pH-Dependent Hydration Change in a Gd-Based MRI Contrast Agent with a Phosphonated Ligand

Area of Science:

• Coordination Chemistry
• Supramolecular Chemistry
• Materials Science

Background:

• Development of stable lanthanide complexes is crucial for applications in medical imaging and sensing.
• Understanding the coordination behavior and solution dynamics of these complexes is essential for optimizing their properties.

Purpose of the Study:

• To synthesize and characterize a novel heptadentate ligand and its lanthanide complexes.
• To investigate the structural, relaxometric, and spectroscopic properties of these complexes, focusing on pH-dependent behavior.
• To elucidate the solution dynamics and hydration states of the complexes.

Main Methods:

• Synthesis of a heptadentate ligand (L) and its complexes with Gd, Tb, Eu, Lu, and Yb.
• X-ray crystallography to determine coordination modes.
• Variable temperature and field-dependent relaxivity measurements.
• 17O NMR, 1H NMR, 31P NMR, and DOSY experiments.
• Density Functional Theory (DFT) calculations.

Main Results:

• The Gd complex exhibits exceptional stability (pGd = 18.4 at pH 7.4).
• Gd and Tb complexes show distinct coordination numbers (octa- and nonacoordinated, respectively).
• Longitudinal relaxivity of the Gd complex significantly increases at acidic pH due to a change in hydration number from one to two water molecules.
• Eu complex luminescence and Yb complex NMR data corroborate the pH-dependent hydration state changes.
• DOSY experiments confirm the absence of dimerization for the Lu analogue in solution.

Conclusions:

• The studied ligand forms highly stable lanthanide complexes with pH-tunable properties.
• The observed changes in hydration state significantly impact the relaxometric and spectroscopic properties.
• A flexible 'breathing' mode of the complex is proposed, influencing its behavior in solution.
• These findings provide insights for designing advanced lanthanide-based contrast agents and sensors.