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

Abstract

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 0.94 V for D16 in tetrahydrofuran as determined by cyclic voltammetry at 25 °C. The prooxidative effects transform into antioxidative effects from D8 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 Δμ, 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°. 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.

The supramolecular chemistry of lipid oxidation and antioxidation in bulk oils

“…An et al [129] Antioxidative and prooxidative properties are determined by internal factors (i.e., the oxidation substrates, structural organization and the microenvironment for the bioactive compound) and external factors (i.e., heat, pressure, and exposure to light). Hydrophobic alkyl chain increased water insolubility of 7-n-alkoxydaidzeins: daidzein, 7-n-butyloxy-daidzein, 7-n-octyloxy-daidzein, 7-n-dodecyloxy-daidzein, and 7-n-hexadecyloxydaidzein.…”

The nonlinear effect of alkyl chain length in the membrane interactions of phenolipids: Evidence by X‐ray diffraction analysis

“…Indeed, the effectiveness of antioxidants has been shown to increase as a function of increasing alkyl chain length until a threshold is reached for medium alkyl chain, beyond which any lengthening of the chain results in a collapse in this activity. This nonlinear effect, also known as a “cut‐off effect,” has been observed with various phenolipids (with saturated mono‐alkyl as lipophilic moiety) in several compartmentalized systems such as emulsions , liposomes , or living cells . These experiments showed that the lipophilic strength has to be finely tuned since a too low or too strong hydrophobic domain may result in a nonoptimal antioxidant activity.…”

Regioselective synthesis of diacylglycerol rosmarinates and evaluation of their antioxidant activity in fibroblasts

“…Indeed, it was recently demonstrated that antioxidant activity increases as the hydrophobicity of the antioxidant rises until a threshold is reached for a medium lipophilic chain, beyond which any lengthening of the chain results in a collapse in this activity. This nonlinear effect, also known as a cut-off effect, has been observed with various phenolipids in oil-in-water emulsions [29][30][31][32][33], liposomes [34][35][36], and living cells [13,14,37,38]. In all of these studies, the lipophilic moiety was a saturated monoalkyl chain linked onto a carboxylic acid, an alcohol, or a phenolic hydroxyl from a phenolic antioxidant.…”