One-pot Research Articles

Synthesis, Antimicrobial and Antioxidant Activity of Some New Pyrazolines Containing Azo Linkages.

Pyrazolines and azo-pyrazolines are influential groups of heterocyclic compounds with two nitrogen atoms inside the five-membered ring. They play an important role in a wide range of biological processes, such as antifungal, antioxidant, antimalarial and other antimicrobial activities. The main objective of this study is to synthesize some new heterocyclic compounds with antioxidant and antimicrobial activity Methods: One-pot three components and traditional synthesis of new azo-pyrazoline compounds were achieved in this work. The preparation process has been started by diazotizing 4-(6-methylbenzothiazol-2-yl) benzamine and its coupling reaction with 4-hydroxy acetophenone producing azo-acetophenone, followed by benzylation with benzyl chloride to form the starting material, azo-benzyloxy acetophenone. A series of substituted benzaldehydes were reacted with the latter compound via one pot and classical methods, forming new chalcones containing azo linkages and benzyloxy moieties, which were then converted into new target azo-pyrazoline derivatives. The structures of the synthesized compounds were confirmed by spectroscopic techniques using FT-IR, 1H-NMR, 13C-NMR, and 13C- DEPT- 135 spectra. Finally, the synthesized compounds were screened for their antioxidant and antimicrobial activities against Staphylococcus aureus and Escherichia coli. Overall, the one-pot three-component synthesis of pyrazoline compounds generally provides advantages in terms of efficiency, simplicity, and time-consumption compared to classical synthesis methods. Hence, the study advocates the one-pot method because it eliminates the tedious process of making chalcones, which takes time, materials, and unnecessary effort. Therefore, this is the most convenient and effective approach to green chemistry.

Recent Progress in Synthetic Chemistry and Biological Activities of Pyrimido[ 4,5-b] Quinoline Derivatives (Part III)

Abstract: Amongst heterocyclic compounds, quinoline and pyrimidine are advantaged scaffolds that appear as significant assembly motifs for the development of new drug entities. Moreover, quinolinepyrimidine- inspired hybrids have a number of biological characteristics that are known. In addition, many pyrimido[4,5-b]quinoline ring systems (PyQs4,5-b), specifically concerning medicinal chemistry, have been reported over the past decade. The synthesis of (PyQs4,5-b) using barbituric acid, thiobarbituric acid, pyrimidine, and their derivatives is presented in this review. The preparation of PyQs4,5-b was clarified through the following chemical reactions: Friedländer, Vilsmeier-Haack formylation, Hantzsch-like reaction, and one-pot three-component reaction.

Facile synthesis and first principles calculations of Li-MoS2/rGO nanocomposite for high-performance supercapacitor applications

Two-dimensional (2D) nanostructured materials such as graphene oxide nanosheets and molybdenum disulfide (MoS2) are potential candidates for electrochemical energy storage applications. The layered structure of MoS2 makes it a promising active electrode material for supercapacitors. Lithium (Li) interacted with MoS2/reduced graphene oxide (Li-MoS2/rGO) nanocomposite has been synthesized in two steps using a sonochemical dispersion method, and a one-pot hydrothermal method resulting in few-layered MoS2/rGO nanosheets of 2D heterointerfaces. The Li-MoS2/rGO nanocomposite exhibits a high specific capacitance of 173.3 F g−1 at a current density of 1 A g−1. Furthermore, an asymmetric supercapacitor device fabricated with Li-MoS2/rGO achieves a good energy density of 10.6 Wh kg−1 at a power density of 686.3 W kg−1 and outstanding cycling stability with 81.2 % capacity retention over 10,000 cycles. The dispersion of 2D-MoS2 in water is due to the strong electrostatic interface. The structural and electronic properties are theoretically calculated for pristine and Li-interacted MoS2/rGO heterostructure using density functional theory. A comparison of the density of states plots of the two heterostructures and the difference charge density plot of Li-MoS2/rGO heterostructure clearly brings out the importance of the presence of Li. A value of 64 μF cm−2 for the quantum capacitance for pristine MoS2/graphene heterostructure increases to a value 99 μF cm−2 corroborating the experimental observations and we assign this change to the transfer of charge from the Li atom to the outer S atoms in the MoS2/graphene heterostructure. This comprehensive approach, combining experimental synthesis with computational modelling, significantly advances the development and optimization of high-performance supercapacitor materials in the energy storage field. The Li-MoS2/rGO nanocomposite has excellent electrochemical specific capacitance and long-term cyclic stability and has been effectively used for supercapacitor applications with high electrochemical performance.

