Showing papers on "Click chemistry published in 2019"
TL;DR: This review discusses the growing number of applications of SuFEx, which can be found in nearly all areas of modern chemistry; from drug discovery to materials science.
Abstract: SuFEx (Sulfur Fluoride Exchange) is a modular, next generation family of click reactions, geared towards the rapid and reliable assembly of functional molecules. This review discusses the growing number of applications of SuFEx, which can be found in nearly all areas of modern chemistry; from drug discovery to materials science.
227 citations
TL;DR: Copper-free click chemistry has resulted in a change of paradigm, showing that artificial chemical reactions can occur on cell surfaces, in cell cytosol, or within the body.
Abstract: Recently, click chemistry has provided important advances in biomedical research fields. Particularly, copper-free click chemistry including strain-promoted azide–alkyne cycloaddition (SPAAC) and inverse-electron-demand Diels–Alder (iEDDA) reactions enable fast and specific chemical conjugation under aqueous conditions without the need for toxic catalysts. Click chemistry has resulted in a change of paradigm, showing that artificial chemical reactions can occur on cell surfaces, in cell cytosol, or within the body, which is not easy with most other chemical reactions. Click chemistry in vitro allows specific labelling of cellular target proteins and studying of drug target engagement with drug surrogates in live cells. Furthermore, cellular membrane lipids and proteins could be selectively labelled with click chemistry in vitro and cells could be adhered together using click chemistry. Click chemistry in vivo enables efficient and effective molecular imaging and drug delivery for diagnosis and therapy. Click chemistry ex vivo can be used to develop molecular tools to understand tissue development, diagnosis of diseases, and therapeutic monitoring. Overall, the results from research to date suggest that click chemistry has emerged as a valuable tool in biomedical fields as well as in organic chemistry.
200 citations
TL;DR: A ‘click’ reaction is developed for the simple and rapid formation of azides from primary amines, and is used to prepare a library of over 1,200 azides for subsequent use in the existing triazole annulation click reaction.
Abstract: Click chemistry is a concept in which modular synthesis is used to rapidly find new molecules with desirable properties1. Copper(i)-catalysed azide–alkyne cycloaddition (CuAAC) triazole annulation and sulfur(vi) fluoride exchange (SuFEx) catalysis are widely regarded as click reactions2–4, providing rapid access to their products in yields approaching 100% while being largely orthogonal to other reactions. However, in the case of CuAAC reactions, the availability of azide reagents is limited owing to their potential toxicity and the risk of explosion involved in their preparation. Here we report another reaction to add to the click reaction family: the formation of azides from primary amines, one of the most abundant functional groups5. The reaction uses just one equivalent of a simple diazotizing species, fluorosulfuryl azide6–11 (FSO2N3), and enables the preparation of over 1,200 azides on 96-well plates in a safe and practical manner. This reliable transformation is a powerful tool for the CuAAC triazole annulation, the most widely used click reaction at present. This method greatly expands the number of accessible azides and 1,2,3-triazoles and, given the ubiquity of the CuAAC reaction, it should find application in organic synthesis, medicinal chemistry, chemical biology and materials science. A ‘click’ reaction is developed for the simple and rapid formation of azides from primary amines, and is used to prepare a library of over 1,200 azides for subsequent use in the existing triazole annulation click reaction.
138 citations
TL;DR: This system constructed a heterogeneous copper catalyst on a metal-organic framework that could preferentially accumulate in the mitochondria of living cells and enabled the localized synthesis of drugs through a site-specific CuAAC reaction in mitochondria with good biocompatibility.
Abstract: As a typical bioorthogonal reaction, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) has been used for drug design and synthesis. However, for localized drug synthesis, it is important to be able to determine where the CuAAC reaction occurs in living cells. In this study, we constructed a heterogeneous copper catalyst on a metal-organic framework that could preferentially accumulate in the mitochondria of living cells. Our system enabled the localized synthesis of drugs through a site-specific CuAAC reaction in mitochondria with good biocompatibility. Importantly, the subcellular catalytic process for localized drug synthesis avoided the problems of the delivery and distribution of toxic molecules. In vivo tumor therapy experiments indicated that the localized synthesis of resveratrol-derived drugs led to greater antitumor efficacy and minimized side effects usually associated with drug delivery and distribution.
