Daidzein as an antioxidant of lipid: effects of the microenvironment in relation to chemical structure.

Isoflavone daidzein (D, pK a1 = 7.47 +/- 0.02 and pK a2 = 9.65 +/- 0.07) was, through a study of the parent compound and its three methyl anisol derivatives 7-methyldaidzein (7-Me-D, pK a = 9.89 +/- 0.05), 4'-methyldaidzein (4'-Me-D, pK a = 7.43 +/- 0.03), and 7,4'-dimethyldaidzein (7,4'-diMe-D), found to retard lipid oxidation in liposomal membranes through two mechanisms: (i) radical scavenging for which the 4'-OH was more effective than the 7-OH group in agreement with the oxidation potentials: 0.69 V for 4'-OH and 0.92 V for 7-OH versus Ag/AgCl in acidic solution and 0.44 V for 4'-O(-) and 0.49 V for 7-O(-) in alkaline solution and (ii) change in membrane fluidity through incorporation of the isoflavones, in effect hampering radical mobility. The radical scavenging efficiency measured by the rate of the reaction with the ABTS(*)(+) in aqueous solution followed the order D > 7-Me-D > 4'-Me-D > 7,4'-diMe-D, as also found for antioxidant efficiency in liposomes when oxidation was initiated with the water-soluble AAPH radical and monitored as the formation of conjugate dienes. For oxidation initiated by the lipid-soluble AMVN radical, the antioxidant efficiency was ranked as 4'-Me-D > D > 7,4'-diMe-D > 7-Me-D, and change in fluorescence anisotropy of fluorescent probes bound to the membrane surface or inside the lipid bilayer confirmed the effects of isoflavones on the membrane fluidity, especially for 7,4'-diMe-D.