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Comprehensive Summary: How to obtain organic electro‐optic materials with large electro‐optic coefficients, high glass transition temperature, and good optical transparency remains a challenge in this field. To solve this problem, we introduce groups that can undergo Huisgen cycloaddition reactions into the donor and electron bridge of chromophores with large hyperpolarizability using tetrahydroquinoline as the donor. Binary cross‐linkable chromophores TLD1‐2 with CF3‐TCF as the acceptor and chromophores TLD3‐4 with 5Fph‐TCF as the acceptor were synthesized. After poling and crosslinking, the Tg of TLD1/TLD2 and TLD3/TLD4 were raised to 152 and 174 °C, respectively. The electro‐optical coefficients of chromophores TLD1/TLD2 and TLD3/TLD4 were as high as 312 pm/V and 287 pm/V, respectively. The long‐term alignment stability test showed that after being left at 85 °C for 500 h, the cross‐linked film TLD3/TLD4 can still maintain more than 98% of the original electro‐optical coefficient value, which is higher than that of TLD1/TLD2 (93%). The chromophore TLD3‐4 exhibited much blue‐shifted maximum absorption wavelengths (~40 nm) compared to TLD1‐2 which was beneficial for reducing optical loss in the device. The combination of high electro‐optic coefficient, strong stability, and excellent optical transparency makes the TLD series of binary cross‐linked materials very promising for practical high‐performance electro‐optic devices. [ABSTRACT FROM AUTHOR]

In the present study, cellulose-supported Schiff base Cu(II) catalyst [(Cell-ThP-Cu(II))] has been developed, synthesized, and characterized by TGA, XRD, FT-IR, SEM, EDS, ICP-OES, XPS, and BET/BJH techniques. The catalytic performance of Cell-ThP-Cu(II) was investigated for one-pot Chan-Lam coupling followed by Huisgen 1,3-cycloaddition. As a result, various 1-aryl-1,2,3-triazoles were prepared using arylboronic acids, sodium azide, and phenyl acetylenes. The notable merits of the proposed approach are low catalyst loading (0.072 mol%), high TONs (up to 1041–1347) and TOFs (up to 190–224), catalyst reusability (up to 5 cycles) and the use of a green solvent at room temperature. [ABSTRACT FROM AUTHOR]

Given the comparatively lower rotational barriers, the catalytic asymmetric construction of axially chiral biaryl structures, especially those containing a five‐membered heterocycle, still remains a challenge. Herein, we described a general and modular protocol to access atropisomeric arylpyrazole scaffolds containing a phosphorus unit by a dipeptide phosphonium salt catalyzed reaction involving an oxidative central‐to‐axial chirality conversion. This reaction features excellent yields and enantioselectivities, broad substrate scope, and a low catalyst loading, delivering axially chiral phosphine compounds. [ABSTRACT FROM AUTHOR]

A convenient method for the synthesis of 2-azido-3-arylpropanoic acids via the Meerwein halogenoarylation reaction of acrylic acid esters with diazonium salts, subsequent nucleophilic substitution of the halogen by an azide, and saponification is developed. The newly formed 2-azido-3-arylpropanoic acids react under the conditions of non-catalytic four-component Ugi reactions, leading to the formation of α-azidoamides in good yields. The use of propargylamine as the amine component allows the formation of Ugi adducts with azide and acetylene motifs ready for intramolecular 1,3-dipolar Huisgen cycloaddition to give the [1,2,3]triazolo[1,5- a ]pyrazine annulated system. The Ugi reaction is found to give 2-azido-3-aryl- N -(2-oxo-1,2-disubstituted ethyl)- N -(prop-2-yn-1-yl)propanamides at room temperature without azide–alkyne cycloaddition. These dipeptides are converted into 4,5-dihydro[1,2,3]triazolo[1,5- a ]pyrazin-6(7 H)-ones in near quantitative yields by heating in toluene. However, when the Ugi reaction is carried out by heating, it results in a one-pot Ugi–Huisgen tandem reaction leading to 4,5-dihydro[1,2,3]triazolo[1,5- a ]pyrazin-6(7 H)-ones in excellent yields. Moreover, the possibility of the incorporation of a bromovinyl fragment (the synthetic equivalent of an acetylene fragment) via the aldehyde component of the Ugi reaction is demonstrated in an alternative preparation of the [1,2,3]triazolo[1,5- a ]pyrazine system. [ABSTRACT FROM AUTHOR]

Dendrimers are attractive macromolecules for a broad range of applications owing to their well-defined shapes and dimensions, highly branched and globular architectures, and opportunities for exploiting multivalency. Triazine dendrimers in particular offer advantages such as ease of synthesis, stability, well-defined spherical structure, multivalency, potential to achieve acceptable drug loadings, and low polydispersity. In this study, the potential utility of alkyne-azide "click" cycloadditions of first-, second-, and third-generation triazine dendrimers containing three or six alkynyl groups with benzyl azide was examined using copper catalysts. "Click-and-grow" and "grow-then-click" strategies were employed. For the first- and second- generation dendrimers, the desired triazole derivatives were obtained in high yields and purified by simple reprecipitation without column chromatography; however, some difficulties were observed in the preparation of third-generation dendrimers. The desired reaction proceeded under microwave irradiation as well as with simple heating. This click chemistry can be utilized for various melamine dendrimers that are fabricated with other amine linkers. [ABSTRACT FROM AUTHOR]

