Metal–organic frameworks (MOFs) have attracted significant research interest in biomimetic catalysis. However, the modulation of the activity of MOFs by precisely tuning the coordination of metal nodes is still a significant challenge. Inspired by metalloenzymes with well-defined coordination structures, a series of MOFs containing halogen-coordinated copper nodes (Cu-X MOFs, X = Cl, Br, I) are employed to elucidate their structure–activity relationship. Intriguingly, experimental and theoretical results strongly support that precisely tuning the coordination of halogen atoms directly regulates the enzyme-like activities of Cu-X MOFs by influencing the spatial configuration and electronic structure of the Cu active center. The optimal Cu–Cl MOF exhibits excellent superoxide dismutase-like activity with a specific activity one order of magnitude higher than the reported Cu-based nanozymes. More importantly, by performing enzyme-mimicking catalysis, the Cu–Cl MOF nanozyme can significantly scavenge reactive oxygen species and alleviate oxidative stress, thus effectively relieving ocular chemical burns. Mechanistically, the antioxidant and antiapoptotic properties of Cu–Cl MOF are achieved by regulating the NRF2 and JNK or P38 MAPK pathways. Our work provides a novel way to refine MOF nanozymes by directly engineering the coordination microenvironment and, more significantly, demonstrating their potential therapeutic effect in ophthalmic disease.

Self‐assembled nanostructures based on biomolecules (e.g., proteins and amino acids) and metal ions have promising applications in mimicking the nanostructure, properties, and functions of natural enzymes. Herein, a metal ion‐mediated self‐assembly method for constructing catalytically active Cu‐wool‐keratin (CuWK) two‐dimensional nanozymes is presented. Specifically, by introducing copper ions as abiological cofactors, WK can serve as a protein scaffold to design and create Cu catalytic sites. The optimized hybrids with Cu‐WK coordination framework exhibit significant superoxide dismutases‐like activity, catalase‐like activity, and hydroxyl radical scavenging ability. These combined antioxidant activities make CuWK a robust nanozyme to effectively remove various reactive oxygen species (ROS). In this work, the as‐prepared CuWK as a new additive can be integrated into a cigarette filter system to effectively remove the produced ROS from the burning of tobacco. More importantly, the CuWK nanozymes as a critical element can be further utilized to construct a recycling cigarette holder. Therefore, the present work shows that nanozymes with advanced catalytic capabilities can be constructed by self‐assembly of metal ions and proteins, thus facilitating the rational design and discovery of this kind of artificial metalloenzymes.

No abstract