Two‐Dimensional Conjugated Metal Organic Frameworks with Dual Metal Catalytic Active Sites Enhance POD Activity for Antibacterial Treatment

The emergence of drug‐resistant bacteria has brought a grand challenge to the treatment of oral ulcers (OUs). Peroxidase (POD) enzymes catalyze the conversion of hydrogen peroxide (H 2 O 2 ) into reactive oxygen species (ROS), offering a promising strategy for treating drug‐resistant bacterial infections and oral wound therapy. Among them, two‐dimensional conjugated metal‐organic frameworks (2D‐cMOFs) with high π‐π conjugated structure and efficient electron transport capability serve as potent POD mimics, enhancing ROS generation for targeted antimicrobial applications. However, the reported single‐metal‐center 2D cMOFs possess the intrinsically weak adsorption interaction with H 2 O 2 , usually decreasing the conversion of H 2 O 2 to ROS, exhibiting relatively low enzymatic activity and antibacterial performance. Herein, we reported a new class of Ni doped Cu 2D cMOFs, defined as CuNi‐HHTP 2D‐cMOFs, for constructing dual activity site to enhance the adsorption and activation of H 2 O 2 , which significantly facilitates the treatment of OUs. Mechanism investigation reveals the introduction of Ni atom upshifts the d‐band center of CuNi‐HHTP 2D‐cMOFs from ‐2.563 to ‐2.084 eV, which enhances the adsorption and activation of H 2 O 2 , endowing its 5.0‐fold enhancement in bactericidal efficiency. Besides, the as‐made CuNi‐HHTP 2D‐cMOFs show improved antibacterial performance in vivo, which significantly promote OU healing, with macroscopic wound closure on the 7 th day.