Copper-mediated Atom Transfer Radical Research Articles

Novel amphiphilic ABC 3-miktoarm star azo-copolymer with polypeptide chain: Synthesis, self-assembly and photo-responsive behavior

Well-defined amphiphilic ABC 3-miktoarm star terpolymer containing hydrophilic methoxy poly(ethylene glycol) (MPEG), hydrophobic poly[6-(4-methoxy-azobenzene-4′-oxy) hexyl methacrylate] (PAzoMA) and poly(γ-benzyl-L-glutamic acid) (PBLG) was synthesized by a combination of copper-mediated atom transfer radical polymerization (ATRP) and ring opening polymerization (ROP). MPEG was modified to bear two different functional groups, which were further modified to the initiator of ATRP and ROP for the preparation of the amphiphilic ABC-type 3-miktoarm star terpolymers (MPEG) (PAzoMA) (PBLG). The spindle-like micelles were formed from the amphiphilic 3-miktoarm star terpolymer through a solution self-assembly due to the rigid ɑ-helical conformation of PBLG block and the π-π interaction between PBLG block with PAzoMA block in the star terpolymer. The investigation of the photo-isomerization behavior of (MPEG) (PAzoMA) (PBLG) in solution and in micellar solution showed that trans–cis isomerization in solution was quicker than that in micellar solution, and H- or J-aggregates of the azobenzene groups in the aggregates did not be observed. On the basis of the experimental results, the formation mechanisms of the spindle-like micelles were suggested and the obtained results may expand the self-assembly research field.

Novel amphiphilic graft block azobenzene-containing copolymer with polypeptide block: synthesis, self-assembly and photo-responsive behavior.

Well-defined amphiphilic graft block azobenzene-containing copolymer with polypeptide block was synthesized via a combination of copper-mediated atom transfer radical polymerization (ATRP), ring-opening polymerization and click reaction. The alkyne-terminated poly[6-(4-methoxy-azobenzene-4′-oxy)hexyl methacrylate] (PAzoMA) was synthesized by ATRP with a bromine-containing alkyne bifunctional initiator, and the azido-terminated poly(γ-2-chloroethyl-l-glutamate) (PCELG) was synthesized by ROP of γ-2-chloroethyl-l-glutamate-N-carboxyanhydride (CELG-NCA), then the two homopolymers were conjugated by click reaction to afford block azobenzene-containing copolymer PAzoMA-b-PCELG. The chloro groups in PCELG block were transformed into azido groups via azide reactions, and the alkyne-terminated MPEG was grafted to the polypeptide block to afford the final product PAzoMA-b-poly((l-glutamate)-graft-methoxy poly(ethylene glycol)) (PAzoMA-b-(PELG-g-MPEG)) by click reaction. Giant vesicles (micrometer size) were obtained from the amphiphilic graft block copolymer PAzoMA-b-(PELG-g-MPEG) through a solution self-assembly due to the rigid PAzoMA chains and polypeptide chains with the α-helical structure. The investigation of the photo-isomerization behavior of PAzoMA-b-(PELG-g-MPEG) in solution and in vesicular solution showed trans–cis isomerization in solution was quicker than that in vesicular solution and azobenzene J-aggregates in the vesicle solution were only observed. The formation mechanisms of the vesicles were also explored. The research results may provide guidelines for the study of complex copolymers containing different types of rigid chains.

Synthesis of P4VP-b-PBLG Diblock Copolymers and Their Self-Assembly Behavior

Well-defined P4VP-b-PBLG diblock polymer composed of poly (4-vinylpyridine) (P4VP) and poly (γ-benzyl-L-glutamate) (PBLG) was synthesized by click reaction with alkyne- and azide-functionalized homopolymers. Besides, P4VP blocks were synthesized by copper-mediated atom transfer radical polymerization (ATRP) with a chlorine-containing alkyne bifunctional initiator, and the azido-terminated PBLG homopolymers were synthesized by ring-opening polymerization (ROP) of γ-benzyl-L-glutamate with an amine-containing azide initiator. In addition, the synthesized P4VP-b-PBLG with different block ratios has been characterized by proton nuclear magnetic resonance (1H NMR), Gel permeation chromatograph (GPC) and fourier transform infrated spectroscopy (FT-IR). Then, the self-assembly behaviors of P4VP-b-PBLG have been studied by changing parameters like dripping speed and block ratio. The morphologies of self-assembly of spherical, disk-like and ellipsoid-like shape particles have been observed and analyzed by scanning electron microscopy (SEM). These results have provided guidelines for the design of macromolecular self-assembly.

