Hitchhiking into a cell: flavonoids may produce complexes with transition metals for transmembrane translocation.

Flavonoids are a group of food polyphenols that are delivered to the human body with plant foods. In recent years, these substances have attracted the attention of researchers due to their effectiveness in preventing a wide variety of diseases, including neurodegenerative, oncological, autoimmune, and cardiovascular. Similar pathologies may also occur with a lack of some first-row transition metals, including Cu(II), Zn(II), Mn(II), Fe(II/III). It is noteworthy that flavonoids are known as transition metal chelators. When a complex with these metals is formed, the therapeutic effect of flavonoids can be enhanced, assuming the possibility of synergy. Molecular models have shown that the lipophilicity of flavonoid-metal complexes can vary significantly depending on their binding stoichiometry. Therefore, a unique process of translocation of flavonoid-metal complexes of various lipophilicity through cell membranes is assumed, based on the possibility of their sequential association and dissociation, called "hitchhiking". It is expected that studies of the interaction of flavonoids with metals will improve the effectiveness of drugs based on flavonoids.