Synthesis of new series of chromen-2-one-1,2,3-Triazoles (6a-6j) was reported using the help of key methods such as [3+2]-cycloaddition and ultrasound. All compounds were further evaluated for their in vitro anticancer activity profile in three human cancer cell lines MCF-7(breast), A-549 (lungs), and HeLa (cervical). Among all, three compounds namely 6c, 6f, and 6j showed the most promising activity against three lines, when compared with the etoposide. [ABSTRACT FROM AUTHOR]

A series of novel thiazolidine-4-one derivatives was synthesized by reacting 1,4-disubstituted hydrazine carbothioamides with diethyl azodicarboxylate. The structures were confirmed by spectroscopic data as well as single-crystal X-ray analyses. The antiproliferative activity of the synthesized compounds was investigated against four human cancer cell lines using an MTT assay. Compounds 5d, 5e, and 5f revealed the most potent antiproliferative activity with GI50 values ranging from 0.70 µM to 1.20 µM, compared to doxorubicin GI50 value = 1.10 µM. Compounds 5d, 5e, and 5f were further investigated for their inhibitory activities against CDK2 and EGFR as potential targets for their molecular mechanism. Compounds 5e and 5f have showed potent inhibitory activity to CDK2 enzyme with IC50 values of 18 and 14 nM, which is more potent than the reference dinaciclib (IC50 = 20 nM). Moreover, compounds 5e and 5f were the most potent EGFR inhibitors, with IC50 values of 93 and 87 nM, respectively, compared to the reference erlotinib (IC50 = 70 nM). In addition, the most potent derivatives were tested for their apoptotic activity against caspases 3, 8, and 9, and the results showed that compounds 5d, 5e, and 5f revealed a greater increase in active caspases 3,8 and 9 than doxorubicin. Also, compounds 5d, 5e, and 5f elevated cytochrome C levels in the MCF-7 human breast cancer cell line by about 15.5, 15.8, and 16.5 times, respectively. Finally, a molecular docking study was performed to investigate the binding sites of these compounds within the active sites of CDK2 and EGFR targets, and the results confirmed that the most potent CDK2 and EGFR inhibitor 5h also have showed the highest docking score.

An effective method to prepare crosslinked polybenzimidazole (PBI) via [2 + 3] Huisgen cycloadditions has been proposed. Propargyl modified PBI (PBI-PG) has been synthesized firstly. In the presence of diazido crosslinkers, PBI-PG can be thermally crosslinked by [2 + 3] Huisgen cycloadditions. Evidences from 1H NMR and ATR spectra imply a small amount of grafting alkenyl structures on PBI-PG. The grafting alkenyl structures provide another crosslinking mechanism named as alkyne-alkene crosslink. The alkyne-alkene crosslink is highly efficient under heat to form crosslinking networks which display toughness, low tensile strengths, and large swelling ratios in phosphoric acid (PA) solutions. Influences of rigidities and chain lengths of crosslinkers on performances of crosslinked PBIs have been investigated. PBIs crosslinked by rigid crosslinkers behave as brittle materials while that crosslinked by flexible crosslinkers behave as tough materials. Addition of crosslinkers leads to decreased gel fractions but improved tensile strengths, which is attributed to competition results of crosslinking and plasticizing effects. PBI-R2-20, which is crosslinked by a long rigid crosslinker, exhibits the highest tensile strength of 102.33 MPa, which is 66.34 MPa higher than that of PBI-PG. With even lower PA uptakes, PBIs crosslinked by rigid crosslinkers display more thermally stable and higher conductivities than that crosslinked by flexible crosslinkers. After doping in 12 mol/L PA solution, PBI-R2-20, with an acid uptake of 163 wt%, displays the highest tensile strength of 8.1 MPa and the most thermally stable and the highest conductivity which reaches a maximum of 2.30 × 10−2 S cm−1 at 188 °C among all crosslinked membranes.

Metal‐catalyzed azide‐alkyne cycloaddition reactions represent the most convenient and atom‐economic way to construct robust 1,2,3‐triazole units. Remarkable copper‐ and ruthenium‐based catalytic systems have been well established for regioselective preparation of 1,4‐ and 1,5‐disubstituted 1,2,3‐triazoles, both of which have been widely utilized in various areas. In comparison, exploitation of efficient methods to promote the cycloaddition of azides with internal alkynes to afford 1,4,5‐trisubstituted 1,2,3‐triazole motifs with high regioselectivity is still challenging and attractive. This review provides a thorough summary of the developments in metal‐catalyzed cycloaddition of azides with internal alkynes. Besides discussions about mechanism and scope, applications of these strategies were also briefly overviewed. [ABSTRACT FROM AUTHOR]

Mid-sized molecules have emerged as an attractive chemical space and potentially provide a robust basis for the development of synthetic agents to control intracellular protein interactions. However, the limited cell permeability and chemical tractability of such agents remain to be addressed. We envisioned that targettemplated synthesis of such mid-sized molecules might provide a solution. Here, we exploited a copper-free Huisgen cycloaddition for template synthesis using a peptide fragment containing a 4,8-diazacyclononyne (DACN) moiety and an azide-containing fusicoccin derivative in the presence or absence of recombinant 14-3-3ζ protein in vitro. Time-course changes in the yield of products demonstrated that the reaction was accelerated in the presence of 14-3-3 and one of the regioisomers was generated predominantly, supporting the template effect. [ABSTRACT FROM AUTHOR]

