Highly substituted cyclams: Stereoselective synthesis and coordination properties

We report here a new synthetic route to highly-substituted tetraazamacrocycles. Raney nickel hydrogenation of macrocyclic phenylenediamine-acetylacetone condensation products gives cyclams in high yield with complete all-cis stereo-selectivity. The extensive C-substitution of the cyclam 2a changes its ligand properties markedly. The X-ray structure analyses of Ni-II, CUII, and Zn-II complexes of 2a reveal a deviation of the metal ion coordination geometry from the usual square-planar arrangement. This may account for the differences in the redox properties of the Ni-II and Cu-II complexes of 2a compared to 3. The highly-substituted structure of the ligand 2a leads to more positive oxidation and reduction potentials compared to the analogous unsubstituted cyclam complexes. While the binding constant between Zn(ClO4)(2) and 2a is lower by a factor of 10(5) compared to cyclam, the subsequent binding of uridine to the zinc-cyclam complexes in methanol/water is slightly stronger in the case of 2a zn(ClO4)(2).