Role of Explicit Hydration in Scavenging of CO3•− by Trolox: A DFT Study

Increasing evidence suggests that, under physiological conditions, the carbonate anion radical CO₃^•- could be the major source of oxidative stress, instead of the commonly accepted hydroxyl radical HO^•. In aqueous solutions, CO₃^•- exists as a hydrated species, which may influence its properties and activities. CO₃^•- acts as a one-electron oxidant via a single electron transfer (SET) mechanism. Impact of the number of explicit water molecules (0, 4, 6, and 9) on inactivation of CO₃^•- by Trolox, a water-soluble analog of α-tocopherol, was theoretically investigated using the DFT approach. Also, the role of Trolox solvation by H-bonded water molecules was examined. The obtained results indicate that an increased number of explicit water molecules in CO₃^•- hydration shell increases exergonicity and decreases the reaction barrier of the SET pathway, causing minor alterations of intrinsic reactivity, i.e., apparent rate constant. Amongst Trolox species, explicit hydration of the dianion has a notable impact on the reaction rate. Trolox belongs to phenolic antioxidants, but electron transfer to CO₃^•- proceeds from the aromatic part of the chroman moiety rather than from the phenoxide or carboxylate group of ionic species. The presented microhydration approach may serve as a way for estimating the potency of natural and synthetic compounds to suppress oxidative damage caused by CO₃^•-, a topic scarcely computationally considered so far.