Direct Atom Transfer Radical Polymerization Research Articles

Nano-Hydroxyapatite Particle Brushes via Direct Initiator Tethering and Surface-Initiated Atom Transfer Radical Polymerization for Dual Responsive Pickering Emulsion.

Well-defined polymer-grafted solid inorganic nanoparticles (NPs) are imperative for practical applications in various fields based on the prerequisite of facile initiator immobilization. Direct atom transfer radical polymerization (ATRP) initiator-tethered solid NPs are described using 2-bromo-2-methylpropionic acid as a tetherable initiator. To illustrate the versatility of the proposed strategy, nano-hydroxyapatite (n-HAP) nanocrystals (NCs) were selected to demonstrate the morphology-controlled synthesis of 2-bromo-2-methylpropionate (2-BrMP) group-immobilized n-HAP (n-HAP-Br) NCs. When water was employed as the sole solvent, the continually introduced 2-BrMP groups altered the surface hydrophobic capacity of the n-HAP-Br NC and thus led to unavoidable aggregation of n-HAP-Br NCs. The synthesis of individually dispersed n-HAP-Br NCs was achieved by rational adjusting polarity of the aqueous medium through adding a portion of water-miscible organic solvents. The type and concentration of added water-miscible organic solvents had critical effects on the morphology and particle size of n-HAP-Br NCs. To verify the efficiency of the tethered initiator, n-HAP-g-poly2-(dimethylamino) ethyl methacrylate (n-HAP-g-PDMAEMA), n-HAP-g-polyacrylonitrile (n-HAP-g-PAN), and n-HAP-g-polymethyl methacrylate (n-HAP-g-PMMA) were fabricated by surface-initiated ATRP (SI-ATRP). Acting as a solid particle emulsifier, the designed n-HAP-g-PDMAEMA-stabilized Pickering emulsion displayed dual pH and temperature response with reversible behaviors. This work presents a versatile and simple way for the fabrication of initiator-immobilized solid NPs (e.g., n-HAP NCs, gibbsite nanoplatelets, and γ-FeOOH nanofibers) ready for polymer grafting and thus enables promising performance in widespread applications.

Direct synthesis of well-defined zwitterionic cyclodextrin polymers via atom transfer radical polymerization

A versatile atom transfer radical polymerization (ATRP) protocol was developed for the direct homo- and copolymerization of a sulfobetaine monomer, [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium (SBMA), and a mono-functionalized β-cyclodextrin (βCD) methacrylate monomer. The polymers were characterized using 1- and 2D NMR spectroscopy and asymmetrical flow field-flow fractionation (AF4). Low dispersities (ĐM = Mw/Mn) and high initiator efficiencies, of both the homo- and copolymers, indicated good control of the polymerization. The work thus represents one of the few reports where low ĐM values are obtained for direct ATRP of SBMA and βCD monomers. The novel βCD copolymer showed salt-dependent upper critical solution temperature (UCST) behavior, while isothermal titration calorimetry revealed excellent binding properties.

Study the role of poly(diethyl aminoethyl methacrylate) as a modified and grafted shell for TiO2 and ZnO nanoparticles, application in flutamide delivery

Diethyl aminoethyl methacrylate (DEAEMA) was polymerized and cross-linked simultaneously with direct atom transfer radical polymerization (ATRP) of the modified TiO2 and ZnO nanoparticles (CH3CHBrCO@ZnO and CH3CHBrCO@TiO2). In the other view, the surface of the TiO2 and ZnO nanoparticles were modified and grafted with poly(DEAEMA). During the ATRP of DEAEMA with CH3CHBrCO@ZnO and CH3CHBrCO@TiO2 nanoparticles, different ratios of flutamide, as an anti-cancer drug and the case for the simulation, were added to the polymerization matrix. Meanwhile, the polymer nanocomposites (PNCs) were obtained as a delivering system. Then, the different PNCs were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetry, and electrochemical investigations. In this regards, electrochemical investigations reveled the fact that the developed delivering systems have the drug release rates of 31.0 over 1560min and 22.8 in 1200min for the flutamide-loaded PDEAEMA-CH3CHBrCO@TiO2 and flutamide-loaded PDEAEMA-CH3CHBrCO@ZnO, respectively. Also, according to the TEM images, the synthesized delivering systems based on CH3CHBrCO@TiO2 shows the bowl-like arrangements, which likely support the obtained electrochemical and high performance liquid chromatography results. Finally, our study shows that the view of the modifying and grafting of TiO2 and ZnO nanoparticles by poly(DEAEMA) confirmed the great success for the introduced simulated drug delivery system than the view of the TiO2 and ZnO, as modifiers for poly(DEAEMA).

