Tris(phosphonomethyl)cyclen Derivatives: Thermodynamic Stability, Kinetics, Solution Structure, and Relaxivity of Ln3+ Complexes

Authors

  • Luís M. P. Lima,

    1. Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal, Fax: +351-214411277
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  • Rita Delgado,

    1. Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal, Fax: +351-214411277
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  • Petr Hermann,

    1. Department of Inorganic Chemistry, Faculty of Science, Universita Karlova (Charles University), Hlavova 2030, 12840 Prague 2, Czech Republic
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  • Radek Ševčík,

    1. Department of Chemistry, Faculty of Science, Masaryk University, Kotlařská 2, 61137 Brno, Czech Republic
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  • Přemysl Lubal,

    1. Department of Chemistry, Faculty of Science, Masaryk University, Kotlařská 2, 61137 Brno, Czech Republic
    2. CEITEC, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic
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  • Henrique F. Carvalho,

    1. Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Apartado 3046, 3001-401 Coimbra, Portugal
    2. Center of Neurosciences and Cell Biology, University of Coimbra, and Coimbra Chemistry Centre, Rua Larga, University of Coimbra, 3004-535 Coimbra, Portugal
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  • André F. Martins,

    1. Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Apartado 3046, 3001-401 Coimbra, Portugal
    2. Center of Neurosciences and Cell Biology, University of Coimbra, and Coimbra Chemistry Centre, Rua Larga, University of Coimbra, 3004-535 Coimbra, Portugal
    3. Centre de Biophysique Moléculaire, CNRS, Rue Charles Sadron, 45071 Orléans, France
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  • Éva Tóth,

    1. Centre de Biophysique Moléculaire, CNRS, Rue Charles Sadron, 45071 Orléans, France
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  • Carlos F. G. C. Geraldes

    1. Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Apartado 3046, 3001-401 Coimbra, Portugal
    2. Center of Neurosciences and Cell Biology, University of Coimbra, and Coimbra Chemistry Centre, Rua Larga, University of Coimbra, 3004-535 Coimbra, Portugal
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Abstract

The lanthanide (Ln3+) complexes of three cyclen-based ligands containing three methylphosphonate pendant arms were studied, the ligands being 1,4,7,10-tetraazacyclododecane-1,4,7-triyltris(methylphosphonic acid) (H6do3p), 3-[4,7,10-tris(phosphonomethyl)-1,4,7,10-tetraazacyclododec-1-yl]propanoic acid (H7do3p1pr), and 10-(3-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyltris(methylphosphonic acid) (H6do3p1ol). The three macrocyclic ligands form complexes of very high thermodynamic stability with all studied Ln3+ ions. Kinetic studies showed that the acid-assisted dissociation of Ce3+ complexes of these ligands is much faster than for the complex of the related ligand H8dotp [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayltetrakis(methylphosphonic acid)]. The number of water molecules coordinated to the Eu3+ and Gd3+ complexes was estimated to be < 1 for the do3p1ol ligand but ca. 1 for the other two ligands, as obtained by time-resolved luminescence spectroscopy and by 1H and 17O relaxometric measurements. The NMR spectroscopic data indicate the existence of a considerable contribution from second-sphere water molecules to the relaxivity of all the Gd3+ complexes studied. The 1H and 31P NMR spectra of the Eu3+, Yb3+ and Lu3+ complexes showed that the propionate arm in the [Ln(do3p1pr)]4– complexes and the propanol arm in the [Ln(do3p1ol)]3– complexes are not bound to the Ln3+ ion. The [Ln(do3p)]3– and [Ln(do3p1pr)]4– complexes have a clear preference for the TSAP (twisted square antiprismatic) isomer, while both SAP (square antiprismatic) and TSAP isomers are present in solutions of the [Ln(do3p1ol)]3– complexes.

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