Anionic Boron-Cluster BODIPY Conjugates As Promising Photosensitizers for Targeted Antimicrobial Photodynamic Therapy

We report the design, synthesis, photophysical characterization, and antimicrobial evaluation of three novel anionic boron-cluster-BODIPY conjugates, <b>BDP-FES</b> (BODIPY-ferrabisdicarbollide), <b>BDP-COS</b> (BODIPY-cobaltabisdicarbollide), and <b>BDP-B</b> _<b>12</b> (BODIPY-<i>closo</i>-dodecaborate), as photosensitizers for antimicrobial photodynamic therapy (aPDT). Covalent attachment of anionic boron clusters to the iodinated BODIPY scaffold was confirmed by multinuclear NMR spectroscopy and resulted in red-shifted absorption (λ_abs,max = 545 nm) and emission (λ_f,max = 600-611 nm) maxima, along with pronounced suppression of fluorescence quantum yields due to heavy-atom-promoted triplet state generation. While singlet oxygen generation decreased compared to the parent <b>BDP-I</b> _<b>2</b> , the new conjugates, particularly <b>BDP-B</b> _<b>12</b> , demonstrated potent, light-dependent bactericidal activity against multidrug-resistant Gram-positive bacteria, including <i>Staphylococcus aureus</i>, <i>Enterococcus faecium</i>, and <i>Enterococcus raffinosus</i>, with complete eradication of <i>S. aureus</i> at 5 μM under green light irradiation. All conjugates exhibited negligible toxicity in the dark, indicating selective photodynamic activity and an improved safety profile. These findings establish anionic boron clusters as versatile molecular tools to modulate the photophysical and biological properties of BODIPY-based photosensitizers. Our results lay the groundwork for the development of next-generation, biocompatible photodynamic agents for targeted disinfection and infection control, bridging inorganic chemistry and biomedical applications.