Expanding the Family of Monosubstituted 15-Membered Pyridine-Based Macrocyclic Ligands for Mn(II) Complexation in the Context of MRI.

As Mn(II) complexes attract continuous interest as alternatives to Gd-based contrast agents (CAs) in clinical magnetic resonance imaging (MRI), we synthesized two monosubstituted derivatives of the 15-membered pyridine-based macrocycle 15-pyNO bearing either a 2-pyridylmethyl () or a 2-benzimidazolylmethyl pendant arm () and characterized their Mn(II) complexes and in the context of MRI contrast agent development. Their X-ray molecular structures confirmed a coordination number of seven and a pentagonal bipyramidal geometry with one coordination site available for inner-sphere water. Protonation constants of and , and stability constants with selected divalent metal ions were determined using potentiometry. and complexes are fully formed at pH 7.4; however, they both display low kinetic inertness due to a significant spontaneous dissociation of the nonprotonated complex. The presence of one inner-sphere water molecule in the Mn(II) complexes was confirmed by O NMR and H NMRD measurements. The water exchange rate constants are very low ( = 0.46 × 10 and 0.23 × 10 s for and , respectively), but typical for Mn(II) complexes of 15-pyNO derivatives. The relaxivities are in good agreement with monohydrated small-molecular-weight Mn(II) chelates ( = 2.49 and 2.77 mM s at 20 MHz, 25 °C, for and , respectively).