Theoretical Study of Radical Inactivation, LOX Inhibition, and Iron Chelation: The Role of Ferulic Acid in Skin Protection against UVA Induced Oxidative Stress

Ferulic acid (FA) is used in skin formulations for protection against the damaging actions of the reactive oxygen species (ROS) produced by UVA radiation. Possible underlying protective mechanisms are not fully elucidated. By considering the kinetics of proton-coupled electron transfer (PCET) and radical-radical coupling (RRC) mechanisms, it appears that direct scavenging could be operative, providing that a high local concentration of FA is present at the place of •OH generation. The resulting FA phenoxyl radical, after the scavenging of a second •OH and keto-enol tautomerization of the intermediate, produces 5-hydroxyferulic acid (5OHFA). Inhibition of the lipoxygenase (LOX) enzyme, one of the enzymes that catalyse free radical production, by FA and 5OHFA were analysed. Results of molecular docking calculations indicate favourable binding interactions of FA and 5OHFA with the LOX active site. The exergonicity of chelation reactions of the catalytic Fe2+ ion with FA and 5OHFA indicate the potency of these chelators to prevent the formation of •OH radicals via Fenton-like reactions. The inhibition of the prooxidant LOX enzyme could be more relevant mechanism of skin protection against UVA induced oxidative stress than iron chelation and assumed direct scavenging of ROS.

From Reduction to Oxidation: pH Controlled Reaction of 1 Hydroxyethyl Radical with Caffeic Acid Analogues.

Aims: The aim is to search for newer and better antioxidants through kinetic spectroscopic studies in combination with product analysis and computation. Background: Antioxidant effect of caffeic acid, its derivative, and analogues have been well reported. The antioxidative efficiencies are related to their molecular structure, and two reaction pathways are well accepted, H-atom transfer (HAT) or single electron transfer. 1-hydroxy ethyl radical (1-HER) being an ethanol-derived free radical might be causing the onset of liver injury detected after alcohol administration. 1-HER has also been reported to react with fatty acids and endogenous antioxidants such as glutathione, ascorbic acid, and alpha-tocopherol Objective: The present study is an attempt to understand the reaction mechanism of 1-HER with caffeic acid, its derivative, and analogues in detail. Method: Pulse radiolysis with kinetic absorption spectroscopy has been employed to follow the reaction pathway and identify the intermediates produced in the reaction. The reaction products have been detected using LCMS/MS. Based on these studies, a consolidated mechanism has been proposed. Cyclic voltammetry measurements and computational calculations have been used in support of the proposed mechanism. Result: In the reaction of 1-hydroxy ethyl radical (1-HER) with caffeic acid and its oligomers, reduction takes place below the pKa1, while oxidation occurs with the deprotonated phenolic moiety. The reduction of caffeic acid generates a carbon-centered radical at the double bond of the side chain with a bimolecular rate constant of 1.5x1010 dm3 mol-1 s-1. Notably, a low concentration of oxygen was able to regenerate a part of the caffeic acid molecules in the reduction process. At pH 10 a phenoxyl radical is formed due to oxidation with a much lower bimolecular rate constant (4.2x108 dm3 mol-1 s-1). In the case of di-hydrocaffeic acid, only phenoxyl radical is formed at pH 10 and, no reaction could be observed below pH 8. Conclusion: Change in reactive pattern from reduction to oxidation with change in pH within the same set of reactants has been evidently established in the present study. The results point towards the importance of  unsaturation in the side chain of caffeic acid oligomers for their reaction with 1-HER at neutral pH. The effect of oxygen concentration on the antioxidative protection offered by this class of molecules might be intriguing for the quest of the effectiveness of antioxidants at low concentrations. Other: It may be inferred that the effect of pH on the reactivity pattern as observed is not 1-HER, but substrate-specific, in the present case, phenolic acids. This study generates further scope for in-depth studies on other polyphenols where unsaturation exists in the side chain.

