A comparative theoretical study on the photoisomerization and antioxidant capacity of resveratrol and its Azo/Dihydro analogs

This study employs a suite of quantum chemical methods to systematically investigate the photoisomerization mechanism and antioxidant activity of resveratrol (Res) and two key derivatives, Azo-Resveratrol (AzoRes) and Dihydro-Resveratrol (dhRes), thereby elucidating the impact of molecular scaffold modification on their structure-activity relationships. Employing density functional theory (DFT), time-dependent DFT (TD-DFT), spin-flip TD-DFT and multistate complete active space second-order perturbation theory (MS-CASPT2), we investigated the geometric configurations, absorption spectra, photoisomerization pathways, and key antioxidant parameters for all three molecules. The results reveal that the substitution of the CC bond with an NN linkage (AzoRes) induces a bathochromic shift in the absorption spectrum, introduces a low-energy n → π* transition, and facilitates a barrierless photoisomerization pathway. Conversely, the saturation of the CC bond to a CC single bond (dhRes) disrupts the π-conjugated system, resulting in a significant hypsochromic shift. Analysis of frontier molecular orbitals and global descriptive parameters established the order of S₀-state antioxidant capacity as AzoRes > Res > dhRes, a trend that correlates with the narrower HOMO-LUMO gap of AzoRes compared to Res (by 0.302 eV and 0.564 eV for trans and cis isomers, respectively). While photoexcitation universally enhanced the antioxidant potential of all molecules, it also reordered the efficacy to Res > AzoRes > DHRes in the S₁ state. Our findings elucidate the intrinsic relationship between the molecular scaffold, photochemical behavior, and antioxidant activity, providing a theoretical framework for the rational design of novel photo-responsive antioxidant materials.