Using Chiral Auxiliaries to Mimic the Effect of Chiral Media on the Structure of Lanthanide(III) Complexes Common in Bioimaging and Diagnostic MRI

[Ln·DOTA]- complexes, and systems derived therefrom, are commonly used in MRI and optical bioimaging. These lanthanide(III) complexes are chiral and, in solution, they are present in eight forms, two sets of four uncapped and four capped forms. Each set of four consist of two sets of enatiomers, with the ligand backbone in either a square antiprismatic, SAP, or twisted square antiprismatic geometry, TSAP. This complex speciation is found in laboratory samples. To investigate speciation in biological media, when Ln·DOTA-like complexes interact with chiral biomolecules, six Eu·DOTA-monoamide complexes were prepared and investigated using 1D and 2D 1H NMR. To emulate the chirality of biological media, the amide pendant arm was modified with one or two chiral centers. It was known that a chiral center on the DOTA scaffold significantly influences the properties of the system. Here, it was found that chirality much further away from the metal changes the available conformational space, and that both chiral centers and cis/trans isomerism are important, a fact that, for the optically pure materials, led to the conclusion that sixteen forms had to be considered, instead of the eight forms necessary for DOTA. The results reported here clearly demonstrate the diverse speciation that must be considered when correlating an observation to a structure of a lanthanide(III) complex.