Showing papers on "Click chemistry published in 2016"
TL;DR: This review highlights the successful advancement of Cu(I)-catalyzed click chemistry in glycoscience and its applications as well as future scope in different streams of applied sciences.
Abstract: Cu(I)-catalyzed azide–alkyne 1,3-dipolar cycloaddition (CuAAC), popularly known as the “click reaction”, serves as the most potent and highly dependable tool for facile construction of simple to complex architectures at the molecular level. Click-knitted threads of two exclusively different molecular entities have created some really interesting structures for more than 15 years with a broad spectrum of applicability, including in the fascinating fields of synthetic chemistry, medicinal science, biochemistry, pharmacology, material science, and catalysis. The unique properties of the carbohydrate moiety and the advantages of highly chemo- and regioselective click chemistry, such as mild reaction conditions, efficient performance with a wide range of solvents, and compatibility with different functionalities, together produce miraculous neoglycoconjugates and neoglycopolymers with various synthetic, biological, and pharmaceutical applications. In this review we highlight the successful advancement of Cu(I)...
557 citations
TL;DR: This review describes the general features and applications of CuAAC in organic synthesis (CuAAC-OS), highlighting the suitability of this kind of reaction for peptides, nucleotides, small molecules, supramolecular structures, and polymers among others.
227 citations
TL;DR: The problems associated with the use of the click reaction in living cells are discussed and important complementary techniques for photo-affinity probes based on the click chemistry reaction are provided.
Abstract: Small-molecule fluorescent probes have been widely used in target identification, but this method has many disadvantages For example, the identified proteins are usually complex, and additional biochemical studies are needed to distinguish real targets from interference results To address this problem, we propose a series of strategies for improving the efficiency of target identification First, pretreatment with a lower concentration of hydrogen peroxide can shield against thiol interference Second, the use of benzophenone as a photo-affinity group is not appropriate, and diazirines are preferred Third, if cytoskeleton proteins or stress proteins are captured, the interference must be carefully eliminated The specificity of target identification can be improved by optimizing these three strategies In this paper, we discuss the problems associated with the use of the click reaction in living cells and provide important complementary techniques for photo-affinity probes based on the click chemistry reaction
216 citations
TL;DR: A copper(I)-catalyzed interrupted click reaction to access diverse 5-functionalized triazoles is reported, which features a broad substrate scope and good functional group compatibility.
Abstract: The 5-heterofunctionalized triazoles are important scaffolds in bioactive compounds, but current click reactions (CuAAC) cannot produce these core structures. A copper(I)-catalyzed interrupted click reaction to access diverse 5-functionalized triazoles is reported. Various 5-amino-, thio-, and selenotriazoles were readily assembled in one step in high yields. The reaction proceeds under mild conditions with complete regioselectivity. It also features a broad substrate scope and good functional group compatibility.
184 citations
183 citations
TL;DR: A broad overview of the first 10 years of research at the intersection of click chemistry and radiochemistry is provided, inspiring synthetic chemists and radiochemists alike to harness click chemistry in even more innovative and ambitious ways as they embark upon the second decade of this fruitful collaboration.
180 citations
TL;DR: The general features and applications of CuAAC in solid-phase synthesis (CuAAC-SP) are described, highlighting the suitability of this kind of reaction for peptides, nucleotides, small molecules, supramolecular structures, and polymers, among others.
Abstract: Click chemistry is an approach that uses efficient and reliable reactions, such as Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC), to bind two molecular building blocks. CuAAC has broad applications in medicinal chemistry and other fields of chemistry. This review describes the general features and applications of CuAAC in solid-phase synthesis (CuAAC-SP), highlighting the suitability of this kind of reaction for peptides, nucleotides, small molecules, supramolecular structures, and polymers, among others. This versatile reaction is expected to become pivotal for meeting future challenges in solid-phase chemistry.
159 citations
TL;DR: The probe is water soluble and non-fluorescent due to the dissipation of energy through free molecular motion of the AIEgen, but the fluorescence is immediately turned on upon click reaction with azide-functionalized glycans on cancer cell surface.