Heterocyclic compounds are widely found in nature, more specifically, five- or six-membered rings nitrogen heterocycles are important in the synthesis of biologically active compounds. An essential class of nitrogen heterocyclic substances are the 1,2,3-triazoles, which contain a five-membered ring embedding three contiguous nitrogen atoms followed by two carbon atoms. These heterocyclic compounds exhibit a wide range of biological activities with important industrial applications. The original method for 1,2,3-triazoles synthesis is the Huisgen 1,3-dipolar cycloaddition of azides and alkynes, which was popularized by Meldal and Sharpless (Nobel Prize in chemistry awardees in 2022) with the use of copper catalysts. This method is commonly called copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and belongs to a class of reactions known as "click" chemistry, which emphasizes mild reaction conditions with high yields, regiospecificity, and stereospecificity. Over the last decades, significant advances in chemical processes have been made applying the twelve principles of Green Chemistry. Not surprisingly, many environmentally friendly methodologies have been reported in "click" chemistry. This review focused on recent articles (last 10 years) that used greener reaction media (water, ethanol, glycerol, PEG, supercritical fluids, EG, ionic liquids, and solvent-free processes) to synthesize 1,2,3-triazoles. Nanocatalysis and mechanochemistry have also been addressed. [Display omitted] [ABSTRACT FROM AUTHOR]

There is considerable interest in using the metalloprotein cofactor vitamin B 12 as a vehicle to deliver drugs and diagnostic agents into mammalian or bacterial cells by exploiting the B 12 -specific active uptake pathways. Conjugation of the cargo via the β-axial site or the 5'-OH of the ribose of the nucleotide are the most desirable sites, to maximise intracellular uptake. Herein we show the potential of conjugation at the beta-azido ligand of the vitamin B 12 derivative azidocobalamin via a click-type azide-alkyne 1,3-dipolar cycloaddition (Huisgen cycloaddition) reaction. Reacting azidocobalamin with dimethyl acetylenedicarboxylate at 40 °C results in essentially stoichiometric conversion of azidocobalamin to the corresponding triazolato complex. The stability of the complex as a function of pH and in the presence of cyanide were investigated. The complex is stable in pD 7.0 phosphate buffer for 24 h. The rate of beta-axial ligand substitution was found to be one order of magnitude slower for the triazolatocobalamin complex compared with azidocobalamin. The beta-axial azido ligand of the vitamin B 12 derivative azidocobalamin reacts with an electron deficient alkyne to form the corresponding triazolato complex. [Display omitted] • A new strategy for vitamin B12 conjugates is presented with derivatization via the beta-azido ligand of azidocobalamin. • Azidocobalamin reacts with dimethyl acetylenedicarboxylate via a 1,3-dipolar cycloaddition to form a triazolato complex • The complex is stable in aqueous solution at neutral pH but partially hydrolyses in acidic or basic solution. • The rate constant for substitution of the triazolato ligand by cyanide is one order of magnitude slower than azidocobalamin. [ABSTRACT FROM AUTHOR]

A series of 1,2,3-triazole-containing tomentosin scaffolds was obtained from tomentosin 1. The synthesis involved a Michael addition of trimethylsilylazide on the α-methylene-γ-lactone function of the natural sesquiterpene lactone 1 to give the diastereoisomers 2 and 3, which were readily separated by column chromatography. These compounds underwent copper-catalyzed Huisgen 1,3-dipolar cycloaddition with various terminal alkynes to provide compounds 4a–h and 5a–h in good yields. [ABSTRACT FROM AUTHOR]

A metal–organic framework (MOF) consisting of Cu-benzenetricarboxylic acid was processed under ultrahigh pressure (5 GPa) and at temperature of up to 500 °C. The products were characterized with TEM, FTIR, and XAFS. The decomposition of the MOF started at 200 °C at 5 GPa. This temperature was much lower than that in the vacuum. Single-nanometer Cu nanoparticles were obtained in carbon matrix, which was significantly smaller than the Cu particles prepared at ambient pressure. The catalytic activity for Huisgen cycloaddition was examined, and the sample processed at 5 GPa showed a much improved performance compared with that of the MOF-derived Cu nanoparticles prepared without high pressure.

Dendrimers are monodisperse polymers grown in a fractal manner from a central point. They are poised to become the cornerstone of nanoscale devices in several fields, ranging from biomedicine to light-harvesting. Technical difficulties in obtaining these molecules has slowed their transfer from academia to industry. In 2001, the arrival of the “click chemistry” concept gave the field a major boost. The flagship reaction, a modified Hüisgen cycloaddition, allowed researchers greater freedom in designing and building dendrimers. In the last five years, advances in click chemistry saw a wider use of other click reactions and a notable increase in the complexity of the reported structures. This review covers key developments in the click chemistry field applied to dendrimer synthesis from 2010 to 2015. Even though this is an expert review, basic notions and references have been included to help newcomers to the field.

