Nano-copper Oxide as Catalyst for Click Reactions

Click reactions are not specific reactions, but they are a way of generating products that follow examples in nature by joining small moieties, with each other producing a huge molecule in a good yield. The mind of that reaction is used in biomolecules synthesis, pharmacological and various biometric applications. The first Click reaction is the Copper compounds-catalyzed reaction of an azide with an alkyne （CuAAC）, this copper-catalyzed ＂click＂ does not require legands on the metal but the metal oxides also can accelerate the reactions. For enhancement the products of Click reactions we were replacing the copper compounds in a classical reaction by the prepared nanocopper compound （NPs）. And measure the consumption of starting material. Behind the evolution is the catalytic effect of nanocopper compounding （NPs） on （H2O2）. Owing to the huge surface area of nanocopper compound （NPs）, it was found that： the （NPs） can speed up decomposition of H2O2, also can accelerate the classical click reaction.

Click-Formed Polymer Gels with Aggregation-Induced Emission and Dual Stimuli-Responsive Behaviors

Stimuli-responsive polymer gels have recently attracted great attention due to their heat/solvent resistance,dimensional stability,and unique sensitivity to external stimuli.In this work,we synthesized thiol-functionalized tetraphenylethylene(TPE)and constructed polymer gels through thiol-ene click reaction.The synthetic process of the polymer gels could be monitored by fluorescence emission of TPE moieties based on aggregation-induced emission mechanism.In addition,due to the dual redox-and acid responsiveness of the polymer gels,in the presence of dithiothreitol and trifluoroacetic acid,fluorescence quenching of the polymer gels can be observed.This stimuli-responsive characteristics endows the polymer gels with potential applications in fluorescent sensing and imaging,cancer diagnosis and selfhealing materials.

Synthesis and Characterization of Compounds Containing 1,2,3-Triazole via Click Reaction and Ag(Ⅰ) Complex

In this work, 1,4-bis(4-phenyl-1,2,3-triazole)benzene, 1,3-bis(4-phenyl-1,2,3-triazole)propane, bis(1-phenyl-1,2,3-triazole)-methylphenylsilane, and 1-ally-4-phenyl-1,2,3-triazole have been designed and synthesized via Click reaction. Fourier transform infrared spectroscopy(FT-IR) and nuclear magnetic resonance spectroscopy(NMR) were used to confirm the compounds' structures. The effect of silicon atom on the optical properties has also been studied. The UV-vis absorption wavelength of silicon-containing compound is about ca. 10 nm red-shifted when compared with that of other three compounds. The fluorescence emission bands of the compounds in CHCl_3 solutions were observed around ca. 440 nm. And the luminescent coordination compound, namely [AgL1?NO_3?3H_2O]n, based on the ligand 1-allyl-4-phenyl-1,2,3-triazole has been prepared. In addition, this complex exhibits a 1 D chain structure. The crystal structure has been determined by single-crystal X-ray diffraction, and the optical properties have been investigated by fluorescence spectrum. In summary, our work may provide new materials with luminescent property which is potentially useful in material fields.

Eutectic Solution Enables Powerful Click Reaction for In-Situ Construction of Advanced Gel Electrolytes

Thiol-ene click reaction is an intriguing strategy for preparing polymer electrolytes due to its high activity,atom economy and less side reaction.However,the explosive reaction rate and the use of non-electrolytic amine catalyst hamper its application in in-situ batteries.Herein,a nitrogen-containing eutectic solution is designed as both the catalyst of the thiol-ene reaction and the plasticizer to in-situ synthesize the gel polymer electrolytes,realizing a mild in-situ gelation process and the preparation of high-performance gel electrolytes.The obtained gel polymer electrolytes exhibit a high ionic conductivity of 4×10^(−4)S cm^(−1)and lithium-ion transference number(t_(Li)^(+))of 0.51 at 60°C.The as-assembled Li/LiFePO_(4)(LFP)cell delivers a high initial discharge capacity of 155.9 mAh g^(-1),and a favorable cycling stability with the capacity retention of 82%after 800 cycles at 1 C is also obtained.In addition,this eutectic solution significantly improves the rate performance of the LFP cell with high specific capacity of 141.5 and 126.8 mAh g^(-1)at 5 C and 10 C,respectively,and the cell can steadily work at various charge–discharge rate for 200 cycles.This powerful and efficient strategy may provide a novel way for in-situ preparing gel polymer electrolytes with desirable comprehensive performances.

