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SCAN: Development of new tetraaza macrocyclic chelators: a search for more efficient lanthanide complexes

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Luís M. P. Lima, Coordination and Supramolecular Chemistry Lab

When 16 Jul, 2008 from
12:00 pm to 01:00 pm
Where Auditorium
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Tetraazamacrocycles with coordinating pendant arms are excellent ligands for transition metal and lanthanide ions, especially those derived from the well-known cyclam and cyclen skeletons. Metal complexes of this type have found applications mainly in the medical field, particularly as contrast agents for Magnetic Resonance Imaging (MRI) and as radiopharmaceuticals for diagnosis or therapy.

Radiopharmaceuticals are radiolabelled conjugates designed to deliver limited doses of radiation to specific disease sites by use of targeting biomolecules capable of binding to specific receptors that are overexpressed in certain regions or organs in the body. The moiety of the conjugate encapsulating the radiometal is a bifunctional chelator (BFC) that also presents a suitable chemical functionality for the covalent binding to the targeting moiety. The use of metallic radionuclides offers wide opportunities for designing new radiopharmaceuticals by modifying the coordination environment around the metal with different chelators. As metal chelates can significantly modify the uptake and biodistribution of radiopharmaceuticals, the design and selection of the BFC is crucial for the development of clinically useful diagnostic and therapeutic agents. The new drugs must have high radiochemical purity, high solution stability, and they must preserve their chemical and biological integrity before and after application. This requires a strong binding of the chelator to the radionuclide translated in very high thermodynamic stability and kinetic inertness.

The synthesis of macrocycles bearing pendant arms of mixed type is an important tool for developing ligands with improved chemical properties or suitable for use as bifunctional chelators. For some years we have focused on the development of such macrocyclic derivatives. Two new ligands have been recently synthesized, one based on cyclam and another one based on cyclen. Both ligands were studied on their acid-base properties by potentiometric and NMR spectroscopic techniques. The thermodynamic stability of the complexes of these chelators with significant transition metal and lanthanide ions were also determined from potentiometric experiments. Globally, these new ligands shows very high overall basicity and their metal complexes present also high stability, particularly in one case. The properties found will be discussed in comparison with those of some related chelators.


Short CV

October 2001 – Degree in Technological Chemistry by the Faculty of Sciences, University of Lisbon;

May 2002 to September 2004 – Graduate Research Student at ITQB, in the Coordination and Supramolecular Chemistry Laboratory;

Since October 2004 – Ph.D. Student at ITQB, in the Coordination and Supramolecular Chemistry Laboratory.


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