Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Chemistry

Supervisor

Gillies, Elizabeth R.

Abstract

Self-immolative polymers (SIPs) are a subset of degradable polymers that can be triggered to fully depolymerize with a single stimulus event. This amplifying behaviour makes them ideal for real-world applications including sensors, recyclable plastics, and drug delivery vehicles. Polyglyoxylates (PGs) are a class of SIPs that can be synthesized in a one-pot reaction and designed to respond to different stimuli including light, heat, reduction, and oxidation. However, with the exception of poly(ethyl glyoxylate) (PEtG), the various glyoxylate monomers must be prepared and purified before polymerization, which can be difficult. Furthermore, PGs typically possess properties such as water-insolubility and low glass transition temperatures that make them unsuited for certain applications. This thesis details the synthesis of a new class of SIPs known as polyglyoxylamides (PGAms). PGAms were prepared from precursor PEtGs using post-polymerization amidation reactions with high conversion. The resulting polymers possessed properties differing from the precursor PEtGs, while still remaining capable of self-immolation. Furthermore, the synthetic method to create PGAms allowed for their properties to be easily tuned. This feature was taken advantage of in subsequent work, where PGAms were developed with a variety of properties including thermo- and pH-responsiveness. Furthermore, PGAms were developed that could form nanovesicles that may potentially serve as drug delivery vehicles and non-viral polycationic agents to assist with the transfection of nucleic acids.

Summary for Lay Audience

Polymers are large molecules composed of many repeating units. They are essential in the modern world, making up the components of life such as proteins as well as natural and synthetic materials such as wood and commodity plastics. Degradable polymers are those that are capable of being broken down into smaller molecules via naturally occurring processes over a reasonable timespan such as a few years, thereby allowing their degradation products to return to the ecosystem. This behaviour contrasts with non- degradable polymers such as polystyrene, which remain intact in the environment long after their disposal and may require hundreds of years to fully degrade. Degradable polymers are ideal candidates for combating plastic pollution and for certain medical applications such as degradable medical devices. Self-immolative polymers (SIPs) are a subset of degradable polymers that are capable of full degradation after the removal of a stabilizing group via a stimulus such as light or heat. This degradation is controlled and proceeds in a domino-like fashion, making these polymers ideal for real-world applications where an amplifying effect is desired. This thesis documents the development of a novel class of SIPs known as polyglyoxylamides (PGAms). PGAms can be prepared via a one- step reaction using another SIP known as poly(ethyl glyoxylate) and a variety of different amines. Depending on the amines used, PGAms can be tuned to possess interesting properties. The thesis further documents the development of PGAms with specific properties, such as the ability to alter themselves to changes in temperature or pH. Additionally, the use of PGAms to form nanoscale assemblies, which may be able to act as responsive drug-delivery vehicles is described. Finally, the application of PGAms for the delivery of nucleic acids into cells for nucleic acid therapy is presented.

Available for download on Wednesday, June 01, 2022

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