One-pot Synthesis of 2,3-disubstituted-4(3H)-quinazolinone from o-aminobenzoic Acid and DMF Derivatives using Imidazole Hydrochloride as a Promoter.

As a novel and environmentally friendly Brönsted acid, imidazole hydrochloride was used to promote the synthesis of 2,3-disubstituted-4(3H)-quinazolinone from o-aminobenzoic acid and DMF derivatives. The essence of this reaction is a multicomponent reaction, which constructs multiple chemical bonds between different components through the transamidation of imidazole hydrochloride. This protocol showed a wide range of functional group tolerance, and a series of quinazolinones were synthesized in low to moderate yields without metal catalysts, oxidants or other additives.

Design and Synthesis of Novel Heterocycles Utilizing 4,6-Dimethyl-1- ((4-methylthiazol-2-yl)amino)-2-oxo-1,2-dihydropyridine-3-carbonitrile

Abstract: Novel hydrazones 4, 5, and oxime 6 were produced from the reaction of ketone 3 with hydrazine, phenylhydrazine, and hydroxylamine HCl, respectively. One pot multicomponent reaction of chalcones 7a-c, 3-(1H-indol-3-yl)-3-oxopropanenitrile 8, and ammonium acetate in MeOH at reflux temperature gave 2-(1H-indol-3-yl)-nicotinonitrile derivatives 10-12. Additionally, a one-pot reaction of chalcone 7a, malononitrile or ethyl cyanoacetate, and ammonium acetate in AcOH at reflux temperature afforded 6-aminopyridine derivatives 13 and 14, respectively.

Visible Light-Driven Metal- and Photocatalyst-Free Synthesis of β-Trifluoromethylated Enamines via Trifluoromethyl Thianthrenium Salts.

A novel protocol for the visible-light-driven synthesis of β-trifluoromethylated enamines has been developed, which operates without the use of transition metals or any photocatalysts, utilizing trifluoromethylthiosulfonium salts as the source of trifluoromethyl groups under mild conditions. According to this new protocol, more than 40 products have been prepared in moderate to good yields. In addition to eliminating the need for expensive or toxic transition metals and photocatalysts, this new methodology proves its potential scalability through air-stability, the use of safe and readily available reagents, a two-step one-pot procedure, and effective gram-scale reactions. This innovative approach not only demonstrates promise for green chemical synthesis but also offers a new pathway for the advancement of fluorine chemistry in sustainable organic synthesis.

A Novel Synthesis Route of Phenyl Quinoline from Nitrochalcone with Hydrazine Hydrate in the Presence of Pd/C

Quinoline is widely known to have many biological activities. Therefore, the development of the synthesis method of a quinoline derivative framework is a priority. A phenyl quinoline derivative, 6,7-dimethoxy-2-phenylquinoline Q1, has been successfully synthesized via a novel one-pot reaction that involves reduction, cyclization, and followed by dehydration of nitrochalcone derivate, 3-(4,5-dimethoxy-2-nitrophenyl)-1-phenylprop-2-en-1-one C1. The reaction was carried out using 80 % hydrazine hydrate in the presence of 10% Pd/C as a catalyst in an ethanol medium. Target compound Q1 was afforded in a good yield of 69.18% in a relatively short reaction time of ±2 h.