Preparation of Magnetic Polyimidazolium Microspheres by Surface-Initiated ATRP

Narrow-disperse magnetic microspheres were prepared by alkaline coprecipitation of Fe2+ and Fe3+ ions within poly (acrylic acid–divinylbenzene) microspheres that were prepared by distillation–precipitation copolymerization. Magnetic microspheres with polyimidazolium that contain imidazolium groups were prepared by graft copolymerization of vinylimidazole and 1-chlorobutane via surface-initiated atom transferradical polymerization (SI-ATRP) from the magnetic microsphere surfaces. The magnetic polyimidazolium microspheres with an initiator group for copper-mediated atom transfer radical polymerization, well defined diblock copolymer brushes consisting of polyimidazolium were obtained by using the initial homopolymer brushes as the macro initiators for the ATRP of the second monomer. Transmission electron microscopy (TEM) displayed that the average particle size was 20 nm in diameter with some nanoaggregation observed. Fourier-transform infrared (FTIR) characterizated the surface modification process of magnetic microspheres (MMPs).

Synthesis of Monodisperse Silica Particles Grafted with Concentrated Ionic Liquid-Type Polymer Brushes by Surface-Initiated Atom Transfer Radical Polymerization for Use as a Solid State Polymer Electrolyte.

A polymerizable ionic liquid, N,N-diethyl-N-(2-methacryloylethyl)-N-methylammonium bis(trifluoromethylsulfonyl)imide (DEMM-TFSI), was polymerized via copper-mediated atom transfer radical polymerization (ATRP). The polymerization proceeded in a living manner producing well-defined poly(DEMM-TFSI) of target molecular weight up to about 400 K (including a polycation and an counter anion). The accurate molecular weight as determined by a GPC analysis combined with a light scattering measurement, and the molecular weight values obtained exhibited good agreement with the theoretical values calculated from the initial molar ratio of DEMM-TFSI and the monomer conversion. Surface-initiated ATRP on the surface of monodisperse silica particles (SiPs) with various diameters was successfully performed, producing SiPs grafted with well-defined poly(DEMM-TFSI) with a graft density as high as 0.15 chains/nm2. Since the composite film made from the silica-particle-decorated polymer brush and ionic liquid shows a relatively high ionic conductivity, we have evaluated the relationship between the grafted brush chain length and the ionic conductivity.

Synthesis and self-assembly of a triarm star-shaped rod-rod block copolymer

We designed and synthesized a triarm star-shaped rod-rod block copolymer (BCP), (poly{2,5-bis[(4-methoxyphenyl)-oxycarbonyl]styrene}-block-poly(γ-benzyl-l-glutamate))3, (PMPCS-b-PBLG)3. The triarm core with three PMPCS-N3 segments was prepared by copper-mediated atom transfer radical polymerization of 2,5-bis[(4-methoxyphenyl)-oxycarbonyl]styrene initiated by a trifunctional initiator and a subsequent azide reaction. And the PBLG block with alkyne functionality was synthesized through ring-opening polymerization of γ-benzyl-l-glutamate N-carboxyanhydride initiated by propargylamine. Finally, Huisgen’s 1,3-dipolar cycloaddition was employed to combine the triarm (PMPCS-N3)3 and PBLG segments. The chemical structure of the BCP was confirmed by 1H-NMR spectroscopy, Fourier-transform infrared spectroscopy, and gel permeation chromatographic analysis. Results from differential scanning calorimetry, polarized light microscopy, one-dimensional and two-dimensional wide-angle X-ray diffraction, and transmission electron microscopy techniques demonstrate that the triarm star-shaped rod-rod BCP self-assembles into a hexagon-in-lamella morphology, with the PMPCS block in the columnar nematic phase and the PBLG block in the hexagonal columnar arrangement packed in bilayers due to the rigid nature of the two blocks and the covalent connections in the star-shaped BCP.

