A planar catechin analogue as a promising antioxidant with reduced prooxidant activity

A planar catechin analogue (1H₂), in which catechol and chroman moieties in (+)-catechin are constrained to be coplanar, is an efficient radical scavenger compared to the native catechin, and are nearly as effective as quercetin, a strong radical scavenger. The dianion (1^2-) of 1H₂ produced by the reaction of 1H₂ with 2 equiv of tetramethylammonium methoxide reduced molecular oxygen (O₂) to generate superoxide anion (O₂^.-). The resulting radical anion (1^.-) from 1H₂ underwent intramolecular proton transfer to give an o-semiquinone radical anion form of 1^.-, which shows a characteristic ESR spectrum with g value of 2.0048. Although the same mechanism has also been shown for (+)-catechin, the rate constant of electron transfer (k_et) from 1^2- to O₂ is about a half of that reported for (+)-catechin, indicating that the electron transfer from 1^2- to O₂ is slower than that from (+)-catechin dianion to O₂. Together with efficient protection against DNA strand breakage induced by the Fenton reaction, the small k_et value for 1H₂ implies that, in physiologically relevant systems, there is less of a possibility of generating oxygen radicals responsible for prooxidant activity with 1H₂ than that with (+)- catechin. The strong radical scavenging ability and less-efficient generation of O_2.- suggest that the planar catechin analogue may be useful for the prevention and/or treatment of free-radical-associated diseases.