Azide-alkyne Cycloaddition Reaction Research Articles

Ultrasound-assisted Cu(II) Strecker-functionalized organocatalyst for green azide-alkyne cycloaddition and Ullmann reactions.

A new aminonitrile-functionalized Fe3O4 has been synthesized via the Strecker reaction, the designed aminonitrile ligand on the surface of the magnetic core coordinated to copper(II) to obtain the final new catalyst. The fabricated nanocatalyst was characterized by Fourier transform Infrared (FT-IR), Field Emission Scanning Electron Microscopy (FESEM), Energy-Dispersive X-ray spectroscopy (EDX), Transmission Electron Microscopy (TEM), Vibrating-Sample Magnetometer (VSM), Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES), and Thermogravimetric Analysis (TGA). The high tendency of nitrogens in the aminonitrile functional group to make a complex with Cu(II) has caused the practical activity of this nucleus in this catalyst. This nanocatalyst performance was investigated in azide-alkyne Huisgen cycloaddition (3 + 2) reaction for achieving to 1,4-disubstituted 1,2,3-triazoles in water as a green media at room temperature. In another try, Classic Ullmann Reaction was investigated for the synthesis of biaryls at 85°C promoted by ultrasonic condition (37 kHz). The reaction scope was explored using different reactants and the results of using this developed catalytic system demonstrated its capacity to reduce the reaction time and enhance the reaction efficiency to provide good to excellent product yield. Conversely, the simple recycling and reusability of this catalyst for at least six times without any noticeable leaching of copper makes it a potential future catalyst for synthesizing such compounds.

Metallo-Glycodendrimeric Materials against Enterotoxigenic Escherichia coli.

Conjugation of carbohydrates to nanomaterials has been extensively studied and recognized as an alternative in the biomedical field. Dendrimers synthesized with mannose at the end group and with entrapped zero-valent copper/silver could be a potential candidate against bacterial proliferation. This study is aimed at investigating the bactericidal activity of metal-glycodendrimers. The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction was used to synthesize a new mannosylated dendrimer containing 12 mannopyranoside residues in the periphery. The enterotoxigenic Escherichia coli fimbriae 4 (ETEC:F4) viability, measured at 600 nm, showed the half-inhibitory concentration (IC50) of metal-free glycodendrimers (D), copper-loaded glycodendrimers (D:Cu) and silver-loaded glycodendrimers (D:Ag) closed to 4.5 × 101, 3.5 × 101 and to 1.0 × 10-2 µg/mL, respectively, and minimum inhibitory concentration (MIC) of D, D:Cu and D:Ag of 2.0, 1.5 and 1.0 × 10-4 µg/mL, respectively. The release of bacteria contents onto broth and the inhibition of ETEC:F4 biofilm formation increased with the number of metallo-glycodendrimer materials, with a special interest in silver-containing nanomaterial, which had the highest activity, suggesting that glycodendrimer-based materials interfered with bacteria-bacteria or bacteria-polystyrene interactions, with bacteria metabolism and can disrupt bacteria cell walls. Our findings identify metal-mannose-dendrimers as potent bactericidal agents and emphasize the effect of entrapped zero-valent metal against ETEC:F4.

Mechanistic Basis of the Cu(OAc)2 Catalyzed Azide-Ynamine (3 + 2) Cycloaddition Reaction.

The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is used as a ligation tool throughout chemical and biological sciences. Despite the pervasiveness of CuAAC, there is a need to develop more efficient methods to form 1,4-triazole ligated products with low loadings of Cu. In this paper, we disclose a mechanistic model for the ynamine-azide (3 + 2) cycloadditions catalyzed by copper(II) acetate. Using multinuclear nuclear magnetic resonance spectroscopy, electron paramagnetic resonance spectroscopy, and high-performance liquid chromatography analyses, a dual catalytic cycle is identified. First, the formation of a diyne species via Glaser-Hay coupling of a terminal ynamine forms a Cu(I) species competent to catalyze an ynamine-azide (3 + 2) cycloaddition. Second, the benzimidazole unit of the ynamine structure has multiple roles: assisting C-H activation, Cu coordination, and the formation of a postreaction resting state Cu complex after completion of the (3 + 2) cycloaddition. Finally, reactivation of the Cu resting state complex is shown by the addition of isotopically labeled ynamine and azide substrates to form a labeled 1,4-triazole product. This work provides a mechanistic basis for the use of mixed valency binuclear catalytic Cu species in conjunction with Cu-coordinating alkynes to afford superior reactivity in CuAAC reactions. Additionally, these data show how the CuAAC reaction kinetics can be modulated by changes to the alkyne substrate, which then has a predictable effect on the reaction mechanism.

