A highly stable gadolinium complex with a fast, associative mechanism of water exchange

The prominence of magnetic resonance imaging (MRI) as a medical diagnostic technique has prompted intense interest in the development of contrast agents. The primary clinical contrast agents are nine-coordinate gadolinium (GdIII) complexes based on a poly-(amino carboxylate) ligand and function by enhancing the relaxation rate of water protons.1-3 The image enhancement capability (proton relaxivity, r1p) of current clinical contrast agents is only a few percent of that theoretically possible2,4 due to the presence of only one inner sphere water molecule and a short rotational correlation time. When the rotational correlation time is optimized, the slow water exchange rate (kex 106 s-1) becomes the limiting factor in attaining higher relaxivities.1 Therefore, any rational design of a high-relaxivity contrast agent requires a thorough understanding of the mechanism of water exchange at the metal center. The GdIII complexes based on a hexadentate, hetero-tripoda