One-pot Research Articles

Synthesis of Piperazine-containing Derivatives and their Antimicrobial, Antimycobacterial, Antimalarial and Antioxidant Activities

Background: One of the most crucial heterocycles is piperazine for the creation of novel medication candidates with a variety of medicinal applications. The piperazine moiety is a cyclic compound with four carbon atoms and two nitrogen atoms in positions 1 and 4. Objective: The objective of this studty is the development of 1-((3,4-dimethoxyphenyl) (substitutedphenyl) substituted -piperazine (A1-A10) analogs via the one-pot synthesis method and evaluation for their preliminary antibacterial, antifungal, antimycobacterial, antioxidant, and antimalarial activity. Methods: Desired piperazine derivatives were obtained in a single step reaction using piperazine, aldehydes, and boronic acid derivatives. The structures of all newly synthesized compounds have been established based on analytical and spectral data. An in silico molecular docking study was carried out for the series. Results: The spectral data using IR, 1 H NMR, and 13C NMR and mass spectra confirmed the structure of the synthesized compounds. Compounds A6 and A10 were found to be the most promising agents for antimalarial activity. A1-A10 showed a higher IC50 value and found less antioxidant activity. Some of the compounds showed higher potency when compared to the standard drugs in this antimicrobial study. Conclusion: The structure-activity study showed that changes in substituents either on aldehyde, piperazine, or boronic acid derivatives can lead to potential active compounds. These facts make the compounds interesting candidates for further evaluation of their efficacy in the treatment of microbial, tubercular and malarial diseases.

Bioorthogonal Cycloadditions of C3-Trifluoromethylated 1,2,4-Triazines with trans-Cyclooctenes.

1,2,4-triazines are a valuable class of heterodienes that can be employed in inverse electron-demand Diels-Alder reactions. However, their broader application in bioorthogonal chemistry is limited due to their low reactivity. This article focuses on 3-(trifluoromethyl)-1,2,4-triazines, which can be efficiently prepared in a one-pot reaction from NH-1,2,3-triazoles. These triazines are highly reactive in reactions with strained cyclooctenes, giving second-order rate constants as high as 230 M-1 s-1. Despite their high reactivity, the compounds remain sufficiently stable under biologically relevant conditions. We show that some of the compounds are fluorogenic, a property of potential use in bioimaging. In addition, we demonstrate the successful application of the triazines in labeling model biomolecules. Our work shows that the reactivity of 1,2,4-triazines can be enhanced by the 3-CF3-substitution, which we consider an important step toward the wider use of this promising class of reagents.

Establishing an Artificial Pathway for the Biosynthesis of Octopamine and Synephrine.

In this study, we designed an artificial pathway composed of tyramine β-hydroxylase (TBH) and phenylethanolamine N-methyltransferase (PNMT) for the biosynthesis of both octopamine and synephrine. As most TBH and PNMT originate from eukaryotic animals and plants, the heterologous expression and identification of functional TBH and PNMT are critical for establishing the pathway in mode microorganisms like Escherichia coli. Here, three TBHs were evaluated, and only TBH from Drosophila melanogaster was successfully expressed in the soluble form in E. coli. Its expression was promoted by evaluating the effects of different expression strategies. The specific enzyme activity of TBH was optimized up to 229.50 U·g-1, and the first step in the biosynthetic pathway was successfully established and converted tyramine to synthesize 0.10 g/L of octopamine. Furthermore, the second step to produce synephrine from octopamine was developed by screening PNMT, enhancing enzyme activity, and optimizing reaction conditions, with a maximum synephrine production of 2.02 g/L. Finally, based on the optimization of the reaction conditions for each individual reaction, the one-pot cascade reaction for synthesizing synephrine from tyramine was constructed by combining the TBH and PNMT. The synthetic synephrine reached 30.05 mg/L with tyramine as substrate in the two-step enzyme cascade system. With further optimization and amplification, the titers of octopamine and synephrine were increased to 0.45 and 0.20 g/L, respectively, with tyramine as substrate. This work was the first achievement of the biosynthesis of octopamine and synephrine to date.