Biocompatible chiral monolithic stationary phase synthesized via atom transfer radical polymerization for high performance liquid chromatographic analysis

Novel biocompatible chiral monolithic stationary phase was prepared by reverse and direct atom transfer radical polymerization (ATRP) methods. By taking advantages of the controlled/living property of ATRP method, the chiral monolith was prepared by reverse ATRP (RATRP) firstly. An attractive feature of RATRP is the prepared polymer containing a terminal radically transferable atom that can initiate another post-polymerization reaction by direct ATRP. Then, the biocompatible poly(hydroxyethyl methacrylate) (PHEMA) was grafted on the surface of the chiral monolith by direct ATRP as a diffusion barrier for proteins. This biocompatible chiral monolith was successfully used as restricted access stationary phase for determination of enantiomers in biological samples with direct injection by high-performance liquid chromatography (HPLC).

A Thermoreversible Poly(Choline Phosphate) Based Universal Biomembrane Adhesive

A new monomer, 2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl methacrylate (AEO4 MA), and its direct atom transfer radical polymerization (ATRP) into poly(AEO4 MA), then "clicked" with prop-2-ynyle choline phosphate (CP) to produce a poly(choline phosphate) are described. This polymer exhibits a lower critical solution temperature (LCST) at ≈ 32 °C, and provides a universal thermally reversible biomembrane adhesive, which can rapidly both bind to any mammalian cell membrane and internalize into the cytoplasm of nucleated cells below the LCST. Moving above the LCST reverses cell surface binding. The use of ATRP implies that such polymers can be applied to modify the surfaces of a wide range of biomaterials. The capacity to bind and immobilize cells at room temperature and release them above the LCST should be particularly useful for in vitro cell manipulation and tissue engineering applications.

Synthesis and properties of novel biomimetic and thermo-responsive dextran-based biohybrids

A new class of biodegradable, biomimetic and thermo-responsive dextran/synthetic glycopolymer biohybrids (dextran-graft-poly(lactobionamidoethyl methacrylate)-block-poly(di(ethylene glycol) methyl ether methacrylate), dextran-g-(PLAMA-b-PDEGMA)), was synthesized by the direct atom transfer radical polymerization (ATRP) of unprotected lactobionamidoethyl methacrylate (LAMA) glycomonomer and di(ethylene glycol) methyl ether methacrylate (DEGMA) monomer. The dextran macroinitiator for ATRP was prepared by partial esterification of the hydroxyl groups of the polysaccharide with 2-bromo-2-methylpropionic acid (BrMPA). The biohybrids containing PDEGMA segments exhibited a lower critical solution temperature (LCST) behavior, which changed from unimers to aggregates in solutions. Moreover, it was demonstrated that these biohybrids had specific biomolecular recognition with ricinus communis agglutinin 120 (RCA120) in comparison with bovine serum albumin (BSA). Furthermore, these biohybrids showed good biocompatibility in the cytotoxicity assays. This hopefully provides a platform for targeted drug delivery and studying the biomolecular recognition between sugar and lectin.

