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Advances in Click Chemistry

A topical collection in Molecules (ISSN 1420-3049). This collection belongs to the section "Organic Chemistry".

Viewed by 235734

Editor

Dr. Arnaud Gautier

E-Mail Website
Collection Editor
Institut de Chimie de Clermont-Ferrand (ICCF) - UMR 6296, Campus Universitaire des Cézeaux, 24 avenue Blaise Pascal, TSA 60026, CS 60026, 63178 Aubiere, CEDEX, France
Interests: organometallic; click chemistry; stable carbene; biological probe

Topical Collection Information

Dear Colleagues,

The rise of "click chemistry" as a toolbox gathering only simple, high yielding and easily workable transformations has facilitated an extraordinary increase in the number of molecules available for catalysis, medicinal chemistry, biology, material science and nanotechnologies. Among the synthetic "click tools", the regioselective copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), is considered as the historical breakthrough in the domain, and has received unrivalled attention. For this reaction, major improvements in the reaction rate and, consequently on the application scopes have arisen from ligand design. However, click chemistry is not restricted to the CuAAC reaction and actually the interest for chemical ligation using strain-promoted alkyne-azide cycloaddition (SPAAC), a copper-free click reaction, is constantly increasing. This allows now pletorious applications at the frontiers of chemistry and biology.
This Special Issue of Molecules will highlight important facets of these milestone reactions, covering all click flavours ranging from methodology to applications. I strongly encourage colleagues to submit their manuscript for this Special Issue to promote and celebrate this exceptional synthetic toolbox.

Dr. Arnaud Gautier
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed Open Access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).

Keywords

  • click chemistry
  • CuAAC
  • RuAAC
  • SPAAC
  • chemical ligation
  • catalysis
  • medicinal chemistry
  • material science
  • nanosciences

Published Papers (23 papers)

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2023

Jump to: 2019, 2018, 2015, 2013

13 pages, 1585 KiB  
Article
An Oxidant-Free and Mild Strategy for Quinazolin-4(3H)-One Synthesis via CuAAC/Ring Cleavage Reaction
by Yueling He, Zhongtao Yang, Danyang Luo, Xiai Luo, Xiaodong Chen and Weiguang Yang
Molecules 2023, 28(15), 5734; https://doi.org/10.3390/molecules28155734 - 28 Jul 2023
Viewed by 733
Abstract
An oxidant-free and highly efficient synthesis of phenolic quinazolin-4(3H)-ones was achieved by simply stirring a mixture of 2-aminobenzamides, sulfonyl azides, and terminal alkynes. The intermediate N-sulfonylketenimine underwent two nucleophilic additions and the sulfonyl group eliminated through the power of aromatization. [...] Read more.
An oxidant-free and highly efficient synthesis of phenolic quinazolin-4(3H)-ones was achieved by simply stirring a mixture of 2-aminobenzamides, sulfonyl azides, and terminal alkynes. The intermediate N-sulfonylketenimine underwent two nucleophilic additions and the sulfonyl group eliminated through the power of aromatization. The natural product 2-(4-hydroxybenzyl)quinazolin-4(3H)-one can be synthesized on a large scale under mild conditions with this method. Full article
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2019

Jump to: 2023, 2018, 2015, 2013

30 pages, 3305 KiB  
Review
A Spotlight on Viruses—Application of Click Chemistry to Visualize Virus-Cell Interactions
by Thorsten G. Müller, Volkan Sakin and Barbara Müller
Molecules 2019, 24(3), 481; https://doi.org/10.3390/molecules24030481 - 29 Jan 2019
Cited by 34 | Viewed by 13813
Abstract
The replication of a virus within its host cell involves numerous interactions between viral and cellular factors, which have to be tightly controlled in space and time. The intricate interplay between viral exploitation of cellular pathways and the intrinsic host defense mechanisms is [...] Read more.
The replication of a virus within its host cell involves numerous interactions between viral and cellular factors, which have to be tightly controlled in space and time. The intricate interplay between viral exploitation of cellular pathways and the intrinsic host defense mechanisms is difficult to unravel by traditional bulk approaches. In recent years, novel fluorescence microscopy techniques and single virus tracking have transformed the investigation of dynamic virus-host interactions. A prerequisite for the application of these imaging-based methods is the attachment of a fluorescent label to the structure of interest. However, their small size, limited coding capacity and multifunctional proteins render viruses particularly challenging targets for fluorescent labeling approaches. Click chemistry in conjunction with genetic code expansion provides virologists with a novel toolbox for site-specific, minimally invasive labeling of virion components, whose potential has just recently begun to be exploited. Here, we summarize recent achievements, current developments and future challenges for the labeling of viral nucleic acids, proteins, glycoproteins or lipids using click chemistry in order to study dynamic processes in virus-cell interactions. Full article
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2018

