RAFT Dispersion Polymerization Research Articles

RAFT dispersion polymerization induced self-assembly (PISA) of boronic acid-substituted acrylamides

For the unprotected monomer, the boroxine core of nanoparticles allows transitions to higher order morphologies, while worms and vesicles are yielded directly from PISA of the pinacol ester-protected monomer.

Kinetically stable sub-50 nm fluorescent block copolymer nanoparticles via photomediated RAFT dispersion polymerization for cellular imaging.

Self-assembled block copolymer nanoparticles (NPs) have emerged as major potential nanoscale vehicles for fluorescence bioimaging. The preparation of NPs with high yields possessing high kinetic stability to prevent the leakage of fluorophore molecules is crucial to their practical implementation. Here, we report a photomediated RAFT polymerization-induced self-assembly (PISA) yielding uniform and nanosized poly((oligo(ethylene glycol) acrylate)-block-poly(benzyl acrylate) particles (POEGA-b-PBzA) with a concentration of 22 wt%, over 20 times more than with micellization and nanoprecipitation. The spherical diblock copolymer nanoparticles have an average size of 10-50 nm controllable through the degree of polymerization of the stabilizing POEGA block. Subsequent dialysis against water and swelling with Nile red solution led to highly stable fluorescent NPs able to withstand the changes in concentration, ionic strength, pH or temperature. A PBzA/water interfacial tension of 48.6 mN m-1 hinders the exchange between copolymer chains, resulting in the trapping of NPs in a "kinetically frozen" state responsible for high stability. A spectroscopic study combining fluorescence and UV-vis absorption agrees with a preferential distribution of fluorophores in the outer POEGEA shell despite its hydrophobic nature. Nile red-doped POEGA-b-PBzA micelles without initiator residues and unimers but with high structural stability turn out to be noncytotoxic, and can be used for the optical imaging of cells. Real-time confocal fluorescence microscopy shows a fast cellular uptake using C2C12 cell lines in minutes, and a preferential localization in the perinuclear region, in particular in the vesicles.

RAFT Dispersion Polymerization of Methyl Methacrylate in Mineral Oil: High Glass Transition Temperature of the Core-Forming Block Constrains the Evolution of Copolymer Morphology

RAFT dispersion polymerization of a prototypical methacrylic monomer, methyl methacrylate (MMA), is performed in mineral oil using various poly(lauryl methacrylate) (PLMA) precursors prepared with a trithiocarbonate-based RAFT agent. GPC analysis indicated reasonably narrow molecular weight distributions (Mw/Mn ≤ 1.39) for all diblock copolymers, with 1H NMR studies indicating high MMA conversions (≥95%) for all syntheses. An efficient one-pot synthesis protocol enabled high blocking efficiencies to be achieved when targeting higher PMMA DPs. However, the relatively high glass transition temperature (Tg) of the corresponding core-forming PMMA block unexpectedly constrains the evolution in copolymer morphology during polymerization-induced self-assembly (PISA). More specifically, well-defined PLMA22–PMMAx spheres (x = 19–39) and relatively short worms (x = 69–97) can be obtained at 90 °C when using a PLMA22 precursor but targeting higher x values (x ≥ 108) invariably leads to colloidally unstable aggregates of spheres, rather than long worms or vesicles. Interestingly, similar constraints were observed when targeting higher solids, when using n-dodecane instead of mineral oil, or when employing an alternative steric stabilizer block. Raising the PISA synthesis temperature from 90 to 115 °C (i.e., from below to above the Tg of the final PMMA block) does not alleviate this unexpected problem. Moreover, only spherical nanoparticles can be obtained at 115 °C when targeting PMMA DPs between 50 and 400 with the same PLMA22 precursor. This suggests that nanoparticle formation may occur by a chain expulsion/insertion mechanism at this relatively high reaction temperature. PLMA22–PMMAx nanoparticles were characterized in terms of their particle size and morphology using dynamic light scattering (DLS), transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS). DLS and TEM studies of a 0.1% w/w dispersion of PLMA22–PMMA69 short worms indicated an irreversible worm-to-sphere transition on heating from 20 to 150 °C. Oscillatory rheology and TEM studies indicated that this thermal transition was only partially reversible for a 20% w/w dispersion of PLMA22–PMMA69 short worms.

