Expanding the scope of responsive polymeric nanostructures

This thesis focuses on expanding the scope of self-assembled polymeric nanostructures and their morphology transitions in response to a variety of applied stimuli. Chapter One gives an introduction to the main concepts and techniques used throughout the thesis. Chapter Two utilises a pH-deprotectable protected acid, incorporated into a diblock copolymer, in order to induce a morphology change in response to a change in pH. In addition, the effect of the hydrophilicity of the end group upon self-assembly is investigated. Chapter Three investigates a reversible pH-responsive system to induce a reversible vesicle to micelle morphology transition. This was achieved via the synthesis of an activated ester polymeric scaffold and the post-polymerisation introduction of backbone and end group functionality. Different end groups are investigated, along with the effect the molecular weight of the polymer has on the speed of transition. In addition, the controlled release of a hydrophilic payload is demonstrated. Chapter Four focuses on the incorporation of hydrophilic blocks, hydrophobic blocks or a combination of the two into sulfobetaine methacrylate containing polymers. The synthesis of these polymers by RAFT polymerisation is discussed and the polymers are thoroughly characterised by 1H NMR spectroscopy, SEC, SLS and multi-angle DLS. Chapter Five investigates the self-assembly and thermo-responsive behaviour of the polymers synthesised in Chapter Four. The subtle differences between the polymers and the effect of these differences on the responsive behaviour are highlighted. In addition the self-assembly of a thermo- pH- and CO2- triply-responsive triblock copolymer is discussed. Chapter Six investigates the synthesis and polymerisation behaviour of a sulfobetaine acrylate, in comparison to the sulfobetaine methacrylate observed in Chapter Four

The direct synthesis of sulfobetaine-containing amphiphilic block copolymers and their self-assembly behavior

Diblock copolymers containing the thermo-responsive sulfobetaine, [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (DMAPS), were synthesized by the aqueous RAFT polymerization of DMAPS, followed by direct chain extension in hexafluoroisopropanol (HFIP) with methyl methacrylate (MMA). This was shown to give lower dispersity polymers than RAFT emulsion polymerization. The diblock copolymers self-assembled in water to form micelles, as analyzed by light scattering (LS) and transmission electron microscopy (TEM). Micelles formed from diblocks bearing a long PDMAPS block were shown to swell with temperature, rather than display a traditional UCST cloud point. This was due to the polymers retaining hydrophilicity, even at temperatures well below the UCST for the corresponding PDMAPS homopolymer, as shown by variable temperature NMR. This swelling behavior was utilized in the release of a hydrophobic dye in response to temperature. This approach has great potential for applications in controlled release whilst maintaining the structure of the carrier nanoparticles

The direct synthesis of sulfobetaine-containing amphiphilic block copolymers and their self-assembly behavior

Diblock copolymers containing the thermo-responsive sulfobetaine, [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (DMAPS), were synthesized by the aqueous RAFT polymerization of DMAPS, followed by direct chain extension in hexafluoroisopropanol (HFIP) with methyl methacrylate (MMA). This was shown to give lower dispersity polymers than RAFT emulsion polymerization. The diblock copolymers self-assembled in water to form micelles, as analyzed by light scattering (LS) and transmission electron microscopy (TEM). Micelles formed from diblocks bearing a long PDMAPS block were shown to swell with temperature, rather than display a traditional UCST cloud point. This was due to the polymers retaining hydrophilicity, even at temperatures well below the UCST for the corresponding PDMAPS homopolymer, as shown by variable temperature NMR. This swelling behavior was utilized in the release of a hydrophobic dye in response to temperature. This approach has great potential for applications in controlled release whilst maintaining the structure of the carrier nanoparticles

Polysulfobetaine-based diblock copolymer nano-objects via polymerization-induced self-assembly

A zwitterionic polysulfobetaine-based macromolecular chain transfer agent (PSBMA38) was prepared by reversible addition–fragmentation chain transfer (RAFT) solution polymerization of [2-(methacryloyloxy)ethyl] dimethyl(3-sulfopropyl) ammonium hydroxide (SBMA) in an aqueous solution containing 0.5 M NaCl at 70 °C. This PSBMA38 macro-CTA was then utilized for the RAFT aqueous dispersion polymerization of a water-miscible monomer, 2-hydroxypropyl methacrylate (HPMA). The growing PHPMA block became hydrophobic in situ, leading to polymerization-induced self-assembly. Systematic variation of the mean degree of polymerization of the PHPMA block and the copolymer concentration enabled access to pure phases of spheres, worms or vesicles, as judged by transmission electron microscopy and dynamic light scattering studies. A detailed phase diagram was constructed and the thermo-responsive behavior of selected PSBMA38-PHPMAX nanoparticles was investigated. Finally, the salt tolerance of PSBMA38-PHPMA400 vesicles was compared to that of PGMA71-PHPMA400 vesicles; the former vesicles exhibit much better colloidal stability in the presence of 1 M MgSO4

