Reversible Addition-fragmentation Chain Transfer Dispersion Polymerization Research Articles

ABC or ACB triblock copolymers? Changing the RAFT group position in diblock copolymer macro-RAFT agents leads to different PISA behaviors in RAFT dispersion polymerization

ACB and ABC triblock copolymer nanoparticles were prepared by reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization using diblock copolymer macromolecular RAFT (macro-RAFT) agents with different RAFT group positions.

Synthesis of Hydrophobic Block Copolymer Nanoparticles in Alcohol/Water Stabilized by Poly(methyl methacrylate) via RAFT Dispersion Polymerization-Induced Self-Assembly

Poly(methyl methacrylate) (PMMA) is an important common polymer widely used in industry. While PMMA has been used as a core-forming block for polymerization-induced self-assembly (PISA), a powerful approach for the synthesis of block copolymer nanoparticles, it has not been utilized as a corona block due to PMMA being insoluble in common solvents for PISA formulations (e.g., water and alcohols). Exploiting the solubility of PMMA-dithiobenzoate (DTB) in ethanol/water mixtures, such macroRAFT agents have in the present work been successfully employed for reversible addition–fragmentation chain transfer (RAFT) PISA in ethanol/water (80/20 by volume). RAFT dispersion polymerization of benzyl methacrylate mediated by PMMA-DTB macroRAFT agents with various degrees of polymerization has been investigated. Transmission electron microscopy analyses revealed well-defined block copolymer nano-objects, including spheres, worms, as well as vesicles. Nanoparticles comprising a PMMA outer layer would have superior compatibility with various hydrophobic polymer matrices, thereby enabling various new applications such as, e.g., use as nanofillers.

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.

Efficient Synthesis and PISA Behavior of Molecular Bottlebrush Block Copolymers via a Grafting-From Strategy through RAFT Dispersion Polymerization

Precise synthesis of molecular bottlebrushes (MBBs) with high yield via the grafting-from strategy using a reversible deactivation radical polymerization (RDRP) technique has remained elusive. Herein, the molecular bottlebrush block copolymers (MBB BCPs) with high yield and varying chemical compositions were synthesized via a polymerization-induced self-assembly (PISA)-assisted grafting-from strategy by reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization. First, the poly(norbornene-g-poly(ethylene oxide))-b-poly(norbornene-g-chain transfer agent) [P(NB-g-PEG45)-b-P(NB-CTA)] BCPs with varied chemical compositions were synthesized by sequential ring-opening metathesis polymerization (ROMP) of norbornene PEG macromonomers (NB-PEG45) and norbornene chain transfer agent (NB-CTA) monomers. Subsequently, these P(NB-g-PEG45)m-b-P(NB-CTA)n BCPs were used as multifunctional macro-CTAs for the synthesis of MBB BCPs with a high yield (up to 80% styrene monomer conversion) and a low dispersity (Đ < 1.15) via a grafting-from strategy through RAFT dispersion polymerization. The PISA behaviors of these MBB BCPs were also investigated, and the results indicated that the MBB BCPs assemblies were transformed from spherical micelles into two-dimensional disk-like micelles because the rigidity of the PS MBB segment increased with the growth of PS side chains.

Scalable Preparation of Cylindrical Block Copolymer Micelles with a Liquid-Crystalline Perfluorinated Core by Photoinitiated Reversible Addition-Fragmentation Chain Transfer Dispersion Polymerization

One-dimensional block copolymer micelles have exhibited considerable promise in various fields. However, the large-scale preparation of one-dimensional block copolymer micelles is always challenging. Here, we report the preparation of cylindrical block copolymer micelles up to 30% w/w solids by photoinitiated reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of 2-(perfluorooctyl)ethyl methacrylate (FMA) in ethanol. Because of the liquid-crystalline ordering effect of the PFMA core-forming block at low temperatures, cylindrical micelles could be obtained over a wide range of degree of polymerization of PFMA. The length of cylindrical micelles could be roughly controlled by changing the molar mass of the macromolecular chain transfer agent (macro-CTA). Finally, the concept of seeded growth was successfully incorporated into photoinitiated RAFT dispersion polymerization, allowing the epitaxial growth of cylindrical micelles from seeds. We expect that this method will offer considerable opportunities for the large-scale preparation of well-defined cylindrical micelles that may find applications in some specific areas.

