Click chemistry approach to functionalize two-dimensional macromolecules of graphene oxide nanosheets

A facile "click chemistry" approach to functionalize 2D macromolecules of graphene oxide nanosheets with poly(ethylene glycol) of different molecular weights,polystyrene,palmitic acid and various amino acids was presented.FTIR,TGA,Raman spectroscopy,XPS,XRD,TEM,AFM and SEM were utilized to characterize the products.High degree of functionalization was achieved on the flat surfaces of graphene oxide,affording polymer-grafted 2D brushes and amino acids-immobilized nanosheets,which show improved solubility in organic solvents.The click chemistry strategy reported herein provides a facile and general method for functionalization of graphene oxide with macromolecules and desired biomolecules.

Preparation of novel chiral stationary phase based on click chemistry for ligand exchange chromatography

Click chemistry was applied to immobilize L-proline derivative onto azide-modified silica gel to give a novel chiral stationary phase （denoted as click-CSP） for ligand exchange chromatography. The developed protocol combines the benefits of operational simplicity, exceptionally mild conditions and high surface loadings. The enantioselectivity α of some DL-arnino acids on the click- CSP were found to be in the range from 1.13 to 3.46. The chromatographic resolutions of some DL-amino acids and the stability study firmly illustrate the potential of click chemistry for preparation chiral stationary phase for ligand exchange chromatography.

SYNTHESIS OF A HYPERBRANCHED POLY(AROYLARYLENE) CONTAINING TRIAZOLE AND FLUORENE FUNCTIONALITIES BY CLICK CHEMISTRY AND METAL-FREE,REGIOSELECTIVE POLYCYCLOTRIMERIZATION

A new bis(aroylacetylene) containing tfiazole and fluorene moieties is synthesized by click chemistry. Polycyclotrimerization of the monomer is catalyzed by piperidine in refluxed dioxane,furnishing a regioregular poly(aroylarylene) in a satisfactory yield.The hyperbranched structure of the polymer is characterized spectroscopically with satisfactory results.The polymer enjoys no metal detriment and is soluble in common organic solvents such as tetrahydrofuran (THF),chloroform,dichloromethane (DCM),and N,N-...

Cardanol-Based Polyurethane Coatings via Click Chemistry:An Eco-friendly Approach

This research work discloses the preparation of polyurethane coatings from cardanol modified using thiolene chemistry,wherein unsaturated long alkyl chain of cardanol was successfully utilized via thiol-ene click reaction to synthesize polyol.For this purpose,cardanol and thioglycerol was reacted in the presence of Irgacure 184(photoinitiator)and 1,8-Diazabicyclo[5.4.0]undec-7-ene(catalyst)and exposed to UV light for 12 h at 80℃.One mole of thioglycerol was successfully added across the double bond of fatty chain of cardanol and confirmed by chemical and spectroscopic analysis.Further,the polyol thus prepared was cured with various polyisocyanates,viz.,N-75(HDI based),L-67/BA(TDI based),Z-4470(IPDI based)and corresponding polyurethane coatings were developed.The coatings were then analyzed for mechanical,chemical,optical,thermal and anticorrosive properties.It was observed that cardanol-based PU coatings exhibited excellent mechanical,chemical and thermal and anticorrosive properties as compared to that of commercial acrylic-PU coatings.

Preparation of Hydrophilic and Shrink-Proofing Wool Fabrics Through Thiol-Ene Click Chemistry Reaction

To improve shrink-proofing performance and hydrophilicity of wool fabrics, the wool fibers were modified by poly(ethylene glycol) dimethacrylate(PEGDMA) through thiol-ene click chemistry reaction. Firstly, wool fabrics were reduced at room temperature with a high-efficiency disulfide bond reducing agent, tris(2-carbonxyethyl) phosphine hydrochloride(TCEP). Then the thiol-ene click chemistry reaction was initiated by dimethyl 2, 2’-azobis(2-methylpropionate)(AIBME) through the heating method. Fourier transform infrared(FTIR) spectroscopy, Raman spectroscopy, and scanning electron microscopy test results all showed that PEGDMA was successfully grafted onto wool fabric surface. Physical properties, hydrophilicity, and shrink-proofing performance were assessed. The wetting time of PEGDMA grafted wool fabrics decreased to about 3 s. After being grafted with PEGDMA, the felting shrinkage of wool fabrics rapidly decreased to about 8%. The anti-pilling properties of wool fabrics were also greatly improved to 5 class after 2 000 times of friction. Meanwhile, the load retention rate of fabrics could reach 90%. It provides a method of wool modification to improve hydrophilicity and anti-felting performance.