127 citations
TL;DR: The discovery and characterization of a unique pathway to produce a terminal alkyne-containing amino acid in the bacterium Streptomyces cattleya is reported, found that l-lysine undergoes an unexpected reaction sequence that includes halogenation, oxidative C–C bond cleavage and triple bond formation through a putative allene intermediate.
Abstract: Living systems can generate an enormous range of cellular functions, from mechanical infrastructure and signalling networks to enzymatic catalysis and information storage, using a notably limited set of chemical functional groups. This observation is especially notable when compared to the breadth of functional groups used as the basis for similar functions in synthetically derived small molecules and materials. The relatively small cross-section between biological and synthetic reactivity space forms the foundation for the development of bioorthogonal chemistry, in which the absence of a pair of reactive functional groups within the cell allows for a selective in situ reaction1–4. However, biologically ‘rare’ functional groups, such as the fluoro5, chloro6,7, bromo7,8, phosphonate9, enediyne10,11, cyano12, diazo13, alkene14 and alkyne15–17 groups, continue to be discovered in natural products made by plants, fungi and microorganisms, which offers a potential route to genetically encode the endogenous biosynthesis of bioorthogonal reagents within living organisms. In particular, the terminal alkyne has found broad utility via the Cu(i)-catalysed azide-alkyne cycloaddition ‘click’ reaction18. Here we report the discovery and characterization of a unique pathway to produce a terminal alkyne-containing amino acid in the bacterium Streptomyces cattleya. We found that l-lysine undergoes an unexpected reaction sequence that includes halogenation, oxidative C–C bond cleavage and triple bond formation through a putative allene intermediate. This pathway offers the potential for de novo cellular production of halo-, alkene- and alkyne-labelled proteins and natural products from glucose for a variety of downstream applications. Microbial generation of a terminal-alkyne-containing amino acid can be encoded into E. coli and provides the potential for in vivo generation of proteins and natural products for click chemistry.
113 citations
TL;DR: To explore new chemical spaces for drug-like molecules containing a high degree of structural diversity, it may be useful to merge the diversity-oriented synthesis and ‘privileged’ substructure-based strategy with bioorthogonal reactions using sophisticated automation and flow systems to improve productivity.
Abstract: Introduction: Click chemistry has been exploited widely in the past to expedite lead discovery and optimization. Indeed, Copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry is a bioorthogonal reaction of widespread utility throughout medicinal chemistry and chemical biology. Areas covered: The authors review recent applications of CuAAC click chemistry to drug discovery based on the literature published since 2013. Furthermore, the authors provide the reader with their expert perspectives on the area including their outlook on future developments. Expert opinion: Click chemistry reactions are an important part of the medicinal chemistry toolbox and offer substantial advantages to medicinal chemists in terms of overcoming the limitations of useful chemical synthesis, increasing throughput, and improving the quality of compound libraries. To explore new chemical spaces for drug-like molecules containing a high degree of structural diversity, it may be useful to merge the diversity-oriented synthesis and 'privileged' substructure-based strategy with bioorthogonal reactions using sophisticated automation and flow systems to improve productivity. Large compound libraries obtained in this way should be of great value for the discovery of bioactive compounds and therapeutic agents.
112 citations
TL;DR: In this article, a type of click chemistry involving the reaction of thiols with isocyanates was used to synthesize polythiourethane (PTU).
Abstract: Polythiourethane (PTU) can be synthesized by a type of click chemistry involving the reaction of thiols with isocyanates. To our knowledge, thiourethane dynamic chemistry has not been significantly...
108 citations
TL;DR: An electrochemical aptasensor based on click chemistry and the DNA hybridization chain reaction (HCR) for signal amplification has been developed for the ultrasensitive detection of tumor exosomes and has high potential for exosome analysis in clinical samples.
108 citations
TL;DR: ClampFISH as discussed by the authors is a click-amplifying FISH that achieves high specificity and high-gain (>400-fold) signal amplification by ligating the ends of the probes together using bio-orthogonal click chemistry, effectively locking the probes around the target.