Synthesis of ultra‐high molecular weight core cross‐linked star (CCS) polymer using high molecular weight spherical nanoparticles and arm‐first method

AbstractP (N,N‐Dimethylacrylamide) ‐b‐P (2‐methoxyethyl acrylate) (PDMA‐b‐PMEA) and Poly (poly (ethylene glycol) methyl ether methacrylate) ‐b‐P (2‐methoxyethyl acrylate) (PPEGMA‐b‐PMEA) di‐block copolymer nanoparticles are prepared by RAFT dispersion polymerization in water at 35°C. By changing the degree of polymerization (DP) of PMEA and the solid content of the reaction solution, only spherical nanoparticles are obtained. Using PDMA and PPEGMA as macromolecular chain transfer agents (Macro‐CTA), the actual DP of PMEA block can be up to 11,520 and 17,000, respectively, the size of the obtained spherical nanoparticles can be close to 600 nm, and the molecular weight of the block copolymer can reach 106. Such large spheres may serve as model sterically stabilized particles for analytical centrifugation studies. In the mixed solvent of ethanol and water (1:1, v/v), we synthesize ultra‐high molecular weight CCS polymer by the arm‐first method. Star polymer with such high molecular weight and small particle size can be used for emulsification.

Small-Angle X-Ray Scattering Studies of Block Copolymer Nano-Objects: Formation of Ordered Phases in Concentrated Solution During Polymerization-Induced Self-Assembly.

We report that polymerization‐induced self‐assembly (PISA) can be used to prepare lyotropic phases comprising diblock copolymer nano‐objects in non‐polar media. RAFT dispersion polymerization of benzyl methacrylate (BzMA) at 90 °C using a trithiocarbonate‐capped hydrogenated polybutadiene (PhBD) steric stabilizer block in n‐dodecane produces either spheres or worms that exhibit long‐range order at 40 % w/w solids. NMR studies enable calculation of instantaneous copolymer compositions for each phase during the BzMA polymerization. As the PBzMA chains grow longer when targeting PhBD80–PBzMA40, time‐resolved small‐angle X‐ray scattering reveals intermediate body‐centered cubic (BCC) and hexagonally close‐packed (HCP) sphere phases prior to formation of a final hexagonal cylinder phase (HEX). The HEX phase is lost on serial dilution and the aligned cylinders eventually form disordered flexible worms. The HEX phase undergoes an order–disorder transition on heating to 150 °C and a pure HCP phase forms on cooling to 20 °C.

Small‐Angle X‐Ray Scattering Studies of Block Copolymer Nano‐Objects: Formation of Ordered Phases in Concentrated Solution During Polymerization‐Induced Self‐Assembly

AbstractWe report that polymerization‐induced self‐assembly (PISA) can be used to prepare lyotropic phases comprising diblock copolymer nano‐objects in non‐polar media. RAFT dispersion polymerization of benzyl methacrylate (BzMA) at 90 °C using a trithiocarbonate‐capped hydrogenated polybutadiene (PhBD) steric stabilizer block in n‐dodecane produces either spheres or worms that exhibit long‐range order at 40 % w/w solids. NMR studies enable calculation of instantaneous copolymer compositions for each phase during the BzMA polymerization. As the PBzMA chains grow longer when targeting PhBD80–PBzMA40, time‐resolved small‐angle X‐ray scattering reveals intermediate body‐centered cubic (BCC) and hexagonally close‐packed (HCP) sphere phases prior to formation of a final hexagonal cylinder phase (HEX). The HEX phase is lost on serial dilution and the aligned cylinders eventually form disordered flexible worms. The HEX phase undergoes an order–disorder transition on heating to 150 °C and a pure HCP phase forms on cooling to 20 °C.

Construction of Highly Ordered Glyco‐Inside Nano‐Assemblies through RAFT Dispersion Polymerization of Galactose‐Decorated Monomer

AbstractGlyco‐assemblies derived from amphiphilic sugar‐decorated block copolymers (ASBCs) have emerged prominently due to their wide application, for example, in biomedicine and as drug carriers. However, to efficiently construct these glyco‐assemblies is still a challenge. Herein, we report an efficient technology for the synthesis of glyco‐inside nano‐assemblies by utilizing RAFT polymerization of a galactose‐decorated methacrylate for polymerization‐induced self‐assembly (PISA). Using this approach, a series of highly ordered glyco‐inside nano‐assemblies containing intermediate morphologies were fabricated by adjusting the length of the hydrophobic glycoblock and the polymerization solids content. A specific morphology of complex vesicles was captured during the PISA process and the formation mechanism is explained by the morphology of its precursor and intermediate. Thus, this method establishes a powerful route to fabricate glyco‐assemblies with tunable morphologies and variable sizes, which is significant to enable the large‐scale fabrication and wide application of glyco‐assemblies.