Synthesis of 1, 2, 3-triazole linked 5 fluorouracil - carbon dots -folate conjugates for target specific anticancer activity and cell imaging applications

This work provides a unique strategy to anchor the individual properties of fluorophores, pharmacophores and receptors in a single platform using a copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC). Notably, this approach counters the long-term dispute associated with the target-specific drug delivery of 5 fluorouracil and its intracellular tracing. Significantly, the luminescence property of the carbon dots (CDs) and the anticancer activity of the 5 fluorouracil drug are well preserved, even after their structural modification. The resulting nano-hybrid conjugate shows good thermal stability, photo-stability and can selectively guide the drug molecule toward cancer cells and remain nontoxic to noncancerous (hFB) cells. The conjugation of folic acid to the nanohybrid surface promoted the folate receptor-facilitated endocytosis to the folate-positive (HeLa) cell lines over the folate-negative (MCF-7) cells, which enhanced cellular uptake and corresponding better cell apoptosis results. Around 18.2% of cell apoptosis (late + early) values were recorded for the folate-conjugated formulation compared to the folate-less formulation (12.3%) and pure 5 FU drug (7.9%) by a flow cytometry study. Cell cycle analysis confirmed that the populations of HeLa cells in the S phase were around 18.20% and 29.8% for the folate-less formulation and the folate-conjugated formulation, indicating all the formulations can hinder the DNA replication and thymidylate synthesis by introducing cell cycle arrest in the S phase, just like the pure 5 FU drug. Also, the location of the drug molecule can be simultaneously traced because of the luminescent nature of the CDs. Therefore, the developed system has potential in target-specific drug delivery and long-term drug molecule tracking applications.

Conjugated molecularly imprinted polymers based on covalent organic frameworks: Fluorescent sensing platform for specific capture of urea and elimination of ethyl carbamate

This study described the preparation of an azide covalent organic framework-embedded molecularly imprinted polymers (COFs(azide)@MIPs) platform for urea adsorption and indirect ethyl carbamate (EC) removal from Chinese yellow rice wine (Huangjiu). By modifying the pore surface of COFs using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, COFs(azide) with a high fluorescence quantum yield and particular recognition ability were inventively produced. In order to selectively trap urea, the COFs(azide) were encased in an imprinted shell layer via imprinting technology. With a detection limit (LOD) of 0.016 μg L-1 (R2 = 0.9874), the COFs(azides)@MIPs demonstrated a good linear relationship with urea in the linear range of 0–5 μg L-1. Using real Huangjiu samples, the spiking recovery trials showed the viability of this sensing platform with recoveries ranging from 88.44 % to 109.26 % and an RSD of less than 3.40 %. The Huangjiu processing model system achieved 38.93 % EC reduction by COFs(azides)@MIPs. This research will open up new avenues for the treatment of health problems associated with fermented alcoholic beverages, particularly Huangjiu, while also capturing and removing hazards coming from food.

Halo-1,2,3-triazoles: Valuable Compounds to Access Biologically Relevant Molecules.

1,2,3-triazole is an important building block in organic chemistry. It is now well known as a bioisostere for various functions, such as the amide or the ester bond, positioning it as a key pharmacophore in medicinal chemistry and it has found applications in various fields including life sciences. Attention was first focused on the synthesis of 1,4-disubstituted 1,2,3-triazole molecules however 1,4,5-trisubstituted 1,2,3-triazoles have now emerged as valuable molecules due to the possibility to expand the structural modularity. In the last decade, methods mainly derived from the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction have been developed to access halo-triazole compounds and have been applied to nucleosides, carbohydrates, peptides and proteins. In addition, late-stage modification of halo-triazole derivatives by metal-mediated cross-coupling or halo-exchange reactions offer the possibility to access highly functionalized molecules that can be used as tools for chemical biology. This review summarizes the synthesis, the functionalization, and the applications of 1,4,5-trisubstituted halo-1,2,3-triazoles in biologically relevant molecules.

