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
Daniela Tapu
Third Advisor
Bharat Baruah
Abstract
Hydroxamic acids (HAs) are an essential class of organic compounds that can be used as precursors in the development of chemotherapeutic drugs for various cancers and as potent metal chelators in the removal of harmful metals from seawater. However, there is a significant limitation with the synthesis and purification of HAs due to their high reactivity, resulting in many polysubstituted by-products. A well-known solution to this obstacle is the use of protecting groups (PGs) to temporarily block the reactivity of highly reactive functional groups such as HAs. Nevertheless, PGs must be removed under harsh conditions such as acidic, basic, or oxidative, which can degrade the protected product. Selective PG removal is also problematic when multiple PGs under similar conditions are applied to the same compound. Photolabile protecting groups (PPGs) such as ortho-nitrobenzyl (o-NB) based PPGs have become a valuable tool to remedy this problem and the use of harsh conditions because they can be selectively removed using only light. Herein, we report the first and only example of a pro-fluorescent thiophene-based PPG as a solution to the limitations of HA synthesis and purification by releasing HAs using only light. Our PPG scaffold is composed of an electron-rich thiophene ring and an electron-poor nitrobenzene ring, resulting in an internal push-pull character that causes intramolecular charge transfer throughout the system, red-shifting the PPG's absorbance and emission wavelengths. When HA is cleaved, a nitroso-ketone diagnostic fluorescent by-product is generated, which can be detected with the naked eye and can be used to quantify the amount of HA product formed by monitoring the increase in emission. Furthermore, the stability of our PPGs was examined by evaluating their shelf lives using 1H NMR experiments. These findings will help in the design of future PPGs that are used to cleave other reactive functional groups and can potentially be used in drug delivery systems.
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), and the National Institutes of Health (NIH) Peach State Bridges to the Doctorate Program.