Single-atom rhodium mimicking the oxidase and peroxidase for NADH cascade oxidation

Constructing high-performance nanozymes for specific biomolecules is crucial but challenging for practical applications and fundamental research. Herein, through the examination of the catalytic reaction paths of natural nicotinamide adenine dinucleotide (NADH) oxidase (NOX), a novel and efficient single-atom rhodium catalyst (Rh₁/NC) was developed to mimic NOX. The Rh₁/NC demonstrated the ability to catalyze the dehydrogenation of NADH and transfer electrons to O₂ to generate H₂O₂ through the typical two-electron pathway. Furthermore, our findings revealed that Rh₁/NC exhibits the ability to catalyze the conversion of produced H₂O₂ into OH under mildly acidic conditions. This process amplifies the oxidation of NADH, showcasing NADH peroxidase-like activity (NPx-like). As a paradigm, this unique dual enzyme-like property of Rh₁/NC with a positive feedback effect holds significance in disrupting cancer cellular homeostasis. Rh₁/NC can effectively consume NADH via cascade biocatalytic reactions within cancer cells, further triggering the elevation of reactive oxygen species (ROS), leading to impaired oxidative phosphorylation and decreased mitochondrial membrane potential, thus damaging the adenosine triphosphate (ATP) synthesis. The resulting 'domino effect' interferes with the energy metabolism homeostasis of cancer cells, ultimately promoting cell apoptosis. This study provides potential guidance for the rational design of materials with greater capabilities.

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