Partner und Internationale Organisationen
(Englisch)
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A, B, HR, CY, CZ, DK, FIN, F, D, GR, H, IRL, I, NL, N, PL, P, SK, SI, E, S, CH, GB
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Abstract
(Englisch)
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Our research within this project is focussed on structure and dynamics of Gd3+ and the iso-electronic Eu2+ ions and their poly(amino carboxylate) complexes in aqueous solutions. Gd3+ has its importance as main constituent in NMR relaxation enhancement agent for magnetic resonance imaging (MRI). ). Eu2+ shows the same favourable electronic properties but it is chemically similar to Ca2+ and Sr2+ and redox instable in aqueous solution. First XAFS measurements of the Eu2+ ion in aqueous solution confirmed that it is structurally similar to Sr2+ although not identical. While Sr2+ was found to be eight coordinated, Eu2+ has a coordination number of 7.2 which means that an equilibrium between seven and eight coordinated species is present in solution. First XAFS analysis on [ML(H2O)] where M=Eu2+, Sr2+ and L= dota and dtpa seem to show that solid state and solution structures of both ions are iso-structural but that Eu2+ complexes are different from the Sr2+ complexes.Classical molecular dynamics (MD) simulations of [Gd(L)(H2O)n]z- (n=1: L= dtpa, dtba-bma, dota; n=0: L=dotp, teta) in aqueous solution showed the existence of outer sphere binding of water molecules to the oxygen atoms of the poly(amino carboxylate) ligands. Water molecules not bound in the first co-ordination shell of the Gd3+ ion can therefore not be simply treated as particles diffusing freely on the surface of the complex. The theoretical calculation of NMR relaxation enhancement of water protons in presence of these Gd3+ complexes has therefore to take into account the molecules bound in the second shell. For the first time classical molecular dynamics simulations have been performed on a Gd3+ poly(amino carboxylate) complex without any artificial constraints on the first coordination sphere. Changes in the conformation of the complex (inversion of several dihedral angles) are observed independently from the dissociation of inner sphere water. Very fast changes of the third-order rotation axis direction of the coordination polyhedron could be related to the mechanism of electron spin relaxation of the complex. It was shown that the two protons of the inner sphere water molecule have different rotational correlation times, tR. Furthermore, the mean tR of the Gd-H vectors is 72% lower than tR of the Gd-O vector. This discrimination of tR has to be taken into account in future analysis of 17O and 1H NMR relaxation data.Electron spin relaxation of Gd3+ has now been measured as function of temperature and frequency (up to 225 GHz) for a variety of complexes used as MRI contrast agents. A theoretical treatment of electron spin relaxation including dynamic frequency shift led to the development of a first computer program which allows a simultaneous fitting of both, experimental EPR linewidths and chemical shifts measured on different gadolinium complexes (including the aqua ion) in aqueous solutions. In a second step the theory and the program were improved including the static zero-field splitting term and analysis with a simultaneous fitting of full EPR spectra as a function of temperature and resonance frequency. In a third step the theoretical treatment was pushed beyond the Redfield limit to allow treatment of very low magnetic field EPR data and of slowly tumbling complexes. In a last paper we have shown that the new theory for electron spin relaxation on Gd-complexes allows simultaneous fitting of EPR, 17O-NMR and 1H NMR results with physically meaningful parameters.
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