Heterochiral coupling to bilateral β-turn structured azapeptides bearing two remote chiral centers

Enantioselective synthesis governed by chiral catalysts has been extensively developed, but that without any chiral auxiliaries or chiral catalysts is rare, particularly when remote stereogenic centers are involved. Here we report an enantioselectivity of heterochiral coupling in the one-pot reaction of racemic hydrazides with achiral 1,4-bis(isothiocyanine)benzene, yielding preferentially the heterochiral bilateral azapeptides over the homochiral ones. Despite bearing two hydrogen-bonded β-turn structures that allow intramolecular chiral transfer, the bilateral azapeptide products have two chiral centers separated by 14 atoms or 15 bonds, which prevent the direct intramolecular asymmetric communication between the two chiral centers. Interestingly, the heterochiral azapeptides feature intermolecular hydrogen bonding stacking between homochiral β-turns to form a superstructure of alternative M- and P-helices in the crystals. In contrast, the homochiral azapeptide counterparts adopt a β-sheet-like structure, which is less favorable compared to the helical-like superstructure from heterochiral azapeptides, accounting for the favored heterochiral coupling of the one-pot reaction. This work demonstrates enantioselective synthesis involving distant chiral centers through the formation of biomimetic superstructures, opening up new possibilities for the regulation of enantioselectivity.

Aggregation-induced emissive copper nanoclusters with peroxidase-like activity for colorimetric detection of cholesterol

Accurate and point-of-care cholesterol detection is of paramount significance for the prevention of cardiovascular diseases. The colorimetric assay based on peroxidase is a commonly used approach for cholesterol detection, without requiring any complicated biomolecular labeling or sophisticated instrumentation. Copper nanoclusters (CuNCs), exhibiting luminescent properties and peroxidase activity, have garnered significant attention in biomedical application recently. Herein, the glutathione-stabilized copper nanoclusters (GSH-CuNCs) were prepared with an easy one-pot method, employing glutathione as both a reducing agent and stabilizer. An optimization of the GSH-CuNCs preparation was carried out to obtain the highest peroxidase-like activity. UV-Vis absorption was measured to explore the steady-state kinetics of the GSH-CuNCs-catalyzed oxidation of 3,3',5,5' - tetramethylbenzidine (TMB) by H2O2. A colorimetric method for cholesterol detection was developed by combining the catalytic reaction of CuNCs and the enzymatic oxidation of cholesterol with cholesterol oxidase (ChOx). Under the optimized conditions, the UV-Vis absorbance of oxidized TMB (oxTMB) is proportional to the concentration of cholesterol within the range of 6.2-187.5 μM, and the limit of detection (LOD) is determined to be 3.0 μM. More importantly, cholesterol levels can be directly distinguished with the naked eye. Furthermore, the practicality of the method for detecting cholesterol in human serum has been verified with promising results. As expected, this simple, cost-effective, and easy-to-operate colorimetric method for cholesterol detection has potential applications in clinical diagnosis and provides valuable insights into the colorimetric sensing based on CuNCs.

A Novel Poly(ε-Caprolactone)-Based Photo-Crosslinkable Liquid Copolymer as a Versatile Drug Delivery Platform

Background/Objectives: Hydrophobic semi-solid or liquid biodegradable polymers have shown unique advantages as injectable matrices for sustained release of a wide range of drugs. Here we report the design, synthesis, and characterization of a new low-melt liquid copolymer based on poly(ε-caprolactone) (PCL) and establish its utility as a versatile delivery platform. Methods: The copolymer, mPA20, consisting of short PCL blocks connected via acid-labile acetal linkages, was synthesized using a one-pot reaction and its properties were comprehensively characterized. Results: mPA20 is an amorphous, injectable liquid at physiological temperature and can undergo pH-sensitive hydrolytic degradation. mPA20 bearing methacrylate end groups can be photo-crosslinked into solid matrices with tunable mechanical properties. A hydrophobic fluorophore, Nile Red (NR), was solubilized in mPA20 without any solvent. Sustained release of NR into aqueous medium was achieved using mPA20, either as an injectable liquid depot or a photo-crosslinked solid matrix. Further, mPA20 self-emulsified in water to form nanodroplets, which were subsequently photo-crosslinked into nanogels. Both the nanodroplets and nanogels mediated efficient intracellular delivery of NR with no cytotoxicity. Conclusions: mPA20, a new photo-crosslinkable, hydrophobic liquid copolymer with pH-sensitive degradability, is highly adaptable as either an injectable or implantable depot or nanoscale carrier for the controlled release and intracellular delivery of poorly soluble drugs.

Construction of an Innovative Nanogel and Its Applications for Achieving Chemo-Immunotherapy of Tumors.

