# Reshaping Antioxidant Activity via Photoisomerization: A Comparative Theoretical Study of Pterostilbene and Resveratrol

## TL;DR

This paper compares how light and chemical structure affect the antioxidant power of pterostilbene and resveratrol using advanced computational methods.

## Contribution

The study reveals how methoxy substitution and photoexcitation influence antioxidant mechanisms and photoisomerization kinetics in pterostilbene and resveratrol.

## Key findings

- Trans isomers show a redshift and higher oscillator strengths than cis isomers.
- Methoxy substitution lowers the isomerization barrier for resveratrol, making pterostilbene more photoisomerizable.
- Trans-pterostilbene binds strongly to the Keap1 Kelch pocket, inhibiting Nrf2 binding.

## Abstract

This study elucidates the regulatory mechanisms of methoxy substitution and photoexcitation on the antioxidant properties of pterostilbene (PTE) versus resveratrol (RES), employing a combined approach of multi-reference calculations, density functional theory (DFT), time-dependent DFT (TD-DFT), and molecular docking. Spectral analysis indicates that trans isomers exhibit a significant redshift (~13 nm) and have oscillator strengths more than double those of cis isomers. A pivotal difference in photoisomerization kinetics was identified: methoxy substitution drastically lowers the isomerization barrier for RES, indicating that PTE is more readily photoisomerized. Regarding radical scavenging, thermodynamic data confirm that Hydrogen Atom Transfer (HAT) and Radical Adduct Formation (RAF) are spontaneous pathways; notably, the O1 site of trans-PTE serves as the optimal hydrogen donor. Conceptual DFT (CDFT) analysis reveals that photoexcitation triggers a dramatic electronic reconfiguration, particularly for cis-PTE, whose ionization potential in the S1 state drops sharply to 4.66 eV, accompanied by an increased softness of 0.38 eV−1, rendering it a highly potent electron donor. Furthermore, molecular docking demonstrates that trans-PTE robustly occupies the Keap1 Kelch pocket (binding energy: −7.478 kcal/mol) to inhibit Nrf2 binding via its favorable planar geometry.