Zinc powder-alkyl halide: a radical initiation system for living/controlled polymerization of vinyl monomers

An initiation system comprising activated zinc powder and alkyl bromide is presented for polymerization of vinyl monomers, including vinyl acetate (VAc). The polymerization was demonstrated to be effected in dry conditions at 70 °C and very sensitive to moisture. A radical mechanism was evidenced by spin-trapping method using TEMPO as capping agent and followed block copolymer formation. First order kinetics with respect to concentration of the monomers, methylmethacrylate(MMA), styrene and VAc, relatively long induction periods, and moderate polydispersities (PDI: 1.6–2.4) were determined as typical characteristics of the polymerization system in bulk conditions. The polymerization system was demonstrated to be living, as evidenced by chain extension of the poly (vinyl acetate) (PVAc) with MMA. A ZnBr radical fragment was proposed as key intermediate controlling the chain growth by reversible combination with the active chain ends. The system was also combined with typical copper-mediated atom transfer radical polymerization (ATRP), in which ATRP-growth polystyrene (PS) was directly used as macroinitiator to initiate VAc polymerization yielding block copolymer.

Sulfolane: an Efficient and Universal Solvent for Copper-Mediated Atom Transfer Radical (co)Polymerization of Acrylates, Methacrylates, Styrene, and Vinyl Chloride.

A very fast and controlled atom transfer radical (co)polymerization (ATRP) of acrylates, methacrylates, styrene, and vinyl chloride is reported in a single dipolar aprotic solvent, sulfolane, with the use of ppm amount of the copper catalyst. The observed rates of polymerization (kpapp) of the monomers studied are similar to those reported using dimethyl sulfoxide (DMSO) and other polar solvents typically employed in single electron transfer (SET)-mediated atom transfer radical polymerization (ATRP) processes. As proof-of-concept, ABA type block copolymers of polystyrene-b-poly(vinyl chloride)-b-polystyrene and poly(methyl acrylate)-b-poly(vinyl chloride)-b-poly(methyl acrylate) were prepared for the first time using a reversible deactivation radical polymerization (RDRP) method in a single solvent. The quantitative preservation of halide chain-ends was confirmed by 1H NMR and MALDI-TOF analysis as well as by the complete shift of the GPC traces. The results presented establish an innovative and robust system to afford a vast portfolio of (co)polymers in a single widely used industrial solvent.

Synthesis and self-assembly in bulk of star-shaped block copolymers based on helical polypeptides

A series of star-shaped copolymers containing poly (styrene) (PS) and poly(γ-benzyl-l-glutamate) (PBLG) were synthesized by click reaction from alkyne- and azide-functionalized homopolymers. The α-azide PS star-shaped homopolymer was synthesized by copper-mediated atom transfer radical polymerization from a bromine-containing star-shaped initiator, and α-alkyne PBLG homopolymers were synthesized by ring-opening polymerization of γ-benzyl-l-glutamate N-carboxyanhydride with an amino-containing α-alkyne initiator. The molecular structures of the homopolymers and star-shaped block copolymers were confirmed by 1H nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy (FTIR), and gel permeation chromatography analysis. The self-assembling behavior of the star-shaped block copolymers in bulk was investigated using wide-angle X-ray diffraction, and small-angle X-ray scattering. For star-shaped block copolymer at lower f PS of ~0.27, PBLG segment was assigned to a hexagonally packed-cylinder structure (Φ H) based on the rod-like α-helix conformation as shown in FTIR spectra. By increasing f PS to ~0.42, a proposed microphase-separated double-hexagonal morphology was observed, in which PBLG rods formed the core of the columns by interdigitated packing in Φ H phase with PS domain as the matrix in a larger hexagonal columnar structure. The proposed structure was based on calculation from the simulated molecular length of each block of the copolymer and experimental analyses.