Synthesis of Estrone Heterodimers and Evaluation of Their In Vitro Antiproliferative Activity.

Directed structural modifications of natural products offer excellent opportunities to develop selectively acting drug candidates. Natural product hybrids represent a particular compound group. The components of hybrids constructed from different molecular entities may result in synergic action with diminished side effects. Steroidal homo- or heterodimers deserve special attention owing to their potentially high anticancer effect. Inspired by our recently described antiproliferative core-modified estrone derivatives, here, we combined them into heterodimers via Cu(I)-catalyzed azide-alkyne cycloaddition reactions. The two trans-16-azido-3-(O-benzyl)-17-hydroxy-13α-estrone derivatives were reacted with 3-O-propargyl-D-secoestrone alcohol or oxime. The antiproliferative activities of the four newly synthesized dimers were evaluated against a panel of human adherent gynecological cancer cell lines (cervical: Hela, SiHa, C33A; breast: MCF-7, T47D, MDA-MB-231, MDA-MB-361; ovarian: A2780). One heterodimer (12) exerted substantial antiproliferative activity against all investigated cell lines in the submicromolar or low micromolar range. A pronounced proapoptotic effect was observed by fluorescent double staining and flow cytometry on three cervical cell lines. Additionally, cell cycle blockade in the G2/M phase was detected, which might be a consequence of the effect of the dimer on tubulin polymerization. Computational calculations on the taxoid binding site of tubulin revealed potential binding of both steroidal building blocks, mainly with hydrophobic interactions and water bridges.

Pyrano[2,3-c]pyrazole fused spirooxindole-linked 1,2,3-triazoles as antioxidant agents: Exploring their utility in the development of antidiabetic drugs via inhibition of α-amylase and DPP4 activity

Environment-benign, multicomponent synthetic methodologies are vital in modern pharmaceutical research and facilitates multi-targeted drug development via synergistic approach. Herein, we reported green and efficient synthesis of pyrano[2,3-c]pyrazole fused spirooxindole linked 1,2,3-triazoles using a tea waste supported copper catalyst (TWCu). The synthetic approach involves a one-pot, five-component reaction using N-propargylated isatin, hydrazine hydrate, ethyl acetoacetate, malononitrile/ethyl cyanoacetate and aryl azides as model substrates. Mechanistically, the reaction was found to proceed via in situ pyrazolone formation followed by Knoevenagel condensation, azide alkyne cycloaddition and Michael's addition reactions. The molecules were developed using structure-based drug design. The primary goal is to identifying anti-oxidant molecules with potential ability to modulate α-amylase and DPP4 (dipeptidyl-peptidase 4) activity. The anti-oxidant analysis, as determined via DPPH, suggested that the synthesized compounds, A6 and A10 possessed excellent anti-oxidant potential compared to butylated hydroxytoluene (BHT). In contrast, compounds A3, A5, A8, A9, A13, A15, and A18 were found to possess comparable anti-oxidant potential. Among these, A3 and A13 possessed potential α-amylase inhibitory activity compared to the acarbose, and A3 further emerged as dual inhibitors of both DPP4 and α-amylase with anti-oxidant potential. The relationship of functionalities on their anti-oxidant and enzymatic inhibition was explored in context to their SAR that was further corroborated using in silico techniques and enzyme kinetics.

A High-Yielding Active Template Click Reaction (AT-CuAAC) for the Synthesis of Mechanically Interlocked Nanohoops.

