title: A starburst-shaped heterometallic compound incorporating six densely packed gd(3+) ions.
abstract: The heterotritopic ligand [bpy(DTTA)2]8- has two diethylenediamine-tetraacetate units for selective lanthanide(III) coordination and one bipyridine function for selective Fe(II) 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 K(GdL) = 18.2; log K(ZnL) = 18.0; log K(ZnHL) = 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 (k(ex)298 = 8.1 +/- 0.3 x 10(6) and 7.4 +/- 0.2 x 10(6) s(-1), respectively), and are comparable to k(ex)298 for similar Gd(III) 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, tau(lO)298 = 190 +/- 15 ps and tau(gO)298 = 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 degrees C). It packs six efficiently relaxing Gd(III) 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 Gd(III) complex. The [bpy(DTTA)2]8- ligand is also a prime candidate as a terminal ligand for constructing larger sized, Fe(II) (or Ru(II))-based metallostars or metallodendrimers loaded with Gd(III) on the surface.
authors.affiliation: Laboratoire de Chimie Inorganique et Bioinorganique, Ecole Polytechnique Fédérale de Lausanne, EPFL-BCH, 1015 Lausanne, Switzerland.
authors.forename: João Bruno
authors.initials: JB
authors.lastname: Livramento
authors.forename: Angélique
authors.initials: A
authors.lastname: Sour
authors.forename: Alain
authors.initials: A
authors.lastname: Borel
authors.forename: André E
authors.initials: AE
authors.lastname: Merbach
authors.forename: Eva
authors.initials: E
authors.lastname: Tóth
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000737:chemistry*; D008024:Ligands; D008279:Magnetic Resonance Imaging; D015394:Molecular Structure; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D011522:Protons; D014867:Water / Q000737:chemistry
chemical_list: D003287:Contrast Media; D008024:Ligands; D011522:Protons; D014867:Water; C060068:diethylenetriaminetetraacetic acid; D004369:Pentetic Acid; D005682:Gadolinium; D007501:Iron