Jean-Claude Bunzli - Towards binuclear polyaminocarboxylate MRI contrast agents? Spectroscopic and MD study of the peculiar aqueous behavior of the Ln(III) chelates of OHEC (Ln = Eu, Gd, and Tb): Implications for relaxivity

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      Nicolle,G.M., Yerly,F., Imbert,D., Bottger,U., Bunzli,J.C.,   Merbach,A.E. Chemistry-A European Journal  2003 9 (22) 5453-5467

      Abstract: We report the study of binuclear   Ln(III) chelates of OHEC (OHEC =   octaazacyclohexacosane-1,4,7,10,14,17,20,23-octaacetate). The   interconversion between two isomeric forms, which occurs in   aqueous solution, has been studied by NMR, UV/Vis, EPR, and   luminescence spectroscopy, as well as by classical molecular   dynamics (MD) simulations. For the first time we have   characterized an isomerization equilibrium for a Ln(III),   polyaminocarboxylate complex (Ln(III) = Y, Eu, Gd and Tb) in   which the metal centre changes its coordination number from nine   to eight, such that: [Ln(2)(ohec)(H2O)(2)](2-) reversible arrow   [Ln(2)(ohec)](2-) +2H(2)O. The variable temperature and pressure   NMR measurements conducted on this isomerization reaction give   the following thermodynamic parameters for Eu-III: K-298 = 0.42   +/- 0.01, DeltaH(0)=+4.0+/-0.2 kJ mol(-1), DeltaS(0) = +6.1+/-0.5   JK(-1)mol(-1) and DeltaV(0)=+3.2+/-0.2 cm 3 mol(-1). The   isomerization is slow and the corresponding kinetic parameters   obtained by NMR spectroscopy are: k(is)(298) = 73.0+/-0.5s(-1),   DeltaH(is)(double dagger) = 75.3+/-1.9 kJ mol(-1),   DeltaS(is)(double dagger) = +43.1+/-5.8 is JK(-1)mol(-1) and   DeltaV(is)(double dagger) = +7.9+/-0.7 cm(3) mol(-1). Variable   temperature and pressure 17 0 NMR studies have shown that water   exchange in [Gd-2(ohec)(H2O)(2)](2-) is slow, k(ex)(298) = (0.40   +/- 0.02) x 10(6) s(-1), and that it proceeds through a   dissociative interchange I, mechanism, DeltaV(double dagger) =   +7.3+/-0.3 cm(3) mol(-1). The anisotropy of this oblong binuclear   complex has been highlighted by MD simulation calculations of   different rotational correlation times. The rotational   correlation time directed on the Gd-Gd axis is 24 % longer than   those based on the axes orthogonal to the Gd-Gd axis. The   relaxivity of this binuclear complex has been found to be low,   since 1) only [Gd-2(ohec)(H2O)(2)](2-), which constitutes 70% of   the binuclear complex, contributes to the inner-sphere relaxivity   and 2) the anisotropy of the complex prevents water molecules   from having complete access to both Gd-III cages; this decreases   the outer-sphere relaxivity. Moreover, EPR measurements for the   Gd-III and for the mixed Gd-III/Y-III binuclear complexes have   clearly shown that the two Gd-III centres interact   intramolecularly; this enhances the electronic relaxation of the   Gd-III electron spins

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