Thermodynamic Inference of the Antioxidant Process of Malic Acid and Its Structural Analogs

Two structural analogs of Malic Acid (MA), 2-isopropylmalic Acid (2-IPMA), and 3-isopropylmalic Acid (3-IPMA) were recently identified and separated from wine. Although they have been shown to have antioxidant activity, the mechanism of their actions is still unclear. Antioxidant activities of 2-IPMA and MA were tested through DPPH, ABTS, and PTIO methods and the antioxidant-related thermodynamic properties were evaluated using Density Functional Theory (DFT) to deduce their thermodynamic process and antioxidant mechanism. Results showed that all three organic acids had the potential to scavenge free radicals and 2-IPMA showed higher antioxidant activity. In addition, the C2-hydroxy groups of 2-IPMA and 3-IPMA showed the antioxidant activity. As the singlet state of most antioxidants is more stable than the triplet state, it was predicted that 2-IPMA and 3-IPMA would lose hydrogen through double Hydrogen Atom Transfer (HAT), Sequential double Proton Loss Double Electron Transfer (SPLET) and Double Electron Transfer Proton Transfer (dET-PT) methods in gas-phase to form 4-methyl-3-oxopentanoic acid and 3-methyl-2-formylbutyric acid, respectively. Based on the principle of minimum consumption first occurrence, the pathways of 2-IPMA and 3-IPMA to radical scavenging were in the following order: HAT, Bond Dissociation Energy (BDE), and SPLET. The results of the calculation confirmed the hypothesis of this study and suggested that the oxidation resistance of the two MA analogs favored the HAT process in terms of reaction enthalpy thermodynamics.