Date of Award
Spring 5-10-2024
Degree Type
Thesis
Degree Name
Master of Science in Chemical Sciences
Department
Department of Chemistry and Biochemistry
Committee Chair/First Advisor
Carl Jacky Saint-Louis
Second Advisor
Carol Chrestensen
Third Advisor
Michelle Head
Abstract
Hydroxamic acids (HAs) are a class of reactive organic compounds that are used as Histone Deacetylase (HDAC) inhibitors in anticancer therapy and to extract heavy metals from industrial wastewater. Due to their high reactivity, traditional synthesis of HAs leads to the formation of poly-substituted side products, resulting in low yields of HAs. To address this drawback, protecting groups (PGs) are used to mask the reactivity of HAs. However, selective deprotection of PGs is challenging, because it involves harsh conditions that can degrade the protected moiety. To solve this problem, photolabile protecting groups (PPGs) such as ortho-nitrobenzyl (o-NB) PPGs are utilized as a less harsh approach since only light is required to cleave PPGs. In this study, we present the first and only thiophene-based visible light-absorbing, fluorescent-quenching PPGs to overcome the limits of traditional HA synthesis and purification by cleaving HAs using visible light. Furthermore, our PPG scaffold is strategically designed with an electron-rich thiophene and electron-poor nitrobenzene rings, which introduces an internal push-pull intramolecular charge transfer within the scaffold and red-shifts our PPGs' absorption wavelength to the visible region of the electromagnetic spectrum. Our PPGs' absorption in the visible region makes them ideal for medical applications such as drug delivery systems. Photolysis of our PPGs produces a di-nitrosoketone byproduct which quenches the fluorescence and can be utilized to measure HA release by monitoring the di-nitrosoketone byproduct's loss of absorption and emission. Finally, the stability of our PPGs is investigated by measuring their shelf lives via 1H NMR. These findings will be used in the design of future visible light-absorbing, fluorescent-quenching PPGs that can be used as drug delivery systems, for light regulation of biomolecules, and to cleave other reactive functional groups.
Included in
Analytical Chemistry Commons, Materials Chemistry Commons, Medicinal-Pharmaceutical Chemistry Commons, Organic Chemistry Commons, Physical Chemistry Commons
Comments
This research project was supported and funded by the National Science Foundation Launching Early-Career Academic Pathways in the Mathematical and Physical Sciences (NSF LEAPS-MPS)