Aluminum(III), iron(III) and copper(II) complexes of luteolin: Stability, antioxidant, and anti-inflammatory properties

In this work complexation of luteolin (H4Lu) with Al(III), Fe(III) and Cu(II) at 37 degrees C and in 0.16 M NaCl is discussed. To evaluate the competition of the ligand for the metal cations and H+, the protonation constant of luteolin was also determined under the same experimental conditions. Speciation profiles obtained by potentiometric titrations show that in aqueous solution a complexation occurs at 1:1 ligand-to-Al(III) ratio, and at 1:1 and 2:1 ligand-to-cation ratios for Fe(III) and Cu(II). The coordination sites of luteolin to the different metal ions were determined by a computational approach, displaying that copper ion shows no selective preference towards any of the complexation sites of luteolin, while the six-membered chelate ring of the 4-5 site (i.e., the 4-carbonyl-5-hydroxyl site of the A and C rings of the ligand) is the preferred one for aluminum and iron ions. Additionally, we have evaluated the antioxidant and anti-inflammatory properties of free luteolin and of the luteolin-metal ion complexes. The complex with iron was found to have a higher activity than the other complexes (i.e., Fe(III)-Lu > Cu(II)-Lu > Al(III)-Lu), and its DPPH radical scavenging ability was even higher than that of free luteolin. Finally, all luteolin metal complexes were found to significantly reduce lipopolysaccharide (LPS)-induced interleukin (IL)-6 levels in monocyte-derived macrophages with the following order: Fe(III)-Lu > Al(III)-Lu > Cu(II)-Lu > free Lu. (C) 2021 Elsevier B.V. All rights reserved.