Flexibility-induced high-entropy cationic Phthalocyanine-Cu borate low-crystallinity COF with suppressed π-stacking...

Aggregation-caused quenching and inefficient bacterial contact remain two major barriers to phthalocyanine-based antimicrobial platforms. Herein, we report a monomer-encoded flexible high-entropy low-crystallinity covalent organic framework (BCuPc-COF) constructed from Cu-phthalocyanine-2,3,9,10,16,17,23,24-octaol (CuPc(OH)₈) and the conformationally adaptive dicationic crosslinker N¹,N³-bis(4‑boronobenzyl)-N¹,N¹,N³,N³-tetramethylpropane-1,3-diaminium (BBTD). Critically, the intrinsic N⁺-C-C-N⁺ rotational freedom and the remarkable B-O-C bond-angle adaptability of BBTD generate an exceptionally large configurational entropy during polymerization. This high-entropy regime kinetically traps BCuPc-COF in a π-stacking-depleted, high-performance state, effectively overcoming the notorious ACQ problem, while fully preserving the aromatic conjugation and photosensitizing capability of the phthalocyanine cores. The dense cationic borate sites further promote tight electrostatic adhesion to anionic bacterial membranes, reducing mass-transport barriers and confining reactive species at the pathogen interface. This interfacial confinement dramatically enhances ROS utilization. Moreover, BCuPc-COF exhibits robust peroxidase-like (POD-like) activity, which drives chemodynamic therapy (CDT) by catalyzing •OH generation from endogenous H₂O₂. Benefiting from these synergistic features, upon 638 nm laser irradiation in the presence of H₂O₂, BCuPc-COF rapidly generates abundant ROS and achieves >99% bacterial eradication within 10 min at remarkably low concentration (50 μg/mL), effectively covering both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli). It also efficiently disassembles mature biofilms and accelerates infected-wound healing to ~100% within 11 days in mice, demonstrating particular promise for managing infections, such as those arising from sports-related soft-tissue injuries (abrasions, lacerations, and post-surgical wounds), with excellent biocompatibility. This work establishes monomer-derived flexibility as an entropy engine that simultaneously suppresses π-stacking (thus defeating ACQ) and amplifies interfacial antimicrobial efficacy, offering a generalizable strategy for high-performance ROS therapy.