Optimization of the high-throughput synthesis of multiblock copolymer nanoparticles in aqueous media: Via polymerization-induced self-assembly

Over the past fifteen years or so, polymerization-induced self-assembly (PISA) has become widely recognized as a powerful and versatile platform technology for the synthesis of a wide range of block copolymer nanoparticles of controlled size, shape and surface chemistry. In the present study, we report that PISA formulations are sufficiently robust to enable high-throughput experiments using a commercial synthesis robot (Chemspeed Autoplant A100). More specifically, we use reversible addition-fragmentation chain transfer (RAFT) aqueous emulsion polymerization of either n-butyl methacrylate and/or benzyl methacrylate to prepare various examples of methacrylic multiblock copolymer nanoparticles using a poly(methacrylic acid) stabilizer block. Adequate stirring is essential to generate sufficiently small monomer droplets for such heterogeneous polymerizations to proceed efficiently. Good reproducibility can be achieved under such conditions, with well-defined spherical morphologies being obtained at up to 45% w/w solids. GPC studies indicate high blocking efficiencies but relatively broad molecular weight distributions (Mw/Mn= 1.36-1.85), suggesting well-defined (albeit rather polydisperse) block copolymer chains. These preliminary studies provide a sound basis for high-throughput screening of RAFT-mediated PISA formulations, which is likely to be required for commercialization of this technology. Our results indicate that methacrylic PISA formulations enable the synthesis of diblock and triblock copolymer nanoparticles in high overall yield (94-99%) within 1-3 h at 70 °C. However, tetrablocks suffer from incomplete conversions (87-96% within 5 h) and hence most likely represent the upper limit for this approach

Solution and Solid-State Behavior of Amphiphilic ABA Triblock Copolymers of Poly(acrylic acid-stat-styrene)-block-poly(butyl acrylate)-block-poly(acrylic acid-stat-styrene)

A combination of statistical and triblock copolymer properties is explored to produce stable aqueous polymer dispersions suitable for the film formation. In order to perform an extensive structural characterization of the products in the dissolved, dispersed, and solid states, a wide range of symmetrical poly(acrylic acid-stat-styrene)x-block-poly(butyl acrylate)y-block-poly(acrylic acid-stat-styrene)x, poly(AA-st-St)x-b-PBAy-b-poly(AA-st-St)x, (x = 56, 108 and 140, y = 100–750; the AA:St molar ratio is 42:58) triblock copolymers were synthesized by reversible addition–fragmentation chain transfer (RAFT) solution polymerization using a bifunctional symmetrical RAFT agent. It is demonstrated that the amphiphilic statistical outer blocks can provide sufficient stabilization to largely hydrophobic particles in aqueous dispersions. Such a molecular design provides an advantage over copolymers composed only of homoblocks, as a simple variation of the statistical block component ratio provides an efficient way to control the hydrophilicity of the stabilizer block, which ultimately affects the copolymer morphology in solutions and solid films. It was found by small-angle X-ray scattering (SAXS) that the copolymers behaved as dissolved chains in methylethylketone (MEK) but self-assembled in water into stable and well-defined spherical particles that increased in size with the length of the hydrophobic PBA block. These particles possessed an additional particulate surface structure formed by the statistical copolymer stabilizer block, which self-folded through the hydrophobic interactions between the styrene units. SAXS and atomic force microscopy showed that the copolymer films cast from the MEK solutions formed structures predicted by self-consistent field theory for symmetrical triblock copolymers, while the aqueous dispersions formed structural morphologies similar to a close-packed spheres, as would be expected for copolymer particles trapped kinetically due to the restricted movement of the blocks in the initial aqueous dispersion. A strong correlation between the structural morphology and mechanical properties of the films was observed. It was found that the properties of the solvent cast films were highly dependent on the ratios of the hard [poly(AA-st-St)] and soft (PBA) blocks, while the aqueous cast films did not show such a dependence. The continuous phase of hard blocks, always formed in the case of the aqueous cast films, produced films with a higher elastic modulus and a lower extension-to-break in a comparison with the solvent-cast films

Self-assembly of amphiphilic statistical copolymers and their aqueous rheological properties

A range of poly(n-butyl methacrylate-stat-methacrylic acid) [P(BMA-stat-MAA)] statistical copolymers of various compositions and molecular weights ranging from 5 to 30 kDa were prepared using either reversible addition-fragmentation chain transfer (RAFT) solution copolymerization or conventional free radical polymerization in isopropanol (IPA). On dilution with water, these amphiphilic copolymers self-assembled to form spherical nano-objects as confirmed by small-angle X-ray scattering (SAXS) and transmission electron microscopy. Various structural particle models were examined to extract information regarding the mean nano-object size and morphology. It is found that nano-object radii are independent of copolymer molecular weight, but depend on the copolymer composition: the smaller the amount of MAA units in the molecules the larger the nanoobjects are formed. Combined SAXS and aqueous electrophoretic measurements indicated that most of the MAA units are located at the nano-object surface. Furthermore, SAXS and rheology measurements were used to monitor the effect of solvent composition on the copolymer morphology both at a fixed copolymer concentration (either 1 wt% or 25 wt%) and also for a gradual variation in copolymer 2 concentrations (from 1 wt% to 40 wt%) when adding water to the initial copolymer solution in IPA. These studies revealed that the copolymers are present in solution as molecularly-dissolved Gaussian chains when the solvent composition is IPA-rich. However, the copolymer chains self-assemble into spherical nano-objects when the solvent composition is water-rich. At intermediate solvent compositions, SAXS analysis confirmed the formation of an interconnected nano-object network, which accounts for the apparently anomalous increase in solution viscosity on dilution indicated by rheology measurements

Control of particle size in the self-assembly of amphiphilic statistical copolymers

A range of amphiphilic statistical copolymers is synthesized where the hydrophilic component is either methacrylic acid (MAA) or 2-(dimethylamino)ethyl methacrylate (DMAEMA) and the hydrophobic component comprises methyl, ethyl, butyl, hexyl, or 2-ethylhexyl methacrylate, which provide a broad range of partition coefficients (log P). Small-angle X-ray scattering studies confirm that these amphiphilic copolymers self-assemble to form well-defined spherical nanoparticles in an aqueous solution, with more hydrophobic copolymers forming larger nanoparticles. Varying the nature of the alkyl substituent also influenced self-assembly with more hydrophobic comonomers producing larger nanoparticles at a given copolymer composition. A model based on particle surface charge density (PSC model) is used to describe the relationship between copolymer composition and nanoparticle size. This model assumes that the hydrophilic monomer is preferentially located at the particle surface and provides a good fit to all of the experimental data. More specifically, a linear relationship is observed between the surface area fraction covered by the hydrophilic comonomer required to achieve stabilization and the log P value for the hydrophobic comonomer. Contrast variation small-angle neutron scattering is used to study the internal structure of these nanoparticles. This technique indicates partial phase separation within the nanoparticles, with about half of the available hydrophilic comonomer repeat units being located at the surface and hydrophobic comonomer-rich cores. This information enables a refined PSC model to be developed, which indicates the same relationship between the surface area fraction of the hydrophilic comonomer and the log P of the hydrophobic comonomer repeat units for the anionic (MAA) and cationic (DMAEMA) comonomer systems. This study demonstrates how nanoparticle size can be readily controlled and predicted using relatively ill-defined statistical copolymers, making such systems a viable attractive alternative to diblock copolymer nanoparticles for a range of industrial applications