Showing papers on "Click chemistry published in 2021"
TL;DR: This review summarizes the recent advances in the development of photoclick reactions and their applications in chemical biology and materials science and places a particular emphasis on the historical contexts and mechanistic insights into each of the selected reactions.
Abstract: The merging of click chemistry with discrete photochemical processes has led to the creation of a new class of click reactions, collectively known as photoclick chemistry. These light-triggered click reactions allow the synthesis of diverse organic structures in a rapid and precise manner under mild conditions. Because light offers unparalleled spatiotemporal control over the generation of the reactive intermediates, photoclick chemistry has become an indispensable tool for a wide range of spatially addressable applications including surface functionalization, polymer conjugation and cross-linking, and biomolecular labeling in the native cellular environment. Over the past decade, a growing number of photoclick reactions have been developed, especially those based on the 1,3-dipolar cycloadditions and Diels-Alder reactions owing to their excellent reaction kinetics, selectivity, and biocompatibility. This review summarizes the recent advances in the development of photoclick reactions and their applications in chemical biology and materials science. A particular emphasis is placed on the historical contexts and mechanistic insights into each of the selected reactions. The in-depth discussion presented here should stimulate further development of the field, including the design of new photoactivation modalities, the continuous expansion of λ-orthogonal tandem photoclick chemistry, and the innovative use of these unique tools in bioconjugation and nanomaterial synthesis.
128 citations
TL;DR: In this article, a review highlights the successful development of CuAAC or click chemistry in emerging areas of glycoscience, including the synthesis of triazole appended carbohydrate-containing molecular architectures (mainly glycohybrids, glycoconjugates, glycopolymers, glycopeptides and glycoproteins, glycolipids, glycoclusters, and glycodendrimers).
Abstract: Copper(I)-catalyzed 1,3-dipolar cycloaddition between organic azides and terminal alkynes, commonly known as CuAAC or click chemistry, has been identified as one of the most successful, versatile, reliable, and modular strategies for the rapid and regioselective construction of 1,4-disubstituted 1,2,3-triazoles as diversely functionalized molecules. Carbohydrates, an integral part of living cells, have several fascinating features, including their structural diversity, biocompatibility, bioavailability, hydrophilicity, and superior ADME properties with minimal toxicity, which support increased demand to explore them as versatile scaffolds for easy access to diverse glycohybrids and well-defined glycoconjugates for complete chemical, biochemical, and pharmacological investigations. This review highlights the successful development of CuAAC or click chemistry in emerging areas of glycoscience, including the synthesis of triazole appended carbohydrate-containing molecular architectures (mainly glycohybrids, glycoconjugates, glycopolymers, glycopeptides, glycoproteins, glycolipids, glycoclusters, and glycodendrimers through regioselective triazole forming modular and bio-orthogonal coupling protocols). It discusses the widespread applications of these glycoproducts as enzyme inhibitors in drug discovery and development, sensing, gelation, chelation, glycosylation, and catalysis. This review also covers the impact of click chemistry and provides future perspectives on its role in various emerging disciplines of science and technology.
120 citations
TL;DR: Azide-alkyne cycloadditions (AAC) are still the leading technology among click reactions due to the facile modification and incorporation of azide and alkyne groups within biological scaffolds.
Abstract: Click chemistry is an immensely powerful technique for the fast and efficient covalent conjugation of molecular entities. Its broad scope has positively impacted on multiple scientific disciplines, and its implementation within the nucleic acid field has enabled researchers to generate a wide variety of tools with application in biology, biochemistry, and biotechnology. Azide-alkyne cycloadditions (AAC) are still the leading technology among click reactions due to the facile modification and incorporation of azide and alkyne groups within biological scaffolds. Application of AAC chemistry to nucleic acids allows labeling, ligation, and cyclization of oligonucleotides efficiently and cost-effectively relative to previously used chemical and enzymatic techniques. In this review, we provide a guide to inexperienced and knowledgeable researchers approaching the field of click chemistry with nucleic acids. We discuss in detail the chemistry, the available modified-nucleosides, and applications of AAC reactions in nucleic acid chemistry and provide a critical view of the advantages, limitations, and open-questions within the field.