Ring-Opening of Donor-Acceptor Cyclopropane Diester for the Synthesis of Oxime Esters and 2,3-Dihydroazete Ester

AbstractA simple and efficient approach for the synthesis of privileged oxime esters by employing donor-acceptor cyclopropane diesters (DACs) as one of the potential precursors is reported. The strategy involves Lewis acid catalyzed ring-opening of DACs, resulting in an open-chain intermediate followed by the base-mediated construction of the corresponding oxime esters in a one-pot reaction. Moreover, the process also features the synthesis of diethyl 4-(4-methoxyphenyl)azete-2,2(3H)-dicarboxylate.

PACRAT: pathogen detection with aptamer-observed cascaded recombinase polymerase amplification-in vitro transcription.

The SARS-CoV-2 pandemic underscored the need for early, rapid, and widespread pathogen detection tests that are readily accessible. Many existing rapid isothermal detection methods use the recombinase polymerase amplification (RPA), which exhibits polymerase chain reaction (PCR)-like sensitivity, specificity, and even higher speed. However, coupling RPA to other enzymatic reactions has proven difficult. For the first time, we demonstrate that with tuning of buffer conditions and optimization of reagent concentrations, RPA can be cascaded into an in vitro transcription reaction, enabling detection using fluorescent aptamers in a one-pot reaction. We show that this reaction, which we term PACRAT (pathogen detection with aptamer-observed cascaded recombinase polymerase amplification-in vitro transcription) can be used to detect SARS-CoV-2 RNA with single-copy detection limits, Escherichia coli with single-cell detection limits, and 10-min detection times. Further demonstrating the utility of our one-pot, cascaded amplification system, we show PACRAT can be used for multiplexed detection of the pathogens SARS-CoV-2 and E. coli, along with multiplexed detection of two variants of SARS-CoV-2.

Utilizing Copper Nanoclusters as a Fluorescent Probe for Quantitative Monitoring of Doxorubicin Anticancer Drug.

Monitoring the amount of chemotherapeutic drugs in biological fluids is extremely important for dose adjustment or control of side effects during the treatment process. In this study, copper nanoclusters (Cu NCs) were synthesized via a one-pot method using ammonium citrate as the reducing agent. Cu NCs exhibited bright blue fluorescence, good optical properties and outstanding photostability. The produced Cu NCs were characterized in detail by UV‒vis absorption, fluorescence spectroscopy and transmission electron microscopy (TEM). The produced Cu NCs showed a high quantum yield of 0.97. A fluorescence system was used for doxorubicin (DOX) determination using Cu NCs as a nanoprobe. The presence of DOX decreased the fluorescence intensity of the CuNCs at 445nm but increased the fluorescence intensity of the CuNCs at 619nm. As a result, quantitative detection of DOX can be achieved by measuring the ratio of fluorescence intensities at 445 and 619nm (F619/F445). The fluorescence quenching activity of the Cu NCs was determined to have a linear relationship with the amount of DOX anticancer drug in the range of 1-15 ppb, and the usability of the Cu NCs as a sensor for detection in biological fluids was demonstrated. It was determined that this method can be used to measure the amount of DOX in biological samples effectively.

Assembly of Copper Alkynyl Clusters into Dimensionally Diverse Coordinated Polymers Mediated by Pyridine Ligands.

Surface ligands play crucial roles in modifying the properties of metal nanoclusters and stabilizing atomically precise structures, and also serve as vital linkers for constructing cluster-based coordination polymers. In this study, we present the results of the solvothermal synthesis of eight novel copper alkynyl clusters incorporating pyridine ligands using a one-pot method. The resulting compounds underwent characterization through elemental analysis, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), and single-crystal X-ray diffraction (SCXRD). Our observations revealed that distinct pyridine ligands with varying lengths and coordination sites exert significant influence on the structure and dimensionality of the clusters. The structural diversity of these clusters led to the formation of one-dimensional (1D), two-dimensional (2D), or dimer arrangements linked by seven pyridine bridging ligands. Remarkably, these complexes exhibited unique UV-vis absorption and photoluminescence properties, which were influenced by the specific bridging ligand and structural framework. Furthermore, density functional theory (DFT) calculations demonstrated the capability of the conjugated system in the pyridine ligand to impact the band gap of clusters. This study not only unveils the inherent structural diversity in coordination polymers based on copper alkynyl clusters but also offers valuable insights into harnessing ligand engineering for structural and property modulation.