Highlights • One-pot synthesis of regioselectivly brominated and silylated cellulose. • Nucleophilic substitution on organosoluble cellulose derivatives. • Huisgen-cycloaddition on the cellulose backbone in water-free media. Abstract Huisgen cycloaddition has proven to be a powerful tool for the derivatization of cellulose, but the choice of reaction partners is limited by the solubility of the cellulose derivative. In this report, we show the efficient synthesis of an azide-bearing, organosoluble cellulose derivative via the 6-bromo-6-deoxy-2,3-O-trimethylsilyl cellulose (Br-TMSC) obtained through a novel one-pot reaction. It opens the possibility to perform the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) under moisture free conditions. First, the one-pot approach was used to synthesize Br-TMSC by combining homogeneous and regioselective bromination at C-6 position and silylation at C-2/C-3 positions. Then, 6-azido-6-deoxy-2,3-O-trimethylsilyl cellulose (N 3 -TMSC) as the starting material for the CuAAC was obtained via nucleophilic substitution of the bromine by azide moiety. Furthermore, N 3 -TMSC was exemplarily reacted with phenylacetylene and 3-cyclopentyl-1-propyne in the CuAAC in dry tetrahydrofuran (THF) as solvent and showed nearly complete conversion of the azide functionality. All products have been characterized by FTIR spectroscopy, NMR spectroscopy, elemental analysis and gel permeation chromatography (GPC). [ABSTRACT FROM AUTHOR]

ABSTRACT: The bonding of layers of silicone elastomers during the manufacturing of microfluidic devices is often accomplished using plasma oxidation. The process can be costly, may require a clean room and materials that ensure the flatness of the bonding layers and, as a consequence of hydrophobic recovery, can lead to high variability in the degree of adhesion. As importantly, the process precludes incorporation of chemical functionalities that work as anchors to immobilize biomolecules within the microfluidic channel. We hypothesized that it would be possible to fabricate microfluidic channels using the Huisgen 1,3‐dipolar cycloaddition of azides to alkynes to crosslink silicones and form PDMS elastomers and, in a subsequent step, bond one PDMS layer to another simply by heating, with the added advantage of producing microfluidic channels with embedded chemical functionalities. After thermal bonding, the microfluidic devices underwent cohesive failure (rupture of the elastomer layer) at ∼145 kPa during pressure tests, but did not exhibit adhesive failure (delamination), showing that the azide–alkyne reaction provides a strong bond between elastomer layers. Furthermore, the internal microfluidic channel surfaces retained alkyne and azide functionality during the process, as shown by the grafting of one or more fluorescent dyes, through Huisgen cyclization. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 589–597 [ABSTRACT FROM AUTHOR]

Research on the synthesis of nanomaterials using metal-organic frameworks (MOFs), which are characterized by multi-functionality and porosity, as precursors have been accomplished through various synthetic approaches. In this study, copper and copper oxide nanoparticles were fabricated within 30 min by a simple and rapid method involving the reduction of a copper(II)-containing MOF with sodium borohydride solution at room temperature. The obtained nanoparticles consist of a copper core and a copper oxide shell exhibited catalytic activity in the oxygen reduction reaction. The as-synthesized Cu@Cu2O core-shell nanocatalyst exhibited an enhanced limit current density as well as onset potential in the electrocatalytic oxygen reduction reaction (ORR). Moreover, the nanoparticles exhibited good catalytic activity in the Huisgen cycloaddition of various substituted azides and alkynes under mild reaction conditions. [ABSTRACT FROM AUTHOR]

In this study, we describe the synthesis of 1,4-disustituted-1,2,3-triazolo-quinazoline ribonucleosides or acyclonucleosides by means of 1,3-dipolar cycloaddition between various O or N-alkylated propargyl-quinazoline and 1'-azido-2',3',5'-tri-O-benzoylribose or activated alkylating agents under microwave conditions. None of the compounds selected showed significant anti-HCV activity in vitro.

A new non-symmetrical zinc(II) phthalocyanine (ZnPc) with an alkynyl functional group was prepared by an efficient mixed statistical condensation of 4-((4-ethynylbenzyl)oxy)phthalonitrile ( 1 ) and 4-(4- tert -butylphenoxy)phthalonitrile ( 2 ). The isolated unsymmetrical phthalocyanine molecule with additional three 4- tert -butylbenzyloxy groups to maintain solubility was used in the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition, better known as the “click chemistry”, as one of the precursors. The second component of the click reaction was polystyrene (PS) which was obtained by atom transfer radical polymerization (ATRP) and then its bromo end group was converted to azide by treatment with sodium azide. FT-IR, 1 H-NMR, 13 C-NMR, MALDI TOF MS, UV–Vis, GPC, and elemental analysis techniques were used to characterize the precursors and targeted ZnPc-functionalized polystyrene. Molecular weight of obtained polymer was examined by gel permeation chromatography (GPC), thermal properties were also evaluated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). It is observed that thermal stability of PS-ZnPc has been improved owing to high thermal stability of phthalocyanine group. Surface properties of PS-ZnPc thin films investigated by contact angle measurements indicate that it has more hydrophobic character when compared with PS-Br film. [ABSTRACT FROM AUTHOR]

A series of substituted diaryltriazoles was prepared by a solid-phase-synthesis protocol using a modified Wang resin. The copper(I)- or ruthenium(II)-catalyzed 1,3-cycloaddition on the polymer bead allowed a rapid synthesis of the target compounds in a parallel fashion with in many cases good to excellent yields. Substituted diaryltriazoles resemble a molecular structure similar to established terphenyl-alpha-helix peptide mimics and have therefore the potential to act as selective inhibitors for protein–protein interactions.

