Theoretical study on the free radical scavenging potency and mechanism of natural coumestans: Roles of substituent, noncovalent interaction and solvent. (March 2023)

• Record Type: Journal Article
• Authors: Chen, Mohan; Li, Zheng; Sun, Gang; Jin, Shuang; Hao, Xiyue; Zhang, Chi; Liu, Ling; Zhang, Ling; Liu, Hongli; Yunsheng Xue,
• Is Part Of: Phytochemistry. Volume 207(2023)
• Publication Date: 2023-03
• Subjects: Coumestans -- Radical scavenging potency -- Mechanism -- Noncovalent interaction -- Solvent effect -- Density functional theory (DFT); Botanical chemistry -- Periodicals; Biochemistry -- Periodicals; Botany -- Periodicals; Chimie végétale -- Périodiques; 572.2
• DOI: 10.1016/j.phytochem.2022.113580
• Languages: English
• ISSNs: 0031-9422

Abstract

Abstract: The free radical scavenging potency and mechanisms of seven representative natural coumestans were systematically evaluated using density functional theory (DFT) approach. Thermodynamic feasibility of different mechanisms was assessed by various physio-chemical descriptors involved in the double (2H + /2e ‒ ) radical-trapping processes. Energy diagram and related transition state structures of the reaction between wedelolactone (WEL) and hydroperoxyl radical were constructed to further uncover the radical-trapping details. Results showed that the studied coumestans prefer to scavenge radicals via formal hydrogen atom transfer (fHAT) mechanism in the gas phase and non-polar environment, whereas sequential proton loss electron transfer (SPLET) is favored in polar media. Moreover, the feasibility of second fHAT and SPLET processes was also revealed. Sequential double proton loss double electron transfer (SdPLdET) mechanism represents the preferred pathway in aqueous solution at physiological pH. Our findings highlight the essential role of ortho-dihydroxyl group, noncovalent interaction and solvents on radical-trapping potency. 4′-OH in D-ring was found to be the most favorable site to trap radical for most of the studied coumestans, whereas 3-OH in A-ring for lucernol (LUN). Graphical abstract: Density functional theory (DFT) calculations were performed to clarify the structure-radical trapping activity relationship and the preferred mechanisms in different environments of seven representative natural coumestans. Image 1 Highlights: Antiradical activity of seven representative coumestans was evaluated by DFT method. Preferred mechanisms were elucidated using thermodynamic descriptors. Effects of substituent, noncovalent interaction and solvents were explored. Potential energy surface of reaction between WEL and HOO. was constructed; Double fHAT, double SPLET and SdPLdET mechanisms are feasible depending on media.