macro-RAFT Agent Research Articles

Glycopolymer Self-Assemblies with Gold(I) Complexed to the Core as a Delivery System for Auranofin

A new glycomonomer 1 containing a thioacetate group in the anomeric position and mimicking the thiosugar ligand of the gold-based drug auranofin was designed and synthesized in four steps from d-glucose. Both CPADB-mediated homopolymerization and chain extension of a hydrophilic poly(OEGMEMA) macroRAFT agent were well-controlled with dispersities (Đ) below 1.2, highlighting the suitability of thioacetate as a thiol protecting group in RAFT polymerization. Using the homopolymer as a test system, the thioacetate protective groups were selectively removed using hydrazine acetate, and AuPEt3Cl was subsequently complexed to the exposed thiols to generate a polymeric auranofin analogue with 52% complexation efficiency. Extension of this successful procedure to three block copolymers with differing hydrophobic block lengths, poly(OEGMEMA)34-b-poly(1)47, poly(F-OEGMEMA)32-b-poly(1)27, and poly(F-OEGMEMA)32-b-poly(1)7 (where “F” in the last two indicates the incorporation of 2 wt % fluorescein methacrylate into th...

Macro-RAFT agent mediated dispersion polymerization: the monomer concentration effect on the morphology of the in situ synthesized block copolymer nano-objects

The great effect of the monomer concentration on the block copolymer morphology under dispersion RAFT polymerization is found and demonstrated.

Doubly thermo-responsive nanoparticles constructed with two diblock copolymers prepared through the two macro-RAFT agents co-mediated dispersion RAFT polymerization

Doubly thermo-responsive nanoparticles constructed with two diblock copolymers were prepared, and the nanoparticles exhibit a two-step phase-transition with increasing temperature.

Fast RAFT aqueous polymerization in a continuous tubular reactor: consecutive synthesis of a double hydrophilic block copolymer

Utilizing a continuous tubular reactor, well-defined double hydrophilic block copolymer PSPMA-b-PPEGMA was successfully synthesized with an extremely high monomer conversion in water without handling the intermediate macro-RAFT agent.

Macro-RAFT agent mediated dispersion copolymerization: a small amount of solvophilic co-monomer leads to a great change

The macro-RAFT agent mediated dispersion copolymerization of two monomers is performed, and the block copolymer morphology can be easily tuned.

Study of Solution Polymerization of Styrene in the Presence of Poly(ethylene glycol)-RAFT Agents Possessing Benzoyl Xanthate Derivatives

In this work, Macro-Reversible addition fragmentation termination (RAFT) agents based on poly(ethylene glycol) (PEG) possessing different molecular weights and bearing benzoyl xanthate moieties were synthesized by the reaction of PEG potassium xanthate salts with benzoyl chloride, 4-methyl benzoyl chloride and 4-chloro benzoyl chloride. Controlled free radical polymerization of the styrene were carried out in the presence of these macro-RAFT agents using 2,2′-azobisizsobutyronitrile (AIBN) as an initiator to yield PS-b-PEG-b-PS block copolymers. The linear kinetic plot ln [M]o/[M] vs. polymerization time indicated that was first order with reference to monomer concentration. The block copolymerization possessed controlled/living character. The controlled character of the RAFT polymerization of the styrene was confirmed by the formation of narrow polydispersity of the polymers, linear increases in the molecular weight with polymerization time and molecular weight of the products that agreed well with theoretical values. Polymers having relatively narrow molecular weight distributions and predetermined number average molecular weights were obtained by the RAFT polymerization of the styrene. However, molecular weights of the polymers deviated from the theoretical values when low molecular weight RAFT agents are used. The results indicate that PEG benzoyl xanthate RAFT agents can more efficiently control the polymerization comparing methyl or chlorobenzoyl derivatives. The block copolymers were characterized by spectroscopic and GPC methods.