Click reaction-induced in situ nanoparticle aggregation for cancer imaging and treatment

With their high drug-loading capacity and enhanced permeability and retention(EPR)effects,nanoparticles possess significant potential for the diagnosis and treatment of tumors.However,unlike active targeting,the complex tumor microenvironment influences the passive accumulation of nanoparticles in tumor areas.Hence,it is necessary to actively control the behavior of nanoparticles when they enter the tumor microenvironment.By utilizing biocompatible and efficient click reactions,the aggregation of nanoparticles at the tumor site can be controlled,thereby enhancing nanoparticle accumulation at the target location with improved imaging signals and enhanced tumor-inhibitory effects.Herein,we introduce and classify in situ nanoparticle aggregation for biomedical imaging and therapeutic applications induced by four types of common click reactions:coppercatalyzed azide–alkyne cycloaddition(CuAAC),strain-promoted azide–alkyne cycloaddition(SPAAC),click condensation between 2-cyanobenzothiazole(CBT)and cysteine(Cys),and inverse electron-demand Diels–Alder(iEDDA).Furthermore,we summarize the main strategies of these click reaction-based nanoparticle aggregation approaches.Finally,we discuss the advantages and disadvantages of click reaction-triggered aggregation and analyze future trends.

Synthesis and characterization of biodegradable amphiphilic PEG-grafted poly(DTC-co-CL)

A novel biodegradable copolymer, poly（5,5-dibromomethyltrimethylene carbonate-co-ε-caprolactone） （poly（DBTC-co-CL）） with pendant bromine groups, was synthesized via ring-opening polymerization （ROP） of ε-caprolactone （CL） and 5,5- dibromomethyltrimethylene carbonate （DBTC） using stannous octoate （Sn（Oct）2） as catalyst. Then the pendant bromine groups were completely converted into azide form, which permitted ＂click＂ reaction with alkyne-terminated polyethylene （A-PEG） by Huisgen 1,3-dipolar cycloadditions preparing biodegradable amphiphilic poly（DTC-co-CL）-g-PEG graft copolymer. The graft copolymer was characterized by nuclear magnetic resonance （NMR） and size-exclusion chromatography （SEC）.

One-pot Synthesis,Crystal Structures and Antimicrobial Activities of Two New 1,4-Disubstituted 1,2,3-Triazole-4-Carboxylates

Two new 1,4-disubstituted 1,2,3-triazoles-4-carboxylates were synthesized via click reaction. Compound 1a was synthesized by the interaction of 6-nitro-tetrazolo[1.5-a]-pyridine with ethyl propynoate at room temperature in the presence of Cu（OAc）2 as a catalyst and THF as solvent. Compound 1b was also synthesized by the same manner except that tert-butyl propionate, instead of ethyl propynoate, was used. The compounds were characterized by IR, 1H-NMR, 13C-NMR and single-crystal X-ray diffraction analysis. Compound 1a（C10H9N5O4） crystallizes in the triclinic system, space group P1 with a = 5.0894（9）, b = 8.9834（13）, c = 13.089（2） ？, α= 83.041（7）, β= 80.256（7）, γ=87.296（8）°, V = 585.24（16）？3, Z = 2, Mr = 263.22, crystal size（mm） = 0.37 × 0.20 ×0.18,（I 〉 2σ（I）） = 8557, 2493, 1229, Rint = 0.057. Compound 1b（C12H13N5O4） crystallizes in the monoclinic system, space group P21/c with a = 6.8854（5）, b = 21.783（2）, c = 9.3986（8） ？,β = 93.239（4）°, V = 1407.4（2）？3, Z = 4, Mr = 291.27, crystal size（mm） = 0.38 × 0.22 × 0.20,（I 〉 2σ（I）） = 11842, 3172, 1866, Rint = 0.047. Antimicrobial assay results showed that the title compounds display excellent activities to different bacterial and fungal strains.

