Electronic Thesis and Dissertation Repository


Doctor of Philosophy


Chemical and Biochemical Engineering


Elizabeth R. Gillies


Self-immolative polymers are a recently developed class of degradable polymers capable of undergoing end-to-end depolymerization following the reaction of their endcaps with appropriate stimuli. Self-immolative materials originated in the field of prodrug chemistry, and evolved into self-immolative oligomers, dendrimers, and most recently, linear polymers. Many stimuli-responsive endcaps have been developed, but typically can only respond to one stimulus. Azobenzenes are a well-known class of stimuli-responsive molecules most commonly used as photoswitches, due to their facile trans-cis isomerization. In addition to their photochemistry, azobenzenes have recently been found to be selectively reduction-sensitive, and are therefore of interest as endcaps in self-immolative polymers. The two fields of azobenzenes and self-immolative polymers have not previously been combined, and it is the work described herein that is the first to do so. This thesis demonstrates that azobenzenes can be useful as multistimuli-responsive units in self-immolative polymers.

First, the reduction-sensitivity of azobenzene was demonstrated in the context of two self-immolative polymer backbones. The synthesis and depolymerization of these materials showed that azobenzene endcaps could be successfully incorporated into – and used to trigger – self-immolative polymers. In the next study, a library of reduction-sensitive azobenzenes was prepared to determine which azobenzene compounds were most suited for use as reduction-sensitive endcaps. A 2-Cl azobenzene derivative was reduced most quickly, and this compound was incorporated as pendant units in an amphiphilic chain-shattering graft copolymer based on a poly(ester amide) backbone. It was found that these azobenzenes imparted both photo- and reduction-sensitivity to aqueous polymer assemblies, and could respond synergistically to both stimuli. In the final study, two distinct linear self-immolative polymer backbones, a polycarbamate and a polyglyoxylate, were synthesized with an azobenzene linker, and conjugated to poly(ethylene oxide) using click chemistry. The synthesized amphiphilic block copolymers were reduction-sensitive, and their aqueous assemblies were shown to encapsulate and release a hydrophobic cargo under reducing conditions. The multifaceted applicability of azobenzene was highlighted in these studies, first as a reduction-sensitive endcap, then as a dual-responsive trigger for chain-shattering poly(ester amide)s, and finally as a reduction-sensitive linker in diblock copolymers.