Polymerization-induced Self-assembly Formulation Research Articles

Low-Viscosity Route to High-Molecular-Weight Water-Soluble Polymers: Exploiting the Salt Sensitivity of Poly(N-acryloylmorpholine).

We report a new one-pot low-viscosity synthetic route to high molecular weight non-ionic water-soluble polymers based on polymerization-induced self-assembly (PISA). The RAFT aqueous dispersion polymerization of N-acryloylmorpholine (NAM) is conducted at 30 °C using a suitable redox initiator and a poly(2-hydroxyethyl acrylamide) (PHEAC) precursor in the presence of 0.60 M ammonium sulfate. This relatively low level of added electrolyte is sufficient to salt out the PNAM block, while steric stabilization is conferred by the relatively short salt-tolerant PHEAC block. A mean degree of polymerization (DP) of up to 6000 was targeted for the PNAM block, and high NAM conversions (>96%) were obtained in all cases. On dilution with deionized water, the as-synthesized sterically stabilized particles undergo dissociation to afford molecularly dissolved chains, as judged by dynamic light scattering and 1H NMR spectroscopy studies. DMF GPC analysis confirmed a high chain extension efficiency for the PHEAC precursor, but relatively broad molecular weight distributions were observed for the PHEAC-PNAM diblock copolymer chains (Mw/Mn > 1.9). This has been observed for many other PISA formulations when targeting high core-forming block DPs and is tentatively attributed to chain transfer to polymer, which is well known for polyacrylamide-based polymers. In fact, relatively high dispersities are actually desirable if such copolymers are to be used as viscosity modifiers because solution viscosity correlates closely with Mw. Static light scattering studies were also conducted, with a Zimm plot indicating an absolute Mw of approximately 2.5 × 106 g mol-1 when targeting a PNAM DP of 6000. Finally, it is emphasized that targeting such high DPs leads to a sulfur content for this latter formulation of just 23 ppm, which minimizes the cost, color, and malodor associated with the organosulfur RAFT agent.

Group-Transfer Polymerization-Induced Self-Assembly (GTPISA) in Non-polar Media: An Organocatalyzed Route to Block Copolymer Nanoparticles at Room Temperature.

Polymerization-induced self-assembly (PISA) enables the synthesis at large scale of a wide variety of functional nanoparticles. However, a large number of works are related to controlled radical polymerization (CRP) methods and are generally undertaken at elevated temperatures (>50 °C). Here is the first report on methacrylate-based nanoparticles fabricated by group transfer polymerization-induced self-assembly (GTPISA) in non-polar media (n-heptane). This GTPISA process is achieved at room temperature (RT) using 1-methoxy-1-(trimethylsiloxy)-2-methylprop-1-ene (MTS) and tetrabutylammonium bis-benzoate (TBABB) as initiator and organic catalyst, respectively. Under these conditions, well-defined metal-free and colorless diblock copolymers are produced with efficient crossover from the non-polar stabilizing poly(lauryl methacrylate) (PLMA) block to the non-soluble poly(benzyl methacrylate) (PBzMA) segment. The resulting PLMA-b-PBzMA block copolymers simultaneously self-assemble into nanostructures of various sizes and morphologies. GTPISA in non-polar solvent proceeds rapidly at RT and avoids the use of sulfur or halogenated compounds or metallic catalysts associated with the implementation of CRP methods, thus expanding the potential of PISA formulations for applications in non-polar environments.

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.

Strong and Tough Nanostructured Hydrogels and Organogels Prepared by Polymerization-Induced Self-Assembly.

In nature, the hierarchical structure of biological tissues endows them with outstanding mechanics and elaborated functions. However, it remains a great challenge to construct biomimetic hydrogels with well-defined nanostructures and good mechanical properties. Herein, polymerization-induced self-assembly (PISA) is for the first time exploited as a general strategy for nanostructured hydrogels and organogels with tailored nanodomains and outstanding mechanical properties. As a proof-of-concept, PISA of BAB triblock copolymer is used to fabricate hydrogels with precisely regulated spherical nanodomains. These nanostructured hydrogels are strong, tough, stretchable, and recoverable, with mechanical properties correlating to their nanostructure. The outstanding mechanical properties are ascribed to the unique network architecture, where the entanglements of the hydrophilic chains act as slip links that transmit the tension to the micellar crosslinkers, while the micellar crosslinkers dissipate the energy via reversible deformation and irreversible detachment of the constituting polymers. The general feasibility of the PISA strategy toward nanostructured gels is confirmed by the successful fabrication of nanostructured hydrogels, alcogels, poly(ethylene glycol) gels, and ionogels with various PISA formulations. This work has provided a general platform for the design and fabrication of biomimetic hydrogels and organogels with tailorable nanostructures and mechanics and will inspire the design of functional nanostructured gels.

