Themed collection Bioorthogonal and click chemistry: Celebrating the 2022 Nobel Prize in Chemistry
Click chemistry in the synthesis of catalytically relevant organoselenium compounds: development and applications of catalysts for organic synthesis
Use of click chemistry in synthesizing organoselenium compounds and the applications of metal complexes of such compounds as catalysts for various chemical transformations have been critically analyzed.
When CuAAC 'Click Chemistry' goes heterogeneous
Within the green chemistry context, heterogeneous catalysis is more and more applied to organic synthesis. The well known ‘click chemistry’ and especially its flagship, the copper-catalyzed azide–alkyne cycloaddition reaction (CuAAC), is now catch up by such heterogenisation process and copper ions or metals have been grafted or deposited on or into various solids, such as (bio)polymers, charcoal, silica, zeolites, POM or MOF.
Photo-controllable bioorthogonal chemistry for spatiotemporal control of bio-targets in living systems
The establishment of photo-controllable bioorthogonal chemistry is one of the most significant advances in chemical biology to perturb and study biological processes.
Imaging beyond the proteome
In this review, we discuss some of the recently developed chemical technologies that enable imaging beyond the proteome.
Labeling and sequencing nucleic acid modifications using bio-orthogonal tools
Labeling nucleic acid modifications using bio-orthogonal tools, then sequencing and imaging the labeled modifications in DNA and RNA.
Bifunctional chelators for radiorhenium: past, present and future outlook
This review highlights some of the past and current bifunctional chelators developed for radiorhenium (186Re and 188Re), as well as providing an outlook on what we may expect in the field of rhenium radiopharmaceuticals in the future.
Metal-free bioorthogonal click chemistry in cancer theranostics
In this Review, recent progress in cancer theranostics on the basis of metal-free bioorthogonal click chemistry is depicted in detail and future prospects in this emerging field are emphasized.
Derivatization based on tetrazine scaffolds: synthesis of tetrazine derivatives and their biomedical applications
The recent advances in tetrazine scaffold-based derivatizations have been summarized. The advantages and limitations of derivatization methods and applications of the developed tetrazine derivatives in bioorthogonal chemistry have been highlighted.
Bio-click chemistry: a bridge between biocatalysis and click chemistry
This review summarizes chemo/biocatalytic syntheses that combine the highly efficient click chemistry reactions with the advantages of biocatalysis. The concept of bio-click chemistry and its implications are introduced in this review.
Recent advances in Cu-catalyzed transformations of internal alkynes to alkenes and heterocycles
Numerous metal-catalyzed reactions involving internal alkynes and aimed towards synthetically and pharmacologically important alkenes and heterocycles have appeared in the literature.
Interrogating the transcriptome with metabolically incorporated ribonucleosides
This review summarizes recent developments in metabolic labeling of RNA to study RNA synthesis and turnover, RNA binding proteins, and RNA modifications and modifying enzymes.
Click-functionalized hydrogel design for mechanobiology investigations
This review article covers the use of click chemistries toward the design of dynamic and instructive hydrogels for understanding cell mechanobiology.
Fluorescent labeling of biocompatible block copolymers: synthetic strategies and applications in bioimaging
This review describes the different chemical approaches and strategies to fluorescently label block copolymers. The review also focuses on the properties of fluorescent markers and the bioimaging applications allowed by the labeling.
Recent advances in bio-orthogonal and dynamic crosslinking of biomimetic hydrogels
This review highlights recent advances in bio-orthogonal and dynamic hydrogels crosslinked by irreversible click chemistry, enzymatic reactions, and covalent-adaptable network.
Chemical proteomics approaches for identifying the cellular targets of natural products
This review focuses on chemical probes to identify the protein binding partners of natural products in living systems.
Design strategies for bioorthogonal smart probes
This review covers approaches used to develop probes activated by bioorthogonal ligation reactions.
Click chemistry for the synthesis of biobased polymers and networks derived from vegetable oils
Click green chemistry as an efficient functionalization and polymerization method of vegetable oils and their derivatives.
Multicomponent encapsulation into fully degradable protein nanocarriers via interfacial azide–alkyne click reaction in miniemulsion allows the co-delivery of immunotherapeutics
Fully biodegradable protein nanocarriers were prepared by metal-free click reaction in inverse miniemulsion and loaded in situ with up to four different cargo molecules to achieve a synergistic therapeutic treatment.
Catalytic machinery in motion: controlling catalysis via speed
The speed and catalytic activity (with regard to a click reaction) of slider-on-deck systems, in which a biped exchanges between three copper(I) centres, is regulated by addition of brake stones.
