Boronic acid functional group is used widely as a recognition moiety for the development of sensors for saccharides, due to its unique strong and reversible interaction with diols. The fluorescence and/or UV spectroscopic method are the easiest and most common methods to signal the binding event of these receptors (boronic acid compounds) with saccharides. This dissertation consists of three major parts. First, a series of fluorescent diboronic acid compounds with an anthracene PET (photoinduced electron transfer) system were designed and synthesized (Chapter 1). These compounds can be used as sensors for cell surface carbohydrates, such as sialyl Lewis X (sLex), which are known to be biomarkers for certain cancers. Among these diboronic acid compounds, the lead compound was found to fluorescently label cells expressing sLex selectively. The structure of the lead compound was modified and new conformationally constrained analogs were synthesized. Second, the mechanism of the fluorescent photoinduced electron transfer (PET) system, which was used in our design of fluorescent sensors for sLex, was examined in detail using both density functional calculation (DFT) and model compound fluorescence studies. Based on the study, a new hydrolysis mechanism was proposed (Chapter 2 and 3). Third, novel nitrophenol-based boronic acid reporter compounds, which show significant UV spectroscopic changes upon addition of sugars at neutral pH in aqueous solution, were designed and synthesized (Chapter 4). The design took advantage of the ability of a boronic acid functional group to modulate the pKa and/or the electron density of a neighboring group. These reporter compounds can be used as the recognition and signaling unit for the construction of polyboronic acid sensors for selective and specific recognitions of saccharides of biological significance.
展开▼
