DFT Investigation of Biocatalytic Mechanisms from pH-Driven, Multi-Enzyme, Biomimetic Behavior in CeO2

TL;DR

This study uses DFT calculations to elucidate how pH influences the biocatalytic antioxidant and prooxidant activities of CeO2 nanoparticles by examining atomic-scale interactions at the {111} surface with oxygen vacancies.

Contribution

It provides a detailed atomic-scale understanding of pH-dependent biocatalytic mechanisms of CeO2, highlighting the role of oxygen vacancies in switching between antioxidant and prooxidant behaviors.

Findings

CeO2 exhibits antioxidant activity at basic pH through SOD and CAT mimetic reactions.

At acidic pH, CeO2's biomimetic reactions are hindered, leading to potential cytotoxicity.

Fenton reactions may occur at low pH, producing hydroxyl radicals.

Abstract

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.