Zwitterionic nano-objects having functionalizable hydrophobic core: Formation via polymerization-induced self-assembly and their morphology

Functionalizable poly(pentafluorophenyl methacrylate) (PPFPMA) and zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) are two polymers with an extremely different solubility. It is, therefore, almost impossible to synthesize their block copolymers in a controlled manner using a conventional approach. Herein, it is demonstrated, for the first time, that the synthesis and in situ formation of nanoassemblies of their diblock copolymers (PMPC-b-PPFPMA) can be achieved via polymerization-induced self-assembly using reversible addition-fragmentation chain-transfer dispersion polymerization in ethanol as a selective solvent. The PMPC was synthesized as the first block and further employed as a macro chain transfer agent (PMPC Macro-CTA) for the synthesis of the PPFPMA second block. In situ self-assembled nanostructures of the diblock copolymers were found to be mostly spherical with a varied degree of inter-micellar aggregation depending on the solid concentration and the relative length of the two blocks. Apparently, the limited chain mobility of the core-forming PPFPMA block, due to π-π stacking and hydrophobic interactions, hampered the formation of nanostructures of high-order morphologies. It is possible to perform core functionalization via post-polymerization modification with 1-pyrenemethylamine to yield fluorescently labeled nanostructures that may be applicable as biocompatible and non-fouling nanocarriers and nanosensors in the future.

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.

Polymerization‐induced self‐assembly of amino‐acid‐based nano‐objects by reversible addition–fragmentation chain‐transfer dispersion polymerization

AbstractA series of amino‐acid‐based amphiphilic diblock copolymer nano‐objects having different morphologies were developed by reversible addition–fragmentation chain‐transfer (RAFT) dispersion polymerization of styrene (St) in methanol. This was mediated by six different hydrophilic poly(N‐acryloyl amino acid) macro‐chain transfer agents (CTAs), including three carboxylic‐acid‐containing ones, poly(N‐acryloyl‐l‐proline) (PAProOH), poly(N‐acryloyl‐4‐trans‐hydroxy‐l‐proline) (PAHypOH), and poly(N‐acryloyl‐l‐threonine) (PAThrOH) prepared by RAFT polymerization, and their methyl ester forms, PAProOMe, PAHypOMe, and PAThrOMe. The effects of polymerization conditions on RAFT dispersion polymerization of St using a dithiocarbamate‐terminated PAProOH was investigated. A systematic study of the effects of monomer conversion and concentration afforded the formation of various morphologies (i.e., spheres, worms, and vesicles). The effects of hydrogen‐bonding and ionic interactions of the macro‐CTAs on the assembled structures of the nano‐objects were evaluated using six different macro‐CTAs. Transforming the products from methanol to water via dialysis produced amino‐acid‐based block copolymer nano‐objects, exhibiting pH‐responsive morphological change, in aqueous solution.

Preparation of Block Copolymer Nano-Objects with Embedded β-Ketoester Functional Groups by Photoinitiated RAFT Dispersion Polymerization.

Herein, a photoinitiated reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of 2-(acetoacetoxy)ethyl methacrylate (AEMA) in ethanol/water at room temperature for in situ preparation of β-ketoester-functionalized block copolymer nano-objects is reported. AEMA is also copolymerized with isobornyl methacrylate (IBOMA) to improve the colloidal stability of PIBOMA-based block copolymer nano-objects prepared by photoinitiated RAFT dispersion polymerization at low temperatures. A series of P(IBOMA-stat-AEMA)-based block copolymer nano-objects are prepared by changing reaction parameters. Finally, lanthanide-doped block copolymer nano-objects with luminescent and magnetic properties are also prepared based on the complexation of various lanthanide ions with the β-ketoester group. It is expected that the current study will provide a facile platform for the in situ preparation of β-ketoester-functionalized block copolymer nano-objects with different morphologies for specific applications.

