Isomerism as a Facile Strategy for Enhancing Spatial Distortion and Optimizing Multifaceted Sterilizing Activities of Conjugated Microporous Polymers via Self-Adaptive Infectious Microenvironment Remodeling Therapy

Here, we have developed a stereochemical engineering strategy utilizing structural isomerism to create multifunctional nonantibiotic biocides. This method allows for precise control of antimicrobial activity by adjusting the steric hindrance in conjugated microporous polymers (CMPs). By strategically managing the spatial arrangement of reactive groups in isomeric configurations (neo-iso and para-iso), we successfully synthesized two isomeric Fe-phthalocyanine-based CMPs (iso-CMP-1 and iso-CMP-2) with triple-enzyme-mimetic activities: peroxidase (POD), oxidase (OXD), and catalase (CAT). Both materials are highly adaptable for antibacterial therapy during different stages of wound healing. The extended π-conjugation architectures of these materials engender broad-band spectral absorption and enhanced photon capture efficiency, thereby synergistically augmenting both photothermal and photodynamic performance. A comparative analysis showed the neo-iso configuration, with higher steric congestion, causes structural distortion, preventing phthalocyanine π-π stacking, and amplifying enzyme-mimetic activities. Mechanistically, the neo-iso stereochemical configuration induces a much pronounced structural distortion compared to the para-iso, which disrupts phthalocyanine π-π stacking while amplifying peroxidase-mimetic activity. The iso-CMPs demonstrate oxygen-adaptive photodynamic functionality, which simultaneously performs Type I and Type II photodynamic therapy (PDT) under oxygen-sufficient conditions but selectively activates Type I pathways in oxygen-deficient environments, overcoming O₂ concentration limitations. The iso-CMP system orchestrates a self-sustaining oxygen metabolic cycle through spatiotemporally programmed enzyme-mimetic cascades. Specifically, the OXD-like capacity catalyzes O₂ to generate bactericidal superoxide radicals (O₂^•-) and concurrently produces H₂O₂, especially during the early infection stage. Then, the CAT-like activity converts the accumulated H₂O₂ into O_2, which restores tissue oxygenation and reignites Type II PDT. Furthermore, the POD-like activity processes residual H₂O₂ into O₂^•-, which synergizes with photothermal and PDT therapy, effectively suppresses bacterial growth and biofilm formation, and accelerating wound healing. This logic-embedded design transforms static materials into smart therapeutic systems, where bacterial pathogenesis directly fuels self-adaptive antimicrobial responses.