Correlation of Water Exchange Rate with Isomeric Composition in

Diastereoisomeric Gadolinium Complexes of Tetra(carboxyethyl)dota

and Related Macrocyclic Ligands
Mark Woods ,† Silvio Aime ,‡ Mauro Botta ,§ Judith A. K. Howard ,† Janet M. Moloney ,† Michel
Navet ,‖ David Parker ,*‖ Marc Port , and Olivier Rousseaux ‖
Contribution from the Department of Chemistry, University of Durham, South Road, Durham, DH1 3LE, U.K.,
the Dipartimento di Chimica I.F.M., Universita di Torino, via P. Giuria 7, 10125 Torino, Italy, Dipartimento di
Scienze e Tecnologie Avanzate, Universita del Piemonte Orientale “Amedeo Avogadro”, Corso Borsalino 54,
10131 Alessandria, and Guerbet s.a., Aulnay-sous-Bois, 95943 Roissy-Charles de Gaulle, France
J. Am. Chem. Soc., 2000, 122 (40), pp 9781–9792
DOI: 10.1021/ja994492v
Publication Date (Web): September 21, 2000
Copyright © 2000 American Chemical Society

Abstract
The solution structure and dynamics of metal-bound water exchange have been studied in a
series of diastereoisomeric gadolinium complexes of tetra(carboxyethyl) derivatives of 1,4,7,10-
tetraazacyclodecane. The structures of the (RRRS), (RSRS), and (RRSS) ligands and the Eu, Gd,
and Tb complexes of the (RRRR) isomer have been determined by X-ray crystallography.
Luminescence measurements on the Eu and Tb complexes revealed an integral hydration state
(q = 1) in each case for the Eu isomers, whereas nonintegral values were measured for the
(RRRR) and (RRRS) Tb isomers (e.g., [(RRRR)-Tb·1]-, q = 0.60). The ratio of the twisted and
regular monocapped square antiprismatic isomers has been measured in solution by 1H NMR for
the Eu and Tb complexes and followed the order, (RRRR) > (RRRS) > (RSRS) > (RRSS). Water
exchange rates in the gadolinium complexe have been determined by 17O NMR and were fastest
for the (RRRR) isomer [τm = 68 ns (298 K)] and correlated very well with the proportion of the
twisted square anti-prismatic isomer. The rate of water exchange in the (RRRR) Gd complexes is
likely to be sufficiently fast so as not to limit the overall relaxivity in higher MW conjugates.