(M/F) Ph.D. in organic synthesis and photophysics as part of the ANR project WEAPONS

Job Description

Thesis Subject

As part of the collaborative ANR project WEAPONS ("Wittig Reactions for Aptamer-based Molecular Sensing") between our team and the ChemBioNAC team (IBMM, UMR CNRS 5247, Montpellier), we are offering a Ph.D. research topic aimed at developing a new molecular approach for applications in fluorogenic biosensing. This thesis will be supervised and directed by Prof. Anthony ROMIEU.

ANR WEAPONS project and research topic: in the field of molecular detection, fluorescent probes whose activation relies on irreversible covalent chemical processes are in high demand. In particular, those based on the principle of covalent assembly allow for maximizing the intensity of the "OFF-ON" fluorogenic response and thus drastically lowering the detection limit of the target analyte[1]. This groundbreaking approach is based on the use of "caged" molecular precursors, which are converted in situ into fluorescent cores via domino reactions, effective in aqueous media and triggered by the analyte. It has already been implemented for the in vitro detection of various substances, but only with fluorophores emitting below 550 nm[1b, 2]. To facilitate analyses in complex biological environments, there is a need to extend this concept to fluorophores emitting beyond the green-yellow region of the visible spectrum. Thus, (bio)organic chemists have a role to play in developing new reactions that function in these aqueous matrices. The goal of the WEAPONS project is to apply the concept of covalent assembly to the in situ formation of dyes from the cyanine family[3]. The originality of the proposed approach lies in the development of a biocompatible Wittig reaction between two "half-cyanine" precursors, functionalized respectively with a stabilized phosphorus ylide and an aldehyde masked by an enzyme-labile protecting group. It will thus be possible to trigger this reaction by adding the appropriate enzyme and to carry out the in situ synthesis of the dye's polymethine chain; this will constitute the main objective of the thesis. In parallel, our partner at IBMM, a specialist in nucleic acid chemistry, will incorporate these two entities at the ends of oligonucleotide sequences (synthetic DNA fragments) to achieve the covalent assembly of a cyanine on a nucleic acid matrix via a "DNA-templated synthesis" (DTS) strategy[4]. Once these validations have been completed, we plan to extend this approach to aptamers targeting analytes of interest, particularly illicit drugs, in order to demonstrate the application potential of this new detection method.

References:
[1] Pour deux revues sur le sujet des sondes fluorescentes de type "covalent-assembly", voir : (a) X. Luo, L. Gu, X. Qian, Y. Yang, Chem. Commun. 2020, 56, 9067-9078 ; (b) X. Chen, Z. Huang, L. Huang, Q. Shen, N.-D. Yang, C. Pu, J. Shao, L. Li, C. Yu, W. Huang, RSC Adv. 2022, 12, 1393-1415.
[2] Pour nos réalisations dans le domaine de l'assemblage covalent, voir : (a) S. Debieu, A. Romieu, Org. Biomol. Chem. 2015, 13, 10348-10361 ; (b) S. Debieu, A. Romieu, Org. Biomol. Chem. 2017, 15, 2575-2584 ; (c) S. Debieu, A. Romieu, Tetrahedron Lett. 2018, 59, 1940-1944 ; (d) K. Renault, S. Debieu, J.-A. Richard, A. Romieu, Org. Biomol. Chem. 2019, 17, 8918-8932 ; (e) G. Dejouy, K. Renault, Q. Bonnin, A. Chevalier, C. Michaudet, M. Picquet, I. E. Valverde, A. Romieu, Org. Lett. 2020, 22, 6494-6499 ; (f) S. Jenni, K. Renault, G. Dejouy, S. Debieu, M. Laly, A. Romieu, ChemPhotoChem 2022, 6, e202100268 ; (g) K. Renault, Y. Capello, S. Yao, S. Halila, A. Romieu, Chem. Asian J. 2023, 18, e202300258 ; (h) V. Gaumerd, K. Renault, P.-Y. Renard, A. Romieu, ChemPhotoChem 2024, 8, e202300324 ; (i) V. Gaumerd, Y. Capello, M. Lebrun, M. Chalot, P.-Y. Renard, A. Romieu, Talanta 2026, 298, 128938.
[3] Pour une revue sur les colorants cyanine, voir : W. Sun, S. Guo, C. Hu, J. Fan, X. Peng, Chem. Rev. 2016, 116, 7768-7817.
[4] Pour une revue sur le concept DTS, voir : X. Li, D. R. Liu, Angew. Chem. Int. Ed. 2004, 43, 4848-4870.

Qualifications and skills: a strong interest in (bio)organic chemistry, preferably with theoretical knowledge and practical skills in photophysics (fluorescence spectroscopy); interested in both organic synthesis and bioanalytical chemistry, particularly chromatographic techniques (analytical and semi-preparative RP-HPLC) and photophysical methods. Great deal of precision and attention in practical work (very small-scale syntheses), strong organizational skills, as well as good writing skills (French-English) and ability to achieve effective bibliographic watch are required. Initial experience in the chemistry of organic fluorophores and/or molecular fluorescent probes is not essential but would be a further asset.

Your Work Environment

The thesis will be conducted within the "Bioactive Molecules" team at the ICN laboratory (Institut de Chimie de Nice, UMR CNRS 7272, https://icn.univ-cotedazur.fr), located on the Valrose campus of the Université Côte d'Azur (UniCA, Nice site), under the supervision of Prof. Anthony ROMIEU. The successful candidate will conduct their research in a laboratory dedicated to organic synthesis and an analytical laboratory that currently houses 1 analytical HPLC system, 1 semi-preparative HPLC system, 2 UV-visible absorption spectrophotometers, 1 spectrofluorometer, and 1 circular dichroism spectrometer. NMR and ESI mass spectrometry analyses will be performed at the ICN Chemistry Technology Platform (PFTC, https://icn.univ-cotedazur.fr/plateforme-technologique).

Constraints and risks

Short-term visits to the project partner laboratory (IBMM, Montpellier) may be considered.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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