This article deal with the parallel synthesis of a 96 product-sized library using a polymer-based copper catalyst that we developed which can be easily separated from the products by simple filtration. This gave us the opportunity to use this catalyst in an automated chemical synthesis station (Chemspeed ASW-2000). Studies and results about the preparation of the catalyst, its use in different solvent systems, its recycling capabilities and its scope and limitations in the synthesis of this library will be addressed. The synthesis of the triazole library and the very good results obtained will finally be discussed.

Binary polystyrene and poly(4-vinylpyridine) mixed grafted silica nanoparticles (PSt/P4VP-g-SNPs) are fabricated using CuI-catalyzed azide-alkyne Huisgen cycloaddition (CuAAC) via grafting-to method. Azide-terminated PSt and P4VP are synthesized via post- and pre-atom transfer radical polymerization modification, respectively. Then, the polymers are simultaneously anchored onto alkyne-modified SNPs by CuAAC yielding mixed brushes as shown by Raman spectroscopy, dynamic light scattering, and thermogravimetric analysis. To the best of our knowledge, this is the first report of simultaneously grafting two distinct polymer chains to synthesize mixed grafted silica nanoparticles using CuAAC technique via grafting-to method. [ABSTRACT FROM AUTHOR]

The synthesis of the four stereoisomers of a new 1,2,3-triazole analogue of rhizobitoxine from serine is described. The key step is a Huisgen 1,3-dipolar cycloaddition on an ethynylglycine synthon. [ABSTRACT FROM AUTHOR]

In order to find novel bioactive compounds with significant antifungal activities, a series of novel 1,4-disubstituted 1,2,3-triazoles containing an indole ring via CuCl2/Zn-catalyzed Huisgen cycloaddition were designed, synthesized, and characterized. Antifungal activity against colletotrichum capsici and cotton physalospora pathogens of all the prepared compounds was evaluated, and the test results indicated that these compounds, especially 4g and 4h, showed significant inhibitory effects for fungi. All the synthesized compounds have been characterized by IR, NMR, and high-resolution mass spectra experiments. The preliminary structure activity relationship is also discussed in this paper. [ABSTRACT FROM AUTHOR]

The development of novel anti-HIV agents remains an important medicinal chemistry challenge given that no cure for the disease is imminent, and the continued use of current NNRTIs inevitably leads to problems associated with resistance. Inspired by the pyrazole-containing NNRTI lersivirine (LSV), we embarked upon a study to establish whether 1,2,3-triazole heterocycles could be used as a new scaffold for the creation of novel NNRTIs. An especially attractive feature of triazoles used for this purpose is the versatility in accessing variously functionalised systems using either the thermally regulated Huisgen cycloaddition, or the related ‘click’ reaction. Employing three alternative forms of these reactions, we were able to synthesise a range of triazole compounds and evaluate their efficacy in a phenotypic HIV assay. To our astonishment, even compounds closely mimicking LSV were only moderately effective against HIV. [ABSTRACT FROM AUTHOR]

The mechanisms of three cascade reactions between N -methylindole and sulfonylazides via Huisgen cycloaddition were investigated using density functional theory, and the polarized continuum model (PCM) was applied to simulate the solvent effects. Fukui functions and dual descriptor have been employed to assess the atomic reactivity. With respect to these three reactions, each has two possible reaction pathways (I and II). The calculated results show that singlet O 2 plays a crucial role in the oxidative dehydrogenation process in the first reaction between 2-imine indole and p-tosylazide (TsN 3 ), when the reaction occurs without O 2 but with N 2 , two pathways via the processes of breaking two covalent bonds, followed by 1,2-H shift and N 2 removal (or by N 2 removal and 1,2-H shift) exist. Water molecule plays an important role in the H-shift process in the third reaction of the methyl substituted N -methylindole with TsN 3 . Our results demonstrated that these reactions can take place at certain condition, in good agreement with the experimental observation. The understanding of the competitive pathways for Huisgen cycloaddition of N -methylindole and sulfonylazides can provide valuable insights into related reactions. [ABSTRACT FROM AUTHOR]

A series of novel indole derivatives linked with the 1,2,3-triazole moiety was designed, synthesised by the CuCl2/Zn-catalysed Huisgen cycloaddition and characterised. The antifungal activity of all the prepared compounds against Colletotrichum capsici and cotton Physalospora pathogens was evaluated and the results indicated that these compounds showed inhibitory effect for fungi and the inhibition ratio of the best was up to 83.3%. The preliminary structure-activity relationship is also discussed in this paper. [ABSTRACT FROM AUTHOR]