Development of sustainable synthesis of glucuronic acid glycodendrimers using ball milling and microwave-assisted CuAAC reaction
Two green strategies for CuAAC reaction based on two activation pathways, solvent free mechanochemistry and microwave irradiation using a recycable biosolvent, are reported for the synthesis of glucuronic acid glycodendrimers with good conversión.
Radical-mediated thiol–ene ‘click’ reactions in deep eutectic solvents for bioconjugation
Herein, we report the first application of deep eutectic solvents (DESs) in radical-mediated hydrothiolation reactions.
Augmenting photosynthesis through facile AIEgen-chloroplast conjugation and efficient solar energy utilization
Two new AIE molecules with activated alkyne groups were successfully conjugated with live chloroplasts by a facile metal-free “Click” reaction, and the formed artificial AIEgen-chloroplast owned the increased photosynthetic activity.
A thermoresponsive crosslinker for reversible micelle stabilization
Herein we report a thermoresponsive crosslinker that can be utilized to stabilize the surface of micelles through “click” reaction and to trigger the disassembly via retro Diels Alder (rDA) mechanism.
C-Terminal lactamization of peptides
New solid-phase based methods have allowed efficient synthesis of natural products and novel peptide hormone derivatives with a C-terminal lactam.
Construction of an IMiD-based azide library as a kit for PROTAC research
As a promising protein degradation strategy, PROTAC technology is increasingly becoming a new star in cancer treatment.
In cell Gd3+-based site-directed spin labeling and EPR spectroscopy of eGFP
A newly synthesized Gd3+ chelate complex allows in cell spin labeling and detection of eGFP by EPR spectroscopy.
Fast-forming BMSC-encapsulating hydrogels through bioorthogonal reaction for osteogenic differentiation
An injectable in situ fast-forming hydrogel was fabricated to encapsulate BMSCs for osteogenic differentiation through the inverse electron demand Diels–Alder click reaction between trans-cyclooctene-modified PEG and tetrazine-modified hyaluronic acid.
CuAAC click chemistry: a versatile approach towards PVDF-based block copolymers
Functionalized benzoyl peroxide-initiated polymerization of vinylidene fluoride allows straightforward preparation of PVDF-based block copolymers with an appealing crystallization behavior.
A fluorogenic screening platform enables directed evolution of an alkyne biosynthetic tool
A fluorogenic screening platform enabled the engineering of a membrane-bound bifunctional desaturase/acetylenase for improved activity in E. coli.
Monodisperse functional microspheres from step-growth “click” polymerizations: preparation, functionalization and implementation
We introduce a new paradigm in microparticles, where “click” chemistry enables the fabrication of functional monodisperse microspheres from step-growth polymerization at ambient conditions.
Gold(I) “click” 1,2,3-triazolylidenes: synthesis,
self-assembly and catalysis
Novel gold(I) “click” carbene(1,2,3-triazolylidene) complexes have been synthesised, characterised and exploited for the self-assembly of a metallomacrocycle and as precatalysts for gold(I)-catalysed reactions.
“Click-switch” – one-step conversion of organic azides into photochromic diarylethenes for the generation of light-controlled systems
New photochromic diarylethenes are reported in which one aryl ring is a 1,2,3-triazole that is formed by “click” chemistry between an azide on the target and a matching alkyne–cyclopentene–thiophene component.
Synthetic methodology towards allylic trans-cyclooctene-ethers enables modification of carbohydrates: bioorthogonal manipulation of the lac repressor
Two novel reagents were developed to direct formation of allylic cis-cyclooctene (CCO) ethers, followed by photochemical isomerization to obtain trans-cyclooctene (TCO) ethers. The method was used to cage a bio-active carbohydrate.
TMTHSI, a superior 7-membered ring alkyne containing reagent for strain-promoted azide–alkyne cycloaddition reactions
TMTHSI was developed as new reagent for strain-promoted azide–alkyne cycloaddition reactions, enabling connection of a diversity of small to large molecular constructs.
Synthesis of unsymmetrical sulfamides and polysulfamides via SuFEx click chemistry
A general, practical, and efficient synthesis of N,N′-disubstituted sulfamides has been developed and applied to the preparation of polysulfamides, a virtually unknown class of polymers.
The hunt for reactive alkynes in bio-orthogonal click reactions: insights from mechanochemical and conceptual DFT calculations
The force required to bend alkynes increases linearly with the angle and depends on the substituent pattern. The reactivity of the triple bond does not readily increase and is less influenced by the substituent pattern for larger bends.
