Transition metal complexes of the (2,2,2-trifluoroethyl)phosphinate NOTA analogue as potential contrast agents for 19 F magnetic resonance imaging.

A new hexadentate 1,4,7-triazacyclononane-based ligand bearing three coordinating methylene-(2,2,2-trifluoroethyl)phosphinate pendant arms was synthesized and its coordination behaviour towards selected divalent (Mg 2+ , Ca 2+ , Mn 2+ , Fe 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ ) and trivalent (Cr 3+ , Fe 3+ , Co 3+ ) transition metal ions was studied. The ligand forms stable complexes with late divalent transition metal ions (from Co 2+ to Zn 2+ ) and the complexes of these metal ions are formed above pH ∼3. A number of complexes with divalent metal ions were structurally characterized by means of single-crystal X-ray diffraction. The complex of the larger Mn 2+ ion adopts a twisted trigonally antiprismatic geometry with a larger coordination cavity and smaller torsion of the pendant arms, whereas the smaller ions Ni 2+ , Cu 2+ and Zn 2+ form octahedral species with a smaller cavity and larger pendant arm torsion. In the case of the Co 2+ complexes, both coordination arrangements were observed. The complexes with paramagnetic metal ions were studied from the point of view of potential utilization in 19 F magnetic resonance imaging. A significant shortening of the 19 F NMR longitudinal relaxation times was observed: a sub-millisecond range for complexes of Cr 3+ , Mn 2+ and Fe 3+ with symmetric electronic states ( t 2g 3 and HS- d 5 ), the millisecond range for the Ni 2+ and Cu 2+ complexes and tens of milliseconds for the Co 2+ complex. Such short relaxation times are consistent with a short distance between the paramagnetic metal ion and the fluorine atoms (∼5.5-6.5 Å). Among the redox-active complexes (Mn 3+ /Mn 2+ , Fe 3+ /Fe 2+ , Co 3+ /Co 2+ , Cu 2+ /Cu + ), the cobalt complexes show sufficient stability and a paramagnetic-diamagnetic changeover with the redox potential lying in a physiologically relevant range. Thus, the Co 3+ /Co 2+ complex pair can be potentially used as a smart redox-responsive contrast agent for 19 F MRI.