Miquel Huix-Rotllant

Rapid advances in X-ray free-electron laser facilities are producing X-ray absorption spectra (XAS) with unprecedented detail, creating a pressing need for theoretical methods that are both accurate and computationally efficient to interpret subtle spectral features. In this study, we benchmark two cost-effective electronic-structure approaches for an accurate description of XAS spectra: mixed-reference spin-flip time-dependent density-functional theory (MRSF-TDDFT) and single- and (extended) multistate restricted active-space perturbation theory (SS/(X)MS-RASPT2). We apply these methods to the near-edge X-ray absorption fine structure (NEXAFS) of small and medium-sized organic molecules from the XABOOM test set [J. Chem. Theory Comput. 17, 1618–1637 (2021)]. We show that MRSF-TDDFT and SS/(X)MSRASPT2 yield average errors below 0.5 eV for the lowest bright transitions compared with available gas-phase experimental K-edge spectra and reproduce both excitation energies and relative intensities across the full preionization region with excellent agreement. Furthermore, we introduce the Stochastic Generalized Active Space (S-GAS) method as a high-level tool to simulate XAS spectra and apply it to a subset of the XABOOM data set. In addition to providing accurate spectra, the S-GAS method serves as a benchmark for assessing the performance of the more approximate electronic-structure approaches. Taken together, these methods offer a robust framework for simulating XAS spectra, allowing us to systematically analyze the influence of orbital relaxation, core-valence separation, basis-set size, configuration space restrictions, relativistic effects, and vibrational zero-point energy. These findings provide practical guidelines for achieving high accuracy at reduced computational cost and for enabling more reliable interpretation of experimental NEXAFS features.

Understanding the excited-state dynamics of nucleobases in aqueous environments is essential for elucidating the mechanisms underlying DNA and RNA photostability. While puckered uracil structures have been theoretically predicted and observed in the gas phase following UV excitation, their behavior in solution remains largely unexplored. Here, we investigate the ultrafast photodynamics of uracil in water using a newly developed nonadiabatic surface-hopping QM/MM approach combined with MRSF-TDDFT, explicitly accounting for solvent effects using periodic boundary conditions. Our simulations characterize the dominant pathways and time scales of internal conversion, showing that twisted conformations previously predicted in the gas phase also emerge in solution. By comparing gas-phase and solution dynamics, we show how water modulates the population of puckered conformers and influences radiationless decay pathways. The simulations further suggest that trajectories reaching the conical intersection region in solution preferentially evolve toward planar or half-boat conformations in the ground state. These findings provide molecular-level insight into nucleobase photodynamics in the condensed phase and demonstrate the potential of the present framework for simulating excited-state dynamics in complex biological environments.

Understanding the excited-state dynamics of nucleobases in aqueous environments is essential for elucidating the mechanisms underlying DNA and RNA photostability. While puckered uracil structures have been theoretically predicted and observed in the gas phase following UV excitation, their behavior in solution remains largely unexplored. Here, we investigate the ultrafast photodynamics of uracil in water using a newly developed nonadiabatic surface-hopping QM/MM approach combined with MRSF-TDDFT, explicitly accounting for solvent effects and periodic boundary conditions. Our simulations characterize the dominant pathways and timescales of internal conversion, showing that twisted conformations previously predicted in the gas phase also emerge in solution. By comparing gas-phase and solution dynamics, we show how water modulates the population of puckered conformers and influences the radiationless decay pathways. The simulations further suggest that trajectories reaching the conical-intersection region preferentially evolve toward planar or twisted geometries in the ground-state. Twisted conformations become more populated during the nonequilibrium dynamics in solution. These findings provide molecular-level insight into nucleobase photodynamics in the condensed phase and demonstrate the potential of the present framework for simulating excited-state dynamics in complex biological environments.

Understanding the excited-state dynamics of nucleobases in aqueous environments is essential for elucidating the mechanisms underlying DNA and RNA photostability. While puckered uracil structures have been theoretically predicted and observed in the gas phase following UV excitation, their behavior in solution remains largely unexplored. Here, we investigate the ultrafast photodynamics of uracil in water using a newly developed nonadiabatic surface-hopping QM/MM approach combined with MRSF-TDDFT, explicitly accounting for solvent effects and periodic boundary conditions. Our simulations characterize the dominant pathways and timescales of internal conversion, showing that twisted conformations previously predicted in the gas phase also emerge in solution. By comparing gas-phase and solution dynamics, we show how water modulates the population of puckered conformers and influences the radiationless decay pathways. The simulations further suggest that trajectories reaching the conical-intersection region preferentially evolve toward planar or twisted geometries in the ground-state. Twisted conformations become more populated during the nonequilibrium dynamics in solution. These findings provide molecular-level insight into nucleobase photodynamics in the condensed phase and demonstrate the potential of the present framework for simulating excited-state dynamics in complex biological environments.

La théorie de la fonctionnelle de la densité dépendante du temps (TDDFT) est une méthode basée sur la densité pour calculer les états excités. Bien que la TDDFT soit une théorie exacte, on doit en pratique partir d'une approximation de la fonctionnelle d'échange-corrélation, qui reste inconnue. L'approximation adiabatique est l'approximation de la fonctionnelle la plus courante. Cette approximation donne de très bons résultats pour les propriétés spectroscopiques, mais elle est inexacte pour les simulations en photochimie. Dans cette thèse, on montre que l'origine du problème réside dans l'approximation de la fonctionnelle de corrélation. Le résultat principal de la thèse consiste en un noyau de corrélation, qui peut être utilisé dans la formulation de la réponse linéaire, noyau dérivée à partir de la théorie des perturbations à plusieurs corps. Le noyau inclut de façon générale les excitations doubles qui donnent l'effet principal à la corrélation dans les états excités. La comparaison de ce noyau avec la fonctionnelle adiabatique nous a permis d'identifier les termes manquants à ce dernier. Nous avons testé la possibilité d'ajouter ces termes comme une correction à l'approximation adiabatique. Le noyau pourrait potentiellement être appliqué à des systèmes de grosse taille.

Molecular photoswitches that undergo Z/E photoisomerization are fundamental components of light-driven molecular machines. Their efficiency is determined by ultrafast isomerization dynamics and high quantum yields, both of which are strongly modulated by the solvent environment. In this work, we examine two protonation states of an oxindole-based photoswitch in methanol. Using a combination of quantum mechanics/molecular mechanics (QM/MM) simulations with semi-empirical and high-level electronic structure methods, we compute radial distribution functions, isomerization free energy barriers, absorption spectra, and nonadiabatic dynamics in solution. We find that the deprotonated oxindole establishes stronger hydrogen bonds with methanol, whereas the protonated form adopts a pre-twisted conformation in solution. Nonadiabatic dynamics reveal that the weaker hydrogen bonding of the protonated state permits coherent isomerization, in contrast to the deprotonated form, where solvent fluctuations exert a stronger influence on individual trajectories. These findings clarify how solvent interactions govern the photoisomerization pathways of molecular photoswitches and inform the design of light-driven molecular machines, thereby enabling precise control of their operation in the condensed phase.