title: Exceptionally Inert Lanthanide(III) PARACEST MRI Contrast Agents Based on an 18-Membered Macrocyclic Platform.
abstract: We report a macrocyclic ligand based on a 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane platform containing four hydroxyethyl pendant arms (L(1)) that forms extraordinary inert complexes with Ln(3+) ions. The [EuL(1)](3+) complex does not undergo dissociation in 1 M HCl over a period of months at room temperature. Furthermore, high concentrations of phosphate and Zn(2+) ions at room temperature do not provoke metal-complex dissociation. The X-ray crystal structures of six Ln(3+) complexes reveal ten coordination of the ligand to the metal ions through the six nitrogen atoms of the macrocycle and the four oxygen atoms of the hydroxyethyl pendant arms. The analysis of the Yb(3+)- and Pr(3+)-induced paramagnetic (1)H NMR shifts show that the solid-state structures are retained in aqueous solution. The intensity of the (1)H NMR signal of bulk water can be modulated by saturation of the signals of the hydroxy protons of Pr(3+), Eu(3+), and Yb(3+) complexes following chemical-exchange saturation transfer (CEST). The ability of these complexes to provide large CEST effects at 25 and 37 °C and pH 7.4 was confirmed by using CEST magnetic resonance imaging experiments.
authors.affiliation: Departamento de Química Inorgánica, Facultad de Ciencias, Universidade de Vigo, As Lagoas, Marcosende 36310 Pontevedra (Spain).
authors.forename: Goretti
authors.initials: G
authors.lastname: Castro
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: 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: Departamento de Química Inorgánica, Facultad de Química Universidad de Santiago de Compostela, Avda. de las Ciencias s/n, 15782, Santiago de Compostela (Spain).
authors.forename: Rufina
authors.initials: R
authors.lastname: Bastida
authors.affiliation: Departamento de Química Inorgánica, Facultad de Química Universidad de Santiago de Compostela, Avda. de las Ciencias s/n, 15782, Santiago de Compostela (Spain).
authors.forename: Alejandro
authors.initials: A
authors.lastname: Macías
authors.affiliation: Departamento de Química Inorgánica, Facultad de Ciencias, Universidade de Vigo, As Lagoas, Marcosende 36310 Pontevedra (Spain).
authors.forename: Paulo
authors.initials: P
authors.lastname: Pérez-Lourido
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). carlos.platas.iglesias@udc.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: Platas-Iglesias
authors.affiliation: Departamento de Química Inorgánica, Facultad de Ciencias, Universidade de Vigo, As Lagoas, Marcosende 36310 Pontevedra (Spain). qilaura@uvigo.es.
authors.forename: Laura
authors.initials: L
authors.lastname: Valencia
keywords: CEST; MRI; NMR spectroscopy; lanthanides; macrocycles