Novel Molecular Complexes Can Improve Affordability, Chiral Selectivity When Testing for Diabetes

Investigators at Sophia University in Japan have designed an all-new system of complexes to diagnose diabetes, according to a study published in ACS Sensors. The tool uses a fluorescence molecular recognition method to detect the chiral monosaccharide D-glucose in water.

“Most approaches for designing D-glucose chemical sensors require complicated syntheses, often have poor solubility in water, and sometimes have poor selectivity,” said Takashi Hayashita of the Department of Materials and Life Sciences at Sophia University, in a press release.

The new mechanism involves fluorescent monoboronic acid-based receptors enclosed in γ-cyclodextrin (γ-CyD) cavity, which could show the future of diagnostic testing for diabetes.

Diabetes mellitus is characterized by abnormally high concentrations of glucose in the blood. Traditional diagnostic techniques collect blood serum samples and separate D-glucose from L-glucose to eventually detect diabetes, which is an expensive and complex process.

D-glucose and L-glucose are enantiomer pairs that stem from chiral (asymmetrical) molecules. They are non-superimposable “mirror images” of the same molecule that share identical physical and chemical properties but have different biological functions. There have been advancements in the field of molecular recognition—the science of detecting compounds through the exploitation of their binding properties—but researchers struggle to differentiate chiral molecules without expensive tools.

First, investigators created the γ-CyD complex. It can capture hydrophobic compounds in an aqueous environment. Then, they created 3-fluorophenylboronic acid-based receptor (1F) and pyridyl boronic acid-based receptor (2N)—simple hydrophobic fluorescent monoboronic acid-based receptors. Finally, 1F or 2N were independently attached to the γ-CyD complex to form the complexes 1F/γ-CyD and 2N/γ-CyD.

The complexes created a “pseudo-diboronic acid moiety” that enhanced the fluorescence of D-glucose relative to L-glucose, while also being recognizable in water versus blood serum. D-fructose, D-galactose, and D-mannose are typical blood saccharides that would also have weak fluorescence.

“To the best of our knowledge, 2N/γ-CyD has the highest D/L selectivity among other reported fluorescent diboronic acid molecule-based receptors,” said Yota Suzuki, Department of Materials and Life Sciences at Sophia University, in the press release.

D-glucose has a higher fluorescence because it bridges the 1F and 2N monoboronic acid molecules, which solidifies its structure while elevating fluorescence. For non-glucose saccharides, different monoboronic acid molecules bind to γ-CyD, which creates a lower fluorescence.

Further, the 1F/γ-CyD and 2N/γ-CyD complexes are sensitive, only needing low limits of detection (LODs) to identify D-glucose concentrations. As a result, they can serve as D-glucose chemical sensors.

“The developed fluorescent sensors are useful for detecting D-glucose selectively and discriminating glucose enantiomers,” Hayashita said in the press release. “Since their chemical structures are quite simple, these sensors will help develop affordable and reproducible kits for its early diagnosis...[and] can potentially also serve as next-generation diagnosing systems for diabetes.”

Reference

Sophia University. New Fluorescent Chiral-Selective Receptor System Represents a Breakthrough in Molecular Detection with Potential for Applications in Diabetes Management. News Release. March 2, 2023. Accessed March 6, 2023. https://www.sophia.ac.jp/eng/article/news/release/press20230302/