Second Harmonic Generation of Spiropyran–Merocyanine Photoswitches: Insights From Hyper‐Rayleigh Scattering and All‐Atom Dynamic Structure Quantum Mechanical Calculations

ABSTRACT This work investigates second harmonic generation and photoswitching of two representative spiropyran/merocyanine (SP/MC) systems in dichloromethane, combining synthesis, hyper‐Rayleigh scattering (HRS) measurements, and novel computational methodologies. HRS measurements use near‐infrared excitation and are performed under continuous UV irradiation to drive photoswitching. To compute (non)linear optical properties of explicitly solvated systems, an all‐atom dynamic structure quantum mechanical (ADQM) protocol is proposed, coupling GFN2‐xTB molecular dynamics with the eXact integral simplified TD‐DFT (XsTD‐DFT). XsTD‐DFT enables efficient evaluation of absorption and second harmonic generation at a fraction of TD‐DFT cost, capturing chromophore–solvent interactions for systems of hundreds of atoms. Predicted first hyperpolarizabilities show striking agreement with HRS measurements, demonstrating the adequacy of ADQM methodologies. To rationalize the origin of the NLO response, we introduce a scheme combining partial least squares regression with non‐equilibrium MD geometries, uncovering key structural and electronic parameters governing the HRS response of MC. Finally, the ADQM protocol estimates the photoconversion efficiency (2%) under continuous UV irradiation and quantifies the HRS contrast upon photoswitching. Overall, this work establishes a robust, computationally efficient framework for predicting molecular NLO properties directly comparable to experiment, illustrating how seamless integration of theory and spectroscopy yields deep structure–property insights for designing NLO photoswitchable materials.