Engineering Porphyrinic MOFs via In-Situ N-H Chlorination for HOCl Generation, Detoxification, Phototheranostics and Antimicrobial Activity

ABSTRACT Reactive chlorine species (RCS), notably hypochlorous acid (HOCl), are central to innate immune defense due to their strong redox activity and broad-spectrum antimicrobial efficacy. Here, we report a porphyrin-based zirconium metal-organic framework, porous coordination network-222-chloride (PCN-222-Cl), engineered for in situ HOCl generation via controlled N–H chlorination of porphyrin ligands using sodium dichloroisocyanurate (NaDCC). Formation of electron-withdrawing N–Cl bonds significantly increases the electron-deficient character of the porphyrin macrocycle, enabling efficient catalytic oxidation of chloride ions under mildly acidic to neutral conditions. Electronic reconfiguration of the ligands, synergistically coupled with Lewis-acidic Zr 6 O 4 (OH) 4 nodes, facilitates HOCl release and enhances photocatalytic activity. The intrinsic photothermal response of the porphyrinic framework further accelerates chloride oxidation kinetics, yielding dual photothermal and oxidative modes. As a result of these combined effects, PCN-222-Cl exhibits a 3.4-fold increase in the photo-oxidation rate of the sulfur mustard simulant 2-chloroethyl ethyl sulfide compared to unmodified the porphyrinic zirconium metal-organic framework (MOF). Biologically, PCN-222-Cl achieves antibacterial inhibition rates of 99.7% against Escherichia coli (E. coli) and 99.9% against Staphylococcus aureus (S. aureus). In this work, PCN-222-Cl achieves 94.5% tumor growth suppression and a 39.1% reduction in the Ki67 proliferation index under dark conditions. Notably, phototherapy increases intratumoral reactive oxygen species levels by 2.4-fold and enhances tumor inhibition to 99.3%. This study establishes a generalizable strategy for integrating reactive chlorine chemistry into MOFs to design multifunctional platforms that combine catalytic, photothermal, and oxidative properties for enhanced antibacterial, detoxifying, and antitumor activity.