Alkaline Earth Metal and Lanthanide(III) Complexes of Ligands Based upon 1,4,7,10-Tetraazacyclododecane-1,7-bis(acetic acid)

The macrocyclic ligand DO2A (1,4,7,10-tetraazacyclododecane-1,7-bis(acetic acid)) was prepared and used as a building block for four new macrocyclic ligands having mixed side-chain chelating groups. These ligands and their complexes with MgII, CaII, and LnIII were studied extensively by potentiometry, high-resolution NMR, and water proton relaxivity measurements. The protonation constants of all compounds compared well with those of other cyclen-based macrocyclic ligands. All CaII complexes were found to be more stable than the corresponding MgII complexes. Trends for the stabilities of the LnIII complexes are discussed and compared with literature data, incorporating the effects of water coordination numbers, LnIII contraction, and the nature of the side chains and the steric hindrance between them. 1H NMR titrations of DO2A revealed that the first and second protonations take place preferentially at the secondary ring nitrogens, while the third and fourth involved protonation of the acetates. 17O NMR shifts showed that the DyDO2A+ complex had two inner-sphere water molecules. Water proton spin−lattice relaxation rates for the GdDO2A+ complex were also consistent with water exchange between bulk water and two inner-sphere GdIII coordination positions. Upon formation of the diamagnetic complexes of DO2A (CaII, MgII, LaIII, and LuIII), all of the macrocyclic ring protons became nonequivalent due to slow conformational rearrangements, while the signals for the acetate CH2 protons remained a singlet.