Cyclen-Based Phenylboronate Ligands and Their Eu^3+ 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 Eu^3+ 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 Eu^3+ 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 Eu^3 +-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.