Thermoreversible block copolymer worm gels using binary mixtures of PEG stabilizer blocks

Two trithiocarbonate-based poly(ethylene glycol) (PEG) macromolecular chain transfer agents (macro-CTAs) with mean degrees of polymerization of 45 and 113 were prepared with ≥94% chain-end functionality. Binary mixtures of these PEG–trithiocarbonate macro-CTAs were then chain-extended via reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA). Systematic variation of the relative proportions of PEG45 and PEG113 macro-CTAs and the degree of polymerization of the PHPMA core-forming block resulted in the formation of [x PEG45 + z PEG113] – PHPMAn block copolymer spheres, worms, or vesicles, where x and z represent the mole fractions of PEG45 and PEG113, respectively. A phase diagram was constructed to establish the relationship between block copolymer composition and nanoparticle morphology. The thermoresponsive behavior of block copolymer worms was assessed by visual inspection, dynamic light scattering (DLS), transmission electron microscopy (TEM) and temperature-dependent oscillatory rheology. Increasing the proportion of PEG45 (x = 0.00–0.40) in the stabilizer block resulted in a moderate increase in worm gel strength, but cooling resulted in irreversible degelation owing to a worm-to-sphere morphology transition. However, the phase diagram enabled identification of a single diblock copolymer composition that exhibited reversible degelation behavior in pure water. This formulation was then further optimized to exhibit the same rheological behavior in a commercial cell culture medium (Nutristem) by fixing the PEG mole fraction at x = 0.70 while lowering the PHPMA DP from 115 to 75. Importantly, the gel strength at physiological temperature can be readily tuned simply by variation of the copolymer concentration. In principle, this study has important implications for the preservation of human stem cells, which can enter stasis when immersed in certain worm gels [see: Canton et al. ACS Cent. Sci. 2016, 2, 65–74]

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

Cross-linked cationic diblock copolymer worms are superflocculants for micrometer-sized silica particles

A series of linear cationic diblock copolymer nanoparticles are prepared by polymerization-induced self-assembly (PISA) via reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) using a binary mixture of non-ionic and cationic macromolecular RAFT agents, namely poly(ethylene oxide) (PEO113, Mn = 4400 g mol−1; Mw/Mn = 1.08) and poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride) (PQDMA125, Mn = 31 800 g mol−1, Mw/Mn = 1.19). A detailed phase diagram was constructed to determine the maximum amount of PQDMA125 stabilizer block that could be incorporated while still allowing access to a pure worm copolymer morphology. Aqueous electrophoresis studies indicated that zeta potentials of +35 mV could be achieved for such cationic worms over a wide pH range. Core cross-linked worms were prepared via statistical copolymerization of glycidyl methacrylate (GlyMA) with HPMA using a slightly modified PISA formulation, followed by reacting the epoxy groups of the GlyMA residues located within the worm cores with 3-aminopropyl triethoxysilane (APTES), and concomitant hydrolysis/condensation of the pendent silanol groups with the secondary alcohol on the HPMA residues. TEM and DLS studies confirmed that such core cross-linked cationic worms remained colloidally stable when challenged with either excess methanol or a cationic surfactant. These cross-linked cationic worms are shown to be much more effective bridging flocculants for 1.0 μm silica particles at pH 9 than the corresponding linear cationic worms (and also various commercial high molecular weight water-soluble polymers.). Laser diffraction studies indicated silica aggregates of around 25–28 μm diameter when using the former worms but only 3–5 μm diameter when employing the latter worms. Moreover, SEM studies confirmed that the cross-linked worms remained intact after their adsorption onto the silica particles, whereas the much more delicate linear worms underwent fragmentation under the same conditions. Similar results were obtained with 4 μm silica particles

Stimulus-responsive non-ionic diblock copolymers: protonation of a tertiary amine end-group induces vesicle-to-worm or vesicle-to-sphere transitions