A set of fifteen triterpenoid pyrazines and pyridines was prepared from parent triterpenoid 3-oxoderivatives (betulonic acid, dihydrobetulonic acid, oleanonic acid, moronic acid, ursonic acid, heterobetulonic acid, and allobetulone). Cytotoxicity of all compounds was tested in eight cancer and two non-cancer cell lines. Evaluation of the structure-activity relationships revealed that the triterpenoid core determined whether the final molecule is active or not, while the heterocycle is able to increase the activity and modulate the specificity. Five compounds (1b , 1c , 2b , 2c , and 8) were found to be preferentially and highly cytotoxic (IC 50 ≈ 1 μM) against leukemic cancer cell lines (CCRF-CEM, K562, CEM-DNR, or K562-TAX). Surprisingly, compounds 1c , 2b , and 2c are 10-fold more active in multidrug-resistant leukemia cells (CEM-DNR and K562-TAX) than in their non-resistant analogs (CCRF-CEM and K562). Pharmacological parameters were measured for the most promising candidates and two types of prodrugs were synthesized: 1) Sugar-containing conjugates, most of which had improved cell penetration and retained high cytotoxicity in the CCRF-CEM cell line, unfortunately, they lost the selectivity against resistant cells. 2) Medoxomil derivatives, among which compounds 26 – 28 gained activities of IC 50 0.026–0.043 μM against K562 cells. Compounds 1b , 8 , 21 , 22 , 23 , and 24 were selected for the evaluation of the mechanism of action based on their highest cytotoxicity against CCRF–CEM cell line. Several experiments showed that the majority of them cause apoptosis via the mitochondrial pathway. Compounds 1b , 8 , and 21 inhibit growth and disintegrate spheroid cultures of HCT116 and HeLa cells, which would be important for the treatment of solid tumors. In summary, compounds 1b , 1c , 2b , 2c , 24 , and 26 – 28 are highly and selectively cytotoxic against cancer cell lines and were selected for future in vivo tests and further development of anticancer drugs. [Display omitted] • Triterpenoid pyridines and pyrazines were prepared and their cytotoxicity tested. • Pharmacological parameters and selectivity were optimized by prodrug synthesis. • Most active compounds cause apoptosis via the intrinsic pathway. • Compounds 1b , 1c , 2b , 2c , 24 , and 26 – 28 were selected for further development. [ABSTRACT FROM AUTHOR]

Chitosan-based glycopolymers having multiple β-lactosides exclusively at their C6-positions were successfully synthesized from partially deacetylated chitin through perfect N -deacetylation/phthaloylation and C6-selective bromination/azidation to afford 6-azide-6-deoxy- N -phthaloyl-chitosan and the subsequent Cu + -catalyzed Huisgen cycloadditions using alkyne-terminated β-lactoside and/or quaternary ammonium modules followed by dephthaloylations. Lectin-affinities of the resultant chitosan-based glycopolymers were assessed through fluorescence titration assays to show their unique sigmoidal binding profiles with amplified binding constants. [ABSTRACT FROM AUTHOR]

The copper catalyzed azide-alkyne cycloaddition (CuAAC), known as “click reaction” is a well-known method used for the construction of complex molecular architectures. Due to its efficiency it has been applied in the porphyrin synthesis in order to prepare elaborated architectures and sophisticated molecules with various applications. Also, this strategy allows the installment of useful functionalities, in the form of polar and function-rich 1,2,3-triazole moieties, directly attached on the porphyrin ring. In this review we summarize the use of click reaction for the synthesis of porphyrin based compounds and the reaction conditions used in each example. All the examples presented herein concern the type and the place of the substrate present on the porphyrin ring. More specifically, this manuscript is divided in two sections where in the first part click reaction using alkynyl porphyrins and in the second part using azido porphyrins are discussed. These main sections are divided in subsections where alkynyl and azido groups are present on the meso -phenyl ring, on an aliphatic chain and on the β -position of the porphyrin ring. [ABSTRACT FROM AUTHOR]

Cellulose fibres have poor reactivity and limited potential for surface engineering with advanced chemical functionalization in water. In this work, cellulose fibres were decorated with azide functions by charge-directed self-assembly of a novel water-soluble multifunctional cellulose derivative yielding reactive fibres. Propargylamine and 1-ethynylpyrene were utilized as a proof of concept that alkyne molecules may react with the azide functions of the reactive fibres via copper(I)-catalyzed azide-alkyne Huisgen cycloaddition (CuAAc) reaction in mild conditions. Chemical characterization of the fibres was carried out using classical techniques such as Raman-, fluorescence-, and UV–vis spectroscopy. Among other techniques, time-of-flight secondary ion mass spectrometry (ToF-SIMS), X-ray spectroscopy (XPS), two-photon microscopy (TPM), and inductively coupled plasma mass spectrometry (ICP-MS) were useful tools for additional characterization of the fibres decorated with amino- or photoactive groups. The information gathered in this work might contribute to the basis for the preparation of reactive cellulose-based interfaces with potential application in CuAAc reactions. [ABSTRACT FROM AUTHOR]

A very mild and highly efficient synthesis of some novel 1 H-1,2,3-triazolyl carboacyclic nucleosides via a 'Click' Huisgen cycloaddition of N-propargyl nucleobases and azido alcohols using Cu/aminoclay/reduced graphene oxide nanohybrid (Cu/AC/r-GO nanohybrid) as nanocatalyst is described. The preparation and characterization of Cu/AC/r-GO nanohybrid are discussed. This catalyst was characterized by X-ray diffraction, FT-IR, TEM, and energy-dispersive analysis of X-ray techniques. Cu/AC/r-GO nanohybrid is a stable and highly efficient heterogeneous nanocatalyst that can be easily prepared, used, and restored from the reaction mixture by simple filtration, and reused for many consecutive trials without significant decrease in activity. [ABSTRACT FROM AUTHOR]

