Hyroxyl groups & Planarity of Quercetin- Essential for antioxidant activity

It is the fact that polyphenols are considered as good antioxidants and have wide range of biological activities. In my earlier posts, role of polyphenol epigallocatechin-3-gallate in cancer prevention and neuroprotection were discussed. Recently, researchers have published the antioxidant activity and structure-activity relationship study (SAR) of polyphenol quercetin and its derivatives. They found that hydroxyl groups and planar conformation of the quercetin has an important role for antioxidant activity.

SAR study

For SAR study, authors have prepared various quercetin derivatives by methylation of hydroxyl groups or incorporation of bulky groups like rutinosyl and hydroxyethyl. O-methylation of all hydroxyl groups resulted in complete loss of antioxidant activity whereas O-methylation at 5 and 7 position has less effect on antioxidant activity. They found that the compound with rutinosyl group at 3-O position has less antioxidant capacity than the quercetin and 3-O methylated compound. They determine the dihedral angles (angle between the plane of the AC-ring and B-ring) for these three compounds. Quercetin, with highest antioxidant capacity, has the least dihedral angle and compound with rutinosyl group has the largest dihedral angle.

According to authors, the planar structure of quercetin allows the conjugated π-system of the AC-ring and B-ring to efficiently interact which distributes the electron donating effect of the OH groups over the whole molecules, enabling the cooperation of electron donors in the different rings. Bulky groups at 3-position forces the B-ring out of the plane of the AC-ring which diminishes the efficiency of the conjugated π-system found in Q, leading to a relatively low antioxidant activity.