Copper-Free Click Chemistry-Mediated Assembly of Single Quantum Dot Nanosensor for Accurately Monitoring Locus-Specific m^(6)A in Cancer Cells

N6-methyladenosine(m^(6)A)plays an important role in embryogenesis,nuclear export,transcription splicing,and protein translation control.Herein,we demonstrate a copper-free click chemistry-mediated assembly of single quantum dot(QD)nanosensor for accurately monitoring locus-specific m^(6)A in cancer cells.The m^(6)A-sensitive endoribonuclease MazF can digest the unmethylated A-RNA,and the intact m^(6)A-RNA then hybridizes with DNA probes a and b to produce a sandwich hybrid,initiating the click chemistry to generate probe a–b ligation product via first tandem ligation detection reaction(LDR)cycle.Subsequently,DNA probes c and d can hybridize with the probe a–b ligation product to generate the probe c–d ligation product via second LDR cycle.Both LDR cycles can be repeated through denaturation and annealing reaction to generate abundant biotin-/fluorophore-modified probe c–d ligation products that can easily assemble on the QD surface to induce distinct fluorescence resonance energy transfer(FRET)between QD and Cy5.This assay can be homogenously performed without the involvement of copper catalyst,m^(6)A-specific antibody,radioactive labeling,ligase enzyme,enzymatic reverse transcription,and next-generation sequencing.Moreover,it can discriminate even 0.01% m^(6)A level in complex samples and accurately measure cellular m^(6)A-RNA expression,providing a promising avenue for clinical diagnostics and biomedical research.

Click chemistry and natural products

The 2022 Nobel Prize in Chemistry was awarded to American scientists Carolyn Bertozzi,K.Barry Sharpless,and Danish scientist Morten P.Merdahl for their contributions to the development of click chemistry and bioorthogonal chemistry.

Visible and selective gel assembly via covalent click chemistry

This study marks the birth of visible and selective click covalent assembly.It is achieved by amplifying orthogonal alkyne−azide click chemistry through interfacial multisite interactions between azide/alkyne functionalized polymer hydrogels.Macroscopic assembly of hydrogels via host−guest chemistry or noncovalent interactions such as electrostatic interactions has been reported.Unlike macroscopic supramolecular assembly,here we report visible and selective“click”covalent assembly of hydrogels at the macroscale.LEGO-like hydrogels modified with alkyne and azide groups,respectively,can click together via the formation of covalent bonds.Monomer concentration-dependent assembly and selective covalent assembly have been studied.Notably,macroscopic gel assembly clearly elucidates click preferences and component selectivity not observed in the solution reactions of competing monomers.

Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries

Central nervous system(CNS)injuries,including stroke,traumatic brain injury,and spinal cord injury,are essential causes of death and long-term disability and are difficult to cure,mainly due to the limited neuron regeneration and the glial scar formation.Herein,we apply extracellular vesicles(EVs)secreted by M2 microglia to improve the differentiation of neural stem cells(NSCs)at the injured site,and simultaneously modify them with the injured vascular targeting peptide(DA7R)and the stem cell recruiting factor(SDF-1)on their surface via copper-free click chemistry to recruit NSCs,inducing their neuronal differentiation,and serving as the nanocarriers at the injured site(Dual-EV).Results prove that the Dual-EV could target human umbilical vascular endothelial cells(HUVECs),recruit NSCs,and promote the neuronal differentiation of NSCs in vitro.Furthermore,10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis,and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs,miR30b-3p,miR-222-3p,miR-129-5p,and miR-155-5p may exert effect of inducing NSC to differentiate into neurons.In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice,potentiate NSCs recruitment,and increase neurogenesis.This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells,and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Water-soluble Cu30 nanoclusters as a click chemistry catalyst for living cell labeling via azide-alkyne cycloaddition

