Huisgen Click Research Articles

Dual-reactive hydrogels functionalizable using "Huisgen click" and "Schiff base" reactions.

Hydrogels incorporating different reactive groups are important platforms for the fabrication of functional materials through the conjugation of diverse molecules. In this study, a dual-reactive hydrogel system was designed utilizing aldehyde and azide groups containing methacrylate monomers. Hydrogels were obtained in the presence of a dimethacrylate crosslinker with a combination of hydrophilic PEG-based monomers via free-radical polymerization. The azide and aldehyde sites of the hydrogel network are reactive towards alkyne and amine functional groups, respectively. The advantage of the different reactivities of these functional groups was demonstrated through the attachment of two different dye molecules onto the hydrogel platform via the "Huisgen click" and "Schiff base" reactions to obtain a sensing platform for various applications, such as indicating change in pH of the environment.

Peptide Nucleic Acid Conjugates of Quinone Methide Precursors Alkylate Ribonucleic Acid after Activation with Light.

Quinone methide precursors 2 and 3 were protected with a photoreactive 2-nitrobenzyl group and conjugated to peptide nucleic acids (PNA) using a Huisgen click reaction. After brief irradiation at 365 nm, cross-linking with complementary RNA strands started and was analyzed with an ALFexpress sequencer. When this method was used, the gel temperature had a major influence on apparent rates. Quinone methides are known to form transient as well as stable bonds with nucleotides. Although both were detected at 25 °C, analysis at 57 °C only recorded the stable types of cross-links, suggesting much slower alkylation kinetics. Linker 11 allowed us to attach quinone methides to internal positions of the PNA/RNA duplex and to capture a model of miR-20a with good efficiency.

Attachment of a 1,8‐Naphthalimide Moiety to a Conjugated Polythiophene Efficiently Improves the Sensing Abilities of Naphthalimide‐Based Materials

AbstractA novel polythiophene‐based conjugated polymer bearing 1,8‐naphthalimide‐based pendants is prepared by a two‐step modification of regioregular poly[3‐(6‐bromohexyl)thiophene] involving a nucleophilic substitution reaction of the bromide end‐groups with sodium azide followed by a robust, copper‐catalyzed Huisgen click reaction with a novel 1,8‐naphthalinmide derivative containing an active, N‐substituted propyne group. Both the polymer and the highly luminescent‐active synthesized dye are extensively studied in solution by UV–vis spectroscopy, photoluminescence, NMR, light‐scattering and isothermal titration calorimetry. The materials prepared are considered potential chemosensors for different transition metals, such as Fe2+, Co2+, Ni2+, Cu2+, Zn2+, and Cd2+. Luminescence quenching shows that these materials have a higher sensitivity to Fe2+ than to the other metal ions tested. Moreover, the 1,8‐naphthalimide‐based conjugated polymer is more efficiently quenched by Fe2+ metal ions, at a significantly lower concentration and with a higher binding constant than its parent 1,8‐naphthalimide derivative, thus indicating a high potential for sensor development.

Microwave-assisted synthesis of pyrazole-based 1,2,3-triazole derivatives and evaluation of their antimicrobial activity

A series of new pyrazole-based 1,2,3-triazole derivatives were synthesized through the microwave-assisted Huisgen click reaction from 1-phenyl-3-[3-(prop-2-yn-1-yloxy)phenyl]-1H-pyrazole-4-carbaldehyde and organic azides with the use of redox system CuSO4·5H2O–sodium ascorbate. The method provided short reaction times and isolation of 1,4-disubstituted 1,2,3-triazoles in high yield. All the prepared compounds were evaluated for antimicrobial activity and the most of them displayed promising results.

Design, synthesis and in vitro biological evaluation of short-chain C12-sphinganine and its 1,2,3-triazole analogs as potential antimicrobial and anti-biofilm agents

A conceptual synthetic approach of short-chain C12-sphinganine 1 and a small library of its 1,2,3-triazole analogs 2(a–f) has been accomplished using the commercially available and inexpensive 10-undecenoic acid as a starting material. Miyashita's C-2 selective endo mode azidolysis and Huisgen click reaction was employed for the synthesis of the designed analogs. Based on biological evaluation studies of all the synthesized compounds, it was observed that, (2S,3R)-2-(4-(3-hydroxyphenyl)-1H-1,2,3-triazol-1-yl)dodecan-1,3-diol (2b) exhibited promising antimicrobial and antifungal activities. Furthermore, compound 2b was able to inhibit the biofilm formation of Candida albicans MTCC 227, Micrococcus luteus MTCC 2470 and Staphylococcus aureus MTCC 96 with IC50 values of 1.9, 2.1 and 2.9 μg/mL, respectively. Compound 2b increased the levels of reactive oxygen species (ROS) in C. albicans MTCC 227.