Photochemical reaction kinetics and mechanism of bisphenol A with K2S2O8 in aqueous solution: a laser flash photolysis study

The photochemical reaction kinetics and mechanism of bisphenol A (BPA) with potassium persulfate (K2S2O8) were investigated by using 266 nm laser flash photolysis and gas chromatography mass spectrum (GC-MS) technique. Sulfate radical (SO4•−), generated upon K2S2O8 photolysis, reacted with BPA with the overall rate constant of (1.61 ± 0.15) × 109 L mol−1 s−1, and two main reaction mechanisms were involved. One was addition channel to generate BPA–SO4•− adduct with a specific second-order rate constant of (1.09 ± 0.15) × 109 L mol−1 s−1. Molecular oxygen was involved in the decay of the BPA–SO4•− adduct with a rate constant of (1.28 ± 0.14) × 108 L mol−1 s−1. Another channel was the formation of BPA’s phenoxyl radical, likely derived from a deprotonation of the cation radical (BPA•+) generated from single electron transfer reactions. The specific rate constant of BPA’s phenoxyl radical formation was determined to be (6.16 ± 0.08) × 108 L mol−1 s−1. The overall rate constant was in line with the sum of aforementioned two specific rate constants for two main reaction channels. By comparing these rate constants, it was indicated that SO4•− addition channel accounted for ∼65% (1.09/1.61) to the overall reaction, and phenoxyl radical formation accounted for only ∼35% (0.62/1.61). The transformation products of BPA were identified by using GC-MS including 4-isopropylphenol, 4-isopropenylphenol, and 2,4-di-tert-butylphenol, and the reaction mechanism was proposed. These results may provide microscopic kinetics and mechanism information on BPA degradation using SO4•−-based advanced oxidation processes.

Formation of the Ni(II)-Phenoxyl Radical Complexes by O2: A Mechanistic Insight into the Reaction of Ni(II)-Phenol Complexes with O2

Reaction of Ni(ClO4)2•6H2O with a tripodal ligand having two di(tert-butyl)phenol moieties, H2tbuL, and 1 equivalent of triethylamine in CH2Cl2/CH3OH (1:1 v/v) under N2 gave a Ni(II)-(phenol)(phenolate) complex, [Ni(HtbuL)(CH3OH)2]ClO4. Formation of...

Polyfunctional Sterically Hindered Catechols with Additional Phenolic Group and Their Triphenylantimony(V) Catecholates: Synthesis, Structure, and Redox Properties

New polyfunctional sterically hindered 3,5-di-tert-butylcatechols with an additional phenolic group in the sixth position connected by a bridging sulfur atom—(6-(CH2-S-tBu2Phenol)-3,5-DBCat)H2 (L1), (6-(S-tBu2Phenol)-3,5-DBCat)H2 (L2), and (6-(S-Phenol)-3,5-DBCat)H2 (L3) (3,5-DBCat is dianion 3,5-di-tert-butylcatecolate)—were synthesized and characterized in detail. The exchange reaction between catechols L1 and L3 with triphenylantimony(V) dibromide in the presence of triethylamine leads to the corresponding triphenylantimony(V) catecholates (6-(CH2-S-tBu2Phenol)-3,5-DBCat)SbPh3 (1) and (6-(S-Phenol)-3,5-DBCat)SbPh3 (2). The electrochemical properties of catechols L1–L3 and catecholates 1 and 2 were investigated using cyclic voltammetry. The electrochemical oxidation of L1–L3 at the first stage proceeds with the formation of the corresponding o-benzoquinones. The second process is the oxidation of the phenolic moiety. Complexes 1 and 2 significantly expand their redox capabilities, owing to the fact that they can act as the electron donors due to the catecholate metallocycle capable of sequential oxidations, and as donors of the hydrogen atoms, thus forming a stable phenoxyl radical. The molecular structures of the free ligand L1 and complex 1 in the crystal state were determined by single-crystal X-ray analysis.