Showing papers on "Click chemistry published in 2006"

Synthesis of neoglycopolymers by a combination of "click chemistry" and living radical polymerization.

Abstract: The synthesis of novel well-defined alkyne side chain functional polymers featuring narrow molecular weight distributions (PDI = 1.09−1.17) by living radical polymerization is described. Grafting of protected and unprotected carbohydrates is achieved via either a C-6 or an anomeric azide (α or β) onto these polymers by Cu(I)-catalyzed “click chemistry”, providing a simple and efficient route to synthetic glycopolymers. The strategy provides an extremely powerful tool for the synthesis of libraries of materials that differ only in the nature of the sugar moiety presented on a well-defined polymer scaffold. A library of multivalent ligands were then prepared following a “coclicking” synthetic protocol, and the reactivity of these glycopolymers in the presence of concanavalin A and Ricinus communis agglutinin, model lectins able to selectively bind appropriate mannose and galactose derivatives, respectively, was assessed.

Synthesis of Star Polymers by a Combination of ATRP and the “Click” Coupling Method

Abstract: Three-arm and four-arm star polystyrene (PS) polymers were synthesized by a combination of atom transfer radical polymerization (ATRP) and click coupling chemistry. The click reaction between an azido-terminated PS (PS−N3) and an alkyne-containing multifunctional compound proved to be fast and efficient. All coupling reactions were finished within 3 h, proven by the disappearance of signals from the azido groups in NMR spectra and the high yields of the coupled products by GPC analysis. For the model coupling reaction between a PS−N3 polymer and a dialkyne-containing compound, the final yield of the coupled PS−PS polymer was ca. 95%. When a PS−N3 polymer was reacted with a trialkyne-containing or tetraalkyne-containing compound, the yields of 3-arm star and 4-arm star polymers were around 90% and 83%, respectively. The influence of several parameters on the efficiency of the click coupling reaction was studied, including the molecular weight of the PS−N3 polymer, the presence of an added reducing agent, C...

Poly(vinyl alcohol)-Based Hydrogels Formed by “Click Chemistry”

Abstract: Novel poly(vinyl alcohols) (PVA) functionalized with pendant acetylene and azide groups were prepared by carbonyldiimidazole (CDI)-mediated couplings of the amines terminated with functional groups, 1-azido-2-aminoethane, propargylamine, or N-methylpropargylamine, to PVA. Low degrees (1−5%) of PVA modification were required in order to retain solubility in water. Azide-modified PVA and alkyne-modified PVA components were cross-linked by mixing of their solutions together with Cu(I) catalyst, a type of Huisgen's 1,3-dipolar azide−alkyne cycloaddition, recently defined as a powerful “click” chemistry. Reaction of the two different polymers results in a chemoselective coupling between alkynyl and azido functional groups with the multiple formation of triazole cross-links to give hydrogel formation. In another version the PVA-based hydrogels were obtained by cross-linking of alkyne-modified PVA with the telechelic bifunctional poly(ethylene glycol)−diazide cross-linker. The hydrogels prepared by these two met...

Toward the Syntheses of Universal Ligands for Metal Oxide Surfaces: Controlling Surface Functionality through Click Chemistry

Abstract: A new means for functionalizing metal oxide surfaces, specifically nanoparticles, is demostrated. This process involves the design of stable ligands that bind strongly to the surface of metal oxides and can undergo further chemical modification via click chemistry, with both small molecules as well as polymers, to yield metal oxide surfaces with tailored functionality. The nanoparticles are stable and easily dispersed in both polar and nonpolar solvents, a property that is controlled by the ligand. The resultant nanoparticles were characterized by TEM, TGA, FTIR, and NMR.

(NHC)Copper(I)‐Catalyzed [3+2] Cycloaddition of Azides and Mono‐ or Disubstituted Alkynes

Abstract: A versatile and highly efficient catalyst for the Huisgen cycloaddition reaction has been developed. Previously isolated or in situ generated azides yielded 1,2,3-triazoles with differently substituted alkynes in the presence of a [(NHC)CuBr] complex (NHC = N-heterocyclic carbene). Extremely high reaction rates and excellent yields were obtained in all cases. This catalytic system fulfils the requirements of "click chemistry" with its mild and convenient conditions, notably in water or solvent free reactions and simple isolation with no purification step. Furthermore, for the first time, an internal alkyne was successfully used in this copper-catalyzed cycloaddition reaction. DFT calculations on this particular system allowed for the proposition of a new mechanistic pathway for disubstituted alkynes.

"Click to chelate": synthesis and installation of metal chelates into biomolecules in a single step.

Abstract: Click chemistry has been employed for the assembly of novel and efficient triazole-based multidentate chelating systems while simultaneously attaching them to molecules of biological interest. The "click-to-chelate" approach offers a powerful new tool for the modification of (bio)molecules with metal chelators for potential diagnostic and therapeutic applications.