117 citations
102 citations
TL;DR: This review highlights the similarities between click and DEL reaction design and deployment in combinatorial library settings, providing a framework for the design of new DEL synthesis technologies to enable next-generation drug discovery.
Abstract: Click chemistry, proposed nearly 20 years ago, promised access to novel chemical space by empowering combinatorial library synthesis with a "few good reactions". These click reactions fulfilled key criteria (broad scope, quantitative yield, abundant starting material, mild reaction conditions, and high chemoselectivity), keeping the focus on molecules that would be easy to make, yet structurally diverse. This philosophy bears a striking resemblance to DNA-encoded library (DEL) technology, the now-dominant combinatorial chemistry paradigm. This review highlights the similarities between click and DEL reaction design and deployment in combinatorial library settings, providing a framework for the design of new DEL synthesis technologies to enable next-generation drug discovery.
82 citations
62 citations
TL;DR: Click-ExM as mentioned in this paper integrates click labeling into Expansion microscopy to enable a 'one-stop-shop' method for nanoscale imaging of various types of biomolecules.
Abstract: Expansion microscopy (ExM) allows super-resolution imaging on conventional fluorescence microscopes, but has been limited to proteins and nucleic acids. Here we develop click-ExM, which integrates click labeling into ExM to enable a 'one-stop-shop' method for nanoscale imaging of various types of biomolecule. By click labeling with biotin and staining with fluorescently labeled streptavidin, a large range of biomolecules can be imaged by the standard ExM procedure normally used for proteins. Using 18 clickable labels, we demonstrate click-ExM on lipids, glycans, proteins, DNA, RNA and small molecules. We demonstrate that click-ExM is applicable in cell culture systems and for tissue imaging. We further show that click-ExM is compatible with signal-amplification techniques and two-color imaging. Click-ExM thus provides a convenient and versatile method for super-resolution imaging, which may be routinely used for cell and tissue samples.
62 citations
TL;DR: The 1,4-conjugate addition reaction between activated alkynes or acetylenic Michael acceptors and nucleophiles is a historically useful organic transformation as discussed by the authors, but the efficiency and outcomes can vary widely and are often closely dependent upon specific reaction conditions.
Abstract: The 1,4-conjugate addition reaction between activated alkynes or acetylenic Michael acceptors and nucleophiles (i.e., the nucleophilic Michael reaction) is a historically useful organic transformation. Despite its general utility, the efficiency and outcomes can vary widely and are often closely dependent upon specific reaction conditions. Nevertheless, with improvements in reaction design, including catalyst development and an expansion of the substrate scope to feature more electrophilic alkynes, many examples now present with features that are congruent with Click chemistry. Although several nucleophilic species can participate in these conjugate additions, ubiquitous nucleophiles such as thiols, amines, and alcohols are commonly employed and, consequently, among the most well developed. For many years, these conjugate additions were largely relegated to organic chemistry, but in the last few decades their use has expanded into other spheres such as bioorganic chemistry and polymer chemistry. Within these fields, they have been particularly useful for bioconjugation reactions and step-growth polymerizations, respectively, due to their excellent efficiency, orthogonality, and ambient reactivity. The reaction is expected to feature in increasingly divergent application settings as it continues to emerge as a Click reaction.
56 citations
TL;DR: This review takes a look at the different bioorthogonal reactions that have recently been developed, the methods of cellular incorporation and the strategies to create orthogonality within the bioorthogsonal landscape.
54 citations
TL;DR: In this article, the main strategies offered by click and bioorthogonal chemistry, with respect to passive and active targeting, for NP functionalization with specific and multiple properties for imaging and cancer therapy are identified.