Poly(methylmethacrylate)-block-poly(N-hydroxyethylacrylamide) diblock copolymers: direct ATRP synthesis and characterization

Diblock copolymers consisting of methylmethacrylate (MMA) and N-hydroxyethylacrylamide (HEAAm) polymer were successfully synthesized via direct two steps atom transfer radical polymerization (ATRP). At first, poly(methylmethacrylate) (PMMA) macroinitiators were prepared using methyl 4-(bromo-methyl) benzoate initiator and were used for synthesizing PMMA-b-PHEAAm block copolymers. PMMA homopolymers were synthesized in N,N′-dimethylformamide (DMF) using CuBr/2, 2′bipyridine catalyst system at 110 °C temperature in nitrogen atmosphere. Block copolymers were synthesized in mixture of DMF/water (8/2 v/v%) and in pure DMF in the presence of CuBr/1,1,4,7,10,10-hexamethyltriethylenetetramine (HMTETA) catalyst system at 85 and 100 °C, respectively, while argon was used for deoxygenation and inert environment. Purification of block copolymers was conducted through dialysis against deionized water using a dialysis tubing (MWCO 3,500, cellulose membrane). Molecular weights of PMMA polymers (M n = 4,400, 6,200 and 8,400 Da) were determined by size exclusion chromatography using tetrahydrofuran (THF) as eluent. The chemical structure and actual copolymer compositions were determined using elemental analysis (EA), attenuated total reflectance infrared (ATR-IR) and proton nuclear magnetic resonance (1H NMR) spectroscopic analysis. Phase separation of diblock copolymers resulting in two glass transition temperatures as detected by differential scanning calorimeter (DSC) proves their amphiphilic behavior. Thermogravimetric analysis (TGA) also showed that diblock copolymer, with two-step decomposition has higher thermal stability than PMMA.

Synthesis and structural chemistry of bis(pyridylimino)isoindolato–ruthenium complexes and their activity as mediators in the atom transfer radical polymerization (ATRP) of styrene

The reaction of the Bispyridyl Isoindole (BPI) type ligands L1 and L2 ( L1 = 1,3-Bis(2-(4- tert-butylpyridyl)imino) isoindole, L2 = 1,3-Bis(2-(5-bromo)imino)-5,6-dimethylisoindole) with [Ru(μ-Cl) 2(cod)] x in presence of triethylamine using coordinating solvents like acetonitrile, dimethyl sulfoxide or pyridine cleanly gave the complexes [{BPI( L1, L2)}Ru II(Cl)(S) 2] ( L1: S = acetonitrile ( 1), dimethyl sulfoxide ( 2), pyridine ( 3); L2: S = acetonitrile ( 4), dimethyl sulfoxide ( 5), pyridine ( 6)). In these complexes the BPI ligands meridionally coordinated to the ruthenium center as established by X-ray diffraction for complexes 3 and 6. The catalytic activity in the direct ATRP (Atom Transfer Radical Polymerization) of styrene was tested for complexes 1– 6.

Poly(sodium styrene sulfonate)-b-poly(methyl methacrylate) diblock copolymers through direct atom transfer radical polymerization: Influence of hydrophilic–hydrophobic balance on self-organization in aqueous solution

A series of poly(sodium styrene sulfonate)-b-poly(methyl methacrylate), PSSNa-b-PMMA, amphiphilic diblock copolymers have been synthesized through atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA) in N,N-dimethylformamide/water mixtures, starting from a PSSNa macroinitiator. The kinetics of the polymerization was followed by 1H NMR, while the chemical composition of the copolymers was verified by a variety of techniques, such as 1H NMR, FTIR and TGA. The MMA content of the copolymers ranges from 0 up to 60mol%, while the number–average molecular weight of the PSSNa macroinitiator was 9000g/mol. The self-association of the diblock copolymers in aqueous solution was compared to the respective behavior of similar random P(SSNa-co-MMA) copolymers through optical density measurements, pyrene fluorescence probing, dynamic light scattering and surface tension measurements. It is shown that the diblock copolymers form micellar structures in water, characterized by an increasing hydrophobic character and a decreasing size as the length of the PMMA block increases. These micelle-like structures turn from surface inactive to surface active as the length of the PMMA block increases. Moreover, contrary to the MMA-rich random copolymers, the respective diblock copolymers form water insoluble polymer/surfactant complexes with cationic surfactants such as hexadecyltrimethyl ammonium bromide (HTAB), leading to materials with antimicrobial activity.

