Interactions of Calcium with Chlorogenic and Rosmarinic Acids: An Experimental and Theoretical Approach

Abstract

Chlorogenic (CA) and rosmarinic (RA) acids are two natural bioactive hydroxycinnamic acids whose antioxidant properties can be modulated by the chelation of metal ions. In this work, the interactions of these two carboxylic phenols with calcium ions and the impact of such interactions on their antioxidant activity were investigated. UV-Vis absorbance, mass spectroscopy and 1H and 13C liquid NMR were used to identify complexes formed by CA and RA with calcium. Antioxidant activities were measured by the Bois method. Density functional theory (DFT) calculations were performed to evaluate the most stable configurations and correlated with NMR data. Taken together, these data suggest that calcium ions mainly interact with the carboxylate groups of both molecules but that this interaction modifies the reactivity of the catechol groups, especially for RA. These results highlight the complex interplay between metal chelation and antioxidant properties of natural carboxylic phenols.

New insights into the competition between antioxidant activities and pro-oxidant risks of rosmarinic acid

“…9,10 Normally, these acids contain -COOH and -OH groups and sometimes have the ester or ether groups that allow the complexation with metal ions. 9,[29][30][31] Rosmarinic acid (RA, Fig. 1) is one of the hydroxycinnamic acids, and was initially isolated and puried from the extract of rosemary, a member of mint family (Lamiaceae), in 1958 by Scarpati and Oriente.…”

Polyphenols: Bioavailability, Microbiome Interactions and Cellular Effects on Health in Humans and Animals

“…The chelating properties of polyphenols are also of notable importance in their ability to relieve oxidative damage brought on by circulating metals in incidences of oxidative stress. Polyphenols with catechol groups are often very good metal chelators as they are able to form bidentate ligands, and similarly, polyphenols with hydroxyl groups in peri positions on phenolic rings also make strong candidates for chelation, although pH is a key factor in their ability to bind with metals [ 146 , 147 ]. Fenton reactions with H 2 O 2 and iron or copper ions can create superoxides capable of damaging biomolecules like DNA [ 148 ].…”

“…Polyphenols with catechol and/or galloyl groups that scavenge free radicals form semi-quinone compounds that are further capable of reducing Fe 3+ ions, causing the polyphenols to become pro-oxidant quinones [ 148 ]. The ability for polyphenols to chelate may be hampered if they are conjugated with other moieties, such as sugars [ 146 ], and conversely, the anti-oxidant capabilities of polyphenols appear to be reduced in the presence of metals, as metal ligands may reduce their reactivity with free radicals [ 147 , 149 ]. Most of the evidence for the reduction of ROS via chelation of polyphenols with iron are based on in vitro studies, and a fairly robust body of evidence suggests that dietary polyphenols may ultimately inhibit the absorption of dietary iron [ 150 ].…”

“…Studies identifying tetracycline and alizarin in bone have argued that these molecules are bound to calcium specifically. In vitro experiments have demonstrated that a range of polyphenolic compounds bind directly with free calcium and hydroxyapatite, and polyphenol interactions with hydroxyapatite are likely the result of chelation with calcium ions [ 17 , 147 ]. At physiological pH (~7.6), polyphenols are generally deprotonated and generate oxygen centres with high charge densities, making them capable of forming hard ligands with transition metals, typically via catechol groups ( Section 3.2 ) [ 146 ].…”

“…At physiological pH (~7.6), polyphenols are generally deprotonated and generate oxygen centres with high charge densities, making them capable of forming hard ligands with transition metals, typically via catechol groups ( Section 3.2 ) [ 146 ]. Carboxylate groups have more recently been argued as better sites for metal ligands, at least in relation to calcium [ 147 ].…”