A concise and simple click reaction catalyzed by immobilized Cu(I) in an ionic liquid leading to the synthesis of β-hydroxy triazoles

This study describes an ecocompatible, concise, and practically reliable approach for the regioselective synthesis of β-hydroxy triazoles via Huisgen's click coupling reaction among varied epoxides, NaN 3 , and suitable acetylenes catalysed by immobilized Cu(I) in ionic liquid (IL). This one-pot, atom-economic, efficient, and highly regioselective green protocol ensures higher yield of β-hydroxy triazole scaffolds (85–95%). To make the process ecofriendly, this study emphasizes on the catalyst immobilization technique along with its possible recycling that gave a high reaction yield in up to three runs. The structures of all synthesized compounds have been characterized by comparing 1 H nuclear magnetic resonance (NMR), 13 C NMR, and mass spectroscopic data with those reported in the literature.

Highly alkynyl-functionalization of cellulose nanocrystals and advanced nanocomposites thereof via click chemistry

Advanced nanocomposites were developed from alkynylated cellulose nanocrystals and the reactive polymer matrix via Huisgen click chemistry.

ChemInform Abstract: Cu(OAc)2·H2O/NH2NH2 ·H2O: An Efficient Catalyst System That in situ Generates Cu2O Nanoparticles and HOAc for Huisgen Click Reactions.

A combination of Cu(OAc)2·H2O and NH2NH2·H2O, which in situ generates Cu2O-NPs and HOAc in water at room temperature, has been developed as a highly efficient catalytic system for Huisgen click reactions. Our results indicate that the in situ generated Cu2O-NPs and HOAc play important roles in the Huisgen click reaction.

Rhenium and technetium bi- and tricarbonyl complexes in a new strategy for biomolecule incorporation using click chemistry.

A versatile strategy to prepare fac-[M(I)(CO)3](+) and cis-[M(I)(CO)2](+) (M = Re, (99m)Tc) complexes was developed using Huisgen click chemistry and monodentate phosphine ligands to readily incorporate biomolecules and tailor the chemical properties.

Cu(OAc)2·H2O/NH2NH2·H2O: an efficient catalyst system that in situ generates Cu2O nanoparticles and HOAc for Huisgen click reactions

A combination of Cu(OAc)2·H2O and NH2NH2·H2O, which in situ generates Cu2O-NPs and HOAc in water at room temperature, has been developed as a highly efficient catalytic system for Huisgen click reactions. Our results indicate that the in situ generated Cu2O-NPs and HOAc play important roles in the Huisgen click reaction.

Investigation of Click Reaction at an Oil-Water Interface Using Hydrophobic and Hydrophilic Polymers

Cu(I)-catalyzed Huisgen click reactions between lipophilic polymer (tri-arm azidofunctionalized polystyrene) and hydrophilic polymer (copolymer of styrene sulfonate sodium and propargyl methacrylate) were investigated and hollow capsules, consisting of composite polymer nanofilms were obtained in chloroform-water biphasic solution. Since the lipophilic polymer, or hydrophilic polymer and copper catalyst were present in the oil or aqueous phase, respectively, the cross-linking reaction proceeded only at the phase interface. The combination of lipophilic and hydrophilic polymers produced hollow capsules consisting of nanofilms with lipophilic core and hydrophilic shell.

Investigation of Click Reaction at an Oil-Water Interface Using Hydrophobic and Hydrophilic Polymers

Cu(I)-catalyzed Huisgen click reactions between lipophilic polymer (tri-arm azidofunctionalized polystyrene) and hydrophilic polymer (copolymer of styrene sulfonate sodium and propargyl methacrylate) were investigated and hollow capsules, consisting of composite polymer nanofilms were obtained in chloroform-water biphasic solution. Since the lipophilic polymer, or hydrophilic polymer and copper catalyst were present in the oil or aqueous phase, respectively, the cross-linking reaction proceeded only at the phase interface. The combination of lipophilic and hydrophilic polymers produced hollow capsules consisting of nanofilms with lipophilic core and hydrophilic shell.

