Recent Progress in Diboronic-Acid-Based Glucose Sensors

Abstract

Non-enzymatic sensors with the capability of long-term stability and low cost are promising in glucose monitoring applications. Boronic acid (BA) derivatives offer a reversible and covalent binding mechanism for glucose recognition, which enables continuous glucose monitoring and responsive insulin release. To improve selectivity to glucose, a diboronic acid (DBA) structure design has been explored and has become a hot research topic for real-time glucose sensing in recent decades. This paper reviews the glucose recognition mechanism of boronic acids and discusses different glucose sensing strategies based on DBA-derivatives-based sensors reported in the past 10 years. The tunable pKa, electron-withdrawing properties, and modifiable group of phenylboronic acids were explored to develop various sensing strategies, including optical, electrochemical, and other methods. However, compared to the numerous monoboronic acid molecules and methods developed for glucose monitoring, the diversity of DBA molecules and applied sensing strategies remains limited. The challenges and opportunities are also highlighted for the future of glucose sensing strategies, which need to consider practicability, advanced medical equipment fitment, patient compliance, as well as better selectivity and tolerance to interferences.

The Rise of Boron-Containing Compounds: Advancements in Synthesis, Medicinal Chemistry, and Emerging Pharmacology

“…Some BCC have been proposed as carbohydrate-selective fluorescent diboronic acid sensors. 298 Peptide boronic acid 49 bound fructose with a K a value of 1971 M −1 , which was 3-fold greater than the corresponding benzoxaborole analog. Compound 49 bound glucose, mannose, and galactose with K a values less than 200 M −1 , which is likely a result of the 1,2 cis-diol present on fructose that is not present on the other sugars tested (Figure 21).…”

“…Boronic acids prefer binding 1,2- and cis -1,3-diols of furanose sugars, , while benzoxaboroles preferentially bind hexapyranosides when complexed with 4,6-diols or cis -3,4-diols. − Recently, Otremba and Ravoo augmented the binding of previously disclosed linear and cyclic peptides by installing a phenyl boronic acid or benzoxaborole. Some BCC have been proposed as carbohydrate-selective fluorescent diboronic acid sensors . Peptide boronic acid 49 bound fructose with a K a value of 1971 M –1 , which was 3-fold greater than the corresponding benzoxaborole analog.…”

Detailed Reaction Mechanism of Anthracene‐Bridged bis‐(3‐Pyridiniumboronic Acid) Chemosensor with D‐Glucose

“…[7,8] Recently, a fluorescent diboronic acid-based sensor, approved by FDA, was commercialized for continuous D-glucose monitoring. [9] However, the most fundamental studies of the boronic acid reactions such as identification of the reactive species and elucidation of detailed reaction mechanism, which are essential to utilize the reaction of boronic acid as a chemosensor, are limited in number. In particular, the studies on the detailed reaction mechanism of boronic acids with saccharides are even scarcer.…”

“…As D‐glucose has two cis ‐diol moieties, diboronic acid compounds, which have two boronic acid moieties, can react with D‐glucose selectively through multi‐point recognition [7,8] . Recently, a fluorescent diboronic acid‐based sensor, approved by FDA, was commercialized for continuous D‐glucose monitoring [9] . However, the most fundamental studies of the boronic acid reactions such as identification of the reactive species and elucidation of detailed reaction mechanism, which are essential to utilize the reaction of boronic acid as a chemosensor, are limited in number [10–30] .…”