Abstract: Over the years, click and bioorthogonal reactions have been the subject of considerable research efforts. These high-performance chemical reactions have been developed to meet requirements not often provided by the chemical reactions commonly used today in the biological environment, such as selectivity, rapid reaction rate, and biocompatibility. Click and bioorthogonal reactions have been attracting increasing attention in the biomedical field for the engineering of nanomedicines. In this review, we study a compilation of articles from 2014 to the present, using the terms "click chemistry and nanoparticles (NPs)" to highlight the application of this type of chemistry for applications involving NPs intended for biomedical applications. This study identifies the main strategies offered by click and bioorthogonal chemistry, with respect to passive and active targeting, for NP functionalization with specific and multiple properties for imaging and cancer therapy. In the final part, a novel and promising approach for "two step" targeting of NPs, called pretargeting (PT), is also discussed; the principle of this strategy as well as all the studies listed from 2014 to the present are presented in more detail.
52 citations
TL;DR: In this article, a review of click reactions is presented, the key aspects, the mechanistic details and merits and demerits of the click reaction, and the recent pharmaceutical applications of click chemistry, ranging from the development of anticancer, antibacterial, and antiviral agents to that of biomedical imaging agents and clinical therapeutics.
TL;DR: In this article, a site-selective tyrosine bioconjugation pathway was developed for the synthesis of structurally defined fluorescent conjugates from native proteins using photoredox catalysis.
Abstract: The growing prevalence of synthetically modified proteins in pharmaceuticals and materials has exposed the need for efficient strategies to enable chemical modifications with high site-selectivity. While genetic engineering can incorporate non-natural amino acids into recombinant proteins, regioselective chemical modification of wild-type proteins remains a challenge. Herein, we use photoredox catalysis to develop a site-selective tyrosine bioconjugation pathway that incorporates bioorthogonal formyl groups, which subsequently allows for the synthesis of structurally defined fluorescent conjugates from native proteins. A water-soluble photocatalyst, lumiflavin, has been shown to induce oxidative coupling between a previously unreported phenoxazine dialdehyde tag and a single tyrosine site, even in the presence of multiple tyrosyl side chains, through the formation of a covalent C–N bond. A variety of native proteins, including those with multiple tyrosines, can successfully undergo both tyrosine-specific and single-site-selective labelling. This technology directly introduces aldehyde moieties onto native proteins, enabling rapid product diversification using an array of well-established bioorthogonal functionalization protocols including the alkyne–azide click reaction. Regioselective chemical modification of wild-type proteins remains challenging. Now, by harnessing the varied SOMOphilicity of native tyrosine residues through photoredox catalysis, a site-selective bioconjugation method has been developed. This technology directly incorporates bioorthogonal formyl groups in one step, forming structurally defined fluorescent conjugates that can be rapidly diversified to biorelevant products.
TL;DR: In this paper, the authors report the synthesis of several structurally diverse SOF4-derived copolymers based on the polymerization of bis(iminosulfur oxydifluorides) and bis(aryl silyl ethers).
Abstract: Sulfur(vi) fluoride exchange (SuFEx) is a category of click chemistry that enables covalent linking of modular units through sulfur(vi) connective hubs. The efficiency of SuFEx and the stability of the resulting bonds have led to polymer chemistry applications. Now, we report the SuFEx click chemistry synthesis of several structurally diverse SOF4-derived copolymers based on the polymerization of bis(iminosulfur oxydifluorides) and bis(aryl silyl ethers). This polymer class presents two key characteristics. First, the [–N=S(=O)F–O–] polymer backbone linkages are themselves SuFExable and undergo precise SuFEx-based post-modification with phenols or amines to yield branched functional polymers. Second, studies of individual polymer chains of several of these new materials indicate helical polymer structures. The robust nature of SuFEx click chemistry offers the potential for post-polymerization modification, enabling the synthesis of materials with control over composition and conformation. Sulfur(vi) fluoride exchange (SuFEx)—a type of click chemistry that generates SVI-centred covalent linkages—has previously been used for polymer synthesis. Now, modular SuFEx polymerization using SOF4 has been used to generate helical polymers. Unlike previous examples of SuFEx polymerization, the backbone retains SVI–F motifs and therefore is able to undergo further SuFEx click reactions, enabling facile and efficient post-polymerization modification.
TL;DR: In this paper, a dual pH/thermo-responsive hydrogel was designed based on a polyelectrolyte complex of polyacrylic acid (PAA) and norbornene-functionalized chitosan (CsNb), which was synergized with chemical crosslinking using bistetrazine-poly(N-isopropyl acrylamide) (bisTz-PNIPAM).
