Transition metal complexes of cyclam with two 2,2,2-trifluoroethylphosphinate pendant arms as probes for (19)F magnetic resonance imaging
Abstract
A new cyclam-based ligand bearing two methylene(2,2,2-trifluoroethyl)phosphinate pendant arms was synthesized and its coordination behaviour towards selected divalent transition metal ions [Co(II), Ni(II), Cu(II), Zn(II)] was studied. The ligand was found to be very selective for the Cu(II) ion according to the common Williams-Irving trend.
Complexes with all the studied metal ions were structurally characterized. The Cu(II) ion forms two isomeric complexes; the pentacoordinated isomer pc-[Cu(L)] is the kinetic product and the octahedral trans-O,O'-[Cu(L)] isomer is the final (thermodynamic) product of the complexation reaction.
Other studied metal ions form octahedral cis-O,O'-[M(L)] complexes. The complexes with paramagnetic metal ions showed a significant shortening of (19)F NMR longitudinal relaxation times (T1) to the millisecond range [Ni(II) and Cu(II) complexes] or tens of milliseconds [Co(II) complex] at the temperature and magnetic field relevant for (19)F magnetic resonance imaging (MRI).
Such a short T1 results from a short distance between the paramagnetic metal ion and the fluorine atoms (approx. 6.1-6.4 Å). The complexes show high kinetic inertness towards acid-assisted dissociation; in particular, the trans-O,O'-[Cu(L)] complex was found to be extremely inert with a dissociation half-time of 2.8 h in 1 M HCl at 90 °C.
Together with the short relaxation time, it potentially enables in vitro/in vivo utilization of the complexes as efficient contrast agents for (19)F MRI.