The water-exchange rate constants for the [Gd(DTPA)(H2O)]2- and [Gd(DOTA)(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 extreme dissociative activation mode for the water-exchange mechanism. The mechanism
(D) is further supported by the large activation enthalpies (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
these two monoaqua complexes there is only space for one water molecule, and thus
the bond breaking of the coordinated water should be the rate-determining step. The
O-17 relaxation contribution of the second coordination sphere was estimated by investigating
[Gd(TETA)]-, which has no water in the first coordination sphere. All these considerations
lead 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 relatively low water-exchange rates
but by T1m, the longitudinal relaxation time of water protons in the first coordination
sphere.