TL;DR: The smart UV-crosslinkable chitosan hydrogel via click chemistry might provide a new drug carrier for active modulating opposite drug release behaviors.
TL;DR: In the two decades since the introduction of the click chemistry concept, the toolbox of "click reactions" has continually expanded, enabling chemists, materials scientists, and biologists to rapidly and selectively build complexity for their applications of interest as discussed by the authors.
Abstract: In the two decades since the introduction of the "click chemistry" concept, the toolbox of "click reactions" has continually expanded, enabling chemists, materials scientists, and biologists to rapidly and selectively build complexity for their applications of interest. Similarly, selective and efficient covalent bond breaking reactions have provided and will continue to provide transformative advances. Here, we review key examples and applications of efficient, selective covalent bond cleavage reactions, which we refer to herein as "clip reactions." The strategic application of clip reactions offers opportunities to tailor the compositions and structures of complex (bio)(macro)molecular systems with exquisite control. Working in concert, click chemistry and clip chemistry offer scientists and engineers powerful methods to address next-generation challenges across the chemical sciences.
TL;DR: Protein lipid modification involves the attachment of hydrophobic groups to proteins via ester, thioester, amide, or thioether linkages as discussed by the authors, and the role of click chemistry in elucidating specific biological features.
Abstract: Protein lipid modification involves the attachment of hydrophobic groups to proteins via ester, thioester, amide, or thioether linkages. In this review, the specific click chemical reactions that have been employed to study protein lipid modification and their use for specific labeling applications are first described. This is followed by an introduction to the different types of protein lipid modifications that occur in biology. Next, the roles of click chemistry in elucidating specific biological features including the identification of lipid-modified proteins, studies of their regulation, and their role in diseases are presented. A description of the use of protein-lipid modifying enzymes for specific labeling applications including protein immobilization, fluorescent labeling, nanostructure assembly, and the construction of protein-drug conjugates is presented next. Concluding remarks and future directions are presented in the final section.
TL;DR: This article highlights the mechanism of reversible kinetics and its applications in chemical biology, medicinal chemistry, biomedical devices, and material chemistry, and emphasizes the fundamental reactivity of these two conjugate chemistries with assorted nucleophiles at variable pHs.
Abstract: Recently, reversible click reactions have found numerous applications in chemical biology, supramolecular chemistry, and biomedical applications. Boronic acid (BA)-mediated cis-diol conjugation is one of the best-studied reactions among them. An excellent understanding of the chemical properties and biocompatibility of BA-based compounds has inspired the exploration of novel chemistries using boron to fuel emergent sciences. This topical review focuses on the recent progress of iminoboronate and salicylhydroxamic-boronate constituted reversible click chemistries in the past decade. We highlight the mechanism of reversible kinetics and its applications in chemical biology, medicinal chemistry, biomedical devices, and material chemistry. This article also emphasizes the fundamental reactivity of these two conjugate chemistries with assorted nucleophiles at variable pHs, which is of utmost importance to any stimuli-responsive biological and material chemistry explorations.
07 Apr 2021
TL;DR: Protein immobilization is an essential method for both basic and applied research into protein, and the covalent, site-specific attachment is the most desirable strategy.
Abstract: Protein immobilization is an essential method for both basic and applied research for protein, and covalent, site-specific attachment is the most desirable strategy. Classic methods typically rely ...
TL;DR: Light-mediated coupling of acyl-silanes with indoles is reported in this paper, where photo click reaction occurs under mild conditions (415 nm) mostly in quantitative yield and provides stable silylated N,O-acetals via light mediated siloxycarbene generation with subsequent indole-N-H insertion.
Abstract: Light-mediated coupling of acylsilanes with indoles is reported. This photo click reaction occurs under mild conditions (415 nm) mostly in quantitative yield and provides stable silylated N,O-acetals via light mediated siloxycarbene generation with subsequent indole-N-H insertion. We show that this very efficient and fully atom economic coupling process can be applied to conjugate complex systems, as documented by the clicking of carbohydrates with indole alkaloids. The method is also applicable to the conjugation of polymer chains. The linking acetal moiety can be readily cleaved and it is also shown that wavelength-selective coupling and cleavage with acyl silanes bearing a second photoactive moiety is possible. This is documented by a successful polymerization/depolymerization sequence and by a polymer folding/unfolding process.
