Browsing by Author "George H. Wahl, Committee Member"

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Using Boronic Acid as the Recognition and Signaling Moiety for Sugar Sensing
(2004-12-26) Yan, Jun; Bruce Eaton, Committee Member; George H. Wahl, Committee Member; Daniel L. Comins, Committee Member; Binghe Wang, Committee Chair
The interaction between a boronic acid and a diol is known to be one of the strongest single-pair reversible functional group interactions in an aqueous environment. During the last decade, much effort has been devoted to the development of boronic acid-based sensors for carbohydrates and other diol-containing compounds, and a great deal of progress has been made in this area. However, there are still several fundamental issues that have not been addressed, which hinder the development of such kind of sensors. For example, several factors have long been recognized as important in influencing the binding affinity of boronic acids to diol-containing compound, but there has never been a systematic examination of the relationship among those factors. To address these issues, in Chapter 2 we carefully examined a series of 25 arylboronic acids with various substituents and selected binding affinities with a series of diols at varying pH value. We have found that (1) the pKa of monosubstituted boronic acids can be predicted based on the substituent effect using a Hammet plot; (2) the common belief that boronic acids with lower pKa's have greater binding affinities at neutral pH is not always true; and (3) the optimal pH for binding is not always above the pKa of the boronic acid, instead it is related to the pKa values of both the boronic acid and the diol, although in a manner that cannot be readily predicted. Second, critical to the construction of fluorescent sensors for carbohydrates is the availability of practical fluorescent reporters that respond to the binding event with significant fluorescence intensity changes under physiological conditions. So far a few boronic acid reporters have been described in the literature, but those reporters have undesirable properties such as low water solubility and poor photochemical stability. As described in chapter 2, we have discovered a novel type of fluorescent carbohydrate reporter, 8-quinolineboronic acid (8-QBA). It showed about 40 fold fluorescence increase upon binding of a carbohydrate compound and has very good water solubilty. All these properties make such a system ideal for the construction of fluorescent carbohydrate biosensors for biological applications. With this reporter compound in hand, we designed and syntesized a series of dibornic acids, developed an effective synthetic route for a different kind of 8-QBA-based diboronic acid compound. These results are described in Chapter 4.