individual steps of a sequence. Herein, we report a different strategy for biocascades based on a single multifunctional enzyme that can promote multiple stereoselective steps of a domino process by mastering distinct catalytic mechanisms of substrate activation in a sequential way. Specifically, we have used an engineered 4-oxalocrotonate tautomerase (4-OT) enzyme with the ability to form both enamines and iminium ions and combine their mechanisms of catalysis in a complex sequence. This approach allowed us to activate aldehydes and enals toward the synthesis of enantiopure cyclohexene carbaldehydes. The multifunctional 4-OT enzymes could promote both a two-component reaction and a triple cascade characterized by different mechanisms and activation sequences.

Enantioselective Biocascade Catalysis with a Single Multifunctional Enzyme

AbstractAsymmetric catalytic cascade processes offer direct access to complex chiral molecules from simple substrates and in a single step. In biocatalysis, cascades are generally designed by combining multiple enzymes, each catalyzing individual steps of a sequence. Herein, we report a different strategy for biocascades based on a single multifunctional enzyme that can promote multiple stereoselective steps of a domino process by mastering distinct catalytic mechanisms of substrate activation in a sequential way. Specifically, we have used an engineered 4‐oxalocrotonate tautomerase (4‐OT) enzyme with the ability to form both enamines and iminium ions and combine their mechanisms of catalysis in a complex sequence. This approach allowed us to activate aldehydes and enals toward the synthesis of enantiopure cyclohexene carbaldehydes. The multifunctional 4‐OT enzymes could promote both a two‐component reaction and a triple cascade characterized by different mechanisms and activation sequences.

Thermodynamic assessment of a triple cascade refrigeration system utilizing hydrocarbon refrigerants for ultra-low temperature applications

• Triple cascade refrigeration system is implemented for ultra-low temperature applications. • System performance analyzed for hydrocarbon-based environment friendly refrigerants. • Temperatures of MTC and LTC condenser are evaluated for maximum COP values. • At different evaporator temperatures, better performance is gained by different pairs. • Heptane and Toluene are recommended in MTC for −120 °C to −110 °C, and −100 °C to −90 °C, respectively. This work presents a detailed thermodynamic analysis of a triple cascade vapor refrigeration system (TCRS) utilizing hydrocarbon refrigerants for ultra-low temperature application. Different hydrocarbon refrigerants pairs are used in different circuits (High temperature circuit HTC, Mid temperature circuit MTC, and Low temperature circuit LTC) to obtain the most suitable refrigerant combination by mathematical modeling of the system. The design and operating parameters considered in this study include (1) evaporator temperature (2) LTC condensation temperature (3) MTC condensation temperature. A thermodynamic analysis consisting of energy and exergy analysis were employed in terms of operating conditions to obtain COP, total compressor work, exergy efficiency, total exergy destruction, mass flow rate and discharge temperatures of compressors. Furthermore, an analysis on component exergy destruction was conducted to show the possibilities of improvement of TCRS utilizing the hydrocarbon refrigerants. The results suggest that at different evaporator temperatures different hydrocarbon refrigerants on TCRS give higher COP and exergy efficiency. The highest COP and exergy efficiency at −100 °C evaporator temperature was calculated to be 0.5931 and 54.446 %, respectively. This study also suggests that hydrocarbon refrigerants can be used in ultra-low temperature applications without compromising the thermodynamic performance of the refrigeration system.

Ultrasensitive quantitation of circulating miR-195-5p with triple strand displacement amplification cascade.

Circulating miR-195-5p has been proposed as a promising peripheral biomarker for the diagnosis, prognosis and severity assessment of various diseases. However, the demand for its sensitive and convenient quantification has not been met yet. Herein, we proposed a one-pot isothermal approach, in which the target signal acquisition, amplification and conversion (fluorescence read-out) system was integrated by a triple strand displacement amplification (SDA) cascade. Using this triple SDA strategy, miR-195-5p can be at least detected at 1 aM, and the linear dynamic range (from 100 aM to 1 pM) is wide enough to meet the detection needs of clinical miRNA level. A proof-of-principle study, using this novel methodology to directly analyze the spiking serum samples with different levels of miR-195-5p, demonstrated the potential of circulating miR-195-5p detection for clinical point-of-care assay. This one-pot isothermal triple SDA approach, we believe, will be a simple and feasible tool for ultrasensitive quantification of circulating miR-195-5p, and may promote the wide application of this potential biomarker in non-invasive clinical diagnosis.