Comparison of photo- and thermally initiated polymerization-induced self-assembly : a lack of end group fidelity drives the formation of higher order morphologies

Polymerization-induced self-assembly (PISA) is an emerging industrially relevant technology, which allows the preparation of defined and predictable polymer self-assemblies with a wide range of morphologies. In recent years, interest has turned to photoinitiated PISA processes, which show markedly accelerated reaction kinetics and milder conditions, thereby making it an attractive alternative to thermally initiated PISA. Herein, we attempt to elucidate the differences between these two initiation methods using isothermally derived phase diagrams of a well-documented poly(ethylene glycol)-b-(2-hydroxypropyl methacrylate) (PEG-b-HPMA) PISA system. By studying the influence of the intensity of the light source used, as well as an investigation into the thermodynamically favorable morphologies, the factors dictating differences in the obtained morphologies when comparing photo- and thermally initiated PISA were explored. Our findings indicate that differences in a combination of both reaction kinetics and end group fidelity led to the observed discrepencies between the two techniques. We find that the loss of the end group in photoinitiated PISA drives the formation of higher order structures and that a morphological transition from worms to unilamellar vesicles could be induced by extended periods of light and heat irradiation. Our findings demonstrate that PISA of identical block copolymers by the two different initiation methods can lead to structures that are both chemically and morphologically distinct

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

Dispersity effects in polymer self-assemblies : a matter of hierarchical control

Advanced applications of polymeric self-assembled structures require a stringent degree of control over such aspects as functionality location, morphology and size of the resulting assemblies. A loss of control in the polymeric building blocks of these assemblies can have drastic effects upon the final morphology or function of these structures. Gaining precise control over various aspects of the polymers, such as chain lengths and architecture, blocking efficiency and compositional distribution is a challenge and, hence, measuring the intrinsic mass and size dispersity within these areas is an important aspect of such control. It is of great importance that a good handle on how to improve control and accurately measure it is achieved. Additionally dispersity of the final structure can also play a large part in the suitability for a desired application. In this Tutorial Review, we aim to highlight the different aspects of dispersity that are often overlooked and the effect that a lack of control can have on both the polymer and the final assembled structure

Core functionalization of semi-crystalline polymeric cylindrical nanoparticles using photo-initiated thiol–ene radical reactions

Sequential ring-opening and reversible addition–fragmentation chain transfer (RAFT) polymerization was used to form a triblock copolymer of tetrahydropyran acrylate (THPA), 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC) and L-lactide. Concurrent deprotection of the THPA block and crystallization-driven self-assembly (CDSA) was undertaken and allowed for the formation of cylindrical micelles bearing allyl handles in a short outer core segment. These handles were further functionalized by different thiols using photo-initiated thiol–ene radical reactions to demonstrate that the incorporation of an amorphous PMAC block within the core does not disrupt CDSA and can be used to load the cylindrical nanoparticles with cargo

Polydimethylsiloxane-Based Diblock Copolymer Nano-objects Prepared in Nonpolar Media via RAFT-Mediated Polymerization-Induced Self-Assembly

Monocarbinol-functionalized polydimethylsiloxane (PDMS; mean degree of polymerization = 66) was converted via esterification into a chain transfer agent (CTA) for reversible addition–fragmentation chain transfer (RAFT) polymerization. The degree of esterification was determined to be 94 ± 1% by 1H NMR spectroscopy and 92 ± 1% by UV absorption spectroscopy. This PDMS CTA was then utilized for the dispersion polymerization of benzyl methacrylate (BzMA) in n-heptane at 70 °C. As the PBzMA block grows, it becomes insoluble in the reaction medium, which drives the in situ formation of PDMS–PBzMA diblock copolymer nanoparticles via polymerization-induced self-assembly (PISA). Depending on the precise reaction conditions, the final diblock copolymer chains can self-assemble to form spheres, worms, or vesicles. Systematic variation of the copolymer concentration and the target degree of polymerization (DP) of the PBzMA block enables construction of a phase diagram that allows the reproducible targeting of pure copolymer morphologies, as judged by transmission electron microscopy and dynamic light scattering studies. 1H NMR spectroscopy studies confirm that relatively high BzMA conversions (>90%) can be achieved within 8 h at 70 °C. Gel permeation chromatography studies (THF eluent) indicate high blocking efficiencies and relatively low final polydispersities (Mw/Mn = 1.14–1.34). Small-angle X-ray scattering (SAXS) has been used to characterize selected examples of the spherical nanoparticles in order to obtain volume-average diameters, which increase monotonically when targeting longer DPs for the core-forming PBzMA block. A relatively high copolymer concentration (>25% w/v) is required to obtain a pure worm phase, which occupies an extremely narrow region within the phase diagram. Selected worm and vesicle dispersions were also analyzed by SAXS, which enables determination of the mean worm cross section, mean worm length and vesicle membrane thickness. In addition, the highly anisotropic worms formed free-standing gels in n-heptane, with rheology measurements indicating viscoelastic behavior and a gel storage modulus of around 104 Pa