Development of Macrocyclic Mn(II)−Bispyridine Complexes as pH‐Responsive Magnetic Resonance Imaging Contrast Agents

Abstract In this study, macrocyclic complexes of Mn (II) with pH‐responsive relaxivities were developed. The ligands were based on the rigid MPi platform, which was composed of a triazacyclononane (TACN) macrocycle and two picolyl pendant arms. An aryl sulfonamide moiety introduced in the skeleton of MPi endowed the final Mn complex (Mn−MPA) with pH‐sensitive relaxivities. Mn−MPA showed a ∼3‐fold increase in longitudinal relaxivity associated with the protonation and decoordination of the sulfonamide group in an acidic environment. We found that it was feasible to tune the pH window of the complexes by choosing proper substituents on the aromatic ring or modifying on the picolyl pendants. Considering the good kinetic inertness, rapid and efficient response to pH stimuli, and easy modulation characteristics, Mn−MPAs can be considered ideal candidates for use as acidic microenvironment‐specific MRI contrast agents.