Synthesis of High Molecular Weight Water-Soluble Polymers as Low-Viscosity Latex Particles by RAFT Aqueous Dispersion Polymerization in Highly Salty Media.

We report the synthesis of sterically-stabilized diblock copolymer particles at 20% w/w solids via reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of N,N′-dimethylacrylamide (DMAC) in highly salty media (2.0 M (NH4)2SO4). This is achieved by selecting a well-known zwitterionic water-soluble polymer, poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC), to act as the salt-tolerant soluble precursor block. A relatively high degree of polymerization (DP) can be targeted for the salt-insoluble PDMAC block, which leads to the formation of a turbid free-flowing dispersion of PDMAC-core particles by a steric stabilization mechanism. 1H NMR spectroscopy studies indicate that relatively high DMAC conversions (>99%) can be achieved within a few hours at 30 °C. Aqueous GPC analysis indicates high blocking efficiencies and unimodal molecular weight distributions, although dispersities increase monotonically as higher degrees of polymerization (DPs) are targeted for the PDMAC block. Particle characterization techniques include dynamic light scattering (DLS) and electrophoretic light scattering (ELS) using a state-of-the-art instrument that enables accurate ζ potential measurements in a concentrated salt solution. 1H NMR spectroscopy studies confirm that dilution of the as-synthesized dispersions using deionized water lowers the background salt concentration and hence causes in situ molecular dissolution of the salt-intolerant PDMAC chains, which leads to a substantial thickening effect and the formation of transparent gels. Thus, this new polymerization-induced self-assembly (PISA) formulation enables high molecular weight water-soluble polymers to be prepared in a highly convenient, low-viscosity form. In principle, such aqueous PISA formulations are highly attractive: there are various commercial applications for high molecular weight water-soluble polymers, while the well-known negative aspects of using a RAFT agent (i.e., its cost, color, and malodor) are minimized when targeting such high DPs.

Morphology Control via RAFT Emulsion Polymerization-Induced Self-Assembly: Systematic Investigation of Core-Forming Blocks.

Polymerization-induced self-assembly (PISA) is a useful formulation for readily obtaining nanoparticles from block copolymers in situ. Reversible addition–fragmentation chain-transfer (RAFT) emulsion polymerization is utilized as one of the PISA formulations. Various factors have so far been investigated for obtaining nonspherical particles via RAFT emulsion polymerization, such as the steric structure of the shell, the glass-transition temperature (Tg) of the core-forming block, and the water solubility of the core-forming monomer. This study focuses on core-forming blocks without changing the structure of the shell-forming block. In particular, we elucidate the balance between Tg for the core-forming block and the water solubility of the core monomer. A series of alkyl methacrylates, such as methyl methacrylate (MMA), ethyl methacrylate (EMA), and n-propyl methacrylate (PrMA), are emulsion-polymerized in the presence of a poly[poly(ethylene glycol) methyl ether methacrylate] (PPEGMA) macromolecular chain-transfer agent via the RAFT process. The resulting in situ morphology changes to form shapes such as spheres, worms (toroids), and vesicles are systematically investigated. The properties of the core that determine whether a morphological change occurs from spheres are (i) the solubility of the core-forming monomer in water, (ii) the relationship between Tg for the core-forming block and the polymerization temperature, and (iii) the hydrophobic core volume, which changes the packing parameter. These factors allow prediction of the block copolymer morphology produced during RAFT emulsion polymerization of other methacrylates such as n-butyl methacrylate (BuMA), tetrahydrofurfuryl methacrylate (THFMA) with physical properties of the homopolymer (poly(tetrahydrofurfuryl methacrylate) (PTHFMA)) between those for poly(MMA) (PMMA) and PBuMA, and 1-adamantyl methacrylate (ADMA) with low monomer solubility in water and high Tg of the homopolymer (PADMA).

Reverse Sequence Polymerization-Induced Self-Assembly in Aqueous Media.