Mechanically interlocked molecules (MIMs) represent an exciting yet underexplored area of research in the context of carbon nanoscience. Recently, work from our group and others has shown that small carbon nanotube fragments-[n]cycloparaphenylenes ([n]CPPs) and related nanohoop macrocycles-may be integrated into mechanically interlocked architectures by leveraging supramolecular interactions, covalent tethers, or metal-ion templates. Still, available synthetic methods are typically difficult and low yielding, and general methods that allow for the creation of a wide variety of these structures are limited. Here we report an efficient route to interlocked nanohoop structures via the active template Cu-catalyzed azide-alkyne cycloaddition (AT-CuAAC) reaction. With the appropriate choice of substituents, a macrocyclic precursor to 2,2'-bipyridyl embedded [9]CPP (bipy[9]CPP) participates in the AT-CuAAC reaction to provide [2]rotaxanes in near-quantitative yield, which can then be converted into the fully π-conjugated catenane structures. Through this approach, two nanohoop[2]catenanes are synthesized which consist of a bipy[9]CPP catenated with either Tz[10]CPP or Tz[12]CPP (where Tz denotes a 1,2,3-triazole moiety replacing one phenylene ring in the [n]CPP backbone).

A 66-Nuclear All-Alkynyl Protected Peanut-Shaped Silver(I)/Copper(I) Heterometallic Nanocluster: Intermediate in Copper-Catalyzed Alkyne-Azide Cycloaddition.

Ligand-protected heterometallic nanoclusters in contrast to homo-metal counterparts show more broad applications due to the synergistic effect of hetero-metals but their controllable syntheses remain a challenge. Among heterometallic nanoclusters, monovalent Ag-Cu compounds are rarely explored due to much difference of Ag(I) and Cu(I) such as atom radius, coordination habits, and redox potential. Encouraged by copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction, comproportionation reaction of Cu(II)X2 and Cu(0) in the presence of (PhC≡CAg)n complex and molybdate generated a core-shell peanut-shaped 66-nuclear Ag(I)-Cu(I) heterometallic nanocluster, [(Mo4O16)2@Cu12Ag54(PhC≡C)50] (referred to as Ag54Cu12). The structure and composition of Ag-Cu heterometallic nanocluster are fully characterized. X-ray single crystal diffraction reveals that Ag54Cu12 has a peanut-shaped silver(I)/copper(I) heterometallic nanocage protected by fifty phenylacetylene ligands in µ3-modes and encapsulated two mutually twisted tetramolybdates. Heterometallic nanocage contains a 54-Ag-atom outer ellipsoid silver cage decorated by 12 copper inside wall. Nanosized Ag54Cu12 is a n-type narrow-band-gap semiconductor with a good photocurrent response. Preliminary experiments demonstrates that Ag54Cu12 itself and activated carbon supported Ag54Cu12/C are effective catalysts for 1,3-dipole cycloaddition between alkynes and azides at ambient conditions. The work provides not only a new synthetic route toward Ag(I)-Cu(I) nanoclusters but also an important heterometallic intermediate in CuAAC catalytic reaction.

Synthesis of block macro-CTAs by HNTs@Cu-catalyzed click reaction: Suitable CTAs for synthesizing multiblock polymers via RAFT polymerization

Multiblock copolymer macrochain-transfer agents (MBP-CTAs) can be used to synthesize MBPs in one pot via reversible addition-fragmentation chain-transfer (RAFT) polymerization. MBP-CTAs can be efficiently synthesized via a copper-catalyzed azide-alkyne cycloaddition reaction. However, traditional purification methods cannot sufficiently purify MBP-CTAs, resulting in the failure of RAFT. In this study, it was discovered that using a supported catalytic system, namely, Cu@A-HNTs, inhibited the connection between Cu and S. The residual Cu content in the MBP-CTA was successfully reduced to a low level (7.88 µg/mg). Then, hydrophilic and hydrophobic MBPs were synthesized through RAFT polymerization using the MBP-CTAs. Subsequently, multiblock copoly(methyl methacrylate-b-butyl methacrylate-CTA)s (PMMA-b-PBMA-c-CTA)s were successfully prepared. The MBP-CTAs and MBPs were characterized using ultraviolet–visible spectroscopy, 1H nuclear magnetic resonance, size-exclusion chromatography, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry, differential scanning calorimetry measurements and uniaxial tensile tests. The results of performance testing of PMMA-b-PBMA-c-CTAs demonstrated that their fracture stress and strain significantly increased comparing with that of PMMA-b-CTAs.

