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The term "click chemistry" was introduced by K. Barry Sharpless et al. and denotes the development of a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links. Their Review in Angewandte Chemie in 2001 still ranks among the most accessed online articles in the journal.
Find all articles on click chemistry in Wiley Online Library...
Audrey Dumont, Annie Malleron, Monzer Awwad, Sam Dukan, Boris Vauzeilles
Click-Mediated Labeling of Bacterial Membranes through Metabolic Modification of the Lipopolysaccharide Inner Core [Communication]
Clicking bugs: Metabolically active Gram-negative bacteria can specifically incorporate an azide-modified analogue of 3-deoxy-D-manno-octulosonic acid (1, see scheme) into the lipopolysaccharides on their membranes. This process adds a bioorthogonal chemical reporter the cell surface and allows the rapid fluorescent labeling of viable cells by click chemistry.
Angew. Chem. Int. Ed., February 9, 2012, DOI: 10.1002/anie.201108127
Caroline Ligeour, Albert Meyer, Jean-Jacques Vasseur, François Morvan
Bis- and Tris-Alkyne Phosphoramidites for Multiple 5'-Labeling of Oligonucleotides by Click Chemistry [Full Paper]
Hui-Qing Peng, Yu-Zhe Chen, Yan Zhao, Qing-Zheng Yang, Li-Zhu Wu, Chen-Ho Tung, Li-Ping Zhang, Qing-Xiao Tong
Artificial Light-Harvesting System Based on Multifunctional Surface-Cross-Linked Micelles [Communication]
A good harvest: Two self-assembling strategies (micellization and electrostatic attraction) and covalent capture were employed to construct a robust, inexpensive, efficient artificial light-harvesting system (see picture). The synthesis was achieved by a one-pot reaction. A high density of the antenna chromophores was achieved without self-quenching and excimer formation, thus affording extremely efficient energy transfer.
Angew. Chem. Int. Ed., January 26, 2012, DOI: 10.1002/anie.201107723
Gabriela de Almeida, Ellen M. Sletten, Hitomi Nakamura, Krishnan K. Palaniappan, Carolyn R. Bertozzi
Thiacycloalkynes for Copper-Free Click Chemistry [Communication]
The heteroatom helps! The introduction of an endocyclic sulfur atom enables fine-tuning of the reactivity and stability of thiacycloalkynes for copper-free click chemistry. The stabilizing effect of the endocyclic sulfur atom allows the use of highly activated seven-membered rings as reagents for bioorthogonal copper-free click chemistry.
Angew. Chem. Int. Ed., January 26, 2012, DOI: 10.1002/anie.201106325
Yuan Lin, Qian Wang
Unlocking the 1,2,3-Triazole Ring Using Mechanical Force [Highlight]
K(l)ick it into reverse: Mechanical force (ultrasound) may be employed to promote a retrocycloaddition reaction of a 1,2,3-triazole to regenerate the parent azide and alkyne, a reaction that cannot be achieved by other means.
Angew. Chem. Int. Ed., January 19, 2012, DOI: 10.1002/anie.201108044
Camille Romuald, Frédéric Coutrot
Combining Coordination Chemistry and Catalysis To Tie a Knot by an Active-Metal Template Strategy [Highlight]
Collar and tie men: The smallest trefoil knot reported to date has been prepared by an active metal template synthesis. Copper(I) ions are able to constrain the well-designed structure so that it can form the loops by complexing to the bipyridine moieties in the core of the thread and the two ends of the entangled lace on opposite faces of the loop, before acting as a catalyst to close the lace (see picture).
Angew. Chem. Int. Ed., January 11, 2012, DOI: 10.1002/anie.201107112
Partha S. Ghosh, Andrew D. Hamilton
Supramolecular Dendrimers: Convenient Synthesis by Programmed Self-Assembly and Tunable Thermoresponsivity [Full Paper]
Treescape: The tetrameric assembly of dendrons through G-quadruplex formation (see figure) is reported. The dynamic character of the self-assembly process can be exploited to create dendrimers with thermoresponsive behavior that can be tuned over a wide temperature range. The approach also promises access to many different dendrimers by using the combination of varied components.
Abdullah Aydogan, Ahmet Akar
Tri- and Pentacalix[4]pyrroles: Synthesis, Characterization and Their Use in the Extraction of Halide Salts [Full Paper]
![Tri- and Pentacalix[4]pyrroles: Synthesis, Characterization and Their Use in the Extraction of Halide Salts](http://www.wiley-vch.de/util/hottopics/img/chem201101605.gif "Tri- and Pentacalix[4]pyrroles: Synthesis, Characterization and Their Use in the Extraction of Halide Salts")
Fishing out the halides: Oligomeric calix[4]pyrrole compounds were synthesized by click chemistry and demonstrated to be capable of extracting tetrabutylammonium chloride and fluoride salts from aqueous media (see figure).
