macro-RAFT Agent Research Articles

Electrochemically-Initiated RAFT Synthesis of Low Dispersity Multiblock Copolymers by Seeded Emulsion Polymerization.

We describe electrochemically initiated emulsion polymerization with reversible addition-fragmentation chain transfer (eRAFT) to form well-defined multiblock copolymers with low molar mass dispersity. We demonstrate the utility of our emulsion eRAFT process with the synthesis of low dispersity multiblock copolymers by seeded RAFT emulsion polymerization at ambient temperature (∼30 °C). Thus, a triblock, poly(butyl methacrylate)-block-polystyrene-block-poly(4-methylstyrene) [PBMA-b-PSt-b-PMS], and a tetrablock, poly(butyl methacrylate)-block-polystyrene-block-poly(styrene-stat-butyl acrylate)-block-polystyrene [PBMA-b-PSt-b-P(BA-stat-St)-b-PSt], were synthesized as free-flowing, colloidally stable latexes commencing with a surfactant-free poly(butyl methacrylate) macroRAFT agent seed latex. A straightforward sequential addition strategy with no intermediate purification steps was able to be employed due to the high monomer conversions achieved in each step. The method takes full advantage of compartmentalization phenomena and the nanoreactor concept described in previous work to achieve the predicted molar mass, low molar mass dispersity (Đ ∼ 1.1-1.2), incrementing particle size (Zav = 100-115 nm), and low particle size dispersity (PDI ∼ 0.02) for each generation of the multiblocks.

Rhenium(I) Block Copolymers Based on Polyvinylpyrrolidone: A Successful Strategy to Water-Solubility and Biocompatibility

A series of diphosphine Re(I) complexes Re1-Re4 have been designed via decoration of the archetypal core {Re(CO)2(N^N)} through the installations of the phosphines P0 and P1 bearing the terminal double bond, where N^N = 2,2'-bipyridine (N^N1), 4,4'-di-tert-butyl-2,2'-bipyridine (N^N2) or 2,9-dimethyl-1,10-phenanthroline (N^N3) and P0 = diphenylvinylphosphine, and P1 = 4-(diphenylphosphino)styrene. These complexes were copolymerized with the corresponding N-vinylpyrrolidone-based Macro-RAFT agents of different polymer chain lengths to give water-soluble copolymers of low-molecular p(VP-l-Re) and high-molecular p(VP-h-Re) block-copolymers containing rhenium complexes. Compounds Re1-Re4, as well as the copolymers p(VP-l-Re) and p(VP-h-Re), demonstrate phosphorescence from a 3MLCT excited state typical for this type of chromophores. The copolymers p(VP-l-Re#) and p(VP-h-Re#) display weak sensitivity to molecular oxygen in aqueous and buffered media, which becomes almost negligible in the model physiological media. In cell experiments with CHO-K1 cell line, p(VP-l-Re2) and p(VP-h-Re2) displayed significantly reduced toxicity compared to the initial Re2 complex and internalized into cells presumably by endocytic pathways, being eventually accumulated in endosomes. The sensitivity of the copolymers to oxygen examined in CHO-K1 cells via phosphorescence lifetime imaging microscopy (PLIM) proved to be inessential.

Aqueous RAFT polymerization-induced self-assembly (PISA): amphiphilic macroRAFT self-assembly vs. monomer droplet nucleation (miniemulsion polymerization)

The effect of monomer droplet size on the particle formation mechanism in aqueous heterogeneous polymerization using a hydrophilic macroRAFT agent has been investigated.

Fluorinated reversed micelles by polymerization-induced self-assembly with main-chain-type semifluorinated alternating copolymer

In this work, based on the semifluorinated macro-RAFT (reversible addition-fragmentation chain transfer) agent and polymerization-induced self-assembly (PISA) strategy, we established a mild and facile method to prepare reversed micelles up to 40 wt% of solid content with main-chain-type semifluorinated alternating copolymer as shell and hydrophilic polymer as core for the first time. The fluorinated macro-RAFT agent was synthesized by combination of step transfer-addition & radical-termination (START) polymerization and post-modification method. The reversed micelles were generated by the PISA of N,N-dimethacrylamide (DMA) in the presence of the fluorinated macro-RAFT agent in the non-polar solvent toluene at 70 °C, and fluorinated reversed micelles can be fixed in the presence of crosslinker ethyleneglycol dimethacrylate (EGDMA). This strategy will facilitate to open a new way in designing novel functional synthetic fluorinated nanomaterials.

