Expanding The Ligand Classes Used For Mn(Ii) Complexation: Oxa-Aza Macrocycles Make The Difference

We report two macrocyclic ligands based on a 1,7-diaza-12-crown-4 platform functionalized with acetate (tO2DO2A(2-)) or piperidineacetamide (tO2DO2AM(Pip)) pendant arms and a detailed characterization of the corresponding Mn(II) complexes. The X-ray structure of [Mn(tO2DO2A)(H2O)]center dot 2H(2)O shows that the metal ion is coordinated by six donor atoms of the macrocyclic ligand and one water molecule, to result in seven-coordination. The Cu(II) analogue presents a distorted octahedral coordination environment. The protonation constants of the ligands and the stability constants of the complexes formed with Mn(II) and other biologically relevant metal ions (Mg(II), Ca(II), Cu(II) and Zn(II)) were determined using potentiometric titrations (I = 0.15 M NaCl, T = 25 degrees C). The conditional stabilities of Mn(II) complexes at pH 7.4 are comparable to those reported for the cyclen-based tDO2A(2-) ligand. The dissociation of the Mn(II) chelates were investigated by evaluating the rate constants of metal exchange reactions with Cu(II) under acidic conditions (I = 0.15 M NaCl, T = 25 degrees C). Dissociation of the [Mn(tO2DO2A)(H2O)] complex occurs through both proton- and metal-assisted pathways, while the [Mn(tO2DO2AM(Pip))(H2O)] analogue dissociates through spontaneous and proton-assisted mechanisms. The Mn(II) complex of tO2DO2A(2-) is remarkably inert with respect to its dissociation, while the amide analogue is significantly more labile. The presence of a water molecule coordinated to Mn(II) imparts relatively high relaxivities to the complexes. The parameters determining this key property were investigated using O-17 NMR (Nuclear Magnetic Resonance) transverse relaxation rates and H-1 nuclear magnetic relaxation dispersion (NMRD) profiles.