Novel macrocyclic EuII complexes: fast water exchange related to an extreme metal-coordinated water oxygen distance

International audienceEuII complexes are potential candidates for pO2-responsive contrast agents in magnetic resonance imaging. In this regard, we have characterized two novel macrocyclic EuII chelates, [EuII(DOTA)(H2O)]2− and [EuII(TETA)]2− (H4DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, H4TETA=1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid) in terms of redox and thermodynamic complex stability, proton relaxivity, water exchange, rotation and electron spin relaxation. Additionally, solid-state structures were determined for the SrII analogues. They revealed no inner-sphere water in the TETA and one inner-sphere water molecule in the DOTA complex. This hydration pattern is retained in solution, as the 17O chemical shifts and 1H relaxation rates proved for the corresponding EuII compounds. The thermodynamic complex stability, determined from the formal redox potential and by pH potentiometry, of [EuII(DOTA)(H2O)]2− (lg KEu(II)=16.75) is the highest among all known EuII complexes, whereas the redox stabilities of both [EuII(DOTA)(H2O)]2− and [EuII(TETA)]2− are inferior to that of 18-membered macrocyclic EuII chelates. Variable-temperature 17O NMR, NMRD and EPR studies yielded the rates of water exchange, rotation and electron spin relaxation. Water exchange on [EuII(DOTA)(H2O)]2− is remarkably fast (k=2.5×109 s−1). The near zero activation volume (ΔV≠=+0.1±1.0 cm3 mol−1), determined by variable-pressure 17O NMR spectroscopy, points to an interchange mechanism. The fast water exchange can be related to the low charge density on EuII, to an unexpectedly long MOwater distance (2.85 Å) and to the consequent interchange mechanism. Electron spin relaxation is considerably slower on [EuII(DOTA)(H2O)]2− than on the linear [EuII(DTPA)(H2O)]3− (H5DTPA=diethylenetriaminepentaacetic acid), and this difference is responsible for its 25 % higher proton relaxivity (r1=4.32 mM−1 s−1 for [EuII(DOTA)(H2O)]2− versus 3.49 mM−1 s−1 for [EuII(DTPA)(H2O)]3−; 20 MHz, 298 K)