Fabrication, biomolecular binding, in vitro drug release behavior of sugar-installed nanoparticles from star poly(ɛ-caprolactone)/glycopolymer biohybrid with a dendrimer core

Abstract Star poly(amido amine)-b-poly(ɛ-caprolactone)-b-poly( d -gluconamidoethyl methacrylate) (PAMAM–PCL–PGAMA) block copolymers with a dendrimer core were synthesized from the ring-opening polymerization of ɛ-caprolactone using a hydroxyl-terminated dendrimer poly(amido amine) initiator followed by the direct atom transfer radical polymerization of unprotected glycomonomer. The self-assembly and the biomolecular binding of PAMAM–PCL–PGAMA with Concanavalin A (Con A) were investigated by NMR, UV–vis, dynamic light scattering, and transmission electron microscopy, respectively. Multivalent sugar-installed vesicles and large compound aggregates were self-assembled from these dendritic copolymers in aqueous solution, demonstrating thermodynamically more stable than those self-assembled from linear counterpart. Moreover, these copolymers presented specific biomolecular binding with Con A lectin compared with bovine serum albumin, while both the lower mobility and the higher spatial hindrance within dendritic copolymers, to some extent, limited the clustering between sugar and Con A. Furthermore, these star copolymer nanoparticles showed a higher drug-loading efficiency and less burst release compared with linear counterpart. This work provides a method not only for the synthesis of star PCL/glycopolymer biohybrid with a dendrimer core but also for the fabrication of sugar-installed nanoparticles with tunable clustering ability, good drug-loading efficiency, and controlled drug-release profile useful for targeted drug delivery system.

Star‐shaped polypeptide/glycopolymer biohybrids: Synthesis, self‐assembly, biomolecular recognition, and controlled drug release behavior

AbstractStar‐shaped polypeptide/glycopolymer biohybrids composed of poly(γ‐ benzyl L‐glutamate) and poly(D‐gluconamidoethyl methacrylate), exhibiting controlled molecular weights and low polydispersities, were synthesized by the combination of ring‐opening polymerization of γ‐benzyl‐L‐glutamate N‐carboxyanhydride and the direct atom transfer radical polymerization of unprotected D‐gluconamidoethyl methacrylate glycomonomer. These biohybrids were characterized in detail by means of FTIR, 1H NMR, gel permeation chromatography, differential scanning calorimetry, and wide angle X‐ray diffraction. Independent of weight fraction of hydrophilic glycopolymer segment, the biohybrids self‐assembled into large spherical micelles in aqueous solution, which had a helical polypeptide core surrounded by a multivalent glycopolymer shell. The deprotected poly(L‐glutamate)/glycopolymer hybrid exhibited a pH‐sensitive self‐assembly behavior, and the average size of the nanoparticles decreased gradually over the aqueous pH value. Moreover, whatever these biohybrids existed in unimolecular level or glycopolymer‐surfaced nanoparticles, they had specific biomolecular recognition with Concanavalin A compared with bovine serum albumin. Furthermore, star‐shaped biohybrids showed a higher doxorubicin loading efficiency and longer drug‐release time than linear analogues. This potentially provides a platform for fabricating targeted anticancer drug delivery system and studying glycoprotein functions in vitro. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2009–2023, 2009

GRAFTING POLY(N-ISOPROPYL ACRYLAMIDE) FROM POLY(VINYLIDENE FLUORIDE) MIROFILTRATION, MEMBRANES VIA DIRECT SURFACE-INITIATED, ATOM TRANSFER RADICAL POLYMERIZATION, AND TEMPERATURE SENSITIVITY

Well-defined poly(N-isopropyl acrylamide) (PNIPAAm) brushes on commercial hydrophobic poly(vinylidene fluoride) (PVDF) microfiltration membrane surfaces were prepared, via direct atom transfer radical polymerization (ATRP) with the secondary fluorinated site of PVDF as initiator and water as solvent at 80°C. The effect of solvents on the ATRP was studied in detail. The water as reaction solvent was in favor of surface-initiated ATRP of N-isopropyl acrylamide (NIPAAm) from secondary fluoride of PVDF membranes. The chemical composition and structure of the modified PVDF membrane surfaces were determined by attenuated total reflectance (ATR) Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The surface and cross-section morphology of membranes were studied by scanning electron microscopy (SEM). The pore sizes of the pristine PVDF membrane and the PNIPAAm-grafted PVDF membranes were measured using micro-image analysis and process software. The introduction of the well-defined PNIPAAm on the PVDF membrane gave rise to hydrophilicity. Water contact angles of PVDF membranes reduced after the surface grafting of PNIPAAm. Water fluxes and protein solution permeation experiments revealed that the PNIPAAm-grafted PVDF membranes exhibited temperature-responsive permeability. The unique microstructure of PNIPAAm brushes facilitated hydrophilicity below the lower critical solution temperature.

