How curcumin works preferentially with water soluble antioxidants

In this study we investigated physicochemical characteristics of the curcumin radical by pulse radiolysis and laser flash photolysis. Two methylated curcumin derivatives, methylcurcumin and trimethylcurcumin, were synthesized to explore the role of phenol hydroxy and beta-diketone moieties in the free radical chemistry of curcumin. Our results show that the initially generated beta-oxo-alkyl transforms rapidly, probably via an intramolecular H-atom shift, into the phenoxyl-type curcumin radical. This phenoxyl does not react with oxygen, k < 10(5) M(-1) s(-1), and can be repaired by any water-soluble antioxidant with appropriate redox potential, E(6) < 0.83 V, for example, with vitamin C, k = (6 +/- 1) x 10(6) M(-1) s(-1). A molecular mechanism of cancer chemoprevention by curcumin is proposed, with special emphasis on the synergism with water-soluble antioxidants.