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 [Mo V 12 Mo VI 18 O 96 ] 24– ( Mo 30 ) wheel demonstrated a 10-fold greater efficacy against methicillin-resistant Staphylococcus aureus (MRSA) than the conventional Keggin-type [PMo 12 O 40 ] 3– ( PMo 12 ), with the reduction of MIC from 1000 μg/mL (532.9 μmol/L, PMo 12 ) to 100 μg/mL (17.7 μmol/L, Mo 30 ). The significant decrease in biofilm mass from 93% ( Mo 30 ) to 16% ( PMo 12 ) signifies that the larger size and higher electronegativity of Mo 30 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.