A New Strategy To Synthesize Temperature- and pH-Sensitive Multicompartment Block Copolymer Nanoparticles by Two Macro-RAFT Agents Comediated Dispersion Polymerization

Multicompartment block copolymer nanoparticles (MCBNs) arouse great interest due to their special structure and wide application. However, synthesis of MCBNs suffers from great inconvenience and difficulty. In this contribution, an efficient strategy to prepare well-defined temperature- and pH-sensitive MCBNs constructed with two diblock copolymers of poly(4-vinylpyridine)-b-polystyrene (P4VP-b-PS) and poly(N-isopropylacrylamide)-b-polystyrene (PNIPAM-b-PS) through the two macro-RAFT agents comediated dispersion polymerization is proposed. In this two macro-RAFT agents comediated dispersion polymerization, two macro-RAFT agents having similar polymerization degree are simultaneously adopted, and onset micellization of PNIPAM-b-PS and P4VP-b-PS occurs simultaneously to form mixed corona–core nanoparticles containing a PNIPAM/P4VP mixed corona and a PS core. In neutral water at room temperature, the corona-forming P4VP block deposits on the PS core to form MCBNs, which contain a solvophobic PS core, discrete P4VP nodules on the PS core, and a solvophilic PNIPAM corona. The parameters affecting the MCBNs structure are investigated. It is found that the higher percent of the poly(4-vinylpyridine) trithiocarbonate (P4VP-TTC) macro-RAFT agent and the shorter PS block, the larger the size of the P4VP nodules on MCBNs. The synthesized MCBNs are temperature- and pH-responsive. Through the phase transition of the temperature-responsive PNIPAM block and the pH-responsive P4VP block, the morphology of MCBNs can be changed. Our strategy of the two macro-RAFT agents comediated dispersion polymerization is believed sufficiently to overcome the inconvenience and difficulty in synthesis of well-defined MCBNs.

One-Step Synthesis of Triblock Copolymers via Simultaneous Reversible-Addition Fragmentation Chain Transfer (RAFT) and Ring-Opening Polymerization Using a Novel Difunctional Macro-RAFT Agent Based on Polyethylene Glycol

One-step synthesis of the triblock copolymers was carried out by reversible addition–fragmentation chain transfer (RAFT) polymerization of methyl methacrylate (MMA) and ring-opening polymerization (ROP) of β-butyrolactone (BL) or ϵ-caprolactone (CL) using a novel difunctional macro-RAFT agent. For this purpose, primarily PEG-Br (polyethylene glycol bromine) was obtained by using 3-bromopropanoyl chloride and PEGs (polyethylene glycols) with different molecular weights. Then, macro-RAFT agent was synthesized by the reaction of potassium ethyl xanthogenate and PEG-Br. By using macro-RAFT agent, poly(MMA-b-EG-b-BL), and poly(MMA-b-EG-b-CL) triblock copolymers were synthesized by changing some polymerization conditions such as monomer/initiator concentration, polymerization time. The effect of the reaction conditions on the polydispersity and molecular weights were also investigated. The block lengths of the triblock copolymers were calculated by using 1H-nuclear magnetic resonance (1H-NMR) spectra. It was observed that the block length could be altered by varying the monomer and initiator concentrations. The characterization of the products were achieved using 1H-NMR, Fourier-transform infrared spectroscopy (FTIR), gel-permeation chromatography (GPC), thermogravimetric analysis (TGA), and fractional precipitation (γ) techniques.

RAFT polymerization kinetics and polymer characterization of P3HT rod-coil block copolymers

Here an in-depth analysis of reversible addition–fragmentation chain transfer (RAFT) polymerization kinetics is reported in order to provide better definition of poly(3-hexylthiophene) (P3HT) rod–coil block copolymers thru a more thorough understanding of the RAFT polymerization of the coil block. To this end, a new P3HT macroRAFT agent is synthesized and utilized to prepare rod–coil block copolymers with P3HT and poly(styrene), poly(tert-butylacrylate), and poly(4-vinylpyridine), and the RAFT polymerization kinetics of each system are fully detailed. This is achieved by a comprehensive analysis of characterization data from 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, and matrix-assisted laser desorption ionization time of flight spectroscopy, which are used as complementary techniques in order to address difficulties in accurately characterizing the synthesized polymer systems. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 3575–3585

Synthesis of Multicompartment Nanoparticles of Block Copolymer through Two Macro-RAFT Agents Co-Mediated Dispersion Polymerization.