Jump to: 2023, 2019, 2015, 2013

18 pages, 3125 KiB  
Review
DNA Replication: From Radioisotopes to Click Chemistry
by Anna Ligasová and Karel Koberna
Molecules 2018, 23(11), 3007; https://doi.org/10.3390/molecules23113007 - 17 Nov 2018
Cited by 13 | Viewed by 7199
Abstract
The replication of nuclear and mitochondrial DNA are basic processes assuring the doubling of the genetic information of eukaryotic cells. In research of the basic principles of DNA replication, and also in the studies focused on the cell cycle, an important role is [...] Read more.
The replication of nuclear and mitochondrial DNA are basic processes assuring the doubling of the genetic information of eukaryotic cells. In research of the basic principles of DNA replication, and also in the studies focused on the cell cycle, an important role is played by artificially-prepared nucleoside and nucleotide analogues that serve as markers of newly synthesized DNA. These analogues are incorporated into the DNA during DNA replication, and are subsequently visualized. Several methods are used for their detection, including the highly popular click chemistry. This review aims to provide the readers with basic information about the various possibilities of the detection of replication activity using nucleoside and nucleotide analogues, and to show the strengths and weaknesses of those different detection systems, including click chemistry for microscopic studies. Full article
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10 pages, 1440 KiB  
Article
Synthesis of a Novel Fluorescent Ruthenium Complex with an Appended Ac4GlcNAc Moiety by Click Reaction
by Qi Cheng, Yalu Cui, Nao Xiao, Jishun Lu and Chen-Jie Fang
Molecules 2018, 23(7), 1649; https://doi.org/10.3390/molecules23071649 - 06 Jul 2018
Cited by 4 | Viewed by 3893
Abstract
The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers. [...] Read more.
The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers. However, the precise connexion between O-GlcNAc-modified proteins and their function in cells is largely undefined for most cases. Confocal microscopy is a powerful and effective tool for in-cell elucidation of the function of biological molecules. Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible. Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac4GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)2(Phen-alkyne)Cl2 (4) to synthesize the fluorescent dye Ru(bpy)2(Phen-Ac4GlcNAc)Cl2 (5) under mild and neutral reaction conditions. Moreover, 5 showed good stability, desirable fluorescence characteristics, and exhibited rather low levels of cytotoxicity against sensitive MCF-7 cells. Additionally, we have achieved successful fluorescent imaging of 5 transported in living MCF-7 cells. Cell images displayed that proteins are potentially labelled with 5 in the cytoplasm. Full article
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2015

