Zhang Xinmiao, Zhang Zengshan, Wang Jun, Zheng Aili, Xiao Lin, Sun Xu, Zhang Jinhong, Zhao Chunzhen, Li Yonghui, Zhou Baolong
Affiliated Hospital of Shandong Second Medical University, Shandong Second Medical University, Weifang 261053, Shandong, P. R. China.
School of Pharmacy, Shandong Second Medical University, Weifang 261053, Shandong, P. R. China.
ACS Appl Mater Interfaces. 2025 Jul 30;17(30):42602-42623. doi: 10.1021/acsami.5c04347. Epub 2025 Jul 18.
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 -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 -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 O 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 O to generate bactericidal superoxide radicals (O) and concurrently produces HO, especially during the early infection stage. Then, the CAT-like activity converts the accumulated HO into O which restores tissue oxygenation and reignites Type II PDT. Furthermore, the POD-like activity processes residual HO into O, 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.
在此，我们开发了一种利用结构异构来创建多功能非抗生素杀菌剂的立体化学工程策略。该方法通过调节共轭微孔聚合物（CMP）中的空间位阻来精确控制抗菌活性。通过策略性地管理异构构型（新异和异）中反应基团的空间排列，我们成功合成了两种具有三重酶模拟活性的基于铁酞菁的异构CMP（异-CMP-1和异-CMP-2）：过氧化物酶（POD）、氧化酶（OXD）和过氧化氢酶（CAT）。这两种材料在伤口愈合的不同阶段都非常适合抗菌治疗。这些材料的扩展π共轭结构产生宽带光谱吸收并提高光子捕获效率，从而协同增强光热和光动力性能。对比分析表明，具有更高空间拥挤度的新异构型会导致结构畸变，阻止酞菁的π-π堆积，并放大酶模拟活性。从机制上讲，与异构型相比，新异立体化学构型诱导出更明显的结构畸变，这会破坏酞菁的π-π堆积，同时放大过氧化物酶模拟活性。异-CMP表现出氧适应性光动力功能，在氧气充足的条件下同时进行I型和II型光动力疗法（PDT），但在缺氧环境中选择性激活I型途径，克服了氧浓度限制。异-CMP系统通过时空编程的酶模拟级联反应协调一个自我维持的氧代谢循环。具体而言，类似OXD的能力催化O生成杀菌超氧自由基（O），并同时产生HO，特别是在早期感染阶段。然后，类似CAT的活性将积累的HO转化为O，恢复组织氧合并重新点燃II型PDT。此外，类似POD的活性将残留的HO加工成O，与光热和PDT疗法协同作用，有效抑制细菌生长和生物膜形成，并加速伤口愈合。这种嵌入逻辑的设计将静态材料转变为智能治疗系统，其中细菌发病机制直接推动自适应抗菌反应。