Construction of Highly Ordered Glyco-Inside Nano-Assemblies through RAFT Dispersion Polymerization of Galactose-Decorated Monomer.

Glyco‐assemblies derived from amphiphilic sugar‐decorated block copolymers (ASBCs) have emerged prominently due to their wide application, for example, in biomedicine and as drug carriers. However, to efficiently construct these glyco‐assemblies is still a challenge. Herein, we report an efficient technology for the synthesis of glyco‐inside nano‐assemblies by utilizing RAFT polymerization of a galactose‐decorated methacrylate for polymerization‐induced self‐assembly (PISA). Using this approach, a series of highly ordered glyco‐inside nano‐assemblies containing intermediate morphologies were fabricated by adjusting the length of the hydrophobic glycoblock and the polymerization solids content. A specific morphology of complex vesicles was captured during the PISA process and the formation mechanism is explained by the morphology of its precursor and intermediate. Thus, this method establishes a powerful route to fabricate glyco‐assemblies with tunable morphologies and variable sizes, which is significant to enable the large‐scale fabrication and wide application of glyco‐assemblies.

Inside Cover: Construction of Highly Ordered Glyco‐Inside Nano‐Assemblies through RAFT Dispersion Polymerization of Galactose‐Decorated Monomer (Angew. Chem. Int. Ed. 20/2021)

An efficient strategy for constructing glyco-inside nano-assemblies is presented by Liang Qiu, Ulrich Glebe, Chengfen Xing et al. In their Communication on page 11098, a series of highly ordered glyco-inside nano-assemblies derived from sugar-decorated block copolymers were obtained via PISA induced by RAFT dispersion polymerization of a galactose-decorated monomer.

Asymmetric Colloidal Particles Fabricated by Polymerization-Induced Surface Self-Assembly Approach

In the past decades, the synthesis of asymmetric colloidal particles has been of wide concern in material science because of their anisotropic morphologies and unique properties. However, the synthesis of the asymmetric particles with controllable anisotropy still remains a big challenge because of the lack of effective methods. In this research, polymerization-induced surface self-assembly (PISSA) approach was demonstrated to be an effective method in the synthesis of colloidal particles with tunable asymmetric core–shell structures. Reversible addition–fragmentation chain transfer agents were covalently anchored onto the surfaces of silica particles and coupled onto the ends of methoxy polyethylene glycol (PEG) chains, leading to the synthesis of CTA-modified silica particles (SiO2-CTA) and PEG macro-CTA agents (PEG-CTA), respectively. PISSA process was conducted by using SiO2-CTA and PEG-CTA as co-RAFT agents in RAFT dispersion polymerization of styrene. In the RAFT polymerizations, polymer layers with PS nodules were formed on the surfaces of SiO2 particles. It was demonstrated that the formation of the nodules was related to the production of the PS homopolymer in the PISSA process. In order to control the asymmetric surface structures, RAFT dispersion polymerizations of styrene with added “free” RAFT agents were performed, and it turned out that the eccentrically positioned core–shell structures with silica cores and polymer layers were prepared. The colloidal particles experience morphology changes from surface nodules to snowman-like structures and finally to asymmetric spherical structures, depending on the monomer conversion and the feeding ratio of the co-RAFT agents. Kinetics studies were performed to investigate the mechanism of the formation of the asymmetric particles. After etching the silica cores with HF solution, asymmetric hollow capsules were fabricated.

Synthesis of Highly Transparent Diblock Copolymer Vesicles via RAFT Dispersion Polymerization of 2,2,2-Trifluoroethyl Methacrylate in n-Alkanes.

