π-Stacking-Resistant Cationic Metalloporphyrin COF with Dual-Enzyme Mimetics for Infected Wound Therapy

The escalating global crisis of antimicrobial resistance demands disruptive therapeutic platforms that can bypass conventional antibiotic mechanisms. Through atomically precise structural evolution integrating Knoevenagel polycondensation, postsynthetic alkylation (–CH3), and transition metal coordination (Fe3+), we constructed a cationic metalloporphyrin covalent organic framework (MC–COF–I) with programmed photonic and double mimic enzymatic behavior. This material uniquely combines staggered octaaldehyde-porphyrin units and π-delocalized vinyl bridges, achieving three critical breakthroughs in bactericidal activity. The distorted porphyrin arrangement disrupts π–π stacking, suppressing aggregation-induced photoactivity quenching. The multiple iron centers (Fe–N coordination sites, Fe2O3 nanoparticles, and FeO clusters) endow the pH-gated enzyme circuitry, realizing the self-adaptive catalytic plasticity switches between peroxidase-mimetic (POD-like, at pH 5.5) and catalase-like (CAT-like, at pH 7.4) activities, establishing a self-perpetuating ROS-O2 cycle for infectious microenvironment (IME) reprogramming. The cationic topological skeleton facilitates electrostatic docking with the bacterial membrane, enabling spatiotemporally gated photothermo-ROS delivery for the bacterium-targeted precision therapy. Consequently, MC–COF–I with excellent biosafety could be used as an intelligent therapy agent, effectively utilizing and regulating the IME, exerting the cascaded synergistic photothermal/photodynamic/cationic/POD/CAT therapy and significantly accelerating the healing of open wounds with bacterial infection. This work establishes that the spatial distortion strategy resolves the century-old phototoxicity–bioactivity trade-off in porphyrin systems.