Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article


Master of Science




Workentin, Mark S.


The glutathione-mediated, retro Michael-type addition reaction is demonstrated to take place at the interface of water-soluble, maleimide-functionalized gold nanoparticles (Maleimide-AuNP). The retro Michael-type addition can be blocked by hydrolyzing the Michael addition thioether adduct at the nanoparticle’s interface. This procedure “locks” the molecule of interest onto the Maleimide-AuNP template, ensuring no loss of the molecular cargo from the nanocarrier. On the other hand, the glutathione-mediated retro Michael-type addition reaction can be exploited for delivering a molecular payload. The Michael donor, 4-mercaptophenylacetic acid was modified with a terminal azide, allowing for addition of cargo through strain-promoted alkyne azide cycloadditions with various functional alkynes. The resulting AuNPs are versatile platforms for the integration of multiple functionalities within a single construct, enabling their use in complex biotic environments. As a proof of concept, a fluorogenic molecular cargo was incorporated onto a Maleimide-AuNP and delivered via the glutathione-mediated, retro Michael-type addition reaction.

Summary for Lay Audience

Nanomaterials are extremely tiny materials that are typically between 1-100 nm in diameter and have unique characteristics and properties compared to the bulk material. They have been identified as promising candidates for application in optics, electronics, and medicine. Gold nanoparticles (AuNPs) are one type of nanomaterial that have been previously used in optical sensing, cancer therapy, and drug delivery due to their compatibility with biological environments and high stability. Flexible, linker chemicals attached to various functional molecules can be bound to the surface of AuNPs to change their physical and chemical properties. Further function (drug, imaging agent, etc.) can be introduced to AuNPs through the manipulation of the peripheral molecules using click reactions. Click chemistry, defined as highly efficient reactions that proceed under mild conditions, is becoming increasingly popular in the materials chemistry field due to its ease of purification and lack of undesired by-products. Previously our research group has demonstrated this reactivity by binding fluorescent molecules to AuNPs, then releasing them under biological conditions. The release was triggered by the addition of glutathione (GSH), a compound commonly found in cancer cells. Therefore, this research helped to develop a “click & release” system on AuNPs to deliver chemical cargo to GSH rich environments, however the system was poorly understood, and potential applications were largely unexplored. The goal of this thesis was to further investigate and improve this “click & release” system to expand its practicality and to widen the scope of its application. By implementing more bio-compatible click reactions in this system, a functional chemical cargo can be attached and released more effectively. The molecular system will be responsive towards GSH concentrations (which varies in tumor cells and healthy cells) and can therefore be exploited for selective release in biological environments. Overall, the goal of my research is to engineer functional and responsive materials that will provide exciting new applications across the sciences.