Fabrication of Poly(ionic liquid) Hydrogels Incorporating Liquid Metal Microgels for Enhanced Synergistic Antifouling Applications.

Hydrogels are ideal for antifouling materials due to their high hydrophilicity and low adhesion properties. Herein, poly(ionic liquid) hydrogels integrated with zwitterionic copolymer-functionalized gallium-based liquid metal (PMPC-GLM) microgels were successfully prepared by a one-pot reaction. Poly(ionic liquid) hydrogels (IL-Gel) were obtained by chemical cross-linking the copolymer of ionic liquid, acrylic acid, and acrylamide, and the introduction of ionic liquid (IL) significantly increased the cross-linking density; this approach consequently enhanced the mechanical and antiswelling properties of the hydrogels. The swelling ratio of IL-Gel decreased eight times compared to the original hydrogels. PMPC-GLM microgels were prepared through grafting the zwitterionic polymer PMPC onto the GLM nanodroplet surface, which exhibited efficient antifouling performance attributed to the bactericidal effect of Ga3+ and the antibacterial effect of the zwitterionic polymer layer PMPC. Based on the synergistic effect of PMPC-GLM microgels and IL, the composite hydrogels PMPC-GLM@IL-Gel not only exhibited excellent mechanical and antiswelling properties but also showed outstanding antibacterial and antifouling properties. Consequently, PMPC-GLM@IL-Gel hydrogels achieved inhibition rates of over 90% against bacteria and more than 85% against microalgae.

Construction ofBenzoxazine-linked One-dimensional Covalent Organic Frameworks Using the Mannich Reaction.

Covalent polymerization of organic molecules into crystalline one-dimensional (1D) polymers is effective for achieving desired thermal, optical, and electrical properties, yet it remains a persistent synthetic challenge for their inherent tendency to adopt amorphous or semicrystalline phases. Here we report a strategy to synthesize crystaline 1D covalent organic frameworks (COFs) composing quasi-conjugated chains with benzoxazine linkages via the one-pot Mannich reaction. Through [4+2] and [2+2] type Mannich condensation reactions, we fabricated stoichiometric and sub-stoichiometric 1D covalent polymeric chains, respectively, using doubly and singly-linked benzoxazine ring. The validity of their crystal structures has been directly visualized through the state-of-the-art cryogenic low-dose electron microscopy techniques. Post-synthetic functionalizations of them with a chiral MacMillan catalyst produce crystaline organic photocatalysts that demonstrated excellent catalytic and recyclable performance in light-driven asymmetric alkylation of aldehydes, affording up to 94% enantiomeric excess.

Enhanced Catalytic Activity of Binuclear Oxidovanadium(IV) Bisbenzimidazole Linked Porphyrin Dimer for the Generation of Biologically Active 3,4-Dihydropyrimidinones and Their Corresponding Thiones.

