Photochemical activation enables selective control over specific bond dissociation pathways by tuning the excitation wavelength. Here, we investigate the photochemical activation of 2-aryl-5-carboxytetrazole (ACT), a highly efficient genetically encoded photo-cross-linker, whose reactivity arises from a coupled interplay of charge transfer, bond cleavage, and excited-state aromaticity modulation. Using CASSCF multireference electronic structure theory combined with semiclassical surface-hopping dynamics, we elucidate the complete reaction mechanism. Our CASSCF based nonadiabatic dynamics simulations reveal that upon photoexcitation, electron density migrates from the pyrrole π-system to the tetrazole π*, initiating N-N bond activation and N2 release via a conical intersection. We also optimized the conical-intersection geometry using the recently developed MRSF-TDDFT (balancing dynamic and non-dynamic electron correlations) method; the resulting structural features closely match those obtained from CASSCF, confirming the robustness of our mechanistic picture. Nucleus Independent Chemical Shift (NICS) calculations along the reaction coordinate confirm an intramolecular electron-catalyzed process, in which the pyrrole ring switches from aromatic to antiaromatic in the excited state and regains aromaticity after bond cleavage. This integrated approach demonstrates that excited-state aromaticity can serve as a powerful driving force for photochemical transformations, offering a mechanistic blueprint for the rational design of next-generation photoactive molecular systems.
Halder et al. (Thu,) studied this question.