Synthesis, Characterization, and Aqueous Lubricating Properties of Amphiphilic Graft Copolymers Comprising 2-Methoxyethyl Acrylate

Amphiphilic anionic and cationic graft copolymers possessing poly(2-hydroxyethyl methacrylate) (PHEMA) backbone and poly(methacrylic acid), poly(2-methoxyethyl acrylate-co-methacrylic acid), and poly(2-methoxyethyl acrylate-co-2-(dimethylamino)ethyl methacrylate) grafts are constructed by merging reversible addition–fragmentation chain transfer (RAFT) polymerization, copper-mediated atom transfer radical polymerization (ATRP), and a selective deprotection reaction. Initially, multifunctional ATRP macroinitiators based on PHEMA backbone are prepared by RAFT polymerization. Then ATRP of the corresponding monomers followed by deblocking reaction leads to well-defined amphiphiles with narrow molecular weight distributions (PDI ≤ 1.29) and varying content of methacrylic acid. The graft copolymers showed effective surface adsorption and lubrication for self-mated poly(dimethylsiloxane) (PDMS) contacts in physiological salt concentration. This is indebted from “dilution” of the charges along the grafted chains by balancing neutral/charged repeating units to minimize the accumulated charge repulsion on neutral surface. Improved lubricating properties of the graft copolymers compared to the block copolymer counterparts further support superior stability of graft copolymers on surfaces.

Neutral, anionic, cationic, and zwitterionic diblock copolymers featuring poly(2-methoxyethyl acrylate) “hydrophobic” segments

Amphiphilic diblock copolymers incorporating “hydrophobic” poly(2-methoxyethyl acrylate) (PMEA) and hydrophilic neutral poly(ethylene glycol) monomethyl ether (mPEG), anionic poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA), cationic poly(2-dimethylaminoethyl methacrylate) (PDMAEMA), and zwitterionic poly(3-(N-(2-methacryloyloxyethyl)-N,N-dimethylammonio)propane sulfonate) (PDMAPS) blocks are constructed. mPEG, poly(tert-butyl acrylate) (PtBA), and poly(tert-butyl methacrylate) (PtBMA) macroinitiators are chain extended with 2-methoxyethyl acrylate (MEA) employing copper-mediated atom transfer radical polymerization (ATRP) garnishing well-defined diblock copolymers with narrow polydispersities (1.11–1.30). Selective cleavage of the tert-butyl esters affords PAA-b-PMEA and PMAA-b-PMEA. ATRP of 2-dimethylaminoethyl methacrylate (DMAEMA) from the PMEA macroinitiator results in PMEA-b-PDMAEMA while the betainisation of the latter provides zwitterionic diblock amphiphile PMEA-b-PDMAPS. Inspection of these macromolecular architectures by NMR spectroscopy and size exclusion chromatography (SEC) confirms a fairly high degree of control over the reactions emphasizing flexibility and precision of the approach.

Functionalization of Magnetic Nanoparticles with Dendritic–Linear–Brush-Like Triblock Copolymers and Their Drug Release Properties

