Computational Study on the Photo-Induced Antibiotic Activity of an Azoquinolone with Promising Applications in Photopharmacology

Abstract

Azocompounds are among the most important group of molecular photoswitches due to their multiple applications in various scientific areas. We studied the thermal and photochemical reactions of an azocompound with photo-induced antibiotic properties using ab-initio calculations based on Kohn-Shan, Spin-Flip and time-dependent Density Functional Theory. Our primary goal is to understand the absorption spectra and isomerization pathways governing the molecule's light-controlled antibiotic activity. The nuclear ensemble approach was used for the most stable trans and cis isomers, and the absorption spectra were calculated and fitted to predict the cis/trans isomer ratios in the carboxylate form, using experimental measurements as a reference. We stablished that rotation is involved in the most favorable cis↔cis and trans↔trans thermal isomerization pathways, while the inversion mechanism is the most likely for cis↔trans isomerizations. We found that the photochemical trans→cis isomerization follows a consistent mechanism across all trans isomers, involving excitation to S₂(ππ*), an in-plane ultrafast internal conversion to S₁(nπ*), followed by rotation of the azo bond up to a twisted S₁(nπ*)/S₀ conical intersection. We used a custom approach to evaluate the most favorable decay pathway from the S₁(nπ*)/S₀ conical intersections to trans and cis photoproducts using static calculations.