Linear and Star Block Copolymer Nanoparticles Prepared by Heterogeneous RAFT Polymerization Using an ω,ω-Heterodifunctional Macro-RAFT Agent.

Herein, an ω,ω-heterodifunctional macromolecular reversible addition-fragmentation chain transfer (macro-RAFT) agent containing two different RAFT end groups was synthesized and employed to mediate aqueous photoinitiated RAFT dispersion polymerization of a methacrylic monomer. Because of the different RAFT controllability of two RAFT end groups toward methacrylic monomers, the RAFT end group with good controllability dominated the polymerization while the other RAFT end group with poor controllability was unreacted, leading to the formation of linear block copolymers. Because of the unique structure of the linear block copolymers, a diverse set of block copolymer nanoparticles with rich RAFT groups at the interface of the hydrophilic corona/the hydrophobic core were successfully prepared. Finally, μ-A(BC)C miktoarm star block copolymer nanoparticles were prepared by RAFT seeded emulsion polymerization of an acrylic monomer, which enables the further morphological control over polymer nanoparticles. We believe that the utilization of an ω,ω-heterodifunctional macro-RAFT agent in heterogeneous RAFT polymerization will offer considerable opportunities for the rational synthesis of well-defined molecular architectures and polymer nanoparticles.

Efficient Synthesis and Self-Assembly of Segmented Hyperbranched Block Copolymers via RAFT-Mediated Dispersion Polymerization Using Segmented Hyperbranched Macro-RAFT Agents

Efficient Synthesis and Self-Assembly of Segmented Hyperbranched Block Copolymers via RAFT-Mediated Dispersion Polymerization Using Segmented Hyperbranched Macro-RAFT Agents

Pluronic based injectable smart gels with coumarin functional amphiphilic copolymers

Temperature responsive Pluronic F127 micelles were combined with light-responsive coumarin bearing amphiphilic copolymers to obtain both mechanically strong and injectable gels. For this purpose two monomers, 7-(2-methacryloyloxyethoxy)-4-methylcoumarin (CEMA) and 7-methacryloyloxy-4-methylcoumarin (CMA), were synthesized and further polymerized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Well-defined amphiphilic diblock terpolymers were obtained by using preliminarily synthesized polyethylene glycol (PEG) based macroRAFT agent. The structures of copolymers were confirmed with proton nuclear magnetic resonance spectroscopy (1H NMR), Fourier-transform infrared(FT-IR) spectroscopy and gel permeation chromatography (GPC) analyses. Amphiphilic diblock terpolymers self-assembled into micelles in aqueous solution spontaneously and crosslinking of the micelle cores through the photodimerization of coumarin groups under UV irradiation at 350 nm was examined by UV spectroscopy. Hydrogels were prepared using two different methods, PF127-Mx gels formed using polymer micelle solutions with PF127 solid and PF127-Px gels formed by mixing solid polymers with 20 % F127 solution. Upon characterization of hydrogels via dynamic light scattering (DLS) and transition electron microscope (TEM), rheological properties of the gels were evaluated as a function of temperature, composition, UV exposure time, strain and frequency. Injectability tests of hydrogel systems were performed on a texture analyzer and all the formulations were found in the injectable range. The study reveals that hydrogels based on combination of PF127 and coumarin functional terpolymer amphiphiles hold great potential as injectable biomaterials.

