Radicaux stables de type trityle en tant qu’agents de contraste pour l’imagerie moléculaire par RPE : synthèse de dérivés fonctionnalisés, élaboration de conjugués peptidiques, et caractérisations physico-chimiques

Driesschaert, Benoît
(2013)

Files

Thèse_driesschaert.pdf
  • Open Access
  • Adobe PDF
  • 9.42 MB
Download

Details

Authors
  • Driesschaert, BenoîtUCLouvain
    author
Supervisors
Marchand-Brynaert, Jacqueline
 ;
Gallez, Bernard
Abstract
Biomedical electron paramagnetic resonance (EPR) spectroscopy and imaging (EPRI) are techniques allowing in vivo assessment of certain physiological parameters such as oxgen concentration, pH, tissues redox status, etc. By contrast with magnetic resonance imaging (MRI), widely used in clinics, which uses the nuclear spin of endogen water's protons, in vivo EPR spectroscopy and EPRI need the use of a spin label (a free radical). This multidisciplinary work focuses on the development of new spin labels, of type triarylmethyl (TAM) radical, for biomedical EPR applications. We developed a water soluble phosphonated TAM radical used to measure pH in vivo in a physiological range while fluorinated TAMs were synthetized to asset oxygen concentration with high sensitivity using biocompatible perfluorocarbon formuations. The static and dynamic stereochemistry of TAM alcohols, alkanes and radicals were also studied. Theses molecules adopt a propeller shape conformation allowing to atropoisomeric conformations to occur that feature enantiomeric relationship. Due to high steric hindrance, the enantiomerization between the two enantiomers is restricted, a phenomenon which is responsible for the chiral properties of TAM compounds. Finally, we synthesized tumor targeted spin labels by binding the TAM radical to targeting moieties such as a small peptide containing the Arg-Gly-Asp (RGD) sequence or a home made peptidomimetic of this sequence.
Affiliations

Citations

  • APA
  • Chicago
  • FWB

Driesschaert, B. (2013). Radicaux stables de type trityle en tant qu’agents de contraste pour l’imagerie moléculaire par RPE : synthèse de dérivés fonctionnalisés, élaboration de conjugués peptidiques, et caractérisations physico-chimiques. https://hdl.handle.net/2078.5/28203