Design and synthesis of substituted boronic acid containing mono-viologen and bis-viologen quenchers: Optimization of the two-component saccharide sensing system

The research described herein involves the development of a synthetic system, which can recognize and sense glucose. The detection of glucose is significant because it is an essential molecule in the human body. Unforeseen variations in glucose levels can result in adverse health effects, such as diabetes mellitus. For diabetics to control the effects of this disease, they must monitor their blood glucose levels throughout the day. This is accomplished by intermittent testing of blood samples acquired from finger pricking. This can be painful and tedious. An alternative method that utilizes a Continuous Glucose Monitor (CGM), is superior. Aside from managing diabetes, a CGM device would prove useful in the Intensive Care Unit (ICU), where tight glycemic control has shown a significant decrease in patient's morbidity and mortality.;In this thesis, research aimed toward the development of a two-component, boronic acid-based CGM is presented. The two components include an anionic fluorescent dye and a boronic acid-appended cationic viologen. When the two components interact electrostatically, the fluorescence of the dye is quenched by the viologen. Addition of glucose results in a disruption of the electrostatics in the quenched complex, and an increase in fluorescence is observed.;The structure of the viologen was systematically modified in order to elucidate the quenching and glucose sensing mechanisms. A series of quenchers with electron-donating or electron-withdrawing groups were screened and a quencher which sensed fructose at high concentrations without saturation was developed. The incorporation of two viologen subunits within a single quencher moiety was found to give heightened fluorescence quenching and glucose signal modulation as well. An anionic fluorescent dye which was insensitive to pH changes within the physiological range was explored. Also, polymerizable dyes and quenchers were synthesized and incorporated into hydrogels which sensed glucose continually and reversibly within the clinically relevant range. The results demonstrate the viability of this system for development into a medical device for in vivo use by diabetics and ICU patients.