Biomimetic Phosphohydrolase Nanozyme Based on Defect- Engineered Metal-Organic Framework

Phosphodiester bonds are the backbone linkages of all the nucleic acids which store and transfer biological information. The hydrolysis of phosphodiester bonds is of great importance to the replication, recombination, and damage repair of DNA as well as the maturation and processing of RNA. However, the spontaneous scission of individual phosphodiester linkages is kinetically challenging under physiological conditions, with an estimated half-life of 30 million years. Here, we discover a defect -engineered Zr-metal-organic framework (Zr-MOF) nanozyme containing cluster-missing reo defects, named UiO-66 REO, that possesses intrinsic phosphodiesterase-like activity that allows for the cleavage of the phosphodiester bond in physiological condition (pH = 7.4 and 37 degrees C), outperforming the activity recording Zr-MOFs. The atomic-level structure of the UiO-66 REO nanozyme has been directly identified by the synchrotron radiation absorption spectrum and integrated differential phase contrast-scanning transmission electron microscopy. We find that both the defective boundary regions and unusual Zr6-clus-ters formed in the reo phase of the UiO-66 REO nanozyme contribute to the improvement in efficiency of phosphodiesterase-like hydrolysis, which realizes the cleavage of DNA in mild conditions. This work offers a new insight into biomimetic enzymology using crystal and defect engineering and opens up new possibilities for the development of low-cost, structurally stable and sustainable phosphodiesterase nanozymes for different biological applications.