Vinylphosphonites for Staudinger-induced chemoselective peptide cyclization and functionalization
Vinylphosphonites react in chemoselective Staudinger-phosphonite reactions (SPhR) with azides to form vinylphosphonamidates for the subsequent modification of cysteine residues in peptides and proteins.
Site-specific PEGylation of
proteins by a Staudinger- phosphite reaction
A Staudinger-phosphite ligation was applied for an efficient, metal-free PEGylation of azido-polypeptides yielding stable and light-cleavable branched oligoethylene glycol scaffolds.
Nucleic acid-based supramolecular structures: vesicular spherical nucleic acids from a non-phospholipid nucleolipid
An original hybrid biomacromolecule, consisting of a lipid-mimetic residue and a 21-base long nucleic acid strand, spontaneously self-associates and co-associates with other lipids into nucleic acid-grafted vesicular structures.
Introducing SuFEx click chemistry into aliphatic polycarbonates: a novel toolbox/platform for post-modification as biomaterials
It is the first time to introduce SuFEx click chemistry into aliphatic polycarbonates. Moreover, the one-pot strategy of ring-opening polymerization of cyclic carbonate and SuFEx click reactions for functionalization could be directly achieved.
Development of a multistep, electrochemical flow platform for automated catalyst screening
An integrated flow platform enables the electrochemical synthesis of base-metal catalysts with high-throughput screening and rapid data generation.
Accelerated synthesis of dendrimers by thermal azide–alkyne cycloaddition with internal alkynes
Optimized reaction conditions and a strict alignment to green chemistry principles allow the accelerated preparation of a G5 dendrimer in less than 12 h by combining the thermal azide–alkyne cycloaddition and azide substitution reactions.
Enzyme-triggered click chemistry combined with surface-enhanced Raman spectroscopy for the simple and sensitive detection of alkaline phosphatase activity from complex biological samples
Schematic of the enzyme-triggered click chemistry combined with the SERS technique for ALP detection.
Synthesis and preliminary evaluation of octreotate conjugates of bioactive synthetic amatoxins for targeting somatostatin receptor (sstr2) expressing cells
Synthetic amanitin is conjugated to octreotate as a targeting agent: three different linkers and two sites of attachment highlight a robust chemical approach leading to targeted cytotoxicity.
SPAAC iClick: progress towards a bioorthogonal reaction in-corporating metal ions
Combining strain-promoted azide–alkyne cycloaddition (SPAAC) and inorganic click (iClick) reactivity provides access to metal 1,2,3-triazolates.
Radiolabelling an 18F biologic via facile IEDDA “click” chemistry on the GE FASTLab™ platform
A fully automated and efficient radiosynthesis of a novel interleukin-2 radioconjugate from a single FASTLab™ cassette.
The liquid crystal Click procedure for oligothiophene-tethered phthalocyanines – self-assembly, alignment and photocurrent
The Click process for oligothienyl star mesogens generates triple nanosegregated columnar LCs – partial homeotropic alignment leads to increased photocurrents.
Defect engineering: an effective tool for enhancing the catalytic performance of copper-MOFs for the click reaction and the A3 coupling
A series of Cu(I)-enriched and Lewis basic site-containing defect-engineering MOFs was investigated for significantly enhanced catalytic performance in the click reaction and the A3 coupling.
Copper(II) complexes of N-propargyl cyclam ligands reveal a range of coordination modes and colours, and unexpected reactivity
Copper(II) complexes of cyclam ligands with 1, 2, 3 or 4 pendant alkynes have been prepared and characterised crystallographically and spectroscopically. An unexpected hydroalkoxylation reaction is observed, affording an enol ether from the alkyne.
The stepwise organization of nanoparticles into a Pickering emulsion
Homogeneous composite nanoparticles undergo stepwise organization from individual nanoparticles that capture oil to stable aggregates to the formation of a Pickering emulsion as oil is continuously fed into the aqueous dispersion.
Cancer cell-targeted cisplatin prodrug delivery in vivo via metabolic labeling and bioorthogonal click reaction
DCL-AAM selectively labels cancer cells with azido groups, and thus allows tumor-targeted delivery of DBCO-cisplatin prodrug via bioorthogonal click chemistry.
Selective analysis of newly synthesized proteins by combining fluorescence correlation spectroscopy with bioorthogonal non-canonical amino acid tagging
FCS with the BONCAT strategy is a promising approach for analysis of newly synthesized proteins and also be extended to further application for studying physiological or pathological processes related to proteins or other metabolic molecular changes.
In vivo vocal fold augmentation using an injectable polyethylene glycol hydrogel based on click chemistry
A click chemistry-based PEG hydrogel was applied for vocal fold augmentation in vivo. In rabbit models, it stably fixed the paralyzed vocal fold and minimized the glottic gap.