Anthracene−Maleimide-Based Diels−Alder “Click Chemistry” as a Novel Route to Graft Copolymers

Abstract: Using the Diels−Alder (DA) “click chemistry” strategy between anthracene and maleimide functional groups, two series of well-defined polystyrene-g-poly(ethylene glycol) (PS-g-PEG) and polystyrene-g-poly(methyl methacrylate) (PS-g-PMMA) copolymers were successfully prepared The whole process was divided into two stages: (i) preparation of anthracene and maleimide functional polymers and (ii) the use of Diels−Alder reaction of these groups First, random copolymers of styrene (S) and chloromethylstyrene (CMS) with various CMS contents were prepared by the nitroxide-mediated radical polymerization (NMP) process Then, the choromethyl groups were converted to anthryl groups via the etherifaction with 9-anthracenemethanol The other component of the click reaction, namely protected maleimide functional polymers, were prepared independently by the modification of commercially available poly(ethylene glycol) (PEG) and poly(methyl methacrylate) (PMMA) obtained by atom transfer radical polymerization (ATRP) usin

Synthesis of 3-miktoarm stars and 1st generation mikto dendritic copolymers by "living" radical polymerization and "click" chemistry

Abstract: The facile synthesis of 3-miktoarm star polymers and 1st generation mikto polymeric dendrimers using atom transfer radical polymerization (ATRP) and "click" chemistry is demonstrated. ATRP was used to synthesize near uniform polymers with Br chain ends, which were easily converted into azido groups. These polymer chains were then attached to a trifunctional alkyne molecule (tripropargylamine) using click reactions in a variety of ways to make the miktoarm stars and miktoarm polymeric dendrimers.

Combining ATRP and “Click” Chemistry: a Promising Platform toward Functional Biocompatible Polymers and Polymer Bioconjugates

Abstract: The bromine chain-ends of well-defined poly(oligo(ethylene glycol) acrylate) (POEGA) (Mn = 6850 g·mol-1, Mw/Mn = 1.21) prepared using ATRP were successfully transformed into various functional end groups (ω-hydroxy, ω-amino, and ω-Fmoc-amino acid) via a two step pathway: (1) substitution of the bromine terminal atom by an azide function, (2) 1,3-dipolar cycloaddition of the terminal azide and functional alkynes (propargyl alcohol, propargylamine, and N-α-(9-fluorenylmethyloxycarbonyl)-l-propargylglycine). The efficient “click” cycloaddition was confirmed in all cases by 1H NMR or SEC−UV analysis. Moreover, this two-step synthetic strategy was also studied for preparing polymer-b-oligopeptide bioconjugates. Well-defined POEGA-b-GGRGDG was obtained in high yields via the “click” ligation of the azido functional POEGA and the alkyne functional oligopeptide GGRGDG.

RAFT and click chemistry: A versatile approach to well-defined block copolymers

Abstract: The combination of reversible chain transfer chemistry with highly orthogonal [2 + 3] cycloadditions ('click chemistry') allows for the synthesis of well-defined block copolymers of monomers with extremely disparate reactivities. © The Royal Society of Chemistry.

A Click Approach to Unprotected Glycodendrimers

Abstract: Click chemistry in combination with ultrafiltration has allowed the quick, efficient, and reliable multivalent conjugation of unprotected alkyne-derived carbohydrates to three generations of azido-terminated gallic acid−triethylene glycol dendrimers under aqueous conditions. The reported procedure allows the atom economical incorporation of up to 27 unprotected fucose, mannose, and lactose residues, in reproducible high yields (up to 92%), requiring only catalytic amounts of Cu. The completion of the conjugation process was clearly established in all cases by both 1H NMR and MALDI-TOF MS.

Catalyst Performance in “Click” Coupling Reactions of Polymers Prepared by ATRP: Ligand and Metal Effects

Abstract: CuI-catalyzed azide−alkyne cycloadditions were conducted in organic media under various conditions. The effects of several parameters (ligand, solvent, reducing agent, metal) on these reactions were studied using the step-growth click coupling of low-molecular-weight α,ω-diazido-terminated polystyrene prepared by atom transfer radical polymerization (ATRP). These reactions were typically conducted in DMF, monitored by size exclusion chromatography (SEC), and semiquantitatively analyzed by Gaussian multipeak fitting and subsequent peak integration. Both the electronic properties of the ligand and the number of coordinating atoms had significant influence on the rates of the click coupling reactions. Aliphatic amine ligands led to significantly faster rates as compared to pyridine-based ligands. Faster rates were also observed with tridentate vs tetradentate ligands. A further rate enhancement was observed when the reactions were conducted in a noncoordinating solvent (toluene) vs a coordinating solvent (DM...

Stabilization of G-Quadruplex DNA by Highly Selective Ligands via Click Chemistry

Abstract: A series of G-quadruplex stabilizing compounds have been prepared via click chemistry employing the Cu(I)-catalyzed Huisgen reaction. These compounds were shown to bind tightly to G-quadruplex DNA even in the presence of competing high concentrations of duplex DNA. Furthermore, a modified TRAP assay has shown that some of these compounds also inhibit telomerase at low micromolar concentration.

Synthesis of degradable model networks via ATRP and click chemistry.