Tailored isatin-derived chemosensor immobilized on silica nanoparticles for targeted detection of Ni(II) ion

In this study, we have designed and synthesized a chemosensor, isatin-based triazole-linked silanes (ITS), employing the Cu(I)-catalyzed Azide-Alkyne cycloaddition reaction (CuAAC) and the synthesized silanes has been well characterized through various analytical techniques, including FT-IR, 1H NMR, 13C NMR, and ESI-MS. The developed sensor exhibited the capability to detect Ni2+ ion in a methanol/water solution (9:1, v/v) by manifesting different absorbance changes and fluorescence. In the fluorescence mode, the addition of Ni2+ ion triggers a “Turn-OFF” response in the sensor, demonstrating an ultratrace detection limit of 2.49 × 10−7 M. Successful grafting of organosilane onto silica nanoparticles has been achieved, and these new silane-coated nanoparticles demonstrate enhanced sensing abilities for Ni2+ ions, with a detection limit of 1.56 × 10−8 M. Stoichiometric data reveals a 1:1 coordination between the sensor and Ni2+ ion. Furthermore, both the synthesized alkyne and silane underwent examination for their drug-likeness profiles, providing valuable insights.

Selective Duplex Formation in Mixed Sequence Libraries of Synthetic Polymers.

Recognition-encoded melamine oligomers (REMO) are synthetic polymers that feature an alternating 1,3,5-triazine-piperazine backbone and side-chains equipped with either a phenol or phosphine oxide recognition unit. An automated method for the solid-phase synthesis (SPS) of REMO of any specified sequence has been developed starting from dichlorotriazine monomer building blocks. Complementary homo-oligomers with either six phenols or six phosphine oxides were synthesized and shown to form a stable duplex in nonpolar solvents by NMR denaturation experiments. The duplex was covalently trapped by equipping the ends of the oligomers with an azide and an alkyne group and using a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The SPS methodology was adapted to synthesize mixed sequence libraries by using a mixture of two different dichlorotriazine building blocks in each coupling cycle of an oligomer synthesis. The resulting libraries contain statistical mixtures of all possible sequences. The self-assembly properties of these libraries were screened by using the CuAAC reaction to trap any duplexes present. In mixed sequence libraries of 6-mers, the trapping experiments showed that only sequence-complementary oligomers formed duplexes at micromolar concentrations in dichloromethane. The automated synthesis approach developed here provides access to large libraries of mixed sequence synthetic polymers, and the covalent trapping experiment provides a convenient tool for screening functional properties of mixtures. The results suggest high-fidelity sequence-selective duplex formation in mixtures of 6-mer sequences of the REMO architecture.

Minimalist Tetrazine N-Acetyl Muramic Acid Probes for Rapid and Efficient Labeling of Commensal and Pathogenic Peptidoglycans in Living Bacterial Culture and During Macrophage Invasion.

N-Acetyl muramic acid (NAM) probes containing alkyne or azide groups are commonly used to investigate aspects of cell wall synthesis because of their small size and ability to incorporate into bacterial peptidoglycan (PG). However, copper-catalyzed alkyne-azide cycloaddition (CuAAC) reactions are not compatible with live cells, and strain-promoted alkyne-azide cycloaddition (SPAAC) reaction rates are modest and, therefore, not as desirable for tracking the temporal alterations of bacterial cell growth, remodeling, and division. Alternatively, the tetrazine-trans-cyclooctene ligation (Tz-TCO), which is the fastest known bioorthogonal reaction and not cytotoxic, allows for rapid live-cell labeling of PG at biologically relevant time scales and concentrations. Previous work to increase reaction kinetics on the PG surface by using tetrazine probes was limited because of low incorporation of the probe. Described here are new approaches to construct a minimalist tetrazine (Tz)-NAM probe utilizing recent advancements in asymmetric tetrazine synthesis. This minimalist Tz-NAM probe was successfully incorporated into pathogenic and commensal bacterial PG where fixed and rapid live-cell, no-wash labeling was successful in both free bacterial cultures and in coculture with human macrophages. Overall, this probe allows for expeditious labeling of bacterial PG, thereby making it an exceptional tool for monitoring PG biosynthesis for the development of new antibiotic screens. The versatility and selectivity of this probe will allow for real-time interrogation of the interactions of bacterial pathogens in a human host and will serve a broader utility for studying glycans in multiple complex biological systems.

