Synthesis of a bifunctional monophosphinic acid DOTA analogue ligand and its lanthanide(III) complexes. A gadolinium(III) complex endowed with an optimal water exchange rate for MRI applications

A new bifunctional octa-coordinating ligand containing an aminobenzyl moiety, DO3AP(ABn) (H(4)DO3AP(ABn) = 1,4,7,10-tetraazacyclododecane-4,7,10-triacetic-1-{methyl [(4-aminophenyl) methyl] phosphinic acid}), has been synthesized. Its lanthanide(III) complexes contain one water molecule in the first coordination sphere. The high-resolution H-1 and P-31 spectra of [Eu(H2O) (DO3AP(ABn))](-) show that the twisted square-antiprismatic form of the complexes is more abundant in respect to the corresponding Eu(III) DOTA complex. The H-1 NMRD and variable-temperature O-17 relaxation measurements of [Gd(H2O)(DO3AP(ABn))](-) show that the water residence time is short ((298)tauM = 16 ns) and falls into the optimal range predicted by theory for the attainment of high relaxivities once this complex would be endowed by a slow tumbling rate. The relaxivity ((298)r(1) = 6.7 mM(-1) s(-1) at 10 MHz) is higher than expected as a consequence of a significant contribution from the second hydration sphere. These results prompt the use of [Gd(H2O)(DO3AP(ABn))](-) as a building block for the set-up of highly efficient macromolecular MRI contrast agents.