Jump to: 2023, 2019, 2018, 2013

967 KiB  
Communication
Synthesis of Phospholipid-Protein Conjugates as New Antigens for Autoimmune Antibodies
by Arindam Maity, Claudia Macaubas, Elizabeth Mellins and Kira Astakhova
Molecules 2015, 20(6), 10253-10263; https://doi.org/10.3390/molecules200610253 - 03 Jun 2015
Cited by 3 | Viewed by 8255
Abstract
Copper(I)-catalyzed azide-alkyne cycloaddition, or CuAAC click chemistry, is an efficient method for bioconjugation aiming at chemical and biological applications. Herein, we demonstrate how the CuAAC method can provide novel phospholipid-protein conjugates with a high potential for the diagnostics and therapy of autoimmune conditions. [...] Read more.
Copper(I)-catalyzed azide-alkyne cycloaddition, or CuAAC click chemistry, is an efficient method for bioconjugation aiming at chemical and biological applications. Herein, we demonstrate how the CuAAC method can provide novel phospholipid-protein conjugates with a high potential for the diagnostics and therapy of autoimmune conditions. In doing this, we, for the first time, covalently bind via 1,2,3-triazole linker biologically complementary molecules, namely phosphoethanol amine with human β2-glycoprotein I and prothrombin. The resulting phospholipid-protein conjugates show high binding affinity and specificity for the autoimmune antibodies against autoimmune complexes. Thus, the development of this work might become a milestone in further diagnostics and therapy of autoimmune diseases that involve the production of autoantibodies against the aforementioned phospholipids and proteins, such as antiphospholipid syndrome and systemic lupus erythematosus. Full article
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1497 KiB  
Review
Recent Advances in Click Chemistry Applied to Dendrimer Synthesis
by Mathieu Arseneault, Caroline Wafer and Jean-François Morin
Molecules 2015, 20(5), 9263-9294; https://doi.org/10.3390/molecules20059263 - 20 May 2015
Cited by 125 | Viewed by 17546
Abstract
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 [...] Read more.
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. Full article
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926 KiB  
Article
Copper(I) Complexes of Mesoionic Carbene: Structural Characterization and Catalytic Hydrosilylation Reactions
by Stephan Hohloch, Fenja Leena Duecker, Margarethe Van der Meer and Biprajit Sarkar
Molecules 2015, 20(4), 7379-7395; https://doi.org/10.3390/molecules20047379 - 22 Apr 2015
Cited by 15 | Viewed by 8273
Abstract
Two series of different Cu(I)-complexes of “click” derived mesoionic carbenes are reported. Halide complexes of the type (MIC)CuI (with MIC = 1,4-(2,6-diisopropyl)-phenyl-3-methyl-1,2,3-triazol-5-ylidene (for 1b), 1-benzyl-3-methyl-4-phenyl-1,2,3-triazol-5-ylidene (for 1c)) and cationic complexes of the general formula [Cu(MIC)2]X (with MIC =1,4-dimesityl-3-methyl-1,2,3-triazol-5-ylidene, X [...] Read more.
Two series of different Cu(I)-complexes of “click” derived mesoionic carbenes are reported. Halide complexes of the type (MIC)CuI (with MIC = 1,4-(2,6-diisopropyl)-phenyl-3-methyl-1,2,3-triazol-5-ylidene (for 1b), 1-benzyl-3-methyl-4-phenyl-1,2,3-triazol-5-ylidene (for 1c)) and cationic complexes of the general formula [Cu(MIC)2]X (with MIC =1,4-dimesityl-3-methyl-1,2,3-triazol-5-ylidene, X = CuI2− (for 2á), 1,4-dimesityl-3-methyl-1,2,3-triazol-5-ylidene, X = BF4− (for 2a), 1,4-(2,6-diisopropyl)phenyl-3-methyl-1,2,3-triazol-5-ylidene, X = BF4− (for 2b), 1-benzyl-3-methyl-4-phenyl-1,2,3-triazol-5-ylidene, X = BF4− (for 2c)) have been prepared from CuI or [Cu(CH3CN)4](BF4) and the corresponding ligands, respectively. All complexes were characterized by elemental analysis and standard spectroscopic methods. Complexes 2á and 1b were studied by single-crystal X-ray diffraction analysis. Structural analysis revealed 2á to adopt a cationic form as [Cu(MIC)2](CuI2) and comparison of the NMR spectra of 2á and 2a confirmed this conformation in solution. In contrast, after crystallization complex 1b was found to adopt the desired neutral form. All complexes were tested for the reduction of cyclohexanone under hydrosilylation condition at elevated temperatures. These complexes were found to be efficient catalysts for this reaction. 2c was also found to catalyze this reaction at room temperature. Mechanistic studies have been carried out as well. Full article
