Date on Master's Thesis/Doctoral Dissertation
12-2014
Document Type
Doctoral Dissertation
Degree Name
Ph. D.
Department
Chemistry
Committee Chair
Nantz, Michael H.
Committee Co-Chair (if applicable)
Burns, Christopher T.
Committee Member
Sethu, Palaniappan
Committee Member
Zamborini, Francis Patrick
Subject
Biotechnology; Nanoparticles--Medical aspects; Combinatorial chemistry
Abstract
The reaction of an aminooxy moiety (RONH2) with an aldehyde or ketone carbonyl, an oximation reaction, results in the formation of robust oxime ether linkages. Oximation is a form of click chemistry and is chemoselective, occurs in a variety of solvents including water, and produces high yields with little to no purification. We were inspired to exploit the advantages of oximation reactions by attaching aminooxy-functionalized molecules to solid supports, thus allowing us to employ aminooxy chemistry in ways that cannot be achieved using solution phase. Chapter 1 provides a review of aminooxy chemistry, its advantages over similar reactions and its
multitude of applications. Chapter 2 describes the use of aminium aminooxy salts fixed to a silicon microreactor to enable the capture of volatile aldehydes and ketones from exhaled breath for early detection of lung cancer. Since only carbonyl compounds were retained and thereby concentrated, the accurate measurements of scarce metabolite cancer markers were realized. Use of an acid-scavenging polymer transformed the aminium salt adducts into a volatile adducts, thus enabling analyses by both high resolution mass spectrometry and gas chromatography. Chapter 3 details our investigation into the use of thermally-induced intramolecular cyclization as a release mechanism. A kinetic study on the cyclization rates of a panel of thermally-labile linkers led to a demonstration involving such an aminooxyfunctionalized linker covalently bonded within a poly(dimethylsiloxane) microchannel. After capture of an aldehyde-functionalized fluorophore that had been passed through the microchannel, the intramolecular cyclization release mechanism was induced by gentle warming to liberate the fluorescent oxime ether adduct. In Chapter 4 we applied our t hermally-labile linkers to iron oxide nanoparticles in an effort to design an externally controlled drug delivery system. Fe3O4 nanoparticles generate heat when subjected to an alternating magnetic field (AMF), thus eliminating the need for an in vivo conventional heat source. During our investigation of AMF-induced release we discovered the unprecedented hydrolysis of robust chemical functionalities that occurs only at the nanoparticle-liquid interface. This discovery was exploited in the development of a delivery system capable of releasing oxime ether adducts. In conclusion, this thesis describes novel innovations that can be immediately applied in a multitude of disciplines, from analytics to diagnoses and to drug delivery.
Recommended Citation
Knipp, Ralph Jacob, "Triggered release of small molecules from solid supports using heat or an applied magnetic field." (2014). Electronic Theses and Dissertations. Paper 1756.
https://doi.org/10.18297/etd/1756
