Pore‐Environment‐Dependent Photoresponsive Oxidase‐Like Activity in Hydrogen‐Bonded Organic Frameworks

Abstract Mimicking the bioactivity of native enzymes through synthetic chemistry is an efficient means to advance the biocatalysts in a cell‐free environment, however, remains long‐standing challenges. Herein, we utilize structurally explicit hydrogen‐bonded organic frameworks (HOFs) to mimic photo‐responsive oxidase, and uncover the important role of pore environments on mediating oxidase‐like activity by means of constructing isostructural HOFs. We discover that the HOF pore with suitable geometry can stabilize and spatially organize the catalytic substrate into a favorable catalytic route, as with the function of the native enzyme pocket. Based on the desirable photo‐responsive oxidase‐like activity, a visual and sensitive HOFs biosensor is established for the detection of phosphatase, an important biomarker of skeletal and hepatobiliary diseases. This work demonstrates that the pore environments significantly influence the nanozymes’ activity in addition to the active center.