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631 KiB  
Article
Phenylglyoxal-Based Visualization of Citrullinated Proteins on Western Blots
by Sanne M. M. Hensen, Wilbert C. Boelens, Kimberly M. Bonger, Remco T. P. Van Cruchten, Floris L. Van Delft and Ger J. M. Pruijn
Molecules 2015, 20(4), 6592-6600; https://doi.org/10.3390/molecules20046592 - 14 Apr 2015
Cited by 5 | Viewed by 7459
Abstract
Citrullination is the conversion of peptidylarginine to peptidylcitrulline, which is catalyzed by peptidylarginine deiminases. This conversion is involved in different physiological processes and is associated with several diseases, including cancer and rheumatoid arthritis. A common method to detect citrullinated proteins relies on anti-modified [...] Read more.
Citrullination is the conversion of peptidylarginine to peptidylcitrulline, which is catalyzed by peptidylarginine deiminases. This conversion is involved in different physiological processes and is associated with several diseases, including cancer and rheumatoid arthritis. A common method to detect citrullinated proteins relies on anti-modified citrulline antibodies directed to a specific chemical modification of the citrulline side chain. Here, we describe a versatile, antibody-independent method for the detection of citrullinated proteins on a membrane, based on the selective reaction of phenylglyoxal with the ureido group of citrulline under highly acidic conditions. The method makes use of 4-azidophenylglyoxal, which, after reaction with citrullinated proteins, can be visualized with alkyne-conjugated probes. The sensitivity of this procedure, using an alkyne-biotin probe, appeared to be comparable to the antibody-based detection method and independent of the sequence surrounding the citrulline. Full article
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2682 KiB  
Article
Solvent-Free Copper-Catalyzed Azide-Alkyne Cycloaddition under Mechanochemical Activation
by Laura Rinaldi, Katia Martina, Francesca Baricco, Laura Rotolo and Giancarlo Cravotto
Molecules 2015, 20(2), 2837-2849; https://doi.org/10.3390/molecules20022837 - 09 Feb 2015
Cited by 51 | Viewed by 10952
Abstract
The ball-mill-based mechanochemical activation of metallic copper powder facilitates solvent-free alkyne-azide click reactions (CuAAC). All parameters that affect reaction rate (i.e., milling time, revolutions/min, size and milling ball number) have been optimized. This new, efficient, facile and eco-friendly procedure has been [...] Read more.
The ball-mill-based mechanochemical activation of metallic copper powder facilitates solvent-free alkyne-azide click reactions (CuAAC). All parameters that affect reaction rate (i.e., milling time, revolutions/min, size and milling ball number) have been optimized. This new, efficient, facile and eco-friendly procedure has been tested on a number of different substrates and in all cases afforded the corresponding 1,4-disubstituted 1,2,3-triazole derivatives in high yields and purities. The final compounds were isolated in almost quantitative overall yields after simple filtration, making this procedure facile and rapid. The optimized CuAAC protocol was efficiently applied even with bulky functionalized β-cyclodextrins (β-CD) and scaled-up to 10 g of isolated product. Full article
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2013

