Date of Award

2025

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Administrative Home Department

Department of Chemistry

Advisor 1

Haiying Liu

Committee Member 1

Tarun K. Dam

Committee Member 2

Thomas Werner

Committee Member 3

Tatyana G. Karabencheva-Christova

Abstract

Understanding the dynamic biochemical and biophysical changes within living systems is vital for advancing disease diagnosis and therapeutic development. This work presents the design and development of innovative fluorescent probes, based on cyanine and coumarin scaffolds, for the highly sensitive and selective detection of key metabolic and biophysical markers, NAD(P)H, mitochondrial viscosity, and sulfur dioxide (SO₂) in live cells and fruit fly larvae. A series of cyanine-based probes were engineered to undergo strong fluorescence enhancement upon reduction by NAD(P)H, enabling real-time visualization of metabolic fluctuations in cancer cells and Drosophila larvae. These probes exhibit excellent sensitivity, mitochondrial targeting capability, and near-infrared emission, making them powerful tools for studying redox dynamics under conditions such as glycolysis, hypoxia, and drug treatment. Additionally, a dual-channel coumarin-based probe was developed to simultaneously detect mitochondrial viscosity and SO₂. This multifunctional probe offered ratiometric SO₂ detection and near-infrared fluorescence for viscosity changes, enabling dynamic monitoring of mitochondrial responses to stress induced by agents such as nystatin, monensin, and LPS. Together, these fluorescent probes provide robust and versatile platforms for real-time bioimaging and metabolic analysis in both physiological and pathological settings, offering valuable insights into cellular function, disease mechanisms, and treatment responses.

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