Abstract: Methods for detecting single nucleic acids in cell and tissues, such as fluorescence in situ hybridization (FISH), are limited by relatively low signal intensity and nonspecific probe binding. Here we present click-amplifying FISH (clampFISH), a method for fluorescence detection of nucleic acids that achieves high specificity and high-gain (>400-fold) signal amplification. ClampFISH probes form a 'C' configuration upon hybridization to the sequence of interest in a double helical manner. The ends of the probes are ligated together using bio-orthogonal click chemistry, effectively locking the probes around the target. Iterative rounds of hybridization and click amplify the fluorescence intensity. We show that clampFISH enables the detection of RNA species with low-magnification microscopy and in RNA-based flow cytometry. Additionally, we show that the modular design of clampFISH probes allows multiplexing of RNA and DNA detection, that the locking mechanism prevents probe detachment in expansion microscopy, and that clampFISH can be applied in tissue samples.
102 citations
TL;DR: Some applications of click chemistry for cell engineering in cell transplantation and for drug delivery in the diagnosis and treatment of diseases are described.
Abstract: Click chemistry has great potential for use in binding between nucleic acids, lipids, proteins, and other molecules, and has been used in many research fields because of its beneficial characteristics, including high yield, high specificity, and simplicity. The recent development of copper-free and less cytotoxic click chemistry reactions has allowed for the application of click chemistry to the field of medicine. Moreover, metabolic glycoengineering allows for the direct modification of living cells with substrates for click chemistry either in vitro or in vivo. As such, click chemistry has become a powerful tool for cell transplantation and drug delivery. In this review, we describe some applications of click chemistry for cell engineering in cell transplantation and for drug delivery in the diagnosis and treatment of diseases.
96 citations
TL;DR: The azide-alkyne 1,3-dipolar cycloaddition was introduced into the field of metal-organic frameworks (MOFs) in 2007 and has become an effective and robust tool in the fabrication and modification of various functional materials.
TL;DR: The SuFEx bioconjugation of iminosulfur oxydifluorides to amine-tagged single-stranded DNA and to BSA protein demonstrate the potential of SOF4 -derived SuFex click chemistry in biological applications.
Abstract: We report here the development of a suite of biocompatible SuFEx transformations from the SOF4 -derived iminosulfur oxydifluoride hub in aqueous buffer conditions. These biocompatible SuFEx reactions of iminosulfur oxydifluorides (R-N=SOF2 ) with primary amines give sulfamides (8 examples, up to 98 %), while the reaction with secondary amines furnish sulfuramidimidoyl fluoride products (8 examples, up to 97 %). Likewise, under mild buffered conditions, phenols react with the iminosulfur oxydifluorides (Ar-N=SOF2 ) to produce sulfurofluoridoimidates (13 examples, up to 99 %), which can themselves be further modified by nucleophiles. These transformations open the potential for asymmetric and trisubstituted linkages projecting from the sulfur(VI) center, including versatile S-N and S-O connectivity (9 examples, up to 94 %). Finally, the SuFEx bioconjugation of iminosulfur oxydifluorides to amine-tagged single-stranded DNA and to BSA protein demonstrate the potential of SOF4 -derived SuFEx click chemistry in biological applications.
TL;DR: A combined experimental and computational study shows that the same CuI-SCNP perform a more efficient click reaction on modified protein surfaces and cell surface glycans than do small-molecule catalysts.
Abstract: Recent work has shown that polymeric catalysts can mimic some of the remarkable features of metalloenzymes by binding substrates in proximity to a bound metal center. We report here an unexpected role for the polymer: multivalent, reversible, and adaptive binding to protein surfaces allowing for accelerated catalytic modification of proteins. The catalysts studied are a group of copper-containing single-chain polymeric nanoparticles (CuI-SCNP) that exhibit enzyme-like catalysis of the copper-mediated azide-alkyne cycloaddition reaction. The CuI-SCNP use a previously observed "uptake mode", binding small-molecule alkynes and azides inside a water-soluble amphiphilic polymer and proximal to copper catalytic sites, but with unprecedented rates. Remarkably, a combined experimental and computational study shows that the same CuI-SCNP perform a more efficient click reaction on modified protein surfaces and cell surface glycans than do small-molecule catalysts. The catalysis occurs through an "attach mode" where the SCNPs reversibly bind protein surfaces through multiple hydrophobic and electrostatic contacts. The results more broadly point to a wider capability for polymeric catalysts as artificial metalloenzymes, especially as it relates to bioapplications.