Tetrazine- and trans-cyclooctene-functionalised polypept(o)ides for fast bioorthogonal tetrazine ligation
Tetrazine- and trans-cyclooctene-functionalised polypeptides and polypetoids were prepared by ring-opening polymerisation of N-carboxyanhydrides using the respective functional initiators and shown to react in fast bioorthogonal tetrazine ligations.
Water-soluble silicon nanocrystals as NIR luminescent probes for time-gated biomedical imaging
In vivo studies demonstrated tumor accumulation of luminescent SiNCs, 48 hours clearance and a 3-fold improvement of signal-to-noise ratio in time-gated imaging compared to steady-state acquisition, demonstrating their potentiality for luminescence guided surgery.
Click chemistry-based imaging to study the tissue distribution of the curcumin–protein complex in mice
Using click chemistry-based fluorescence imaging, here we show that curcumin, a bioactive dietary compound with a thiol-reactive α,β-unsaturated carbonyl moiety, can covalently modify protein thiols in colon and liver tissues in mice.
The first thiol–yne click chemistry approach for the preparation of liquid crystalline elastomers
A new synthetic strategy based on thiol–yne click chemistry is presented to prepare liquid crystalline elastomers, allowing us to obtain mixed side-chain/main-chain structures able to undergo contraction up to 48%.
Direct and two-step bioorthogonal probes for Bruton's tyrosine kinase based on ibrutinib: a comparative study
Direct and two-step activity-based probes allow for profiling of Bruton's tyrosine kinase in vitro and in situ.
Design of thiol–ene photoclick hydrogels using facile techniques for cell culture applications
Thiol–ene photoclick hydrogels with tunable biomechanical and biochemical properties for biological applications, including controlled cell culture, regenerative medicine, and drug delivery.
oligosaccharide engineering of glycoproteins by UDP-N-acetylglucosamine 2-epimerase/ N-acetylmannosamine kinase ( GNE) knock-down
Efficient incorporation of chemically modified sugar analogues into cell surface glycans and recombinantly expressed CEACAM was achieved by shRNA-mediated knock down of the key enzyme of sialic acid biosynthesis.
(NHC)CuX] complexes: Synthesis, characterization and catalytic activities in reduction reactions and Click Chemistry. On the advantage of using well-defined catalytic systems
A thorough synthetic and catalytic study of [(NHC)CuX] complexes led to major improvements for this family of compounds.
Covalent and orthogonal multi-functionalization of terpolymers
A unique methodology for the quantitative multi-functionalization of terpolymers has been developed via highly efficient and versatile covalent synthetic strategies using click reactions: maleimide–thiol coupling, 1,3-dipolar cycloaddition, and hydrazone formation.
A simple and efficient method for epoxidation of terminal alkenes
α-Vinyl azide–cysteine click coupling reaction enabled bioorthogonal peptide/protein modification
α-Alkyl and α-aryl vinyl azides were found to be able to couple with cysteine-derived alkyl thiols chemoselectively under mild conditions, providing the corresponding β-ketosulfides with simultaneous extrusion of N2 and ammonia.
Development of 2-deoxystreptamine–nucleobase conjugates for the inhibition of oncogenic miRNA production
2-deoxystreptamine (2-DOS) conjugates with artificial nucleobases were designed and synthesized to inhibit pre-miR-372 processing into oncogenic miRNA and were discovered to be promising inhibitors when compared to their neomycin counterpart.
Metabolic labelling of cancer cells with glycodendrimers stimulate immune-mediated cytotoxicity
Combining glycometabolism and bio-orthogonal chemistry to label cells with antigenic glycodendrimers lead to the activation of immune response against cancer cells.
Prolinamide plays a key role in promoting copper-catalyzed cycloaddition of azides and alkynes in aqueous media via unprecedented metallacycle intermediates
Room temperature copper-catalyzed cycloaddition of azides and alkynes (CuAAC) proceeds in the presence of a prolinamide ligand in aqueous media via unique metallacycles.
About this collection
This cross-journal collection is dedicated to bioorthogonal and click chemistry, in honour of the 2022 Nobel Prize in Chemistry. Click chemistry is best represented by its most elegant and widespread example, the copper catalysed azide-alkyne cycloaddition (CuAAC). Bioorthogonal reactions are click reactions that take place without disrupting the normal chemistry of the cell, inside living organisms, and these are now used to track biological processes. The scope of this collection highlights key historic works in bioorthogonal and click chemistry alongside showcasing recent developments and applications of these now ubiquitous techniques.