Date of Award

2026

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

Christo Z. Christov

Committee Member 3

Thomas Werner

Abstract

Fluorescent probes have emerged as powerful tools for investigating complex biological processes due to their high sensitivity, selectivity, and capability for real-time, non-invasive imaging. In particular, the detection of key biomolecules such as NAD(P)H, viscosity-related parameters, human serum albumin (HSA), and pH is essential for understanding cellular metabolism, redox homeostasis, and disease progression. In Chapter 2, three coumarin-based fluorescent probes (A–C) were designed, synthesized, and characterized for monitoring NAD(P)H levels in living cells. Probes A and B feature coumarin–cyanine hybrid structures linked via vinyl and thiophene bridges to 3-quinolinium acceptors, respectively, while probe C incorporates a dicyano moiety to replace the lactone carbonyl group, resulting in an enhanced reaction rate with NAD(P)H. These probes were applied to investigate the influence of metabolites and sweeteners on intracellular NAD(P)H levels. Chapter 3 describes the development of red and deep-red cyanine-based probes (A and B) with large Stokes shifts for NAD(P)H detection in live cells using a simple and cost-effective synthetic approach. These probes incorporate thiophene-based π-conjugated bridges linking a 1-methylquinolinium acceptor and a formyl group. Notably, probe A exhibits a large Stokes shift of 144 nm, which minimizes spectral overlap and enhances the accuracy of fluorescence measurements. In Chapter 4, hemicyanine-based probes incorporating 1,8-naphthalimide (probe A) and rhodamine (probe B) derivatives were developed to monitor viscosity changes in live cells. Probe A additionally responds to human serum albumin (HSA), with fluorescence intensity increasing as a function of HSA concentration, whereas probe B shows negligible response due to steric hindrance from the bulky rhodamine moiety. Overall, the fluorescent probes xi developed in this work provide robust tools for the detection of NAD(P)H, viscosity, and HSA in live cells. These systems contribute to a deeper understanding of cellular metabolism, disease mechanisms, and therapeutic responses, and offer promising platforms for future bioimaging and diagnostic applications.

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