A new and efficient strategy to synthesize multicompartment block copolymer nanoparticles (MCBNs) by two macro-RAFT agents comediated dispersion polymerization is proposed. By simultaneously employing two macro-RAFT agents in dispersion RAFT polymerization, one-pot synthesis of well-defined MCBNs constructed with two diblock copolymers of poly(tert-butyl methyl acrylate)-block-polystyrene (PtBMA-b-PS) and poly[N-(4-vinylbenzyl)-N,N-diethylamine]-block-polystyrene (PVEA-b-PS) is achieved. These MCBNs contain a PS core and discrete PVEA and/or PtBMA nodules on the PS core. By changing the ratio of the two macro-RAFT agents or the polymerization degree of the solvophobic block in the two diblock copolymer mixture, the structure of MCBNs can be tuned. Our strategy overcomes the inconvenience and difficulty in synthesis of MCBNs, and it introduces a valid way to prepare well-defined MCBNs constructed with two or more diblock copolymers.

Synthesis of graphene-polystyrene nanocomposites via RAFT polymerization

Synthesis of graphene-polymer nanocomposites is of current interest due to their exceptionally physical and chemical properties. However, the ability to produce conductive inks/coatings retaining the properties of the graphene is still a major challenge. In this study, functionalized polydopamine-coated reduced graphene oxide (PDA/RGO) was reacted with a RAFT agent, 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT), to form macro-RAFT agents via an esterification reaction. The chemistry and kinetics of RAFT living/controlled polymerization of styrene was examined from the surface of these macro-RAFT agents to form polystyrene-grafted PDA/RGO (PS-g-PDA/RGO). By examination of the kinetics and GPC traces of the free and grafted polymer, living/controlled polymerization was confirmed. To examine the utility of this approach, the synthesized PS-g-PDA/RGO samples containing different amounts of grafted PS were employed in the preparation of graphene-PS nanocomposites by mixing them with commercial PS. Graphene was found to be well distributed in the PS matrix by this approach, increasing the decomposition temperature range. This research provides an efficient route towards the design and development of value-added functional graphene-PS composites.

Ab Initio Emulsion and Miniemulsion Polymerization of Styrene Mediated by a Cyclohexenyl-Functionalized Amphiphilic RAFT Agent

We designed and used a cyclohexenyl-functionalized amphiphilic macromolecular reversible addition–fragmentation chain transfer (macro-RAFT) agent as surfactant and polymerization mediator for (mini)emulsion polymerization of styrene (St), aiming at synthesizing nanoparticles with vinyl-enriched surface and well-defined polymer chains. Unexpectedly, the pendent cyclohexenyl units in the macro-RAFT agent were found to undergo significant copolymerization with St exclusively during the nucleation period in the ab initio emulsion polymerization, leading to the consumption of cyclohexenyl groups, positive deviation of molecular weights, and broad molecular weight distributions. By contrast, in miniemulsion polymerization, the radical polymerization exhibited superb selectivity toward St monomers relative to the pendent cyclohexene vinyl units just as in the solution polymerization. The obtained polymer chains retained designed molecular weights, low polydispersity indexes, and quantitative cyclohexenyl functio...

Synthesis and self-assembly of stimuli-responsive amphiphilic block copolymers based on polyhedral oligomeric silsesquioxane

A novel POSS-containing methacrylate monomer (HEMAPOSS) was fabricated by extending the side chain between polyhedral oligomeric silsesquioxane (POSS) unit and methacrylate group, which can efficiently decrease the steric hindrance in free-radical polymerization of POSS-methacrylate monomer. POSS-containing homopolymers (PHEMAPOSS) with a higher degree of polymerization (DP) can be prepared using HEMAPOSS monomer via reversible addition–fragmentation chain transfer (RAFT) polymerization. PHEMAPOSS was further used as the macro-RAFT agent to construct a series of amphiphilic POSS-containing poly(N, N-dimethylaminoethyl methacrylate) diblock copolymers, PHEMAPOSS-b-PDMAEMA. PHEMAPOSS-b-PDMAEMA block copolymers can self-assemble into a plethora of morphologies ranging from irregular assembled aggregates to core-shell spheres and further from complex spheres (pearl-necklace-liked structure) to large compound vesicles. The thermo- and pH-responsive behaviors of the micelles were also investigated by dynamic laser scattering, UV spectroscopy, SEM, and TEM. The results reveal the reversible transition of the assembled morphologies from spherical micelles to complex micelles was realized through acid-base control. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2669-2683

Synthesis of Organic/Inorganic Polyhedral Oligomeric Silsesquioxane-Containing Block Copolymers via Reversible Addition–Fragmentation Chain Transfer Polymerization and Their Self-Assembly in Aqueous Solution

