Blanc SIMI 7 - Blanc - SIMI 7 - Chimie moléculaire, organique, de coordination, catalyse et chimie biologique

Cationic Boranes and boronic compounds: New tools for fluorination and radiofluorination – BoBo

Boron and fluoride: the perfect partners

Boron and fluorides are easily forming strong bonds, although the latter can be smoothly broken in water. This project aims at making this bond more stable these bonds in a range of media, including biological ones. Yet we are willing to maintain the ability to release the fluoride at will in order to perform fluorination and radiofluorination.

Fluorine : From API to imaging

Fluorine is found in a range of API and is also used as a probe in medical imaging, especially as its radioactive isotope. <br />A wide array of methods of fluorination has been developed recently. Yet their mass efficiency is usually low. Moreover these fluorination agents are scarcely recyclable. Our project aims at developing “low cost” new fluorination agents which can moreover be easily regenerated. <br />

The target compounds are synthesized using the classical reactions of organic chemistry and by taking advantage of the various transition metal catalysed reactions, which are all combined with the rich and specific chemistry of main group elements. As various synthetic strategies are designed for each target, the success rate is expected to be high.

The first boron containing coumpounds bearing a cationic moiety for the stabilisation of the B–F bond have been obtained. The stability of the boron-fluoride adducts will be investigated in a very near future.

The synthetic methods explored so far on one kind of molecular template will now be applied to a range of substrates in order to systematically investigate the structure/stability relationship.
The introduction of fluorine of biomolecules of interest for diagnostic purposes will soon start.

A publication has recently been accepted. It reviews the most recent results achieved in the fight against Alzheimer’s disease in terms of diagnostic and therapeutic options.

Cationic boranes have proved to be excellent anion sensors capable of forming highly stable adducts with fluoride in water and even transfer the fluoride from an aqueous phase to an organic phase. Based on preliminary results from our consortium which have established that their use for fluorination purposes is a reality, our proposal aims at developping recyclable moieties in order to perform nucleophilic fluorations starting from cheap aqueous fluoride solutions. The method will be extended to radiofluorations processes as they are expected to avoid time consuming drying sequences. This would clearly significantly ease the production of radiolabelled molecules for Positron Emission Tomography (PET).
Another interesting feature is the ability of cationic boronic compounds to form trifluoroborate zwitterions in the presence of fluorides stable in buffered solutions at physiological pH. We will perform the functionnalization of the boronate (making them cationic) in order to allow their conjugation to biomolecules. The obtained compounds will also be used in order to radiolabel biomolecules such as peptides and oligonucleotides. This is expected to ease the exploitation of the exceptionnal biological properties of the latter in medical imaging. We will pay a particular attention to the specific activity issue.

Project coordinator

Monsieur Emmanuel GRAS (Laboratoire de Chimie de Coordination) – emmanuel.gras@lcc-toulouse.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LSPMIB - Université Paul Sabatier Toulou Laboratoire de Synthèse et Physico-Chimie des Molécules d'Intérêt Biologique
ISTCT - Université de Basse Normandie/CE Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales
LCC - CNRS Laboratoire de Chimie de Coordination

Help of the ANR 348,994 euros
Beginning and duration of the scientific project: October 2012 - 36 Months

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