Abstract: Bioorthogonal turn-on probes have been widely utilized in visualizing various biological processes. Most of the currently available bioorthogonal turn-on probes are blue or green emissive fluorophores with azide or tetrazine as functional groups. Herein, we present an alternative strategy of designing bioorthogonal turn-on probes based on red-emissive fluorogens with aggregation-induced emission characteristics (AIEgens). The probe is water soluble and non-fluorescent due to the dissipation of energy through free molecular motion of the AIEgen, but the fluorescence is immediately turned on upon click reaction with azide-functionalized glycans on cancer cell surface. The fluorescence turn-on is ascribed to the restriction of molecular motion of AIEgen, which populates the radiative decay channel. Moreover, the AIEgen can generate reactive oxygen species (ROS) upon visible light (λ=400-700 nm) irradiation, demonstrating its dual role as an imaging and phototherapeutic agent.
159 citations
TL;DR: The wide range of applications for thiol-ene hydrogels are reviewed, from the prolonged release of anti-inflammatory drugs in the spine to the release of protein-based therapeutics in response to cell-secreted enzymes, with a focus on their clinical relevance.
Abstract: Hydrogels are of growing interest for the delivery of therapeutics to specific sites in the body. For use as a delivery vehicle, hydrophilic precursors are usually laden with bioactive moieties and then directly injected to the site of interest for in situ gel formation and controlled release dictated by precursor design. Hydrogels formed by thiol–ene click reactions are attractive for local controlled release of therapeutics owing to their rapid reaction rate and efficiency under mild aqueous conditions, enabling in situ formation of gels with tunable properties often responsive to environmental cues. Herein, we will review the wide range of applications for thiol–ene hydrogels, from the prolonged release of anti-inflammatory drugs in the spine to the release of protein-based therapeutics in response to cell-secreted enzymes, with a focus on their clinical relevance. We will also provide a brief overview of thiol–ene click chemistry and discuss the available alkene chemistries pertinent to macromolecule ...
156 citations
TL;DR: It is shown that copper-containing metal-organic nanoparticles (MONPs) are readily synthesized via Cu(II)-mediated intramolecular cross-linking of aspartate-containing polyolefins in water via In situ reduction with sodium ascorbate, yielding Cu(I)-containing MONPs that serve as highly efficient supramolescular catalysts for alkyne-azide "click chemistry" reactions, yielding the desired 1,4-adducts
Abstract: We show that copper-containing metal–organic nanoparticles (MONPs) are readily synthesized via Cu(II)-mediated intramolecular cross-linking of aspartate-containing polyolefins in water. In situ reduction with sodium ascorbate yields Cu(I)-containing MONPs that serve as highly efficient supramolecular catalysts for alkyne–azide “click chemistry” reactions, yielding the desired 1,4-adducts at low parts per million catalyst levels. The nanoparticles have low toxicity and low metal loadings, making them convenient, green catalysts for alkyne–azide “click” reactions in water. The Cu-MONPs enter cells and perform efficient, biocompatible click chemistry, thus acting as intracellular nanoscale molecular synthesizers.
155 citations
TL;DR: Application in polysaccharide modification of six groups of click reactions are reviewed, including CuAAC, metal-free [3+2] cycloaddition, Diels–Alder reaction, oxime click, Thiol-Michael reaction, and thiol-ene reaction, as well as one click-like reaction that is the subject of the authors' own research, olefin cross-metathesis.
TL;DR: Tetrazoles were incorporated into Bodipy and Acedan dyes, providing novel photo-crosslinkers with one- and two-photon fluorescence Turn-ON properties that may be developed into protein-detecting biosensors that are capable of photoinduced, no-wash imaging of endogenous kinase activities in live mammalian cells.
Abstract: The bioorthogonality of tetrazole photoclick chemistry has been reassessed. Upon photolysis of a tetrazole, the highly reactive nitrile imine formed undergoes rapid nucleophilic reaction with a variety of nucleophiles present in a biological system, along with the expected cycloaddition with alkenes. The alternative use of the tetrazole photoclick reaction was thus explored: tetrazoles were incorporated into Bodipy and Acedan dyes, providing novel photo-crosslinkers with one- and two-photon fluorescence Turn-ON properties that may be developed into protein-detecting biosensors. Further introduction of these photo-activatable, fluorogenic moieties into staurosporine resulted in the corresponding probes capable of photoinduced, no-wash imaging of endogenous kinase activities in live mammalian cells.
TL;DR: The efforts of late in developing the fundamental principles and practical applications of a new copper-free click reaction - namely, cooperative capture synthesis, whereby introducing a cyclodextrin (CD) as an accelerator in CB-AAC, hydrogen bonding networks are formed between the rims of CD and CB6 in a manner that is positively cooperative, giving rise to a high level of pre-organisation during efficient and quick rotaxane formation.
