Thesis Title: New gadolinium complexes for the development of high efficiency MRI contrast agents

Lanthanide chemistry attracts an increasing number of studies due to the numerous applications of lanthanide complexes in medical diagnostics, in material science and in catalysis. The unique electronic properties of lanthanide ions (long-lived luminescence and sharp emission spectra) make them particularly suitable for the development of luminescent probes in time-resolved high-throughput assays and fluorescence imaging because of their ability to discriminate between the background fluorescence and the target signal. The favourable magnetic and electronic properties of gadolinium have led to the application of gadolinium complexes in magnetic resonance medical imaging to improve contrast. The efficiency of these complexes, also called contrast agents, is measured by their relaxivity.The subject of this thesis aims to develop new high relaxivity contrast agents containing two or three water molecules coordinated to the metal which results in an important increase of the relaxivity. The fonctionalisation of different macromolecular biological molecules will also be studied. In particular we will investigate through independent experimental studies the molecular dynamic and structural parameters determining the relaxivity. A better understanding of the molecular factors influencing the relaxivity is necessary for a more efficient design of high relaxivity contrast agents. This multidisciplinary thesis will involve organic and inorganic synthesis, physicochemical studies and theoretical interpretation of the relaxivity. A part of the project will also be dedicated to the synthesis of bimodal probes presenting both high relaxivity and intense fluorescence.

References :

Y. Bretonniere, M. Mazzanti, J. Pecaut, F.Dunand, A. Merbach, "Solid-State and Solution Properties of The Lanthanide Complexes of a New Heptadentate Tripodal Ligand: A Route to Gadolinium Complexes with an Improved Relaxation Efficiency" Inorg. Chem. 2001, 40, 6737-6745.

Nicholas Chatterton, Christelle Gateau, Marinella Mazzanti, Jacques Pécaut, Alain Borel, Lothar Helm, André Merbach “The effect of pyridinecarboxylate chelating groups on the stability and electronic relaxation of gadolinium complexes” Dalton Trans. 2005, 1129-1135.

Nicholas Chatterton, Yann Bretonnière, Marinella Mazzanti, Jacques Pécaut “An Efficient Design for the Rigid Assembly of Four Bidentate Chromophores in Water Stable Highly Luminescent Lanthanide Complexes” Angew. Chem., Intl. Ed. Engl., 2005, 44, 7595-7598.

Aline Nonat, Christelle Gateau, Pascal H. Fries and Marinella Mazzanti, “Lanthanide Complexes of a Picolinate Ligand Derived from 1,4,7-Triazacyclononane with Potential Application in Magnetic Resonance Imaging and Time-Resolved Luminescence Imaging“ Chem. Eur. J., 2006, 12, 7133-7150.

Aline Nonat, Pascal H. Fries, Jacques Pécaut and Marinella Mazzanti, “Structure, Stability, Dynamics, High-Field Relaxivity, and Ternary Complex Formation of a New Triaquo Gadolinium Complex“ Chem. Eur. J., 2007, 13, 8489-8506.

Web: http://www-drfmc.cea.fr/Pisp/51/marinella.mazzanti

Potential candidates should send a CV and a recommendation letter by E-mail to Marinella Mazzanti before end february 2008. The chosen candidate will be submitted to evaluation after formal application for a CEA fellowship (one of the most prestigious French research Institutions) and will receive a formal offer in July 2008.

Email: The thesis lasts exactly three years with an approximate salary of 1600 euros.