Synthesis and characterization of star-shaped block copolymers composed of poly(3-hydroxy octanoate) and styrene via RAFT polymerization

This study investigated a macro reversible addition fraction chain transfer (RAFT) agent based on three-arm hydroxylated star-shaped poly(3-hydroxy octanoate). The utilization of this star-shaped poly(3-hydroxy octanoate) macro-RAFT agent in the RAFT process resulted in efficient control in the preparation of star-shaped block styrene copolymers. Poly(3-hydroxy octanoate) (PHO) was reacted with diethanol amine (DEA) in order to obtain three-arm hydroxylated poly(3-hydroxy octanoate) (PHO-DEA). A carboxylic acid-functionalized RAFT agent (2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid) was reacted with the PHO-DEA in order to obtain a star-shaped PHO macro-RAFT agent (PHO-R2). A series of AB3 type PHO-polystyrene (PHO-PS) star-shaped block copolymers were obtained via the polymerization of styrene (S) using the PHO-R2 in toluene at 80 °C. The RAFT polymerization was seen to obey the polymerization kinetics of controlled free radical polymerization. The plasticizing effect of the PHO soft segments was influenced by the glass transition temperature (Tg) of polystyrene. This was clearly observed in the block copolymers. Moreover, it was clear that this plasticizing effect disappeared in the block copolymers as a result of the increase in polymerization time. The molar masses of the obtained copolymers increased in parallel with increases in the polymerization time. Structural, physiochemical, and thermal characterization of the obtained products was carried out using size-exclusion chromatography (SEC), proton nuclear magnetic resonance (1H NMR), differential scanning calorimetry (DSC), and thermal gravimetric analysis (TGA) techniques. The polymerization kinetics of the star-shaped block copolymers were also investigated in detail.

Dispersion polymerization of styrene/acrylonitrile in polyether stabilized by macro-RAFT agents

A series of poly(acrylate polyether)s (RPA) was designed and synthesized by reversible addition-fragmentation chain transfer (RAFT) copolymerization, which were then used as dispersants for the dispersion copolymerization of styrene/acrylonitrile in polyethers in a semicontinuous approach to prepare graft polyether polyol (POP) with high solid content. The effects of structure, dosage, and feed ratio for macro-RAFT agent RPA on the stability, viscosity, and particle size of POP were examined and discussed. The dispersion polymerization process was also characterized by gradient elution polymer chromatography, and the results indicated that RPA was rapidly consumed and block-type stabilizer formed in the initial stage of polymerization. A portion of RPA added with monomer feeding provided better stability for the semicontinuous polymerization process.

Exploiting Wavelength Orthogonality in Photoinitiated RAFT Dispersion Polymerization and Photografting for Monodisperse Surface-Functional Polymeric Microspheres.

We report a strategy toward surface-functional polymeric microspheres using a wavelength orthogonality technique that employs photoinitiated reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization and the subsequent photografting under different wavelengths of light. Initial screening of reaction conditions indicated photoreactive polymeric microsphere with uniform sizes could be prepared by using photoinitiator-functionalized macro-RAFT agents under purple light irradiation. Photoreactive polymeric microspheres allowed photografting polymerizations under UV light irradiation, and we further demonstrated the broad scope of this method by photografting acrylamide, acrylic, and methacrylic monomers. Finally, carboxyl-functionalized polymeric microspheres with an exceptional high number of carboxyl groups were successfully prepared by this technique, which permitted extensive surface bioconjugation of model proteins (e.g., streptavidin). This method should expand the capabilities of RAFT dispersion polymerization to afford diverse surface-functional polymeric microspheres for some specific applications.

Synthesis and physicochemical characterization of PMMA and PNIPAM based block copolymers by using PEG based macro RAFT agents

Synthesis and physicochemical characterization of PMMA and PNIPAM based block copolymers by using PEG based macro RAFT agents

Facile and tunable method for polymeric surface modification of magnetic nanoparticles via RAFT polymerization: Preparation, characterization, and drug release properties

