Macro Reversible Addition-fragmentation Chain Transfer Research Articles

Kinetic Modeling of the Synthesis of Poly(4-vinylpyridine) Macro-Reversible Addition-Fragmentation Chain Transfer Agents for the Preparation of Block Copolymers

Reversible addition-fragmentation chain transfer (RAFT) polymerization is one of the most common controlled polymerization techniques to prepare well-defined, rather narrow dispersed polymers due to reduced demands in reactant preparation. Despite these advantages, RAFT polymerization was so far primarily utilized on small laboratory scales. This study presents a first step to a scaled-up RAFT polymerization by developing and experimentally validating a kinetic model on the example of the polymerization of 4-vinylpyridine (4VP), which to date is not described in the literature. With the implementation of the results from modeling, the synthesis process was extended to a medium scale (from 6 to 36 g), while the same high conversions, molar mass, and low dispersity as in the smaller scale were achieved. The process is also optimized regarding the high degree of livingness necessary for using the 4VP polymers as a macro-RAFT agent in the subsequent reaction step for the synthesis of poly(4-vinylpyridine)-b-polystyrene diblock copolymers by RAFT dispersion polymerization.

Dual Role of Doxorubicin for Photopolymerization and Therapy.

In this study, we report dual roles for doxorubicin (DOX), which can serve as an antitumor drug as well as a cocatalyst for a photoliving radical polymerization. DOX enhances the polymerization rates of a broad range of monomers, including acrylamide, acrylate, and methacrylates, allowing for high monomer conversion and well-defined molecular weights under irradiation with a blue light-emitting diode light (λmax = 485 nm, 2.2 mW/cm2). Utilizing this property, the photopolymerization of N,N-diethylacrylamide was performed in the presence of a poly(oligo(ethylene glycol) methyl ether acrylate) macroreversible addition-fragmentation chain transfer (macroRAFT) agent to prepare polymeric nanoparticles via aqueous polymerization-induced self-assembly (PISA). By varying the monomer:macroRAFT ratio, spherical polymeric nanoparticles of various diameters could be produced. Most notably, DOX was successfully encapsulated into the hydrophobic core of nanoparticles during the PISA process. The DOX-loaded nanoparticles were effectively uptaken into tumor cells and significantly inhibited the proliferation of tumor cells, demonstrating that the DOX bioactivity was not affected by the polymerization reaction.

Flame Retardant Submicron Particles via Surfactant-Free RAFT Emulsion Polymerization of Styrene Derivatives Containing Phosphorous.

The reversible addition–fragmentation chain transfer (RAFT) emulsion polymerization of diethyl-(4-vinylbenzyl) phosphate (DEVBP) was performed using PEG-TTC as a macro RAFT agent. PEG-TTC (MW 2000, 4000) was synthesized by the esterification of poly (ethylene glycol) methyl ether with a carboxylic-terminated RAFT agent, composed a hydrophilic poly (ethylene glycol) (PEG) block and a hydrophobic dodecyl chain. The RAFT emulsion polymerization of DEVBP was well–controlled with a narrow molecular size distribution. Dynamic light scattering and confocal laser scanning microscopy were used to examine the PEG-b-PDVBP submicron particles, and the length of the PEG chain (hydrophilic block) was found to affect the particle size distribution and molecular weight distribution. The submicron particle size increased with increasing degree of polymerization (35, 65, and 130), and precipitation was observed at a high degree of polymerization (DP) using low molecular weight PEG-TTC (DP 130, A3). The flame retardant properties of the PEG-b-PDVBP were evaluated by thermogravimetric analysis (TGA) and micro cone calorimeter (MCC). In the combustion process, the residue of PEG-b-PDEVBP were above 500 °C was observed (A1 ~ B3, 27 ~ 38%), and flame retardant effect of PEG-b-PDEVBP submicron particles/PVA composite were confirmed by increasing range of temperature and decreasing total heat release with increasing contents of PEG-b-PDEVBP. The PEG-b-PDEVBP submicron particles can provide flame retardant properties to aqueous, dispersion and emulsion formed organic/polymer products.