Biosurfaces Fabricated by Polymerization-Induced Surface Self-Assembly.

Surface biofunctionalization provides an approach to the fabrication of surfaces with improved biological and clinical performances. Biosurfaces have found increasing applications in many areas such as sensing, cell growth, and disease detection. Efficient synthesis of biosurfaces without damages to the structures and functionalities of biomolecules is a great challenge. Polymerization-induced surface self-assembly (PISSA) provides an effective approach to the synthesis of surface nanostructures with different compositions, morphologies, and properties. In this research, application of PISSA in the fabrication of biosurfaces is investigated. Two different reversible addition-fragmentation chain transfer (RAFT) agents, RAFT chain transfer agent (CTA) on silica particles (SiO2-CTA) and CTA on bovine serum albumin (BSA-CTA), were employed in RAFT dispersion polymerization of N-isopropylacrylamide (NIPAM) in water at a temperature above the lower critical solution temperature (LCST) of poly-(isopropylacrylamide) (PNIPAM). After polymerization, PNIPAM layers with BSA on the top surfaces are fabricated on the surfaces of silica particles. Transmission electron microscopy results show that the average PNIPAM layer thickness increases with monomer conversion. Kinetics study indicates that there is a turn point on a plot of ln([M]0/[M]t) versus polymerization time. After the critical point, surface coassembly of PNIPAM brushes and BSA-PNIPAM bioconjugates is performed on the silica particles. The secondary structure and the activity of BSA immobilized on top of the PNIPAM layers are basically kept unchanged in the PISSA process. To prepare permanently immobilized protein surfaces, PNIPAM layers on silica particles are cross-linked. BSA on the top surfaces presents a reversible "on-off" switching property. At a temperature below the LCST of PNIPAM, the activity of the immobilized BSA is retained; however, the BSA activity decreases significantly at a temperature above the LCST because of the hydrophobic interaction between PNIPAM and BSA. Based on this approach, many different biosurfaces can be fabricated and the materials will find applications in many fields, such as enzyme immobilization, drug delivery, and tissue engineering.

R-RAFT or Z-RAFT? Well-Defined Star Block Copolymer Nano-Objects Prepared by RAFT-Mediated Polymerization-Induced Self-Assembly

Reversible addition-fragmentation chain transfer (RAFT)-mediated polymerization-induced self-assembly (PISA) has served as a versatile platform for the large-scale preparation of block copolymer nano-objects with a diverse set of morphologies. However, almost all PISA formulations are focused on the syntheses of linear block copolymers rather than star block copolymers. Owing to the asymmetrical structure of the RAFT agent, herein, we report a direct comparison between Z-RAFT (the nonfragmenting group attached to the core) and R-RAFT (the fragmenting group attached to the core) strategies for preparing well-defined star block copolymer nano-objects via RAFT-mediated PISA. We showed that the Z-RAFT strategy is a more suitable strategy for the preparation of star block copolymer nano-objects without compromising the control over the molecular weight and morphology. A binary mixture of Z-type and R-type tetrafunctional macro-RAFT agents was used to control the morphologies of star block copolymer assemblies. The effect of numbers of the RAFT group on polymerization kinetics and morphologies of block copolymer nano-objects was also investigated in detail. Finally, (ABC)4 four-arm star triblock copolymer vesicles were prepared by seeded RAFT dispersion polymerization of solvophobic and solvophilic monomers using (AB)4 four-arm star diblock copolymer vesicles as seeds. This research not only expands the scope for preparing well-defined star block copolymer nano-objects but also provides important insights into the effect of the polymer architecture on RAFT-mediated PISA.