Anas Allam, Laurent Dupont, Jean-Bernard Behr, Richard Plantier-Royon
Convenient Synthesis of a Galacturonic Acid Based Macrocycle with Potential Copper-Complexation Ability [Full Paper]
A galacturonic acid based macrocycle containing an amide group and a triazole ring has been synthesized by a procedure involving a copper-catalysed intramolecular cycloaddition reaction as the key step. The results of a preliminary study of the complexation properties of this macrocycle towards CuII cations are described.
Moritz M. Rubner, Carolin Holzhauser, Peggy R. Bohländer, Hans-Achim Wagenknecht
A “Clickable” Styryl Dye for Fluorescent DNA Labeling by Excitonic and Energy Transfer Interactions [Communication]
Turn on and turn red: The CyIQ dye as an internal DNA label can be combined with itself and thiazole red as intrastrand fluorophore pairs (see figure). Excitonic and energy transfer interactions provide interesting alternatives for fluorescence readouts, which are either fluorescence enhancement or fluorescence color change, respectively.
Ferdinand Gonzaga, John B. Grande, Michael A. Brook
Morphology-Controlled Synthesis of Poly(oxyethylene)silicone or Alkylsilicone Surfactants with Explicit, Atomically Defined, Branched, Hydrophobic Tails [Full Paper]
Heads and tails: The synthesis of explicit silicone moieties allows for the preparation of well-defined silicone–poly(ethylene glycol) surfactants by click chemistry (see scheme). This, in turn, allows structure–surface-activity relationships to be explored for the first time.
Tobias Harschneck, Sara Hummel, Stefan F. Kirsch, Philipp Klahn
Practical Azidation of 1,3-Dicarbonyls [Full Paper]
Click into place! An operationally simple, direct azidation of 1,3-dicarbonyl compounds has been developed (see scheme). The reaction proceeds readily under ambient conditions using sodium azide and an iodine-based oxidant, such as I2 or 2-iodoxybenzoic acid (IBX)-SO3K/NaI. The oxidative methods show excellent functional-group tolerance and substrate scope and thus allow access to a variety of tertiary 2-azido and 2,2-bisazido 1,3-dicarbonyl compounds.
Sampa Saha, Davor Copic, Srijanani Bhaskar, Nicholas Clay, Alessandro Donini, A. John Hart, Joerg Lahann
Chemically Controlled Bending of Compositionally Anisotropic Microcylinders [Communication]
The bends: Surface modification of multi-compartmental microcylinders by spatio-selective click chemistry and subsequent surface-initiated atom-transfer radical polymerization (ATRP) yield novel amphiphilic microcylinders (see scheme). Depending on the aspect ratio of the microcylinders, they can be bent or coiled.
Balázs R. Varga, Mihály Kállay, Krisztina Hegyi, Szabolcs Béni, Péter Kele
A Non-Fluorinated Monobenzocyclooctyne for Rapid Copper-Free Click Reactions [Full Paper]
A COMBO please! The preparation of carboxymethylmonobenzocyclooctyne (COMBO) was carried out in four synthetic steps. This simple, non-fluorinated, copper-free click reagent showed excellent stability and reaction kinetics (see scheme). A COMBO-modified fluorescent label was employed in glycan imaging of metabolically modified HeLa cells.
Ibai E. Valverde, Fabien Lecaille, Gilles Lalmanach, Vincent Aucagne, Agnès F. Delmas
Synthesis of a Biologically Active Triazole-Containing Analogue of Cystatin A Through Successive Peptidomimetic Alkyne–Azide Ligations [Communication]
“Click” protein: CuI-catalyzed cycloaddition of azides and terminal alkynes has been applied to the successive ligations of three unprotected peptide fragments. Peptidomimetic triazole ligation (PTL, see scheme) as a new method for the chemical production of bioactive proteins is applied for the synthesis of a triazole-containing analogue of the 97 amino acid protein cystatin A.
Christophe Orain, Nicolas Le Poul, Antoine Gomila, Jean-Michel Kerbaol, Nathalie Cosquer, Olivia Reinaud, Françoise Conan, Yves Le Mest
A Generic Platform for the Addressable Functionalisation of Electrode Surfaces through Self-Induced “Electroclick” [Full Paper]
Let it e− click: A two-step procedure based on a biphasic chemical “click” reaction followed by a self-induced “electroclick” process is described for the immobilisation of functionalised groups onto gold-modified electrodes (see scheme). The versatility of the strategy is demonstrated for two different probes (R=phenylpropyl and methylferrocenyl) by voltammetry.
