Aromatic Polyphenol π-π Interactions with Superoxide Radicals Contribute to Radical Scavenging and Can Make Polyphenols Mimic Superoxide Dismutase Activity

Abstract

Polyphenols are valuable natural antioxidants present in our diet that likely mitigate aging effects, neurodegenerative conditions, and other diseases. However, because of their poor absorption in the gut and consequent low concentration in biological fluids (µM range), reservations about polyphenol antioxidant efficiency have been raised. In this review, it is shown that after scavenging superoxide radicals, coumarin, chalcone, and flavonoid polyphenols can reform themselves, becoming ready for additional cycles of scavenging, similar to the catalytic cycle in superoxide dismutase (SOD) action. The π-π interaction between one polyphenol ring and superoxide is associated with oxidation of the latter due to transfer of its unpaired electron to a polyphenolic aromatic ring, and consequent formation of a molecule of O2 (one product of SOD action). Mechanistically, it is very difficult to establish if this π-π interaction proceeds before or after the most common mode of scavenging superoxide, e.g., abstraction of an aromatic polyphenol H(hydroxyl), which then is used to form H2O2 (the other molecule produced by SOD action). At the end of this cycle of superoxide scavenging, 4-methyl-7,8-di-hydroxy-coumarin and the flavonoid galangin reform themselves. An alternative mechanistic pathway by galangin forms the η-(H2O2)-galangin-η-O2 complex that includes additional H2O2 and O2 molecules. Another mode of action is seen with the chalcone butein, in which the polyphenol system incorporates a molecule of O2, e.g., a η-O2-butein complex is formed, ready for additional scavenging. Of the several families of polyphenols analyzed in this review, only butein was able to circumvent an initial π-π interaction, directing the superoxide towards H(hydroxyl) in position 4, e.g., acting as a typical polyphenol scavenger of superoxide. This fact did not impede an additional superoxide to later react with the aromatic ring in π-π fashion. It is concluded that by mimicking SOD enzyme action, the low concentration of polyphenols in biological fluids is not a limiting factor for effective scavenging of superoxide.

Antioxidant Properties of Thymoquinone, Thymohydroquinone and Black Cumin (Nigella sativa L.) Seed Oil: Scavenging of Superoxide Radical Studied Using Cyclic Voltammetry, DFT and Single Crystal X-ray Diffraction

“…However, the independent process (a), shown in Figure 4 B, suggests O 2 formation. In any case, H 2 O 2 is not produced, and so TQ does not mimic SOD action, unlike behavior recently described for some polyphenols [ 23 ]. We conclude that TQ scavenging of superoxide can be described only in terms of stoichiometric reactions.…”

“…As recently described, molecular oxygen is an important product when polyphenols act as mimics of superoxide dismutase enzymes, following reaction (3) [ 23 ]. 2 O 2 • − + 2H + → O 2 + H 2 O 2 …”

“…The reacting proton component of reaction (3) is associated with a polyphenol hydroxyl H atom transfer (HAT, σ attack, [ 23 ]) and is more often described in polyphenol antioxidant studies than the π-π attack. According to our DFT results, in TQ scavenging of superoxide, the reaction (3) reactants are involved, since two protons ( Figure 4 C,D) are captured as well as two superoxide radicals ( Figure 4 F and Figure 5 ), but the products of reaction (3), O 2 and H 2 O 2 , are not produced by process (b).…”

Scavenging of Superoxide in Aprotic Solvents of Four Isoflavones That Mimic Superoxide Dismutase

“…Scavenging of superoxide was analyzed with DFT methods. In a recent review we described two ways of scavenging this radical by polyphenols: (1) superoxide interaction with an aromatic H(hydroxyl) (conventional polyphenol scavenging, that we call σ) and (2) interaction through the π–π approach [ 19 ], see Scheme 1 .…”

Safe-Shields: Basal and Anti-UV Protection of Human Keratinocytes by Redox-Active Cerium Oxide Nanoparticles Prevents UVB-Induced Mutagenesis

“…To prevent this health hazard, the inclusion of antioxidants into nanoparticle-based sunscreens was often attempted, using carotenoids, vitamins (C and E), and plant extracts; however, these organic compounds have the main limitation of short-term duration due to lack of recycling ability in an abiotic environment such as outer skin. The consequence is that their topical use requires too frequent re-application, being, in fact, a non-sensible option [ 55 , 56 , 57 ]. To overcome this problem, in a recent work, it has been proposed to add biodegradable nanoparticles presenting both durable superoxide dismutase and catalase enzyme activity [ 58 ].…”