title: Gd(3+)-Based Magnetic Resonance Imaging Contrast Agent Responsive to Zn(2+).
abstract: We report the heteroditopic ligand H5L, which contains a DO3A unit for Gd(3+) 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((5)D4) excited state measured for the TbL complex point to the absence of coordinated water molecules. Density functional theory calculations and (1)H 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 Zn(2+) 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 Tb(3+) ion upon Zn(2+) binding to the NO2A moiety. The relaxivity of the GdL complex recorded at 7 T (25 °C) increases by almost 150% in the presence of 1 equiv of Zn(2+), while Ca(2+) and Mg(2+) induced very small relaxivity changes. In vitro magnetic resonance imaging experiments confirmed the ability of GdL to provide response to the presence of Zn(2+).
authors.affiliation: Grupo QUICOOR, Centro de Investigaciones Científicas Avanzadas (CICA) and Departamento de Química Fundamental, Universidade da Coruña , Campus da Zapateira, Rúa da Fraga 10, 15008 A Coruña, Spain.
authors.forename: Martín
authors.initials: M
authors.lastname: Regueiro-Figueroa
authors.affiliation: MR Neuroimaging Agents, Max Planck Institute for Biological Cybernetics , Spemannstr. 41, 72076 Tübingen, Germany.
authors.forename: Serhat
authors.initials: S
authors.lastname: Gündüz
authors.affiliation: UFR des Sciences et Techniques, Université de Bretagne Occidentale, UMR-CNRS 6521 , 6 avenue Victor le Gorgeu, C.S. 93837, 29238 BREST Cedex 3, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Patinec
authors.affiliation: Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics , Tübingen, Germany.|Department of Imaging Science and Biomedical Engineering, University of Manchester , Manchester, U.K.
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Logothetis
authors.affiliation: Grupo QUICOOR, Centro de Investigaciones Científicas Avanzadas (CICA) and Departamento de Química Fundamental, Universidade da Coruña , Campus da Zapateira, Rúa da Fraga 10, 15008 A Coruña, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Esteban-Gómez
authors.affiliation: UFR des Sciences et Techniques, Université de Bretagne Occidentale, UMR-CNRS 6521 , 6 avenue Victor le Gorgeu, C.S. 93837, 29238 BREST Cedex 3, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Tripier
authors.affiliation: MR Neuroimaging Agents, Max Planck Institute for Biological Cybernetics , Spemannstr. 41, 72076 Tübingen, Germany.
authors.forename: Goran
authors.initials: G
authors.lastname: Angelovski
authors.affiliation: Grupo QUICOOR, Centro de Investigaciones Científicas Avanzadas (CICA) and Departamento de Química Fundamental, Universidade da Coruña , Campus da Zapateira, Rúa da Fraga 10, 15008 A Coruña, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Platas-Iglesias
mesh_terms: D003287:Contrast Media; D005682:Gadolinium / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D066244:Proton Magnetic Resonance Spectroscopy; D015032:Zinc / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D005682:Gadolinium; D015032:Zinc