Polymerization‐Induced Thermal Self‐Assembly of Functional and Thermo‐Responsive Diblock Copolymer Nano‐Objects via RAFT Aqueous Polymerization

AbstractThe polymerization‐induced self‐assembly (PISA) of amphiphilic diblock copolymer nano‐objects, which are synthesized via reversible addition‐fragmentation chain‐transfer (RAFT) aqueous polymerization, is discussed. First, the effectiveness of the (S)‐2‐(ethyl propionate)‐(O‐ethyl xanthate) as a RAFT chain transfer agent for the polymerization of N,N‐dimethylacrylamide (DMAm) yielding a water‐soluble macro RAFT agent is investigated. In a second step, poly(DMAm) macro‐CTA is chain‐extended with acrylate monomers in water inducing a PISA process. Besides the use of pentafluorophenyl acrylate (PFPA) as core‐forming block, the thermo‐responsive nature of N‐isopropylacrylamide (NIPAm) and the reactive character of pentafluorophenyl acrylate (PFPA) for a subsequent post‐modification is exploited. Monomer conversion and reaction kinetics are determined via nuclear magnetic resonance spectroscopy, while gel permeation chromatography is used to evaluate the molecular weight distribution of the polymers. The obtained spherical nanostructures are analyzed via dynamic light scattering, scanning electron microscopy, transmission electron microscopy and atomic force microscopy.

Preparation of pH- and reductive-responsive prodrug nanoparticles via polymerization-induced self-assembly

pH- and reductive-responsive prodrug nanoparticles are constructed via a highly efficient strategy, polymerization-induced self-assembly (PISA). First, reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(diisopropylamino) ethyl methacrylate (DIPEMA) and camptothecin prodrug monomer (CPTM) using biocompatible poly( N -(2-hydroxypropyl) methacrylamide) (PHPMA-CPDB) as the macro RAFT agent is carried out, forming prodrug diblock copolymer PHPMA-P(DIPEMA- co -CPTM). Then, simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation are achieved via RAFT dispersion polymerization of benzyl methacrylate (BzMA) using the PHPMA-P(DIPEMA- co -CPTM) as the macro RAFT agent. The prodrug nanoparticles have three layers, the biocompatible shell (PHPMA), the drug-conjugated middle layer (P(DIPEMA- co -CPTM)) and the PBzMA core, and relatively high concentration (250 mg/g). The prodrug nanoparticles can respond to two stimuli (reductive and acidic conditions). Due to reductive microenvironment of cytosol, the cleavage of the conjugated camptothecin (CPT) within the prodrug nanoparticles could be effectively triggered. pH-Induced hydrophobic/hydrophilic transition of the PDIPEMA chains results in faster diffusion of GSH into the CPTM units, thus accelerated release of CPT is observed in mild acidic and reductive conditions. Cell viability assays show that the prodrug nanoparticles exhibit well performance of intracellular drug delivery and good anticancer activity.

Surfactant-free nanoencapsulation using reactive oligomers obtained by reversible addition fragmentation chain transfer polymerization of styrene and maleic anhydride

Reactive oligomers of styrene–maleic anhydride having controlled architecture were prepared using reversible addition fragmentation chain transfer (RAFT) polymerization. The co-oligomers were characterized by FTIR, Raman, NMR and GPC. The arrangement of co-monomers (i.e. the architecture) in the co-oligomeric RAFT agents could be controlled by changing the molar feed ratio of styrene to maleic anhydride in the range of 1–5.25 under controlled polymerization conditions. Non-alternating (homopolymer) blocks of styrene could be suppressed even at high mole ratios > 1 and the resultant co-oligomeric RAFT agents consisting of mainly alternating (SMS) and semi-alternating (SSM) sequences of styrene and maleic anhydride were obtained. These macro RAFT agents behaved as efficient reactive surfactants and their self-aggregation behavior was greatly influenced by their architecture. These could be successfully used for surfactant-free nanoencapsulation of active hydrophobic materials, such as n-octadecane, indicating their suitability for various applications.

