Cycloaddition Of Azides Research Articles

Synthesis of 1,2,3-triazoles in the presence of mixed Mg/Fe oxides and their evaluation as corrosion inhibitors of API 5L X70 steel submerged in HCl

The 1-benzyl-4-phenyl-1,2,3-triazoles, synthesised from alkyne–azide cycloaddition in presence of mixed Mg/Fe oxides, exhibited excellent properties as corrosion inhibitors.

Three‐Dimensional Ordered Antibody Arrays Through Self‐Assembly of Antibody–Polymer Conjugates

AbstractThree‐dimensional (3D) ordered arrays of human immunoglobulin G (IgG) were fabricated using well‐defined full‐length antibody–polymer conjugates (APCs). The conjugates were prepared through a two‐step sequential click approach with a combination of oxime ligation and strain promoted alkyne–azide cycloaddition. They were able to self‐assemble into lamellar nanostructures with alternating IgG and poly(N‐isopropylacrylamide) (PNIPAM) nanodomains. As a proof‐of‐concept, these materials were fabricated into thin films and their specific binding ability was tested. The nanostructure not only improves the packing density and the proper orientation of the IgG, but also provides nanochannels to facilitate substrate transport.

Copper nanoparticles in glycerol-polyvinyl alcohol matrix: In situ preparation, stabilisation and antimicrobial activity

Herein, we present a simple and affordable green synthesis of a nanocomposite material consisting of copper nanoparticles stabilized in a polyvinyl alcohol-glycerol matrix. TEM, UV-Vis and XRPD (X-ray Powder Diffraction) techniques were used to characterize the nanoparticles; properties of the polymer matrix were studied by NMR, IR and Raman spectroscopy as well as DSC measurements. The nanocomposite can be produced in two forms: gel and moldable plastic. Both the forms can be easily shaped at elevated temperature. The materials show very good long-term stability in air, protecting the produced copper nanoparticles from oxidation.Furthermore, we proved the application potential of the new nanocomposite as catalyst in copper catalyzed Huisgen 1,3-dipolar cycloaddition of azide and alkyne (frequently used in click-chemistry). In addition, antibacterial tests have proven inhibition of bacterial growth of both Gram-negative (Escherichia coli) and Gram-positive (Enterococcus faecalis) bacteria in the presence of the nanocomposite.

Photo‐Tethers for the (Multi‐)Cyclic, Conformational Caging of Long Oligonucleotides

AbstractIntramolecular circularization of DNA oligonucleotides was accomplished by incorporation of alkyne‐modified photolabile nucleosides into DNA sequences, followed by a CuI‐catalyzed alkyne–azide cycloaddition with bis‐azido linker molecules. We determined a range of ring sizes, in which the caged circular oligonucleotides exhibit superior duplex destabilizing properties. Specific binding of a full‐length 90 nt C10 aptamer recognizing human Burkitt's lymphoma cells was then temporarily inhibited by locking the aptamer in a bicircularized structure. Irradiation restored the native aptamer conformation resulting in efficient cell binding and uptake. The photo‐tether strategy presented here provides a robust and versatile tool for the light‐activation of longer functional oligonucleotides, noteworthy without prior knowledge on the structure and the importance of specific nucleotides within a DNA aptamer.

Silver and Copper-Supramolecular Coordination Polymers Inspired Alkyne–Azide Click Reactions

Two 3D-supramolecular coordination polymers (SCP); {[SnMe3(bpe)] [Ag(CN)2].2H2O}, 1, (bpe) = 1,2-bis(4-pyridyl)ethane and {[CuI(CN)(phen)2][CuII(CN)2(phen)]·5H2O}, 2, (phen) = phenanthroline, have been synthesized and characterized by physicochemical and spectroscopic methods. The SCP 1 and 2 exhibit good catalytic activity for the formation of substituted triazoles (1-benzyl- 4-bromomethyl triazole and 1-benzyl-4-phenyl triazole) in 98–100% yield. Of the factors investigated, the ratio of reactants and the amount of catalyst had the largest impact on yield. The use of the SCP 2 reduced by sodium ascorbate gave generally higher yields than a direct source of Cu owing to the high degree of efficiency. The general utility of the catalyst 1 and 2 indicated the formation of 1,4-substituted 1,2,3-triazoles in very good yield at shorter time in direct comparison to reactions performed in the presence of catalysts Cu(OAc)2 and AgNO3. In this case, the SCP 1 and 2-catalyzed alkyne–azide cyclo-addition provide 1,4-disubstituted 1,2,3-triazoles with such efficiency and scope that the transformation has been described as “click” chemistry.