Cu(I)-catalyzed azide-alkyne cycloadditions(CuAAC)have gained increasing interest in the selective labeling of living cells and organisms with biomolecules.However,their application is constrained either by the high cytotoxicity of Cu(I)ions or the low activity of CuAAC in the internal space of living cells.This paper reports the design of a novel Cu-based nanocatalyst,watersoluble thiolated Cu30 nanoclusters(NCs),for living cell labeling via CuAAC.The Cu30 NCs offer good biocompatibility,excellent stability,and scalable synthesis(e.g.,gram scale),which would facilitate potential commercial applications.By combining the highly localized Cu(I)active species on the NC surface and good structural stability,the Cu30 NCs exhibit superior catalytic activities for a series of Huisgen cycloaddition reactions with good recyclability.More importantly,the biocompatibility of the Cu30 NCs enables them to be a good catalyst for CuAAC,whereby the challenging labeling of living cells can be achieved via CuAAC on the cell membrane.This study sheds light on the facile synthesis of atomically precise Cu NCs,as well as the design of novel Cu NCs-based nanocatalysts for CuAAC in intracellular bioorthogonal applications.

Research strategies in click chemistry: Measuring its cognitive contents and knowledge flow

The issue about how outstanding scientists obtained innovative findings has drawn the interest of researchers in science, policy and scientometrics. Here, we attempt to address this question by using computational methods to measure the cognitive content and concepts of K. Barry Sharpless’ research and estimate the knowledge flow of his click chemistry to other fields. First, we traced Sharpless’ conceptual journey over time through topic modeling approach, mapping and clustering of the epistemic network from distant reading his publications. We find that connectivity and functions, the core features of click chemistry, are embodied in his constant search for simplicity. What makes simplicity possible is his continuous work with collaborators on reactivity and reaction mechanisms. Moreover, citation and link analysis show that click chemistry had a much richer impact on other research fields than what is generally acknowledged, and drew solutions to significant and practical questions back to chemistry from biology.Together with these findings, we propose that the click chemistry philosophy follows the way that values nature’s principle. Chemistry has a clear-cut epistemic domain in modeling Nature. Thus, click chemistry as a concept on doing science beyond a connective technology goes across the boundaries between disciplines and impacts many other fields.

Click chemistry in the design of AIEgens for biosensing and bioimaging

The development of rapid,selective,and sensitivefluorescent sensors is essential for visualizing and quantifying biological molecules and processes in vitro,ex vitro,and in vivo,which is important for not only fundamental biological studies but the accurate diagnosis of diseases.The emergingfield of activity-based sensing(ABS),a sensing method that utilizes molecular reactivity for analyte detection possesses many advantages including high specificity,sensitivity and accuracy.The aggrega-tion caused quenching phenomenon which occurs in most conventionalfluorophores results in reduced labeling efficiency of the target analytes and low photobleaching resistance,therefore limiting the applications of the ABS strategy.In contrast,aggre-gation induced emission(AIE)active luminogens(AIEgens)provide exceptional molecular frameworks for ABS.Of the many reaction classes utilized in the AIEgen ABS approach,click chemistry has become increasing popular.In this review,the sensing concepts of the ABS approach with AIEgens and the principles of click chemistry are discussed,followed by a systematic summary of the application of specific click chemistry reactions in AIEgen ABS protocols for the detection of an array of target analytes.Furthermore,the utility of click chemistry in the construction of AIEgens for bioimaging will also be showcased throughout the review.

Modular Click Chemistry Library:Searching for Better Functions

High throughput screening towards chemical libraries is the primary way to discover lead compounds in developing innovative drugs,especially new molecular entities.Accordingly,the preparation of chemical libraries is the key step for drug development.Now,con-ventional small molecule chemical libraries and DNA-encoded chemical libraries are the main models of chemical libraries for high-throughput screening.Recently,a new model of chemical library,calledmodular click chemistry library,was proposed,which gives us an alternative choice to construct chemical libraries for high throughput screening and exhibits broad prospects to accelerate drug development.Herein,this article mainly focuses on the strategy to prepare the modular click chemistry library.

Postsynthetic Modification of Metal-Organic Frameworks through Click Chemistry

The postsynthetic modification （PSM） of metal-organic frameworks （MOFs） has emerged as a powerful tool to chemically tailor the interior of MOFs. In this review, we summarize the research progress of PSM of MOFs through click chemistry, including azide-alkyne click reaction and thiol-ene reaction.

