Thermodynamic analysis of the selectivity enhancement obtained by using smart hydrogels that are zwitterionic when detecting glucose with boronic acid moieties

Abstract

Because the boronic acid moiety reversibly binds to sugar molecules and has low cytotoxicity, boronic acid-containing hydrogels are being used in a variety of implantable glucose sensors under development, including sensors based on optical, fluorescence, and swelling pressure measurements. However, some method of glucose selectivity enhancement is often necessary, because isolated boronic acid molecules have a binding constant with glucose that is some forty times smaller than their binding constant with fructose, the second most abundant sugar in the human body. In many cases, glucose selectivity enhancement is obtained by incorporating pendant tertiary amines into the hydrogel network, thereby giving rise to a hydrogel that is zwitterionic at physiological pH. However, the mechanism by which incorporation of tertiary amines confers selectivity enhancement is poorly understood. In order to clarify this mechanism, we use the osmotic deswelling technique to compare the thermodynamic interactions of glucose and fructose with a zwitterionic smart hydrogel containing boronic acid moieties. We also investigate the change in the structure of the hydrogel that occurs when it binds to glucose or to fructose using the technique of small angle neutron scattering.

Glucose Sensing in Supramolecular Chemistry

“…This property had been attributed to the formation of reversible crosslinks in the hydrogels with glucose. However, Horkay and Magda and co-workers 200 have shown that changes in the thermodynamic mixing interactions between polymer network and solvent are the most important factors controlling swelling and shrinking of the hydrogels.…”

Biomolecule‐Responsive Hydrogels in Medicine

“…Novel research, establishing spectroscopic evidence for glucose–bis (boronate) crosslinks formed in hydrogels, was proposed by Magda and co‐workers . They fabricated a zwitterionic hydrogel via copolymerization of glucose‐responsive hydrogels, including boronic acid, with tertiary amines (Lewis bases).…”

“…In addition, the properties of a polymer such as the number of charged groups, density of crosslinking, monomer distribution, and chemical quality play key roles in the dynamic characteristics. For example, using a low concentration of tertiary amines in a boronic acid hydrogel was found to highly increase glucose selectivity and cause hydrogel shrinkage in response to glucose addition …”

Carbon Nanotube Yarn‐Based Glucose Sensing Artificial Muscle

“…To introduce the reversible glucose‐sensing property, we selected the BA‐containing compound and conjugated it to the HC NG. BA is known to be highly selective and sensitive for the cis ‐diol on glucose and has reproducible and stable reversible binding properties . There have been many studies of the application of BA for glucose sensing using various methods, including colorimetric, fluorescent, or electrochemical changes, but many problems remain, such as photochemical instability and particular difficulty in electrical connections …”

“…BA is known to be highly selective and sensitive for the cis -diol on glucose and has reproducible and stable reversible binding properties. [ 8,25,26 ] There have been many studies of the application of BA for glucose sensing using various methods, including colorimetric, fl uorescent, or electrochemical changes, but many problems remain, such as photochemical instability and particular diffi culty in electrical connections. [ 9,[27][28][29][30] We designed compact polymeric nanoparticles of HA (modifi ed by hydrophobic cholesterol and phenylboronic acid) as a guest material for MWNT yarn, and then utilized their reversible swelling/ deswelling for yarn actuation.…”