Microwave-assisted Click Chemistry Research Articles

New quinoline-triazole conjugates: Synthesis, and antiviral properties against SARS-CoV-2

At present therapeutic options for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are very limited. We designed and synthesized three sets of small molecules using quinoline scaffolds. A series of quinoline conjugates (10a-l, 11a-c, and 12a-e) by incorporating 1,2,3-triazole were synthesized via a modified microwave-assisted click chemistry technique. Among the synthesized conjugates, 4-((1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-6-fluoro-2-(trifluoromethyl)quinoline (10g) and 6-fluoro-4-(2-(1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)ethoxy)-2-(trifluoromethyl)quinoline (12c) show high potency against SARS-CoV-2. The selectivity index (SI) of compounds 10g and 12c also indicates the significant efficacy compared to the reference drugs.

Rapid Synthesis of Silk-Like Polymers Facilitated by Microwave Irradiation and Click Chemistry.

Silk is a natural fiber that surpasses most man-made polymers in its combination of strength and toughness. Silk fibroin, the primary protein component of silk, can be synthetically mimicked by a linear copolymer with alternating rigid and soft segments. Strategies for chemical synthesis of such silk-like polymers have persistently resulted in poor sequence control, long reaction times, and low molecular weights. Here, we present a two-stage approach for rapidly synthesizing silk-like polymers with precisely defined rigid blocks. This approach utilizes solid-phase peptide synthesis to create uniform oligoalanine "prepolymers", followed by microwave-assisted step-growth polymerization with bifunctional poly(ethylene glycol). Multiple coupling chemistries and reaction conditions were explored, with microwave-assisted click chemistry yielding polymers with Mw ∼ 14 kg/mol in less than 20 min. These polymers formed antiparallel β-sheets and nanofibers, which is consistent with the structure of natural silk fibroin. Thus, our strategy demonstrates a promising modular approach for synthesizing silk-like polymers.

A dual crosslinked self-healing system: Supramolecular and covalent network formation of four-arm star polymers

Restoration of large volume damage together with mechanical stability of self-healing polymers requires fast and efficient reversible crosslinking processes together with the presence of a static network. We investigate four-arm star polymers as a dual self-healing material, equipped with hydrogen bonding moieties and azide endgroups applicable for crosslinking based on “click” cycloaddition reaction (CuAAC). The concepts takes advantage of additional supramolecular network formation due to supramolecular cluster formation. To this effect four-arm star poly(isobutylene)s were prepared via living carbocationic polymerization (LCCP) in combination with simple endgroup transformation steps and microwave-assisted click-chemistry to introduce thymine moieties as supramolecular tie points. Four-arm star thymine-telechelic PIB was obtained as a tough rubbery material as proven via melt-rheology and SAXS measurements with clusters of ≈10 hydrogen bonding moieties resulting in a self-healing response at room temperature. To enable the design of a doubly crosslinked self-healing system, four-arm star PIBs bearing an average of 1.7 azide groups and 2.3 thymine endgroups/polymer were crosslinked with a three-arm star alkyne-telechelic PIB. A weakly crosslinked covalent network reinforced by supramolecular hydrogen bonding interactions was obtained in which “click”-crosslinking reduces the number of clustered hydrogen bonds from ≈10 to ≈8. Macroscopic self-healing studies of the double covalent and supramolecular network structure revealed fast and multiple self-healing at 20 °C within 24 h. The now designable four-arm star polymers enabled the design of a highly efficient self-healing system based on double network formation due to “click”-crosslinking and supramolecular cluster formation.

Design and synthesis of 1H-1,2,3-triazoles derived from econazole as antitubercular agents

Econazole has been known to be active against Mycobacterium tuberculosis. We have designed and synthesized 1H-1,2,3-triazoles derived from econazole as antitubercular agents. The majority of triazole derivatives have been prepared by microwave-assisted click chemistry. It turned out that all of the prepared triazoles had no antifungal activities. However, most of the hydroxy-triazoles (6a and 10) apparently turned out to have antitubercular activities. Overall, hydroxy-triazoles 10 were more active than their corresponding ether-triazoles 11. While the MIC value of hydroxy-triazole 10d was as good as econazole (16μg/mL), the MIC value of 10a was two-fold more active than econazole, suggesting that this 1H-1,2,3-triazole scaffold (3) could be further optimized to develop Mtb specific agents.