Activated Fuller’s earth as an inexpensive, eco-friendly, efficient catalyst for the synthesis of 5-aryl 1-H-tetrazole via [3+2] cycloaddition of nitriles and sodium azide

A simple and efficient method for the preparation of 5-aryl 1-H-tetrazoles was developed from various aryl nitriles and sodium azide (NaN3) via [3+2] cycloaddition reaction using activated Fuller’s earth as an efficient heterogeneous catalyst. This catalyst has advantageous of cost, stability, recovery, reusability, and ecological benefits along with high product yield, and mild protocol.

Base-Promoted Synthesis of N-Substituted 1,2,3-Triazoles via Enaminone-Azide Cycloaddition Involving Regitz Diazo Transfer.

The domino reactions between NH-based secondary enaminones and tosyl azide have been developed for the synthesis of various N-substituted 1,2,3-triazoles by employing t-BuONa as the base promoter. Through a key Regitz diazo-transfer process with tosyl azide, the reactions proceed efficiently at room temperature with good substrate tolerance.

Another Example of Organo‐Click Reactions: TEMPO‐Promoted Oxidative Azide–Olefin Cycloaddition for the Synthesis of 1,2,3‐Triazoles in Water

The water‐mediated, metal‐free, 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) promoted oxidative [3+2] cycloaddition of organic azides with electron‐deficient terminal and internal olefins was explored. A library of 1,4‐disubstituted and 1,4,5‐trisubstituted‐1,2,3‐triazoles were synthesized in moderate to excellent yields. This method was also found to be compatible not only with open‐chain olefins but also with cyclic olefins.

Immobilized [Cu(cdsalMeen)] on silica gel: a highly efficient heterogeneous catalyst for ‘Click’ [3 + 2] Huisgen cycloaddition

A facile and simple protocol for the ‘Click’ cycloaddition of organic azides with terminal alkynes catalyzed by immobilized [Cu(cdsalMeen)] on silica as a new and convenient heterogeneous catalyst is described. In this synthetic methodology, [Cu(cdsalMeen)]–SiO2 catalyzes 1,3-dipolar Huisgen cycloaddition of different functionalized β-azido alcohols and alkynes in the presence of ascorbic acid and a solution of THF/H2O (2:1, V/V) at room temperature. Good to excellent yields of β-hydroxytriazolylalkyl derivatives were afforded using [Cu(cdsalMeen)]–SiO2. Immobilization of [Cu(cdsalMeen)] on silica was approved as a chemically and thermally stable catalyst that can be reused for many consecutive trials without a significant decline in its reactivity.

Synthesis of Substituted 1,2,3-Triazoles via Metal-Free Click Cycloaddition Reactions and Alternative Cyclization Methods

Click chemistry is one of the most efficient and widely used methodologies for selective C–N bond forming reactions, encompassing the synthesis of 1,2,3-triazoles, and it has been continued to be of great interest in synthetic and medicinal chemistry since its discovery. Diversely substituted 1,2,3-triazoles synthesized by classical Huisgen 1,3-dipolar cycloaddition of azides with alkynes have a broad spectrum of biological properties and they are widely accessed using transition-metal catalysts, such as copper- and ruthenium-catalyzed azide-alkyne cycloaddition [MAAC] reactions. In contrast, the development of organocatalyzed click chemistry has recently emerged as one of the most important alternative strategies to transition-metal-mediated reactions, because of its sustainability, environmentally benign processes and, moreover the absence of metals toxic to biological systems including living cells and biomolecules such as DNA. The focus of this review is on the recent advances in the organocatalytic click chemistry of enamine and enolate-mediated [3+2] cycloadditions and alternative metal-free cyclization reactions for the preparation of diversely functionalized 1,2,3-triazoles. The scope and limitations of these methods and also their applications for the synthesis of bioactive hybrid molecules are discussed. 1 Introduction 2 Enamine-Mediated Triazole Synthesis 3 Enolate-Mediated Triazole Synthesis 4 Alternative Metal-Free Triazole Synthesis 5 Applications to the Synthesis of Bioactive Compounds 6 Summary

Synthesis of Multicomponent Peptide-Based Vaccine Candidates against Group A Streptococcus

Group A streptococcus (GAS; Streptococcus pyogenes), known as the ‘flesh-eating bacterium’, is a human bacterial pathogen that normally causes benign infections (e.g. sore throat and pyoderma), but is also responsible for severe invasive infections (e.g. ‘flesh-eating’ disease and toxic shock syndrome), heart disease, and kidney failure. A safe commercial GAS vaccine is yet to be developed. Individual GAS antigens demonstrate potential universal expression across all GAS serotypes (>200 known), with dramatically reduced concern for autoimmune complications, and compelling efficacy in preclinical testing in mice. In this study, we developed a stepwise conjugation strategy, copper-catalysed alkyne–azide cycloaddition reaction (CuAAC), followed by mercapto–maleimide conjugation, to synthesise a multiantigenic, self-adjuvanting, peptide-based vaccine candidate against GAS. This multiantigenic vaccine includes two GAS antigens, J8 and NS1, a T-helper epitope, PADRE, and a self-adjuvanting moiety, dipalmitoyl serine.

