On the radical scavenging activity of isoflavones: thermodynamics of O–H bond cleavage

Abstract

We have performed Density Functional Theory B3LYP/6-311++G** calculations of reaction enthalpies of antioxidant action mechanisms for nine isoflavones. O-H bond dissociation enthalpies, ionization potentials, proton dissociation enthalpies, proton affinities and electron transfer enthalpies related to Hydrogen Atom Transfer (HAT), Single Electron Transfer-Proton Transfer (SET-PT) and Sequential Proton-Loss Electron-Transfer (SPLET) mechanisms were investigated in gas- and solution-phases. Studies on the radical scavenging ability of isoflavones, contrary to various flavonoids, are still scarce. Thus, understanding of its thermodynamics can be considered beneficial. The selection of isoflavones (daidzein, formononetin, genistein, biochanin A, prunetin, 6-hydroxydaidzein, glycitein, orobol and santal) enables us to evaluate the effects of various structural features, such as the presence of methoxy (4'-OMe, 6-OMe, 7-OMe) and hydroxy (3'-OH, 5-OH, 6-OH) groups, on studied reaction enthalpies. The obtained results show that HAT can be attributed predominantly to the B ring, while SPLET takes place preferentially in the A ring, as was also indicated in experimental works.

Biological activity of clovers – Free radical scavenging ability and antioxidant action of sixTrifoliumspecies

“…of clovamides. A considerable anti-free radical activity has been found for daidzein (Cai et al, 2012), genistein (Cai et al, 1997), and other isoflavones (Lengyel et al, 2013). The presence of clovamides (caffeic acid esters) in T. alexandrinum extract may additionally enhance its free radical scavenging action.…”

Reaction enthalpies of OH bonds splitting-off in flavonoids: The role of non-polar and polar solvent

“…In general, three independent pathways of the antioxidant activity of phenolic compounds (ArOH) were described [2, 3,6] and they are outlined in Scheme 1. The hydrogen atom transfer (HAT) represents the single step radical termination via OAH bond homolytic splitting-off.…”

Theoretical Study of Primary Antioxidant Action Thermodynamics

“…These results are in accordance to the experimental work of Musialik et al (2009), where the authors observed that in ionization supporting solvents, SPLET runs in ring A via deprotonation of 7-OH group of quercetin and HAT/SET-PT occurs from 3',4'-dihydroxy moiety. In the case of isoflavones (Lengyel et al 2013), the situation is very simple: in all environments, the lowest PA values were obtained exclusively for 7-OH groups. This indicates that ring A can play significant role in the SPLET reaction pathway.…”

“…In water, very large drop in PAs was observed, all values are considerably lower than BDEs. Therefore, in water, SPLET represents the thermodynamically preferred mechanism, followed by HAT and SET-PT , Lengyel et al 2013). Here, one should keep in mind that these studies are focused on the thermodynamic preference of studied compounds to enter individual reaction pathways and the dominating process may depend on the type of scavenged free radical.…”

“…Besides, used methods may provide more or less reliable results (Klein and Lukeš 2006b). For 10 flavonoids (apigenin, luteolin, fisetin, kaempferol, quercetin, epicatechin, taxifolin, tricetin, tricin and cyanidin) and 9 isoflavones (daidzein, formononetin, genistein, biochanin A, prunetin, 6-hydroxydaidzein, glycitein, orobol and santal), all three mechanisms of phenolic antioxidant action have been studied in the gas-phase, benzene and water , Lengyel et al 2013. Selected group of compounds enabled to evaluate the effects of various structural features, such as the presence of hydroxy groups in different positions (3'-OH, 3-OH, 5-OH), C2=C3 double bond or C4=O keto group in flavonoids, as well as the effect of 4'-OMe, 6-OMe, 7-OMe, 3'-OH, 5-OH and 6-OH groups in isoflavones on relevant reaction enthalpies, see carbon atoms numbering in Fig.…”