New Receptors for Glucose Recognition in Water

Abstract

Glucose recognition in water is highly challenging but also very important. A synthetic glucose binding receptor, christened GluHUT, has been shown to bind glucose strongly and selectively. Building on the previous success of GluHUT, this thesis aims to make new receptors to further their performance towards glucose through cooperativity and other non-covalent interactions.
A derivative of GluHUT with three added hydroxyl groups, that serves as a common intermediate for making further modifications (with sulfonate and sulphate groups) has been successfully synthesized. All these receptors show spectroscopic responses indicating glucose binding in water.
To mimic the S-shaped curve of insulin secretion in the human body, a divalent “double-decker” receptor was designed and synthesized successfully. Based on preliminary results, it exhibits a very high binding affinity towards glucose (Ka=3.3×104 M-1) and even stronger binding affinity to divalent guest.
A receptor equipped with an elongated binding site was designed to accept two glucose molecules with cooperativity. The eclipsed isomer was selectively synthesized over the staggered version by the employment of a template. It can bind two glucosides in organic solvents with negative cooperativity. Its water-soluble version can selectively bind cellobiose with high binding affinity (Ka=1622 M-1).
One of the driving forces for effective glucose binding is overall hydrophobicity of the GluHUT core. A receptor with benzene incorporated on the GluHUT roof was designed and made successfully to quantify the hydrophobic effect relative to the classic GluHUT. Its binding affinity is still under investigation.

Date of Award	16 Dec 2025
Original language	English
Awarding Institution	University of Bristol
Supervisor	Anthony P Davis (Supervisor) & Will M Dawson (Supervisor)