ABSTRACT
CONTEXT: This theoretical study explores the antioxidant activity of five bromophenol analogs, with a particular focus on their interaction with different solvent environments of varying polarities. Key findings include the correlation between increased solvent polarity and enhanced antioxidant activity of these analogs, comparable in some instances to ascorbic acid. Notably, compound 5, developed by our research team, demonstrates superior antioxidant activity in both lipid and aqueous solutions, surpassing that of ascorbic acid and other tested analogs. This research contributes to the understanding of bromophenol analogs, presenting the first known kinetic and chemical stability data such as rate constants, pKa values, and branching ratios for reactions with the methylperoxyl radical (CH3OOâ¢). METHODS: The computational analyses were conducted using the Gaussian 09 software suite at the M05-2X/6-31 + G(d) computational level. These analyses employed conventional transition state theory to account for various potential mechanisms and effects of solvent polarity on the antioxidant activities of bromophenol analogs. The study meticulously calculated enthalpy under standard conditions (298.15 K and 1 atm) with necessary thermodynamic corrections. Additionally, the Quantum Mechanics-based Test for Overall Radical Scavenging Activity (QMORSA) protocol guided the evaluation of radical scavenging activity, ensuring a comprehensive assessment of the antioxidant potential of the compounds.
ABSTRACT
CONTEXT: In this study, we investigated the antioxidant potential of a novel ascorbic acid analog, DsD, assessing its interactions with the methylperoxyl (CH3OO·) radical in aqueous and lipid environments. Our focus was on understanding the acid-base equilibrium and how pH affects DsD's primary reaction mechanisms. Our findings indicate a marked preference for hydrogen atom transfer in lipid media, contrasting with sequential proton loss electron transfer (SPLET) in aqueous solutions. Remarkably, DsD's radical scavenging activity significantly outperforms ascorbic acid, being 4.05 and 9469.70 times more potent in polar and lipid contexts, respectively. This suggests DsD's superior efficacy as an antioxidant, potentially offering enhanced protection in biological systems. Additionally, we have demonstrated DsD's synthetic feasibility through a straightforward condensation reaction between ascorbic acid and 1,2-diaminoethane, followed by comprehensive physicochemical and spectroscopic characterization. METHODS: All computational analyses in this study were conducted using the Gaussian 09 software suite, employing the M05-2X functional and the 6-31 + G(d) basis set. Enthalpy calculations were executed under standard conditions (298.15 K and 1 atm), incorporating appropriate thermodynamic corrections. Rate constants were evaluated using transition state theory (TST), and the overall assessment of radical scavenging activity was guided by the Quantum Mechanics-based Test for Overall Radical Scavenging Activity (QMORSA) protocol.
