Modeling Excited State Phenomena in Solution with QM/MM Approaches : from Theory to Applications ​

Solvation plays a crucial role in shaping the electronic structure of molecular systems and, in particular, their excited-state (ES) properties and spectroscopic response. Accurate simulations of ES phenomena in the condensed phase therefore require theoretical approaches that incorporate solvent effects into electronic-structure calculations whileremaining computationally feasible.In this context, this thesis develops and applies polarizable multiscale quantum-mechanics/molecular-mechanics (QM/MM) frameworksbased on the Fluctuating Charge (FQ) and Fluctuating Charge and Dipole (FQFμ) models, which describe specific solvation effects and mutual solute–solvent polarization.These approaches are employed to investigate ES phenomena in solution within time-dependent density-functional theory (TDDFT). Beyond the widely used linear-response(LR)-TDDFT regime, a state-specific approach is introduced to capture solvent relaxation to the ES electron density, enabling a more accurate description of absorption andfluorescence processes. Solution dynamics is further investigated by combining polarizable QM/MM approaches with molecular dynamics and enhanced-sampling techniques,highlighting how configurational sampling influences the final properties. Furthermore, to address molecules exhibiting strong static correlation, the FQ model is extended to mul tireference electronic-structure methods, such as Complete Active Space Self-Consistent Field (CASSCF) and Density Matrix Renormalization Group (DMRG). Overall, theproposed models are benchmarked against alternative theoretical approaches and tested against available experimental data, demonstrating their reliability for quantitativesolution-phase simulations across different molecular systems.