Degradable polymers have gained a lot of attention in recent years for applications in biotechnology and medicine. External control over polymer degradation can be obtained by incorporating functional groups that cleave in the presence of triggers that would normally be absent in biological environments, i.e. are bioorthogonal. This thesis explores the use of chemically cleavable α-azidoethers as a new method to obtain external control over the degradation behavior of polymers. My first goal is to illustrate the potential of α-azidoethers toward developing cleavable linkers. We have studied the relationship between α-azidoether structure and hydrolytic stability, to prepare linkers that withstand background hydrolytic cleavage until they are exposed to the cleaving trigger. The cleavage kinetics of the &alpha-azidoether functional group was quantified. In addition to the conventionally used tris(2-carboxyethyl)phosphine (TCEP), dihydrolipoic acid (DHLA), a previously unexplored, biocompatible reducing agent, was also evaluated as a cleaving trigger. Based on these results, we have proposed design rules for utilizing α-azidoethers as cleavable linkers in applications that require bioorthogonal control over linker cleavage. Secondly, the α-azidoether cleavable linker chemistry was implemented into the development of polymeric materials. Two different types of polymers were developed. Polyamides incorporating α-azidoethers along the backbone were synthesized, and their physical properties and chemically triggered degradation behavior were characterized. The degradation timescale of these polymers can be tuned simply by manipulating the concentration of the externally applied chemical trigger. The α-azidoether functional group was then utilized to develop a unique triggered-release polymeric adhesive for potential applications in dental adhesive formulations. A methacrylamide-phosphonate adhesive monomer incorporating an α-azidoether group was designed and synthesized. The monomer was polymerized to adhere polymer-composite substrates. Adhesion strength was quantified, and on-demand release of bonded substrates was demonstrated using DHLA as a trigger. The results presented here shed some light on the scope, advantages and drawbacks of utilizing α-azidoethers to develop new types of cleavable linkers and degradable polymers. In principle, the triggered degradation method described here could be incorporated into polymers with different chemical structures, to develop a variety of materials that offer an external control over degradation.
University of Minnesota Ph.D. dissertation.September 2014. Major: Chemistry. Advisor: Andrew Taton. 1 computer file (PDF); xvi, 151 pages.
Development of Bioorthogonally Degradable Linkers and Polymers Using alpha-Azidoethers.
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