Investigating Opportunities for Enhancing the Sustainability of Polymerisation-Induced Self-Assembly

Polymerisation-Induced Self-Assembly (PISA) is a convenient and highly rational method of producing block copolymer nanoparticles in a single step, crucially avoiding post-polymerisation processing. PISA typically requires petroleum sourced reagents, stringent reaction conditions and produces non-degradable nanoparticles. Consequently, attempts to improve the safety and sustainability of PISA by incorporating the principles of ‘green chemistry’, are sought after. This thesis investigates several potential areas of improvement. RAFT PISA was attempted in dihydrolevoglucosenone (cyrene), a green solvent alternative for dimethylformamide (DMF). A number of acrylate, methacrylate and acrylamide monomers successfully underwent polymerisation, and N-hydroxyethylacrylamide precipitated out of cyrene on polymerising. This was then used as a solvophobic block in PISA, using two different macro-chain transfer agents (macro-CTA) to produce spherical nanoparticles in situ. Following this, N-carboxyanhydride ring-opening polymerization-induced self-assembly (NCA ROPISA) was investigated to produce poly(amino acid)-based nanoparticles in a single step. This was first investigated under aqueous conditions using a polyethylene glycol (PEG113-NH2) macro-initiator, which was successfully chain extended with L-Phenylalanine-NCA (Phe-NCA) and Alanine-NCA (Ala-NCA). The resultant block copolymers self-assembled to form moderately polydisperse nanoparticles in situ. Most examples of NCA ROPISA make use of a PEG hydrophilic stabilizing block, however this non-degradable, oil-derived polymer may cause an immunological response in some individuals, so the use of an alternative water-soluble polymer is investigated. The synthesis of wholly poly(amino acid)-based nanoparticles, produced through the chain-extension of a polysarcosine (PSar) macroinitiator with Phe-NCA and Ala-NCA, via aqueous NCA ROPISA was demonstrated. The morphologies of the resultant nanoparticles were primarily influenced by the secondary structure of the hydrophobic poly(amino acid). Finally, the feasibility of mediating PISA with diketopiperazine (DKP) ROP was explored. These 6 membered rings can be produced in a facile, phosgene-free synthesis and may undergo ROP. This was successfully carried out in DMF, chain extending a PEG113-NH2 macro-initiator with Ala-DKP and then in water using a benzylamine initiator to produce insoluble PAla. ROPISA was then attempted using a PSar macro-initiator.