Solvent-free Povarov reaction for synthesizing ferrocenyl quinolines: Antioxidant abilities deriving from ferrocene moiety

• Twenty-two ferrocenyl quinolines were synthesized by solvent-free Povarov reaction.
• Ferrocenyl instead of hydroxyl group can reduce radicals directly.
• Ferrocenyl exhibits higher ability to inhibit DNA oxidation than hydroxyl group.

Twenty-two 2-phenyl-4-ferrocenylquinolines are synthesized by Povarov three-component-reaction (3CR) among the substituted anilines, benzaldehydes, and ferrocenylacetylene with Ce(OTf)3 being catalyst in the absence of solvents. The antioxidative effects of the obtained quinolines are estimated by quenching 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+), 2,2′-diphenyl-1-picrylhydrazyl (DPPH), and galvinoxyl radicals, and by inhibiting Cu2+/glutathione (GSH)-, hydroxyl radical (OH)–, and 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidations of DNA. It is found that the ferrocenyl group instead of hydroxyl group generates the antioxidative effect for quinoline to quench radicals and to protect DNA against radical-induced oxidations. The antioxidative effect generated by ferrocenyl group can be further increased by the electron-donating moieties such as furan, –N(CH3)2, –OCH3, and ferrocenyl group, while the electron-withdrawing groups such as –NO2 and –Cl are not beneficial for quinolines to be antioxidants. The ferrocenyl group in quinoline exhibits higher antioxidant activity than hydroxyl group in Trolox.

The ferrocenyl group instead of hydroxyl group makes quinoline an antioxidant to inhibit DNA oxidation and to scavenge radicals.Figure optionsDownload as PowerPoint slide