Herein, the facile and tunable technique for the preparation of novel multi-stimuli-responsive nanocomposites via RAFT polymerization for DOX delivery is reported. The influence of the molecular weight of pH- and thermo-sensitive poly (acrylic acid-co-NIPAM) (PNAx), as a macro-RAFT agent, on the nanocomposites size and drug release rate was investigated. The outcome of this study reveals that macro-RAFT agent with lower molecular weight can be attached to the surface of magnetic nanoparticles with higher content of polymeric layer than can macro-RAFT agent with higher molecular weight. Also, it was observed that the particle size, polymer grafting density, DOX loading capacity, and DOX release rate could well be influenced by the molecular weight of PNAx. The in vitro drug release of doxorubicin was examined in various conditions (pH and temperature) and the results established a strong pH and thermal dependence. The order of drug-loading and releasing level rate for synthesized nanocarriers toward PNAx molecular weight are PNA3 < PNA2 < PNA1. These magnetic nanocarriers displayed excellent biocompatibility, stability, and dispersibility in aqueous solutions. Therefore, experimental data and results showed that nanocarriers synthesized with various molecular weights of PNAx by RAFT polymerization could be deployed for practical biomedicine applications and that the RAFT polymerization ushers in an excellent technique for tunable and facile surface modification of various nanoparticles with distinct sizes and morphologies.

Inside Back Cover Picture

The inside back cover picture shows that polymer vesicles with low‐polydispersity (&lt; 0.1) and controllable size in the scope of sub‐100 nm are fabricated by polymerization‐induced self‐assembly (PISA) using ternary macro RAFT agents of different lengths. The ternary stabilizers play a crucial role in the formation of small and low‐polydispersity vesicles. More details are given in the article by Hong et al. on page 453—459. image

Segmented Copolymers Synthesized by Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization Using an Asymmetric Difunctional RAFT Agent and the Utilization in RAFT-Mediated Dispersion Polymerization

Reversible addition-fragmentation chain transfer (RAFT)-mediated polymerization-induced self-assembly (PISA) is an in situ growth method of increasing interest for the preparation of block copolymer nano-objects with diverse morphologies at high solids contents (10–50 wt %). Recent reports have shown that structures of multifunctional macro-RAFT agents can significantly affect RAFT-mediated PISA and the formed block copolymer nano-objects, but all these multifunctional macro-RAFT agents are limited to symmetric structures. In this study, we synthesized a novel difunctional RAFT agent with an asymmetric structure and employed in RAFT solution polymerization to prepare segmented macro-RAFT agents. Size exclusion chromatography (SEC) analysis showed that the redistribution of blocks occurred during RAFT polymerization, leading to the formation of segmented copolymers with different blocks (block number up to 4). Control experiments demonstrated that this redistribution process was derived from the unique structure of the asymmetric difunctional RAFT agent rather than monomers. The obtained segmented macro-RAFT agent was then used in RAFT-mediated dispersion polymerization to prepare well-defined block copolymer nano-objects. Owing to the unique structure of segmented block copolymers, shorter micellar nucleation was observed and a certain number of trithiocarbonate groups could be introduced on the surface of block copolymer nano-objects. The trithiocarbonate groups located on the surface of block copolymer nano-objects provide a landscape for further chain extension and functionalization. As a proof-of-concept experiment, vesicles loaded with silver nanoparticles were successfully prepared by in situ reduction of AgNO3 and employed as a catalyst to reduce methylene blue in the presence of NaBH4. We expect that this study will not only provide important mechanistic insights into RAFT polymerization mediated by multifunctional RAFT agents but also enable the preparation of functional block copolymer nano-objects.

Synchronous Synthesis of Polymeric Vesicles with Controllable Size and Low‐Polydispersity by Polymerization‐Induced Self‐Assembly

Comprehensive SummaryThe size and size distribution of polymeric nanoparticles have great impact on their physicochemical and biological properties. Polymerization‐induced self‐assembly (PISA) has been demonstrated to be an efficient method to fabricate various polymeric nanoparticles, among which polymeric vesicles have attracted great interest due to their unique hollow structure. However, polymeric vesicles with relatively broad size distributions and random size are normally formed, which is problematic for many potential applications. Herein, we report the synthesis of polymeric vesicles with low‐polydispersity and controllable size by polymerization‐induced self‐assembly. A mixed macro RAFT agent of three different poly(ethylene glycol) (PEGm‐CPADB) was used to mediate the RAFT dispersion copolymerization of 7‐(2‐methacryloyloxyethoxy)‐4‐methylcoumarin (CMA) and benzyl methacrylate (BzMA), which generated vesicles with low‐polydispersity (&lt; 0.1) and controllable size in the scope of sub‐100 nm. In comparison, RAFT dispersion copolymerization of CMA and BzMA using a single PEG‐CPADB as the macro RAFT agent generated vesicles with adjustable but obviously larger size and broader size distributions (&gt; 0.1). The results demonstrate that the ternary stabilizers play a crucial role in the formation of small and low‐polydispersity vesicles.