Heparin-Mimicking Sulfonated Polymer Nanoparticles via RAFT Polymerization-Induced Self-Assembly.

Heparin plays a significant role in wound healing and tissue regeneration applications, through stabilization of fibroblast growth factors (FGF). Risks associated with batch-to-batch variability and contamination from its biological sources have led to the development of synthetic, highly sulfonated polymers as promising heparin mimics. In this work, a systematic study of an aqueous polymerization-induced self-assembly (PISA) of styrene from poly(2-acrylamido-2-methylpropane sodium sulfonate) (P(AMPS)) macro reversible addition-fragmentation chain transfer (macro-RAFT) agents produced a variety of spherical heparin-mimicking nanoparticles, which were further characterized with light scattering and electron microscopy techniques. None of the nanoparticles tested showed toxicity against mammalian cells; however, significant hemolytic activity was observed. Nonetheless, the heparin-mimicking nanoparticles outperformed both heparin and linear P(AMPS) in cellular proliferation assays, suggesting increased bFGF stabilization efficiencies, possibly due to the high density of sulfonated moieties at the particle surface.

Aqueous Polymeric Hollow Particles as an Opacifier by Emulsion Polymerization Using Macro-RAFT Amphiphiles.

A robust polymerization technique that enables the surfactant-free aqueous synthesis of a high solid content latex containing polymeric hollow particles is presented. Uniquely designed amphiphilic macro-reversible addition fragmentation chain transfer (RAFT) copolymers were used as sole stabilizers for monomer emulsification as well as for free-radical emulsion polymerization. The polymerization was found to be under RAFT control, generating various morphologies from spherical particles, wormlike structures to polymer vesicles. The final particles were dominantly polymeric vesicles which had a substantially uniform and continuous polymer layer around a single aqueous filled void. They produced hollow particles once dried and were successfully used as opacifiers to impart opacity into polymer paint films. This method is simple, can be performed in a controllable and reproducible manner, and may be performed using diverse procedures.

Template‐Directed Fabrication of Anatase TiO2 Hollow Nanoparticles and Their Application in Photocatalytic Degradation of Methyl Orange

Polymerization‐induced self‐assembly (PISA) was used to fabricate polymeric nanoparticles via reversible addition‐fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate (BzMA) using diblock copolymer poly(glycerol monomethacrylate)‐block‐poly(2‐dimethylaminoethyl methacrylate) (PGMMA‐ PDMAEMA‐CTA) as the macro RAFT agent. The dispersion of polymeric nanoparticles with a final concentration of about 210 mg/g (solid content of 21%) was obtained via this efficient method (PISA). The resultant polymeric nanoparticles consisting of corona‐shell‐core three layers with weak polyelectrolyte PDMAEMA as the shell were used as sacrificial template to fabricate TiO2 hollow nanoparticles. The negatively charged titanium precursor was absorbed into the PDMAEMA shell via the electrostatic interaction, and hydrolyzed to form polymer/TiO2 hybrid nanoparticles. Anatase TiO2 hollow nanoparticles were formed after removing the polymeric templates by calcination at 550 °C. The experiments of photocatalytic degradation of methyl orange showed that the resultant anatase TiO2 hollow nanoparticles had high photocatalytic activity and good reusability.

Effect of rGO on polymer-dispersed liquid crystal fabricated by RAFT polymerisation

In this study, we demonstrated that doping polymer matrix with a small amount of reduced graphene oxide (rGO) component (0.05–0.2%) had significant influence on the polymerisation kinetics and electro-optical performances of polymer-dispersed liquid crystal films (PDLCs) fabricated with macro reversible addition-fragmentation chain transfer agents. The effects of rGO content were studied in terms of morphology, compound viscosity, polymer conductivity, polymerisation kinetics and driving voltage of PDLCs. The results exhibited that higher rGO content increased the compound viscosity and the entire process proceeded slowly. Furthermore, the addition of rGO increased the polymer conductivity and local electric field, and reduced the saturation voltage as well as the threshold voltage from 27.3 to 19.5 V and 13.2 to 6.41 V, respectively.