RAFT Dispersion Polymerization of Benzyl Methacrylate in Silicone Oil Using a Silicone-Based Methacrylic Stabilizer Provides Convenient Access to Spheres, Worms, and Vesicles

Reversible addition–fragmentation chain transfer (RAFT) solution polymerization of 3-[tris(trimethylsiloxy)silyl] propyl methacrylate (SiMA) was conducted in toluene to prepare three PSiMA precurso...

Blue Light-Initiated Alcoholic RAFT Dispersion Polymerization of Benzyl Methacrylate: A Detailed Study.

Blue light-initiated alcoholic reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate (BzMA) using bis (acyl) phosphane oxide (BAPO) as the photo-initiator is developed to prepare diblock copolymer nano-objects. High monomer conversion (95%) was achieved within 2 h of blue light irradiation in an isopropanol/water mixture. Effects of solvent, light intensity, and reaction temperature on the polymerization kinetics were evaluated. Finally, the effect of reaction temperature on the morphologies of diblock copolymer nano-objects was investigated and two morphological phase diagrams were constructed at 25 and 70 °C. Transmission electron microscopy (TEM) measurement confirmed that increasing the reaction temperature promoted the evolution of higher order morphology. We believe this study will provide more mechanistic insights into alcoholic RAFT dispersion polymerization for the creation of diblock copolymer nano-objects with well-defined structures.

RAFT dispersion polymerization of glycidyl methacrylate for the synthesis of epoxy-functional block copolymer nanoparticles in mineral oil

Epoxy-functional poly(stearyl methacrylate)-poly(glycidyl methacrylate) (PSMA-PGlyMA) diblock copolymer nanoparticles are synthesized via reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of glycidyl methacrylate (GlyMA) in mineral oil at 70 °C.

In Situ Spectroscopic Studies of Highly Transparent Nanoparticle Dispersions Enable Assessment of Trithiocarbonate Chain-End Fidelity during RAFT Dispersion Polymerization in Nonpolar Media.

We report the synthesis of highly transparent poly(stearyl methacrylate)-poly(2,2,2-trifluoroethyl methacrylate) (PSMA–PTFEMA) diblock copolymer nanoparticles via polymerization-induced self-assembly (PISA) in nonpolar media at 70 °C. This was achieved by chain-extending a PSMA precursor block via reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of TFEMA in n-tetradecane. This n-alkane has the same refractive index as the PTFEMA core-forming block at 70 °C, which ensures high light transmittance when targeting 33 nm spherical nanoparticles. Such isorefractivity enables visible absorption spectra to be recorded with minimal light scattering even at 30% w/w solids. However, in situ monitoring of the trithiocarbonate RAFT end-groups during PISA requires selection of a weak n → π* band at 446 nm. Conversion of TFEMA into PTFEMA causes a contraction in the reaction solution volume, leading to an initial increase in absorbance that enables the kinetics of polymerization to be monitored via dilatometry. At ∼98% TFEMA conversion, this 446 nm band remains constant for 2 h at 70 °C, indicating surprisingly high RAFT chain-end fidelity (and hence pseudoliving character) under monomer-starved conditions. In situ 19F NMR spectroscopy studies provide evidence for (i) the onset of micellar nucleation, (ii) solvation of the nanoparticle cores by TFEMA monomer, and (iii) surface plasticization of the nanoparticle cores by n-tetradecane at 70 °C. Finally, the kinetics of RAFT chain-end removal can be conveniently monitored by in situ visible absorption spectroscopy: addition of excess initiator at 70 °C causes complete discoloration of the dispersion, with small-angle X-ray scattering studies confirming no change in nanoparticle morphology under these conditions.

Photoinitiated Seeded RAFT Dispersion Polymerization: A Facile Method for the Preparation of Epoxy-Functionalized Triblock Copolymer Nano-Objects.