01 Nov 2019
TL;DR: An overview of recent developments in bio-orthogonal click chemistry for bioimaging in living organisms is provided and potential future directions of this exciting area are presented.
Abstract: The rapid advancement of bio-orthogonal click chemistry in the past decade has enabled the study and precise manipulation of biological processes within living organisms. The capability to induce fast and selective chemical reactions between two exogenous complementary moieties in living systems, with negligible perturbation to their native activities, have rendered bio-orthogonal click chemistry highly promising for a multitude of bioapplications. This review provides an overview of recent developments in bio-orthogonal click chemistry for bioimaging in living organisms. Bio-orthogonal click reactions commonly performed in in vivo systems and their in vivo biological labeling and imaging applications, particularly for the visualization of biomolecular processes, therapeutic cells, tumors, and bacteria, are discussed. Potential future directions of this exciting area are also presented.
TL;DR: A strong in vivo antimicrobial efficacy with a log reduction above 3 in a mouse bacterial sepsis model has been obtained and present a promising prospect for Dex- g-K nF m in biomedical applications.
24 Apr 2019
TL;DR: This Perspective is concerned with the pre-assembly of molecular conjugates or surface-coated nanoparticles and the in situ capture of tagged biomolecular targets for imaging or analysis in non-covalent click chemistry.
Abstract: Molecular conjugation refers to methods used in biomedicine, advanced materials and nanotechnology to link two partners — from small molecules to large and sometimes functionally complex biopolymers. The methods ideally have a broad structural scope, proceed under very mild conditions (including in H2O), occur at a rapid rate and in quantitative yield with no by-products, enable bioorthogonal reactivity and have zero toxicity. Over the past two decades, the field of click chemistry has emerged to afford us new and efficient methods of molecular conjugation. These methods are based on chemical reactions that produce permanently linked conjugates, and we refer to this field here as covalent click chemistry. Alternatively, if molecular conjugation is undertaken using a pair of complementary molecular recognition partners that associate strongly and selectively to form a thermodynamically stable non-covalent complex, then we refer to this strategy as non-covalent click chemistry. This Perspective is concerned with this latter approach and highlights two distinct applications of non-covalent click chemistry in molecular conjugation: the pre-assembly of molecular conjugates or surface-coated nanoparticles and the in situ capture of tagged biomolecular targets for imaging or analysis. The selective conjugation of two or more molecules is readily achieved using covalent click chemistry or non-covalent click chemistry. The latter approach makes use of complementary molecular recognition partners, and its speed and reversibility are advantageous for many biological applications.
TL;DR: Stimuli-responsive polymeric micelles via click chemistry are divided into six major sections (temperature, light, ultrasound, pH, enzymes, and redox).
TL;DR: A mild method is presented for the modification of the basal planes of 2H-MoS2 and WS2, exploiting the soft nucleophilicity of sulfur to react it with maleimide derivatives, achieving covalent functionalization of 2D-TMDCs under very mild conditions.
Abstract: The physical properties of ultrathin transition metal dichalcogenides (2D-TMDCs) make them promising candidates as active nanomaterials for catalysis, optoelectronics, and biomedical applications. Chemical modification of TMDCs is expected to be key in modifying/adding new functions that will help make such promise a reality. We present a mild method for the modification of the basal planes of 2H-MoS2 and WS2. We exploit the soft nucleophilicity of sulfur to react it with maleimide derivatives, achieving covalent functionalization of 2H-TMDCs under very mild conditions. Extensive characterization proves that the reaction occurs through Michael addition. The orthogonality and versatility of the thiol–ene “click” chemistry is expected to allow the a la carte chemical manipulation of TMDCs.