Synthesis and Characterization of Temperature-Responsive N-Cyanomethylacrylamide-Containing Diblock Copolymer Assemblies in Water.

We have previously demonstrated that poly(N-cyanomethylacrylamide) (PCMAm) exhibits a typical upper-critical solution temperature (UCST)-type transition, as long as the molar mass of the polymer is limited, which was made possible through the use of reversible addition-fragmentation chain transfer (RAFT) radical polymerization. In this research article, we use for the first time N-cyanomethylacrylamide (CMAm) in a typical aqueous dispersion polymerization conducted in the presence of poly(N,N-dimethylacrylamide) (PDMAm) macroRAFT agents. After assessing that well-defined PDMAm-b-PCMAm diblock copolymers were formed through this aqueous synthesis pathway, we characterized in depth the colloidal stability, morphology and temperature-responsiveness of the dispersions, notably using cryo-transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), small angle X-ray scattering (SAXS) and turbidimetry. The combined analyses revealed that stable nanometric spheres, worms and vesicles could be prepared when the PDMAm block was sufficiently long. Concerning the thermoresponsiveness, only diblocks with a PCMAm block of a low degree of polymerization (DPn,PCMAm < 100) exhibited a UCST-type dissolution upon heating at low concentration. In contrast, for higher DPn,PCMAm, the diblock copolymer nano-objects did not disassemble. At sufficiently high temperatures, they rather exhibited a temperature-induced secondary aggregation of primary particles. In summary, we demonstrated that various morphologies of nano-objects could be obtained via a typical polymerization-induced self-assembly (PISA) process using PCMAm as the hydrophobic block. We believe that the development of this aqueous synthesis pathway of novel PCMAm-based thermoresponsive polymers will pave the way towards various applications, notably as thermoresponsive coatings and in the biomedical field.

Polymer/C.I. Pigment Red 170 hybrid latexes prepared by RAFT-mediated surfactant-free emulsion polymerization

By using organic pigment-based ink-jet inks, the digital ink-jet printing of textiles is one kind of environmentally friendly technology for cleaner dyeing. Due to the shortcomings of easy agglomeration and poor water dispersion stability of organic nanoparticles, however, the encapsulation and dispersion of organic pigment nanoparticles are also hot and difficult research problems. In this work, we report the reversible addition-fragmentation chain transfer (RAFT) polymerization technology was used to synthesize random copolymer of 2-(dimethylamino) ethyl methacrylate (DMAEMA), poly(ethylene glycol) methyl ether methacrylate (PEGA), and methyl methacrylate (MMA) or butyl acrylate (BA) with a trithiocarbonate reactive end-group. These cationic macromolecular RAFT agents (macro-RAFT) with a pH of 5 were subsequently adsorbed at the surface of size-monodisperse colloidal Pigment Red 170 particles. The absorbed macro-RAFT agents were considered to be the living points to mediate the RAFT polymerization of monomers (MMA and BA) by starved feed emulsion polymerization. TEM results shown that the resulting hybrid latexes synthesized in presence of the tri-copolymer macro-RAFT agents resulted in the formation of individually encapsulated pigment particles. In addition, the dynamic light scattering (DLS), zeta potential and stability tests found that the macro-RAFT agent participated in the growing latex stabilization which is the key to obtaining the stable and uniform core-shell hybrid latex. More importantly, the preparation of film-forming copolymer/pigment hybrid latex in this study shown that the high potential of the P(DMAEMA- co -PEGA- co -MMA or BA) macro-RAFT agent for the development of polymer-pigment hybrid latexes which has good application properties. • Cationic and brush-type macro-RAFT agents were synthesized through RAFT polymerization. • Amphiphilic macro-RAFT agent has good adsorption and dispersion properties for the C.I. Pigment Red 170. • The film-forming polymers with lower T g are successfully encapsulated on the surface of pigment. • The encapsulated polymer/pigment hybrid latexes exhibit excellent dispersion stability with freeze-thaw, storage and pH.