Precise localization of metal nanoparticles in dendrimer nanosnakes or inner periphery and consequences in catalysis

Understanding the relationship between the location of nanoparticles (NPs) in an organic matrix and their catalytic performances is essential for catalyst design. Here we show that catalytic activities of Au, Ag and CuNPs stabilized by dendrimers using coordination to intradendritic triazoles, galvanic replacement or stabilization outside dendrimers strongly depends on their location. AgNPs are found at the inner click dendrimer periphery, whereas CuNPs and AuNPs are encapsulated in click dendrimer nanosnakes. AuNPs and AgNPs formed by galvanic replacement are larger than precursors and only partly encapsulated. AuNPs are all the better 4-nitrophenol reduction catalysts as they are less sterically inhibited by the dendrimer interior, whereas on the contrary CuNPs are all the better alkyne azide cycloaddition catalysts as they are better protected from aerobic oxidation inside dendrimers. This work highlights the role of the location in macromolecules on the catalytic efficiency of metal nanoparticles and rationalizes optimization in catalyst engineering.

Insights into Copper-Poly(pyrazolyl)methane-Catalyzed Reactions for Organic Transformations

Copper-poly(pyrazolyl)methane complexes have been proven to be highly useful in a variety of catalytic organic transformations. A multitude of poly(pyrazolyl)methane ligands have been developed for this effort and are summarized in this work. Their tailored electronic properties and steric hindrance are easily modified, demonstrating their diversity and high potential as spectator ligands for copper catalysis. The listed examples of organic reactions range from cycloadditions to nitrene transfer and bioinorganic monooxygenase chemistry. 1 Introduction 2 Cycloadditions of Azides and Alkynes 3 Copper-Mediated Nitrene and Carbene Transfer 4 Csp–Csp2, C–N and C–S Cross-Coupling Reactions 5 Copper–Tpm-Catalyzed Aldol Reactions 6 A Bpm Ligand for the Polymerization of Methyl Methacrylate 7 Copper-Catalyzed Oxidations 8 Concluding Remarks

Handling Hazards Using Continuous Flow Chemistry: Synthesis of N1-Aryl-[1,2,3]-triazoles from Anilines via Telescoped Three-Step Diazotization, Azidodediazotization, and [3 + 2] Dipolar Cycloaddition Processes

The conversion of commercially available anilines into triazole products was realized using a telescoped three-reactor flow diazotization, azidodediazotization, and [3 + 2] dipolar cycloaddition process. The diazotization–azidodediazotization sequence was accelerated by means of an ultrasonic bath resulting in a degassed, segmented effluent. An automated continuous flow unit controlled by custom software created in-house was used to collect the aryl azide stream and restore it to a continuous column of the reagent. When combined with a variety of dipolarophiles, 1-aryl-[1,2,3]-triazoles were thus assembled by either copper catalyzed alkyne–azide cycloaddition (CuAAC) or Huisgen cycloaddition reactions.

A two-step strategy to radiolabel choline phospholipids with 99mTc in S180 cell membranes via strain-promoted cyclooctyne–azide cycloaddition reaction

As tumor markers, the radiolabeling of choline (Cho)-containing phospholipids in cellular membranes with 99mTc is a challenge. The conventional strategy to combine the metallic radionuclide with Cho by large ligand damages the bioactivity of Cho, resulting in low tumor-to-nontumor ratios. Pretargeting strategy based on strain-promoted cyclooctyne–azide cycloaddition (SPAAC) reaction was applied to solve this general problem. Functional click synthons were synthesized as pretargeting components: azidoethyl-choline (AECho) serves as tumor marker and azadibenzocyclooctyne (ADIBO) conjugated to bis(2-pieolyl) amine (BPA) ligand (ADIBO-BPA) as 99mTc(CO)3-labeling and azido-binding group. Both in vitro cell experiment and in vivo biodistribution experiment indicate that it is versatile to radiolabel Cho in cellular membranes via this two-step pretargeting strategy. We believe that this pretargeting strategy can indeed enhance the target-specificity and also reduce background signals to optimize imaging quality.

