Monosaccharide detection with boronic acid-substituted viologens and fluorescent dyes: Towards the in vivo sensing of glucose.

摘要

Glucose is the chief source of energy for all living organisms. The ability to detect glucose concentrations in vivo in a continuous manner would benefit both the scientific as well as medicinal community.; The research reported herein involves the design, synthesis, characterization, and testing of different fluorescent chemosensors with the ultimate objective being the development of an in vivo optical glucose sensor. In particular, the preparation of two-component sensing systems composed of boronic acid substituted-viologens and fluorescent dyes is reported.; Two types of boronic acid-substituted viologens were synthesized and studied: those based on 4,4'-dipyridyl and those based on 4,7-phenanthroline. The fluorophores were derivatives of HPTS (trisodium 8-hydroxy-1,3,6-pyrenetrisulfonate).; The dipyridyl-based quencher exemplified by N,N '-4,4'-bis(benzyl-2-boronic acid)-bipyridinium dibromide (o-BBV2+) quenches the fluorescence of HPTS through static and dynamic processes, although the static component is the main driving force. The quenching is modulated in the presence of saccharide at pH 7.4. The combination of o-BBV2+/HPTS acts as a saccharide sensor that operates under physiological conditions. The two-component system displays sugar sensitivity in the physiological range of 5--20 mM and shows selectivity for fructose over galactose over glucose.; The phenanthroline-based quencher exemplified by N,N '-bis-(benzyl-2-boronic acid)-4,7-phenanthrolinium dibromide (o-PBBV2+) also quenches the fluorescence of HPTS. In comparison to o-BBV2+, o-PBBV2+ is a much stronger fluorescence quencher as determined by Stern-Volmer analysis. The combination of o-PBBV 2+/HPTS allowed for the detection of glucose, fructose, or galactose in aqueous solution at pH 7.4 and showed more selectivity for glucose than what was observed for o-BBV2+.; When the two-component sensing system was immobilized in a thin film hydrogel it retained its sensing characteristics and detected saccharides under dynamic conditions. A dipyridyl-derived quencher containing four positive charges and two boronic acids (BP4+) displayed the most sensitivity to glucose when used in combination with a negatively charged HPTS derivative (HPTS-Lys-MA). The sensor was found to detect glucose in the concentration range of 0--20 mM and could sense under physiological conditions (temperature, ionic strength, and pH). Consequently, the two-component sensing system reported here shows promise as the basis for a continuous glucose monitoring system.