New functionalized 1,2,3-triazoloquinolines were achieved by intramolecular azide-alkyne Huisgen [3+2] cycloaddition. These derivatives were synthesized via the key Baylis-Hillman adduct under mild, neutral conditions in short duration and consistently good yield. The structures of final compounds were characterized by spectral analysis. Antifungal activities of these analogues against Trichophyton mentagrophytes, Candida albicans, and Aspergillus niger were also assayed. [ABSTRACT FROM AUTHOR]

We report the successful combination of the convergent ‘click coupling’ of the divergently derived dendrons for synthesizing poly(aminoester) dendrimers. The concept of integrating ‘click’ chemistry into the combined convergent/divergent strategy has proven beneficial and rewarding, allowing the otherwise lengthy synthesis of poly(aminoester) dendrimers to be achieved with reduced synthetic steps and improved yields. [ABSTRACT FROM AUTHOR]

Racemic 1′- homo- 3′-isoazanucleosides have been obtained by microwave-assisted 1,3-dipolar cycloaddition of 3,5-disubstituted proline derivative (±)- 2 with different alkynes. The compounds obtained were evaluated for their cytotoxic activities in vitro against human breast carcinoma cell lines (MCF-7), human ovary carcinoma cell lines (A2780) and human lung carcinoma cell lines (NCI–H460). [ABSTRACT FROM AUTHOR]

The synthesis of α,γ-diazido-α,β-unsaturated esters is carried out via a Lewis acid-mediated 1,3-diazidation of α,α-dimethoxy-β,γ-unsaturated esters using two equivalents of trimethylsilyl azide. The reaction proceeds in a highly stereoselective manner to provide only the ( Z )-stereoisomers of the diazide products. The optimization and scope of the new method are discussed, and the utility of the products is demonstrated in the synthesis of bis-1,2,3-triazole derivatives. [ABSTRACT FROM AUTHOR]

Dendrimers are monodisperse polymers grown in a fractal manner from a central point. They are poised to become the cornerstone of nanoscale devices in several fields, ranging from biomedicine to light-harvesting. Technical difficulties in obtaining these molecules has slowed their transfer from academia to industry. In 2001, the arrival of the "click chemistry" concept gave the field a major boost. The flagship reaction, a modified Hüisgen cycloaddition, allowed researchers greater freedom in designing and building dendrimers. In the last five years, advances in click chemistry saw a wider use of other click reactions and a notable increase in the complexity of the reported structures. This review covers key developments in the click chemistry field applied to dendrimer synthesis from 2010 to 2015. Even though this is an expert review, basic notions and references have been included to help newcomers to the field. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of thiazolidine-4-one derivatives as dual EGFR/CDK2 inhibitors has been developed. • Compounds 5d , 5e , and 5f were the most active antiproliferative agents. • Compounds 5d , 5e , and 5f display potent antiproliferative activity with strong inhibition of EGFR/CDK2. • Docking study revealed high binding affinities toward EGFR and CDK2. A series of novel thiazolidine-4-one derivatives was synthesized by reacting 1,4-disubstituted hydrazine carbothioamides with diethyl azodicarboxylate. The structures were confirmed by spectroscopic data as well as single-crystal X-ray analyses. The antiproliferative activity of the synthesized compounds was investigated against four human cancer cell lines using an MTT assay. Compounds 5d , 5e , and 5f revealed the most potent antiproliferative activity with GI 50 values ranging from 0.70 µM to 1.20 µM, compared to doxorubicin GI 50 value = 1.10 µM. Compounds 5d , 5e , and 5f were further investigated for their inhibitory activities against CDK2 and EGFR as potential targets for their molecular mechanism. Compounds 5e and 5f have showed potent inhibitory activity to CDK2 enzyme with IC 50 values of 18 and 14 nM, which is more potent than the reference dinaciclib (IC 50 = 20 nM). Moreover, compounds 5e and 5f were the most potent EGFR inhibitors, with IC 50 values of 93 and 87 nM, respectively, compared to the reference erlotinib (IC 50 = 70 nM). In addition, the most potent derivatives were tested for their apoptotic activity against caspases 3, 8, and 9, and the results showed that compounds 5d , 5e , and 5f revealed a greater increase in active caspases 3,8 and 9 than doxorubicin. Also, compounds 5d , 5e , and 5f elevated cytochrome C levels in the MCF-7 human breast cancer cell line by about 15.5, 15.8, and 16.5 times, respectively. Finally, a molecular docking study was performed to investigate the binding sites of these compounds within the active sites of CDK2 and EGFR targets, and the results confirmed that the most potent CDK2 and EGFR inhibitor 5h also have showed the highest docking score. [ABSTRACT FROM AUTHOR]

Preliminary results on a novel zinc-mediated, ultrasound-promoted chain extension of glycofuranosylamines with a propargyl group are reported. The procedure was applied to D-arabino and D-xylo substrates to give, via Cram-chelate transition states, 1-C-1-(3-trimethylsilyl-2-propynyl)-1-benzylamino pentionols in moderate to good yields and acceptable stereoselectivities (syn/anti ≥4:1). To apply the reaction to the synthesis of galactofuranoside mimics, the D-xylo intermediate was cyclized to afford a 1-C-1-(2-propynyl)-1,4-dideoxy-1,4-imino-L-arabinitol derivative in excellent yield. This building block was used in three examples of CuAAC click reactions with azide compounds to provide the corresponding galactofuranoside mimics. [ABSTRACT FROM AUTHOR]