We report a new aqueous polymerization‐induced self‐assembly (PISA) formulation that enables the hydrophobic block to be prepared first when targeting diblock copolymer nano‐objects. This counter‐intuitive reverse sequence approach uses an ionic reversible addition–fragmentation chain transfer (RAFT) agent for the RAFT aqueous dispersion polymerization of 2‐hydroxypropyl methacrylate (HPMA) to produce charge‐stabilized latex particles. Chain extension using a water‐soluble methacrylic, acrylic or acrylamide comonomer then produces sterically stabilized diblock copolymer nanoparticles in an aqueous one‐pot formulation. In each case, the monomer diffuses into the PHPMA particles, which act as the locus for the polymerization. A remarkable change in morphology occurs as the ≈600 nm latex is converted into much smaller sterically stabilized diblock copolymer nanoparticles, which exhibit thermoresponsive behavior. Such reverse sequence PISA formulations enable the efficient synthesis of new functional diblock copolymer nanoparticles.

Reverse Sequence Polymerization‐Induced Self‐Assembly in Aqueous Media

We report a new aqueous polymerization-induced self-assembly (PISA) formulation that enables the hydrophobic block to be prepared first when targeting diblock copolymer nano-objects. This counter-intuitive reverse sequence approach uses an ionic reversible addition–fragmentation chain transfer (RAFT) agent for the RAFT aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) to produce charge-stabilized latex particles. Chain extension using a water-soluble methacrylic, acrylic or acrylamide comonomer then produces sterically stabilized diblock copolymer nanoparticles in an aqueous one-pot formulation. In each case, the monomer diffuses into the PHPMA particles, which act as the locus for the polymerization. A remarkable change in morphology occurs as the ≈600 nm latex is converted into much smaller sterically stabilized diblock copolymer nanoparticles, which exhibit thermoresponsive behavior. Such reverse sequence PISA formulations enable the efficient synthesis of new functional diblock copolymer nanoparticles.

Polymerization-Induced Self-Assembly Toward Micelle-Crosslinked Tough and Ultrastretchable Hydrogels

As a promising class of tough and ultrastretchable hydrogels, micelle-crosslinked hydrogels have been restrained by the scarcity of micellar crosslinkers with a high concentration, controlled nanostructure, and uniform size distribution. Herein, polymerization-induced self-assembly (PISA) was demonstrated to be a general and powerful platform for micellar crosslinkers, affording micelle-crosslinked hydrogels with tailorable chemical structures, mechanics, and functionality. Poly(N,N-dimethylacrylamide)-b-poly(diacetone acrylamide) (PDMAc-b-PDAAM) micellar crosslinkers with a controlled nanostructure and uniform size distribution were prepared via PISA and one-step post-polymerization modification at high concentrations. Copolymerization of these micellar crosslinkers with acrylamide generated tough and ultrastretchable hydrogels, whose mechanical properties were found correlated with the concentration, nanostructure, and chemical composition of the micelles. The energy dissipation mechanism of these micelle-crosslinked hydrogels was analyzed via cyclic mechanical tests and stress relaxation experiments. The general feasibility of PISA toward micelle-crosslinked hydrogels was verified by systematic evaluation of both aqueous (including 2-methoxyethyl acrylate, tetrahydro-2-furanylmethyl acrylate, and 4-hydroxybutyl acrylate) and alcoholic (including benzyl methacrylate, lauryl methacrylate, styrene, and benzyl acrylate) PISA formulations, producing hydrogels with diverse chemical structures, mechanics, and functionalities depending on the micellar crosslinkers. The modularity of this strategy was further demonstrated by the fabrication of fluoro-functionalized hydrogels with fluoro-containing micellar crosslinkers. This strategy has significantly enlarged the scope and application of micelle-crosslinked hydrogels.

Exploring the topological effect of linear and cyclic macroCTAs during polymerization-induced self-assembly (PISA)

Polymerization-induced self-assembly (PISA) is a robust strategy for the syntheses of block copolymer nano-objects with various morphologies. Although PISA has been extensively studied, the use of cyclic macromolecular chain transfer agents (macroCTAs) as the hydrophilic block has not been reported. We explored the effects of macroCTA topology on the polymerization kinetics and morphologies of block copolymer assemblies during reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization. To this end, linear and cyclic poly (ethylene oxide) (PEO) with 4-(4-cyanopentanoic acid) dithiobenzoate (CPADB) groups were synthesized and used as CTAs to mediate the RAFT polymerization of benzyl methacrylate (BzMA) and 2,3,4,5,6-pentafluorostyrene (PFSt) under PISA formulation. Interestingly, the nucleation period of the linear PEO is slightly shorter than that of its cyclic analog, and the cyclic hydrophilic segment leads to a delayed morphological transition during PISA.