Jump to: 2023, 2019, 2018, 2015

1173 KiB  
Review
Peptide Conjugation via CuAAC ‘Click’ Chemistry
by Abdullah A. H. Ahmad Fuaad, Fazren Azmi, Mariusz Skwarczynski and Istvan Toth
Molecules 2013, 18(11), 13148-13174; https://doi.org/10.3390/molecules181113148 - 24 Oct 2013
Cited by 88 | Viewed by 14957
Abstract
The copper (I)-catalyzed alkyne azide 1,3-dipolar cycloaddition (CuAAC) or ‘click’ reaction, is a highly versatile reaction that can be performed under a variety of reaction conditions including various solvents, a wide pH and temperature range, and using different copper sources, with or without [...] Read more.
The copper (I)-catalyzed alkyne azide 1,3-dipolar cycloaddition (CuAAC) or ‘click’ reaction, is a highly versatile reaction that can be performed under a variety of reaction conditions including various solvents, a wide pH and temperature range, and using different copper sources, with or without additional ligands or reducing agents. This reaction is highly selective and can be performed in the presence of other functional moieties. The flexibility and selectivity has resulted in growing interest in the application of CuAAC in various fields. In this review, we briefly describe the importance of the structural folding of peptides and proteins and how the 1,4-disubstituted triazole product of the CuAAC reaction is a suitable isoster for an amide bond. However the major focus of the review is the application of this reaction to produce peptide conjugates for tagging and targeting purpose, linkers for multifunctional biomacromolecules, and reporter ions for peptide and protein analysis. Full article
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426 KiB  
Communication
Comparative Analysis of Click Chemistry Mediated Activity-Based Protein Profiling in Cell Lysates
by Yinliang Yang, Xiaomeng Yang and Steven H. L. Verhelst
Molecules 2013, 18(10), 12599-12608; https://doi.org/10.3390/molecules181012599 - 11 Oct 2013
Cited by 29 | Viewed by 10513
Abstract
Activity-based protein profiling uses chemical probes that covalently attach to active enzyme targets. Probes with conventional tags have disadvantages, such as limited cell permeability or steric hindrance around the reactive group. A tandem labeling strategy with click chemistry is now widely used to [...] Read more.
Activity-based protein profiling uses chemical probes that covalently attach to active enzyme targets. Probes with conventional tags have disadvantages, such as limited cell permeability or steric hindrance around the reactive group. A tandem labeling strategy with click chemistry is now widely used to study enzyme targets in situ and in vivo. Herein, the probes are reacted in live cells, whereas the ensuing detection by click chemistry takes place in cell lysates. We here make a comparison of the efficiency of the activity-based tandem labeling strategy by using Cu(I)-catalyzed and strain-promoted click chemistry, different ligands and different lysis conditions. Full article
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456 KiB  
Article
Click Reactions as a Key Step for an Efficient and Selective Synthesis of D-Xylose-Based ILs
by Nadège Ferlin, Sylvain Gatard, Albert Nguyen Van Nhien, Matthieu Courty and Sandrine Bouquillon
Molecules 2013, 18(9), 11512-11525; https://doi.org/10.3390/molecules180911512 - 17 Sep 2013
Cited by 19 | Viewed by 6046
Abstract
D-Xylose-based ionic liquids have been prepared from D-xylose following a five steps reaction sequence, the key step being a click cycloaddition. These ionic liquids (ILs) have been characterized through classical analytical methods (IR, NMR, mass spectroscopy, elemental analysis) and their stability constants, Tg [...] Read more.
D-Xylose-based ionic liquids have been prepared from D-xylose following a five steps reaction sequence, the key step being a click cycloaddition. These ionic liquids (ILs) have been characterized through classical analytical methods (IR, NMR, mass spectroscopy, elemental analysis) and their stability constants, Tg and Tdec, were also determined. Considering their properties and their hydrophilicity, these compounds could be alternative solvents for chemical applications under mild conditions. Full article
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702 KiB  
Review
Click Chemistry in Peptide-Based Drug Design
by Huiyuan Li, Rachna Aneja and Irwin Chaiken
Molecules 2013, 18(8), 9797-9817; https://doi.org/10.3390/molecules18089797 - 16 Aug 2013
Cited by 157 | Viewed by 17823
Abstract
Click chemistry is an efficient and chemoselective synthetic method for coupling molecular fragments under mild reaction conditions. Since the advent in 2001 of methods to improve stereochemical conservation, the click chemistry approach has been broadly used to construct diverse chemotypes in both chemical [...] Read more.
Click chemistry is an efficient and chemoselective synthetic method for coupling molecular fragments under mild reaction conditions. Since the advent in 2001 of methods to improve stereochemical conservation, the click chemistry approach has been broadly used to construct diverse chemotypes in both chemical and biological fields. In this review, we discuss the application of click chemistry in peptide-based drug design. We highlight how triazoles formed by click reactions have been used for mimicking peptide and disulfide bonds, building secondary structural components of peptides, linking functional groups together, and bioconjugation. The progress made in this field opens the way for synthetic approaches to convert peptides with promising functional leads into structure-minimized and more stable forms. Full article