Rapid polythioether synthesis and thioether network formation using thiol-yne chemistry of electron-deficient alkynes

The preparation of polythioethers has gained importance again after the development of click chemistry reactions. The thiol-X reactions, i.e., thiol-ene reactions based on free radical mechanism facilitated by light or heat, and thiol-Michael and thiol-epoxy reactions, which are the main synthetic pathways for the synthesis of polymers (linear, hyperbranched (HB), and network) with thioether linkages and meet most of the features of click reactions strategy, have currently been revisited. For a while, our group has focused on synthesizing linear, HB, and network polythioethers based on electron-deficient alkyne-containing precursors. We have shown that electron-deficient alkyne-containing monomers and polymers offer a suitable platform for thiol-Michael (i.e., thiol-yne) click reactions to yield linear, HB, and network structures rapidly under ambient conditions. The central structure in these polythioether syntheses is electron-deficient alkyne bonds of acetylenedicarboxylates, which are then reacted with dithiols in chloroform through an organobase 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) at ambient temperatures. Moreover, acetylenedicarboxylates are functionalized using copper-free azide-alkyne cycloaddition reaction followed by reacting with multifunctional allyl and SH derivatives through thiol-ene photopolymerization resulting in polymeric networks with thioether linkages. This feature article highlights our contribution to the synthesis of linear, HB, and network polythioether based on various electron-deficient alkyne precursors.

Chloromethylation of Lignin as a Route to Functional Material with Catalytic Properties in Cross-Coupling and Click Reactions.

We present a novel, greener chloromethylation procedure for organosolv aspen lignin under mild reaction conditions without Lewis acid as a catalyst and in acetic acid as a solvent. This synthetic protocol provides a reliable approach to chloromethylated lignin (CML) and means to obtain valuable lignin derivatives. The resulted CML was subsequently transformed into 1-methylimidazolium lignin (ImL), which effectively serves as a stabilizing agent for Pd/CuO nanoparticles (Pd/CuO-NPs). To evaluate the versatility of developed lignin-based catalyst, we investigate its performance in a series of carbon-carbon bond formation reactions, including Suzuki-Miyaura, Sonogashira, Heck reactions, and azide-alkyne cycloaddition (click) reaction. Remarkably, this catalyst exhibited a high degree of catalytic efficiency, resulting in reactions with yields ranging from average to excellent. The heterogeneous catalyst demonstrated outstanding recyclability, enabling its reuse for at least 10 consecutive reaction cycles, with yields consistently falling within the range of 42 % to 84 %. A continuous flow reactor cartridge prototype employing Lignin@Pd/CuO-NPs was developed, yielding results comparable to those achieved in batch reactions. The utilization of Lignin@Pd/CuO-NPs as a catalyst showcases its potential to facilitate diverse carbon-carbon bond formation reactions and underscores its promising recyclability, aligning with the green chemistry metrics and principles of sustainability in chemical processes.

Exploring the potential of the vitamin B12 derivative azidocobalamin to undergo Huisgen 1,3-dipolar azide-alkyne cycloaddition reactions

There is considerable interest in using the metalloprotein cofactor vitamin B12 as a vehicle to deliver drugs and diagnostic agents into mammalian or bacterial cells by exploiting the B12-specific active uptake pathways. Conjugation of the cargo via the β-axial site or the 5’-OH of the ribose of the nucleotide are the most desirable sites, to maximise intracellular uptake. Herein we show the potential of conjugation at the beta-azido ligand of the vitamin B12 derivative azidocobalamin via a click-type azide-alkyne 1,3-dipolar cycloaddition (Huisgen cycloaddition) reaction. Reacting azidocobalamin with dimethyl acetylenedicarboxylate at 40 °C results in essentially stoichiometric conversion of azidocobalamin to the corresponding triazolato complex. The stability of the complex as a function of pH and in the presence of cyanide were investigated. The complex is stable in pD 7.0 phosphate buffer for 24 h. The rate of beta-axial ligand substitution was found to be one order of magnitude slower for the triazolatocobalamin complex compared with azidocobalamin.

