Organo-Pt ii Complexes for Potent Photodynamic Inactivation of Multi-Drug Resistant Bacteria and the Influence of Configuration.

Pt ^II based organometallic photosensitizers (PSs) have emerged as novel potent photodynamic inactivation (PDI) reagents through their enhanced intersystem crossing (ISC) processes. Currently, few Pt ^II PSs have been investigated as antibacterial materials, with relatively poor performances reported and with structure-activity relationships not well described. Herein, a pair of configurational isomers are reported of Bis-BODIPY (4,4-difluoro-boradizaindacene) embedded Pt ^II PSs. The cis-isomer (cis-BBP) displayed enhanced ¹ O ₂ generation and better bacterial membrane anchoring capability as compared to the trans-isomer (trans-BBP). The effective PDI concentrations (efficiency > 99.9%) for cis-BBP in Acinetobacter baumannii (multi-drug resistant (MDR)) and Staphylococcus aureus are 400 nM (12 J cm ^-2 ) and 100 nM (18 J cm ^-2 ), respectively; corresponding concentrations and light doses for trans-BBP in the two bacteria are 2.50 µM (30 J cm ^-2 ) and 1.50 µM (18 J cm ^-2 ), respectively. The 50% and 90% minimum inhibitory concentration (MIC ₅₀ and MIC ₉₀ ) ratio of trans-BBP to cis-BBP is 22.22 and 24.02 in A. baumannii (MDR); 21.29 and 22.36 in methicillin resistant S. aureus (MRSA), respectively. Furthermore, cis-BBP displays superior in vivo antibacterial performance, with acceptable dark and photoinduced cytotoxicity. These results demonstrate cis-BBP is a robust light-assisted antibacterial reagent at sub-micromolecular concentrations. More importantly, configuration of Pt ^II PSs should be an important issue to be considered in further PDI reagents design.
(© 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH.)