Soutenance publique de thèse de doctorat en Sciences chimiques - Lou D'haese

Raman Optical Activity Signatures of Flexible Systems – Main Focus on Cryptophane Derivatives

Jury

• Prof. Francesca CECCHET (UNamur), Présidente
• Prof. Vincent LIÉGEOIS (UNamur), Secrétaire
• Prof. Benoît CHAMPAGNE (UNamur)
• Prof. Carine CLAVAGUÉRA (Université Paris-Saclay)
• Dr Nicolas DAUGEY (Université de Bordeaux)

Résumé

In this work, I aimed at simulating accurately the Raman optical activity (ROA) signatures of flexible solute molecules in their environment. Indeed, these systems are quite challenging due to potentially huge number of conformers, i.e. local minimum on the potential energy surface (PES). Moreover, the environment can drastically change the PES which can be observed on the experimental ROA spectra that vary quite a lot with the conformation of the molecule and its surroundings. In order to tackle this issue, we have designed a hierarchy of methodology named M1, M2, M3. In M1 and M2, the so-called static approach is used: one or more conformers are found, their geometry are reoptimized at the Density Functional Theory (DFT) level, and their vibrational signatures are simulated, usually at the harmonic approximation. The initial list of conformers was obtained by using the CREST algorithm. In M1, the solvent is considered implicitly while in M2, explicit solvent molecules are added around the solute molecule. In M3, we perform an ab-initio molecular dynamics of the solute molecule surrounded by explicit solvent molecules. The spectrum is obtained by evaluation time-correlation functions along the trajectory. Our first systems of interest were cryptophane derivatives. They are flexible cage-like systems made of two hemispheres connected by three -O-(CH₂)_n-O- (denoted Cr–nnn) linkers that exhibit chiroptical properties. For Cr–111, the smallest cryptophane possible, M1 methodology gave a good agreement with respect to experiment, especially in the fingerprint region. However, we have demonstrated that the relative ratio between the different conformers was strongly impacted by the choice of the exchange-correlation (XC) functional in our DFT calculations demonstrating the sensibility of the description of the PES. Cr–222 molecules have shown to be more flexible, as demonstrated by a greater number of significant conformers. The overall agreement with experiment was also satisfactory. Finally, to test our different approaches (M1-M3), I have performed new ROA measurements of amino acids in water at the University of Bordeaux in the lab of Dr. Daugey. When compared to our simulations, we have clearly seen an improvement on the ROA signatures when explicit water molecules are added in our simulations (M2 vs M1). Unfortunately, M3 method did not perform as expected and further investigations are needed. Overall, I have shown that the PES as described by our various methodologies is very sensitive to various parameters of the simulation such as the XC functional, the number and position of explicit solvent molecules, … and that all these impact strongly the simulated ROA signatures.

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