Synthesis and Anticancer Activity of 4b-Triazolepodophyllotoxin Glycosides

A series of novel 4b-triazole-podophyllotoxin glycosides were synthesized by utilizing the Click reaction.Evaluation of cytotoxicity against a panel of five human cancer cell lines(HL-60,SMMC-7721,A-549,MCF-7,SW480)using MTT assay shows that most of these compounds show weak cytotoxicity.It was observed that compound 16 shows the highest activity with IC50 values ranging from 2.85 to 7.28 lM,which is more potent than the control drugs etoposide and cisplatin against four of five cancer cell lines tested.Compound 16 is characterized with an a-D-galactosyl residue directly linked to the triazole ring and a 40-OH group on the E ring of the podophyllotoxin scaffold.HPLC investigation of representative compound indicates that incorporation of a sugar moiety seems to improve the chemical stability of the podophyllotoxin scaffold.

Block and Hetero Ethyl Cellulose Graft Copolymers Synthe- sized via Sequent and One-pot ATRP and ＂Click＂ Reactions

Ethyl cellulose graft copolymers with block and hetero side chains, ethyl cellulose graft [polystyrene-b-poly- （ethylene glycol）] [EC-g-（PS-b-PEG）] and ethyl cellulose graft polystyrene and polyethylene glycol [EC-g-（PS-PEG ）] were synthesized by atomic transfer radical polymerization （ATRP） and alkyne-azide ＂click＂ reactions and ＂one-pot＂ ATRP and ＂click＂ reactions, respectively. For the synthesis of EC-g-（PS-b-PEG）, the macroinitiator for ATRP was first synthesized via the esterification of hydroxyl groups of EC with 2-bromoisobutyryl bromide to re- sult ethyl cellulose 2-bromoisobutyryl ester （EC-Br）. The degree of substitution of bromide groups, which deter- mined the graft density, can be tailored by varying the feeding ratios of the hydroxyl groups to 2-bromoisobutyryl bromide. Then ATRP was carried out for preparing EC-g-PS-Br with well-defined length of PS chains. The EC-g-PS-Br copolymers were then converted to EC-g-PS-N3 and then reacted with end alkyne-functionalized PEG via click to result in EC-g-（PS-b-PEG）. The EC-g-（PS-PEG） copolymers were synthesized by converting bromide groups of EC-Br to azide groups （EC-Br-N3） and then by one-pot ATRP and ＂click＂ reactions. The resultant graft copolymers were characterized by FTIR and IH NMR. The results indicate the success of the synthetic procedure of the cellulose grail copolymers with block and hetero side chains.

Copper(Ⅰ)-catalyzed interrupted click/radical relay:A four-component modular synthesis of triazole sulfones

A new,four component copper(Ⅰ)-catalyzed interrupted click/radical relay cascade has been developed.This unprecedented interrupted click reaction provides a rapid modular synthesis of triazole sulfones,important privileged heterocyclic pharmacophores which cannot be accessed by a traditional click reaction.Radical interception of cuprate-triazole,the key reaction intermediate formed in situ,is an important feature of this process.

Ultrasound-activated in situ click chemistry to trigger autophagosome tracking for enhanced autophagy blockade and synergistic cancer therapy

The blockade of cytoprotective autophagy has been demonstrated to effectively enhance the efficacy of sonodynamic therapy(SDT).However,the limited recognition of antiautophagy agents for autophagosomes impedes the clinical application of autophagy inhibition.To efficiently deliver hydroxychloroquine(HCQ),an autophagy inhibitor,to autophagosomes,we utilized a strategy based on in situ click chemistry between sulfhydryl(-SH)and maleimide(Mal)groups to trigger autophagosomes tracking and suppress tumor growth synergistically.A cascade nanoreactor was synthesized by encapsulating Mal-modified HCQ(MHCQ)into a manganese porphyrin-based metal-organic framework with sonosensitizer properties,followed by poly(ethylene glycol)ylated liposomal membrane coating.After ultrasound irradiation,SDT-induced apoptotic cells released damaged proteins with free-SH groups,which MHCQ rapidly captured in situ via a Malthiol click reaction.When autophagosomes actively wrapped damaged proteins for detoxification,they simultaneously internalized HCQ anchored on proteins.In this scenario,antiautophagy drugs could actively track intracellular autophagosomes instead of undergoing passive diffusion in the cytosol.The interaction between HCQ and autophagic vesicles was greatly enhanced,which strengthened the blocking efficiency of autophagy and resulted in complete cell death.Overall,this study with smart design provides a promising strategy for improving intracellular targeted delivery to autophagosomes,thereby enhancing antitumor therapy.

