Insight into the antioxidant mechanism of astaxanthin geometric isomers by quantum chemical calculations and molecular simulations.

Astaxanthin (Asta) demonstrates structure-dependent antioxidant efficacy, with geometric isomers differing significantly. This study elucidated the antioxidant mechanisms of three Asta isomers and proposed a novel O quenching mechanism. 9-cis Asta outperformed 13-cis Asta in free radical scavenging, with both outperforming the all-trans Asta. Density functional theory analysis confirmed stronger chemical activity of 9-cis and 13-cis Asta by ΔE, which were 22.01 % and 15.92 % lower than that of all-trans Asta, respectively. Bond length and reduced density gradient analyses confirmed these findings. The cis isomers also demonstrated a stronger single-electron transfer capability. The O quenching ability of 9-cis Asta was 1.27 and 1.49 times than those of 13-cis and all-trans Asta, and it had doubled binding sites for O and higher lowest unoccupied molecular orbital electron density. Especially, it formed a unique hydrogen bond with Arg483 of Keap1. These findings comprehensively explain Asta's antioxidant mechanism based on its geometric isomers.