Solution structures, stabilities, kinetics, and dynamics of DO3A and DO3A-sulphonamide complexes

Area of Science:

• Inorganic Chemistry
• Radiochemistry
• Magnetic Resonance Imaging (MRI)

Background:

• Gadolinium(III)-based complexes are widely used as MRI contrast agents.
• Development of pH-sensitive MRI agents is crucial for advanced diagnostics.
• The DO3A-SA complex offers potential for improved MRI performance and pH sensitivity.

Purpose of the Study:

• To investigate the stability, coordination chemistry, and solution dynamics of lanthanide(III)-DO3A-SA complexes.
• To evaluate the potential of Gd(3+)-DO3A-SA as a pH-sensitive MRI contrast agent.
• To elucidate the structural and dynamic properties influencing the complex's behavior.

Main Methods:

• Synthesis and characterization of Ln(III)-DO3A-SA complexes.
• Determination of stability constants and protonation constants using potentiometry.
• NMR spectroscopy (1H, 13C, COSY, EXSY, HSQC) for structural and dynamic analysis.
• Theoretical calculations (in vacuo and PCM) for conformational analysis.
• X-ray crystallography for solid-state structure determination.

Main Results:

• Ln(DO3A-SA) complexes exhibit significantly higher stability constants compared to Ln(DO3A) complexes.
• A strong interaction between Ln(3+) ions and the sulphonamide nitrogen atom was observed.
• Two coordination isomers (SAP and TSAP) exist in solution for Eu-, Y-, and Lu(DO3A-SA) complexes.
• Ln(DO3A-SA) complexes show faster arm rotation and lower activation entropy than Ln(DOTA) complexes, indicating reduced rigidity.
• Transmetalation of Gd(HDO3A-SA) with Cu(2+) is very slow, primarily occurring via proton-assisted dissociation.

Conclusions:

• The Gd(3+)-DO3A-SA complex is a stable and promising pH-sensitive MRI agent.
• The flexibility and isomerization dynamics of Ln(DO3A-SA) complexes are key features for their application.
• Further research into the application of DO3A-SA complexes in MRI is warranted.