Bond dissociation enthalpies calculated by the PM3 method confirm activity cliffs in radical scavenging of flavonoids

Radical scavenging potency of flavonoids is associated with activity cliffs, i.e., small chemical modifications on flavonoid core can have a significant effect on activity. The presence or absence of the 3',4'-diOH and/or 3-OH group may serve as an activity switch for radical scavenging. The physicochemical background of such an indicator variable, defined previously (Ami&Aumlaut double dagger et al. (2003) Croat Chem Acta 76:55-61), is confirmed by computation of bond dissociation enthalpies and selecting the minimal of all values relating to flavonoid OH groups. Bond dissociation enthalpies for hydrogen abstraction from OH groups for 29 flavonoids were calculated by the PM3 method. Minimal bond dissociation enthalpy values were obtained for OH groups attached to C-3, C-3' and C-4' positions, and they correspond to the previously introduced indicator variable. Taking into account some driving forces of the radical scavenging mechanism, it is possible to relate structural characteristics of flavonoids to their radical scavenging potency as well as to develop reliable structure-activity models.