Coordination equilibrium— a clue for fast water exchange on potential magnetic resonance imaging contrast agents?

Abstract

A temperature-dependent UV–visible spectrophotometric study on [Eu(DO3A)(H2O)n] proved the presence of a hydration equilibrium (n = 1, 2), strongly shifted towards the bisaqua species [DO3A = 1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane]. The thermodynamic parameters and the reaction volume were determined for the equilibrium [Eu(DO3A)(H2O)] + H2O ⇌ [Eu(DO3A)(H2O2)] and the same results were extra-polated for the Gd(III) analogue (ΔH° = −12.6 kJ mol−1, ΔS° = −25.2 J mol−1 K−1, KEu298 = 7.7 and ΔV° = −7.5 cm3 mol−1). The variable-temperature 17O NMR data on [Gd(DO3A)(H2O)n] were analysed by two approaches: (i) with the Swift–Connick equations (two-site exchange) and (ii) with the Kubo–Sack formalism (three-site exchange). The comparison of the results obtained by the two different analyses show that, despite the crude approximation of treating the system as a two-site exchange problem, the Swift–Connick method gives a correct value for the water exchange rate. Based on previous observations on the relationship between inner sphere structure and water exchange rate, one can expect higher rates for complexes with a hydration equilibrium. Indeed, the water exchange on [Gd(DO3A)(H2O)n] is about twice as fast as on [Gd(DOTA)(H2O)]− (kex298 = 11 × 106 and 4.8 × 106 s−1, respectively), although it is still much slower than that on [Gd(H2O)8]3+ (kex298 = 804 × 106 s−1). The limited gain in the water exchange rate is explained in terms of a rigid inner sphere structure introduced by the macrocyclic ligand which makes difficult the transition from the reactant to the transition state, and consequently, results in a slower exchange as compared to the Gd3+ aqua ion. The activation parameters of the water exchange are and , and the mechanism is proposed to be dissociatively activated. Copyright © 1999 John Wiley & Sons, Ltd.