Well-controlled ATRP of 2-(2-(2-Azidoethyoxy)ethoxy)ethyl Methacrylate for High-density Click Functionalization of Polymers and Metallic Substrates.
ABSTRACT: The combination of atom transfer radical polymerization (ATRP) and click chemistry has created unprecedented opportunities for controlled syntheses of functional polymers. ATRP of azido-bearing methacrylate monomers (e.g. 2-(2-(2-azidoethyoxy)ethoxy)ethyl methacrylate, AzTEGMA), however, proceeded with poor control at commonly adopted temperature of 50 °C, resulting in significant side reactions. By lowering reaction temperature and monomer concentrations, well-defined pAzTEGMA with significantly reduced polydispersity were prepared within a reasonable timeframe. Upon subsequent functionalization of the side chains of pAzTEGMA via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry, functional polymers with number-average molecular weights (Mn) up to 22 kDa with narrow polydispersity (PDI < 1.30) were obtained. Applying the optimized polymerization condition, we also grafted pAzTEGMA brushes from Ti6Al4 substrates by surface-initiated ATRP (SI-ATRP), and effectively functionalized the azide-terminated side chains with hydrophobic and hydrophilic alkynes by CuAAC. The well-controlled ATRP of azido-bearing methacrylates and subsequent facile high-density functionalization of the side chains of the polymethacrylates via CuAAC offers a useful tool for engineering functional polymers or surfaces for diverse applications.
Project description:Asymmetric molecular brushes emerge as a unique class of nanostructured polymers, while their versatile synthesis keeps a challenge for chemists. Here we show the synthesis of well-defined asymmetric molecular double-brushes comprising two different side chains linked to the same repeat unit along the backbone by one-pot concurrent atom transfer radical polymerization (ATRP) and Cu-catalyzed azide/alkyne cycloaddition (CuAAC) reaction. The double-brushes are based on a poly(Br-acrylate-alkyne) homopolymer possessing an alkynyl for CuAAC reaction and a 2-bromopropionate initiating group for ATRP in each repeat unit. The versatility of this one-shot approach is demonstrated by CuAAC reaction of alkynyl/poly(ethylene oxide)-N3 and ATRP of various monomers. We also show the quantitative conversion of pentafluorophenyl ester groups to amide groups in side chains, allowing for the further fabrication of diverse building blocks. This work provides a versatile platform for facile synthesis of Janus-type double-brushes with structural and functional control, in a minimum number of reactions.Producing well-defined polymer compositions and structures facilitates their use in many different applications. Here the authors show the synthesis of well-defined asymmetric double-brushes by a one-pot concurrent atom transfer radical polymerization and Cu-catalyzed Click reaction.
Project description:The combination of highly efficient polymerizations with modular "click" coupling reactions has enabled the synthesis of a wide variety of novel nanoscopic structures. Here we demonstrate the facile synthesis of a new class of clickable, branched nanostructures, polyethylene glycol (PEG)-branch-azide bivalent-brush polymers, facilitated by "graft-through" ring-opening metathesis polymerization of a branched norbornene-PEG-chloride macromonomer followed by halide-azide exchange. The resulting bivalent-brush polymers possess azide groups at the core near a polynorbornene backbone with PEG chains extended into solution; the structure resembles a unimolecular micelle. We demonstrate copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click-to" coupling of a photocleavable doxorubicin (DOX)-alkyne derivative to the azide core. The CuAAC coupling was quantitative across a wide range of nanoscopic sizes (?6-?50 nm); UV photolysis of the resulting DOX-loaded materials yielded free DOX that was therapeutically effective against human cancer cells.
Project description:Multifunctional dendrimers bearing two or more surface functionalities have the promise to provide smart drug delivery devices that can for example combine tissue targeting and imaging or be directed more precisely to a specific tissue or cell type. We have developed a concise synthetic methodology for efficient dendrimer assembly and heterobifunctionalization based on three sequential azide-alkyne cycloadditions. The methodology is compatible with biologically important compounds rich in chemical functionalities such as peptides, carbohydrates, and fluorescent tags. In the approach, a strain-promoted azide-alkyne cycloaddition (SPAAC) between polyester dendrons modified at the focal point with an azido and 4-dibenzocyclooctynol (DIBO) moiety provided dendrimers bearing terminal and TMS-protected (TMS=trimethylsilyl) alkynes at the periphery. The terminal alkynes were outfitted with azido-modified polyethylene glycol (PEG) chains or galactosyl residues by using Cu(I) -catalyzed azide-alkyne cycloadditions (CuAAC). Next, a one-pot TMS deprotection and second click reaction of the resulting terminal alkyne with azido-containing compounds gave multifunctional dendrimers bearing complex biologically active moieties at the periphery.
Project description:Combing active ester chemistry and click chemistry, a cyclic double-grafted polymer was successfully demonstrated via a "grafting onto" method. Using active ester chemistry as post-functionalized modification approach, cyclic backbone (c-P2) was synthesized by reacting propargyl amine with cyclic precursor (poly(pentafluorophenyl 4-vinylbenzoate), c-PPF4VB6.5k). Hydroxyl-containing polymer double-chain (l-PS-PhOH) was prepared by reacting azide-functionalized polystyrene (l-PSN?) with 3,5-bis(propynyloxy)phenyl methanol, and further modified by azide group to generate azide-containing polymer double-chain (l-PS-PhN?). The cyclic backbone (c-P2) was then coupled with azide-containing polymer double-chain (l-PS-PhN?) via CuAAC reaction to construct a novel cyclic double-grafted polymer (c-P2-g-Ph-PS). This research realized diversity and complexity of side chains on cyclic-grafted polymers, and this cyclic double-grafted polymer (c-P2-g-Ph-PS) still exhibited narrow molecular weight distribution (Mw/Mn < 1.10).
