Synthesis of Macrocyclic Lanthanide Chelates for Anion Sensing and Magnetic Resonance Imaging Applications

Novel Eu³⁺-containing macrocyclic complexes were synthesized and studied as anion sensing probe molecules. Several of these macrocycles exhibited unique luminescence responses to hydrogen-bond accepting anions (fluoride, acetate, and dihydrogen phosphate) in DMSO, even in the presence of a chloride ion background. The first series of compounds highlighted a high-yielding synthetic route for highly functional macrocycles that incorporate a Eu³⁺ chelate, aromatic antennae, thiourea groups as anion-binding units, and a variable linker that tunes the size and rigidity of the pocket. These macrocycles exhibited Eu³⁺ luminescence where emission intensity (λ_exc = 272 nm, λ_em = 614 nm) was correlated to the linker length. Anion-induced changes in emission intensity were dependent on the basicity of the anion, and emission enhancements were observed up to 77% upon titration with fluoride in one case. Through luminescence lifetime studies of the Eu³⁺ macrocycles and the study of a newly synthesized series of organic model compounds, it was determined that the luminescence response to anions was the result of interaction with the thiourea moieties and no evidence was observed for anion coordination to Eu³⁺. Additionally, two second-generation macrocycles were synthesized, incorporating an amine unit for stronger binding affinity. One of these macrocycles, featuring a pendant naphthalene antenna, responded to several anions in aqueous solution by means of a luminescence decrease of up to 30%. This general macrocyclic design shows promise for the development of Eu³⁺-based anion sensors that function in competitive solvents.

In continuing work with lanthanide complexes, a new targeted Gd³⁺-based magnetic resonance imaging contrast agent was designed and synthesized for specific binding to the dopamine receptor protein. A relaxivity of 7.1 mM^-1s^-1 was measured for this complex at 400 mHz and 310 K. A Eu³⁺ analogue was also synthesized and structurally characterized. Luminescence lifetime measurements revealed the presence of 2 coordinated water molecules in aqueous solution, consistent with the observed relaxivity of the Gd³⁺ complex. The synthetic scheme described herein can be extended to the synthesis of a series of targeted complexes for enhanced dopamine receptor binding and imaging studies.