Gd3+-Based Magnetic Resonance Imaging Contrast Agent Responsive to Zn2+

We report the heteroditopic ligand H5L, which contains a DO3A unit for Gd3+ complexation connected to an NO2A moiety through a N-propylacetamide linker. The synthesis of the ligand followed a convergent route that involved the preparation of 1,4-bis(tert-butoxycarbonylmethyl)-1,4,7-triazacyclononane following the orthoamide strategy. The luminescence lifetimes of the Tb(D-5(4)) excited state measured for the TbL complex point to the absence of coordinated water molecules. Density functional theory calculations and H-1 NMR studies indicate that the EuL complex presents a square antiprismatic coordination in aqueous solution, where eight coordination is provided by the seven donor atoms of the DO3A unit and the amide oxygen atom of the N-propylacetamide linker. Addition of Zn2+ to aqueous solutions of the TbL complex provokes a decrease of the emission intensity as the emission lifetime becomes shorter, which is a consequence of the coordination of a water molecule to the Tb3+ ion upon Zn2+ binding to the NO2A moiety. The relaxivity of the GdL complex recorded at 7 T (25 degrees C) increases by almost 150% in the presence of 1 equiv of Zn2+, while Ca2+ and Mg2+ induced very small relaxivity changes. In vitro magnetic resonance imaging experiments confirmed the ability of GdL to provide response to the presence of Zn2+.