Malignant tumors, also known as cancers, are a global public health problem. Nanogels are promising carriers for the delivery of anticancer medicines. Therefore, based on the unique microenvironment of tumor cells and the advantages of nanogels, a simple and economical one-pot synthesis method was designed to construct natural polysaccharide-based redox-responsive nanogels (LDD NGs). The enhanced permeability and retention (EPR) effect enriched LDD NGs in tumor cells, which then rapidly collapsed and released the natural antitumor drug diosgenin (DG) and the natural polysaccharide lentinan (LNT) via the depletion of a high level of reduced glutathione (GSH) in tumor cells, resulting in a synergistic therapeutic effect of chemotherapy and immunotherapy. In vivo antitumor experiments showed that LDD NGs could inhibit the proliferation and metastasis of the A549 lung cancer cells. Further studies indicated that LDD NGs could increase the production of ROS and induce apoptosis of A549 cells. In addition, LNT released from LDD NGs could promote the proliferation of dendritic cells, increase the production of NO, and upregulate the expressions of the costimulatory molecules CD40, CD80, CD86, and MHC-II. The construction of LDD NGs was a novel drug synthesis approach that could provide fresh ideas for the development of polysaccharide-based redox-responsive drug delivery systems.

Efficient and one-pot synthesis of 2,4,5-trisubstituted imidazoles in the presence of CuI immobilized on LDH coated with 1,3-benzenedisulfonylamide

Efficient and one-pot synthesis of 2,4,5-trisubstituted imidazoles in the presence of CuI immobilized on LDH coated with 1,3-benzenedisulfonylamide

Fabrication of Zinc(II) Mediated Poly(Acrylamide Co Acrylic Acid) Hydrogel with Thixotropic and Tribological Properties.

Hydrogels have emerged as promising candidates for biomedical applications, such as replacing natural articular cartilage, owing to their unique viscoelastic properties. However, sufficient mechanical properties, self-healing ability, and adhesive nature are some issues limiting its application window. Here, a facile one-pot synthesis of dual cross-linked zinc-coordinated copolymer hydrogels is presented. The network structure of the copolymer hydrogels is strategically developed via dynamic and reversible physical cross-linking by Zn2+ ions and simultaneous covalent cross-linking through a covalent cross-linker viz methylene bisacrylamide. Fourier-transform infrared (FTIR), X-ray diffraction (XRD) scanning electron microscopy (SEM), and Brunauer-Emmett-Teller (BET) analysis have thoroughly characterized the structure of the synthesized hydrogels. The introduction of Zn2+ offers dynamic and reversible complexation, leading to excellent mechanical properties and self-healing features. Moreover, the percentage of the equilibrium water content of zinc-coordinated copolymer hydrogel samples is comparable with that of natural articular cartilage. The Shear sliding study shows the dominant adhesive behavior of HGel-Zn(NO3)2 sample compared to the parent HGel sample. This facile dual cross-linked hydrogel, HGel-Zn(NO3)2, with a combination of good mechanical properties, efficient self-recovery, adequate water content, and favorable adhesive nature, seems very promising to mimic the articular cartilage.

Catalyst-free one-pot three-component synthesis and in silico bioactivity of new 4-pyrazolyl pyrano[3,4-c] pyrrole derivatives

Catalyst-free one-pot three-component synthesis and in silico bioactivity of new 4-pyrazolyl pyrano[3,4-c] pyrrole derivatives

Tumor therapy utilizing dual-responsive nanoparticles: A multifaceted approach integrating calcium-overload and PTT/CDT/chemotherapy

