Pyridine-Based Lanthanide Complexes Combining MRI and NIR Luminescence Activities

Authors

  • Dr. Célia S. Bonnet,

    1. Centre de Biophysique Moléculaire, CNRS rue Charles Sadron, 45071 Orléans (France)
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  • Dr. Frédéric Buron,

    1. Institut de Chimie Organique et Analytique, UMR 6005 CNRS, Université d'Orléans rue de Chartres, 45067 Orléans (France)
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  • Dr. Fabien Caillé,

    1. Centre de Biophysique Moléculaire, CNRS rue Charles Sadron, 45071 Orléans (France)
    2. Institut de Chimie Organique et Analytique, UMR 6005 CNRS, Université d'Orléans rue de Chartres, 45067 Orléans (France)
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  • Dr. Chad M. Shade,

    1. Department of Chemistry, The University of Pittsburgh, 219 Parkman Avenue, 15260 Pittsburgh (USA)
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  • Dr. Bohuslav Drahoš,

    1. Centre de Biophysique Moléculaire, CNRS rue Charles Sadron, 45071 Orléans (France)
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  • Dr. Laurent Pellegatti,

    1. Centre de Biophysique Moléculaire, CNRS rue Charles Sadron, 45071 Orléans (France)
    2. Institut de Chimie Organique et Analytique, UMR 6005 CNRS, Université d'Orléans rue de Chartres, 45067 Orléans (France)
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  • Dr. Jian Zhang,

    1. Department of Chemistry, The University of Pittsburgh, 219 Parkman Avenue, 15260 Pittsburgh (USA)
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  • Dr. Sandrine Villette,

    1. Centre de Biophysique Moléculaire, CNRS rue Charles Sadron, 45071 Orléans (France)
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  • Prof. Dr. Lothar Helm,

    1. Laboratory of Inorganic and Bioinorganic Chemistry, Ecole Polytechnique Fédérale de Lausanne, BCH, 1015 Lausanne (Switzerland)
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  • Prof. Dr. Chantal Pichon,

    1. Centre de Biophysique Moléculaire, CNRS rue Charles Sadron, 45071 Orléans (France)
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  • Dr. Franck Suzenet,

    Corresponding author
    1. Institut de Chimie Organique et Analytique, UMR 6005 CNRS, Université d'Orléans rue de Chartres, 45067 Orléans (France)
    • Institut de Chimie Organique et Analytique, UMR 6005 CNRS, Université d'Orléans rue de Chartres, 45067 Orléans (France)
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  • Prof. Dr. Stéphane Petoud,

    Corresponding author
    1. Centre de Biophysique Moléculaire, CNRS rue Charles Sadron, 45071 Orléans (France)
    2. Department of Chemistry, The University of Pittsburgh, 219 Parkman Avenue, 15260 Pittsburgh (USA)
    • Centre de Biophysique Moléculaire, CNRS rue Charles Sadron, 45071 Orléans (France)
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  • Dr. Éva Tóth

    Corresponding author
    1. Centre de Biophysique Moléculaire, CNRS rue Charles Sadron, 45071 Orléans (France)
    • Centre de Biophysique Moléculaire, CNRS rue Charles Sadron, 45071 Orléans (France)
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  • MRI=magnetic resonance imaging; NIR=near infrared.

Abstract

A series of novel triazole derivative pyridine-based polyamino–polycarboxylate ligands has been synthesized for lanthanide complexation. This versatile platform of chelating agents combines advantageous properties for both magnetic resonance (MR) and optical imaging applications of the corresponding Gd3+ and near-infrared luminescent lanthanide complexes. The thermodynamic stability constants of the Ln3+ complexes, as assessed by pH potentiometric measurements, are in the range log KLnL=17–19, with a high selectivity for lanthanides over Ca2+, Cu2+, and Zn2+. The complexes are bishydrated, an important advantage to obtain high relaxivities for the Gd3+ chelates. The water exchange of the Gd3+ complexes (kex298=7.7–9.3×106 s−1) is faster than that of clinically used magnetic resonance imaging (MRI) contrast agents and proceeds through a dissociatively activated mechanism, as evidenced by the positive activation volumes (ΔV=7.2–8.8 cm3 mol−1). The new triazole ligands allow a considerable shift towards lower excitation energies of the luminescent lanthanide complexes as compared to the parent pyridinic complex, which is a significant advantage in the perspective of biological applications. In addition, they provide increased epsilon values resulting in a larger number of emitted photons and better detection sensitivity. The most conjugated system PheTPy, bearing a phenyl–triazole pendant on the pyridine ring, is particularly promising as it displays the lowest excitation and triplet-state energies associated with good quantum yields for both Nd3+ and Yb3+ complexes. Cellular and in vivo toxicity studies in mice evidenced the non-toxicity and the safe use of such bishydrated complexes in animal experiments. Overall, these pyridinic ligands constitute a highly versatile platform for the simultaneous optimization of both MRI and optical properties of the Gd3+ and the luminescent lanthanide complexes, respectively.

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