Synthesis, Characterization, and pH-Dependent Relaxivity of the Mn(II) Complex of a Novel Cyclen-Based Ligand

Previously, the Mn(II) complexes of macrocyclic ligands H4DOTA and DOTAM have been studied to better understand their solution dynamics and investigate their potential use as MRI contrast agents. It has been shown that MnDOTA has a strong pH dependence to its relaxivity and a low stability under acidic conditions. MnDOTAM has been shown to be more stable, but its relaxivity is low and shows no pH dependence. As pH variation in the body is a potential target application of MRI contrast agents, some pH dependence of relaxivity is desirable. This work focuses on the synthesis of a novel macrocylic cyclen-based ligand, 1,4,7,10-tetraazacyclododecane-1,7-bis(acetate)-4,10-bis(acetamide), containing both acetate and amide functional groups. The ligand and its Mn(II) complex are characterized in solution and the solid state. The Mn(II) complex is believed to be at least six-coordinate over a large pH range, and is stable at relatively low pH. Its relaxivity is pH dependent, and at low pH can be attributed to both inner-sphere water exchange as well as prototropic exchange. This new ligand and Mn(II) complex provide insight into the roles different functional groups play in the structure of these types of complexes which can aid in the future design of pH-sensitive, stable MRI contrast agents.