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

• Published in: The journal of physical chemistry. B 2024-12
• Main Authors: Gallmetzer, Hans Georg, Sangiogo Gil, Eduarda, González, Leticia
• Format: Article
• Language: English
• ISSN: 1520-6106; 1520-5207; 1520-5207
• DOI: 10.1021/acs.jpcb.4c06924

The photoisomerization dynamics of azo-escitalopram, 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 floating occupation molecular orbital-configuration interaction semiempirical method to calculate on-the-fly energies, forces, and couplings. The inclusion of explicit water molecules is enabled using an electrostatic quantum mechanics/molecular mechanics framework. We find that the photoisomerization quantum yield of trans-azo-escitalopram is wavelength- and environment-dependent, with → π* excitation yielding higher quantum yields than π → π* excitation. Additionally, we observe the formation of two distinct cis-isomers in the photoisomerization from the most thermodynamically stable trans-isomer, with formation rates influenced by both the excitation window and the surrounding environment. We predict longer excited-state lifetimes than those reported for azobenzene, suggesting that the escitalopram moiety contributes to prolonged lifetimes and slower torsional motions.