High relaxivity Mn(2+)-based MRI contrast agents.

Area of Science:

• Inorganic Chemistry
• Biomedical Imaging
• Materials Science

Background:

• Manganese(II) complexes are explored as contrast agents for Magnetic Resonance Imaging (MRI).
• Relaxivity, a measure of MRI contrast enhancement, is crucial for effective imaging.
• Designing ligands that stabilize Mn(II) and enhance water exchange is key to improving relaxivity.

Purpose of the Study:

• To synthesize and characterize novel mononuclear and dinuclear manganese(II) complexes.
• To investigate the binding interactions of these complexes with human serum albumin (HSA).
• To evaluate the relaxivity of these complexes, particularly upon protein binding, for potential MRI applications.

Main Methods:

• Synthesis of pentadentate 6,6'-((methylazanediyl)bis(methylene))dipicolinic acid ligands.
• Coordination of Mn(II) to form mono- and binuclear complexes.
• Binding studies with HSA using techniques like isothermal titration calorimetry.
• Relaxivity measurements at various magnetic field strengths and temperatures.

Main Results:

• Stable Mn(II) mono- and binuclear complexes were successfully synthesized.
• The mononuclear complex binds HSA with a high association constant (3372 M⁻¹), leading to water molecule replacement.
• The dinuclear complex also binds HSA, retaining solvent-accessible water molecules and exhibiting significantly enhanced relaxivity (39.05 mM⁻¹s⁻¹ per Mn at 20 MHz, 37°C).

Conclusions:

• The presence of two inner-sphere water molecules in the complexes contributes to high intrinsic relaxivity.
• HSA binding modulates the water coordination environment, impacting relaxivity.
• The dinuclear complex demonstrates exceptional protein-activated relaxivity, highlighting its potential as an advanced MRI contrast agent.