Structural Analysis of the Michael-Michael Ring Closure (MIMIRC) Reaction Products.

A representative number of decalin and hydrindane derivatives 2a–l were prepared in 11–91% yield by means of a cascade reaction of cyclohexanone/cyclopentanone enolates and methyl acrylate through a Michael–Michael ring closure (MIMIRC) process. The relative stereochemistry of the four stereogenic centers formed in all products was determined by analyzing the vicinal coupling constants from the 1H NMR and X-ray crystallography. Such a stereochemical outcome was corroborated by conformational analysis supported by DFT calculations and simulating the 1H NMR spectra of representative products. All products showed the same relative stereochemistry at C-1 and C-8a, while at C-3 and bridgehead carbon C-4a, configurational changes were observed. The present results provide some insights about the scope and limitations of the triple cascade reaction between cycloalkanone enolates with methyl acrylate. This synthetic protocol is still a simple and very practical alternative to generate decalin and hydrindane derivatives with great structural diversity.

A triple cascade approach towards the diastereoselective synthesis of spiro trans-decalinol scaffolds.

A [2+2+2] annulation reaction between cyclohexanone, β-nitrostyrene and 2-arylidene-1,3-indanedione afforded multisubstituted spiro trans-decalinol derivatives in high chemical yields (up to 75%) and excellent diastereoselectivity (up to >20 : 1) at room temperature. This one-pot three-component system follows a triple cascade sequence via the Michael/nitro-Michael/Aldol process, resulting in the formation of three C-C bonds, five contiguous stereocenters as well as a spiro quaternary carbon center.

An efficient triple cascade process for synthesis of novel disperse dyes from lawsone: A modification of natural colorant

This article describes the synthesis of novel dihydropyrimidone derivatives that have been paid attention in organic, medicinal, dyes and many other chemistry disciplines. Here we have developed an efficient triple cascade process to prepare novel disperses dyes with dihydropyrimidine-thiones scaffold. These 3, 4-dihydropyrimidin-2-(1H)-thione derivatives were prepared by simple triple cascade reaction via formal [1+2+3] cyclization among 2-hydroxy-1, 4-naphthoquinone, thiourea and various aromatic aldehyde. This process has varied substrate scope and shortened reaction duration with isolated yield up to 95% resulting in situ formation of one carbon–carbon as well as two carbon–nitrogen bonds. The structures of all the prepared molecules are confirmed with NMR, HRMS and IR spectroscopies. The color properties, UV visible spectral studies are also performed with all the prepared molecules.

Ultrasensitive Detection of Multiple Cancer Biomarkers by Single Particle Inductively Coupled Plasma Mass Spectrometry Based on a Triple Cascade Amplification Strategy

Ultrasensitive Detection of Multiple Cancer Biomarkers by Single Particle Inductively Coupled Plasma Mass Spectrometry Based on a Triple Cascade Amplification Strategy

Organocascade Synthesis of Spiro[chroman‐3,2′‐indanedione] Scaffolds via [4+2] or [1+1+4] Cyclisation

AbstractA simple and convenient protocol has been demonstrated for the construction of spiro[chroman‐3,2′‐indanedione] via Oxa‐Michael/Michael cascade reaction sequence using 2‐arylidene‐1,3‐indanedione and (E)‐2‐(2‐nitrovinyl)phenol. This [4+2] cyclisation protocol results in the generation of two stereocentres along with an all carbon quaternary centre in good to high chemical yields of upto 93 %. A triple cascade reaction approach was carried out for the construction of spiro[chroman‐3,2′‐indanedione] using [1+1+4] cyclisation protocol.