TL;DR: The studies suggest that TAAC reaction can be implemented in diverse molecular categories and has high potential to develop into a field with practical applications.
Abstract: Topochemical reactions are solid-state reactions that transpire under the strict control of molecular packing in the crystal lattice. Due to this lattice control, these reactions generate products in a regio-/stereospecific manner and in very high yields. In a broader sense, topochemical reactions mimic nature's way of carrying out reactions in a confined environment of enzymes giving specific products. Apart from their remarkable specificity, topochemical reactions have many other interesting features that make these reactions more attractive than solution-phase reactions. Solution-phase reactions necessitate the use of reactants, reagents, catalysts, and solvents and often give products along with varying amounts of byproducts, necessitating complex workup and chromatographic purification using various chemicals. These inevitable chemical wastes from solution-state reactions could be avoided by topochemical reactions, as they are solvent-free and catalyst-free and often do not require any chromatographic purification in view of their specificity and high yielding nature. Also the confinement offered by the crystal lattice gives products that are not possible by solution-phase reactions. Another interesting feature of topochemical reactions is the possibility of formation of products in an ordered (crystalline) form, which imparts interesting properties. Thus, topochemical reactions have control not only at the molecular level (regio-/stereospecificity) but also at the supramolecular level (packing). Many topochemical reactions happen in single-crystal-to-single-crystal (SCSC) fashion, and crystal structure analysis of such reactions often gives mechanistic insights and knowledge about the geometrical criteria required for the reaction. Despite all these attractive features, reactions that can be done topochemically are limited. There is tremendous interest in the development of new categories of topochemical reactions and strategies to achieve reactivity in crystals. In this Account, we will summarize our attempts to develop topochemical azide-alkyne cycloaddition (TAAC) reactions. We have used hydrogen-bonding as the main noncovalent interaction for aligning azide-and-alkyne-substituted derivatives of various biomolecules in orientations suitable for their proximity-driven cycloaddition reaction in crystals. Overall, three major classes of biomolecules; carbohydrates, nucleosides, and peptides were successfully exploited for their TAAC reactions using conventional O-H···O, N-H···O, and N-H···N hydrogen bonds as supramolecular glues for controlling their assembly in crystals. The crystals of these monomers underwent TAAC reaction either spontaneously at room temperature or under heating yielding triazole-linked biopolymer mimics. The ordered packing of product molecules imparted special properties to the products formed. The legendary "cream of the crop" azide-alkyne click reaction has diverse applications in the areas of bioconjugation, material science, polymer synthesis, and so forth. Belonging to the same genre, TAAC is a novel metal-free approach for making the triazole-linked products employing the ordered crystal/gel as a reaction medium. In brief, our studies suggest that TAAC reaction can be implemented in diverse molecular categories and has high potential to develop into a field with practical applications.
TL;DR: An enantioselective CuAAC (E-CuAAC), enabled by dynamic kinetic resolution (DKR), is reported, which can directly generate α-chiral triazoles in a complex molecular environment.
Abstract: The copper(I) catalyzed alkyne-azide cycloaddition (CuAAC), a click reaction, is one of the most powerful catalytic reactions developed during the last two decades. Conducting CuAAC enantioselectively would add a third dimension to this reaction and would enable the direct synthesis of α-chiral triazoles. Doing so is demanding because the two precursors have linear geometries, and the triazole product is a flat heterocycle. Designing a chiral catalyst is further complicated by the complex mechanism of CuAAC. We report an enantioselective CuAAC (E-CuAAC), enabled by dynamic kinetic resolution (DKR). The E-CuAAC is high yielding and affords up to 99:1 er. The E-CuAAC can directly generate α-chiral triazoles in a complex molecular environment.
TL;DR: Flow cytometric analysis revealed that compounds 3, 6f and 6h arrested cell cycle at G0/G1 phase in MCF-7 cells, therefore, synthesized aminonaphthoquinone-1,2,3-triazole derivatives can be introduced as promising molecules for further development as potential anticancer agents.
TL;DR: A new concept of click hydrogel fabrication that combines a traditional sugar-based boronic ester and a novel nopoldiol-based benzoxaborolate as a dual-crosslink network (DCN) system is reported.
