Antioxidant Activity of Sulfate Metabolites of Chlorogenic Acid

Abstract

This study aimed to determine the antioxidant properties of the sulfate monoesters of ferulic, caffeic, dihydroferulic and dihydrocaffeic acids, the main metabolites of chlorogenic acids. These compounds are not commercially available, so they were synthesized in the laboratory. The LC-MS/MS analysis allowed for the full characterization of these derivatives, which has made them reliable standards for further research. Purified metabolites including ferulic acid-4-O-sulfate, caffeic acid-4-O-sulfate and caffeic acid-3-O-sulfate, dihydrocaffeic acid-4-O-sulfate and caffeic acid-3-O-sulfate were examined for their antioxidant capacities and compared to their precursor compounds using Folin–Ciocalteu, CUPRAC (cupric ion—reducing) and DPPH• (2,2-diphenyl-1-picrylhydrazyl) methods. This study shows that hydrogenation of caffeic and ferulic acids into dihydrocaffeic and dihydroferulic acids has a positive influence on their reducing properties. Moreover, all synthesized sulfate monoesters exhibited very weak antioxidant properties compared to precursor compounds. The presented results show that the transformation of phenolic acids via sulfation leads to the inhibition of antioxidant properties due to the blockage of hydroxyl groups.

Dihydrocaffeic Acid—Is It the Less Known but Equally Valuable Phenolic Acid?

“…In the case of dihydrocaffeic acid, as well as other phenolic acids used in the study, it was observed that sulfation of the hydroxyl group in the aromatic ring caused a significant reduction in antioxidant activity. Comparing DHCA to its monosulfate derivative (mixture of both sulfates at an unknown ratio), the authors obtained the following results: (a) in the CUPRAC method, 0.49 mM of Trolox equivalents (TE) for DHCA, and no activity for monosulfates; (b) using Folin-Ciocalteu assay, 72.07 to 2.19 ppm of gallic acid equivalents; (c) in the DPPH radical test, 0.563 mM of TE (39.96% of scavenging effect), which was approximately 10 times higher than the values for monosulfates (0.051 mM and 3.61%) [84].…”

“…The most common antioxidant assays are based on simple chemical reactions between an antioxidant and model free radicals such as 2,2-diphenyl-1-picrylhydrazyl radical (DPPH • ) or the radical cation of 2,2 -Azino-bis(3ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS +• ), or on metal ions, as in FRAP (Ferric Reducing Antioxidant Power) and CUPRAC (CUPric Reducing Antioxidant Capacity) methods. As well, in the case of dihydrocaffeic acid and its derivatives, these tests were successfully used [1,5,25,26,[81][82][83][84].…”

“…The unsaturated bond found in the carbon chain of caffeic acid may participate in the stabilization of the phenoxyl radicals by resonance. Due to the presence of the catechol ring in both compounds, the observed results were comparable and disputable, and this group probably masked the influence of other structural Other derivatives of the described phenolic acid which were subjected to antioxidant activity measurements were dihydrocaffeic acid-3-O-sulfate (35) and dihydrocaffeic acid-4-O-sulfate (36) [84], i.e., the compounds that are formed during the metabolism of chlorogenic, caffeic, and dihydrocaffeic acids [51]. In the case of dihydrocaffeic acid, as well as other phenolic acids used in the study, it was observed that sulfation of the hydroxyl group in the aromatic ring caused a significant reduction in antioxidant activity.…”

Special Issue on the Application of Analytical Chemistry in Pharmaceutical and Biomedicine

“…Similarly, Ali et al established a precise and eco-friendly approach for the determination of a novel TKI (erdafitinib) in human plasma samples through a validated UPLC-MS/MS method, and the developed assay was further applied in metabolic stability studies [5]. Rogozinska et al investigated the antioxidant activity of the main metabolites of chlorogenic acid (ferulic, caffeic, dihydroferulic, and dihydrocaffeic acids) by synthesizing them in the laboratory, and they were characterized via LC-MS/MS analysis [6]. Sobolewska et al reported a post-column derivative HPLC-based fluorescence detection method for the quantitative analysis of a new boronic acid derivative, which is clinically developed as an anticancer agent [7].…”