Photoisomerization Dynamics of Azo-Escitalopram Using Surface Hopping and a Semiempirical Method

The photoisomerization dynamics of azoescitalopram, a synthetic photoswitchable inhibitor of the human serotonin transporter, is investigated in both gas-phase and water. We use the trajectory surface hopping method, as implemented in SHARC, interfaced with the semiempirical Floating Occupation Molecular Orbitals-Configuration Interaction (FOMO-CI) electronic structure method to calculate on-the fly energies, forces and couplings. The inclusion of explicit water molecules is enabled using a quantum mechanics/molecular mechanics (QM/MM) framework. We find that the photoisomerization quantum yield of trans-azoescitalopram is wavelength and environment dependent, with n→π* excitation yielding higher quantum yields than π→π* excitation. Additionally, we observe the formation of two distinct cis-isomers during photoisomerization from the most thermodynamically stable trans-isomer, with formation rates influenced by both the excitation window and surrounding environment. Longer excited-state lifetimes are found than those reported for azobenzene, suggesting that the escitalopram moiety contributes to these extended lifetimes and slower torsional motions.