Excited-state antioxidant activity for apigenin based on external electric field-modulated ESIPT behavior: TD-DFT and molecular docking calculations

Xingzhu Tang; Ye Wang; Lingling Wang; Yajie Zhang; Chaofan Sun

doi:10.1016/j.jphotobiol.2024.113087

Excited-state antioxidant activity for apigenin based on external electric field-modulated ESIPT behavior: TD-DFT and molecular docking calculations

J Photochem Photobiol B. 2024 Dec 27:262:113087. doi: 10.1016/j.jphotobiol.2024.113087. Online ahead of print.

Authors

Xingzhu Tang¹, Ye Wang², Lingling Wang³, Yajie Zhang¹, Chaofan Sun⁴

Affiliations

¹ College of Science, Northeast Forestry University, Harbin 150040, China.
² College of Physics and Electronic Information, Baicheng Normal University, Baicheng 137000, China. Electronic address: wangye@bcnu.edu.cn.
³ College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China; Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China; Heilongjiang Provincial Key Laboratory of Ecological Utilization of Forestry-Based Active Substances, Northeast Forestry University, Harbin 150040, China. Electronic address: llwang91@126.com.
⁴ College of Science, Northeast Forestry University, Harbin 150040, China. Electronic address: sunchaofan91@126.com.

PMID: 39733526
DOI: 10.1016/j.jphotobiol.2024.113087

Abstract

Apigenin (Api), a flavonoid possessing dual features of antioxidant activity and intramolecular hydrogen bond (IMHB), is subjected to an external electric field (EEF) to investigate its excited-state antioxidant activity after excited state intramolecular proton transfer (ESIPT) behavior employing the density functional theory (DFT) and time-dependent DFT (TD-DFT) methods, as well as molecular docking. The existence of IMHB is demonstrated by structural parameters and AIM topological analysis, where Api in the enol^⁎ form under an EEF of +60 × 10^-4 a.u. possesses strong IMHB. The potential energy curves confirm that the ESIPT process varies from barrierless to barriered as the positive EEF grows, thus determining the excited-state form. Api exhibits strong excited-state antioxidant activity in vitro whether or not under an EEF, especially under the EEF of -40 × 10^-4 a.u., utilizing HOMO energy. According to average local ionization energy (ALIE), the electrophilic reaction site also changes after ESIPT process under the EEF, and the activity is significantly increased. Furthermore, activation of the antioxidant Keap1-Nrf2-ARE pathway in vivo, namely, the interaction of Keap1 protein with Api, calculated by molecular docking, suggests that an interaction between the Keap1 and excited-state Api exists accompanying lower and variable bind energy under the distinct EEFs. Taken together, combining the modulation of the ESIPT process with the excited-state antioxidant activity is an effective approach to enhance the antioxidant activity of compounds.

Keywords: Excited state intramolecular proton transfer; Excited-state antioxidant activity; External electric field; Molecular docking; TD-DFT.