Boronic acid fluorescent sensors for monosaccharide signaling based on the 6-methoxyquinolinium heterocyclic nucleus: progress toward noninvasive and continuous glucose monitoring

Abstract

The synthesis, characterization, and spectral properties of strategically designed boronic acid containing fluorescent sensors, o-, m-, p-BMOQBA, for the potential detection of tear glucose concentrations when immobilized in plastic disposable contact lenses is described. The new probes, BMOQBAs, consist of the 6-methoxyquinolinium nucleus as a fluorescent indicator, and the boronic acid moiety as a glucose chelating group. A control compound BMOQ, which has no boronic acid group and therefore does not bind monosaccharides has also been prepared. In this paper, we show that structural design considerations of the new probes have afforded for their compatibility within the lenses, with reduced probe sugar-bound pK(a) favorable with the mildly acidic lens environment. In addition, the new probes are readily water soluble, have high quantum yields, and can be prepared by a simple one-step synthetic procedure.

Ophthalmic Glucose Monitoring Using Disposable Contact Lenses

“…A geometrically placed diboronic acid containing fluorophore shows higher affinity towards D-glucose over D-fructose. Hence glucose sensitive probes can be made with a variety of affinities, in the mM range for blood glucose [34][35][36], and in the \iM range for tear glucose [39,40]. Also the p/Cg of the boronic acid can be modulated according to the medium of interest.…”

Ophthalmic Glucose Monitoring Using Disposable Contact Lenses—A Review

“…Equilibrium for the boronic acid/diol (sugar) interaction. the molecular geometry and the aromatic species where the boronic acid group is present, hence glucose sensitive probes can be made with a variety of affinities, in the mM range for blood glucose [34][35][36], and in the µM range for tear glucose [39,40].…”

Development of Smart Contact Lenses for Ophthalmic Glucose Monitoring

“…A geometrically suitably placed diboronic acid containing fluorophore, ANDBA, shows higher affinity towards D-glucose over D-fructose. Hence glucose sensitive probes can be made with a variety of affinities, in the mM range for blood glucose [42][43][44], and in the ^iM range for tear glucose [47,48]. Also the p^a of the boronic acid can be modulated according to the medium of interest.…”

“…This is clear from the apparent pK^ values of DSTBA and CSTBA (see section 17.3.2.1 and Table 17.2). We therefore considered the interaction between the electron accepting quaternary nitrogen of the 6-methyl-and methoxyquinolinium moieties and the boronic acid group, which reduces the pKa of the probe [47,48]. In this regard we have synthesized 2 new classes of isomeric boronic acid containing probes.…”

“…Here we have used strategic design logic by using an electron withdrawing quaternary nitrogen center within the interacting space of boronic acid to reduce the boronic acid p^a-Also, in contrast to the other probes, because of the positively charged quinolinium moiety, these probes are readily water soluble and are therefore potentially useful for physiological applications. In essence we have several options to fine tune the glucose response of the probes within the medium of interest [47,48].…”