Binuclear vanadyl(IV) porphyrin (V2BP), where two vanadium(IV) porphyrin macrocycles are linked through benzimidazole units at the β-positions, has been prepared and characterized with various techniques, such as UV-vis, Fourier transform-infrared, electron paramagnetic resonance, cyclic voltammetry, density functional transform calculations, and mass spectrometry. V2BP exhibits a red shift (Δλmax = 10 nm) in the Soret band as compared with unsubstituted parent vanadyl(IV) meso-tetraphenylporphyrin (VP). The synthesized binuclear vanadyl(IV) porphyrin (V2BP) has further been studied as a catalyst to explore a single-pot multicomponent Biginelli reaction producing biologically active 3,4-dihydropyrimidin-2-(1H)-one (DHPM)-based biomolecules and the corresponding thiones under solvent-free conditions and its catalytic activity has been compared with vanadyl(IV) meso-tetraphenylporphyrin (VP). Several reaction conditions, such as the amount of catalyst, time, solvent, and temperature, have been optimized to obtain the maximum yield of DHPMs or thiones. The synthesized β-functionalized V2BP porphyrin dimer manifests much higher conversion (84-95% yield) of DHPMs or the corresponding thiones under the optimized reaction conditions with high TON (4454-5037) and TOF (1113-1259 h-1) values for the one-pot multicomponent Biginelli reaction as compared to the literature. The catalyst exhibited excellent recyclability up to 10 cycles.

Pivotal MoOx-decorated Ru/C with a monomeric structure boosts the room temperature and low-pressure hydrogenation of levulinic acid to γ−valerolactone

Pivotal molybdenum oxide-decorated ruthenium on charcoal catalysts exhibited high efficiency and selectivity for the room temperature and low pressure hydrogenation of levulinic acid (LA) to renewable fuel γ−valerolactone (GVL). The Ru-(y)MoOx/C (y = the amount of co-loaded Mo in wt%) catalysts were synthesised by using a one-pot coprecipitation-hydrothermal method of a solution that consisted of Ru and Mo species at 150 °C for 24 h, followed by reduction with H2 at 300–600 °C for 1.5 h. The Ru-(0.55)/MoOx/C catalyst (pre-reduced at 500 °C) exhibited high dispersion of Ru nanoparticles on the surface of MoOx/C composite support, demonstrating the highest yield of GVL (>99) with a turnover frequency (TOF) reaching up to 2730 h−1 at 30 °C, 10 bar H2, and 1 h. The Ru-(0.55)/MoOx/C also catalysed various carboxylic acids to corresponding alcohols and was reusable without any significant loss of selectivity.

Enhanced catalytic efficiency for chiral alcohol pharmaceutical intermediate production using polyacrylic acid (PAA)-based nano-bienzyme conjugates at the organic-buffer biphasic interface

Nano-bienzyme conjugates (nano-BECs) for catalysing one-pot reactions can simplify the reaction process and improve the efficiency of biocatalytic reactions. In this work glucose dehydrogenase (GDH) and Candida parapsilosis secondary alcohol dehydrogenase (CpSADH) were immobilised with polyacrylic acid (PAA) to form two types of PAA-based nano-BECs (2-S, 2-P), which achieved in situ regeneration of NADH for the production of chiral alcohols in oil-water biphasic systems, such as the key chiral pharmaceutical intermediate of (S)-1-(3-trifluoromethylphenyl)ethanol ((S)-TMPE). At a substrate concentration of 100 mM 3-trifluoromethylacetophenone (TMAP), the conversion catalyzed by nano BEC was 98.2 % in dipentyl phthalate-phosphate buffer biphasic system. In contrast, the conversion was only 39.5 % and 38.9 % in the PB buffer and 8.4 % and 7.7 % in dipentyl phthalate system. The experiments on kinetic constants demonstrated that the catalytic efficiencies (Kcat/Km) of nano-BECs (2-S, 2-P) were enhanced by 6.7-fold and 7-fold, respectively, compared to free CpSADH. Additionally, nano-BECs showed stronger coenzyme regeneration ability. Under optimal reaction conditions, nano-BECs achieved 96.2 % conversion of TMAP to (S)-TMPE in an organic-buffer system with e.e. > 99.6 % at 300 mM substrate concentration. This research expands the potential applications of polymers and proteins, and offers valuable insights into the synergistic effects of PAA on bienzyme catalytic systems in biocatalysis.

NHC-Cu Three-Coordinate Complex as a Promising Photocatalyst for Energy and Electron Transfer Reactions.

