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 (O-center dot(2)- 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)-O-center dot) is predicted to occur simultaneously with the SOD and CAT biomimetic reactions, resulting in the formation of hydroxyl radicals, making CeO2 a cytotoxic prooxidant.

Automated summary

There is significant interest in the pH-dependent properties of cerium oxide nanoparticles, which exhibit antioxidant activity at basic pH but cytotoxic prooxidant activity at acidic cancer cell pH. This study investigates the atomic-scale behavior of CeO2 nanoparticles with oxygen vacancies under different pH conditions using density functional theory calculations. The results suggest that pH plays a critical role in the interaction between reactive oxygen species and the defective CeO2 surface, leading to either antioxidant or prooxidant activity.