# Origin and Function of Structural Diversity in the Plant Specialized Metabolome
## 3 Structure-Antioxidant Activity Relationships of Flavonoids
Even the effect of the oxonium ion in the core structure of anthocyanins, leading to a higher redox potential than the more electron-rich oxygen-ether in flavonoids, is annihilated by increasing numbers of -OH substituents on the B-ring. For example, the redox potential of kaempfer is much lower than the redox potential of pelargonidin (both carrying a single -OH group on the B-ring); however, myricetin and delphinidin (both carrying three -OH groups on the B-ring) have similar redox potentials [90]. In flavones, which lack a 3-OH group, the most reactive hydroxyl group is the 7-OH group, situated on the A-ring [13]. The efficiency of flavonoids as antioxidants depends not only on the radical scavenging capacity, but also on the stability of the radical formed after scavenging. Highly reactive secondary radicals would propagate a chain reaction rather than interrupting it [84]. A  
Figure 6: Structures of flavonoids. measure of the reactivity of radicals is their decay rate in a second-order dismutation (also called disproportionation) process, in which two radicals convert to one compound of higher and one of lower oxidation state. The stability of flavonoid radicals is expected to increase with the extension of the conjugated system. Three structural groups are determining for the radical scavenging and/or antioxidative potential of flavonoids [84]. First, a \(3^{\prime}A^{\prime}\)-dihydroxy (catechol) structure of the B-ring, as in epicatechin, rutin or quercetin, is a major radical target site, and participates in electron delocalization, conferring a higher stability of the aroxyl radical. The aroxyl radical formed is, in that case, an \(o\)-semiquinone (\(Q^{\bullet-}\)). Flavonoids that lack the catechol structure, even if they can be highly efficient radical scavengers such as kaempfer, decay too fast to be potent antioxidants [84]. The determining role of the catechol structure for antioxidant activity has similarly been observed in lignans. Lignans with catechol moieties exhibit the highest radical scavenging capacity, whereas the corresponding guaiacyl (i.e., 3-methoxy-4-hydroxyphenyl) derivatives show a slightly weaker scavenging capacity [98]. A second determining structural group is the 2,3-double bond in conjugation with a 4-oxo function. This combination allows tautomerization of the aroxyl (\(o\)-semiquinone) radical into a semiquinone method, which results in a conjugated system involving all three ring systems (A, B and C). Such extensive electron delocalization provides extra stability to the aroxyl radical [84]. For example, especially in monocots, the flavonoid tricin, which does not contain a catechol B-ring but does contain the 2,3-double bond in conjugation with a 4-oxo function, is oxidized in the cell wall and used as a monomer during lignin polymerization [99]. Finally, the third important functional group is the additional presence of 3- and 5-OH groups in the A-ring [84]. All polyphenol \(o\)-semiquinone radicals can decay by bi-molecular disproportionation to form the more stable \(o\)-quinone (Q) and the parent hydroxy compound, as follows in the case of quercetin [87]:  
\[2Q^{\bullet-}\to Q+quercetin \tag{1}\]  
The 3- and 5-OH groups in the A-ring allow tautomerization of o-quinone into three quinone methides and contribute to an increased radical-scavenging potential [84; 88]. The tautomerization depends on the rearrangement of the 3-OH group on the heterocyclic (the C-ring) to form a 3-keto group. Lack of the 3-OH thus prevents quinone methide isomerization. The availability of the 3-OH group, however, also depends on the presence of a 5-OH group on the A-ring. In flavonoids lacking a 5-OH, the 4-keto group forms a hydrogen bond with the 3-OH group, making the latter unavailable for tautomerization to a 3-keto group. A 5-OH group, however, forms an alternative hydrogen bond with the 4-keto group, leaving the 3-OH group more available for tautomerization [88]. The presence of both 3- and 5-OH groups enables, thus, the formation of stable quinonic structures upon flavonoid oxidation.