The One-Pot Ternary Synthesis of the Vinylene-Linked Ferrocenyl Cationic Covalent Organic Polymer for Enzyme-Mimicking Infectious Wound Therapy

Antibiotic resistance and biofilm formation pose as the primary challenges in the bacterial infectious diseases. Herein, a ferrocenyl cationic covalent organic polymer (COP) artificial peroxidase (POD) enzyme catalytic system (iTAFc-COP) was constructed based on the ternary Knoevenagel condensation of 2,4,6-trimethyl-triazine (TMT), ferrocene dicarboxaldehyde (Fc), and bromoethane (BE). The peroxidase-mimicking (POD-like) therapeutic activity of iTAFc-COP demonstrates dual stimuli-responsive activation, specifically triggered by both endogenous hydrogen peroxide (H2O2) and the pathologically weak acidic microenvironment (pH ∼ 5.5). This unique responsive mechanism enables precise spatiotemporal control for targeted in situ antibacterial therapy, which is particularly effective against localized bacterial infections. The cationic framework of iTAFc-COP significantly enhances electrostatic interactions with negatively charged bacterial membranes, thereby promoting localized generation and efficient utilization of transient hydroxyl radicals (•OH) at the bacteria–material interface. Notably, iTAFc-COP exhibits remarkable photoresponsive behavior, demonstrating significantly enhanced photothermal conversion efficiency compared to its nonionic counterpart (TAFc-COP). This unique photothermal property enables light-mediated activation of enzymatic catalytic activity, establishing a photoenzyme synergistic system. TAFc-COP exhibits exceptional bacterial adhesion properties, enabling a self-amplifying therapeutic cascade through the synergistic interplay of cationic interactions, photothermal effects, and enzymatic activities. This trimodal antimicrobial strategy demonstrates superior efficacy in bacterial inactivation and biofilm disruption, effectively promoting wound healing progression in infectious conditions. The integrated multifunctionality establishes iTAFc-COP as an advanced therapeutic platform, offering a robust solution for combating infection-related pathologies through its unique combination of therapeutic modalities.