Novel water-soluble dendritic-linear-brush-like triblock copolymer polyamidoamine-b-poly(2-(dimethylamino)ethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) (PAMAM-b-PDMAEMA-b-PPEGMA)-grafted superparamagnetic iron oxide nanoparticles (SPIONs) were successfully prepared via a two-step copper-mediated atom transfer radical polymerization (ATRP) method. The macroinitiators were immobilized on the surface of Fe(3)O(4) nanoparticles via effective ligand exchange of oleic acid with the propargyl focal point PAMAM-typed dendron (generation 2.0, denoted as propargyl-D(2.0)) containing four carboxyl acid end groups, following a click reaction with 2'-azidoethyl-2-bromoisobutylate (AEBIB). PDMAEMA and PPEGMA were grown gradually from nanoparticle surfaces using the "grafting from" approach, which rendered the SPIONs soluble in water and reversed aggregation. To the best of our knowledge, this is the first report that describes the functionalization of magnetic nanoparticles with dendritic-linear-brush-like triblock copolymers. The modified nanoparticles were systematically studied via TEM, FT-IR, DLS, XRD, NMR, TGA, and magnetization measurements. DLS measurement confirmed that the obtained dendritic-linear-brush-like triblock copolymer-grafted SPIONs had a uniform hydrodynamic particle size of average diameter less than 30 nm. The dendritic-linear-brush-like triblock copolymer-grafted SPIONs possessed excellent biocompatibility by methyl tetrazolium (MTT) assays against NIH3T3 cells and hemolysis assays with rabbit erythrocytes. Furthermore, an anticancer drug, doxorubicin (Dox), was used as a model drug and loaded into the dendritic-linear-brush-like triblock copolymer-grafted SPIONs, and subsequently, the drug releases were performed in phosphoric acid buffer solution pH = 4.7, 7.4, or 11.0 at 37 °C. The results verify that the dendritic-linear-brush-like triblock copolymer-grafted SPIONs possess pH-responsive drug release behavior. The Dox dose of the loaded and free drug required for 50% cellular growth inhibition was 2.72 and 0.72 μm/mL, respectively, according to MTT assay against a Hella cell line in vitro. Therefore, on the basis of its biocompatibility and drug release effect, the modified SPION could provide a charming opportunity to design some excellent drug delivery systems for therapeutic applications.

Core Cross‐Linked Amphiphilic Star‐Block Copolymers with (Meth)acrylic Acid Shells Prepared by Atom Transfer Radical Polymerization

AbstractCore cross‐linked amphiphilic star‐block copolymers were prepared by hydrolysis of the outer shell of star‐block copolymers prepared using copper mediated atom transfer radical polymerization (ATRP). In an arm‐first approach, linear poly(tert‐butyl methacrylate) macroinitiators (PtBMA‐Cl) were extended with styrene to yield PtBMA‐b‐PS‐Cl and then cross‐linked with divinylbenzene (DVB) in order to yield (PtBMA‐b‐PS)arms‐PDVBcore star‐block copolymers. Then, PMAA‐b‐PS block and (PMAA‐PS)arms‐PDVBcore star‐block copolymers were obtained by hydrolysis of the PtBMA blocks in both linear and cross‐linked copolymers, as confirmed by 1H NMR analyses. The amphiphilic character of these copolymers was confirmed by solubilisation in water. Several factors affecting the polymer aggregation and solubility such as the length, the composition of the arms and the catalyst used were studied. An acrylate analogue, that is, (PAA‐b‐PS)arms‐PDVBcore, was also prepared for comparison purposes. Atomic force microscopy (AFM) and differential scanning calorimetry (DSC) were used to elucidate the morphology and the thermal behaviour of the star‐block copolymers.

Cellular interactions of monodisperse poly(GDMA) latex particles-containing DMAEM brushes

Monodisperse latex particles, 791 nm in diameter, were synthesized by single-stage precipitation polymerization of glycerol dimethacrylate (GDMA). Then N,N-(dimethylamino) ethyl methacrylate (DMAEM) brushes were created on the surface of poly(GDMA) particles by copper-mediated atom transfer radical polymerization (ATRP). The poly(GDMA–DMAEM) particles exhibit thermosensitive properties since DMAEM brushes give cationic character to the poly(GDMA) latex particles. In L929 mouse fibroblast cell cultures no toxicity against cell proliferation was observed when the particle concentration was 25 ng per cell. Poly (GDMA) and poly(GDMA–DMAEM) latex particles attached well onto the polystyrene cell culture dishes. Cellular interactions between fibroblasts and latex particles were investigated on these particle-coated culture plates by means of microscopic observations (optic microscope and scanning electron microscope, SEM) and MTT assay. The results indicated that the poly(GDMA–DMAEM) particles can facilitate cell attachment and proliferation due to the presence of positively charged amino groups on their surfaces. These surface coated latex particles may find useful applications as adhesion modifiers for cells in biomedical devices.

