Elucidating the Molecular Interactions of Flavonoid-Metal Complexes via Isothermal Titration Calorimetry

Flavonoids exhibit many proven health benefits and play critical roles in preventing, delaying, or even reversing chronic disease conditions. The biological activities of flavonoids strongly depend on their structures, and they interact with many biological components, such as proteins, nucleic acids, and inorganic ions. The coordination of metal-flavonoid complexes has previously been shown to increase the biological activity of flavonoids. Additionally, the complexation of metal ions and flavonoids serves as a great strategy to create advanced structures, such as nanoparticles or thin films. Among various metal ions, ferric ions are essential for many biological processes and have a high affinity for binding with flavonoids to form advanced structures. Therefore, understanding the molecular interactions between flavonoids and ferric ions (Fe(III)) is of great fundamental and practical importance. In this paper, using quercetin and its glycoside form, rutin, as model systems, we systematically investigated their complexation behaviors with Fe(III). The presence of a sugar molecule on rutin leads to differences between rutin and quercetin in solubility, stability, and the number of metallic ion coordination sites. Here, our studies specifically investigated the effects of solvents and temperature on their complexation behaviors with Fe(III) using isothermal titration calorimetry (ITC). The complexation processes of both flavonoids with Fe(III) were similar and primarily exothermic. However, the solvent significantly affected the thermodynamic parameters of the interactions. These findings offer valuable guidance for understanding the interactions between flavonoids and metal ions and provide insights into the development of flavonoid-based advanced structures.