Solid-state and solution properties of the lanthanide complexes of a new heptadentate tripodal ligand: a route to gadolinium complexes with an improved relaxation efficiency.
The tripodal ligand (alpha,alpha',alpha' 'nitrilotri(6-methyl-2-pyridinecarboxylic acid)) (H(3)tpaa) forms a Gd(III) complex which has a relaxivity (r(1p) = 13.3 mM(-1) s(-1) at 25 degrees C and at 60 MHz) remarkably higher than those of the currently clinically used contrast agents based on octacoordinate polyaminocarboxylate complexes (3.5-4.7 mM(-1) s(-1)) and a reasonably good thermodynamic stability. The crystal structure of the ligand and of its La, Nd, Eu, Gd, Tb, Ho, Tm, Yb, and Lu complexes have been determined by X-ray crystallography. The neutral H(3)tpaa molecule adopts, in the solid state, a preorganized tripodal conformation in which the three H(3)tpaa arms are located on the same side of the molecule, ready to bind a metal ion in a heptadentate coordination mode. The structures of the Ln(III) complexes vary along the series for their nuclearity and number of water molecules coordinated to the metal, and a tetrameric structure is observed for the La(3+) ion (9- and 10-coordinate metal centers), dimeric structures are formed from the Nd(3+) ion through the Yb(3+) ion (9-coordinate), and a monomeric structure results for Lu(3+) (8-coordinate). The relaxivity studies presented here suggest that the high relaxivity of the Gd(tpaa) complex is mainly the consequence of a shorter bound water proton-Gd(III) distance associated with a probable water coordination equilibrium between tris(aqua) and bis(aqua) complexes, giving raise to a mean number of coordinated water molecules q > 2. Both effects are strongly related to the ligand flexibility, which allows for a large volume available for water binding. The observed rapid water exchange rate is probably due to the presence of a low-energy barrier between 10-, 9-, and 8- coordinate geometries. Although the low solubility of the Gd complex of tpaa prevents its practical application as an MRI contrast agent, the straightforward introduction of substituents on the pyridine rings allows us to envisage ligands with a higher water solubility, containing functional groups leading to macromolecular systems with very high relaxivity.
Bretonnière
Y
Y
Laboratoire de Reconnaissance Ionique and Laboratoire de Chimie de Coordination, Service de Chimie Inorganique et Biologique (UMR 5046), Département de Recherche Fondamentale sur la Matière Condensée, CEA-Grenoble, 38054 Grenoble, Cedex 09, France.
Mazzanti
M
M
Pécaut
J
J
Dunand
F A
FA
Merbach
A E
AE