Exploring the Thermal and Mechanochemical Reactivity of 1,2-Oxazine Hetero Diels-Alder Adducts for Stimuli-Responsive Polymers

Abstract

Stimuli-responsive materials is an area of significant research with a broad scope of applications in fields such as drug delivery, self-healing materials, and lithography. The ideal stimuli-responsive polymer construct is engineered in such a way that the desired activation occurs only when the proper stimuli is spatially and temporally applied. Light-, pH-, redox-, thermal-, mechanical- and enzymatic-stimuli have successfully been harnessed to trigger various responses in polymeric materials. The continued growth of this field relies upon the development of new stimuli-responsive chemical motifs. To this end, my research has focused on the potential of 1,2-oxazines as a new stimuli-responsive moiety within the context of polymer systems. These compounds have been demonstrated to undergo a thermally induced [4 + 2] cycloreversion to release a diene and nitrosocarbonyl dienophile. My research has sought to study and harness the thermal reversibility of this adduct and the subsequent breakdown of the dienophile component to trigger processes such as depolymerization of a polymer chain as well as releasing the therapeutically relevant gaseous small molecule, nitroxyl (HNO). Collectively, these constructs can achieve slow, sustained activation at physiologically relevant temperatures or rapid activation at higher temperatures by exogenous means such as the use of photothermal dyes. I have also looked at the propensity of 1,2-oxazines to undergo mechanochemical activation in solution under strong elongational fields. A fundamental understanding of not only how polymer topology may affect mechanophore activation in general but also the regiochemical application of force across the oxazine itself was explored.