Microwave-Assisted Click Chemistry Synthesis of 1,2,3-Triazoles from Aryldiazonium Silica Sulfates in Water

A microwave-assisted click chemistry synthesis of 1,4-disubstituted 1,2,3-triazoles is studied by in situ generation of aryl azides via the reaction of aryldiazonium silica sulfates and sodium azide, followed by coupling with a terminal alkyne in the presence of copper catalyst. These reactions are carried out in water under mild and heterogeneous conditions without using any additional ligands.

Click to Join Peptides/Proteins Together

Copper(I) is able to catalyze Huisgen 1,3-dipolar cycloaddition in a "click" fashion. This copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction presents excellent chemoselectivity and occurs over a wide-range of reaction conditions. It shows tolerance to variation in both pH and solvent polarity, thereby facilitating the ligation of peptides and proteins to produce peptidomimetics and synthetic proteins. In addition, the only product formed is a 1,4-disubstituted-1,2,3-triazole moiety, in many aspects resembling the natural peptide bond, including hydrogen-bonding capability, planarity, distance between the 1 and 4 substituents, and conformational restriction of the peptide backbone; thus the triazole-backbone-modified peptide, in which a triazole replaces the amide bond, may be anticipated to present a secondary structure similar to that of its natural counterpart. This Focus Review describes the scope and applications of copper(I)-catalyzed alkyne–azide cycloaddition in synthetic peptide/protein chemistry.

Microwave assisted click chemistry on a conductive polymer film

Microwave (MW) irradiation has been used to accelerate the functionalization of an azide functional poly(3,4-ethylenedioxythiophene) film by click chemistry. The absorption of MW energy by the conductive polymer has been exploited for localized activation of the reaction on the polymer surface. By use of an alkyne modified fluorescein derivative the reaction conditions have been optimized in a conventional MW oven, enabling the use of different sizes of substrates. The optimization resulted in a reduction of reaction times of approximately 20 h to only 2 min for bulk film functionalization. The method has been applied for anchoring of the chelating agent nitrilotriacetic acid (NTA) on the conductive polymer. The chelating linkage ability of NTA on the surface was investigated through a sandwich ELISA study confirming the selective bonding of a histidine tagged protein.

Design, synthesis, and drug solubilising properties of the first folate–calix[4]arene conjugate

The first example of a folate-calix[4]arene conjugate was designed and synthesized via microwave-assisted click chemistry. In PBS medium at physiological pH, the conjugate formed soluble aggregates and showed the capability to improve the water-solubility of a hydrophobic drug model, such as indomethacin.

Microwave-assisted click chemistry: synthesis of mono and bis-1,2,3-triazole acyclonucleoside analogues of ACV via copper(I)-catalyzed cycloaddition

We report a short and efficient synthesis of 1,2,3-triazole and bis-1,2,3-triazoles acyclonucleoside analogues of Acycolovir. A series of novel 1,2,3-triazole acyclonucleosides linked to nucleobases were prepared via copper(I)-catalyzed 1,3-dipolar cycloaddition of N-9 propargylpurine , N-1-propargylpyrimidines or N-1-propargylindazoles with the azido-pseudosugar under Microwave-assisted synthesis followed by treatment with K2CO3/MeOH.

Efficient synthesis of a fluorescent tripod detection system for pesticides by microwave-assisted click chemistry

A new tripod molecule containing an aromatic core bearing three peracetylated cyclodextrins was synthesized via a microwave-assisted Huisgen 1,3-dipolar cycloaddition and was studied by fluorescence spectroscopy. The photoluminescent properties of complexation phenomena with different pesticides were evaluated in acetonitrile. Fluorescence titrations have been performed to calculate binding constants, sensitivity factors, and limit of detection of the resulting complexes. 2D NMR experiments confirmed the inclusion of pesticide in the hydrophobic cavity of the macrocycle and validated the supramolecular association responsible for the quenching of the fluorescence.