A Starburst-Shaped Heterometallic Compound Incorporating Six Densely Packed Gd3+ Ions

Authors

  • João Bruno Livramento,

    1. Laboratoire de Chimie Inorganique et Bioinorganique, Ecole Polytechnique Fédérale de Lausanne, EPFL-BCH, 1015 Lausanne, Switzerland, Fax: (+41) 21-693-9875
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  • Angélique Sour Dr.,

    1. Laboratoire de Chimie Inorganique et Bioinorganique, Ecole Polytechnique Fédérale de Lausanne, EPFL-BCH, 1015 Lausanne, Switzerland, Fax: (+41) 21-693-9875
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  • Alain Borel Dr.,

    1. Laboratoire de Chimie Inorganique et Bioinorganique, Ecole Polytechnique Fédérale de Lausanne, EPFL-BCH, 1015 Lausanne, Switzerland, Fax: (+41) 21-693-9875
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  • André E. Merbach Prof.,

    1. Laboratoire de Chimie Inorganique et Bioinorganique, Ecole Polytechnique Fédérale de Lausanne, EPFL-BCH, 1015 Lausanne, Switzerland, Fax: (+41) 21-693-9875
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  • Éva Tóth Dr.

    1. Laboratoire de Chimie Inorganique et Bioinorganique, Ecole Polytechnique Fédérale de Lausanne, EPFL-BCH, 1015 Lausanne, Switzerland, Fax: (+41) 21-693-9875
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Abstract

The heterotritopic ligand [bpy(DTTA)2]8− has two diethylenediamine-tetraacetate units for selective lanthanide(III) coordination and one bipyridine function for selective FeII coordination. In aqueous solution and in the presence of these metals, the ligand is capable of self-assembly to form a rigid supramolecular metallostar structure, {Fe[Gd2bpy(DTTA)2(H2O)4]3}4−. We report here the physicochemical characterization of the dinuclear complex [Gd2bpy(DTTA)2(H2O)4]2− and the metallostar {Fe[Gd2bpy(DTTA)2(H2O)4]3}4− with regard to potential MRI contrast agent applications. A combination of pH potentiometry and 1H NMR spectroscopy has been used to determine protonation constants for the ligand [bpy(DTTA)2]8− and for the complexes [Fe{bpy(DTTA)2}3]22− and [Y2bpy(DTTA)2]2−. In addition, stability constants have been measured for the dinuclear chelates [M2bpy(DTTA)2]n formed with M = Gd3+ and Zn2+ (log KGdL = 18.2; log KZnL = 18.0; log KZnHL = 3.4). A multiple field, variable-temperature 17O NMR and proton relaxivity study on [Gd2bpy(DTTA)2(H2O)4]2− and {Fe[Gd2bpy(DTTA)2(H2O)4]3}4− yielded the parameters for water exchange and the rotational dynamics. The 17O chemical shifts are indicative of bishydration of the lanthanide ion. The exchange rates of the two inner-sphere water molecules are very similar in the dinuclear [Gd2bpy(DTTA)2(H2O)4]2− and in the metallostar (kex298 = 8.1±0.3×106 and 7.4±0.2×106 s−1, respectively), and are comparable to kex298 for similar GdIII poly(amino carboxylates). The rotational dynamics of the metallostar has been described by means of the Lipari–Szabo approach, which involves separating global and local motions. The difference between the local and global rotational correlation times, τlO298 = 190±15 ps and τgO298 = 930±50 ps, respectively, shows that the metallostar is not completely rigid. However, the relatively high value of S2 = 0.60±0.04, describing the restriction of the local motions with regard to the global one, points to a limited flexibility compared with previously reported macromolecules such as dendrimers. As a result of the two inner-sphere water molecules, with their near-optimal exchange rate, and the limited flexibility, the metallostar has a remarkable molar proton relaxivity, particularly at high magnetic fields (r1 = 33.2 and 16.4 mM−1 s−1 at 60 and 200 MHz, respectively, at 25 °C). It packs six efficiently relaxing GdIII ions into a small molecular space, which leads, to the best of our knowledge, to the highest relaxivity per molecular mass ever reported for a GdIII complex. The [bpy(DTTA)2]8− ligand is also a prime candidate as a terminal ligand for constructing larger sized, FeII (or RuII)-based metallostars or metallodendrimers loaded with GdIII on the surface.

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