Herein, we describe a simple three-coordinate complex of Cu(I) with an NHC and 1,10-phenanthroline ligands as an effective photocatalyst for energy (e.g., olefin E/Z isomerization) and electron transfer (e.g., aryl halide dehalogenation) reactions under blue-light irradiation. This complex can be obtained in a one-pot procedure starting from commercially available reagents and green solvents (EtOH, water). We hereby present a study of its activity and mechanistic insight into its mode of operation.

Preparation of Few-Layered MoS2 by One-Pot Hydrothermal Method for High Supercapacitor Performance.

Molybdenum disulfide (MoS2), a typical layered material, has important applications in various fields, such as optoelectronics, catalysis, electronic devices, sensors, and supercapacitors. Extensive research has been carried out on few-layered MoS2 in the field of electrochemistry due to its large specific surface area, abundant active sites and short electron transport path. However, the preparation of few-layered MoS2 is a significant challenge. This work presents a simple one-pot hydrothermal method for synthesizing few-layered MoS2. Furthermore, it investigates the exfoliation effect of different amounts of sodium borohydride (NaBH4) as a stripping agent on the layer number of MoS2. Na+ ions, as alkali metal ions, can intercalate between layers to achieve the purpose of exfoliating MoS2. Additionally, NaBH4 exhibits reducibility, which can effectively promote the formation of the metallic phase of MoS2. Few-layered MoS2, as an electrode for supercapacitor, possesses a wide potential window of 0.9 V, and a high specific capacitance of 150 F g-1 at 1 A g-1. This work provides a facile method to prepare few-layered two-dimensional materials for high electrochemical performance.

Solid-state green synthesis of two (1:1) organic intermolecular compounds; their physico-chemical, thermal, single crystal growth, and atomic packing studies

The solid-state solvent free reaction method has been adopted for the one-pot synthesis of novel organic materials with utmost 100 % yield. To identify the composition forming the intermolecular compound (IMC), the solid-liquid equilibria of entire compositions have been studied by establishing the phase diagram of n, n-dimethylaminobenzaldehyde (DMAB) with anthranilamide (AN) and 2-chloro-4-nitro benzoic acid (CNBA). The structural changes and novelty of the IMCs to that of parents are studied using FTIR, NMR and X-ray diffraction. The studies of optical properties of intermolecular compounds using UV–vis absorption and fluorescence spectroscopy infer the significant fluorescence emission. The single crystals of both intermolecular compounds, ANDMAB and DMABCNBA, are grown from solution using slow evaporation technique. The single crystal X-ray diffraction studies reveal that IMC of AN and DMAB is a racemic mixture whereas IMC of DMAB and CNBA is a co-crystal, and both the crystals have crystallized in triclinic P1‾ space group. The thermal stability and thermal behaviors are also studied using the experimental heat of fusion values obtained from differential scanning calorimetry (DSC).

Real-time detection of gastrointestinal leaks via bismuth chelate-enhanced X-ray gastroenterography

Anastomotic leaks are among the most dreaded complications following gastrointestinal (GI) surgery, and contrast-enhanced X-ray gastroenterography is considered the preferred initial diagnostic method for GI leaks. However, from fundamental research to clinical practice, the only oral iodinated contrast agents currently available for GI leaks detection are facing several challenges, including low sensitivity, iodine allergy, and contraindications in patients with thyroid diseases. Herein, we propose a cinematic contrast-enhanced X-ray gastroenterography for the real-time detection of GI leaks with an iodine-free bismuth chelate (Bi-DTPA) for the first time. The Bi-DTPA, synthesized through a straightforward one-pot method, offers distinct advantages such as no need for purification, a nearly 100 % yield, large-scale production capability, and good biocompatibility. The remarkable X-ray attenuation properties of Bi-DTPA enable real-time dynamic visualization of whole GI tract under both X-ray gastroenterography and computed tomography (CT) imaging. More importantly, the leaky site and severity can be both clearly displayed during Bi-DTPA-enhanced gastroenterography in a rat model with esophageal leakage. The proposed movie-like Bi-DTPA-enhanced X-ray imaging approach presents a promising alternative to traditional GI radiography based on iodinated molecules. It demonstrates significant potential in addressing concerns related to iodine-associated adverse effects and offers an alternative method for visually detecting gastrointestinal leaks.