Rapid Synthesis of Functional Polymer Brushes by Surface-Initiated Atom Transfer Radical Polymerization of an Acidic Monomer

The combination of a highly reactive monomer, 2-(methacryloyloxy)ethyl succinate (MES), and active catalyst systems, e.g., Cu(I) complexed with 1,1,4,7,10,10-hexamethyltriethylenetetramine (HMTETA), allows rapid formation of poly(carboxylic acid) brushes by atom transfer radical polymerization (ATRP) from a surface. ATRP from initiators immobilized on Au-coated Si wafers yields films with an ellipsometric thickness of 120 nm in less than 15 min. To the best of our knowledge, this is the first example of direct ATRP of protonated acidic monomers that is capable of yielding such thick films, and MES polymerizes much more rapidly than methacrylic acid both in solution and on a surface. The MES films are attractive for a number of applications, including immobilization of proteins. Assuming that a lysozyme monolayer has a thickness of 2 nm, a 55 nm poly(MES) brush binds ∼70 monolayers of lysozyme via ion-exchange interactions. Additionally, when derivatized with nitrilotriacetate−Cu2+ complexes, poly(MES) films bind ∼34 monolayers of BSA through metal-ion affinity interactions (assuming a BSA monolayer thickness of 4 nm). These binding capacities are similar to those of poly(acrylic acid) brushes prepared by polymerization of tert-butyl acrylate and subsequent hydrolysis, but the poly(MES) synthesis is a one-step, aqueous process.

Direct synthesis of amphiphilic block copolymers, consisting of poly(methyl methacrylate) and poly(sodium styrene sulfonate) blocks through atom transfer radical polymerization

Amphiphilic block copolymers of methyl methacrylate (MMA) and sodium styrene sulfonate (SSNa) were successfully synthesized via direct atom transfer radical polymerization (ATRP) of SSNa. First, poly(sodium styrene sulfonate) (PSSNa) or poly(methyl methacrylate) (PMMA) macroinitiators were prepared using proper ATRP systems for each case. In some cases, functional initiators, which allow further reactions, were used. The macroinitiators were characterized and further used to synthesize PSSNa/PMMA block copolymers, by using proper solvent combinations, such as N, N-dimethylformamide/water or methanol/water at appropriate volume ratios, in order to ensure solubility of the synthesized amphiphilic copolymers. The molecular weight of the copolymers was determined by gel permeation chromatography, using water as eluent. By using a combination of analytical techniques like 1H NMR, FTIR and thermogravimetry, the chemical structure and the actual copolymer composition were determined. Since, the block copolymers were soluble in water, forming hydrophilic/hydrophobic domains in aqueous solution, their micellization behavior was further studied by pyrene fluorescence probing.

Supramolecular and Biomimetic Polypseudorotaxane/Glycopolymer Biohybrids: Synthesis, Glucose-Surfaced Nanoparticles, and Recognition with Lectin