1H-1,2,3-triazolyl-1,6-naphthyridin-7(6H)-ones as Potential Fluorescent Nucleoside Analogues: Synthesis and Optical Properties.

In this article, we present the synthesis and the optical properties of three original molecules as potential fluorescent ribonucleoside analogues incorporating a 1,6-naphthyridin-7(6H)-one scaffold as a fluorescent nucleobase and a 1,2,3-triazole as a linkage. The nucleosides were prepared via a Cu alkyne-azide cycloaddition (CuAAC) reaction between a ribofuranosyl azide and a 4-ethynylpyridine partner. Construction of substituted 1,6-naphthyridin-7(6H)-ones was achieved through two additional steps. Optical property studies were investigated on nucleoside analogues. Powerful fluorescence properties have been evidenced with a remarkable change of emissivity depending on the polarity of the solvent, making these molecules suitable as a new class of artificial fluorescent nucleosides for investigating enzyme binding sites as well as probing nucleic acids. In addition, we are convinced that such analogues could be of great interest in the search for new antiviral or antitumoral drugs based on nucleosides.

MOFs Modulate Copper Trafficking in Tumor Cells for Bioorthogonal Therapy.

In situ drug synthesis using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has attracted considerable attention in tumor therapy because of its satisfactory effectiveness and reduced side-effects. However, the exogenous addition of copper catalysts can cause cytotoxicity and has hampered biomedical applications in vivo. Here, we design and synthesize a metal-organic framework (MOF) to mimic copper chaperone, which can selectively modulate copper trafficking for bioorthogonal synthesis with no need of exogenous addition of copper catalysts. Like copper chaperones, the prepared ZIF-8 copper chaperone mimics specifically bind copper ions through the formation of coordination bonds. Moreover, the copper is unloaded under the acidic environment due to the dissipation of the coordination interactions between metal ions and ligands. In this way, the cancer cell-targeted copper chaperone mimics can selectively transport copper ions into cells. Regulation of intracellular copper trafficking may inspire constructing bioorthogonal catalysis system with reduced metal cytotoxicity in live cells.

Synthesis and characterization of a new copper-based polyoxomolybdate and its catalytic activity for azide-alkyne cycloaddition reaction under UV light irradiation

A new organic-functionalized Cu-based Anderson-type polyoxomolybdate, namely (C7H15N4)2[Na(H2O)4]2[C6H12CuMo6N2O24]·2(H2O) (CuII-POM), was synthesized via a simple one-pot reaction and subsequently characterized using a range of analytical and spectral techniques. Structural investigation by single crystal X-ray diffraction analysis revealed that the polyanion component of the synthesized compound (i.e. [C6H12CuMo6N2O24]4−) possesses a δ-isomer Anderson-type structure, which is surrounded by four lattice water molecules and four [C7H15N4–NaH15(H2O)8]4+ cations in the crystal packing arrangement. The resulting double-sided tris-functionalized Anderson-type compound can function as highly effective heterogeneous photocatalysts for the copper(I)-catalyzed Huisgen azide-alkyne cycloaddition (Cu-AAC) reaction of terminal alkyne, benzyl halides, and sodium azide (acts as the azidonation and reducing agent) in aqueous media. Ultraviolet light irradiation enhances the catalytic activity of CuII-POM ~ 4.4 times of the “off” situation under reaction conditions of 0.00239 mmol cat., 80 °C, 8 h, 2 mL H2O, So that the isolated yields for the AAC reaction involving a variety of terminal alkynes and benzyl halides using the CuII-POM catalyst ranged between 19–97%. The current study is the first report about using an efficient and economical Cu(II)-POM/UV/NaN3 catalytic system in the Cu-AAC reaction and reveals its significant potential for applying to other Cu(I)-catalyzed reactions.