On the Inhibition of Hydroxyl Radical Formation by Hydroxycinnamic Acids: The Case of Caffeic Acid as a Promising Chelating Ligand of a Ferrous Ion

Density functional theory has been employed here to explore the ability of caffeic acid (CA) to trap Fe­(II) to prevent the Fenton reaction thus limiting the hydroxyl radical formation. Electronic and structural features of complexes for metal-to-ligand different ratios were fully elucidated. Results confirm that the anionic forms of CA are able to form very stable complexes and show that all the possible coordination modes lead to formation of complexes that are thermochemically accessible. In addition, the change in free energies for the oxidation reaction, according to which hydrogen peroxide directly interacts with the metal center to produce the hydroxyl radical, confirms that Fe­(II) complexed by CA is less active toward H₂O₂ than the purely solvated one. Even the energy required for the ligand exchange (H₂O₂ in place of water), supposed to be the first step involved in the Fenton reaction in a physiological environment, supports the propensity of CA to deactivate the hydroxyl radical formation by sequestering the ferrous ion. The rationalization of absorption spectra for various Fe­(II)–CA complexes shows neutral and monoanionic species as conceivable ligands of the ferrous ion and the carboxylic group as the most probable site of coordination.