RAFT dispersion polymerization of 2,2,2-trifluoroethyl methacrylate (TFEMA) is performed in n-dodecane at 90 °C using a relatively short poly(stearyl methacrylate) (PSMA) precursor and 2-cyano-2-propyl dithiobenzoate (CPDB). The growing insoluble poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA) block results in the formation of PSMA–PTFEMA diblock copolymer nano-objects via polymerization-induced self-assembly (PISA). GPC analysis indicated narrow molecular weight distributions (Mw/Mn ≤ 1.34) for all copolymers, with 19F NMR studies indicating high TFEMA conversions (≥95%) for all syntheses. A pseudo-phase diagram was constructed to enable reproducible targeting of pure spheres, worms, or vesicles by varying the target degree of polymerization of the PTFEMA block at 15–25% w/w solids. Nano-objects were characterized using dynamic light scattering, transmission electron microscopy, and small-angle X-ray scattering. Importantly, the near-identical refractive indices for PTFEMA (1.418) and n-dodecane (1.421) enable the first example of highly transparent vesicles to be prepared. The turbidity of such dispersions was examined between 20 and 90 °C. The highest transmittance (97% at 600 nm) was observed for PSMA9–PTFEMA294 vesicles (237 ± 24 nm diameter; prepared at 25% w/w solids) in n-dodecane at 20 °C. Interestingly, targeting the same diblock composition in n-hexadecane produced a vesicle dispersion with minimal turbidity at a synthesis temperature of 90 °C. This solvent enabled in situ visible absorption spectra to be recorded during the synthesis of PSMA16–PTFEMA86 spheres at 15% w/w solids, which allowed the relatively weak n→π* band at 515 nm assigned to the dithiobenzoate chain-ends to be monitored. Unfortunately, the premature loss of this RAFT chain-end occurred during the RAFT dispersion polymerization of TFEMA at 90 °C, so meaningful kinetic data could not be obtained. Furthermore, the dithiobenzoate chain-ends exhibited a λmax shift of 8 nm relative to that of the dithiobenzoate-capped PSMA9 precursor. This solvatochromatic effect suggests that the problem of thermally labile dithiobenzoate chain-ends cannot be addressed by performing the TFEMA polymerization at lower temperatures.

Synthesis and self-assembly of star multiple block copolymer of poly(4-vinylpyridine)-block-polystyrene

Star multiple block copolymer of poly (4-vinylpyridine)-block-polystyrene (s-P4VP-b-PS) is synthesized via initial synthesis of linear poly (4-vinylpyridine)-block-polystyrene (l-P4VP-b-PS) by dispersion RAFT polymerization to form l-P4VP-b-PS nano-assemblies and then cross-linking within the l-P4VP-b-PS nano-assemblies. The synthesized s-P4VP-b-PS has a high molecular weight and exists 25–47 nm nanospheres in the common solvent of N,N-dimethylformamide. The self-assembly of s-P4VP-b-PS in two block selective solvents, e.g., toluene and methanol, is investigated, and great difference from l-P4VP-b-PS is demonstrated. In methanol, s-P4VP-b-PS forms core-corona nanospheres. In toluene, s-P4VP-b-PS forms dispersed nanoparticles or nanoparticle clusters dependent on polymer concentration. In the s-P4VP-b-PS nanoparticle clusters, poly (4-vinylpyridine) forms dispersed nano-domains, the size of which is firmly dependent on the degree of polymerization of the P4VP block. It is thought that the great difference between s-P4VP-b-PS and l-P4VP-b-PS will arouse new interest on self-assembly of block copolymers.

Well-defined polyvinylpyridine-block-polystyrene diblock copolymers via RAFT aqueous-alcoholic dispersion polymerization: synthesis and isoporous thin film morphology

This work presents the synthesis of polyvinylpyridine-polystyrene (PVP-b-PS) diblock copolymers via RAFT dispersion polymerization. Spin-coated PVP-b-PS films were converted into porous surfaces by a controlled alignment and swelling strategy.

RAFT dispersion polymerization of N,N-dimethylacrylamide in a series of n-alkanes using a thermoresponsive poly(tert-octyl acrylamide) steric stabilizer

Poly(tert-octyl acrylamide)-poly(N,N-dimethylacrylamide) nanoparticles are prepared by RAFT dispersion polymerization at 70 °C in various n-alkanes. Thermoreversible flocculation occurs in higher n-alkanes on cooling to 20 °C.

In situ formation of core–shell nanoparticles in epoxy resin via reversible addition–fragmentation chain transfer dispersion polymerization

RAFT dispersion polymerization and preparation of a core–shell particle dispersed epoxy resin.

Influence of structure and solubility of chain transfer agents on the RAFT control of dispersion polymerisation in scCO2.

Reversible addition–fragmentation chain transfer (RAFT) dispersion polymerisation of methyl methacrylate (MMA) is performed in supercritical carbon dioxide (scCO2) with 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT) present as chain transfer agent (CTA) and surprisingly shows good control over PMMA molecular weight. Kinetic studies of the polymerisation in scCO2 also confirm these data. By contrast, only poor control of MMA polymerisation is obtained in toluene solution, as would be expected for this CTA which is better suited for acrylates. In this regard, we select a range of CTAs and use them to determine the parameters that must be considered for good control in dispersion polymerisation in scCO2. A thorough investigation of the nucleation stage during the dispersion polymerisation reveals an unexpected “in situ two-stage” mechanism that strongly determines how the CTA works. Finally, using a novel computational solvation model, we identify a correlation between polymerisation control and degree of solubility of the CTAs. All of this ultimately gives rise to a simple, elegant and counterintuitive guideline to select the best CTA for RAFT dispersion polymerisation in scCO2.