Synthesis and characterization of novel ABA-type azobenzene-containing tri-block copolymers from telechelic polystyrene

The telechelic polystyrene (tPS) was used as a macro-reversible addition fragmentation chain transfer (RAFT) agent to prepare the ABA-type tri-block copolymers (TBCs), poly{4-[4-(11-acryloyloxyundecyloxy)phenylazo]benzonitrile}-b-polystyrene-b-poly{4-[4-(11-acryloyloxyundecyloxy)phenylazo]benzonitrile} [poly(AUPAB)-b-PS-b-poly(AUPAB)] with 4-[4-(11-acryloyloxyundecyloxy)phenylazo]benzonitrile (AUPAB) as a monomer by the RAFT polymerization process. The poly(AUPAB) was used as a reference to probe the role of polystyrene block in poly(AUPAB)-b-PS-b-poly(AUPAB) macromolecular chain. The TBCs were characterized by spectral techniques, thermal analysis, and polarizing optical microscopic studies and compared the results with individual blocks, poly(AUPAB), and tPS. The TBCs exhibited higher thermal stability and liquid crystal–isotropic phase transition peak temperature (TLC-I), and glass transition temperature (Tg) values compared to the poly(AUPAB). TBC TLC-I value was dependent on the AUPAB wt% in macromolecular chain. Furthermore, the acquired results by optical microscopy suggest that after incorporation of the polystyrene block in acrylate-based pendant azobenzene polymer chain resulted in lower domain size of focal conic texture, which is characteristic of smectic-A liquid crystalline phase compared to the homopolymer. The photophysical properties of the TBCs were similar to those of the poly(AUPAB). Microphase-separated nano-segregation was observed in annealed thin films of TBCs.

Reversible addition-fragmentation chain transfer polymerization of vinyl acetate and vinyl pivalate in supercritical carbon dioxide

Two highly supercritical CO2-soluble, poly(vinyl acetate) (PVAc)-based macro-reversible addition-fragmentation chain transfer (RAFT) agents were synthesized. The RAFT agents were used for the first time in RAFT/macromolecular design via the interchange of xanthates (MADIX) and polymerization of vinyl acetate (VAc) and vinyl pivalate (VPi) in supercritical carbon dioxide (scCO2). A homopolymer PVAc and a block copolymer PVAc-b-PVPi made by RAFT/MADIX polymerization were characterized, and the effects of time and RAFT agents on polymerization were examined. For the 8.4 wt% RAFT agent in VAc, the molecular mass (M n ) of homopolymer PVAc was 26,000 g mol−1 and PDI was 1.35. For the copolymerization of VPi using 9.8 wt% PVAc-RAFT agent in VPi for 24 h, the M n and PDI of PVAc-b-PVPi reached 32,400 g mol−1 and 1.42, respectively. These results suggest that the polydispersity can be controlled during the clean production of PVAc and PVPi by RAFT/MADIX polymerization in scCO2.

Biomimetic star-shaped porphyrin-cored poly(l-lactide)-b-glycopolymer block copolymers for targeted photodynamic therapy

Porphyrin-cored poly(l-lactide) (SPPLA) was successfully synthesized from ring-opening polymerization (ROP) of l-lactide initiated with porphyrin core. Then, SPPLA was coupled with benzylsulfanylthiocarbonylsufanylpropionic acid (BSPA), and a macro-reversible addition-fragmentation chain transfer (macroRAFT) polymerization agent SPPLA-BSPA was obtained. Finally, star-shaped porphyrin-cored poly(l-lactide)-b-poly(gluconamidoethyl methacrylate) (SPPLA-b-PGAMA) block copolymers were synthesized via RAFT of unprotected gluconamidoethyl methacrylate (GAMA) in 1-methyl-2-pyrrolidinone (NMP) solution at 70 °C. The structure of this block copolymer was thoroughly studied by nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). Under the irradiation, such SPPLA-b-PGAMA copolymer exhibits efficient singlet oxygen generation and indicates high fluorescence quantum yields. Notably, with UV–vis and dynamic light scattering (DLS) analysis, SPPLA-b-PGAMA showed a very specific recognition with concanavalin A (ConA). Particularly, MTT shows that the cytotoxicity of SPPLA-b-PGAMA against COS-7 cells was very low and, when given a longer irradiation time, more BEL-7402 cancer cells died, which will be investigated in this study.

