Unexpected Role of pH and Microenvironment on the Antioxidant and Synergistic Activity of Resveratrol in Model Micellar and Liposomal Systems

Abstract

Experimental and theoretical studies indicate that resveratrol (RSV, dietary polyphenol that effectively reduces cellular oxidative stress) is a good scavenger of hydroxyl, alkoxyl, and peroxyl radicals in homogeneous systems. However, the role of RSV as a chain-breaking antioxidant is still questioned. Here, we describe pH dependent effectiveness of RSV as an inhibitor of peroxidation of methyl linoleate in Triton X-100 micelles and in 1,2-dimyristoyl- sn -glycero-3-phosphocholine (DMPC) liposomes, with the best effectiveness at pH 6 (stoichiometric factors, n , are 4.9 and 5.6, and the rate constants for reaction with peroxyl radicals, k inh , are 1200 and 3300 M –1 s –1 in micellar and liposomal systems, respectively). We propose the mechanism in which RSV-derived radicals are coupled to dimers with recovered ability to trap lipidperoxyl radicals. The formation of such dimers is facilitated due to increased local concentration of RSV at the lipid–water interface. Good synergy of RSV with α-tocopherol analogue in micelles and liposomes is in contrast to the previously reported lack of synergy in non-polar solvents; however, the increased persistency of tocopheroxyl radicals in dispersed lipid/water systems and proximal localization of both antioxidants greatly facilitate the possible recovery of α-TOH by RSV.

Mutual Activation of Two Radical Trapping Agents: Unusual “Win–Win Synergy” of Resveratrol and TEMPO during Scavenging of dpph• Radical in Methanol

“… f The literature values of p K a1 for RSV are within the range of 6.4–9.7, with the most reliable value ca. 9, see discussion in ref . …”

“…Methanol is also a donor for HB, its parameter of HB acidity, α 2 H = 0.367 . The relative permittivities of methanol and ethyl acetate are 32.7 and 6.0, respectively. c p K a values for RSV: 9.0 (for the 4’OH group), 9.8 and 11.3 (for the 3 and 5 OH group), see the discussion in ref ; p K a predicted for 3,5-DHA is 9.4 …”

“… f The literature values of p K a1 for RSV are within the range of 6.4–9.7, with the most reliable value ca. 9, see discussion in ref . g BDE for the weakest O–H bond in RSV are discussed elsewhere; the values are scattered from 75.3 to 88.5 kcal/mol h In water / methanol (1:1) …”

“…9, see discussion in ref 18. g BDE for the weakest O−H bond in RSV are discussed elsewhere; the values are scattered from 75.3 to 88.5 kcal/mol. 18 The kinetic consequences of reaction 8 were demonstrated in a separate experiment, with TEMPOH introduced to the system (equimolar mixture with RSV), and the reaction was even faster than for RSV/TEMPO • , as can be seen in Table 1. Such an acceleration observed for the RSV/TEMPOH acid/ base pair can be assigned to the SPLET mechanism in the presence of an RSV anion generated in reaction 8, not to HAT from TEMPOH 2 + to dpph • , because BDE O−H for TEMPOH 2 + is much higher than for TEMPOH, see Table 2.…”

Chain-Breaking Antioxidant and Peroxyl Radical Trapping Activity of Phenol-Coated Magnetic Iron Oxide Nanoparticles

“…This mathematical analysis was shown to correctly describe the behaviour of antioxidants at low temperatures (i.e., if ROOH decomposition is negligible) with different oxidizable substrates (methyl linoleate [ 37 ], tetrahydrofuran [ 38 ], squalene [ 39 ], etc.) under various conditions (homogeneous solutions [ 37 , 38 , 39 ], micelles [ 40 ], liposomes [ 41 ]). Equation (1) indicates that the duration of the inhibition period (τ) is proportional to AH concentration and to the stoichiometry of the reaction of AH with radicals, n , while is inversely proportional to the initiation rate R i .…”