Polyhedral oligomeric silsesquioxane (POSS)-containing homopolymers (PHEMAPOSS) with a high degree of polymerization (DP) were synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization. PHEMAPOSS was used as a macro-RAFT agent to construct a series of amphiphilic diblock copolymers, PHEMPOSS-b-PMAA (poly (methyl methacrylate)), which possessed a different length of hydrophilic chains. The self-assembly behavior of PHEMPOSS-b-PMAA in aqueous solution was studied by transmission electron microscopy (TEM), atomic force microscopy (AFM), and dynamic light scattering (DLS), respectively. The results showed that PHEMAPOSS45-b-PMAA523 forms typical core–shell spherical micelles where the hydrophobic PHEMAPOSS blocks as the core and hydrophilic PMAA blocks as the shell. With increasing PMAA chain length, PHEMAPOSS45-b-PMAA1173 with a longer PMAA chain self-assembled into irregular aggregates with POSS moieties dispersed in the aggregates. On the other hand, PHEMAPOSS45-b-PMAA308 with ...

A pH-sensitive micelle for codelivery of siRNA and doxorubicin to hepatoma cells

Aiming to effectively codeliver chemotherapeutic drugs (DOX) and siRNA (BCL-2 siRNA) into tumor cells, well-defined triblock copolymers composed of hydrophilic and hydrophobic blocks were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The poly(ethylene glycol) (PEG) macroRAFT agent and two pH-sensitive monomers (2-(diethylamino)ethyl methacrylate, DEA and 2-(dimethylamino)ethyl methacrylate, DMA) were used for synthesizing the copolymers consisting of pH-sensitive PDEA, PDMA and PEG blocks. At pH 10, the copolymer in aqueous solution self-assembled into a micelle with hydrophobic core consisting of PDEA and PDMA for doxorubicin (DOX) encapsulation, owing to the deprotonation of the side tertiary amino groups. At neutral pH, the hydrophobic core became porous and positively charged to allow siRNA complexation due to PDMA solubilization (the pKa of PDMA is around 8.0). Inside the acidic lysosomal compartments, PDEA was protonated and thus became hydrophilic to result in rapid release of DOX. Moreover, existence of two pH-sensitive blocks PDMA and PDEA endowed the copolymer with proton buffering effect that facilitated lysosomal escape of nanocomplex and siRNA release inside cells. Our results showed that the two codelivered therapeutic agents acted synergistically on the human hepatic carcinoma HepG2 cells to induce apoptosis in a highly effective manner.

Emulsion Polymerization of Vinyl Acetate in the Presence of Different Hydrophilic Polymers Obtained by RAFT/MADIX

The surfactant-free emulsion polymerization of vinyl acetate (VAc) was achieved using RAFT/MADIX-mediated polymerization-induced self-assembly (PISA) process in water. First, well-defined hydrophilic macromolecular RAFT agents (macroRAFT) bearing a xanthate chain end were synthesized by RAFT/MADIX polymerization of N-vinylpyrrolidone (NVP) and N-acryloylmorpholine (NAM) or by post-modification of commercial poly(ethylene glycol). Chain extension of the macroRAFT with VAc in water led to the block copolymer nanoscale organization and the subsequent formation of stable and isodisperse PVAc latex nanoparticles with high solids content (35–37 wt %). The influence of various parameters, including the nature and functionality of the macroRAFT agent precursor, on the polymerization kinetics and particle morphology was also studied.

Doubly thermoresponsive brush-linear-linear ABC triblock copolymer nanoparticles prepared through dispersion RAFT polymerization

Doubly thermoresponsive ABC brush-linear-linear triblock copolymer nanoparticles of poly[poly(ethylene glycol) methyl ether vinylphenyl]-block-poly(N-isopropylacrylamide)-block-polystyrene [P(mPEGV)-b-PNIPAM-b-PS] containing two thermoresponsive blocks of poly[poly(ethylene glycol) methyl ether vinylphenyl] [P(mPEGV)] and poly(N-isopropylacrylamide) (PNIPAM) are prepared by macro-RAFT agent mediated dispersion polymerization. The P(mPEGV)-b-PNIPAM-b-PS nanoparticles exhibit two separate lower critical solution temperatures or phase-transition temperatures (PTTs) corresponding to the linear PNIPAM block and the brush P(mPEGV) block in water. Upon temperature increasing above the first and then the second PTT, the hydrodynamic diameter (Dh) of the triblock copolymer nanoparticles undergoes an initial shrinkage at the first PTT and the subsequent shrinkage at the second PTT. The effect of the chain length of the PNIPAM block on the thermoresponsive behavior of the triblock copolymer nanoparticles is investigated. It is found that, the longer chains of the thermoresponsive PNIPAM block, the greater contribution on the transmittance change of the aqueous dispersion of the triblock copolymer nanoparticles. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2266–2278

Photodegradable neutral-cationic brush block copolymers for nonviral gene delivery.

