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 , Ca , Mn , Fe , Co , Ni , Cu , Zn ) and trivalent (Cr , Fe , Co ) transition metal ions was studied. The ligand forms stable complexes with late divalent transition metal ions (from Co to Zn ) 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 ion adopts a twisted trigonally antiprismatic geometry with a larger coordination cavity and smaller torsion of the pendant arms, whereas the smaller ions Ni , Cu and Zn form octahedral species with a smaller cavity and larger pendant arm torsion. In the case of the Co complexes, both coordination arrangements were observed. The complexes with paramagnetic metal ions were studied from the point of view of potential utilization in F magnetic resonance imaging. A significant shortening of the F NMR longitudinal relaxation times was observed: a sub-millisecond range for complexes of Cr , Mn and Fe with symmetric electronic states ( and HS- ), the millisecond range for the Ni and Cu complexes and tens of milliseconds for the Co 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 /Mn , Fe /Fe , Co /Co , Cu /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 /Co complex pair can be potentially used as a smart redox-responsive contrast agent for F MRI.