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1424 KiB  
Review
Alkyne-Azide “Click” Chemistry in Designing Nanocarriers for Applications in Biology
by Pramod K. Avti, Dusica Maysinger and Ashok Kakkar
Molecules 2013, 18(8), 9531-9549; https://doi.org/10.3390/molecules18089531 - 08 Aug 2013
Cited by 56 | Viewed by 12258
Abstract
The alkyne-azide cycloaddition, popularly known as the “click” reaction, has been extensively exploited in molecule/macromolecule build-up, and has offered tremendous potential in the design of nanomaterials for applications in a diverse range of disciplines, including biology. Some advantageous characteristics of this coupling include [...] Read more.
The alkyne-azide cycloaddition, popularly known as the “click” reaction, has been extensively exploited in molecule/macromolecule build-up, and has offered tremendous potential in the design of nanomaterials for applications in a diverse range of disciplines, including biology. Some advantageous characteristics of this coupling include high efficiency, and adaptability to the environment in which the desired covalent linking of the alkyne and azide terminated moieties needs to be carried out. The efficient delivery of active pharmaceutical agents to specific organelles, employing nanocarriers developed through the use of “click” chemistry, constitutes a continuing topical area of research. In this review, we highlight important contributions click chemistry has made in the design of macromolecule-based nanomaterials for therapeutic intervention in mitochondria and lipid droplets. Full article
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418 KiB  
Review
The Click Reaction as an Efficient Tool for the Construction of Macrocyclic Structures
by Dario Pasini
Molecules 2013, 18(8), 9512-9530; https://doi.org/10.3390/molecules18089512 - 08 Aug 2013
Cited by 119 | Viewed by 10400
Abstract
The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC, known as the click reaction) is an established tool used for the construction of complex molecular architectures. Given its efficiency it has been widely applied for bioconjugation, polymer and dendrimer synthesis. More recently, this reaction has been utilized [...] Read more.
The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC, known as the click reaction) is an established tool used for the construction of complex molecular architectures. Given its efficiency it has been widely applied for bioconjugation, polymer and dendrimer synthesis. More recently, this reaction has been utilized for the efficient formation of rigid or shape-persistent, preorganized macrocyclic species. This strategy also allows the installment of useful functionalities, in the form of polar and function-rich 1,2,3-triazole moieties, directly embedded in the macrocyclic structures. This review analyzes the state of the art in this context, and provides some elements of perspective for future applications. Full article
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537 KiB  
Article
Synthesis and Relaxivity Studies of a DOTA-Based Nanomolecular Chelator Assembly Supported by an Icosahedral Closo-B122− -Core for MRI: A Click Chemistry Approach
by Lalit N. Goswami, Lixin Ma, Peter J. Kueffer, Satish S. Jalisatgi and M. Frederick Hawthorne
Molecules 2013, 18(8), 9034-9048; https://doi.org/10.3390/molecules18089034 - 29 Jul 2013
Cited by 20 | Viewed by 7224
Abstract
An icosahedral closo-B122− scaffold based nano-sized assembly capable of carrying a high payload of Gd3+-chelates in a sterically crowded configuration is developed by employing the azide-alkyne click reaction. The twelve copies of DO3A-t-Bu-ester ligands were [...] Read more.
An icosahedral closo-B122− scaffold based nano-sized assembly capable of carrying a high payload of Gd3+-chelates in a sterically crowded configuration is developed by employing the azide-alkyne click reaction. The twelve copies of DO3A-t-Bu-ester ligands were covalently attached to an icosahedral closo-B122− core via suitable linkers through click reaction. This nanomolecular structure supporting a high payload of Gd3+-chelate is a new member of the closomer MRI contrast agents that we are currently developing in our laboratory. The per Gd ion relaxivity (r1) of the newly synthesized MRI contrast agent was obtained in PBS, 2% tween/PBS and bovine calf serum using a 7 Tesla micro MRI instrument and was found to be slightly higher (r1 = 4.7 in PBS at 25 °C) compared to the clinically used MRI contrast agents Omniscan (r1 = 4.2 in PBS at 25 °C) and ProHance (r1 = 3.1 in PBS at 25 °C). Full article
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717 KiB  
Article
Synthesis and Luminescence Properties of Iridium(III) Azide- and Triazole-Bisterpyridine Complexes
by Daniel C. Goldstein, Joshua R. Peterson, Yuen Yap Cheng, Raphael G. C. Clady, Timothy W. Schmidt and Pall Thordarson
Molecules 2013, 18(8), 8959-8975; https://doi.org/10.3390/molecules18088959 - 26 Jul 2013
Cited by 10 | Viewed by 9227
