Polymerization-induced self-assembly

Solution self-assembly of BCPs is generally prepared by post-polymerization methods, including direct dissolution, solvent switch, and thin-film hydration, where polymers are first prepared and then self-assembled by a second process. These methods are robust and lead to the formation of various self-assembled morphologies which were introduced in Section 1.3. However, this method of self-assembly has disadvantages: mainly the high dilution of the resultant nanostructures and the difficulties in large-scale preparation of self-assemblies. Therefore, a new strategy by which the synthesis of block copolymers and the preparation of well-defined self- assemblies could be performed simultaneously in high concentration is favored. In recent years, a strategy called polymerization-induced self-assembly (PISA) is of interest as it meets the above demands, where block copolymers are prepared in a selective solvent using soluble macroinitiator or macromolecular chain transfer agent (macro-CTA) and self-assembly is formed simultaneously during the polymerization as the growing block is insoluble in this selective solvent (Figure 1.8).48

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PISA is now well established to allow access to different morphologies of self- assembly under both dispersion and emulsion polymerization conditions.47,48,82-86 This approach has enormous advantages in the design of systematic morphologies, as these can be achieved by simply varying the polymerization conditions (e.g., ratio of monomer to macro-CTA). Self-assemblies with controlled sizes and morphologies are formed during the polymerization process without any further assembly and purification steps. Controlled radical polymerization techniques such as NMP, ATRP, and RAFT polymerization have been broadly applied in this process,87 although RAFT polymerization is still the most popular method due to its versatility.48 Moreover, both dispersion polymerization and emulsion polymerization have been studied to polymerize soluble/insoluble monomers respectively in either aqueous or organic medium.48 For example, RAFT dispersion polymerizations in aqueous solution have been utilized to grow a water-insoluble new block from the water- soluble/miscible monomers in the presence of a solvent-soluble macro-CTA via a PISA process. Armes and coworkers performed the RAFT aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) using a water-soluble macro-CTA poly(glycerol monomethacrylate) (PGMA), where spherical micelles, worm-like micelles, bilayer octopi-like micelles, jellyfish-like micelles and vesicles were obtained sequentially as the polymerization proceeded for a target PGMA47-b-

PHPMA200 diblock copolymer (Figure 1.9). Similar morphologies and transitions

were also observed from separate polymerizations at full conversion but with increasing the initial ratio of monomer to macro-CTA. In addition, the resultant block copolymers were well-controlled in terms of molecular weight and molecular weight distributions.47

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Figure 1.9 TEM images obtained for (a) spheres, (b) short worms, (c) long worms, (d) branched worms, (e,f) partially coalesced worms, (g) jellyfish, and (h–j) vesicles generated

in situ after various reaction times for a target PGMA47-b-PHMA200 diblock copolymer

prepared by RAFT aqueous dispersion polymerization at 70 °C and 10% w/v solids. Scale bars = 200 nm.47

Similar to solution self-assembly of BCPs prepared by post-polymerization processes, there are many factors affecting the resultant polymers, morphologies and morphology transitions of PISA. In general, the factors affecting solution self- assemblies prepared by post-polymerization processes should be also considered in the process of PISA. Additionally, according to previous literature on PISA, factors affecting the results of PISA mainly include the nature of the macro-CTA (e.g., length, composition),88,89 monomers,48 core-forming polymer (e.g., LCST),90 and solvent,48 total solid content,91 feed ratio of polymerization components,91 cross linker,92 and the addition of monomers,82,93 amongst others.48

The nature of macro-CTA/macroinitiator is very important to the resultant morphologies and morphology transitions. For example, Armes and coworkers

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demonstrated RAFT dispersion polymerization of benzyl methacrylate (BzMA) using poly(lauryl methacrylate) (PLMA) as macro-CTA in non-polar solvents.88 It was found that a sphere-cylinder-vesicle transition occurred when using PLMA with a DP of 17. However, if longer PLMA with a DP of 37 was used, only spheres were observed even when the studied polymer was PLMA37-b-PBzMA900, which was

unexpected as in principle this system should form high order structures like vesicles due to the highly asymmetric chains. The proposed reason for this behaviour was that the longer PLMA block was sufficiently long to ensure effective steric stabilization and thus prevent the fusion of spheres to high order structures.

