Structure-antioxidant activity relationship of methoxy, phenolic hydroxyl, and carboxylic acid groups of phenolic acids

Jinxiang Chen,Jun Li,Lanlan Ma,Nasir Shahzad,Jing Yang,Chan Kyung Kim

doi:10.1038/s41598-020-59451-z

Abstract

The antioxidant activities of 18 typical phenolic acids were investigated using 2, 2′-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) assays. Five thermodynamic parameters involving hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT), and sequential proton-loss electron transfer (SPLET) mechanisms were calculated using density functional theory with the B3LYP/UB3LYP functional and 6–311++G (d, p) basis set and compared in the phenolic acids. Based on the same substituents on the benzene ring, -CH2COOH and -CH = CHCOOH can enhance the antioxidant activities of phenolic acids, compared with -COOH. Methoxyl (-OCH3) and phenolic hydroxyl (-OH) groups can also promote the antioxidant activities of phenolic acids. These results relate to the O-H bond dissociation enthalpy of the phenolic hydroxyl group in phenolic acids and the values of proton affinity and electron transfer enthalpy (ETE) involved in the electron donation ability of functional groups. In addition, we speculated that HAT, SET-PT, and SPLET mechanisms may occur in the DPPH reaction system. Whereas SPLET was the main reaction mechanism in the FRAP system, because, except for 4-hydroxyphenyl acid, the ETE values of the phenolic acids in water were consistent with the experimental results.

Highlights

The antioxidant activities of 18 typical phenolic acids were investigated using 2, 2′-diphenyl-1picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) assays
Three key antioxidant mechanisms involved in the process of quenching free radicals are hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT), and sequential proton-loss electron transfer (SPLET)
HAT is a one-step reaction related to O-H bond dissociation enthalpy (BDE), whereas SET-PT and SPLET are two-step reactions, the former is related to ionization potential (IP) and proton dissociation enthalpy (PDE), and the latter is related to proton affinity (PA) and electron transfer enthalpy (ETE)[13,14]

Summary

Introduction

The antioxidant activities of 18 typical phenolic acids were investigated using 2, 2′-diphenyl-1picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) assays. HAT is a one-step reaction related to O-H bond dissociation enthalpy (BDE), whereas SET-PT and SPLET are two-step reactions, the former is related to ionization potential (IP) and proton dissociation enthalpy (PDE), and the latter is related to proton affinity (PA) and electron transfer enthalpy (ETE)[13,14] These reaction mechanisms under different micro-environments may occur independently or simultaneously at different rates[15]. To elucidate the structure-activity relationships (SAR) of phenolic antioxidants, 18 typical phenolic acids, hydroxybenzoic acid (6), hydroxyphenylacetic acid (6), and hydroxycinnamic acid (6), from natural products or/and colon metabolites of polyphenols with corresponding structures, were investigated by experimental and computational methods[16] Their antioxidant activities were evaluated using a 2,2′-diphenyl-1-picrylhydrazyl (DPPH) assay in an ethanol system and ferric ion reducing antioxidant power (FRAP) assay in a water system. The effects of the methoxy, phenolic hydroxyl, and carboxylic acid groups on the antioxidant activity of phenolic acids and the possible mechanism of these effects will be discussed

Methods

Results

Conclusion