Complexes of large metal ions with symmetrically substituted 6-N-donor macrocyclic ligands: Synthesis, structural studies, and characterization of isomers

The complexes of certain lanthanide(III) ions with a six-nitrogen-donor macrocyclic ligand have properties that make them potentially useful for biomedical applications. Specifically, the luminescent complexes of europium(III) can serve as markers in cell analysis and immunology, provided they contain functional groups for covalent linking to bio-substrates. The complexes of gadolinium(III), which have high relaxivity, could be useful as contrast enhancer for in vivo magnetic resonance imaging, if their tolerance were enhanced by appropriate functional groups---e.g. carboxylates---incorporated into the periphery of the macrocyclic ligand. Therefore, functionalization of the macrocycle is an essential prerequisite for these bio-medical applications.; For macrocyclic complexes that are formed by the in-situ metal-templated condensation of small precursors and contain ligands that do not exist as metal free-species, functionalization may generally be achieved either by modifying a non-functionalized pre-formed complex or by using already substituted precursors for the in-situ synthesis. The second option is more promising, as it avoids the risk that the pre-formed metal-macrocycle entity may decompose under the conditions required to introduce functional groups into its periphery.; A second general objective was to investigate the factors that influence the metal-templated synthesis of macrocyclic complexes with two identical substituents, one at each of the di-imine side-chains. Accordingly, a broad investigation was undertaken with the following specific goals: (1) To attempt the separation and structural identifications of the isomers produced in the metal-templated synthesis. (2) To investigate the factors (temperature, size and charge of metal ion, type of counterion) that may be expected to influence the ratio of isomers obtained in a metal-templated synthesis.; The results of this work also provided useful guidelines for the future synthesis of other peripherally substituted macrocycles, as they showed that substituents attached to the carbonyl groups of the pyridine precursor can have an adverse effect on the in-situ synthesis, whereas substituents attached to the carbon atoms of the diamine precursors permit the synthesis of di-functionalized macrocyclic complexes in excellent yields. (Abstract shortened by UMI.)...