Employing the thiol-ene click reaction via metal-organic frameworks for integrated sonodynamic-starvation therapy as an oncology treatment

Hypoxia in the tumor microenvironment(TME)greatly limits the tumor-killing therapeutic efficacy of sonodynamic therapy(SDT);this phenomenon is further exacerbated by increased glutathione(GSH)levels in cancer cells.Simultaneously,cancer starvation therapy is increasingly recognized nowadays as a promising clinical translation,but the efficacy of glucose oxidase(GOx)-based starvation therapy is also limited by the lack of oxygen in the tumor.Glyceraldehyde-3-phosphate dehydrogenase(GAPDH)is a key glycolytic enzyme and can therefore be a target for starvation therapy in the absence of oxygen engagement.Here,we proposed thiol-ene click reactions based on a two-dimensional metal-organic framework(MOF)modification for tumor treatments to enable the combination of SDT and starvation therapy.Experimental studies demonstrated that the prepared material could consume GSH and GAPDH free from oxygen in TME,which benefited from the thiol-ene click reactions between the MOFs and thiol substances in cancer cells.Further experiments in vitro and in vivo indicated the prepared MOF materials could kill cancer cells efficiently.This study is expected to create a promising avenue for thiol-ene click reactions in SDT and starvation therapy for cancer.

Synthesis, Structure and H＋/K＋-ATPase Inhibitory Activity of Novel Triazolyl Substituted Tetrahydrobenzofuran Derivatives via One-pot Three-component Click Reaction

Eleven triazolyl substituted tetrahydrobenzofuran derivatives were synthesized in high yields as novel H＋/K＋- ATPase inhibitor via one-pot Cul-catalyzed three-component click reaction of azide, secondary amine and 3-bromopropyne under mild conditions in water. Their structures were characterized by NMR, IR, ESI-MS, ele- mental analysis and single-crystal X-ray diffraction analysis. Most of the target compounds exhibited better H＋/K＋- ATPase inhibitory activity than commercial omeprazole with IC50 values less than 15 gmol＇L-~. The initial struc- ture-activity analysis suggested that the triazole substituted by cycloalkyl, aromatic ring or O-containing side-chain seemed to be beneficial for enhancing the activity.

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.

Spatial control of palladium nanoparticles in flexible click-based porous organic polymers for hydrogenation of olefins and nitrobenzene

Two flexible click-based porous organic polymers （CPP-F1 and CPP-F2） have been readily synthesized. SEM images show CPP-F1 is a 3D network, while CPP-F2 exhibits a granular morphology. Pd（OAc）2 can be easily incorporated into CPP-F1 and CPP-F2 to form Pd@CPP-F1 and Pd@CPP-F2, respectively. The interactions between the polymers and palladium are confirmed by solid-state 13C NMR, IR and XPS. Palladium nanoparticles （NPs） are formed after hydrogenation of olefins and nitrobenzene. Palladium NPs in CPP-F1 are well dispersed on the external surface of the polymer, while palladium NPs in CPP-F2 are located in the interior pores and on the external surface. In comparison with NPs in CPP-F1, the dual distribution of palladium NPs in CPP-F2 results in higher selectivity in the hydrogenation of 1,3-cyclohexadiene to cyclohexane. The catalytic systems can be recycled several times without obvious loss of catalytic activity or agglomeration of palladium NPs. Hot filtration, mercury drop tests and ICP analyses suggest that the catalytic systems proceed via a heterogeneous pathway.