Elucidating preparation-structure relationships for the morphology evolution during the RAFT dispersion polymerization of N-acryloyl thiomorpholine

Depending on the conditions, nearly monodisperse spherical micelles or complex morphologies are formed during a polymerization induced self-assembly (PISA) process based on the water-soluble monomer N-acryloylthiomorpholine.

Preparation of zwitterionic microspheres of PDMAEMA-b-PMAA by RAFT dispersion polymerization in alcohol, their pH-sensitivity in water, and self-assembly in KCl solution

Zwitterionic microspheres of poly2-(dimethylamino) ethyl methacrylate (PDMAEMA) block polymethacrylic acid (MAA) were prepared by RAFT dispersion polymerization in alcohols. 4-Cyano-4-(phenylcarbonothioylthio) pentanoic acid (CPDB) was used as the RAFT agent. 2,2′-Azobis(2,4-dimethyl) valeronitrile (V65) was used as the initiator, and PDMAEMA-CPDB was used as the macro-chain transfer agent (CTA). 1HNMR was applied to determine the polymerization degrees of both PDMAEMA-CTA and PDMAEMA-b-PMAA. SEM, dynamic light scattering (DLS), and small-angle X-ray diffraction (SAX) were employed to characterize the microspheres. It was observed that the polarity of alcohols impacted the partition of MAA and V65 between the mini-droplets of PDMAEMA-CTA/MAA complexes and the continuous phase, thereby affected on the diameters of microspheres, the total conversion of MAA, and the polymerization degree of PMAA in the copolymers. For example, in methanol, the smallest diameter and polymerization degree of PMAA in the block copolymers were obtained, whereas the total conversion of MAA of the RAFT polymerization system was the highest. Most of RAFT polymerization of MAA occurred nearby PDMAEMA-CTA chains; thus, PDMAEMA-CTA acted as a template to regulate the length of PMAA in the copolymers. pH-sensitive characteristics of microspheres were dependent to the extra length of PDMAEMA-CTA, i.e., the difference of lengths between two blocks. When the length of PMAA was too short, e.g., PDMAEMA600-b-PMAA87, or the length of PMAA was closed to that of PDMAEMA, e.g., PDMAEMA79-b-PMAA93 and PDMAEMA102-b-PMAA131, the amphoteric characteristics of microspheres disappeared. The self-assembly behavior of diblock copolymers in KCl alcohol-water solution was also determined by the extra length of PDMAEMA. Microspheres turned into nanofibers or nano-ribbons, but for PDMAEMA600-b-PMAA87, the microspheres maintained their original spheric morphology. These results indicated that the charge-screening effects of salts played the key roles in the self-assembly.

Facile synthesis of temperature-sensitive ABA triblock copolymers by dispersion RAFT polymerization

The dispersion RAFT polymerization was applied for the first time to synthesize the well-defined ABA triblock copolymer core–shell nanoparticles of temperature-sensitive poly(N-isopropylacrylamide-co-acrylic acid)-block-poly(n-butyl acrylate)-block-poly(N-isopropylacrylamide-co-acrylic acid) and poly(n-butyl acrylate-co-N-isopropylacrylamide)-blockpoly(n-butyl acrylate)-block-poly(n-butyl acrylate-co-N-isopropylacrylamide).

Tailoring the droplet size of Pickering emulsions by PISA synthesized polymeric nanoparticles

Pickering emulsions, water or oil droplets stabilized solely by solid particles, are attracting increasing attention, due to the fascinating possibilities for applications in food, pharmaceuticals and preparation of hybrid materials. In this paper, we report oil-in-water (O/W) Pickering emulsions stabilized solely by polymerization-induced self-assembly (PISA) synthesized diblock copolymer spherical nanoparticles. Poly (N,N-dimethylaminoethyl methacrylate)-b-poly (benzyl methacrylate) (PDMA-b-PBzMA) diblock copolymer nanoparticles with 20 wt% solid content were prepared in ethanol via RAFT dispersion polymerization. Then PDMA-b-PBzMA nanoparticles were used as emulsifiers to prepare O/W Pickering emulsions by homogenization. The regulation of droplet size of the O/W Pickering emulsion was systemically investigated by adjusting the size of emulsifiers, the concentration of emulsifiers, and the ratio of oil/water. Moreover, Pickering emulsion polymerization was successfully applied to prepare poly (laurate methacrylate) microparticles. These results provide instructive insights to choose proper nanoparticles for the preparation of Pickering emulsions and control over the size of emulsion droplets.