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 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.
Trokowski
Robert
R
Department of Chemistry, The University of Texas at Dallas, P.O. Box 830688, Richardson, Texas 75083-0688, USA.
Zhang
Shanrong
S
Sherry
A Dean
AD
D001897:Boronic Acids / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D000080027:Cyclams; D004305:Dose-Response Relationship, Drug; D005063:Europium / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D005947:Glucose / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000379:methods
D001897:Boronic Acids; D000080027:Cyclams; D006571:Heterocyclic Compounds; D008024:Ligands; D005063:Europium; C038072:cyclen; D005947:Glucose; C010686:benzeneboronic acid