Robust, Solvent-Free, Catalyst-Free Click Chemistry for the Generation of Highly Stable Densely Grafted Poly(ethylene glycol) Polymer Brushes by the Grafting To Method and Their Properties

Herein we report a robust, highly selective, and efficient method to prepare dense poly(ethylene glycol) (PEG) polymer brushes on silicon substrates via solvent-free, catalyst-free, strain-promoted acetylene–azide cycloaddition (SPAAC) reaction. First, poly(glycidyl methacrylate) was grafted to the silicon substrate as an anchoring layer to immobilize cyclopropenone-caged dibenzocyclooctyne-amine (photo-DIBO-amine) via an epoxy ring-opening reaction providing protected, stable, and functionalized substrates. Next, three synthesized α-methoxy-ω-azido-PEGs of different molecular weights (5, 10, and 20 kg/mol) were successfully grafted to the photo-DIBO-modified silicon substrates from melt after the deprotection of DIBO with UV-irradiation. PEG molecular weight, reaction temperature, and reaction time were all used to control the grafting reaction for targeted brush thicknesses and grafting densities. The highest grafting density obtained was close to 1.2 chains/nm2 and was achieved for 5 kg/mol PEG. The pr...

Bioorthogonal Strategy for Bioprocessing of Specific-Site-Functionalized Enveloped Influenza-Virus-Like Particles.

Virus-like particles (VLPs) constitute a promising platform in vaccine development and targeted drug delivery. To date, most applications use simple nonenveloped VLPs as human papillomavirus or hepatitis B vaccines, even though the envelope is known to be critical to retain the native protein folding and biological function. Here, we present tagged enveloped VLPs (TagE-VLPs) as a valuable strategy for the downstream processing and monitoring of the in vivo production of specific-site-functionalized enveloped influenza VLPs. This two-step procedure allows bioorthogonal functionalization of azide-tagged nascent influenza type A hemagglutinin proteins in the envelope of VLPs through a strain-promoted [3 + 2] alkyne–azide cycloaddition reaction. Importantly, labeling does not influence VLP production and allows for construction of functionalized VLPs without deleterious effects on their biological function. Refined discrimination and separation between VLP and baculovirus, the major impurity of the process, is achieved when this technique is combined with flow cytometry analysis, as demonstrated by atomic force microscopy. TagE-VLPs is a versatile tool broadly applicable to the production, monitoring, and purification of functionalized enveloped VLPs for vaccine design trial runs, targeted drug delivery, and molecular imaging.

ChemInform Abstract: DBU Catalyzed Metal Free Synthesis of Fused 1,2,3‐Triazoles Through [3 + 2] Cycloaddition of Aryl Azides with Activated Cyclic C—H Acids.

Abstract DBU catalyzed synthesis of fused 1,2,3-triazoles by [3+2] cycloaddition of aryl azides with activated cyclic C–H acids such as dimedone, cyclohexane-1,3-dione, 5-methylcyclohexane-1,3-dione, and 2-hydroxynaphthalene-1,4-dione in PEG-400 has been reported under heating. The important features of this reaction are high yield products, short reaction times, easy availability of starting materials, and recyclability of both reaction medium and catalyst.

ChemInform Abstract: A Tunable Route to Oxidative and Eliminative [3 + 2] Cycloadditions of Organic Azides with Nitroolefins: CuO Nanoparticles Catalyzed Synthesis of 1,2,3‐Triazoles under Solvent‐Free Condition.

AbstractIn the presence of the CuO nanoparticles catalyst under solvent‐free condition, the nitro group is retained in the product while it gets eliminated in the absence of the catalyst.

P-tert-Butylcalix[4]arene core based ferrocenyl dendrimers: Novel sensor for toxic Hg2+ ion even in presence of Zn2+, Cu2+ and Ag+ ions

A new class of p-tert-butylcalix[4]arene cored triazolyl ferrocene conjugates 1–3 has been synthesized in good yield using copper(I) catalyzed alkyne azide cycloaddition (CuAAC). In UV–vis spectrum the absorption intensity increases as the dendrimer generation increases though λmax remains almost constant for all the synthesized dendrimers. All the synthesized calixarene conjugated ferrocenyl dendrimers 1, 2 and 3 sense toxic Hg2+ ion at the lowest concentration of 2×10−5M even in the presence of Zn2+, Cu2+, Ag+ as revealed by Cyclic Voltammetric and through NMR titration studies.