Polymerization-induced self-assembly and disassembly during the synthesis of thermoresponsive ABC triblock copolymer nano-objects in aqueous solution.

Polymerization-induced self-assembly (PISA) has been widely utilized as a powerful methodology for the preparation of various self-assembled AB diblock copolymer nano-objects in aqueous media. Moreover, it is well-documented that chain extension of AB diblock copolymer vesicles using a range of hydrophobic monomers via seeded RAFT aqueous emulsion polymerization produces framboidal ABC triblock copolymer vesicles with adjustable surface roughness owing to microphase separation between the two enthalpically incompatible hydrophobic blocks located within their membranes. However, the utilization of hydrophilic monomers for the chain extension of linear diblock copolymer vesicles has yet to be thoroughly explored; this omission is addressed for aqueous PISA formulations in the present study. Herein poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) (G-H) vesicles were used as seeds for the RAFT aqueous dispersion polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA). Interestingly, this led to polymerization-induced disassembly (PIDA), with the initial precursor vesicles being converted into lower-order worms or spheres depending on the target mean degree of polymerization (DP) for the corona-forming POEGMA block. Moreover, construction of a pseudo-phase diagram revealed an unexpected copolymer concentration dependence for this PIDA formulation. Previously, we reported that PHPMA-based diblock copolymer nano-objects only exhibit thermoresponsive behavior over a relatively narrow range of compositions and DPs (see Warren et al., Macromolecules, 2018, 51, 8357–8371). However, introduction of the POEGMA coronal block produced thermoresponsive ABC triblock nano-objects even when the precursor G-H diblock copolymer vesicles proved to be thermally unresponsive. Thus, this new approach is expected to enable the rational design of new nano-objects with tunable composition, copolymer architectures and stimulus-responsive behavior.

Enzyme-assisted Photoinitiated Polymerization-induced Self-assembly in Continuous Flow Reactors with Oxygen Tolerance

Polymerization-induced self-assembly (PISA) is an emerging method for the preparation of block copolymer nano-objects at high concentrations. However, most PISA formulations have oxygen inhibition problems and inert atmospheres (e.g. argon, nitrogen) are usually required. Moreover, the large-scale preparation of block copolymer nano-objects at room temperature is challenging. Herein, we report an enzyme-assisted photoinitiated polymerization-induced self-assembly (photo-PISA) in continuous flow reactors with oxygen tolerance. The addition of glucose oxidase (GOx) and glucose into the reaction mixture can consume oxygen efficiently and constantly, allow the flow photo-PISA to be performed under open-air conditions. Polymerization kinetics indicated that only a small amount of GOx (0.5 μmol/L) was needed to achieve the oxygen tolerance. Block copolymer nano-objects with different morphologies can be prepared by varying reaction conditions including the degree of polymerization (DP) of core-forming block, monomer concentration, reaction temperature, and solvent composition. We expect this study will provide a facile platform for the large-scale production of block copolymer nano-objects with different morphologies at room temperature.

Influence of Spacer Lengths on the Morphology of Biphenyl-Containing Liquid Crystalline Block Copolymer Nanoparticles via Polymerization-Induced Self-Assembly

Polymerization-induced self-assembly (PISA) combining liquid crystallization has been proved an effective approach to one-dimensional block copolymer (BCP) nanoparticles (NPs). However, the liquid crystalline (LC) monomer library for the PISA systems is desired to be expanded. Moreover, the influence of molecular structure of LC moieties on the self-assembled morphology needs to be investigated in detail. In this work, we proposed a new PISA formulation based on biphenyl mesogen-containing BCPs with different spacer lengths. The thermal property, dispersion polymerization kinetics, and morphological evolution of BCP NPs with different spacer lengths were systematically investigated. The results indicate that the spacer length plays an important role in the physical appearance, micromorphology, and internal molecular arrangement of the NPs. The longer spacer is conducive to LC ordering within NPs, which induced the formation of rigid nanowires/nanorods. Owing to the strong coupling effect between backbone and mesogen, the NPs exhibit no LC property and form self-supporting gels when the spacer is short. This work expands the scope of LC monomer for PISA and provides the experimental reference for the design of new PISA formulations combining LC ordering.

Exploring the Upper Size Limit for Sterically Stabilized Diblock Copolymer Nanoparticles Prepared by Polymerization-Induced Self-Assembly in Non-Polar Media.

Reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate is used to prepare a series of well-defined poly(stearyl methacrylate)–poly(benzyl methacrylate) (PSMA–PBzMA) diblock copolymer nanoparticles in mineral oil at 90 °C. A relatively long PSMA54 precursor acts as a steric stabilizer block and also ensures that only kinetically trapped spheres are obtained, regardless of the target degree of polymerization (DP) for the core-forming PBzMA block. This polymerization-induced self-assembly (PISA) formulation provides good control over the particle size distribution over a wide size range (24–459 nm diameter). 1H NMR spectroscopy studies confirm that high monomer conversions (≥96%) are obtained for all PISA syntheses while transmission electron microscopy and dynamic light scattering analyses show well-defined spheres with a power-law relationship between the target PBzMA DP and the mean particle diameter. Gel permeation chromatography studies indicate a gradual loss of control over the molecular weight distribution as higher DPs are targeted, but well-defined morphologies and narrow particle size distributions can be obtained for PBzMA DPs up to 3500, which corresponds to an upper particle size limit of 459 nm. Thus, these are among the largest well-defined spheres with reasonably narrow size distributions (standard deviation ≤20%) produced by any PISA formulation. Such large spheres serve as model sterically stabilized particles for analytical centrifugation studies.

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.

Effect of Butyl α-Hydroxymethyl Acrylate Monomer Structure on the Morphology Produced via Aqueous Emulsion Polymerization-induced Self-assembly

Polymerization-induced self-assembly (PISA) is an efficient and versatile method to afford polymeric nano-objects with polymorphic morphologies. Compared to dispersion PISA syntheses based on soluble monomers, the vast majority of emulsion PISA formulations using insoluble monomers leads to kinetically-trapped spheres. Herein, we present aqueous emulsion PISA formulations generating worms and vesicles besides spheres. Two monomers with different butyl groups, n-butyl (nBHMA) and tert-butyl (tBHMA) α-hydroxymethyl acrylate, and thus possessing different water solubilities were synthesized via Baylis-Hillman reaction. Photoinitiated aqueous emulsion polymerizations of nBHMA and tBHMA employing poly(ethylene glycol) macromolecular chain transfer agents (macro-CTAs, PEG45-CTA, and PEG113-CTA) at 40 °C were systematically investigated to evaluate the effect of monomer structure and solubility on the morphology of the generated block copolymer nano-objects. Higher order morphologies including worms and vesicles were readily accessed for tBHMA, which has a higher water solubility than that of nBHMA. This study proves that plasticization of the core-forming block by water plays a key role in enhancing chain mobility required for morphological transition in emulsion PISA.

Emerging Trends in Polymerization-Induced Self-Assembly

In this Perspective, we summarize recent progress in polymerization-induced self-assembly (PISA) for the rational synthesis of block copolymer nanoparticles with various morphologies. Much of the PISA literature has been based on thermally initiated reversible addition-fragmentation chain transfer (RAFT) polymerization. Herein, we pay particular attention to alternative PISA protocols, which allow the preparation of nanoparticles with improved control over copolymer morphology and functionality. For example, initiation based on visible light, redox chemistry, or enzymes enables the incorporation of sensitive monomers and fragile biomolecules into block copolymer nanoparticles. Furthermore, PISA syntheses and postfunctionalization of the resulting nanoparticles (e.g., cross-linking) can be conducted sequentially without intermediate purification by using various external stimuli. Finally, PISA formulations have been optimized via high-throughput polymerization and recently evaluated within flow reactors for facile scale-up syntheses.

In Situ Small-Angle X-ray Scattering Studies During Reversible Addition-Fragmentation Chain Transfer Aqueous Emulsion Polymerization.