Abstract
We describe here the synthesis of azide-functionalised iridium(III) bisterpyridines using the “chemistry on the complex” strategy. The resulting azide-complexes are then used in the copper(I)-catalysed azide-alkyne Huisgen 1,3-dipolar cycloaddition “click chemistry” reaction to from the corresponding triazole-functionalised iridium(III) bisterpyridines. The photophysical characteristics, including [...] Read more.
We describe here the synthesis of azide-functionalised iridium(III) bisterpyridines using the “chemistry on the complex” strategy. The resulting azide-complexes are then used in the copper(I)-catalysed azide-alkyne Huisgen 1,3-dipolar cycloaddition “click chemistry” reaction to from the corresponding triazole-functionalised iridium(III) bisterpyridines. The photophysical characteristics, including lifetimes, of these compounds were also investigated. Interestingly, oxygen appears to have very little effect on the lifetime of these complexes in aqueous solutions. Unexpectedly, sodium ascorbate acid appears to quench the luminescence of triazole-functionalised iridium(III) bisterpyridines, but this effect can be reversed by the addition of copper(II) sulfate, which is known to oxidize ascorbate under aerobic conditions. The results demonstrate that iridium(III) bisterpyridines can be functionalized for use in “click chemistry” facilitating the use of these photophysically interesting complexes in the modification of polymers or surfaces, to highlight just two possible applications. Full article
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240 KiB  
Article
Well-Defined Diimine Copper(I) Complexes as Catalysts in Click Azide-Alkyne Cycloaddition Reactions
by Jordi Markalain Barta and Silvia Díez-González
Molecules 2013, 18(8), 8919-8928; https://doi.org/10.3390/molecules18088919 - 26 Jul 2013
Cited by 18 | Viewed by 6521
Abstract
A series of 1,4-disubstituted 1,2,3-triazoles have been prepared in high yields while respecting the stringent Click criteria. In these reactions, highly stable pre-formed complexes bearing diimine ligands were used. Full article
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866 KiB  
Review
Recent Trends in Bioorthogonal Click-Radiolabeling Reactions Using Fluorine-18
by Marc Pretze, Doreen Pietzsch and Constantin Mamat
Molecules 2013, 18(7), 8618-8665; https://doi.org/10.3390/molecules18078618 - 22 Jul 2013
Cited by 72 | Viewed by 12449
Abstract
The increasing application of positron emission tomography (PET) in nuclear medicine has stimulated the extensive development of a multitude of novel and versatile bioorthogonal conjugation techniques especially for the radiolabeling of biologically active high molecular weight compounds like peptides, proteins or antibodies. Taking [...] Read more.
The increasing application of positron emission tomography (PET) in nuclear medicine has stimulated the extensive development of a multitude of novel and versatile bioorthogonal conjugation techniques especially for the radiolabeling of biologically active high molecular weight compounds like peptides, proteins or antibodies. Taking into consideration that the introduction of fluorine-18 (t1/2 = 109.8 min) proceeds under harsh conditions, radiolabeling of these biologically active molecules represents an outstanding challenge and is of enormous interest. Special attention has to be paid to the method of 18F-introduction. It should proceed in a regioselective manner under mild physiological conditions, in an acceptable time span, with high yields and high specific activities. For these reasons and due to the high number of functional groups found in these compounds, a specific labeling procedure has to be developed for every bioactive macromolecule. Bioorthogonal strategies including the Cu-assisted Huisgen cycloaddition and its copper-free click variant, both Staudinger Ligations or the tetrazine-click reaction have been successfully applied and represent valuable alternatives for the selective introduction of fluorine-18 to overcome the afore mentioned obstacles. This comprehensive review deals with the progress and illustrates the latest developments in the field of bioorthogonal labeling with the focus on the preparation of radiofluorinated building blocks and tracers for molecular imaging. Full article
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679 KiB  
Review
Applications of Azide-Based Bioorthogonal Click Chemistry in Glycobiology
by Xiu Zhang and Yan Zhang
Molecules 2013, 18(6), 7145-7159; https://doi.org/10.3390/molecules18067145 - 19 Jun 2013
Cited by 72 | Viewed by 15137
Abstract
Click chemistry is a powerful chemical reaction with excellent bioorthogonality features: biocompatible, rapid and highly specific in biological environments. For glycobiology, bioorthogonal click chemistry has created a new method for glycan non-invasive imaging in living systems, selective metabolic engineering, and offered an elite [...] Read more.