11 Jan 2021
TL;DR: In this article, a dual-functional polyurethane elastomer having disulfide as well as furfuryl functionality was used for a variety of applications, including medical applications.
Abstract: Functional polyurethanes have several important advanced applications. In this investigation, a dual-functional polyurethane (PU) elastomer having disulfide as well as furfuryl functionality was de...
TL;DR: In this article, the most recent and relevant developments in click chemistry as a functionalization and polymerization method of vegetable oils and their derivatives are discussed. But the focus of this paper is the development of this efficient chemistry for the synthesis of polymer materials derived from vegetable oils.
TL;DR: In this article, a review of the most versatile Cu(I) catalyzed catalyzed azide-alkyne cycloaddition (CuAAC) complexes has been presented, focusing on those versatile Cu (I) complexes having tailoring capability similar to those available commercially.
TL;DR: In this paper, the authors discuss the hurdles encountered when targeting biomolecules localized in cell organelles and give an easily accessible summary of the strategies at hand for imaging intracellular targets.
Abstract: The surging development of bioorthogonal chemistry has profoundly transformed chemical biology over the last two decades. Involving chemical partners that specifically react together in highly complex biological fluids, this branch of chemistry now allows researchers to probe biomolecules in their natural habitat through metabolic labelling technologies. Chemical reporter strategies include metabolic glycan labelling, site-specific incorporation of unnatural amino acids in proteins, and post-synthetic labelling of nucleic acids. While a majority of literature reports mark cell-surface exposed targets, implementing bioorthogonal ligations in the interior of cells constitutes a more challenging task. Owing to limiting factors such as membrane permeability of reagents, fluorescence background due to hydrophobic interactions and off-target covalent binding, and suboptimal balance between reactivity and stability of the designed molecular reporters and probes, these strategies need mindful planning to achieve success. In this review, we discuss the hurdles encountered when targeting biomolecules localized in cell organelles and give an easily accessible summary of the strategies at hand for imaging intracellular targets.
TL;DR: This review covering the synthetic access to main mesoionics, their reaction with dipolarophiles, and recent applications in chemical biology and heterocycle synthesis is focused on the emerging click chemistry that uses mesoionic compounds as dipole partners.
Abstract: Click and bio-orthogonal reactions are dominated by cycloaddition reactions in general and 1,3-dipolar cycloadditions in particular. Among the dipoles routinely used for click chemistry, azides, nitrones, isonitriles, and nitrile oxides are the most popular. This review is focused on the emerging click chemistry that uses mesoionic compounds as dipole partners. Mesoionics are a very old family of molecules, but their use as reactants for click and bio-orthogonal chemistry is quite recent. The facility to derivatize these dipoles and to tune their reactivity toward cycloaddition reactions makes mesoionics an attractive opportunity for future click chemistry development. In addition, some compounds from this family are able to undergo click-and-release reactions, finding interesting applications in cells, as well as in animals. This review covers the synthetic access to main mesoionics, their reaction with dipolarophiles, and recent applications in chemical biology and heterocycle synthesis.
TL;DR: In this article, new thienopyrimidine conjugates bearing 1,2,3-triazole core and different sugar moieties have been designed and synthesized by Cu(I)-catalysed click dipolar cycloaddition.
Abstract: In the current study, new thienopyrimidine conjugates bearing 1,2,3-triazole core and different sugar moieties have been designed and synthesized by Cu(I)-catalysed click dipolar cycloaddition. The cytotoxic activity of the synthesised conjugates 2, 5, 7, and 13-18 was studied against HCT-116 and MCF-7 cell lines by the MTT assay. The triazole glycosides 16 and 18 provided significant cytotoxic activities against HCT-116 cell lines comparable to that of doxorubicin and other studied compounds. The cytotoxic behaviour against MCF-7 exhibited that all the investigated compounds were more potent than doxorubicin. Moreover, all screened targets were evaluated against mutant EGFR kinase type L858R and the results revealed that the acetylated 1,2,3-triazole glycosides 13-18 exhibited excellent EGFR inhibitory activity in comparison with gefitinib. Furthermore, molecular modelling studies were performed to investigate the binding affinity of the most active compounds to EGFR enzyme.