Preparation of amphiphilic graft copolymer with polyisoprene backbone by combination of anionic polymerization and "click" reaction

A novel graft copolymer consisting of polyisoprene backbone and hydrophilic side chain with carbamic acid ester functional group was prepared via thiol-ene＂click＂reaction and alcohol-isocyanate reactions.Polyisoprene was synthesized by anionic polymerization using n-butyl lithium as initiator,and the pendant hydroxyl groups were introduced by the thiol-ene reaction of mercaptoethanol with the double bond of 1,2-addition units of PI backbone in the presence of radical initiator azobisisobutyronitrile. Isocyanate end group capped poly（ethylene glycol）（mPEG-NCO） was grafted onto the PI backbone through alcoholisocyanate reaction between the pendant hydroxyl groups and isocyanate group of mPEG-NCO.The structure of the graft copolymer were characterized and confirmed by means of size-exclusion chromatography,~1H NMR and FTIR spectroscopy.

Copper Salt of 12-Tungstophosphoric Acid： An Efficient and Reusable Heteropoly Acid for the Click Chemistry

Three components coupling of alkyl bromide, sodium azide and alkyne has been achieved using a catalytic amount of copper-exchanged phosphotungstic acid （Cu-TPA） in the presence of triethyl amine in DMF to afford substituted triazoles in good yields with high selectivity. Interestingly, the coupling of alkyl azide with alkyne pro- ceeds readily at room temperature to furnish 1,2,3-triazoles in excellent yields. The catalyst can be recovered and reused for three to four subsequent runs with a minimal decrease of activity. The use of copper modified heter- opolyacids makes this procedure simple, convenient and environmentally friendly.

Recent advances in click-derived macrocycles for ions recognition

The Cu（I）-catalyzed azide-alkyne 1,3-dipolar cycloaddition（CuAAC） reaction, popularly known as the ＂click reaction＂, have been widely used in chemosensor field. This reaction gives a mild and efficient coupling reaction between the binding site and the reporter. In addition, the formation 1,4-disubstituted1,2,3-triazole linker shows a high binding affinity toward both anions and metal ions. Recently researches revealed this reaction is also an efficient tool to form rigid or shape-persistent, preorganized macrocyclic species. This review summarized the recent advances in click derived macrocyclic receptors for recognition of anion, metal ion and ions pair.

Preparation of click-driven cross-linked anion exchange membranes with low water uptake

Significant advancement in anion exchange membrane(AEM)fuel cell(AEMFC)technology is important in the field of renewable energy.AEMs with comb-shaped architectures have attracted considerable research interest because of some unique features,including high anion conductivity,low swelling,and high alkaline stability.Here,we report preparation,characterization,and performance evaluation of a novel comb-shaped cross-linked AEM synthesized by the thiol-ene click and Menshutkin reactions.The prepared ionomer decreases the trade-off between the water uptake and the conductivity.The thiol-ene click reaction was used to synthesize the 1,14-di(1H-imidazol-1-yl)-6,9-dioxa-3,12-dithiatetradecane(IDDT)cross-linker.IDDT was then introduced into the brominated poly(2,6-dimethyl-1,4-phenylene oxide)backbone by the Menshutkin reaction.The prepared ionomers show high thermomechanical stability,which is needed in AEMFC technology.The CLINK-15-100 membrane(ion exchange capacity 1.23 mmol/g)shows relatively good conductivities of 19.66 and 34.91 mS/cm at 30 and 60℃,respectively.Interestingly,the membrane shows water uptake of only 14.22%at room temperature,which is considerably lower than many previously reported membranes.After 16 days of alkaline treatment in 1 M NaOH solution at 60℃,the CLINK-15-100 membrane retains 77%of its initial conductivity,which is much better than the traditional quaternized poly(2,6-dimethyl-1,4-phenylene oxide)membrane.

Applications of CBT-Cys click reaction: past, present, and future

Herein, we review the development, applications and potential prospects of CBT-Cys click reaction. This click condensation reaction is based on the condensation reaction between 2-cyanobenzothiazole(CBT) and D-cysteine(D-Cys) in fireflies and has high biocompatibility and controllability in physiological solutions. Under the control of p H, reduction, or enzyme, this CBTbased click reaction has been widely applied to a wide range of biomedical fields such as protein labeling, molecular imaging(e.g., optical imaging, nuclear imaging, magnetic resonance imaging and photoacoustic imaging), nanomaterial fabrication, cancer therapy, and other potentialities.