The Design and Synthesis of Highly Branched and Spherically Symmetric Fluorinated Macrocyclic Chelators.

Two novel, highly fluorinated macrocyclic chelators with highly branched and spherically symmetric fluorocarbon moieties have been designed and efficiently synthesized. This is achieved by conjugating a spherically symmetric fluorocarbon moiety to the macrocyclic chelator DOTA, with or without a flexible oligo-oxyethylene linker between these two parts. As a result of the spherical symmetry, all 27 fluorine atoms in each fluorinated chelator give a sharp singlet (19)F NMR signal. The hydrophilicity and the (19)F relaxation behavior of fluorinated chelators can be modulated by the insertion of a flexible linker between the fluorocarbon moiety and the macrocyclic linker. These chelators serve as prototypes for (1)H-(19)F dual-nuclei magnetic resonance imaging agents.