TL;DR: In this article, click chemistry has generated significant research interest due to its high reaction efficiency, high selectivity for a single product, harmless byproducts, and processing simplicity, which enables the production of alginate derivatives with enhanced physical and chemical properties.
TL;DR: This review focuses on a series of chemical reactions, i.e., nucleophilic substitution, click chemistry, supramolecular modification, photochemical reaction, and other reactions, which have been applied for the modification of hydroxyl-terminated substrates, like silicon and glass, which has been reported during the last 10 years.
Abstract: In this review, we aim to update our review “Chemical modification of self-assembled silane-based monolayers by surface reactions” which was published in 2010 and has developed into an important guiding tool for researchers working on the modification of solid substrate surface properties by chemical modification of silane-based self-assembled monolayers. Due to the rapid development of this field of research in the last decade, the utilization of chemical functionalities in self-assembled monolayers has been significantly improved and some new processes were introduced in chemical surface reactions for tailoring the properties of solid substrates. Thus, it is time to update the developments in the surface functionalization of silane-based molecules. Hence, after a short introduction on self-assembled monolayers, this review focuses on a series of chemical reactions, i.e., nucleophilic substitution, click chemistry, supramolecular modification, photochemical reaction, and other reactions, which have been applied for the modification of hydroxyl-terminated substrates, like silicon and glass, which have been reported during the last 10 years.
TL;DR: In this article, a tumor-targeting drug-loaded MOF using click chemistry to anchor functional folic acid (FA) molecules on the surface of N3-bio-MOF-100 was discussed.
Abstract: Metal-organic frameworks (MOFs) offer many opportunities for applications across biology and medicine. Their wide range of chemical composition makes toxicologically acceptable formulation possible, and their high level of functionality enables possible applications as delivery systems for therapeutics agents. Surface modifications have been used in drug delivery systems to minimize their interaction with the bulk, improving their specificity as targeted carriers. Herein, we discuss a strategy to achieve a tumor-targeting drug-loaded MOF using "click" chemistry to anchor functional folic acid (FA) molecules on the surface of N3-bio-MOF-100. Using curcumin (CCM) as an anticancer drug, we observed drug loading encapsulation efficiencies (DLEs) of 24.02 and 25.64% after soaking N3-bio-MOF-100 in CCM solutions for 1 day and 3 days, respectively. The success of postsynthetic modification of FA was confirmed by 1H NMR spectroscopy, Fourier transform infrared spectroscopy (FTIR), and liquid chromatography-mass spectrometry (LC-MS). The stimuli-responsive drug release studies demonstrated an increase of CCM released under acidic microenvironments. Moreover, the cell viability assay was performed on the 4T1 (breast cancer) cell line in the presence of CCM@N3-bio-MOF-100 and CCM@N3-bio-MOF-100/FA carriers to confirm its biological compatibility. In addition, a cellular uptake study was conducted to evaluate the targeting of tumor cells.
TL;DR: A survey highlights key recent achievements in the use of the strain-promoted azide-alkyne cycloaddition to produce a variety of polymeric constructs for disparate applications.
Abstract: Highly efficient reactions that enable the assembly of molecules into complex structures have driven extensive progress in synthetic chemistry. In particular, reactions that occur under mild conditions and in benign solvents, while producing no by-products and rapidly reach completion are attracting significant attention. Amongst these, the strain-promoted azide-alkyne cycloaddition, involving various cyclooctyne derivatives reacting with azide-bearing molecules, has gained extensive popularity in organic synthesis and bioorthogonal chemistry. This reaction has also recently gained momentum in polymer chemistry, where it has been used to decorate, link, crosslink, and even prepare polymer chains. This survey highlights key achievements in the use of this reaction to produce a variety of polymeric constructs for disparate applications.