Polymerization-induced self-assembly (PISA) is a powerful platform technology for the rational and efficient synthesis of a wide range of block copolymer nano-objects (e.g., spheres, worms or vesicles) in various media. In situ small-angle X-ray scattering (SAXS) studies of reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization have previously provided detailed structural information during self-assembly (see M. J. Derry et al., Chem. Sci.2016, 7, 5078–509030155157). However, conducting the analogous in situ SAXS studies during RAFT aqueous emulsion polymerizations poses a formidable technical challenge because the inherently heterogeneous nature of such PISA formulations requires efficient stirring to generate sufficiently small monomer droplets. In the present study, the RAFT aqueous emulsion polymerization of 2-methoxyethyl methacrylate (MOEMA) has been explored for the first time. Chain extension of a relatively short non-ionic poly(glycerol monomethacrylate) (PGMA) precursor block leads to the formation of sterically-stabilized PGMA-PMOEMA spheres, worms or vesicles, depending on the precise reaction conditions. Construction of a suitable phase diagram enables each of these three morphologies to be reproducibly targeted at copolymer concentrations ranging from 10 to 30% w/w solids. High MOEMA conversions are achieved within 2 h at 70 °C, which makes this new PISA formulation well-suited for in situ SAXS studies using a new reaction cell. This bespoke cell enables efficient stirring and hence allows in situ monitoring during RAFT emulsion polymerization for the first time. For example, the onset of micellization and subsequent evolution in particle size can be studied when preparing PGMA29-PMOEMA30 spheres at 10% w/w solids. When targeting PGMA29-PMOEMA70 vesicles under the same conditions, both the micellar nucleation event and the subsequent evolution in the diblock copolymer morphology from spheres to worms to vesicles are observed. These new insights significantly enhance our understanding of the PISA mechanism during RAFT aqueous emulsion polymerization.

Block copolymer microparticles comprising inverse bicontinuous phases prepared via polymerization-induced self-assembly.

Traditionally, post-polymerization processing routes have been used to obtain a wide range of block copolymer morphologies. However, this self-assembly approach is normally performed at rather low copolymer concentration, which precludes many potential applications. Herein, we report a facile method for the preparation of block copolymer particles exhibiting complex internal morphology via polymerization-induced self-assembly (PISA). More specifically, a series of diblock copolymers were synthesized by reversible addition-fragmentation chain transfer (RAFT) alternating copolymerization of styrene (St) with N-phenylmaleimide (NMI) using a poly(N,N-dimethylacrylamide) (PDMAC) stabilizer as a soluble precursor. Conducting such PISA syntheses in a 50 : 50 w/w ethanol/methyl ethyl ketone (MEK) mixture leads directly to the formation of micrometer-sized PDMAC-P(St-alt-NMI) diblock copolymer particles at 20% w/w solids. Adjusting the degree of polymerization (DP) of the core-forming P(St-alt-NMI) block to target highly asymmetric copolymer compositions provides convenient access to an inverse bicontinuous phase. TEM studies of intermediate structures provide useful insights regarding the mechanism of formation of this phase. SEM studies indicate that the final copolymer particles comprise perforated surface layers and possess nanostructured interiors. In addition, control experiments using 1,4-dioxane suggest that the high chain mobility conferred by the MEK co-solvent is essential for the formation of such inverse bicontinuous structures. One-pot PISA formulations are reproducible and involve only cheap, commercially available starting materials, so they should be readily amenable to scale-up. This augurs well for the potential use of such nanostructured micrometer-sized particles as new organic opacifiers for paints and coatings.

Reactive Polymorphic Nanoparticles: Preparation via Polymerization‐Induced Self‐Assembly and Postsynthesis Thiol–para‐Fluoro Core Modification

The use of 2,3,4,5,6-pentafluorobenzyl methacrylate (PFBMA) as a core-forming monomer in ethanolic reversible addition-fragmentation chain transfer dispersion polymerization formulations is presented. Poly[poly(ethylene glycol) methyl ether methacrylate] (pPEGMA) macromolecular chain transfer agents were chain-extended with PFBMA leading to nanoparticle formation via polymerization-induced self-assembly (PISA). pPEGMA-pPFBMA particles exhibited the full range of morphologies (spheres, worms, and vesicles), including pure and mixed phases. Worm phases formed gels that underwent a thermo-reversible degelation and morphological transition to spheres (or spheres and vesicles) upon heating. Postsynthesis, the pPFBMA cores were modified through thiol-para-fluoro substitution reactions in ethanol using 1,8-diazabicyclo[5.4.0]undec-7-ene as the base. For monothiols, conversions were 64% (1-octanethiol) and 94% (benzyl mercaptan). Spherical and worm-shaped nano-objects were core cross-linked using 1,8-octanedithiol, which prevented their dissociation in nonselective solvents. For a temperature-responsive worm sample, cross-linking additionally resulted in the loss of the temperature-triggered morphological transition. The use of the reactive monomer PFBMA in PISA formulations presents a simple method to prepare well-defined nano-objects similar to those produced with nonreactive monomers (e.g., benzyl methacrylate) and to retain morphologies independent of solvent and temperature.