Project description:The preparation of patterned ultrathin films (sub-10 nm) composed of end-anchored fluorescently labeled poly(methyl methacrylate) (PMMA) is presented. Telechelic PMMA was synthesized utilizing activator regenerated by electron transfer atom transfer radical polymerization and consecutively end-functionalized with alkynylated fluorescein by Cu-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. The polymers were grafted via the ?-carboxyl groups to silica or glass substrates pretreated with (3-aminopropyl)triethoxysilane (APTES). Patterned surfaces were prepared by inkjet printing of APTES onto glass substrates and selectively grafted with fluorescently end-labeled PMMA to obtain emissive arrays on the surface.
Project description:Copper-catalyzed azide-alkyne cycloadditions (CuAAC or click chemistry) are convenient methods to easily couple various pharmacophores or bioactive molecules. A new series of 1,2,3-triazole-linked nucleoside-amino acid conjugates have been designed and synthesized in 57-76% yields using CuAAC. The azido group was introduced on the 5'-position of uridine or the acyclic analogue using the tosyl-azide exchange method and alkylated serine or proparylglycine was the alkyne. Modeling studies of the conjugates in the active site of LpxC indicate they have promise as antibacterial agents.
Project description:Dual thermo- and pH-responsive comb-type grafted hydrogels of poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) and poly(N-isopropylacrylamide) (PNIPAM) with reversed network-graft architectures were synthesized by the combination of atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT) polymerization and click chemistry. Two kinds of macro-cross-linkers with two azido groups at one chain-end and different chain length [PNIPAM⁻(N₃)₂ and PDMAEMA⁻(N₃)₂] were prepared with N,N-di(β-azidoethyl) 2-halocarboxylamide as the ATRP initiator. Through RAFT copolymerization of DMAEMA or NIPAM with propargyl acrylate (ProA) using dibenzyltrithiocarbonate as a chain transfer agent, two network precursors with different content of alkynyl side-groups [P(DMAEMA-co-ProA) and P(NIPAM-co-ProA)] were obtained. The subsequent azido-alkynyl click reaction of macro-cross-linkers and network precursors led to the formation of the network-graft hydrogels. These dual stimulus-sensitive hydrogels exhibited rapid response, high swelling ratio and reproducible swelling/de-swelling cycles under different temperatures and pH values. The influences of cross-linkage density and network-graft architecture on the properties of the hydrogels were investigated. The release of ceftriaxone sodium from these hydrogels showed both thermal- and pH-dependence, suggesting the feasibility of these hydrogels as thermo- and pH-dependent drug release devices.
Project description:Polystyrene microparticles were covalently impregnated into the networks of functional polyelectrolyte chains designed via a tandem run of three reactions: (i) synthesis of water-soluble polyelectrolyte, (ii) fast azidation and (iii) a 'click' reaction, using the single-catalyst, single-pot strategy at room temperature in mild aqueous media. The model polyelectrolyte sodium polystyrenesulfonate (NaPSS) was synthesized via the well-controlled atom transfer radical polymerization (ATRP) whose halogen living-end was transformed to azide and subsequently coupled with an alkyne carboxylic acid through a 'click' reaction using the same ATRP catalyst, throughout. Halogen to azide transformation was fast and followed the radical pathway, which was explained through a plausible mechanism. Finally, the success of microparticle impregnation into the NaPSS network was evaluated through Kaiser assay and imaging. This versatile synthetic procedure, having a reduced number of discrete reaction steps and eliminated intermediate work-ups, has established a fast and simple pathway to design functional polymers required to fabricate stable polymer-particle composites where the particles are impregnated covalently and controllably.
Project description:The amphiphilic copolymers of poly(ethylene glycol) methyl ether methacrylate (MPEGMA) and alkyne functionalized 2-hydroxyethyl methacrylate (AlHEMA) were synthesized by controlled atom transfer radical polymerization (ATRP). The reactions were carried out using the standard ATRP initiator ethyl ?-bromoisobutyrate, (EiBBr) and the "bio"initiator bromoester derivative of 4-n-butylresorcinol (4nBREBr2). Two substances with antioxidant activity used in cosmetology, (±)-?-lipoic acid (LA) and ferulic acid (FA), were subjected to esterification reactions to introduce azide groups. The "click" reactions between the alkyne contained copolymers and functionalized acids (LA-N3, FA-N3) were performed to obtain polymer-antioxidant conjugates (P((HEMA-click-FA)-co-MPEGMA) and P((HEMA-click-LA)-co-MPEGMA)). The conjugation was performed with an efficiency of 20-75%. In vitro experiments in a phosphate buffer saline (PBS) solution at neutral conditions demonstrated that the sufficient release was reached after 2.5 h for FA and 1 h for LA. The rapid release kinetics as well as the polymer carriers, which were applied to regulate the delivery of antioxidant substances, are beneficial in cosmetology.
Project description:The synthesis of new multivalent architectures based on a trihydroxypiperidine ?-fucosidase inhibitor is reported herein. Tetravalent and nonavalent dendrimers were obtained by means of the click chemistry approach involving the copper azide-alkyne-catalyzed cycloaddition (CuAAC) between suitable scaffolds bearing terminal alkyne moieties and an azido-functionalized piperidine as the bioactive moiety. A preliminary biological investigation is also reported towards commercially available and human glycosidases.