Effect of geometrical and electronic alteration on the n → π* vertical excitation energy and thermodynamic stability of locked azobenzene (LAB) with protein confinement.

Locked azobenzenes (LAB) derivatives are recognized as photoswitchable potassium ion channel blockers. Here we report the effect of tetraethyl ammonium ion (TEA) substituent and KcsA K+‐ion channel protein environment on the thermodynamic stability and vertical excitation energy of locked azobenzene. The complete active space self‐consistent field (CASSCF and state‐averaged CASSCF, SA2‐CAS) with complete active space perturbation theory (state‐averaged CASPT2, SA2‐CASPT2) and our own n‐layered integrated molecular orbital and molecular mechanics—mechanical embedding (ONIOM‐ME) followed by electronic embedding (ONIOM‐EE) methods were employed for the study. The Z‐isomer of LAB is thermodynamically more stable as compared to E‐isomer. The substitution of tetraethyl ammonium ion does not influence the thermodynamic stability. On the other hand, the thermodynamic stability is reversed in the protein environment. Furthermore, the vertical excitation energies (VEE) and geometrical parameters show that the photochemistry of LAB is unaffected by para‐substituted TEA. However, geometrical changes imposed by the protein on the confined LAB‐TEA decreases the VEE. [ABSTRACT FROM AUTHOR]