O-17 NMR-STUDY OF WATER EXCHANGE ON [GD(DTPA)(H2O)]2- AND [GD(DOTA)(H2O)]- RELATED TO NMR IMAGING

The water-exchange rate constants for the [Gd(DTPA)(H2O)]2- and [Gd(DO TA)(H2O)]-complexes as determined by variable-temperature O-17 NMR are respectively k(ex)298 = (4.1 +/- 0.3) X 10(6) and (4.8 +/- 0.4) X 10( 6) s-1. The activation volumes (DELTAV(double dagger)), measured up to 200 MPa, are 12.5 +/- 0.2 and 10.5 +/- 0.2 cm3 mol-1, indicating an e xtreme dissociative activation mode for the water-exchange mechanism. The mechanism (D) is further supported by the large activation enthalp ies (DELTAH(double dagger) = +52.0 +/- 1.4 and +48.8 +/- 1.6 kJ mol-1) and positive entropies (DELTAS(double dagger) = +56.2 +/- 5 and +46.6 +/- 6 kJ mol-1 K-1) obtained for the [Gd(DTPA)(H2O)]2- and [Gd(DOTA)( H2O)]- complexes, respectively. In the first coordination sphere of th ese two monoaqua complexes there is only space for one water molecule, and thus the bond breaking of the coordinated water should be the rat e-determining step. The O-17 relaxation contribution of the second coo rdination sphere was estimated by investigating [Gd(TETA)]-, which has no water in the first coordination sphere. All these considerations l ead to the conclusion that the effectiveness of [Gd(DTPA)(H2O)]2- and [Gd(DOTA)(H2O)]- as contrast agents in MRI is not limited by the relat ively low water-exchange rates but by T1m, the longitudinal relaxation time of water protons in the first coordination sphere.