Manganese Complex of a Rigidified 15-Membered Macrocycle: A Comprehensive Study.

Owing to the increasing importance of manganese(II) complexes in the field of magnetic resonance imaging (MRI), large efforts have been devoted to find an appropriate ligand for Mn(II) ion encapsulation by providing balance between the seemingly contradictory requirements (i.e., thermodynamic stability and kinetic inertness vs low ligand denticity enabling water molecule(s) to be coordinated in its metal center). Among these ligands, a large number of pyridine or pyridol based open-chain and macrocyclic chelators have been investigated so far. As a next step in the development of these chelators, 15-pyN3O2Ph and its transition metal complexes were synthesized and characterized using established methods. The 15-pyN3O2Ph ligand incorporates both pyridine and ortho-phenylene units to decrease ligand flexibility. The thermodynamic properties, protonation and stability constants, were determined using pH-potentiometry; the solid-state structures of two protonation states of the free ligand and its manganese complex were obtained by single crystal X-ray diffractometry. The results show a seven-coordinate metal center with two water molecules in the first coordination sphere. The longitudinal relaxivity of [Mn(15-pyN3O2Ph)]2+ was found to be 5.16 mM-1 s-1 at 0.49 T (298 K). Furthermore, the r2p value of 11.72 mM-1 s-1 (0.49 T), which is doubled at 1.41 T field, suggests that design of this Mn(II) complex does achieve some characteristics required for contrast imaging. In addition, 17O NMR measurements were performed in order to access the microscopic parameters governing this key feature (e.g., water exchange rate). Finally, manganese complexes of ligands with analogous polyaza macrocyclic scaffold have been investigated as low molecular weight Mn(CAT) mimics. Here, we report the H2O2 disproportionation study of [Mn(15-pyN3O2Ph)]2+ to demonstrate the versatility of this ligand scaffold as well.