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Development of a proton-electron double-resonance imaging - pedri - instrumentfor radio frequency imaging of free radicals in whole rats and comparison with fourier-transform electron-paramagnetic-resonance - ft-epr - imaging

Objective



Research objectives and content
A. Learning the principle of combinatorial synthesis (2 months) A1 & A2. Design, Methods & Techniques of combinatorial synthesis. A3 & A4. Combinatorial synthesis in solution vs solid phase A5. Automation & data-processing.
B. Planning a combinatorial synthesis (solid Phase Chemistry) (6 months): .
B1. Adaptation and optimization of new reaction sequence(s) -including reaction(s) not yet described on solid supports-enable subsequently the preparation, in an automated way, of original compound libraries in a format suitable for wide testing (7/8 months): - Choose the reaction sequence(s) allowing the preparation of the target molecules using individual and structurally diverse sets of building blocks. - Define the rection conditions for both the individual reactions and the whole sequence(s) amenable to automation.
B2. Selection of a set of representative molecules (diversity measurements, computational approaches involving virtual library(ies), molecular modeling...) in order to maximize the range of application (using commercially available or in-house data-processing softwares) and to identify suitable reaction conditions for a successfull library(ies) synthesis (2/3 months): - Identify a particular set of diverse and sensible building blocks using data-processing softwares in order to get a fine balance it the universe of diversity, shape, functional groups distribution and electro-static surfaces. - Define scope and limitations of each individual step of the seuence(s) for a successful library(ies) synthesis.
B3. Designing and developing new type(s) of linker(s) most suitable for the reaction sequence(s) previously adapted and optimized on solid supports (6 months).
At no time I will be involved in a production team.
Training content (objective, benefit and expected impact)
A. To participate to an applied research project in a broad, well-integrated, interdisciplinary approach to drug discovery in which chemistry, engineering, biochemistry, molecular biology & screening technology, data-processing expertise must all be coordinated for the best results.
B. To increase my knowledge in organic chemistry, biochemistry, analytical methods on solid supports (FT-IR microspectroscopy / gel-Phase & MAS NMR spectroscopy / ES-MS, TOF-MALDI-MS, TOF-SIMS).
C. To learn principle of combinatorial synthesis and methods & techniques of solid phase organic chemistry.
D. To use commercially available or in-house data-processing softwares for designing libraries and processing, monitoring, interpreting thus generated chemical & biological data.
E. One or two full-paper(s) published in good scientific level review(s) and valuable for the whole scientific community.
Links with industry / industrial relevance (22)
I will be hosted in an interdisciplinary industrial research center (CRLD-Rhone-Poulenc Agro) with a high scientific level, directly involved in developing new technologies.

Funding Scheme

RGI - Research grants (individual fellowships)

Coordinator

Rhône-Poulenc Agrochimie SA
Address
14-20,Rue Pierre Baizet
69263 Lyon
France

Participants (1)

Not available
Italy