Shape-Controlled Nanoparticles from a Low-Energy Nanoemulsion.

Nanoemulsion technology enables the production of uniform nanoparticles for a wide range of applications. However, existing nanoemulsion strategies are limited to the production of spherical nanoparticles. Here, we describe a low-energy nanoemulsion method to produce nanoparticles with various morphologies. By selecting a macro-RAFT agent (poly(di(ethylene glycol) ethyl ether methacrylate-co-N-(2-hydroxypropyl) methacrylamide) (P(DEGMA-co-HPMA))) that dramatically lowers the interfacial tension between monomer droplets and water, we can easily produce nanoemulsions at room temperature by manual shaking for a few seconds. With the addition of a common ionic surfactant (SDS), these nanoscale droplets are robustly stabilized at both the formation and elevated temperatures. Upon polymerization, we produce well-defined block copolymers forming nanoparticles with a wide range of controlled morphologies, including spheres, worm balls, worms, and vesicles. Our nanoemulsion polymerization is robust and well-controlled even without stirring or external deoxygenation. This method significantly expands the toolbox and availability of nanoemulsions and their tailor-made polymeric nanomaterials.

Polymer/Laponite Nanocomposite Films Produced from Surfactant-Free Latexes using Cationic Macromolecular Reversible Addition-Fragmentation Chain Transfer Copolymers

In this work, the use of positively charged macromolecular reversible addition-fragmentation chain transfer (RAFT) copolymers (macro-RAFTs) in the synthesis of Laponite RD-based nanocomposite latex particles is described. For this purpose, two different amphiphilic copolymers composed of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and nbutyl acrylate (BA) units are investigated. In the first step, the macroRAFT is adsorbed onto Laponite, and then, in the second step, the macroRAFTmodified clay platelets are used in the emulsion copolymerization of methyl methacrylate (MMA), methyl acrylate (MA), or styrene (Sty), with BA. By acting as both coupling agents and stabilizers, the macroRAFT agents lead to the formation of partially encapsulated particles and dumbbell structures. When hydrophobic monomer mixtures that can form film are used, these morphologies result in nanocomposite films with increased stiffness, in comparison to the pure polymer matrix. As observed by dynamic mechanical analysis, the high Young's modulus level presented by the composite films in the rubbery plateau (above 100 MPa when filled with 10 wt% of clay) highlights the strong mechanical reinforcement. Such an improvement can be attributed to the formation of two percolating networks, one of homogeneously distributed and connected platelets and one of macroRAFT chains, within the polymer matrix.

Selective Bond Cleavage in RAFT Agents Promoted by Low-Energy Electron Attachment.

Radical polymerization with reversible addition‐fragmentation chain transfer (RAFT polymerization) has been successfully applied to generate polymers of well‐defined architecture. For RAFT polymerization a source of radicals is required. Recent work has demonstrated that for minimal side‐reactions and high spatio‐temporal control these should be formed directly from the RAFT agent or macroRAFT agent (usually carbonothiosulfanyl compounds) thermally, photochemically or by electrochemical reduction. In this work, we investigated low‐energy electron attachment to a common RAFT agent (cyanomethyl benzodithioate), and, for comparison, a simple carbonothioylsulfanyl compound (dimethyl trithiocarbonate, DMTTC) in the gas phase by means of mass spectrometry as well as quantum chemical calculations. We observe for both compounds that specific cleavage of the C−S bond is induced upon low‐energy electron attachment at electron energies close to zero eV. This applies even in the case of a poor homolytic leaving group (.CH3 in DMTTC). All other dissociation reactions found at higher electron energies are much less abundant. The present results show a high control of the chemical reactions induced by electron attachment.