Xiyan Duan, Yan Zhang, Yahui Ding, Jianping Lin, Xianglei Kong, Quan Zhang, Changming Dong, Guoan Luo, Yue Chen
Synthesis of Triazole-Epothilones by Using Cu2O Nanoparticles to Catalyze 1,3-Dipolar Cycloaddition [Full Paper]
The total synthesis of a triazole-epothilone analogue 1 is described. The key step involved the use of Cu2O nanoparticles (Cu2O-NPs) to catalyze a 1,3-dipolar cycloaddition. The conformation of 1 and its bioactivity in MCF cancer cell lines were investigated.
James McNulty, Kunal Keskar, Ramesh Vemula
The First Well-Defined Silver(I)-Complex-Catalyzed Cycloaddition of Azides onto Terminal Alkynes at Room Temperature [Communication]
Silver(I)-catalyzed click chemistry: Substituted 1,2,3-triazoles are versatile intermediates with an expanding array of applications. The discovery and application of a general AgI-catalyzed azide–alkyne cycloaddition reaction (AAC) leading to 1,2,3-triazoles is reported. The synthesis of a stable, well-defined AgI complex of type [AgI(L2)(OAc)] is described, along with the unprecedented ability of this complex to promote the general Ag-AAC at room temperature (see scheme).
André Dallmann, Afaf H. El-Sagheer, Lars Dehmel, Clemens Mügge, Christian Griesinger, Nikolaus P. Ernsting, Tom Brown
Structure and Dynamics of Triazole-Linked DNA: Biocompatibility Explained [Communication]
Blending in: A triazole-modified DNA duplex is perturbed in structure and dynamics, but this is delocalized over five base pairs. The conformation remains B-DNA and hydrogen bonds between the DNA phosphate oxygen and polymerases can be mimicked by the triazole nitrogen (see figure). The results explain the surprising biocompatibility of triazole-linked DNA.
Thierry Muller, Stefan Bräse
Click Chemistry Finds Its Way into Covalent Porous Organic Materials [Highlight]
Click the CMPs and POPs: The Huisgen 1,3-dipolar cycloaddition reaction can be used to generate covalent porous organic materials such as conjugated microporous polymers (CMPs) and porous organic polymers (POPs). A triazole-linked network based on complementary tetrahedral monomers has been prepared by means of click chemistry.
Sezin Yigit, Rana Sanyal, Amitav Sanyal
Fabrication and Functionalization of Hydrogels through “Click” Chemistry [Focus Review]
Chemical jigsaw puzzles! This Focus Review highlights the tremendous impact of click chemistry on the design and fabrication of functional hydrogels. The efficiency and specificity of click reactions have enabled precise ‘programming’ of assembly and disassembly of these materials by ‘snapping’ together complementary building blocks like pieces of a puzzle to create the intended functional material.
Sandip G. Agalave, Suleman R. Maujan, Vandana S. Pore
Click Chemistry: 1,2,3-Triazoles as Pharmacophores [Focus Review]
Easy as 1,2,3: Click chemistry is used for the synthesis of 1,2,3-triazole wherein the CuI is used as catalyst to obtain 1,4-disubstituted triazole as the sole product (see scheme). This review explains the excellent use of click chemistry for the synthesis of a number of biologically important intermediates, linkers, lead molecules, and various drugs.
Albert C. Fahrenbach, J. Fraser Stoddart
Reactions under the Click Chemistry Philosophy Employed in Supramolecular and Mechanostereochemical Systems [Focus Review]
Click into action: The philosophy of click chemistry has taken the chemistry community by storm over the past 10 years. This Focus Reviews highlights some of the recent developments in supramolecular and mechanostereochemistry, which employ one of the click reactions depicted here in their syntheses.
J. Hu, J. R. Lu, Y. Ju
Steroid/Triterpenoid Functional Molecules based on “Click Chemistry” [Focus Review]
They're on steroids and triterpenoids! This Focus Review highlights the design and synthesis of various functional molecules based on steroid/triterpenoid units through the copper-catalyzed azide–alkyne cycloaddition (CuAAC) “click” reaction, as well as their applications in bioactivity, recognition, and assembly.
Xuechen Li
Click to Join Peptides/Proteins Together [Focus Review]
Click to join: The copper(I)-catalyzed azide–alkyne cycloaddition has allowed the merger of peptide chains in a “click” fashion with the generation of the peptide-bond-like triazole structure at the ligation site. It holds great potential in the non-native chemical synthesis of polypeptides and proteins.
