Development of novel near-infrared dyes for biomedical applications

Near-infrared (NIR) dyes are a type of contrast agent that can absorb and emit light in the near-infrared region of the electromagnetic spectrum, typically above 650 nm. They are widely applied in biomedical imaging and chemical biology applications to visualize structures and processes that are not visible to the naked eye.
NIR dyes are capable of providing deeper tissue penetration, reduced background, and higher sensitivity compared to dyes in the visible region. These benefits have inspired dye chemists to pursue new NIR dye scaffolds with improved properties for imaging. Existing NIR dyes typically have large molecular weights, poor water solubility, and reduced stability and biocompatibility compared to dyes in the visible region. This thesis describes the design, synthesis, and evaluation of a novel series of NIR dyes that overcome the above issues and could potentially be applied for imaging applications in both cultured cells and multicellular organisms. Initial efforts focusing on probe development are described.
This thesis starts with a brief introduction of commonly used optical imaging techniques, focusing on recent research progress in the development of small molecule NIR dyes and their applications (Chapter 1). Next, we describe our efforts to design, synthesize and characterize a novel NIR dye scaffold termed azaphosphinate Nebraska Red. We investigated its utility in both fluorescence and photoacoustic imaging (Chapter 2). A novel strategy for improving fluorescence output from this scaffold is described (Chapter 3). Demonstrating the versatility of azaphosphinate dyes, we present our preliminary efforts toward developing a turn-on photoacoustic probe for a potential diagnostic marker of acute myeloid leukemia (Chapter 4). In the concluding chapter (Chapter 5), an outlook for future applications of azaphosphinate dyes is provided.