Nicholas J. W. Penfold

Semi-crystalline diblock copolymer nano-objects prepared via RAFT alcoholic dispersion polymerization of stearyl methacrylate

The RAFT dispersion polymerization of stearyl methacrylate (SMA) is conducted in ethanol at 70 °C using a poly(2-(dimethylamino)ethyl methacrylate) [PDMA] chain transfer agent. The growing PSMA block becomes insoluble in ethanol, which leads to polymerization-induced self-assembly (PISA) and hence produces a range of copolymer morphologies depending on the precise PDMAy–PSMAx formulation. More specifically, pure phases corresponding to either spherical nanoparticles, worm-like nanoparticles or vesicles can be prepared as judged by transmission electron microscopy. However, the worm phase space is relatively narrow, so construction of a detailed phase diagram is required for reproducible syntheses of this morphology. Inter-digitation of the stearyl (C18) side-groups leads to a semi-crystalline PSMA core block and the effect of systematically varying the mean degree of polymerization of both the PDMA and PSMA blocks on the Tm and Tc is investigated using differential scanning calorimetry. Finally, it is demonstrated that these cationic nanoparticles can be employed as colloidal templates for the in situ deposition of silica from aqueous solution.

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.

Cationic and reactive primary amine-stabilised nanoparticles via RAFT aqueous dispersion polymerisation

The synthesis of primary amine-functionalised diblock copolymer nanoparticles via polymerisation-induced self-assembly (PISA) using a RAFT aqueous dispersion polymerisation formulation is reported. The primary amine steric stabiliser is a macromolecular chain transfer agent (macro-CTA) based on 2-aminoethyl methacrylate AMA, which can be readily polymerised in its hydrochloride salt form with good control (Mw/Mn < 1.30) using RAFT aqueous solution polymerisation. Subsequent chain extension of this macro-CTA with 2-hydroxypropyl methacrylate (HPMA) leads to the formation of relatively monodisperse spherical nanoparticles (68 to 288 nm) at pH 6. However, worms or vesicles could not be obtained, because strong lateral repulsion between the highly cationic PAMA stabiliser chains impedes the formation of these higher order copolymer morphologies. Deprotonation of the primary amine stabiliser chains at or above pH 9 results in flocculation of these spherical nanoparticles as the PAMA block becomes uncharged. Diblock copolymer spheres, worms or vesicles can be synthesised that remain stable at pH 9 by supplementing the PAMA macro-CTA with a poly(glycerol monomethacrylate) (PGMA) macro-CTA, since this non-ionic block confers effective steric stabilisation in alkaline media. A series of diblock copolymer nanoparticles with the general formula ([1 − n]PGMAx + nPAMAy)–PHPMAz can be synthesised by optimising: (i) the mean degree of polymerisation (DP, or x) of the PGMA block, (ii) the PHPMA core-forming DP (or z); (iii) the mol fraction (n) of the PAMA stabiliser; and (iv) the copolymer concentration. These spheres, worms and vesicles are both cationic at low pH and colloidally stable at high pH. Furthermore, deprotonation of the protonated primary amine groups on the PAMA stabiliser chains at high pH renders these particles susceptible to epoxy-amine conjugation. This is demonstrated by the reaction between the primary amine groups on (0.8PGMA101 + 0.2PAMA96)–PHPMA1000 diblock copolymer spheres, and epoxide-functionalised diblock copolymer nanoparticles in aqueous solution at pH 8.