Synthesis of a novel class of natural product inspired cinnamyl-containing 1,4,5-triazole and the potent inhibition of human aromatase (CYP 450 19A1) by select members is described. Structure–activity data generated provides insights into the requirements for potency particularly the inclusion of an aryl bromide or chloride residue as a keto-bioisostere. [ABSTRACT FROM AUTHOR]

2H-1,2,3-Triazoles (2) were synthesized by [3+2] cycloaddition of (Z)-2,3-diaryl substituted acrylonitriles (1) with sodium azide and ammonium chloride in DMF/water. This method represents a facile and efficient reaction procedure for the synthesis of 4,5-diaryl-2H-1,2,3-triazoles in modest to good yields. [ABSTRACT FROM AUTHOR]

The O-linked β- N-acetylglucosamine (O- GlcNAc) posttranslational modification was first discovered 30 years ago and is highly concentrated in the nuclear pore. In the years since the discovery of this single sugar modification, substantial progress has been made in understanding the biochemistry of O- GlcNAc and its regulation. Nonetheless, O- GlcNAc modification of proteins continues to be overlooked, due in large part to the lack of reliable methods available for its detection. Recently, a new crop of immunological and chemical detection reagents has changed the research landscape. Using these tools, approximately 1000 O- GlcNAc-modified proteins have been identified. While other forms of glycosylation are typically associated with extracellular proteins, O- GlcNAc is abundant on nuclear and cytoplasmic proteins. In particular, phenylalanine-glycine nucleoporins are heavily O- GlcNAc-modified. Recent experiments are beginning to provide insight into the functional implications of O- GlcNAc modification on certain proteins, but its role in the nuclear pore has remained enigmatic. However, tantalizing new results suggest that O- GlcNAc may play roles in regulating nucleocytoplasmic transport. [ABSTRACT FROM AUTHOR]

Abstract: Positron emission tomography (PET) is a highly sensitive quantitative imaging technique for studying molecular pathways and interactions in vivo. This imaging technique plays a key role in drug discovery, pharmacokinetics, pharmacodynamics, and assessing in vivo distribution. In this study, we designed an ethynylbenzene-substituted glycol (ME) as a versatile probe for PET labeling of oligonucleotides through a click reaction. [Copyright &y& Elsevier]

In this study, we describe the synthesis of 1,4-disustituted-1,2,3-triazoloquinazoline ribonucleosides or acyclonucleosides by means of 1,3-dipolar cycloaddition between various O or N-alkylated propargyl-quinazoline and 1'-azido-2',3',5'-tri-Obenzoylribose or activated alkylating agents under microwave conditions. None of the compounds selected showed significant anti-HCV activity in vitro. [ABSTRACT FROM AUTHOR]

Abstract: Synthesis of unsymmetrically terminalalkynyl substituted zinc (II) phthalocyanine (ZnPc) through an efficient statistical condensation reaction with the unprotected phthalonitrile (2) is reported for the first time. Isolated ZnPc bearing one terminalalkynyl group is a good precursor for Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction which is classified under the term “click chemistry”. This was approved by the successful click reaction between ZnPc and azide end-functional well-defined polymers obtained by atom transfer radical polymerization (ATRP), and consecutive azidation of corresponding bromo end-functional polymers. The click-reaction efficiencies for the formation of Pc-end functional poly(tert-butyl acrylate) (PtBA), and polystyrene (PS) have been found to be 75, 93% respectively. Functionalization of ZnPc with PS increased the chemical stability of the complex but decreased the electrochemical reversibility during redox reactions. In-situ electrocolorimetric measurements of the complexes allowed the quantification of color coordinates of the each electrogenerated anionic and cationic redox species. [Copyright &y& Elsevier]

Highlights: [•] Alkyl triazole xylopyranosides were synthesized from xylose using ‘click chemistry’. [•] Alkyl triazole xylopyranosides were moderately toxic to non-toxic in cells in culture. [•] Alkyl xylopyranosides with intermediate chain length caused apoptosis, not necrosis. [•] Long chain alkyl xylopyranosides form stable monolayers at the air–water interface. [ABSTRACT FROM AUTHOR]

A small library of compounds was prepared by a combination of toluene dioxygenase (TDO)-catalyzed enzymatic dihydroxylation and copper(I)-catalyzed Hüisgen cycloaddition. Some compounds were obtained by coupling an alkyne and a conduritol derivative, while more complex structures were obtained by a double Hüisgen reaction of a dialkyne and two molecules of the cyclitol. The compounds were fully characterized and subjected to preliminary biological screening. [ABSTRACT FROM AUTHOR]

A model octapeptide segment derived from vasoactive intestinal peptide (VIP) was utilised to investigate the effect of several conventional cyclisation methods on the α-helical conformation in short peptide fragments. Three of the classical macrocyclisation techniques (i.e. lactamisation, ring-closing metathesis and Huisgen cycloaddition) were applied, and the conformations of the resulting cyclic peptides, as well as their linear precursors, were compared by CD analysis. The visibly higher folding propensity of the triazole-tethered peptide after azide-alkyne CuAAC macrocyclisation illustrates that the secondary structure of a short peptide fragment can differ significantly depending on the chemical strategy used to covalently cross-link side chain residues in a 'helical' fragment. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]