Bakthan Singaram

CHAPTER 5:Boronic Acid Functionalized Viologens as Saccharide Sensors

Monitoring blood glucose levels in diabetics is an important global problem. We introduced a two-component sensing system, consisting of a fluorescent dye and a boronic acid-containing molecule that acts dually as a fluorescence quencher and a saccharide receptor, for continuous glucose monitoring in blood. The object of this chapter is to trace major developments, largely in our own research program, which led from the initial observation of the exceptional sugar signaling capabilities of the ortho-borobenzyl viologen–hydroxypyrene trisulfonic acid (o-BBV–HPTS) system to the present time when it is possible to monitor glucose in the whole blood continuously. Through this research, we have identified several two-component sensing configurations and probes for the detection of saccharides in biological fluids. In this chapter, particular emphasis has been given to the development of the two-component boronic acid-based fluorescent glucose sensors. Mechanistically, in the absence of saccharide, a non-fluorescent ground-state complex forms through ionic association between the dye and the viologen boronic acid, resulting in a greatly reduced fluorescence of the dye. The electrostatic attraction between the dye and the quencher is lost, however, upon the binding of the viologen to the saccharide causing the dye–quencher complex to dissociate. This produces a fluorescence recovery that is directly dependent on the saccharide concentration. These boronic acid appended bipyridinium salts are tunable receptors and can be designed to increase glucose selectivity over that of other boronate-forming analytes. Fluorescent quantum dots can also be used as the reporter component in our system. Powerful solution-phase sensor arrays for neutral and anionic carbohydrates were created with these probes. They can be also used in new label-free fluorescent assays for carbohydrate-modifying enzymes. Immobilizing the two-component chemistry in a hydrogel allowed for continuous monitoring of saccharides. Hydrogels were incorporated in fiber optic devices for continuous monitoring of glucose. Most importantly, our two-component glucose sensing capabilities have contributed significantly to both the basic science of fluorescence-based sensor chemistry and to improving methods for detection of glucose and other carbohydrates in biological fluids.