Abstract: The use of click chemistry as a hydrogel cross-linking reaction is often limited by slow reaction rates and harsh conditions, such as exposure to UV light and/or use of nonspecific or toxic reagent...
TL;DR: In this article, a thiol-ene click reaction was used to graft styrene-butadiene-block-copolymer with carboxylic acid at an optimal concentration.
Abstract: Recent studies of all-solid-state batteries (ASSBs) have identified sulfide-based electrolytes with comparable ionic conductivities as those of liquid counterparts. Nevertheless, solution-based manufacturing is unestablished, since it is challenging to find adhesive polymeric binders that can be dispersed in common solvents with sulfide electrolytes. Currently available binders exhibit insufficient electrode adhesion due to their low polarity and are compromised by the chemical stability of a slurry. Here, we report a thiol–ene click reaction used to graft styrene–butadiene-block-copolymer with carboxylic acid at an optimal concentration. With polarity tuning, the click binder results in a uniform electrode slurry without ruining the structure of the sulfide electrolytes, while enabling electrode adhesion 1.4 times as high as that of commercial lithium-ion battery electrodes. The click binder also allows ASSBs to deliver decent electrochemical performance, implying that fine polarity tuning of functional ...
TL;DR: In this paper, a series of benzothiazole-1,2,3-triazoles were designed and synthesized through the click chemistry approach; the DNA binding constants (Kb) were in the range of 1.732
TL;DR: It is shown that fluorescent molecularly imprinted polymer nanogels (MIP-NPs), can localize and detect intracellular HA and are endowed with improved binding site homogeneity and specificity, reminiscent of monoclonal antibodies.
Abstract: Hyaluronic acid (HA) is a glycosaminoglycan that plays many roles in health and disease and is a key biomarker of certain cancers. Therefore, its detection at an early stage, by histochemical methods, is of importance. However, intracellular HA can be masked by other HA-binding macromolecules, rendering its visualization somehow problematic. We show that fluorescent molecularly imprinted polymer nanogels (MIP-NPs), can localize and detect intracellular HA. MIP-NPs were synthesized by solid-phase synthesis on glass beads (GBs). GBs were functionalized with terminal alkyne groups on which an azide derivative of the template molecule glucuronic acid was immobilized via click chemistry. Immobilization via the anomeric carbon left the template's carboxyl moiety free to enable strong stoichiometric electrostatic interactions with a benzamidine-based functional monomer, to confer selective recognition to the MIP-NPs. Due to the two-point orientation of the template, the resulting MIP-NPs were endowed with improved binding site homogeneity and specificity, reminiscent of monoclonal antibodies. These synthetic antibodies were then applied for probing and staining HA, of which glucuronic acid is a substructure (epitope), on human epidermal cells. Their excellent sensitivity, small size and water compatibility, enabled the MIP-NPs to visualize HA, as evidenced by confocal fluorescence micrographs.
TL;DR: A method of SO2F2-mediated direct clickable coupling of carboxylic acids with amines was developed for the synthesis of a broad scope of amides in a simple, mild, highly efficient, robust and practical manner.
Abstract: The construction of amide bonds and peptide linkages is one of the most fundamental transformations in all life processes and organic synthesis. The synthesis of structurally ubiquitous amide motifs is essential in the assembly of numerous important molecules such as peptides, proteins, alkaloids, pharmaceutical agents, polymers, ligands and agrochemicals. A method of SO2F2-mediated direct clickable coupling of carboxylic acids with amines was developed for the synthesis of a broad scope of amides in a simple, mild, highly efficient, robust and practical manner (>110 examples, >90% yields in most cases). The direct click reactions of acids and amines on a gram scale are also demonstrated using an extremely easy work-up and purification process of washing with 1 M aqueous HCl to provide the desired amides in greater than 99% purity and excellent yields.
TL;DR: This smartphone app-assisted platform enables rapid (within 1 h) detection of Escherichia coli with high sensitivity in the complex artificial sepsis blood samples, showing great potential for clinical early diagnosis of bacterial infections.
