| As an important water-soluble antioxidant, Vitamin C (Vc, L-ascorbic acid) exists universally in various biological systems and has multiple physiological functions. In the present study, both the molecular structures of Vc and its derivatives and the process of antioxidation behaviors of Vc are studied using the density functional theory (DFT) in combination with the atoms in molecules (AIM) theory, natural bond orbital (NBO) theory and energy decomposition analysis (EDA). The relations between the antioxidant properties of Vc and its stucture are discussed. Furthermore, the mechanisms of scavenging free radicals (·H and·OH) by Vc as well as the coupling of Vc with a functional molecule, i.e., methylglyoxal (MG), is investigated.Three aspects are investigated systematically in the study:Firstly, the most stable conformer of Vc in the gas phase is obtained on the basis of two crystal structures of Vc at the B3LYP/6-311++G** level of theory. Based on the most stable conformer, some important properties of Vc, such as the gas phase acidity (AGacid), bond dissociation energy (BDE) and so on, are calculated to further evaluate the acidity and antioxidation of Vc. As a result, the sequence of stepwise proton dissociation of Vc has been determined. The BDEs of different forms of Vc (AAH2, AAH-, AA2-, AAH3+, and AA) are obtained to investigate the possible environment influences, especially for the pH values, on the antioxidation of Vc. Comparing the BDE values of different forms of Vc, it is found that the antioxidation of Vc is stronger under neutral or basic conditions.In the second part, the process of the capture of free radicals (·H and·OH) by Vc is investigated, which mainly involves two mechanisms, i.e., free radical addition and H-abstraction. Both mechanisms are studied systematically. As for the free radical addition reactions, all of the sites associated with the double bond in the five-membered ring of Vc are considered. It is found that the most reactive site is confirmed to be the C2 site for the monoanionic form of Vc (AAH-) while it is the C3 site for the neutral Vc, which suggests that the reactivity of Vc has a strong pH dependence for the radical addition reactions. Moreover, it is a diffusion-controlled reaction for the radical addition. As for the H-abstraction reactions, all of the hydrogen sites have been investigated. Generally, the H-abstraction occurs more readily than the free radical addition, especially for the H13, H14, and H15 abstraction. However, it is difficult to detect the radicals produced by H14 and H15 abstractions experimentally due to the instabilities of them thermodynamically. Moreover, two types of concerted proton-electron transfer (CPET) mechanisms involved in the H13 abstraction are discussed in detail, which are the predominant source for the formation of anion free radical (AFR) detected experimentally. Finally, the nature of the coupling interactions between Vc and MG has been systematically investigated. It is well known that MG is a potent anticancer agent, and the anticancer effect can be significantly enhanced in the presence of Vc. In the present study, the possible complexes formed between Vc and MG have been investigated to clarify the possitive role of Vc in the augment of the anticancer effect of MG. As a result, twenty three stable complexes are obtained with the binding energies varying from -1.73 to -6.91 kcal/mol. All the complexes are characterized by the single or double intermolecular H-bonds. Moreover, further AIM analyses suggest that these H-bonds are predominated by the closed-shell (electrostatic) interactions. Additionally, the one-electron oxidation behaviors of the most stable complex have been studied. It is found that MG can be effectively protected at the cost of the oxidation of Vc. Thus, the intrinsic strong reduction property of Vc should be responsible for its augment role in the anticancer process for MG. |
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