Triple cascade nanocatalyst with laser-activatable O2 supply and photothermal enhancement for effective catalytic therapy against hypoxic tumor

Nanozymes have been combined with glucose oxidase (GOx) for dual-enzyme cascade catalytic therapy. However, their catalysis efficiency is restricted because of the hypoxia tumor microenvironment (TME). Although many methods are developed for O2 supply, the O2 leakage and consumption of H2O2 compromised their practical application. Herein, a biocompatible carbon nitride (C3N4)/nanozyme/GOx triple cascade nanocatalyst was designed with laser-activatable O2 self-supply via water splitting to relieve tumor hypoxia and thus improve the catalysis efficiency. To this end, polydopamine (PDA) nanosphere was prepared and attached with C3N4 nanosheet to improve water splitting efficiency and realize photothermal-enhanced catalysis, simultaneously. The PDA@C3N4 composite was then coated with MIL-100 (Fe), where GOx was loaded, to form C3N4/MIL-100/GOx triple cascade nanocatalyst. The triple cascade catalysis was realized with laser-activatable O2 supply from PDA@C3N4, H2O2 generation with GOx, and •OH production from peroxidase-like MIL-100 (Fe) for tumor therapy. Upon 808 nm irradiation, PDA, as a photothermal agent, realized photothermal therapy and enhanced the catalytic therapy. Thus, the synergy of laser-activatable O2 supply and photothermal enhancement in our triple cascade nanocatalyst improved the performance of catalytic therapy without drug resistance and toxicity to normal tissues.

The influence of impurities on the erosion of tungsten by low energy high flux deuterium plasma irradiation

The erosion behavior of tungsten (W) exposed to low-energy, high flux deuterium (D) plasma has been investigated. The samples were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM) and ion beam analysis (IBA). The eroded thicknesses increase with increasing irradiation fluence from 4.8 × 10 25 to 1.64 × 10 26 m −2 for 100 eV D plasma bombardment at a temperature of approximately 600 K, however, the corresponding sputtering yields gradually decrease as a function of fluence. A number of possible erosion mechanisms for enhanced sputtering of W by D near the energy threshold which include impurities in the plasma and sample, retained D, surface roughness and morphology, were analyzed. As the sputtering threshold energy predicted by theory and simulation for deuterium on pure W is ~216 eV and for W with carbon contamination is ~85 eV, a sputtering yield of 2.32 × 10 −6 which was measured for W with only C impurity exposed to a 60 eV deuterium fluence of 1.08 × 10 26 m −2 indicates that there were a little amount of impurities such as carbon or oxygen in the D plasma but they show an important contribution to the sputtering yield of the W under 100 eV D plasma erosion. The C impurity in the sample can significantly enhance the sputtering yield of W through increasing energy transfer efficiency in a triple collision cascade system, and the change of C concentration from 14 at.% at the surface to 5.6 at.% in the deeper region of the sample dominates the change of erosion rate under 100 eV plasma bombardment. It is recommended to reducing the impurity concentration to very low levels, whether from background D plasma or contaminants in the near-surface of W wall, will be very beneficial for decreasing W erosion in Tokamak operation.

Highly sensitive magnetic relaxation sensing method for aflatoxin B1 detection based on Au NP-assisted triple self-assembly cascade signal amplification

