  There is considerable interest in the pH-dependent, switchable, biocatalytic
properties of cerium oxide (CeO2) nanoparticles (CeNPs) in biomedicine, where
these materials exhibit beneficial antioxidant activity against reactive oxygen
species (ROS) at basic physiological pH but cytotoxic prooxidant activity in
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 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+ and Ce4+ and formation and
annihilation of oxygen vacancies. A Fenton biomimetic reaction is predicted to
occur simultaneously with the SOD and CAT biomimetic reactions, resulting in
the formation of hydroxyl radicals, making CeO2 a cytotoxic prooxidant.
