A Bridge to Coordination Isomer Selection in Lanthanide(III) DOTA-tetraamide Complexes

Interest in macrocyclic lanthanide complexes such as DOTA is driven largely through interest in their use as
contrast agents for MRI. The lanthanide tetraamide derivatives of DOTA have shown considerable promise as
PARACEST agents, taking advantage of the slow water exchange kinetics of this class of complex. We postulated
that water exchange in these tetraamide complexes could be slowed even further by introducing a group to sterically
encumber the space above the water coordination site, thereby hindering the departure and approach of water
molecules to the complex. The ligand 8O2-bridged DOTAM was synthesized in a 34% yield from cyclen. It was
found that the lanthanide complexes of this ligand did not possess a water molecule in the inner coordination
sphere of the bound lanthanide. The crystal structure of the ytterbium complex revealed that distortions to the
coordination sphere were induced by the steric constraints imposed on the complex by the bridging unit. The
extent of the distortion was found to increase with increasing ionic radius of the lanthanide ion, eventually resulting
in a complete loss of symmetry in the complex. Because this ligand system is bicyclic, the conformation of each
ring in the system is constrained by that of the other; in consequence, inclusion of the bridging unit in the complexes
means only a twisted square, antiprismatic coordination geometry is observed for lanthanide complexes of 8O2-bridged DOTAM.