We report on the fabrication of a photodegradable gene-delivery vector based on PEO-b-P(GMA-g-PDMAEMA) neutral-cationic brush block copolymers that possess cationic poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) brushes for DNA compaction, poly(ethylene oxide) (PEO) as a hydrophilic block, and poly(glycidyl methacrylate) (PGMA) as the backbone. The PEO-b-P(GMA-g-PDMAEMA) copolymers were synthesized through the combination of reversible addition-fragmentation transfer (RAFT) polymerization and postmodification. A photocleavable PEO-based macroRAFT agent was first synthesized; next, the PEO-b-PGMA block copolymer was prepared by RAFT polymerization of GMA; this was followed by a click reaction to introduce the RAFT initiators on the side chains of the PGMA block; then, RAFT polymerization of DMAEMA afforded the PEO-b-P(GMA-g-PDMAEMA) copolymer. The obtained neutral-cationic brush block copolymer could effectively complex plasmid DNA (pDNA) into nanoparticles at an N/P ratio (i.e., the number of nitrogen residues per DNA phosphate) of 4. Upon UV irradiation, pDNA could be released owing to cleavage of the pDNA-binding cationic PDMAEMA side chains as well as the nitrobenzyl ester linkages at the diblock junction point. In addition, in vitro gene transfection results demonstrated that the polyplexes could be effectively internalized by cells with good transfection efficiency, and the UV irradiation protocol could considerably enhance the efficiency of gene transfection.

Synthesis of poly(acrylic acid) grafted carbon black and its application for sensing ethanol

Surface initiated reversible addition-fragmentation chain transfer (RAFT) polymerization techniques have been used to produce poly (acrylic acid) (PAA)-grafted carbon black (CB) nanoparticles. The surface of CB nanoparticles was functionalized in the presence of CB-supported macroRAFT agents. The resultant CB-g-PAA composites were characterized by Fourier transformed infrared spectra, thermal gravimetric analysis and energy dispersive spectrometry. The composites were dip-coated on epoxy resin electrodes to prepare novel thin film gas sensors, and the electrical responses of sensors towards ethanol were investigated. It was found that the sensors exhibited positive correlation electrical response towards ethanol vapor.

Well-Defined Hydrophilic Molecularly Imprinted Polymer Microspheres for Efficient Molecular Recognition in Real Biological Samples by Facile RAFT Coupling Chemistry

A facile and highly efficient new approach (namely RAFT coupling chemistry) to obtain well-defined hydrophilic molecularly imprinted polymer (MIP) microspheres with excellent specific recognition ability toward small organic analytes in the real, undiluted biological samples is described. It involves the first synthesis of "living" MIP microspheres with surface-bound vinyl and dithioester groups via RAFT precipitation polymerization (RAFTPP) and their subsequent grafting of hydrophilic polymer brushes by the simple coupling reaction of hydrophilic macro-RAFT agents (i.e., hydrophilic polymers with a dithioester end group) with vinyl groups on the "living" MIP particles in the presence of a free radical initiator. The successful grafting of hydrophilic polymer brushes onto the obtained MIP particles was confirmed by SEM, FT-IR, static contact angle and water dispersion studies, elemental analyses, and template binding experiments. Well-defined MIP particles with densely grafted hydrophilic polymer brushes (∼1.8 chains/nm(2)) of desired chemical structures and molecular weights were readily obtained, which showed significantly improved surface hydrophilicity and could thus function properly in real biological media. The origin of the high grafting densities of the polymer brushes was clarified and the general applicability of the strategy was demonstrated. In particular, the well-defined characteristics of the resulting hydrophilic MIP particles allowed the first systematic study on the effects of various structural parameters of the grafted hydrophilic polymer brushes on their water-compatibility, which is of great importance for rationally designing more advanced real biological sample-compatible MIPs.