ABSTRACT The stabilization of radical species in aqueous environments remains a central challenge for radical‐based antibacterial applications, as rapid quenching severely limits its efficacy. Herein, we report a strategy to sustain radical by coupling diffusional confinement with electronic delocalization in π‐conjugated hydrogen‐bonded organic frameworks (HOFs). Using a pyrene‐based HOF (PFC‐1) as a model system, we systematically modulate the longitudinal dimensions of 1D channels to generate frameworks with three distinct aspect ratios while maintaining topology. The higher‐aspect‐ratio channels impose a more pronounced kinetic barrier to the outward diffusion of radical‐generating trigger (ceric ammonium nitrate), thereby retaining a trigger‐inclusive oxidative microenvironment. Simultaneously, the extended π‐π stacking enhances electronic delocalization, stabilizing the resulting radicals through favorable host‐guest interactions. As a result, radicals confined within the longest‐channel framework remain persistent for over 30 days in water and up to 8 months under ambient conditions. This prolonged radical persistence enables potent antibacterial activity against Escherichia coli via radical‐induced oxidative stress. This work establishes a trigger‐inclusive microenvironment capable of simultaneously retaining both the radical species and its trigger as a generalizable design principle for engineering persistent radical states.
Li et al. (Fri,) studied this question.