Tang Xingzhu, Wang Ye, Wang Lingling, Zhang Yajie, Sun Chaofan
College of Science, Northeast Forestry University, Harbin 150040, China.
College of Physics and Electronic Information, Baicheng Normal University, Baicheng 137000, China.
J Photochem Photobiol B. 2025 Jan;262:113087. doi: 10.1016/j.jphotobiol.2024.113087. Epub 2024 Dec 27.
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 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 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.
芹菜素（Api）是一种具有抗氧化活性和分子内氢键（IMHB）双重特性的黄酮类化合物，采用密度泛函理论（DFT）和含时密度泛函理论（TD-DFT）方法以及分子对接，对其在经历激发态分子内质子转移（ESIPT）行为后的激发态抗氧化活性进行了外部电场（EEF）作用下的研究。通过结构参数和AIM拓扑分析证明了IMHB的存在，其中在+60×10 a.u.的EEF下烯醇形式的Api具有很强的IMHB。势能曲线证实，随着正EEF的增加，ESIPT过程从无障碍变为有障碍，从而决定了激发态形式。无论是否在EEF下，Api在体外均表现出很强的激发态抗氧化活性，尤其是在-40×10 a.u.的EEF下，利用最高占据分子轨道（HOMO）能量。根据平均局部电离能（ALIE），在EEF下ESIPT过程后亲电反应位点也发生变化，且活性显著增加。此外，通过分子对接计算得出，体内抗氧化Keap1-Nrf2-ARE途径的激活，即Keap1蛋白与Api的相互作用，表明在不同的EEF下，Keap1与激发态Api之间存在相互作用，且结合能较低且可变。综上所述，将ESIPT过程的调控与激发态抗氧化活性相结合是增强化合物抗氧化活性的有效方法。