Abstract: Click chemistry describes a family of modular, efficient, versatile and reliable reactions which have acquired a pivotal role as one of the most useful synthetic tools with a potentially broad range of applications. While copper(I)-catalysed alkyne–azide cycloaddition is the most widely adopted click reaction in the family, the fact that it is cytotoxic restricts its practice in certain situations, e.g., bioconjugation. Consequently, researchers have been exploring the development of copper-free click reactions, the most popular example so far being strain-promoted alkyne–azide cycloadditions. An early example of copper-free click reactions that is rarely mentioned in the literature is the cucurbit[6]uril (CB6) catalysed alkyne–azide cycloaddition (CB-AAC). Despite the unique ability of CB-AAC to generate mechanically interlocked molecules (MIMs) – in particular, rotaxanes – its slow reaction rate and narrow substrate acceptance limit its scope. In this Tutorial Review, we describe our efforts of late in developing the fundamental principles and practical applications of a new copper-free click reaction – namely, cooperative capture synthesis, whereby introducing a cyclodextrin (CD) as an accelerator in CB-AAC, hydrogen bonding networks are formed between the rims of CD and CB6 in a manner that is positively cooperative, giving rise to a high level of pre-organisation during efficient and quick rotaxane formation. For example, [4]rotaxanes can be prepared nearly quantitatively within a minute in water. Furthermore, we have demonstrated that CB-AAC can accommodate a wider substrate tolerance by introducing pillararenes as promoters. To date, we have put cooperative capture synthesis into practice by (i) preparing polyrotaxanes containing up to 200 rings in nearly quantitative yields, (ii) trapping conformational isomers of polymacrocycles as rings in rotaxanes, (iii) demonstrating solid-state fluorescence and Forster resonance energy transfer (FRET) processes by fixing the fluorophores in a rotaxane and (iv) establishing the principle of supramolecular encryption in the preparation of dynamically and reversibly tunable fluorescent security inks.
TL;DR: In this article, the authors present a review of various reliable heterogeneous methods, alternative to the commonly used Meldal-Sharpless method for click chemistry, including those involving flow chemistry, and that they could be applied to a variety of compounds, solving some problems faced by more conventional methods.
TL;DR: The rapid assembly and in situ screening of focused combinatorial fragment libraries using CuAAC click chemistry is a highly robust and efficient strategy for establishing SAR and for discovering bioactive molecules.
TL;DR: The efforts in the development of CuAAC are discussed to better fit the bioorthogonal reaction criteria and its bioorthogsonal applications both in vivo and in vitro.
Abstract: The emergence of bioorthogonal reactions has greatly broadened the scope of biomolecule labeling and detecting. Of all the bioorthogonal reactions that have been developed, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is the most widely applied one, mainly because of its relatively fast kinetics and high efficiency. However, the introduction of copper species to in vivo systems raises the issue of potential toxicity. In order to reduce the copper-induced toxicity and further improve the reaction kinetics and efficiency, different strategies have been adopted, including the development of diverse copper chelating ligands to assist the catalytic cycle and the development of chelating azides as reagents. Up to now, the optimization of CuAAC has facilitated its applications in labeling and identifying either specific biomolecule species or on the omics level. Herein, we mainly discuss the efforts in the development of CuAAC to better fit the bioorthogonal reaction criteria and its bioorthogonal applications both in vivo and in vitro.
TL;DR: Gelatin polymers with pendant norbornene or tetrazine groups can quickly and spontaneously crosslink upon mixing, allowing for high viability of encapsulated cells, establishment of 3D elongated cell morphologies, and biodegradation when injected in vivo.
Abstract: Injectable gelatin hydrogels formed with bioorthogonal click chemistry (ClickGel) are cell-responsive ECM mimics for in vitro and in vivo biomaterials applications. Gelatin polymers with pendant norbornene (GelN) or tetrazine (GelT) groups can quickly and spontaneously crosslink upon mixing, allowing for high viability of encapsulated cells, establishment of 3D elongated cell morphologies, and biodegradation when injected in vivo.
TL;DR: The β-arylethenesulfonyl fluorides are found to be selectively addressable bis-electrophiles for sulfur(VI) fluoride exchange (SuFEx) click chemistry, in which either the alkenyl moiety or the sulfonyl fluoride group can be the exclusive site of nucleophilic attack under defined conditions, making these rather simple cores attractive for covalent drug discovery.