Yan Li, Chengzhi Cai
Click Chemistry-Based Functionalization on Non-Oxidized Silicon Substrates [Focus Review]
Silicon ally: The stable Si-C-bound organic layer combined with highly reliable click chemistry serves as an efficient tool for the modification of silicon substrates (see scheme). This review covers the advances in the development of the copper-catalyzed azide–alkyne cycloaddition on non-oxidized silicon and highlights its application in the immobilization of complex biomolecules that makes it useful in the fabrication of silicon-based biomedical devices.
Seok Hwan Kim, Sae Hume Park, Ji Ho Choi, Sukbok Chang
Sulfonyl and Phosphoryl Azides: Going Further Beyond the Click Realm of Alkyl and Aryl Azides [Focus Review]
Versatile middleman: Whereas alkyl or aryl azides undergo Cu-catalyzed cycloaddition with 1-alkynes to afford 1,4-triazoles in excellent yields and selectivity, the use of sulfonyl, phosphoryl, and certain acyl azides allows additional chemistry upon ring-opening of the corresponding triazole intermediates (see scheme). The ketenimine species generated in situ show amazing reactivity and can react with a range of nucleophilic coupling partners.
Venkataraman Ganesh, V. Sai Sudhir, Taraknath Kundu, Srinivasan Chandrasekaran
10 Years of Click Chemistry: Synthesis and Applications of Ferrocene-Derived Triazoles [Focus Review]
Focus on ferrocene: We discuss the synthesis of ferrocene–triazole and the importance of using a copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction for the conjugation of two molecular fragments. We also highlight applications of ferrocene-based click reactions in conjugate chemistry, asymmetric catalysis, medicinal chemistry, host–guest interactions, and materials chemistry (see graphic).
Enrique Lallana, Ricardo Riguera, Eduardo Fernandez-Megia
Reliable and Efficient Procedures for the Conjugation of Biomolecules through Huisgen Azide–Alkyne Cycloadditions [Minireview]
Efficient and benign bioconjugation: CuI-catalyzed azide–alkyne cycloaddition (CuAAC) is an established coupling method because of its high reliability and straightforward experimental procedure. However, the Cu catalyst has often proved detrimental to proteins, nucleic acids, and polysaccharides. CuI ligands and Cu-free strain-promoted procedures (SPAAC) have been developed that are efficient and avoid degradation of the resulting bioconjugates.
Radostina Manova, Teris A. van Beek, Han Zuilhof
Surface Functionalization by Strain-Promoted Alkyne–Azide Click Reactions [Highlight]
Clicks without Cu: There is a growing demand for reproducible site-specific functionalization of surfaces with biomolecules without introduction of unwanted groups or catalysts, as they may interfere with later applications. The title reactions (see picture) could fulfill these requirements, and four recent applications are discussed.
Suman L. Jain, Jomy K. Joseph, Fritz E. Kühn, Oliver Reiser
Retraction: An Efficient Synthesis of Poly(ethylene glycol)-Supported Iron(II) Porphyrin using a Click Reaction and its Application for the Catalytic Olefination of Aldehydes [Retraction]
Daniel Sejer Pedersen, Andrew Abell
1,2,3-Triazoles in Peptidomimetic Chemistry [Microreview]
The incorporation of 1,4- and 1,5-substituted 1,2,3-triazoles in peptidomimetics enables both shape and function to be controlled by covalent or non-covalent interactions. The approach has many applicationsin the synthesis of, for example, natural product analogues, turn structures and α-helical architectures that have been shown to retain their shape and function in aqueous solution.
Christopher Barner-Kowollik, Filip E. Du Prez, Pieter Espeel, Craig J. Hawker, Thomas Junkers, Helmut Schlaad, Wim Van Camp
“Clicking” Polymers or Just Efficient Linking: What Is the Difference? [Essay]
The “click” trick: Many reactions are classified as click reactions even though some are limited to certain applications. Thus, there is danger that the term “click” will become meaningless over time and simply a synonym for “successful”. To prevent this, the original click criteria are evaluated in this Essay specifically for the synthetic polymer field and a set of criteria are specified that distinguishes click from other efficient reactions.
© Wiley-VCH 2011.
RSS feed![Facile Construction of [6,6]-, [6,7]-, [6,8]-, and [6,9]Ring-Fused Triazole Frameworks by Copper-Catalyzed, Tandem, One-Pot, Click and Intramolecular Arylation Reactions: Elaboration to Fused Pentacyclic Derivatives](http://www.wiley-vch.de/util/hottopics/img/ejoc201101816.jpg "Facile Construction of [6,6]-, [6,7]-, [6,8]-, and [6,9]Ring-Fused Triazole Frameworks by Copper-Catalyzed, Tandem, One-Pot, Click and Intramolecular Arylation Reactions: Elaboration to Fused Pentacyclic Derivatives")