Highly sensitive detection of aflatoxin B1 (AFB1) is of great significance because of its high toxicity and carcinogenesis. We propose a magnetic relaxation sensing method based on gold nanoparticles (Au NPs)-assisted triple self-assembly cascade signal amplification for highly sensitive detection of AFB1. Both AFB1 antibody and initiator DNA (iDNA) are labeled on Au NPs to form Ab-Au-iDNA probe. iDNA is enriched by Au NPs to achieve first signal amplification. Different amounts of Ab-Au-iDNA were bound with AFB1 antigen by indirect competitive immunoassay, and then hybridization chain reaction event was initiated by iDNA to produce long hybridization chain reaction products to enrich more horseradish peroxidase-streptavidin for the second signal amplification. Dopamine could be rapidly converted to polydopamine by HRP catalysis, which is used as the third signal amplification. The Fe3+ solution, providing paramagnetic ions with a strong magnetic signal, could be adsorbed by the polydopamine due to the formation of coordination bonds of phenolic hydroxyl groups with Fe3+. This effective interaction between polydopamine and Fe3+ significantly changes the transverse relaxation time signal of Fe3+ supernatant solution, which can be used as a magnetic probe for highly sensitive detection of AFB1. The sensor exhibited high specificity and sensitivity with a detection limit of 0.453 pg/mL owing to the Au NP-assisted triple self-assembly cascade signal amplification strategy. It has been successfully employed for AFB1 detection in animal feed samples with consistent results of enzyme linked immune sorbent assay and high-performance liquid chromatography.

The dumbbell probe mediated triple cascade signal amplification strategy for sensitive and specific detection of uracil DNA glycosylase activity

Uracil DNA glycosylase (UDG) is a key base excision repair (BER) enzyme and its abnormal expression is nearly relevant to several diseases including cancer. The sensitive detection of UDG activity is beneficial for biomedical studies and clinic diagnosis. In this work, we proposed a dumbbell probe mediated triple cascade signal amplification strategy for sensitive and specific detection of UDG activity. The specially designed dumbbell probe contained two uracil bases, two recognition sites for nicking enzyme and a split sequence of DNAzyme. Unsealed dumbbell probes were first connected into sealed dumbbell probes by T4 DNA ligase, and then the unsealed probes were hydrolyzed by exonuclease to ensure the purity of probes. Under the influence of UDG, two uracil bases were removed to produce two apyrimidinic (AP) sites, which were subsequently cleaved by Endo.IV. The probes after cleavage acted as primers and templates for double nicking sites strand displacement amplification (SDA) to produce a mass of two products. The products of SDA continued to act as primers and templates for rolling circle amplification (RCA) to produce repeats containing complete DNAzyme sequences. The DNAzyme repeatedly cleaved multiple molecular beacons (MB), resulting in remarkable fluorescence enhancement. Benefiting from the triple cascade signal amplification, the sensitivity was improved and the detection limit was 7.2 × 10−5 U mL−1. The method could well distinguish UDG from other interfering enzymes and detect UDG activity in real biological samples, showing good specificity. In addition, this method could be used for screening inhibitors. The above results suggested that the method provided a promising analytical means for UDG related biomedical research and clinic diagnosis.

Cascaded Amplifier Nanoreactor for Efficient Photodynamic Therapy.

Photodynamic therapy (PDT) utilizes reactive oxygen species (ROS) to treat established diseases and has attracted growing attention in the field of cancer therapy. However, in a tumor microenvironment (TME), the inherent hypoxia and high level of antioxidants severely hamper the efficacy of ROS generation. Here, we describe a cascaded amplifier nanoreactor based on self-assembled nanofusiforms for persistent oxygenation to amplify ROS levels. The nanofusiform assembly is capable of photothermal and photodynamic treatment and regulation of redox oxidation stress by antioxidant depletion to prevent ROS tolerance. The Pt nanozyme decoration of the nanofusiform enables efficient oxygen supplements via Pt nanozyme-catalyzed decomposition of H2O2 overexpressed in TME and generation of O2. Furthermore, the temperature elevation resulted from the photothermal effect of the nanofusiform increases the catalase-like catalytic activity of the Pt nanozyme for boosted oxygen generation. Thus, such a triple cascade strategy using nanozyme-based nanofusiforms amplifies the ROS level by continuous oxygenation, enhancing the efficacy of PDT in vitro and in vivo. Meanwhile, an in vivo multi-modal imaging including near-infrared fluorescence imaging, photothermal imaging, and magnetic resonance imaging achieves precise tumor diagnosis. The rationally designed nanofusiform acts as an efficient ROS amplifier through multidimension strengthening of continuous oxygenation, providing a potential smart nanodrug for cancer therapy.