Thèse Modélisation de la Chiralité Ultra-Rapide Induite par le Mouvement Électronique Sub-Femtoseconde dans les Molécules H/F

Chimie ParisTech / École Nationale Supérieure de Chimie de Paris (ENSCP)

Établissement : Chimie ParisTech / École Nationale Supérieure de Chimie de Paris (ENSCP)
École doctorale : Chimie Physique & Chimie Analytique de Paris-Centre
Laboratoire de recherche : Institute of Chemistry for Life and Health Sciences
Direction de la thèse : Ilaria CIOFINI ORCID 0000000025391452
Début de la thèse : 2026-10-01
Date limite de candidature : 2026-05-11T23:59:59

Le projet vise à comparer et à développer des protocoles pour modéliser l'évolution de la chiralité induite par les électrons dans des systèmes moléculaires, après excitation par des impulsions attosecondes. La création et l'évolution d'un paquet d'ondes électroniques seront modélisées avec la méthode Ab Initio Multiple Spawning et la méthode Real-Time Time-Dependent Density Functional. Les deux approches seront comparées, puis combinées pour développer un protocole qui couple l'évolution des électrons et celle des noyaux. Le protocole comprendra une analyse des descripteurs basés sur la densité permettant de surveiller l'évolution de la densité électronique, cruciale pour comprendre la chiralité. La validation impliquera de tester divers paramètres nucléaires et électroniques. Les dérivés du camphre, en raison de leur pertinence biologique, seront utilisés comme cas d'étude. Le projet permettra de réaliser un outil unique permettant d'obtenir des informations sur le contrôle énantiosélectif ultra-rapide et ses applications en biologie, pharmacologie et catalyse.

Chirality is a central property of asymmetric molecules, exploited in paramount applications in the fields of biology, pharmacology, catalysis, and many more. Recent advances in spectroscopy opened new frontiers in the field of chirality that were before impossible to achieve. Thanks to the generation of attosecond UV pulses, it has been shown to be possible to monitor molecular chirality in neutral molecules by controlling the electron dynamics in the sub-femtosecond timescale. This allows an unprecedented understanding of molecular chirality and the possibility of modifying and influencing physicochemical molecular properties and the enantioselective response of chromophores to light. The complexity of such experiments and their interpretation call for support from computational chemistry, to get a clear picture of what happens after irradiation with an attosecond pulse and describe the coherent electron dynamics. Computational chemistry has indeed significantly supported the development of attosecond science, but it struggles to keep pace with the latest experimental progress. Therefore, developing new, generalizable theoretical and computational tools capable of accurately describing sub-femtosecond electron dynamics, without neglecting nuclear effects, and explicitly incorporating the influence of laser pulses, will be the key to unlocking the required understanding of electron-driven chirality to exploit it in breakthrough applications.

The overall scope of the doctoral project is to advance the theoretical knowledge of attosecond dynamics and apply existing and new tools to the dynamics of chiral molecules. The first goal is to compare and develop protocols for modeling and understanding electron-driven chirality evolution in molecules to provide an understanding on the performances of different existing methods, towards the development of new accurate and feasible protocol. The new, developed strategy will then be applied to exemplary applications of biologically relevance. The goals are: i) extend our implementation of explicit laser pulses in the code PySpawn to model the creation and evolution of an electron wavepacket in the excited states of molecules; ii) compare AIMS with real time TD-DFT (RT-TD-DFT) dynamics iii) interface PySpawn with codes where RT-TD-DFT is implemented (i.e. Gaussian or NWChem) to combine the two methods to couple nuclear end electron dynamic iv) use the new, unique protocol to study the dynamics of biologically relevant chiral chromophores.

Méthode (stratégies envisagées pour atteindre les objectifs).

After excitation with an attosecond pulse, an electronic wavepacket is created, which coherently evolves on the excited states' surfaces. This can be modelled either with a quantum method such as AIMS, with the inclusion of implicit pulses that create the electronic wavepacket, or in a mean-field approach, like in methods such a RT-TD-DFT. We will compare the two approaches. In AIMS, the nuclear wavepacket is approximated as a series of coupled Gaussian functions evolving semi-classically that exchange electronic population. Within the AIMS formalism, explicit laser excitation can be included to generate the electronic wavepacket, which can later be propagated using the same principle of coupled Gaussians. For this, the code PySpawn will be enhanced with the necessary implementations. For the electron dynamics, methods such a RT-TD-DFT will be used. RT-TD-DFT can efficiently describe the time response of the electrons to an excitation, in a different fashion from AIMS, using an Ehrenfest-like approach. The two methods will be compared, and strengths and limitations of the approaches will be unveiled. This will be the groundwork to interface PySpawn with an electronic structure code that includes TD-DFT, with a wide combination of exchange-correlation functionals (such as NWChem or Gaussian). However, the coherence can be broken due to vibronic coupling and coupling between excited states. Ideally, a method that couples both electron and nuclear motion is required to model the effect of electron dynamics on the photochemistry of chiral molecules. We will develop a new algorithm that will combine the sub femtosecond electron dynamics propagated with RT-TD-DFT and the femstosecond nuclear dynamics with AIMS. This will combine the strengths of both methods, making computationally feasible and sound the modelling of electron-dynamics and apply it to chiral molecules. The analysis of the dynamics through density-based descriptors will be crucial, which will be used to monitor the evolution of the spatial extent of the electron density, a key aspect of evaluating the chirality induced by electronic motion. Several exchange-correlation functionals will be tested in the validation phase of the newly developed protocol. Camphor derivatives will be used as test case due to their biological role and the broad range of applications of their chiral properties, such as enantioselective interaction that allows chemical recognition of biological units.