A new class of supramolecular and biomimetic glycopolymer/poly(epsilon-caprolactone)-based polypseudorotaxane/glycopolymer triblock copolymers (poly(D-gluconamidoethyl methacrylate)-PPR-poly(D-gluconamidoethyl methacrylate), PGAMA-PPR-PGAMA), exhibiting controlled molecular weights and low polydispersities, was synthesized by the combination of ring-opening polymerization of epsilon-caprolactone, supramolecular inclusion reaction, and direct atom transfer radical polymerization (ATRP) of unprotected D-gluconamidoethyl methacrylate (GAMA) glycomonomer. The PPR macroinitiator for ATRP was prepared by the inclusion complexation of biodegradable poly(epsilon-caprolactone) (PCL) with alpha-cyclodextrin (alpha-CD), in which the crystalline PCL segments were included into the hydrophobic alpha-CD cavities and their crystallization was completely suppressed. Moreover, the self-assembled aggregates from these triblock copolymers have a hydrophilic glycopolymer shell and an oligosaccharide threaded polypseudorotaxane core, which changed from spherical micelles to vesicles with the decreasing weight fraction of glycopolymer segments. Furthermore, it was demonstrated that these triblock copolymers had specific biomolecular recognition with concanavalin A (Con A) in comparison with bovine serum albumin (BSA). To the best of our knowledge, this is the first report that describes the synthesis of supramolecular and biomimetic polypseudorotaxane/glycopolymer biohybrids and the fabrication of glucose-shelled and oligosaccharide-threaded polypseudorotaxane-cored aggregates. This hopefully provides a platform for targeted drug delivery and for studying the biomolecular recognition between sugar and lectin.

Direct and Reverse ATRP of MMA in Aqueous Dispersed Medium in the Presence of a Bipyridine‐Functionalized Block Copolymer Support

AbstractSummary: In a recent communication (Macromol. Rapid Commun. 2002, 23, 871), we reported the synthesis of a bipyridine containing amphiphilic polymer and its usage as macroligand in the atom transfer radical polymerization (ATRP) of MMA in aqueous dispersed medium. Investigations on the mechanism and locus of nucleation by transmission electron microscopy (TEM) studies herein of latex particles prepared by direct ATRP using oil‐soluble ethyl 2‐bromoisobutyrate as initiator revealed a broad particle size distribution between 250 nm and 1 μm, suggesting two nucleation sites, micelles and monomer droplets. By using the water‐soluble initiator 2,2′‐azoisobutyramidine‐dihydrochloride (V‐50) reverse ATRP experiments were conducted at 90 °C. Kinetic measurements showed a sigmoidal slope of monomer conversion versus time as a first indication for an emulsion‐like process. Controlled polymerization behavior was achieved at a ratio of radicals versus Cu(II) deactivator of 1:8. TEM measurements of polymer latex particles obtained by reverse ATRP revealed particle sizes between 100 and 400 nm. Residual copper content of eight PMMA samples prepared by direct and reverse ATRP was determined to be 0.01–0.03 wt.‐% (theoretical 0.73 wt.‐%) and indicated that on average 96–99% of all copper used in a polymerization experiment can be removed from the polymer latex particles by a simple precipitation/washing step.Direct and reverse ATRP experiments of MMA in aqueous media in the presence of an amphiphilic, water‐soluble block copolymer with pendent bipyridine units.magnified imageDirect and reverse ATRP experiments of MMA in aqueous media in the presence of an amphiphilic, water‐soluble block copolymer with pendent bipyridine units.

Atom Transfer Radical Polymerization of Methyl Methacrylate in Water-Borne System

The controlled/living polymerization of methyl methacrylate was carried out by atom transfer radical polymerization (ATRP) in a water-borne system. Both the direct and reverse processes were performed in the presence of a copper halide/4,4‘-di(5-nonyl)-2,2‘-bipyridine (dNbpy) complex and a nonionic surfactant. In direct ATRP, ethyl 2-bromoisobutyrate (EBiB) was used as the oil-soluble initiator. Several surfactants with a large range of hydrophile−lypophile balance (HLB) values were tested. The critical micellar concentration (cmc) and the pH of the medium were also measured to determine their effects on the emulsion stability. The direct ATRP most likely proceeds via the suspension mechanism. In reverse ATRP, 2,2‘-azobis[2-(2-dimidazolin-2-yl)propane] dihydrochloride (VA-044) was used as the water-soluble initiator, and the results suggest an emulsion polymerization mechanism. In both approaches, the kinetics were followed along with the particle size (measured by laser diffraction and SEM), and the influence of the halogen atom associated with the catalyst (i.e., CuBr or CuCl) was examined. It was demonstrated that utilizing the halide exchange could improve the control over both the molecular weight and end functionality of the polymers.