The advancement of rational nano drug delivery systems offers robust tools for achieving synergistic therapeutic outcomes in tumor treatment. In this study, we present the development of pH and near-infrared laser dual-responsive nanoparticles (DOX-CuS@CaCO3@PL-PEG, DCCP NPs) based on calcium carbonate, utilizing a one-pot gas diffusion reaction. These nanoparticles enable combined photothermal therapy (PTT), chemodynamic therapy (CDT), chemotherapy, and Ca2+-overloading synergistic therapy. Doxorubicin (DOX) and copper sulfide (CuS) NPs were co-loaded in CaCO3, followed by PEG surface functionalization. The presence of PEG enhanced the stability of DCCP NPs in aqueous environments. Controlled release of DOX, CuS NPs, and Ca2+ occurs specifically in the acidic tumor microenvironment. Released DOX enhances chemotherapy efficiency, while CuS NPs, upon laser irradiation, induce thermal damage, promoting further drug release and cellular uptake. Additionally, CuS NPs in our system consume excess GSH and generate toxic hydroxyl radicals (·OH) through a Fenton-like reaction, contributing to CDT. These radicals not only directly eliminate tumor cells but also disrupt mitochondrial Ca2+ buffering capacity. Furthermore, Ca2+ released from CaCO3 induces Ca2+-overloading, intensifying mitochondrial disruption and oxidative damage. The synergistic combination of PTT, CDT, chemotherapy, and Ca2+-overloading showcases significant therapeutic potential, indicating broad applications in tumor therapy. This multifaceted approach holds promise for advancing the field of tumor therapeutics.

Molecular Probing Coupled with Density Functional Theory Calculation to Reveal the Influence of Fe Doping on Fe-NiOOH Electrode for High Current Density of Water Splitting.

Fe-doped NiOOH electrocatalysts have attracted wide interest for the exceptional oxygen evolution reaction (OER) performance, but the precise role of Fe doping on the improved intrinsic activity remains unclear. Herein, the molecular probe technique combined with density functional theory calculation is used to reveal the influence of the Fe atom on the rate-determining step of the OER reaction, where the pre-catalyst of hierarchical self-supporting NiFe layered double hydroxide [LDH] nanosheets equipped on nickel foam (NiFe LDH/NF) is generated via a facile and industrially well-matched one-pot corrosion method. The physical characterization results reveal the reconstruction of NiFe LDH into Fe-doped NiOOH for promoted OER, which has a lower OH* adsorption energy with fast subsequent steps that help in obtaining an improved charge injection efficiency compared to NiOOH. In addition, more exposed electroactive species and facile delivery of mass/electron inside the catalytic procedure actually have a high-quality contribution to the outstanding catalytic activity. Therefore, the NiFe LDH36/NF electrocatalyst provides high catalytic activities of 241 and 320mV at 10mA cm-2 toward the OER and overall water-splitting in 1m KOH. This work provides a promising avenue for the rational design of durable self-supporting electrodes toward large-scale water splitting.

Ambient Air-Synthesized CsPbBr3 Nanocrystals Coupled with TiO2 Film as an Efficient Hybrid Photoanode for Photoelectrochemical Methanol-to-Formaldehyde Conversion.

Due to its exceptional optoelectronic properties in the visible spectrum, cesium lead bromide (CsPbBr3) perovskite has attracted considerable attention in solar-driven organic transformations via photoelectrochemical (PEC) cells. However, the performance of the devices is adversely affected by electron-hole recombination occurring between a transparent conductive substrate, such as fluorine-doped tin dioxide (FTO), and a perovskite layer. Herein, to mitigate this issue, a compact layer of titanium dioxide (TiO2) was employed as both an electron transport layer and a hole blocking layer to diminish charge recombination while facilitating electron transfer in such perovskite material. At the oxidation peak potential of 0.70 V vs Ag/AgNO3, a hybrid photoanode of CsPbBr3/TiO2/FTO exhibited a significant increase in photocurrent density, from 15 to 41 μA/cm2, compared to a configuration without a TiO2 layer. Furthermore, the introduction of methanol as a hole scavenger in the PEC system using the hybrid photoanode facilitated the separation of electron-hole pairs, which led to an enhanced photocurrent density of 60 μA/cm2 and promoted the production of formaldehyde. High-performance liquid chromatography (HPLC) confirmed the generation of formaldehyde at a concentration of 26.69 μM with a Faradaic efficiency of 92% under an applied potential of 0.50 V vs Ag/AgNO3 for 60 min of PEC reaction. In addition to the enhanced PEC performance achieved from this hybrid photoanode, CsPbBr3 nanocrystals (NCs) in this work were synthesized by the modified one-pot method under ambient air, where highly uniform and high-purity NCs were obtained. This work signifies the groundbreaking exploration of CsPbBr3 NCs with TiO2 as a photoelectrode material in the organic-based PEC cells, which efficiently improved the interfacial charge transfer within the photoanode for the conversion of methanol to formaldehyde, marking a significant advancement in the field.

