Lanthanide(III) complexes of six-nitrogen-donor macrocyclic ligands with peripheral functionalities

The complexes of lanthanide(III) ions with 18-member six-nitrogen-donor macrocyclic ligands possess a combination of properties-solubility in water and water-compatible organic solvents, inertness of the metal-macrocycle entity with respect to metal release or exchange, lability of the exocyclic anions--that makes them suitable for biomedical applications. Specifically, the complexes of Eu(III) can serve as luminescent markers in cell analysis and immunology, provided the macrocyclic ligands include functional groups suitable for coupling to bio-substrates. Complexes of mono-substituted and symmetrically di-substituted macrocycles were synthesized by the lanthanide-templated condensation of a carbon-substituted 1,2-diaminoethane with a non-substituted diimine-dicarbonyl precursor or 2,6-diacetylpyridine, respectively. The substituents included -CH3, -CH2-OH, -CH2-C6H5, -CH2-C6H4-OH and -CH2-C6H4-NH2. The di-substituted complexes exist as constitutional as well as steric isomers and their separation and structural identification were investigated. As a model for this class of luminescent bio-markers, a SCN-functionalized Eu-macrocycle obtained from the NH2-analogue by reaction with thiophosgene was coupled to avidin; the luminescence as well as the biotin-affinity of the resulting conjugate were evaluated.