Impact of solvation on the photoisomerization mechanism of oxindole switches with electron-donating substituents

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.