Themed collection Bioorthogonal and click chemistry: Celebrating the 2022 Nobel Prize in Chemistry

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.

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.

The establishment of photo-controllable bioorthogonal chemistry is one of the most significant advances in chemical biology to perturb and study biological processes.

In this review, we discuss some of the recently developed chemical technologies that enable imaging beyond the proteome.

Labeling nucleic acid modifications using bio-orthogonal tools, then sequencing and imaging the labeled modifications in DNA and RNA.

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.

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.

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.

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.

Numerous metal-catalyzed reactions involving internal alkynes and aimed towards synthetically and pharmacologically important alkenes and heterocycles have appeared in the literature.

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.

This review article covers the use of click chemistries toward the design of dynamic and instructive hydrogels for understanding cell mechanobiology.

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.

This review highlights recent advances in bio-orthogonal and dynamic hydrogels crosslinked by irreversible click chemistry, enzymatic reactions, and covalent-adaptable network.

This review focuses on chemical probes to identify the protein binding partners of natural products in living systems.

This review covers approaches used to develop probes activated by bioorthogonal ligation reactions.

Click green chemistry as an efficient functionalization and polymerization method of vegetable oils and their derivatives.

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.

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.

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.

Herein, we report the first application of deep eutectic solvents (DESs) in radical-mediated hydrothiolation reactions.

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.

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.

New solid-phase based methods have allowed efficient synthesis of natural products and novel peptide hormone derivatives with a C-terminal lactam.

As a promising protein degradation strategy, PROTAC technology is increasingly becoming a new star in cancer treatment.

A newly synthesized Gd³⁺ chelate complex allows in cell spin labeling and detection of eGFP by EPR spectroscopy.

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.

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 enabled the engineering of a membrane-bound bifunctional desaturase/acetylenase for improved activity in E. coli.

We introduce a new paradigm in microparticles, where “click” chemistry enables the fabrication of functional monodisperse microspheres from step-growth polymerization at ambient conditions.

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.

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.

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 was developed as new reagent for strain-promoted azide–alkyne cycloaddition reactions, enabling connection of a diversity of small to large molecular constructs.

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 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 react in chemoselective Staudinger-phosphonite reactions (SPhR) with azides to form vinylphosphonamidates for the subsequent modification of cysteine residues in peptides and proteins.

A Staudinger-phosphite ligation was applied for an efficient, metal-free PEGylation of azido-polypeptides yielding stable and light-cleavable branched oligoethylene glycol scaffolds.

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.

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.

An integrated flow platform enables the electrochemical synthesis of base-metal catalysts with high-throughput screening and rapid data generation.

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.

Schematic of the enzyme-triggered click chemistry combined with the SERS technique for ALP detection.

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.

Combining strain-promoted azide–alkyne cycloaddition (SPAAC) and inorganic click (iClick) reactivity provides access to metal 1,2,3-triazolates.

A fully automated and efficient radiosynthesis of a novel interleukin-2 radioconjugate from a single FASTLab™ cassette.

The Click process for oligothienyl star mesogens generates triple nanosegregated columnar LCs – partial homeotropic alignment leads to increased photocurrents.

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 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.

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.

DCL-AAM selectively labels cancer cells with azido groups, and thus allows tumor-targeted delivery of DBCO-cisplatin prodrug via bioorthogonal click chemistry.

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.

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 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.

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.

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.

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 activity-based probes allow for profiling of Bruton's tyrosine kinase in vitro and in situ.

Thiol–ene photoclick hydrogels with tunable biomechanical and biochemical properties for biological applications, including controlled cell culture, regenerative medicine, and drug delivery.

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.

A thorough synthetic and catalytic study of [(NHC)CuX] complexes led to major improvements for this family of compounds.

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.

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.

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.

Combining glycometabolism and bio-orthogonal chemistry to label cells with antigenic glycodendrimers lead to the activation of immune response against cancer cells.

Room temperature copper-catalyzed cycloaddition of azides and alkynes (CuAAC) proceeds in the presence of a prolinamide ligand in aqueous media via unique metallacycles.