Engineering Polyoxomolybdate Wheels for Enhanced Antibacterial Activity: A Structure-Driven Approach

Albeit the development of polyoxometalate (POM)-based antibiotics has spanned more than three decades, the antibacterial potential of Mo-based POMs (POMos) remains largely untapped. Given the prominent structure-dependent bioactivity of POMs, this study focuses on the structural engineering of wheel-shaped POMos in an attempt to boost their antibacterial performance. Adopting a dimethylarsinate-involved synthetic strategy, unprecedented iso- and hetero-POMo wheels constructed by emerging building blocks and assembly routes have been obtained. Of these, the [MoV₁₂MoVI₁₈O₉₆]²⁴⁻ (Mo30) wheel demonstrated a 10-fold greater efficacy against methicillin-resistant Staphylococcus aureus (MRSA) than the conventional Keggin-type [PMo₁₂O₄₀]³⁻ (PMo12), with the reduction of MIC from 1000 μg/mL (532.9 μmol/L, PMo12) to 100 μg/mL (17.7 μmol/L, Mo30). The significant decrease in biofilm mass from 93% (Mo30) to 16% (PMo12) signifies that the larger size and higher electronegativity of Mo30 might intensify the interaction with cell membrane proteins, resulting in membrane disruption and subsequent bacterial death. The established structure-bioactivity relationship for POMo wheels promises to revitalize research efforts toward POM-based antibiotics of the next generation.