# Origin and Function of Structural Diversity in the Plant Specialized Metabolome
## 3 Structure-Antioxidant Activity Relationships of Flavonoids
Interestingly, the catechol structure on the B-ring and the 4-oxo function, in combination with the 3- and 5-OH groups, not only improve the ROS scavenging capacities of flavonoids, but confer also their metal chelation capacities, as they form binding sites for metal cations [13]. In summary, flavonoids carrying at least two \(o\)-hydroxyl groups on their B-ring are easily oxidized to quinones by ROS, and their antioxidant capacity is further improved by the presence of a 2,3-double bond, a 4-carbonyl function and 3- and 5-OH groups. Flavores lacking the catechol system exhibit generally weak antioxidant potential because oxidation leads to the formation of unstable radicals that would rather propagate a chain reaction instead of interrupting it [84; 89; 100]. Flavonoids with a phenol-type B-ring, however, have a greater ability to absorb UV-wavelengths than flavonoids with a catechol-type B-ring, indicating that, at least to some extent, structural diversity correlates with functional diversity [101]. Under certain conditions, flavonoids also act as prooxidants, and many different mechanisms have been proposed to explain this phenomenon [102]. Several studies have shown that the prooxidant activity is related to the same functional groups as the antioxidant activity, with quercetin being a strong prooxidant. For example, in human lymphocytes, the generation of superoxide anion radical and products of lipid peroxidation increased with increasing concentration of quercetin, hesperetin or naringenin, and this effect was associated with increasing aroxyl radical formation [103]. The effect of quercetin was much stronger than that of the flavanones hesperetin and naringenin, and this was attributed to the \(\sigma\)-semiquinone and \(\sigma\)-quinone oxidation products, typical for catechol carrying compounds. Quercetin-derived \(\sigma\)-semiquinones and quinones can undergo (futile) redox cycling, with superoxide formed in a pro-oxidant effect [87]. For example, \(Q^{\bullet-}\) can initiate redox cycling by reacting with O\({}_{2}\) to form superoxide and Q [87]:  
\[2Q^{\bullet-}+O_{2}\to Q+O_{2}^{\bullet-} \tag{2}\]  
Moreover, \(\sigma\)-semiquinone and quinone type metabolites may act as electrophiles, forming covalent adducts with DNA, and are therefore mutagenic [88; 104]. Some of the strongest antioxidants in plants are catechins and proanthocyanidins, although they do not fulfill the above criteria [105]. Catechins are flavour-3-ol derivatives and lack the 2,3-double bond, allowing four possible stereoisomers, of which (+)-catechin and (-)-epicatechin are the most common [105]. Catechins carry a catechol B-ring, whereas galloacethins carry a pyrogallol B-ring (3\({}^{\prime}\)- 4\({}^{\prime}\)-, and 5\({}^{\prime}\)-OH groups). Moreover, a gallate (G)-ring is often added to catechins or galloacethins by the esterification of gallic acid with the 3-OH group of the C-ring [85]. Since they lack a 2,3-double bond and often have an esterified 3-OH substituent, the strong antioxidant activity of catechins cannot be attributed to the structural groups mentioned above. Instead, the antioxidant capacity of catechins and their derivatives is directly related to their capacity to multiply the number of neighboring hydroxyl groups within the same molecule [105]. Both the catechol and pyrogallol groups (B- and G-rings) are potential sites for radical attack. The scavenging rates for gallate esters exceed those of diffusion-controlled reactions, because of the presence of several radical target sites within the same molecule (B- and G-rings) [105]. Similarly to flavonoids, disproportionation of the aroxyl (semiquinone) radicals results in the formation of a quinone structure [105]. The semiquinones and quinones formed from proper flavonoids behave, however, distinctly from those derived from flavian-3-ols. Those of catechins (flavan-3-ols) preferentially oligomerize via phenolic coupling reactions.