Date of Award:
12-2020
Document Type:
Dissertation
Degree Name:
Doctor of Philosophy (PhD)
Department:
Chemistry and Biochemistry
Committee Chair(s)
Lisa M. Berreau
Committee
Lisa M. Berreau
Committee
Alvan C. Hengge
Committee
Abby D. Benninghoff
Committee
Cheng-Wei T. Chang
Committee
Nicholas E. Dickenson
Abstract
Long known as a toxic gas, carbon monoxide (CO) has been recently redefined as a health beneficial molecule produced endogenously in humans. The biological activity of CO has been extensively examined in inflammatory conditions, vasoprotection, anti-apoptotic and anticancer studies, although the mechanisms of action are still not well defined. Because CO is a gaseous molecule, a straightforward administration would be inhalation. However, this delivery method is limited to use in hospital settings under professional supervision. For improved control over the amount and location of CO delivery, metal-free and light-triggered carbon monoxide-releasing molecules are of particular current interest. Our lab is developing molecules based on flavonol scaffold that can be triggered with visible light to release CO. These molecules are also trackable in cells via their fluorescence. Conveniently, flavonols are abundant in nature in a wide variety of fruits and vegetables being well known for their anti-oxidant and anticancer properties. One of the important advantages of flavonol-based compounds is their structural amenability and ease in tuning their physical properties.
The research presented in this dissertation outlines our approach toward the development and application of highly-controlled flavonol-based CO donors as chemical tools applied to study the biological effects of CO in cellular environments. Through small structural changes of the flavonol scaffold, we developed molecules that can deliver CO outside and inside cells as well as at specific cellular compartments, such as mitochondria, endoplasmic reticulum and lysosomes. We have also developed flavonol-based molecules that can be activated to release CO only in the presence of molecules characteristic of pathological conditions. The CO-releasing compounds developed in this project are of particular current interest as they can be rigorously controlled in terms of the time, location and amount of CO released.
Checksum
685dce38419a95a810ccc6bf672a4862
Recommended Citation
Lazarus, Livia S., "Triggerable, Targetable, and Trackable Flavonol-Based Carbon Monoxide-Releasing Molecules" (2020). All Graduate Theses and Dissertations, Spring 1920 to Summer 2023. 7928.
https://digitalcommons.usu.edu/etd/7928
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