Document Type

Dissertation

Date of Award

8-31-2025

Degree Name

Doctor of Philosophy in Chemistry - (Ph.D.)

Department

Chemistry and Environmental Science

First Advisor

Pier Alexandre Champagne

Second Advisor

Kevin D. Belfield

Third Advisor

Yanchao Zhang

Fourth Advisor

Genoa R. Warner

Fifth Advisor

Shang Jia

Abstract

Reactive sulfur species (RSS) such as hydrogen sulfide (H2S) and hydropersulfides (RSSH) are crucial mediators in a variety of physiological and pathological processes. Their regulatory roles span from maintaining cellular redox balance to influencing signaling pathways critical for homeostasis and stress responses. This dissertation investigates H2S and RSSH as biologically important molecules and explores the development of boron-dipyrromethene (BODIPY)-based photocages for its controlled, light-triggered release. Given H2S and RSSH's critical role in redox regulation and cellular protection, achieving spatiotemporal control over its delivery is essential for both therapeutic and research applications. BODIPY scaffolds offer favorable photophysical properties, including visible-light activation and structural tunability, making them well-suited for biological use.

The study is structured around two core aims. First, density functional theory (DFT) calculations were employed to explore the photoinduced heterolytic bond cleavage mechanisms in BODIPY derivatives. These computational insights identified key electronic and energetic factors that influence efficient photorelease, guiding the design of improved photocages. Second, novel thionocarbamate- and carbamate-functionalized BODIPY compounds were synthesized and characterized for their absorption profiles, photolysis behavior, and H2S release under physiological conditions. Biological validation using C2C12 cells confirmed intracellular H2S delivery using a fluorescent probe. Further efforts expanded the chemical scope through isothiocyanate-based thiocarbamate synthesis and the development of disulfide-linked BODIPY derivatives for RSSH release. Overall, this work establishes a framework for designing tunable, visible-light-activated donors for 112S and RSS, offering new tools for targeted chemical biology and therapeutic strategies.

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