Density Functional Theory Investigation of the Biocatalytic Mechanisms of pH-Driven Biomimetic Behavior in CeO₂

There is considerable interest in the pH-dependent, switchable, biocatalytic properties of cerium oxide (CeO₂) nanoparticles in biomedicine, where these materials exhibit beneficial antioxidant activity against reactive oxygen species (ROS) at a basic physiological pH but cytotoxic prooxidant activity in an acidic cancer cell pH microenvironment. While the general characteristics of the role of oxygen vacancies are known, the mechanism of their action at the atomic scale under different pH conditions has yet to be elucidated. The present work applies density functional theory (DFT) calculations to interpret, at the atomic scale, the pH-induced behavior of the stable {111} surface of CeO₂ containing oxygen vacancies. Analysis of the surface-adsorbed media species reveals the critical role of pH on the interaction between ROS (^•O₂^– and H₂O₂) and the defective CeO₂ {111} surface. Under basic conditions, the superoxide dismutase (SOD) and catalase (CAT) biomimetic reactions can be performed cyclically, scavenging and decomposing ROS to harmless products, making CeO₂ an excellent antioxidant. However, under acidic conditions, the CAT biomimetic reaction is hindered owing to the limited reversibility of Ce³⁺ ↔ Ce⁴⁺ and formation ↔ annihilation of oxygen vacancies. A Fenton biomimetic reaction (H₂O₂ + Ce³⁺ → Ce⁴⁺ + OH^– + ^•OH) is predicted to occur simultaneously with the SOD and CAT biomimetic reactions, resulting in the formation of hydroxyl radicals, making CeO₂ a cytotoxic prooxidant.