Spiropyran-Based Hyperbranched Star Copolymer: Synthesis, Phototropy, FRET, and Bioapplication

Photo- and pH-responsive amphiphilic hyperbranched star copolymers, poly(6-O-methacryloyl-1,2;3,4-di-O-isopropylidene-d-galactopyranose)[poly(2-(N,N-dimethylaminoethyl) methacrylate)-co-poly(1'-(2-methacryloxyethyl)-3',3'-dimethyl-6-nitro-spiro(2H-1-benzo-pyran-2,2'-indoline))](n)s [HPMAlpGP(PDMAEMA-co-PSPMA)(n)], were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of the DMAEMA and the SPMA using hyperbranched PMAlpGP as a macro RAFT agent. In aqueous solution, the copolymers self-assembled to form core-shell micelles with HPMAlpGP core and PDMAEMA-co-PSPMA shell. The hydrophobic fluorescent dye nitrobenzoxadiazolyl derivative (NBD) was loaded into the spiropyran-containing micelles. The obtained micelles not only have the photochromic properties, but also modulate the fluorescence of NBD through fluorescence resonance energy transfer (FRET), which was also observed in living cells. Slight fluorescence intensity decrease of the spiropyran in merocyanine (ME) form was observed after five UV-visible light irradiation cycles. The cytotoxicity of the HPMAlpGP(PDMAEMA-co-PSPMA)(n) micelles was lower than that of 25k PEI. All the results revealed that these photoresponsive nanoparticles are a good candidate for cell imaging and may find broad applications in biological areas such as biological diagnosis, imaging, and detection.

Synthesis of Surface-Functionalized Poly(styrene-co-butadiene) Nanoparticles via Controlled/Living Radical Mini-emulsion Copolymerization Stabilized by Ammonolyzed Poly(styrene-alt-maleic anhydride) (SMA) RAFT Agent

A process for reversible addition-fragmentation chain transfer (RAFT) radical polymerization in a mini-emulsion system stabilized by ammnolyzed poly(styrene-alt- maleic anhydride) copolymer (SMA) as an amphiphilic macro RAFT agent has been applied to the copolymerization of styrene and butadiene to prepare nanoparticles. First, for the RAFT polymerization of styrene, the results of molecular weights (Mns) and polydispersity index (PDIs) determined by GPC showed that the RAFT mini-emulsion polymerization of styrene exhibited good controlled/living nature with a lower degree of aminolysis (∼30%). Second, for the copolymerization of styrene and butadiene, before the gel point the molecular weight growth was followed during the polymerization by GPC and the results revealed that the GPC curve moves to the higher molecular weight indicating the formation of the copolymer. At low conversion, molecular weights (Mns) are in good agreement with theoretical prediction. The microphase separation of the copolymer nanoparticles was confirmed by transmission electron microscopy (TEM).

Preparation of macro reversible addition-fragmentation chain transfer copolymers and their application in pigment dispersion

By using reversible addition–fragmentation chain transfer (RAFT) controlled polymerization, we prepared styrene–maleic anhydride copolymers with RAFT end groups. The resulting copolymers were characterized by Fourier transform infrared and 1H-NMR spectroscopy. The molecular weights and molecular weight distributions were determined with gel permeation chromatography. The dispersing ability of the hydrolyzed macro reversible addition–fragmentation chain transfer (macro-RAFT) copolymers was evaluated. An organic phthalocyanine blue pigment (P.B.15 : 3) was dispersed with the macro-RAFT copolymers by vigorous stirring and ultrasonic processing. The properties (particle size and polydispersity index) of the pigment dispersions were measured. The results show that with prolonged ultrasonication time, the particle size and polydispersity index decreased first and increased slightly later. There were no remarkable differences in the particle size and particle size distribution between the macro-RAFT copolymer and poly(styrene-co-maleic anhydride) dispersed pigment dispersions. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Macro reversible addition–fragmentation chain transfer agent mixture as a means to enhance the electro‐optical performance of polymer‐dispersed liquid crystals

