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-pyN3O2 bearing either a 2-pyridylmethyl (L2) or a 2-benzimidazolylmethyl pendant arm (L3) and characterized their Mn(II) complexes MnL2 and MnL3 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 L2 and L3, and stability constants with selected divalent metal ions were determined using potentiometry. MnL2 and MnL3 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 17O NMR and 1H NMRD measurements. The water exchange rate constants are very low (kex298 = 0.46 × 107 and 0.23 × 107 s-1 for MnL2 and MnL3, respectively), but typical for Mn(II) complexes of 15-pyN3O2 derivatives. The relaxivities are in good agreement with monohydrated small-molecular-weight Mn(II) chelates (r1 = 2.49 and 2.77 mM-1 s-1 at 20 MHz, 25 °C, for MnL2 and MnL3, respectively).

Centre de Biophysique Moléculaire CNRS UPR 4301 Université d'Orléans rue Charles Sadron 45071 Orléans France

Department of Inorganic Chemistry Faculty of Science Palacký University Olomouc 17 listopadu 12 771 46 Olomouc Czech Republic

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