Chain Length Effects in Isoflavonoid Daidzein Alkoxy Derivatives as Antioxidants: A Quantum Mechanical Approach

Daidzein, an isoflavonoid with known prooxidative effects, in heterogeneous lipid/water systems, changes to an antioxidant for 7-n-alkoxy derivatives of daidzein. For an alkyl length increasing from 4 to 8, 12, and 16 carbons, the oxidation potential decreases gradually. from 1.09 V (vs NHE) for daidzein (D) to 0.9.4V for D16 in tetrahydrofuran as determined by cyclic voltammetry at 25 degrees C. The prooxidative effects transform into antioxidative effects from 68 with a maximal effect for D12 for aqueous phase initiation of lipid oxidation in liposomes despite a gradual decrease in Trolox equivalent antioxidant capacity (TEAC) with increasing alkyl chain length. Quantum mechanical calculations using density functional theory (DFT) showed that the bond dissociation energy of the O-H bond of the 4'-phenol is constant along the homologue series in contrast to Delta mu, the change in dipole moment upon hydrogen atom donation, which increases for increasing chain length: The frontier orbital energy gap goes through a maximum for D12. The change in the A-to-B dihedral angle upon hydrogen atom donation further shows a maximum for D12 of 6.45 degrees. The importance of these microscopic properties for antioxidative activity was confirmed by a change in liposome fluorescence anisotropy using a fluorescent probe showing maximal penetration into the lipid bilayer for D12 along the homologue series.