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

Bioconjug Chem. 2004 Nov-Dec;15(6):1431-40. doi: 10.1021/bc0498976.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Boronic Acids / analysis*
  • Boronic Acids / chemistry
  • Boronic Acids / metabolism
  • Cyclams
  • Dose-Response Relationship, Drug
  • Europium / analysis*
  • Europium / chemistry
  • Europium / metabolism
  • Glucose / analysis*
  • Glucose / chemistry
  • Glucose / metabolism
  • Heterocyclic Compounds / analysis*
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / metabolism
  • Ligands
  • Magnetic Resonance Imaging / methods

Substances

  • Boronic Acids
  • Cyclams
  • Heterocyclic Compounds
  • Ligands
  • Europium
  • cyclen
  • Glucose
  • benzeneboronic acid