Persulphate assisted photoelectrochemical degradation of organic pollutants in water on a silver nanoparticle modified Cu2O photoanode

This work presents the photoelectrochemical production of sulphate radicals using fluorine-doped tine oxide – silver nanoparticles – copper(I) oxide (FTO-AgNPs-Cu2O) photoanode in the presence of peroxydisulphate salt for the enhanced degradation of selected organic pollutants in water. Firstly, Cu2O was prepared via a facile and template-free one-pot method, then AgNPs were photo-reduced on the surface of the Cu2O, and the resultant product was immobilised on an FTO conductive substrate to form FTO-AgNPs-Cu2O photoanode. When the electrode was applied for the abatement of tetracycline in the presence of 3 mM peroxydisulphate salt and 1.5 V external potential, the degree of tetracycline degradation and mineralisation after 90 min was 82 % and 78 % respectively. Furthermore, the same system was able to achieve degradation of 81 % sulfamethoxazole degradation within 90 min and 100 % orange II dye degradation within 30 min. The photoanode was efficient in the treatment of real wastewater containing tetracycline. Scavenger studies reveal that holes, hydroxyl, and sulphate radicals significantly participated in the degradation process. The electrode is stable and therefore applicable for the abatement of other organic pollutants in a persulphate-assisted photoelectrochemical degradation system.

One-pot synthesis of HKUST-1 monolith for CO2 adsorption

Abstract Shape-forming technology is essential for the widespread utilization of metal-organic frameworks. We developed a one-pot synthesis method for an HKUST-1 monolith. An HKUST-1 monolith was successfully prepared by the hydrothermal treatment of a Cu monolith in an aqueous solution of 1,3,5-benzenetricarboxylic acid, ethanol, and nitric acid without the addition of a metal source. The prepared HKUST-1 monolith showed CO2 adsorption properties comparable to those of commercially available HKUST-1 powdery crystals.

Synthesis of Polysubstituted Pyridines via Nitrogen-doped Graphene Catalyzed One-Pot Multicomponent Reaction under Solvent-Free Conditions

Abstract: Polysubstituted pyridine derivatives were produced with high to excellent yields in the presence of nitrogen-doped graphene (NDG) as a dual acid-based catalyst. NDG efficiently catalyzes the multicomponent reaction between arylaldehydes, diethyl-acetylene dicarboxylates, malononitrile, and ammonium acetate under solvent-free conditions at 80°C to afford the polysubstituted pyridines in short reaction times. The structures of the synthesized pyridines were established by Ft-IR, 1H, and 13C NMR spectroscopic analysis. The advantages of this method include the in-situ oxidation of prepared 1,4-dihydropyridines, one-pot procedure, solventless system, operational simplicity, and no column chromatography. Additionally, neither toxic solvents nor catalysts are needed, and the procedure can be very reliable among the reported methodologies. The yields and reaction times in the presence of four times recycled catalyst are in comparable to the fresh catalyst.

Activation of PMS by MIL-53(Fe)@AC composites contributes to tetracycline degradation: Properties and mechanisms

The one-pot method was employed to synthesize MIL-53(Fe)@AC, which achieved a degradation efficiency of 92.14% for tetracycline (TC) within 120 min compared with activated carbon (AC) and MIL-53(Fe). Moreover, it demonstrated excellent TC degradation efficiency across the pH range of 2.5-10.5. It retained 89% of the degradation performance after 5 cycles, showcasing its good stability. The quenching experiments and EPR analyses revealed that the SO4∙− /OH⋅/ ∙O2− / 1O2 active species were mainly produced in the catalytic system, and three pathways for TC degradation were analyzed. MIL-53(Fe)@AC emerged as a reliable choice for PMS activation in a wide range of practical applications in antibiotic catabolism due to its excellent performance, stability, and adaptability.