Abstract: A Heck–Matsuda process for the synthesis of the otherwise difficult to access compounds, β-arylethenesulfonyl fluorides, is described. Ethenesulfonyl fluoride (i.e., vinylsulfonyl fluoride, or ESF) undergoes β-arylation with stable and readily prepared arenediazonium tetrafluoroborates in the presence of the catalyst palladium(II) acetate to afford the E-isomer sulfonyl analogues of cinnamoyl fluoride in 43–97 % yield. The β-arylethenesulfonyl fluorides are found to be selectively addressable bis-electrophiles for sulfur(VI) fluoride exchange (SuFEx) click chemistry, in which either the alkenyl moiety or the sulfonyl fluoride group can be the exclusive site of nucleophilic attack under defined conditions, making these rather simple cores attractive for covalent drug discovery.
TL;DR: Recent progress is highlighted on the current and emerging strategies to introduce functional groups to the C-5 position of triazoles in a regioselective manner.
TL;DR: Some of the progress is summarized, covering the period 2010 to mid-2015, in Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition CuAAC "click chemistry" of carbohydrate derivatives, in the context of potential therapeutic and diagnostic tool development.
TL;DR: In this article, the potential of externally stimulated click reactions in the preparation of various macromolecular structures is discussed along with the selected examples, which can be used in a wide variety of research areas, including materials sciences, polymer chemistry, and pharmaceutical science.
TL;DR: In this article, a review of the oxime click reaction for the development of functional polymeric materials is presented, focusing on the use of oxime carbonyl-condensations for the synthesis of self-healing and dynamic polymers.
TL;DR: Efficient metal-free photoredox pathway to the thiol–yne click reaction is described using Eosin Y as a catalyst and dedicated 3D-printed photoreactor.
Abstract: The carbon–sulfur bond formation reaction is of paramount importance for functionalized materials design, as well as for biochemical applications. The use of expensive metal-based catalysts and the consequent contamination with trace metal impurities are challenging drawbacks of the existing methodologies. Here, we describe the first environmentally friendly metal-free photoredox pathway to the thiol–yne click reaction. Using Eosin Y as a cheap and readily available catalyst, C–S coupling products were obtained in high yields (up to 91%) and excellent selectivity (up to 60 : 1). A 3D-printed photoreactor was developed to create arrays of parallel reactions with temperature stabilization to improve the performance of the catalytic system.
TL;DR: In this article, the authors discuss the fundamental aspects of the thiol-epoxy reaction and its utility in the preparation and post-polymerization functionalization of polymers and crosslinked networks.
Abstract: Base-catalyzed reaction between a thiol and an epoxide group is a simple fusion process that leads to the formation of a β-hydroxythio-ether linkage. This reaction is efficient, regio-selective, and fast. In addition, it produces a reactive hydroxyl group upon completion. Therefore, it is of considerable potential in synthesis of reactive and functional soft materials. Here, we discuss the fundamental aspects of this process, the so-called thiol-epoxy “click” reaction, and its utility in the preparation and post-polymerization functionalization of polymers and crosslinked networks. Furthermore, its application in surface modification of solid substrates is also considered. Finally, utility of multifunctional materials created using the thiol-epoxy reaction is discussed in the biomedical arena. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3057–3070
TL;DR: The synthesis and reactivity of 4-fluorosydnones, a unique class of mesoionic dipoles displaying exquisite reactivity towards both copper-catalyzed and strain-promoted cycloaddition reactions with alkynes, are reported.
Abstract: We report the synthesis and reactivity of 4-fluorosydnones, a unique class of mesoionic dipoles displaying exquisite reactivity towards both copper-catalyzed and strain-promoted cycloaddition reactions with alkynes. Synthetic access to these new mesoionic compounds was granted by electrophilic fluorination of σ-sydnone Pd(II) precursors in the presence of Selectfluor. Their reactions with terminal and cyclic alkynes were found to proceed very rapidly and selectively, affording 5-fluoro-1,4-pyrazoles with bimolecular rate constants up to 10(4) m(-1) s(-1) , surpassing those documented in the literature with cycloalkynes. Kinetic studies were carried out to unravel the mechanism of the reaction, and the value of 4-fluorosydnones was further highlighted by successful radiolabeling with [(18) F]Selectfluor.
