Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Chemistry

Supervisor

Prof. Mark S. Workentin

Abstract

The goal of this Ph.D. thesis work is the development of novel reactive nanomaterial templates that can be chemically modified in a facile and robust (i.e., formation of covalent bonds) way for the further modification of the nanomaterial’s physical-chemical properties by the reaction partner molecular system. This type of technology was employed to further expand the application of nanomaterials in nanomedicine, chemical biology and materials science.

In order to reach this goal, as a proof of concept, small (d = 3nm) gold nanoparticles (AuNPs) and carbon nanotubes (CNT) were used as the nanomaterial substrates. Innovative synthetic strategies for the introduction of click and bioorthogonal functional groups onto the surface of these nanomaterials were developed. These functional groups include a maleimide that can undergo three click reactions with different functional groups (i.e., Michael addition with nucleophiles, Diels-Alder cycloaddition with dienes, dipolar cycloadditions with dipolar molecules), strained alkynes for bioorthogonal strain-promoted cycloaddition reactions with azides and nitrones, and methyl-2-(diphenylphosphino)benzoate moieties for the bioorthogonal Staudinger-Bertozzi ligation with azides.

In order to study and characterize these clickable and bioorthogonal nanomaterial templates, methodologies for the determination of the amount of reactive functionalities introduced onto the nanomaterial’s surface and the evaluation of their proper reactivity were also developed. 1H NMR spectroscopy, transmission electron microscopy, and thermogravimetric analysis, were methodically used for the quantification of the interfacial reactive functionalities. 1H NMR spectroscopy was also employed to follow the correct interfacial reactivity of the nanomaterial template. Finally, in collaboration with Surface Science Western, the use of X-ray photoelectron spectroscopy (XPS) was developed as a method to independently confirm all the previously obtained results and, more specifically, quantitate the amount of interfacial reactive molecules that were introduced, track the interfacial organic chemistry of the nanomaterial template, and determine interfacial reaction yields. In all cases the clickable and bioorthogonal nanomaterial templates were found to react quickly, efficiently and chemoselectively with their chemical reporter through a simple pour-and-mix type of chemistry. The utility of these clickable and bioorthogonal nanomaterial templates was finally showcased in bioconjugation, for the synthesis of fluorogenic biosensors, nanomaterial hybrids and nanomaterial-based MRI contrast agents.


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