Poly(disubstituted acetylene)s With Pendant Naphthalimide‐Based Fluorophore Groups

AbstractNew stable polyacetylenes whose quantum yield of fluorescence is increased up to 62% because of the presence of pendant 4‐(piperidine‐1‐yl)‐1,8‐naphtalimide groups are described. The polymers are prepared by two‐step modification of copolymers of 1‐(4‐tert‐butylphenyl)‐6‐chlorohex‐1‐yne and 1‐phenylhex‐1‐yne consisting of the exchange of chlorine atoms at side groups for azide groups and subsequent Huisgen click reaction of the azide groups with ethynyl groups of N‐(prop‐1‐yne‐3‐yl)‐4‐(piperidine‐1‐yl)‐1,8‐naphthalimide. Modification is evidenced by 1H NMR, IR, Raman and UV–vis spectroscopy. Modified polymers show the excitation energy transfer from their main chains on fluorophores and nearly preservation of fluorescence properties of fluorophores upon their binding to polymer chains.

Modular Construction of Fluorescent Lipophosphoramidates by Click Chemistry

AbstractThe synthesis of fluorescent lipophosphoramidates is reported. Their modular construction allows several variations of the molecular structure including the separation of the fluorescent probe from the lipophosphoramidate moiety by a short methylene or by a tetraethylene glycol spacer. The last step of the convergent synthesis is a Huisgen click reaction, which assembles the fluorescent probe with the lipophosphoramidate part. Five fluorescent probes have been considered in this study including coumarin, NBD, fluorescein, naphthalimide and cyanine.

Multivalent Presentation of Mannose on Hyperbranched Polyglycerol and their Interaction with Concanavalin A Lectin

We describe the synthesis of multivalent mannose derivatives by using hyperbranched polyglycerols (hPG) as a scaffold with different linker structures. Grafting of protected mannose (Man) units is achieved by using Cu(I) -catalyzed Huisgen click chemistry with either an anomeric azide or propargyl ether onto complementarily functionalized alkyne or azido polymer surfaces. NMR spectroscopy, dynamic light scattering (DLS), IR spectroscopy, size-exclusion chromatography (SEC), and elemental analysis have been used to characterize the hPG-Man compounds. The surface availability and bioactivity of Man-modified polymers were evaluated by using a competitive surface plasmon resonance (SPR)-based binding assay by interactions of the glycopolymers with concanavalin A (Con A), a lectin that binds mannose containing molecules. The results indicated that the novel glycoarchitectures presented in this work are efficient inhibitors of Con A-mannose recognition and resulted in inhibitor concentrations (mean IC(50)) from the micro- to the nanomolar range, whereas the corresponding monovalent mannoside (methyl-Man) requires millimolar concentrations. The results provide an interesting structure-activity relationship for libraries of materials that differ in the linkage of the sugar moiety presented on a biocompatible polyglycerol scaffold.

Composite Polymer Materials Consisting of Nanofilms Formed by Click Reaction between Polymers at an Oil–Water Interface

Abstract New polymer materials, including thin films, soft gels, and hollow capsules, consisting of composite polymer nanofilms were prepared by the Cu(I)-catalyzed Huisgen click reaction between lipophilic polymers or between lipophilic and hydrophilic polymers. Because the lipophilic polymer, or hydrophilic polymer and copper catalyst were present in the oil or aqueous phase, respectively, the crosslinking reaction proceeded only at the phase interface. The combination of lipophilic and hydrophilic polymers produced “Janus” nanofilms with both hydrophilic and lipophilic surfaces.

ChemInform Abstract: Cyclic Peptidomimetics and Pseudopeptides from Multicomponent Reactions

AbstractReview: 107 refs.

Click chemistry as a route to surface functionalization of polymer particles dispersed in aqueous media

Proof-of-principle studies are described which show unequivocally that Huisgen click coupling can be performed successfully at the surface of polymer nano/submicron-size particles dispersed in aqueous media, thereby defining a generic strategy for attachment of a wide variety of functional molecules and providing a powerful, versatile route for the synthesis of surface functional particles.