Photoisomerization\nDynamics of Azo-Escitalopram Using\nSurface Hopping and a Semiempirical Method

The photoisomerization dynamics of azo-escitalopram,\na synthetic\nphotoswitchable inhibitor of the human serotonin transporter, is investigated\nin both gas-phase and water. We use the trajectory surface hopping\nmethodas implemented in SHARCinterfaced with the floating\noccupation molecular orbital–configuration interaction semiempirical\nmethod to calculate on-the-fly energies, forces, and couplings. The\ninclusion of explicit water molecules is enabled using an electrostatic\nquantum mechanics/molecular mechanics framework. We find that the\nphotoisomerization quantum yield of trans-azo-escitalopram is wavelength-\nand environment-dependent, with <i>n</i> → π*\nexcitation yielding higher quantum yields than π → π*\nexcitation. Additionally, we observe the formation of two distinct\ncis-isomers in the photoisomerization from the most thermodynamically\nstable trans-isomer, with formation rates influenced by both the excitation\nwindow and the surrounding environment. We predict longer excited-state\nlifetimes than those reported for azobenzene, suggesting that the\nescitalopram moiety contributes to prolonged lifetimes and slower\ntorsional motions.