Paramagnetic Cobalt(II) Complexes with Cyclam Derivatives: Toward 19F MRI Contrast Agents

In order to develop novel, more efficient, and/or selective contrast agents for magnetic resonance imaging (MRI), differen modi operandi are explored as alternatives to water-relaxation enhancement. In this work, cobalt(II/III) complexes of bis( N -trifluoroethyl)cyclam derivatives with two acetate or two phosphonate pendant arms, H 2 e2f2a and H 4 e2f2p , were prepared and investigated. X-ray diffraction structures confirmed octahedral coordination with a very stable rans - III cyclam conformation and with fluorine atoms located about 5.3 Å from the metal center. The Co(II) complexes are kinetically inert, decomposing slowly even in 1 M aqueous HCl at 80 °C. The Co(II) complexes exhibited well-resolved paramagnetically shifted NMR spectra. These were interpreted with the help of quantum chemistry calculations. The 13 C NMR shifts of the rans -[Co II ( e2f2p )] 2- complex were successfully assigned based on spin density delocalization within the ligand molecule. The obtained spin density also helps to describe d -metal-induced NMR relaxation properties of 19 F nuclei, including the contribution of a Fermi contact relaxation mechanism. The paramagnetic complexes show convenient relaxation properties to be used as 19 F MRI contrast agents.