Synthesis of Original Resveratrol Derivatives By Mechanochemistry

The Institute Charles Gerhardt Montpellier (ICGM) is a multidisciplinary research laboratory with five departments and nearly 500 staff. The ICGM contributes to the development of research in chemistry with the aim of developing and characterizing complex functional materials with a strong societal impact, particularly in the fields of health, environment and energy.

The mastery of the entire chain of expertise in the development of complex materials positions the ICGM’s research activities favorably not only in the Montpellier landscape but also nationally and internationally.

The project “A chemistry of materials at the service of human and society” led by the entire Institute, is structured around five axes:

Molecular materials

Macromolecular materials

Porous and hybrid materials

Materials for energy

Theoretical physical chemistry

These five axes, in strong interaction with each other, make it possible to organize research around the different scales of time and space that it is necessary to master in order to design innovative complex functional materials for applications in the fields of health, environment and energy.

One of the cornerstones of all this research is the desire to understand and use the different types of intermolecular interactions to propose synthesis strategies highlighting cooperative processes and synergies between different functional patterns.

Project description

Although efficient to fight phytopathogenic fungi, conventional fungicides are increasingly restricted due to environmental concerns.¹ Polyphenols, and resveratrol derivatives in particular,² emerge as promising antifungal alternatives. Given their natural origin, low-toxicity and biodegradability, they are at the center of new ecoconception strategies. Yet their development is limited by poor water solubility, autoaggregation and limited bioavailability. To address these challenges, we propose the green synthesis of biomimetic resveratrol derivatives containing an original and ionizable functional group, by using mechanochemistry. Mechanochemical reactions, that are induced by mechanical forces,³ are typically run by using ball-mills, which will be used throughout this project. Of note, mechanochemistry has been widely recognized for its ability to improve yields, shorten reaction times, and reduce solvent usage and energy consumption for a wide range of organic reactions.⁴ To synthesize this resveratrol derivatives, two retrosynthetic disconnections will be studied (see figure below), which builds upon previously published syntheses of resveratrol derivatives in solution.⁵

The introduction of the original ionizable functional group is expected to enhance the water solubility of the derivatives, thereby improving their bioavailability. Interestingly, some of such resveratrol derivatives already exist in nature. Thus, designing novel fungicides by targeting such derivatives offers a bioinspired approach. Once obtained, the water solubility and the antifungal activity of these original resveratrol derivatives will be evaluated by our collaborators at INRAE.

In this project, the successful candidate will perform the experiments to target the final molecules, by using ball-mills. He/She will perform the synthetic steps, from reaction setup to purification, and will fully characterise the products (MS, ¹H and ¹³C NMR). He/She will present his/her results in technical meetings and group seminars as needed. Full training and support will be provided by the supervisors throughout the project.

Research environment

This M2 project will be carried out in the new Pôle Chimie Balard building on the CNRS campus, within the ICGM institute and the MISOTOP team in Montpellier, France. The successful candidate will thus benefit from a high-quality scientific environment in which to carry out his/her project. Indeed, the MISOTOP team has an internationally reknown expertise in mechanochemistry, and is equipped with 7 ball-mills and a dedicated platform for operando analyses. On a daily basis, the recruited student will work under the supervision of Dr Thomas-Xavier Métro (CNRS researcher) and Marco Darseno (PhD student). He/she will also have the opportunity to interact with many researchers, engineers, and students, including with the group of Prof. H. Fulcrand at INRAE Montpellier.

References

(1) Environ. Pollut. 2024, 348, 123836, https://doi.org/10.1016/j.envpol.2024.123836.

(2) https://cordis.europa.eu/project/id/815904/reporting.

(3) https://goldbook.iupac.org/terms/view/MT07141.

(4) ChemSusChem 2021, 14, 2145-2162, https://doi.org/10.1002/cssc.202100478.

(5) Mini-Rev. Org. Chem. 2020, 17, 546-558, https://doi.org/10.2174/1570193x16666190617155558.

The ideal profile is a student interested in organic and green synthesis with competences in synthetic and analytical chemistry and molecule characterisation (mass spectrometry, 1H & 13C NMR).