Bespoke cationic nano-objects via RAFT aqueous dispersion polymerisation

A range of cationic diblock copolymer nanoparticles are synthesised via polymerisation-induced self-assembly (PISA) using a RAFT aqueous dispersion polymerisation formulation. The cationic character of these nanoparticles can be systematically varied by utilising a binary mixture of two macro-CTAs, namely non-ionic poly(glycerol monomethacrylate) (PGMA) and cationic poly[2-(methacryloyloxy)ethyl]trimethylammonium chloride (PQDMA), with poly(2-hydroxypropyl methacrylate) (PHPMA) being selected as the hydrophobic core-forming block. Thus a series of cationic diblock copolymer nano-objects with the general formula ([1 − n] PGMAx + [n] PQDMAy) − PHPMAz were prepared at 20% w/w solids, where n is the mol fraction of the cationic block and x, y and z are the mean degrees of polymerisation of the non-ionic, cationic and hydrophobic blocks, respectively. These cationic diblock copolymer nanoparticles were analysed in terms of their chemical composition, particle size, morphology and cationic character using 1H NMR spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), and aqueous electrophoresis, respectively. Systematic variation of the above PISA formulation enabled the formation of spheres, worms or vesicles that remain cationic over a wide pH range. However, increasing the cationic character favors the formation of kinetically-trapped spheres, since it leads to more effective steric stabilisation which prevents sphere–sphere fusion. Furthermore, cationic worms form a soft free-standing gel at 25 °C that undergoes reversible degelation on cooling, as indicated by variable temperature oscillatory rheology studies. Finally, the antimicrobial activity of this thermo-responsive cationic worm gel towards the well-known pathogen Staphylococcus aureus is examined via direct contact assays.

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 (macro-CTA) 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 stimulus-responsive 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.

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.

Layer-By-Layer Self-Assembly of Polyelectrolytic Block Copolymer Worms on a Planar Substrate

Cationic and anionic block copolymer worms are prepared by polymerization-induced self-assembly via reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion copolymerization of 2-hydroxypropyl methacrylate and glycidyl methacrylate (GlyMA), using a binary mixture of a nonionic poly(ethylene oxide) macromolecular RAFT agent and either a cationic poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride) or an anionic poly(potassium 3-sulfopropyl methacrylate) macromolecular RAFT agent. In each case, covalent stabilization of the worm cores was achieved via reaction of the epoxide groups on the GlyMA repeat units with 3-mercaptopropyltriethoxysilane. Aqueous electrophoresis studies indicated a pH-independent mean zeta potential of +40 mV and −39 mV for the cationic and anionic copolymer worms, respectively. These worms are expected to mimic the rigid rod behavior of water-soluble polyelectrolyte chains in the absence of added salt. The kinetics of adsorption of the cationic worms onto a planar anionic silicon wafer was examined at pH 5 and was found to be extremely fast at 1.0 w/w % copolymer concentration in the absence of added salt. Scanning electron microscopy (SEM) analysis indicated that a relatively constant worm surface coverage of 16% was achieved at 20 °C for adsorption times ranging from just 2 s up to 2 min. Furthermore, the successive layer-by-layer deposition of cationic and anionic copolymer worms onto planar surfaces was investigated using SEM, ellipsometry, and surface zeta potential measurements. These techniques confirmed that the deposition of oppositely charged worms resulted in a monotonic increase in the mean layer thickness, with a concomitant surface charge reversal occurring on addition of each new worm layer. Unexpectedly, two distinct linear regimes were observed when plotting the mean layer thickness against the total number of adsorbed worm layers, with a steeper gradient (corresponding to thicker layers) being observed after the deposition of six worm layers.

Epoxy-Functional Sterically Stabilized Diblock Copolymer Nanoparticles via RAFT Aqueous Emulsion Polymerization: Comparison of Two Synthetic Strategies

Polymerization-induced self-assembly (PISA) is a powerful and versatile technique for the synthesis of a wide range of sterically stabilized diblock copolymer nano-objects. Recently, PISA has been used to prepare epoxy-functional diblock copolymer worms and spheres directly in aqueous solution by incorporating glycidyl methacrylate (GlyMA) into the core-forming hydrophobic block. Herein, the synthesis of diblock copolymer spheres via reversible addition-fragmentation chain transfer (RAFT) aqueous emulsion polymerization of benzyl methacrylate is examined, in which the epoxy groups are exclusively located within a non-ionic poly(glycerol monomethacrylate)-based stabilizer block. Two synthetic strategies are explored: i) using an epoxy-functional RAFT chain transfer agent (CTA) to place an epoxy group at the terminus of every stabilizer block and ii) incorporation of ≈1 epoxy group per stabilizer chain via copolymerization of GlyMA with glycerol monomethacrylate (GMA). The epoxy groups conferred by the GlyMA comonomer are significantly more resistant to hydrolysis than those introduced using the epoxy-functional RAFT CTA. The epoxy-functional nanoparticles are subsequently reacted with various water-soluble thiols to modify their electrophoretic behavior. Such nanoparticles are expected to offer potential applications in the context of mucoadhesion.