Rigid Bispyclen Ligand Appended with Two Malonate Groups: Fast, Highly Stable, and Inert Gd(III) Complexation

Area of Science:

• Inorganic Chemistry
• Materials Science
• Radiochemistry

Background:

• Gadolinium(III) chelators are crucial for MRI contrast agents.
• Developing stable and inert chelators remains a key challenge.
• Novel ligand design is essential for improved performance and safety.

Purpose of the Study:

• To synthesize and characterize a novel chelator, H4BPDMA, for Gadolinium(III) complexation.
• To evaluate the thermodynamic stability, kinetic inertness, and structural properties of the [Gd(BPDMA)]- complex.
• To assess the potential of [Gd(BPDMA)]- as an MRI contrast agent.

Main Methods:

• Synthesis of the H4BPDMA ligand.
• Equilibrium and kinetic studies (Cu-transmetalation).
• Structural analysis using DFT calculations and NMR spectroscopy (13C, 17O).
• Relaxivity measurements and luminescence lifetime studies.

Main Results:

• H4BPDMA forms stable Gd(III) complexes rapidly, even in acidic conditions.
• The [Gd(BPDMA)]- complex exhibits high thermodynamic and conditional stability (pGd = 15.6).
• Dissociation half-life is 3.2 years at 37 °C, pH 7.4, indicating high kinetic inertness.
• DFT and NMR confirm a nine-coordinate complex with one water molecule.
• Relaxivity (r1 = 4.6 mM-1s-1) and water exchange rate are comparable to clinical agents.

Conclusions:

• H4BPDMA is a promising ligand for developing stable and inert Gd(III) complexes.
• The [Gd(BPDMA)]- complex demonstrates excellent stability and favorable properties for MRI applications.
• This research contributes to the design of next-generation MRI contrast agents.