title: Approaching the Kinetic Inertness of Macrocyclic Gadolinium(III)-Based MRI Contrast Agents with Highly Rigid Open-Chain Derivatives.
abstract: A highly rigid open-chain octadentate ligand (H4 cddadpa) containing a diaminocylohexane unit to replace the ethylenediamine bridge of 6,6'-[(ethane-1,2 diylbis{(carboxymethyl)azanediyl})bis(methylene)]dipicolinic acid (H4 octapa) was synthesized. This structural modification improves the thermodynamic stability of the Gd(3+) complex slightly (log KGdL =20.68 vs. 20.23 for [Gd(octapa)](-) ) while other MRI-relevant parameters remain unaffected (one coordinated water molecule; relaxivity r1 =5.73 mm(-1)  s(-1) at 20 MHz and 295 K). Kinetic inertness is improved by the rigidifying effect of the diaminocylohexane unit in the ligand skeleton (half-life of dissociation for physiological conditions is 6 orders of magnitude higher for [Gd(cddadpa)](-) (t1/2 =1.49×10(5)  h) than for [Gd(octapa)](-) . The kinetic inertness of this novel chelate is superior by 2-3 orders of magnitude compared to non-macrocyclic MRI contrast agents approved for clinical use.
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Debrecen, 4010, Debrecen, Egyetem tér 1, Hungary. gyula.tircso@science.unideb.hu.|Centre de Biophysique Moléculaire, CNRS, rue Charles Sadron, 45071, Orléans, Cedex 2, France).. gyula.tircso@science.unideb.hu.|Le Studium, Loire Valley Institute for Advanced Studies, 1 Rue Dupanloup, 45000, Orléans, France. gyula.tircso@science.unideb.hu.
authors.forename: Gyula
authors.identifier: http://orcid.org/0000-0002-7896-7890
authors.initials: G
authors.lastname: Tircsó
authors.affiliation: Departamento de Química Fundamental, Universidade da Coruña, Campus da Zapateira, Rúa da Fraga 10, 15008A, Coruña, Spain.
authors.forename: Martín
authors.initials: M
authors.lastname: Regueiro-Figueroa
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Debrecen, 4010, Debrecen, Egyetem tér 1, Hungary.
authors.forename: Viktória
authors.initials: V
authors.lastname: Nagy
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Debrecen, 4010, Debrecen, Egyetem tér 1, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Garda
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Debrecen, 4010, Debrecen, Egyetem tér 1, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Garai
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Debrecen, 4010, Debrecen, Egyetem tér 1, Hungary.
authors.forename: Ferenc Krisztián
authors.initials: FK
authors.lastname: Kálmán
authors.affiliation: Departamento de Química Fundamental, Universidade da Coruña, Campus da Zapateira, Rúa da Fraga 10, 15008A, Coruña, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Esteban-Gómez
authors.affiliation: Centre de Biophysique Moléculaire, CNRS, rue Charles Sadron, 45071, Orléans, Cedex 2, France).
authors.forename: Éva
authors.initials: É
authors.lastname: Tóth
authors.affiliation: Departamento de Química Fundamental, Universidade da Coruña, Campus da Zapateira, Rúa da Fraga 10, 15008A, Coruña, Spain. carlos.platas.iglesias@udc.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: Platas-Iglesias
keywords: NMR imaging; contrast agents; coordination compounds; gadolinium; lanthanides