FULL PAPER Experimental Evidence for a Second Coordination Sphere Water Molecule in the Hydration Structure of YbDTPA – Insights for a Re-Assessment of the Relaxivity Data of GdDTPA Kenneth Irvin Hardcastle,* [a] Mauro Botta,* [b] Mauro Fasano, [c] and Giuseppe Digilio [d] Keywords: Lanthanides / Ytterbium / MRI contrast agents / Solid-state structures / Hydration The low temperature (–100 °C) X-ray structure of the com- plex K 2 [Yb(DTPA)(H 2 O)] has been determined. The metal ion is at the center of a tricapped trigonal prism and is nine- coordinate, binding to the three nitrogens and five oxygens of the ligand and one water molecule. From the structure ob- tained, three well-defined hydration shells can be observed consisting of: i) one coordinated water molecule; ii) several water molecules in the outer coordination sphere of the Yb III Introduction The use of paramagnetic metal complexes to alter the nuclear magnetic relaxation times of water protons in tis- sues is a well established procedure in clinical diagnosis for enhancing the contrast between healthy and diseased re- gions in MRI (Magnetic Resonance Imaging) images. [1] Currently, about 35% of the MRI examinations are per- formed with the use of contrast enhancing agents (CA). The most common class of these compounds are neutral or negatively charged polyaminocarboxylate complexes of Gd III , both linear and macrocyclic, which are extracellular, nonspecific CA which rapidly diffuse throughout the body after injection and are excreted via the renal route. [2–4] The first of these complexes to be considered as a CA and to be tested on humans was [Gd(DTPA)(H 2 O)] 2– (DTPA 5– = diethylenetriamine-N,N',N''-pentaacetate). [5] Much is known about this compound; the ligand is octadentate and fully exploits its chelating ability towards lanthanide(III) ions to form thermodynamically stable tricapped trigonal structures where one of the capping positions is occupied by a water molecule. In solution the complexes are stereo- [a] Department of Chemistry, California State University Northridge, 18111 Nordhoff Street, Northridge, CA 91330–8262 (USA) Fax: (internat.) +1–818–677–2912 E-mail: ken.hardcastle@csun.edu [b] Dipartimento di Scienze e Tecnologie Avanzate, Universita‘ del Piemonte Orientale ‘‘Amedeo Avogadro’’, Corso Borsalino 54, 15400 Alessandria (Italy) Fax: (internat.) +39–011–670–7524 E-mail: botta@ch.unito.it [c] Dipartimento di Chimica I.F.M., Universita‘ di Torino, Via P. Giuria 7, 10125 Torino (Italy) [d] Bioindustry Park del Canavese, Via Ribes 5, Colleretto Giacosa (TO) Eur. J. Inorg. Chem. 2000, 971-977  WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000 1434-1948/00/0505-0971 $ 17.50+.50/0 971 ion and iii) one water molecule surprisingly close to the metal center and hydrogen-bonded to proximate carboxylate groups. A variable-field and temperature NMRD study of the corresponding Gd complex has been performed and the data interpreted by taking into account the presence of second- sphere water molecule(s). The results of the analysis are in excellent agreement with the X-ray structural data. chemically non-rigid and the fluxional process involves con- formational inversion of the ethylenediamine rings and ro- tation of the acetate arms which corresponds to the in- terconversion between two enantiomeric forms; [6,7] isostructurality across the lanthanide series has been sug- gested by the analysis of NMR data. [8] The coordination sphere of the Gd III complex is completed by a water molec- ule that has a mean residence lifetime of about 300 ns at 298 K, as assessed by Merbach et al. by 17 O NMR. [9] It is common practice to evaluate the efficacy of a given Gd complex as a CA in terms of the relaxivity parameter, r 1p (m –1 s –1 ), the net increment in the water proton longitud- inal relaxation rate per millimolar concentration of the paramagnetic compound. [1,2] The relaxivity reflects the effi- ciency of the nuclear-electron dipolar coupling between the nuclear magnetic moment of the water protons and the elec- tronic magnetic moment of the metal ion and is tradition- ally described on the basis of a model that considers two distinct contributions: inner sphere , related to the exchange of the bound water molecule(s) from the coordination site to the bulk, and outer sphere , which involves the water mo- lecules diffusing near the paramagnetic center during their translational diffusion. [10] The relaxivity has a strong de- pendence upon the applied magnetic field strength and from the analysis of this dependence (NMRD, Nuclear Magnetic Relaxation Dispersion profiles) several important structural and dynamic parameters may be obtained. [11] However, the polar nature of these complexes, featuring negative charges localized on the carboxylate groups, has recently suggested the presence of structured, hydrogen- bonded water molecules in the second coordination sphere of Gd III and thus a possible inadequacy in the physical model used for the interpretation of the relaxation data and the analysis of the NMRD profiles. [1,12–14] The contribution