Abstract: A simple scheme involving atom transfer radical polymerization (ATRP) from a bifunctional initiator, conversion of the bromine end groups of the resulting telechelic polymer to azides, and cross-linking of this azido−telechelic macromonomer with multi-acetylene functionalized small molecules via copper-catalyzed azide−alkyne cycloaddition was employed to prepare the first tert-butyl acrylate model networks. This general scheme is wide in scope, enabling synthesis of model networks possessing defined pore size from any monomer polymerizable by ATRP. Introduction of an olefin moiety into the ATRP initiator enabled degradation of the materials by ozonolysis to yield star polymer products bearing three or four arms depending on which cross-linker was employed in the parent network. Size-exclusion chromatography of the ozonolysis products confirmed the pore size of the parent network and yielded insight into the number of unreacted functionalities. Model networks derived from a trifunctional alkyne were found ...

Click Chemistry with Polysaccharides

Abstract: Summary: The copper-catalyzed Huisgen reaction as a typical example of click chemistry was realized with the polysaccharide cellulose for the first time The generality, selectivity, and the efficiency of click chemistry perfectly fit the requirements of polysaccharide modification, which is demonstrated by the introduction of triazole-spacer bound functional groups, ie, carboxylic ester, thiophene, and aniline moieties Azide moieties introduced into cellulose via the tosyl derivative were simply transferred with ethynyl compounds under Cu(I) catalysis and mild and easily applicable conditions Hydrolytically stable cellulose derivatives soluble in organic solvents, eg, DMSO or DMF with DS up to 09 are obtained The triazole substituted cellulose derivatives were characterized by elemental analysis, FTIR, 1H NMR, and 13C NMR spectroscopies and show no impurities or substructures resulting from side reactions 6-Azido-6-deoxy cellulose

An Efficient Route to Macromonomers via ATRP and Click Chemistry

Abstract: The combination of atom transfer radical polymerization (ATRP) and click chemistry was employed to prepare well-defined ω-(meth)acryloyl macromonomers in an efficient manner. Poly(n-butyl acrylate) (PBA), polystyrene (PS), and PS-b-PBA were prepared by ATRP and subsequently derivatized to contain azido end groups. The reaction of the azido-terminated polymers with alkyne-containing acrylate and methacrylate monomers resulted in near-quantitative chain end functionalization. Macromonomers of various molecular weights [PBA: Mn = 2.2−6.4 × 103 g/mol (DPn = 16−49); PS: Mn = 3.2−5.9 × 103 g/mol (DPn = 29−55)] and architectures were prepared by this method. The end group transformations required to incorporate the polymerizable functionality were accomplished either as a stepwise series of discrete reactions or as an in situ process, wherein azidation was immediately followed by azide−alkyne coupling in situ. In both cases, the degree of end group functionalization generally exceeded 90%. To demonstrate polym...

Reactive Polymer Coatings that “Click”

Abstract: Future advances in the design of biologically active interfaces require novel strategies for the robust and specific attachment of biological ligands onto surfaces. Herein, a new type of biofunctional surface based on alkyne-containing vapordeposited polymer coatings is reported. These reactive coatings are applicable to a wide range of substrates and can be modified by subsequent spatially directed “click chemistry”. Click chemistry represents a family of powerful and efficient chemical reactions, which are modular, widely applicable, relatively insensitive to solvents and pH value, while resulting in stereoselective conversions with high to very high yields. The most widely used click reaction is the Huisgen 1,3-dipolar cycloaddition between azides and terminal alkynes. This coupling reaction has been employed for drug discovery applications and for the target-guided synthesis of enzymeinhibitors. Moreover, Huisgen 1,3-dipolar cycloadditions of azideand alkyne-functionalized self-assembled monolayers (SAMs) have been used as a versatile tool for tailoring surface functionalities.Their bioorthogonality, that is, the dependence on proximity and proper alignment of the reactants make click reactions promising candidates for biointerface design. However, further use is currently hampered by the availability of polymer coatings that can undergo surface-directed dipolar cycloadditions. In the past, chemical vapor deposition (CVD) polymerization of substituted [2,2]paracyclophanes has been instrumental in creating a wide array of functionalized poly-(p-xylylenes) with a diverse class of functional groups, such as amines, esters, aldehydes, and alcohols, which enable the immobilization of biomolecules. To further extend the concept of click-chemistry-based immobilization, we use CVD polymerization for synthesizing alkyne-containing polymer coatings (Scheme 1). Moreover, we demonstrate the applicability of these reactive coatings by

Microwave Assisted “Click” Chemistry for the Synthesis of Multiple Labeled-Carbohydrate Oligonucleotides on Solid Support†

Abstract: A versatile approach has been developed for the multiple labeling of oligonucleotides. First, three linkers as a H-phosphonate monoester derivative were condensed on a solid-supported T12 to introduce H-phosphonate diester linkages which were oxidized in the presence of propargylamine. Second, three galactosyl azide derivatives were conjugated to the solid-supported three-alkyne-modified T12 by a 1,3-cycloaddition so-called “click chemistry” in the presence of Cu(I) assisted by microwaves.