A well-defined poly(glycerol monomethacrylate) (PGMA) macromolecular chain transfer agent (macroCTA) with a mean degree of polymerisation (DP) of 43 was prepared by reversible addition–fragmentation chain transfer (RAFT) polymerisation using a morpholine-functionalised trithiocarbonate-based chain transfer agent (MPETTC). Chain extension of this macro-CTA by RAFT aqueous dispersion polymerisation of 2-hydroxypropyl methacrylate (HPMA) at pH 7.0–7.5 produced a series of four MPETTC-PGMA43- PHPMAy vesicles (where y = 190, 200, 220 or 230). Protonation of the morpholine end-group increases the hydrophilic character of the PGMA stabiliser block, which leads to a reduction in the packing parameter for the diblock copolymer chains. However, such pH-responsive behaviour critically depends on the value of y. For y = 190 or 200, lowering the solution pH to pH 3 induces a vesicle-to-worm transition at 20 °C according to dynamic light scattering, aqueous electrophoresis, transmission electron microscopy and turbidimetry studies. This order–order transition is suppressed in the presence of added electrolyte, which screens the cationic end-groups. In addition, no change in copolymer morphology was observed on lowering the solution temperature at neutral pH, regardless of the y value. The diblock copolymer nano-objects obtained at pH 3 were also cooled to 4 °C to examine their dual stimulusresponsive behaviour to both pH and temperature triggers. In all four cases, a change in morphology from either worms or vesicles to afford spheres (or spheres plus relatively short worms) was observed. Temperature-dependent oscillatory rheology experiments performed on cationic worms at pH 3 indicated a worm-to-sphere transition on cooling from 20 °C to 4 °C, which leads to reversible degelation. In summary, spheres, worms or vesicles can be obtained for MPETTC-PGMA-PHPMA diblock copolymers on first lowering the solution pH to pH 3, followed by cooling from 20 °C to 4 °C

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

pH-Responsive non-ionic diblock copolymers: protonation of a morpholine end-group induces an order-order transition

A new morpholine-functionalised, trithiocarbonate-based RAFT agent, MPETTC, was synthesised with an overall yield of 80% and used to prepare a poly(glycerol monomethacrlyate) (PGMA) chain transfer agent. Subsequent chain extension with 2-hydroxypropyl methacrylate (HPMA) using a RAFT aqueous dispersion polymerisation formulation at pH 7.0–7.5 resulted in the formation of morpholine-functionalised PGMA-PHPMA diblock copolymer worms via polymerisation-induced self-assembly (PISA). These worms form soft, free-standing aqueous hydrogels at 15% w/w solids. Acidification causes protonation of the morpholine end-groups, which increases the hydrophilic character of the PGMA stabiliser block. This causes a subtle change in the copolymer packing parameter which induces a worm-to-sphere morphological transition and hence leads to in situ degelation at pH 3. This order–order transition was characterised by dynamic light scattering, transmission electron microscopy and gel rheology studies. On returning to pH 7, regelation is observed at 15% w/w solids, indicating the reversible nature of the transition. However, such diblock copolymer worm gels remain intact when acidified in the presence of electrolyte, since the terminal cationic charge arising from the protonated morpholine end-groups is screened under these conditions. Moreover, regelation is also observed in relatively acidic solution (pH < 2), because the excess acid acts as a salt under these conditions and so induces a sphere-to-worm transition

Stimulus-responsive block copolymer nano-objects and hydrogels via dynamic covalent chemistry

Herein we demonstrate that dynamic covalent chemistry can be used to induce reversible morphological transitions in block copolymer nano-objects and hydrogels. Poly(glycerol monomethacrylate)–poly(2- hydroxypropyl methacrylate) (PGMA–PHPMA) diblock copolymer nano-objects (vesicles or worms) were prepared via polymerization-induced self-assembly. Addition of 4-carboxyphenylboronic acid (CPBA) leads to the formation of phenylboronate ester bonds with the 1,2-diol pendent groups on the hydrophilic PGMA stabilizer chains; such binding causes a subtle reduction in the packing parameter, which in turn induces either vesicle-to-worm or worm-to-sphere transitions. Moreover, CPBA binding is pH-dependent, so reversible transitions can be achieved by switching the solution pH, with relatively high copolymer concentrations leading to associated (de)gelation. This distinguishes these new physical hydrogels from the covalently cross-linked gels prepared using dynamic covalent chemistry reported in the literature

What dictates the spatial distribution of nanoparticles within calcite?