Abstract: Bacterial infections pose mounting public health concerns and cause an enormous medical and financial burden today. Rapid and sensitive detection of pathogenic bacteria at the point of care (POC) remains a paramount challenge. Here, we report a novel concept of bacteria-instructed click chemistry and employ it for POC microbial sensing. In this concept of bacteria-instructed click chemistry, we demonstrate for the first time that pathogenic bacteria can capture and reduce exogenous Cu2+ to Cu+ by leveraging their unique metabolic processes. The produced Cu+ subsequently acts as a catalyst to trigger the click reaction between gold nanoparticles (AuNPs) modified with azide and alkyne functional molecules, resulting in the aggregation of nanoparticles with a color change of the solution from red to blue. In this process, signal amplification from click chemistry is complied with the aggregation of functionalized AuNPs, thus presenting a robust colorimetric strategy for sensitive POC sensing of pathogenic bacteria. Notably, this colorimetric strategy is easily integrated in a smartphone app as a portable platform to achieve one-click detection in a mobile way. Moreover, with the help of the magnetic preseparation process, this smartphone app-assisted platform enables rapid (within 1 h) detection of Escherichia coli with high sensitivity (40 colony-forming units/mL) in the complex artificial sepsis blood samples, showing great potential for clinical early diagnosis of bacterial infections.
TL;DR: The basics of these chemical reactions are explained and their recent applications in the field of radiopharmacy and chemical biology are introduced and the significance, current challenges, and prospects of using bioorthogonal conjugation reactions are discussed.
Abstract: In recent years, several catalyst-free site-specific reactions have been investigated for the efficient conjugation of biomolecules, nanomaterials, and living cells. Representative functional group pairs for these reactions include the following: (1) azide and cyclooctyne for strain-promoted cycloaddition reaction, (2) tetrazine and trans-alkene for inverse-electron-demand-Diels–Alder reaction, and (3) electrophilic heterocycles and cysteine for rapid condensation/addition reaction. Due to their excellent specificities and high reaction rates, these conjugation methods have been utilized for the labeling of radioisotopes (e.g., radiohalogens, radiometals) to various target molecules. The radiolabeled products prepared by these methods have been applied to preclinical research, such as in vivo molecular imaging, pharmacokinetic studies, and radiation therapy of cancer cells. In this review, we explain the basics of these chemical reactions and introduce their recent applications in the field of radiopharmacy and chemical biology. In addition, we discuss the significance, current challenges, and prospects of using bioorthogonal conjugation reactions.
TL;DR: It has been proved that the reaction underwent via an unprecedented metalloradical activation mechanism, which successfully overturn the ionic click reaction, which will enable to discover new drug candidates.
Abstract: A unique concept for the intermolecular denitrogenative annulation of 1,2,3,4-tetrazoles and alkynes was discovered by using a catalytic amount of Fe(TPP)Cl and Zn dust. The reaction precludes the traditional, more favored click reaction between an organic azide and alkynes, and instead proceeds by an unprecedented metalloradical activation. The method is anticipated to advance access to the construction of important basic nitrogen heterocycles, which will in turn enable discoveries of new drug candidates.
TL;DR: This phenylboronic acid-functionalized COF is promising as a new sorbent for selective removal of catechol from aqueous solution with high adsorption capacity and good reusability.
Abstract: We report a thiol-ene click strategy for the preparation of a novel phenylboronic acid-functionalized covalent organic framework (COF) for selective removal of catechol in aqueous solution. Vinyl-functionalized 2,5-diallyloxyterephthalaldehyde (Da-V) was prepared as a building ligand. Da-V was then condensed with 1,3,5-tris(4-aminophenyl)benzene (Tab) to give a vinyl-functionalized COF DhaTab-V. Subsequently, 4-mercaptophenylboronic acid (4-MPBA) was covalently linked on DhaTab-V via thiol-ene click reaction to give phenylboronic acid-functionalized COF DhaTab-PBA. The adsorption isotherms, energetics and kinetics, and reusability of DhaTab-PBA for the adsorption and removal of catechol from aqueous solution were investigated in detail. This phenylboronic acid-functionalized COF is promising as sorbent for selective removal of catechol from aqueous medium with large adsorption capacity and good reusability.