AbstractMacro reversible addition–fragmentation chain transfer (RAFT) agents, i.e. RAFT polystyrene (RAFT‐PS) and RAFT poly(n‐butyl acrylate) (RAFT‐PBA), were mixed. Polymer‐dispersed liquid crystals (PDLCs) were prepared using the mixture together with methyl acrylate and liquid crystal E7. The electro‐optical properties of the PDLCs obtained were investigated. The results showed that the advantages of the electro‐optical properties of RAFT‐PS‐ and RAFT‐PBA‐dependent PDLCs could be combined in RAFT agent mixture‐dependent PDLCs. Copyright © 2011 Society of Chemical Industry

Preparation of Self-Crosslinking Core-Shell Latex at Ambient Temperature

A reversible addition fragmentation chain transfer (RAFT) agent, 2- (dodecylthiocarbonothioylthio)propanoic acid (RAFT-1), was synthesized and characterized. Equimolar doses of acrylic acid (AA) and n-butyl acrylate were successively polymerized in the presence of RAFT-1 to give an amphiphilic macro RAFT agent (RAFT-2), which had a calculated average degree of polymerization of ten. Core-shell poly (butyl acrylate-co-diacetoneacrylamide) latex was prepared by using RAFT-2 as a reactive surfactant. The latex was narrowly distributed and very stable, which had a solid concentration as high as 45 wt.% and an average diameter of about 50 nm, Latex films were prepared with the core-shell emulsion and small amount of cross-linking agent, adipic dihydrazide. Results showed that cross-linking reaction occurred with the evaporation of water. The resulting cross-linked latex film was tough and transparent.

One-pot synthesis of polymeric nanomaterials via RAFT dispersion polymerization induced self-assembly and re-organization

A novel strategy for preparation of multiple nanostructural materials, which is the creation of such materials directly from controlled radical dispersion polymerization in one pot, has been developed. In the formation of polymeric nanomaterials, the chain length ratio of the hydrophobic to hydrophilic blocks is altered continuously, which induces two phase transitions, phase separation to form spherical micelles and re-organization of the resulting spheres to yield multiple morphologies including nanorods, nanotubes, vesicles and doughnuts. This is quite different from self-assembly of the block copolymer in a selective solvent, where nature and solubility parameter of the solvents are changed. In the reversible addition-fragmentation chain transfer (RAFT) polymerization of styrene in methanol using poly(4-vinylpyridine) as macro RAFT agent, the resultant polymeric nanomaterials with various morphologies coexisted generally, however, uniform nanowires and vesicles could be prepared by appropriately selecting concentration of monomer and feed ratio, as well as by strict control of reaction conditions. One advantage of this strategy is that the nanomaterials with a concentration as high as 0.5 g mL−1 can be achieved, this provides possibility for studying extensive applications of the various nanomaterials.

Preparation and Characterization of Nano-Sized Silver Particles

This study presents an approach to prepare nano-sized silver particles via in-situ reduction process. First, a reversible addition fragmentation chain transfer (RAFT) agent, 2-(dodecylthiocarbonothioylthio)propanoic acid (DTPA), was synthesized and characterized. Acrylic acid (AA) was polymerized in the presence of DTPA to afford an amphiphilic macro RAFT agent (DTPA-AC-10) with a calculated average degree of polymerization of ten. Latex particles with a sodium salt-containing shell were prepared by using sodium DTPA-AC-10 as a reactive surfactant. Then, through silver ion-exchange processs of the latex particles, the latex particles with silver salt at the surface were obtained. Finally, the silver salt at the particle surface was reduced through chemical reduction to give the silver-coated polymer particles. Dynamic Laser Scattering (DLS) was used to measure the particle size and distribution; X ray diffraction analysis (XRD) was employed to characterize the formed silver crystal in the particle surface. The diameter of the silver particles was about 76 nm and was narrowly distributed. The silver nanoparticles might be used to prepare conductive ink for ink-jet applications.