Another key parameter is the total solid content of the polymerization. Armes and coworkers showed that in the system of RAFT dispersion polymerization using HPMA as the monomer and poly(2-(methacryloyloxy) ethylphosphorylcholine) (PMPC) as the macro-CTA, different morphologies could be obtained from polymerizations with the same target polymer but at different solid contents (Figure 1.10, a-d, PMPC25-b-PHPMA400).91 On the other hand, it was found that

polymerizations with low solid content could only lead to the formation of spheres rather than high order structures like cylinders or vesicles (e.g., only spheres were formed from PMPC25-b-PHPMAx when the solid content was 10%, Figure 1.10).

One possible reason for this, reported in the study, was that the nature of PMPC, which is sensitive to solvation resulted in different pervaded block volumes between in dilute solution and in concentrated solution.91

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Figure 1.10 Detailed phase diagram constructed for the PMPC25-b-PHPMAx system and

TEM images for PMPC25-b-PHPMA400 at different solid contents and PMPC25-b-PHPMAx

at the same solid content (where M is PMPC, H is PHPMA, and x the DP of PHPMA).91

Besides common morphologies such as spheres, cylinders and vesicles, a few new morphologies can also be formed using PISA with the introduction of special monomers or polymerization conditions.82,92,93 Armes and coworkers prepared polymeric vesicles from PGMA58-b-PHPMA350 through aqueous RAFT dispersion

polymerization and then used it as a precursor to chain extend a third monomer.82 Four different types of monomer were investigated. If HPMA was used, vesicles with thick membranes were observed. When water-immiscible monomer benzyl methacrylate (BzMA) was employed which contributed to a second hydrophobic block, a distinctive framboidal morphology was observed due to the phase separation between the PHPMA and PBzMA blocks. When using water-immiscible methyl methacrylate (MMA) as monomer, a similar yet less framboidal morphology was observed, suggesting weaker microphase separation between PMMA and PHPMA. The use of ethylene glycol dimethacrylate (EGDMA) led to the formation of highly cross-linked vesicles. In addition, Pan and coworkers showed the formation of

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interesting unusual spaced concentric vesicles (SCVs) from poly(4-vinylpyridine)-b- polystyrene (P4VP-b-PS) by optimizing the conditions of RAFT dispersion polymerization in methanol. They showed that the concentration of the residual polymer chains in the lumen of nascent vesicles was a determining factor for the formation of SCVs.93

Recently, studies have also focused on introducing stimuli-responsive or functional polymers into PISA systems90,94 and moving towards exploiting the potential applications of PISA.94-96 For example, Sumerlin and coworkers demonstrated polymerization-induced thermal self-assembly (PITSA) using thermally responsive polymer, poly(N-isopropylacrylamide) (PNIPAm), as the growing core-forming block which induced the formation of self-assemblies above the lower critical solution temperature (LCST) of PNIPAm (Figure 1.11).90 To characterize the resultant nanoparticles, the particles were crosslinked immediately following polymerization at elevated temperature. This approach expands the PISA system to allow for preparation of ‘smart’ polymeric nanoparticle delivery vehicles.90 In addition, Davis and coworkers investigated guest molecule encapsulation through the PISA process.95 In their study, a guest molecule (Nile Red) was encapsulated with high efficiency during PISA process, without disturbing the resultant morphology or kinetics of PISA system.95 This study demonstrated that PISA has a significant potential for preparation of delivery vehicles in the medical or agricultural fields.95 In this thesis, inspired by previous work, we have investigated the formation of nucleobase-containing self-assemblies via PISA.

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Figure 1.11 (a) A representation of a PITSA process using RAFT dispersion polymerization; (b) Progression of polymeric nanoparticle morphology with increasing the degree of

polymerization of hydrophobic block.90