In this study, a novel photoinitiated seeded reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization is developed for the preparation of epoxy-functionalized triblock copolymer nano-objects at room temperature. Epoxy-functionalized worms and vesicles prepared by photoinitiated RAFT dispersion polymerization of glycidyl methacrylate are used as seeds for chain extension by photoinitiated seeded RAFT dispersion polymerization of methacrylic and acrylic monomers. Good control is maintained during the polymerization with a high polymerization rate. Pure triblock copolymer worms can be prepared by the photoinitiated seeded RAFT dispersion polymerization with a broad degree of polymerization range of the third block. The room temperature feature of photoinitiated seeded RAFT dispersion polymerization is critical to ensure the survival of epoxy moiety after the polymerization. The obtained triblock copolymer nano-objects can be cross-linked by reacting with a diamine. Finally, cross-linked worms are used as the stationary phase of chromatography for selective separation of organic dyes from water.

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.

Poly(Pentafluorophenyl Methacrylate)-Based Nano-Objects Developed by Photo-PISA as Scaffolds for Post-Polymerization Functionalization.

The preparation of a functional fluorine-containing block copolymer using reversible addition-fragmentation chain-transfer dispersion polymerization in DMSO as a "platform/scaffold" is explored. The nanostructures, comprised of poly(ethyleneglycol)-b-poly(pentafluorophenyl methacrylate) or PEG-b-P(PFMA), are formulated via photo-initiated polymerization-induced self-assembly (PISA) followed by post-polymerization modification using different primary amines. A combination of light scattering and microscopy techniques are used to characterize the resulting morphologies. It is found that upon varying the degree of polymerization of the core-forming block of PFMA, only uniform spheres (with textured surfaces) are obtained. These nanostructures are subsequently modified by cross-linking using a non-responsive and a redox-responsive diamine, thus imparting stability to the particles in water. In response to intracellular glutathione (GSH) concentration, destabilization of the micelles occurs as evidenced by dynamic light scattering. The well-defined size, inherent reactivity of the nanoparticles toward nucleophiles, and GSH-responsiveness of the nanospheres make them ideal scaffolds for drug delivery to intracellular compartments with reductive environments.

Sodium Bis(acyl)phosphane oxide (SBAPO): An efficient photoinitiator for blue light initiated aqueous RAFT dispersion polymerization

We report a novel blue light initiated aqueous reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) with a poly (glycerol monomethacrylate) homopolymer as the macro-RAFT agent and sodium bis(acyl)phosphane oxide (SBAPO) as the photoinitiator. High monomer conversions were achieved within 1 h of blue light irradiation. Taking advantage of the temperature-insensitive feature of photoinitiator, the effect of reaction temperature on the blue light initiated aqueous RAFT dispersion polymerization was studied in detail. A new morphological phase diagram was constructed for the first time by changing the degree of polymerization (DP) of the core-forming block and the reaction temperature. Moreover, a typical morphological phase diagram for the blue light initiated aqueous RAFT dispersion polymerization at 70 °C was also built and various morphologies have been prepared. Effect of wavelength of light (405 and 465 nm) on copolymer compositions and morphologies was studied. Finally, a fully one-pot blue light initiated aqueous RAFT polymerization was developed for the synthesis of various diblock copolymer nano-objects.

Enzyme-PISA: An Efficient Method for Preparing Well-Defined Polymer Nano-Objects under Mild Conditions.

Enzyme catalysis is a mild, efficient, and selective technique that has many applications in organic synthesis as well as polymer synthesis. Here, a novel enzyme-catalysis-induced reversible addition-fragmentation chain transfer (RAFT)-mediated dispersion polymerization for preparing AB diblock copolymer nano-objects with complex morphologies at room temperature is described. Taking advantage of the room-temperature feature, it is shown that pure, worm-like polymer nano-objects can be readily prepared by just monitoring the viscosity. Moreover, it is demonstrated that inorganic nanoparticles and proteins can be loaded in situ into vesicles by this method. Finally, a novel oxygen-tolerant RAFT-mediated dispersion polymerization initiated by enzyme cascade reaction that can be carried out in open vessels is developed. The enzyme-initiated RAFT dispersion polymerization provides a facile platform for the synthesis of various functional polymer nano-objects under mild conditions.