Liens transverses ENS de Lyon

Agenda de l'ENS de Lyon

KOLANOWSKI - Bispidine-iron (II) complexes as a novel platform for the design of magentogenic probes

Soutenance de thèse

Mercredi 30 oct 2013
14h00
Soutenance de M. Jacek-Lukasz KOLANOWSKI du Laboratoire de Chimie de Lyon sous la direction de M. Jens HASSERODT.

Intervenant(s)

Soutenance de M. Jacek-Lukasz KOLANOWSKI du Laboratoire de Chimie de Lyon sous la direction de M. Jens HASSERODT.

Description générale

Résumé : Multiple technological, environmental and biomedical applications depend on the detection of a chemical analyte in liquid samples using an activatable molecular probe. A magnetic detection of the activation of such probe may be performed by Magnetic Resonance Imaging and has multiple advantages over optical detection modes. Nevertheless, probes reporting on an analyte by changing their magnetic properties are virtually inexistent. Bispidine-iron(II) chelates seem particularly attractive for the design of such tools as they promise high stability even in competitive solvents such as water, and theoretically offer the possibility to create pairs of structural isomers that have a magnetic off-on relationship. So far however, only (para)-magnetic isomers have been reported.

In the course of this thesis, I have established robust synthetic protocols for the large-scale preparation of a variety of bispidine-based ligands and their iron(II) chelates which were thoroughly characterized in solution (1D/2D NMR, MS, UV/Vis, CV) and in the solid state (X-ray and SQUID). By judicious functionalisation of a novel synthetic intermediate, I succeeded in preparing for the first time multiple examples of low-spin, diamagnetic iron(II)-bispidine chelates and possess now a magnetic off-on system for the efficient design of responsive probes. Its high potential was demonstrated by the selective magnetic response to chemical stimuli (anions and pH). Relaxivity measurements of model MRI-silent and MRI-active chelates and in vivo experiments of the active form in mice bode well for the design of a truly activatabe probe for MRI. In order to study the in vivo behavior of such probes, I developed the first ever method for radiolabelling any iron(II) complex with Fe-59 isotope and validated it in biodistribution studies in mice.

Complément

Salle des Thèses - Site Monod - ENS Lyon