C-BODIPY Dyads Based on Fused-Ring Organoboron Scaffolds for Efficient Photodynamic Therapy Targeting Candida albicans Yeast and Biofilms.

A series of heavy-atom-free C-BODIPY photosensitizers based on five different types of fused-ring organoboron scaffolds was designed for the application in antifungal photodynamic therapy. The dyes were functionalized with a positively charged quaternary ammonium group or zwitterionic 3-(ethyldimethylammonio)propane-1-sulfonate unit. Spectroscopic, electrochemical, and photocatalytic studies supported by DFT calculations revealed the crucial role of the organoboron structure on triplet-state generation. Most of the BODIPY complexes display high ROS generation with a type I/type II ROS ratio depending on the electronic structure of the boracycle unit. Antifungal studies demonstrated remarkable efficacy against the opportunistic yeast Candida albicans at low concentrations (1.6 μg/mL), achieving up to a 7-log reduction in the planktonic cells and significant photoactivity toward the fungal biofilm, reaching up to 4.3-log reduction in MFC values. The studies on the cell death mechanism revealed that cells undergo apoptosis upon photoinactivation. Furthermore, complexes were proven to reduce cell adhesion to biotic surfaces, preventing biofilm formation.