Cyclen-based phenylboronate ligands and their Eu³⁺ complexes for sensing glucose by MRI

Novel cyclen-based phenylboronate ligands and their corresponding Eu ³⁺ complexes have been examined as glucose sensors using chemical exchange saturation transfer (CEST) MR imaging for detection. Two isomeric bis-phenylboronate complexes, Eu(4) and Eu(10), and a mono-phenylboronate complex, Eu(12), had been prepared and characterized by UV and circular dichroism spectroscopy, mass spectrometry, and CEST imaging. Both the free ligands and their Eu³⁺ complexes bind to simple sugars, but their selectivity and binding affinities vary with sugar structure. Interestingly, the free ligands, 4 and 10, are selective for fructose over glucose, but this selectivity order switches in the respective Eu³⁺ complexes. Of the complexes examined, Eu(4) shows the highest selectivity and binding affinity for glucose (2275 ± 266 M^-1 at pH 10.2 and 339 ± 29 M ^-1 at pH 7). Glucose acts as a "capping" moiety in the Eu(4)-glucose binary complex and modulates water exchange between a single Eu³⁺-bound water molecule and bulk water, an effect that can be detected by CEST imaging. Thus, Eu(4) represents a new class of metabolite-specific imaging agents that may allow mapping of metabolites by MRI of the bulk water signal.