Crystallization is widely used by synthetic chemists as a purification technique because it usually involves the expulsion of impurities. In this context, the efficient occlusion of guest nanoparticles within growing host crystals can be regarded as a formidable technical challenge. Indeed, although there are various reports of successful nanoparticle occlusion within inorganic crystals in the literature, robust design rules remain elusive. Herein, we report the synthesis of two pairs of sterically stabilized diblock copolymer nanoparticles with identical compositions but varying particle size, morphology, stabilizer chain length, and stabilizer chain surface density via polymerization-induced self-assembly (PISA). The mean degree of polymerization of the stabilizer chains dictates the spatial distribution of these model anionic nanoparticles within calcite (CaCO3): relatively short stabilizer chains merely result in near-surface occlusion, whereas sufficiently long stabilizer chains are essential to achieve uniform occlusion. This study reconciles the various conflicting literature reports of occluded nanoparticles being either confined to surface layers or uniformly occluded throughout the host matrix and hence provides important new insights regarding the criteria required for efficient nanoparticle occlusion within inorganic crystals

Incorporating Diblock Copolymer Nanoparticles into Calcite Crystals: Do Anionic Carboxylate Groups Alone Ensure Efficient Occlusion?

New spherical diblock copolymer nanoparticles were synthesized via RAFT aqueous dispersion polymerization of 2- hydroxypropyl methacrylate (HPMA) at 70 °C and 20% w/w solids using either poly(carboxybetaine methacrylate) or poly(proline methacrylate) as the steric stabilizer block. Both of these stabilizers contain carboxylic acid groups, but poly(proline methacrylate) is anionic above pH 9.2, whereas poly(carboxybetaine methacrylate) has zwitterionic character at this pH. When calcite crystals are grown at an initial pH of 9.5 in the presence of these two types of nanoparticles, it is found that the anionic poly(proline methacrylate)-stabilized particles are occluded uniformly throughout the crystals (up to 6.8% by mass, 14.0% by volume). In contrast, the zwitterionic poly(carboxybetaine methacrylate)- stabilized particles show no signs of occlusion into calcite crystals grown under identical conditions. The presence of carboxylic acid groups alone therefore does not guarantee efficient occlusion: overall anionic character is an additional prerequisite

How do charged end-groups on the steric stabilizer block influence the formation and long-term stability of Pickering nanoemulsions prepared using sterically stabilized diblock copolymer nanoparticles?

Reversible addition–fragmentation chain transfer (RAFT) solution polymerization is used to prepare well-defined poly(glycerol monomethacrylate) (PGMA) chains bearing carboxylic acid, tertiary amine, or neutral end-groups. Each of these PGMA precursors was then chain-extended in turn via RAFT aqueous emulsion polymerization of 2,2,2-trifluoroethyl methacrylate to form spherical nanoparticles as confirmed by transmission electron microscopy (TEM) analysis. Dynamic light scattering studies indicated an intensity-average diameter of approximately 25 nm. Aqueous electrophoresis measurements confirmed that the amine-functional nanoparticles became cationic at low pH owing to end-group protonation. In contrast, carboxylic acid-functional nanoparticles became appreciably anionic at pH 10 owing to end-group ionization. Finally, nanoparticles bearing neutral end-groups exhibited zeta potentials close to zero over a range of solution pH. High-shear homogenization of n-dodecane in the presence of such sterically stabilized nanoparticles led to the formation of oil-in-water Pickering macroemulsions with volume-average diameters of 20–30 μm. High-pressure microfluidization was then used to prepare the three corresponding Pickering nanoemulsions. Each Pickering nanoemulsion was characterized by analytical centrifugation and TEM studies of the dried nanoemulsion droplets confirmed their original nanoparticle superstructure. The nanoparticle adsorption efficiency at the oil–water interface was assessed by gel permeation chromatography (using a UV detector) for each nanoparticle type at both pH 3 and 7. Nanoparticles with charged end-groups exhibited relatively low adsorption efficiency, whereas up to 90% of the neutral nanoparticles were adsorbed onto the oil droplets. This observation was supported by small-angle X-ray scattering experiments, which indicated that the packing efficiency of neutral nanoparticles around oil droplets was higher than that of nanoparticles bearing charged end-groups. Analytical centrifugation was used to evaluate the colloidal stability of the aged Pickering nanoemulsions. Pickering nanoemulsions stabilized with nanoparticles bearing charged end-groups proved to be significantly less stable than those prepared using neutral end-groups