Thiol-disulfide exchange promotes Fe2+/Fe3+ cycle to enhance peroxidase mimetic antibacterial activities of FeOCl.

Thiol-disulfide exchange, one of the most popular dynamical combinatorial chemistries under physiological conditions, typically requires long equilibration times to reach the desired equilibrium composition. We successfully synthesized Cysteine-iron oxychloride (Cys-FeOCl) nanobelts by introducing L-cysteine as a dispersing agent during the liquid-phase exfoliation of FeOCl. This material utilizes the L-cysteine thiol group (SH) to accelerate the Fe3+/Fe2+ cycle, significantly enhancing the peroxidase-like (POD-like) activity, and constructing a coupling network of "cysteine-cystine" biochemical redox pair and "Fe2+-Fe3+ chemical metal valence state cycling", thereby continuously generating reactive oxygen species (ROS). Experimental results reveal that Cys-FeOCl exhibited 100% antibacterial efficiency against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) at 2 μg·mL-1, and 99% antibacterial activity against Gram-negative extended-spectrum β-lactamase-producing Escherichia coli (ESBL-producing E. coli) at 10 μg·mL-1. The mechanism lies in the ROS burst, causing bacterial structure rupture, DNA damage and protein leakage. Interestingly, excessive addition of exogenous hydrogen peroxide (H₂O₂) will destroy the coupling cycle constructed by Cys-FeOCl, thereby weakening its bactericidal efficacy. This study confirms that cysteine, ultrasound-assisted, and FeOCl are the three essential factors for constructing the efficient nanozyme bactericidal agent Cys-FeOCl, providing a novel and powerful strategy for combating drug-resistant bacterial infections.