ChemInform Abstract: Copper‐Catalyzed Atom Transfer Radical Addition (ATRA) and Cyclization (ATRC) Reactions in the Presence of Reducing Agents

AbstractReview: 209 refs.

Synthesis and Hierarchical Self-Assembly of Rod−Rod Block Copolymers via Click Chemistry between Mesogen-Jacketed Liquid Crystalline Polymers and Helical Polypeptides

A series of novel rod−rod diblock copolymers containing poly{2,5-bis[(4-methoxyphenyl)oxycarbonyl]styrene} (PMPCS) and poly(γ-benzyl-l-glutamate) (PBLG) were synthesized by click chemistry from alkyne- and azide-functionalized homopolymers. The α-alkyne PMPCS homopolymers were synthesized by copper-mediated atom transfer radical polymerization with a bromine-containing α-alkyne bifunctional initiator, and α-azido PBLG homopolymers were synthesized by ring-opening polymerization of γ-benzyl-l-glutamate N-carboxyanhydride with an amino-containing α-azide initiator. The molecular structures of the rod−rod block copolymers were confirmed by 1H NMR spectroscopy, Fourier transform infrared spectroscopy, and gel permeation chromatography analysis. The self-assembling behavior of the rod−rod block copolymers in bulk was investigated using differential scanning calorimetry, polarized light microscopy, wide-angle X-ray diffraction, and transmission electron microscopy techniques. A lamellar structure was observed w...

Copper Catalyzed Atom Transfer Radical Addition (ATRA) and Cyclization (ATRC) Reactions in the Presence of Reducing Agents

This article reports on recent advances in the area of catalyst regeneration in copper mediated atom transfer radical addition (ATRA) and cyclization (ATRC) reactions using free‐radical diazo initiators as reducing agents. The role of reducing agent in both processes is to continuously regenerate the activator (copper(I) complex) from the deactivator (copper(II) complex). As a result, single addition adducts in ATRA and ATRC reactions can be synthesized using very low concentrations of copper catalysts (5–100 pm). Previously, efficient catalysis for both processes required as much as several thousands ppm of copper. It is envisioned that the recent developments in this area could have important industrial implications on the synthesis of small organic molecules, natural products and pharmaceutical drugs.

Hydrated Clay for Catalyst Removal in Copper Mediated Atom Transfer Radical Polymerization

AbstractA simple method has been described to remove catalyst from the copper mediated atom transfer radical polymerization (ATRP) of benzyl methacrylate and methyl methacrylate in anisole at 25 °C using hydrated natural clay (sodium montmorillonite, Na‐clay). The method consists of (1) addition of hydrated clay (CuI/clay ≈ 5 wt.‐%) either during or after the polymerization, (2) oxidation of catalyst complex by exposing the terminated reaction mixture in air, and (3) filtration to obtain catalyst free polymer solution. A strong coordination of CuBr‐ligand complex onto hydrated clay (10 wt.‐% < H2O/clay < 30 wt.‐%) upon oxidation resulted in polymers with no or insignificant residual catalyst (<1.74 ppm), as determined by UV‐vis and atomic absorption spectroscopy. The recovered clay exhibited expanded intercalary layers and absence of polymer within it.magnified image

Copper mediated atom transfer radical cyclisations with AIBN

We have shown that it is possible to mediate a range of 5- exo trig and 5- exo dig atom transfer radical cyclisations of bromoacetamides using 0.1–1 mol % CuBr or CuBr 2 in conjunction with 0.1–1 mol % tri(pyridin-2-ylmethyl)amine and 10 mol % AIBN. This equates to a 30–300-fold reduction in the amount of catalyst previously reported for these reactions and allows cyclisation to be carried out with the more oxidatively stable CuBr 2 without the requirement of an inert atmosphere.

Copper-mediated controlled radical ring-opening polymerization (RROP) of a vinylcycloalkane

This investigation reports controlled ring-opening polymerization of a vinylcyclopropane via copper-mediated atom transfer radical polymerization which leads to predominantly 1,5 ring-opening polymerization.