Efficient Side-chain Modification of Dextran via Base-catalyzed Epoxide Ring-opening and Thiol-ene Click Chemistry in Aqueous Media

In this study, a novel approach by combining base-catalyzed epoxide ring-opening and thiol-ene click chemistry is presented for the side-chain modification of dextran. The vinyl-modified dextran is prepared by a basic epoxide ring opening reaction of allyl glycidyl ether in 0.1 mol/L NaOH, followed by thiol-addition click reaction of three model sulfhydryl compounds using water-soluble Irgacure 2959 as the photoinitiator, leading to side-chain functionalized dextran modified with carboxyl, bidentate dicarboxyl or amino groups. This is the first example of combining epoxide ring-opening and thiol- ene click chemistry for side-chain modification of dextran in aqueous media. Importantly, it may also be extended as a convenient and efficient method for the side-chain modification of other polysaccharides.

Combining Metabolic Alkyne Labeling and Click Chemistry for Secretome Analysis of Serum-Containing Conditioned Medium

Main observation and conclusion Bioorthogonal click chemistry has emerged as a powerful tool for the specific modification of proteins in complex mixtures.Metabolic labeling of proteins with azide followed by the copper-catalyzed azide−alkyne cycloaddition(CuAAC)with alkyne-based affinity probes/beads is widely applied to study protein turnover and post-translational modifications(PTMs).

Recent progress in the synthesis of sulfonyl fluorides for SuFEx click chemistry

Since the sulfur(Ⅵ)fluoride exchange reaction(SuFEx)was introduced by Sharpless and co-workers in 2014,this new-generation click chemistry has emerged as an efficient and reliable tool for creating modular intermolecular connections.Sulfonyl fluorides,one of the most important sulfur(Ⅵ)fluoride species,have attracted enormous attention in diverse fields,ranging from organic synthesis and material science,to chemical biology and drug discovery.This review aims to introduce seminal and recent progresses on the synthetic methods of sulfonyl fluorides,which include aromatic,aliphatic,alkenyl,and alkynyl sulfonyl fluorides.While not meant to be exhaustive,the purpose is to give a timely overview and insight in this field,and stimulate the development of more efficient synthetic methods of sulfonyl fluorides.

Synthesis of 7-Triazole-substituted Camptothecin via Click Chemistry and Evaluation of in vitro Antitumor Activity

Camptothecin(CPT)is a natural topoisomerase I inhibitor with powerful antineoplastic activity against colorectal,breast,lung and ovarian cancers.To discover more potent antitumor agents,a series of new CPT derivatives were synthesized utilizing click chemistry.All compounds were assessed for cytotoxicity against A549,HCT-116,HT-29,LoVo,MDA-MB-231 cell lines,and some compounds exhibited good in vitro potency.Furthermore,all compounds kept or enhanced Topo I inhibition.

Synthesis of peptide dendrimers with polyhedral oligomeric silsesquioxane cores via click chemistry

Inorganic polyhedral oligomeric silsesquioxane （POSS） was used as the core for the synthesis of poly（t- lysine） peptide dendrimer via copper-catalyzed azide-alkyne click chemistry. The inorganic/organic composite dendrimer was characterized by MS, 1H NMR, FTIR, GPC and DLS.

Combination of Click Chemistry and Enzymatic Ligation for Stable and Efficient Protein Immobilization for Single-Molecule Force Spectroscopy

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 on a heterobifunctional cross-linker,such as N-hydroxysuccinimide(NHS)-linker-maleimide,or a similar two-step process.It utilizes the amino-reactive NHS and the thiolreactive maleimide to conjugate protein to the solid support.However,NHS as a chemical is susceptible to hydrolysis during storage and handling,and maleimide reacts nonspecifically with all cysteines available in the protein,leading to an inconsistent result.To solve these problems,we have developed a method by combining a strain-promoted azide–alkyne cycloaddition(SPAAC)click reaction and an OaAEP1(C247A)-based enzymatic ligation.The method was demonstrated by the successful immobilization of enhanced green fluorescent protein(eGFP),which was visualized by fluorescent imaging.Moreover,the correct folding and stability of the immobilized protein were verified by atomic force microscopy-based single-molecule force spectroscopy(AFM-SMFS)measurement with a high success rate(89%).Finally,the strength of the 1,2,3-triazole linkage from the azide-dibenzocyclooctyne(DBCO)-based SPAAC reaction was quantified with an ultrahigh rupture force>1.7 nN.Thus,this stable,efficient,and site-specific immobilization method can be used for many challenging systems,especially SMFS studies.