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

Abstract

A new bifunctional octa-coordinating ligand containing an aminobenzyl moiety, DO3AP^ABn (H₄DO3AP^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 ¹H and ³¹P 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 ¹H NMRD and variable-temperature ¹⁷O relaxation measurements of [Gd(H₂O)(DO3AP^ABn)]⁻ show that the water residence time is short (²⁹⁸τ_M = 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 (²⁹⁸r₁ = 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.