Electronic Thesis and Dissertation Repository


Doctor of Philosophy




Workentin, Mark S.


This thesis describes the development of bioorthogonal chemical tools — originally designed to form bonds cleanly and selectively in living systems — on gold nanoparticles (AuNPs) as a model reactive nanomaterial template to showcase chemical modifications in a facile and robust manner. To achieve this goal, new methodologies to cleanly incorporate strained alkyne (SA) and cargo-bearing triarylphosphine derivatives onto AuNPs were developed. The protocols described herein provide well-defined reactive AuNP interfaces that undergo bioorthogonal bond-forming and breaking reactions cleanly, selectively, and rapidly to enable chemical tuning of their properties and function.

In order to circumvent the high reactivity of SAs, which hindered their incorporation onto AuNPs, a cyclopropenone-caging strategy was employed to successfully mask the SA until post-AuNP incorporation. Interfacial cyclopropenones were photochemically decarbonylated using ultraviolet A (UV-A) irradiation, which proceeded cleanly and rapidly, to afford the unmasked SA moieties. This versatile reactive AuNP template exhibited rapid reactivity with azides (via strain-promoted alkyne-azide cycloaddition, SPAAC) and nitrones (via strain-promoted alkyne-nitrone cycloaddition, SPANC) to form robust covalent bonds with the partner molecule, which provides an efficient and reliable route towards derivatizing AuNP surfaces.

To further expand the scope of bioorthogonal chemistry on AuNPs, cargo-bearing triarylphosphines were used to demonstrate the release of molecules off AuNPs via the Staudinger-Bertozzi ligation (SBL) with azides. It was shown that functionalized AuNPs undergo SBL in a highly specific manner to release a Rhodamine B dye — a model cargo — from its surface. The release event was monitored from immediate turn-on of fluorescence upon treatment with an azide. Building on this “click-to-release” design, a dual-bioorthogonal molecular tool was developed to feature unprecedented versatile reactivity on AuNPs. Four bioorthogonal transformations (SPAAC, SPANC, SBL, and a modified perfluoroaryl Staudinger reaction, PFAA-SR) were deployed on AuNP surfaces to demonstrate the clean and versatile reactivity this new chemical tool offers.

In total, this thesis work describes innovative strategies to successfully incorporate bioorthogonal functionalities onto AuNPs, methods to quantitate and follow their interfacial chemistry, and the creation of versatile reactive AuNP templates that can be chemically modified with ease under mild and biocompatible conditions.