Click chemistry is a powerful chemical reaction with excellent bioorthogonality features: biocompatible, rapid and highly specific in biological environments. For glycobiology, bioorthogonal click chemistry has created a new method for glycan non-invasive imaging in living systems, selective metabolic engineering, and offered an elite chemical handle for biological manipulation and glycomics studies. Especially the [3 + 2] dipolar cycloadditions of azides with strained alkynes and the Staudinger ligation of azides and triarylphosphines have been widely used among the extant click reactions. This review focuses on the azide-based bioorthogonal click chemistry, describing the characteristics and development of these reactions, introducing some recent applications in glycobiology research, especially in glycan metabolic engineering, including glycan non-invasive imaging, glycomics studies and viral surface manipulation for drug discovery as well as other applications like activity-based protein profiling and carbohydrate microarrays. Full article
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1476 KiB  
Article
[Fe2L3]4+ Cylinders Derived from Bis(bidentate) 2-Pyridyl-1,2,3-triazole “Click” Ligands: Synthesis, Structures and Exploration of Biological Activity
by Sreedhar K. Vellas, James E. M. Lewis, Madhu Shankar, Alia Sagatova, Joel D. A. Tyndall, Brian C. Monk, Christopher M. Fitchett, Lyall R. Hanton and James D. Crowley
Molecules 2013, 18(6), 6383-6407; https://doi.org/10.3390/molecules18066383 - 29 May 2013
Cited by 61 | Viewed by 11650
Abstract
A series of metallosupramolecular [Fe2L3](BF4)4 “click” cylinders have been synthesized in excellent yields (90%–95%) from [Fe(H2O)6](BF4)2 and bis(bidentate) pyridyl-1,2,3-triazole ligands. All complexes were characterized by elemental analysis, IR, UV-vis, [...] Read more.
A series of metallosupramolecular [Fe2L3](BF4)4 “click” cylinders have been synthesized in excellent yields (90%–95%) from [Fe(H2O)6](BF4)2 and bis(bidentate) pyridyl-1,2,3-triazole ligands. All complexes were characterized by elemental analysis, IR, UV-vis, 1H-, 13C- and DOSY-NMR spectroscopies and, in four cases, the structures confirmed by X-ray crystallography. Molecular modeling indicated that some of these “click” complexes were of similar size and shape to related biologically active pyridylimine-based iron(II) helicates and suggested that the “click” complexes may bind both duplex and triplex DNA. Cell-based agarose diffusion assays showed that the metallosupramolecular [Fe2L3](BF4)4 “click” cylinders display no antifungal activity against S. cerevisiae. This observed lack of antifungal activity appears to be due to the poor stability of the “click” complexes in DMSO and biological media. Full article
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358 KiB  
Review
Advances in Click Chemistry for Single-Chain Nanoparticle Construction
by Ana Sanchez-Sanchez, Irma Pérez-Baena and José A. Pomposo
Molecules 2013, 18(3), 3339-3355; https://doi.org/10.3390/molecules18033339 - 14 Mar 2013
Cited by 110 | Viewed by 10074
Abstract
Single-chain polymeric nanoparticles are artificial folded soft nano-objects of ultra-small size which have recently gained prominence in nanoscience and nanotechnology due to their exceptional and sometimes unique properties. This review focuses on the current state of the investigations of click chemistry techniques for [...] Read more.
Single-chain polymeric nanoparticles are artificial folded soft nano-objects of ultra-small size which have recently gained prominence in nanoscience and nanotechnology due to their exceptional and sometimes unique properties. This review focuses on the current state of the investigations of click chemistry techniques for highly-efficient single-chain nanoparticle construction. Additionally, recent progress achieved for the use of well-defined single-chain nanoparticles in some promising fields, such as nanomedicine and catalysis, is highlighted. Full article
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519 KiB  
Review
Click-to-Chelate: Development of Technetium and Rhenium-Tricarbonyl Labeled Radiopharmaceuticals
by Christiane A. Kluba and Thomas L. Mindt
Molecules 2013, 18(3), 3206-3226; https://doi.org/10.3390/molecules18033206 - 12 Mar 2013
Cited by 84 | Viewed by 11227
Abstract
The Click-to-Chelate approach is a highly efficient strategy for the radiolabeling of molecules of medicinal interest with technetium and rhenium-tricarbonyl cores. Reaction of azide-functionalized molecules with alkyne prochelators by the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC; click reaction) enables the simultaneous synthesis and conjugation of [...] Read more.
The Click-to-Chelate approach is a highly efficient strategy for the radiolabeling of molecules of medicinal interest with technetium and rhenium-tricarbonyl cores. Reaction of azide-functionalized molecules with alkyne prochelators by the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC; click reaction) enables the simultaneous synthesis and conjugation of tridentate chelating systems for the stable complexation of the radiometals. In many cases, the functionalization of (bio)molecules with the ligand system and radiolabeling can be achieved by convenient one-pot procedures. Since its first report in 2006, Click-to-Chelate has been applied to the development of numerous novel radiotracers with promising potential for translation into the clinic. This review summarizes the use of the Click-to-Chelate approach in radiopharmaceutical sciences and provides a perspective for future applications. Full article
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