Penicillamine-directed <i>in-situ</i> synthesis of covalently integrated silver nanoclusters as a robust nano-antibiotic

The development of antimicrobial agents with long-term stability and sustained efficacy remains a formidable challenge in materials science and biomedicine. Conventional hybrid nanomaterials, though promising, are frequently compromised by the leaching of functional molecules, which undermines their durability and performance. Herein, we report a facile, one-pot, aqueous-phase strategy for the synthesis of a covalently integrated nano-antibiotic. In this approach, D-penicillamine (DPA) uniquely served a dual role as both the sole reducing and capping agent to form ultrastable silver nanoclusters (DPA-AgNCs). This synthesis accompanies the functionalization paradigm, yielding a robust hybrid material in which DPA was securely anchored to the silver core via strong Ag-S covalent bonds. The resultant DPA-AgNCs exhibited potent, bactericidal activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli). Critically, the robust covalent linkage prevented DPA detachment, endowing the nano-antibiotic with exceptional long-term inhibitory performance and excellent reusability across multiple cycles. This overcomes a key limitation of conventional nano-antibacterial systems. Our findings establish a new and relatively green synthetic paradigm for the rational design of highly effective and durable nano-antibiotics.