TL;DR: The generation of azide groups on the tumor cell surface was exogenously and specifically controlled by the amount of RR-S-Ac3 ManNAz that was fed to target tumor cells.
Abstract: Recently, metabolic glycoengineering with bioorthogonal click reactions has focused on improving the tumor targeting efficiency of nanoparticles as delivery vehicles for anticancer drugs or imaging agents. It is the key technique for developing tumor-specific metabolic precursors that can generate unnatural glycans on the tumor-cell surface. A cathepsin B-specific cleavable substrate (KGRR) conjugated with triacetylated N-azidoacetyl-d-mannosamine (RR-S-Ac3 ManNAz) was developed to enable tumor cells to generate unnatural glycans that contain azide groups. The generation of azide groups on the tumor cell surface was exogenously and specifically controlled by the amount of RR-S-Ac3 ManNAz that was fed to target tumor cells. Moreover, unnatural glycans on the tumor cell surface were conjugated with near infrared fluorescence (NIRF) dye-labeled molecules by a bioorthogonal click reaction in cell cultures and in tumor-bearing mice. Therefore, our RR-S-Ac3 ManNAz is promising for research in tumor-specific imaging or drug delivery.
TL;DR: Recent progress in the application of efficient copper-catalyzed and copper-free azide-alkyne cycloaddition (CuAAC and CuFAAC) reactions in the syntheses of dendrimers, hyperbranched polymers, star Polytriazole-based nanostructured polymers are summarized to illustrate their potential applications as self-healing polymer materials and polymer carriers for drug and imaging molecules.
Abstract: The rapid development of efficient organic click coupling reactions has significantly facilitated the construction of synthetic polymers with sophisticated branched nanostructures. This Feature Article summarizes the recent progress in the application of efficient copper-catalyzed and copper-free azide–alkyne cycloaddition (CuAAC and CuFAAC) reactions in the syntheses of dendrimers, hyperbranched polymers, star polymers, graft polymers, molecular brushes, and cyclic graft polymers. Literature reports on the interesting properties and functions of these polytriazole-based nanostructured polymers are also discussed to illustrate their potential applications as self-healing polymers, adhesives, polymer catalysts, opto-electronic polymer materials and polymer carriers for drug and imaging molecules.
TL;DR: Recent advances in the field of CuAAC are reviewed, with particular emphasis on systems immobilized onto polymeric organic or inorganic supports.
Abstract: The explosively-growing applications of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition reaction between organic azides and alkynes (CuAAC) have stimulated an impressive number of reports, in the last years, focusing on recoverable variants of the homogeneous or quasi-homogeneous catalysts. Recent advances in the field are reviewed, with particular emphasis on systems immobilized onto polymeric organic or inorganic supports.
TL;DR: A new photoelectrochemical (PEC) sensing platform has been established based on the signal amplification of click chemistry via hybridization chain reaction (HCR) for highly sensitive microRNA (miRNA) assay, showing good quantitative detection capability.
Abstract: The efficiency of photon-to-electron conversion is extremely restricted by the electron–hole recombinant. Here, a new photoelectrochemical (PEC) sensing platform has been established based on the signal amplification of click chemistry (CC) via hybridization chain reaction (HCR) for highly sensitive microRNA (miRNA) assay. In this proposal, a preferred electron donor dopamine (DA) was first assembled with designed ligation probe (probe-N3) via amidation reaction to achieve DA-coordinated signal probe (PDA-N3). The PDA-N3 served as a flexible trigger to signal amplification through efficiently suppressing the electron–hole recombinant. Specifically, the PDA-N3 can be successfully ligated into the trapped hairpins (H1 and H2) via the superior ligation method of metal-catalyst-free CC, in which the electron donor DA was introduced into the assay system. Moreover, the enzyme-free HCR, employed as a versatile amplification way, ensures that lots of PDA-N3 can be attached to the substrate. This PEC sensing for ...
TL;DR: New catalysts for copper-doped semiconductors designed to photoassist the alkyne-azide cycloaddition catalysis by Cu(I) are developed and can be readily recovered after use and reused several times.
Abstract: Copper-doped semiconductors are designed to photoassist the alkyne–azide cycloaddition catalysis by Cu(I). Upon irradiation, injection of electrons from the semiconductor into copper oxide nanostructures produces the catalytic Cu(I) species. The new catalysts are air- and moisture-tolerant and can be readily recovered after use and reused several times.