One-pot aqueous-phase synthesis of polyimides from typical monomers

One-pot aqueous-phase synthesis of polyimides (PIs) offers great economic and environmental benefits and improves the hydrolytic stability of the precursor (polyamic acid) obviously. However, this method is only suitable for the polymerization of very limited dianhydride and diamine monomers up to now. In this study, the most commonly used dianhydrides and diamines for the preparation of commercially available PI products were selected for one-pot aqueous-phase synthesis of various polyamic acid salts (PAAS). The effects of the structure of monomers, the reaction temperature and the adding process of the organic base on the polymerization reaction were explored by rotational rheology, nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopy. The polymerization products obtained via the aqueous-phase route show high molecular weight when the reaction conditions have been optimized. Various PI films prepared by the thermal imidization of corresponding PAAS demonstrate good optical transparency, excellent thermal stability, and outstanding mechanical and electrical properties. This work proposes the reaction mechanism of PAAS via one-pot aqueous-phase route and utilizes this novel polymerization strategy to synthesize high-molecular-weight PIs from typical aromatic dianhydride and diamine monomers.

Construction of Spatially Separated Acid-Base Sites inside and outside Metal-Organic Framework Nanocrystals for Efficient Cascade Reactions.

The development of acid-base catalysts for one-pot cascade reactions remains challenging because of the inherent incompatibility of inorganic acid and base active sites. Here, we introduced an innovative approach that employs spatial separation to construct separated inorganic acid-base sites, achieving sequence control of acid-base cascade reactions. The as-prepared bifunctional catalyst applied metal-organic framework (MOF) nanocrystals as spatial separators, with the inside microcavities loaded with 1 nm inorganic polyoxometalate acid H3PMo12O40 clusters (NENU-5) and the outside crystal surface covered with basic CuCo layered double hydroxide (CuCo-LDH) nanosheets. By applying the resultant NENU-5@CuCo-LDH catalyst to cascade deacetalization-Knoevenagel condensation, over 99% of the benzaldehyde dimethyl acetal (BDMA) was transformed into the final benzylidene cyanoacetate (BCA) with a 99% yield at 80 °C and solvent-free conditions. Compared to the random NENU-5+CuCo-LDH, the NENU-5@CuCo-LDH with spatially separated acid-base sites indicated a higher reaction rate due to the designed reaction sequence and the shorter mass transfer pathway. Moreover, this hierarchical structure showed inherent shape selectivity and extraordinary stability. This study introduces spatial separation to address the incompatibility issue between inorganic acid and base active sites, offering novel perspectives for acid-base systems.

Development of Controllable Hetero-Pauson-Khand Polymerization to Functional Stimuli-Responsive Poly(γ-lactam)s.

Polymers containing lactam structures play a crucial role in both natural biological systems and human life, and their synthesis, functions and applications are of utmost importance for biomimetics and the creation of new materials. In this study, we developed an efficient heterogeneous Pauson-Khand polymerization (h-PKP) method for the controlled synthesis of main-chain poly(γ-lactam)s containing α, β-unsaturated γ-lactam functionalities using readily available internal alkynes and imines. The molecular weights of the resulting poly(N-Ts/γ-lactam)s can be precisely controlled by adjusting the ratio of phenyl formate and nickel. These polymers exhibit high solid-state luminescence and demonstrate rapid and sensitive dual responsiveness to light and acid stimuli. They further demonstrate strong reactive oxygen species (ROS) generation capability. The unique dual-emission peaks observed in poly(N-H/γ-lactam)s obtained through post-treatment under acidic conditions demonstrate a mechanism of aggregation-induced intermolecular excited-state proton transfer specific to lactam structures. The efficient one-pot synthetic method for poly(γ-lactam) provides a novel strategy for constructing polymers with γ-lactam structures in the main chain and the simple and efficient post-modification method offer a versatile toolbox for functionalizing poly(γ-lactam)s to expand their potential applications.