Molecular Engineering of a cationic Pyrene-Based Photosensitizer for Antimicrobial Photodynamic Therapy Against Drug-Resistant Pathogens

Multidrug-resistant (MDR) bacterial infections require alternative therapeutic strategies because effective new antibiotics are limited in availability. Skin and soft-tissue infections, in particular, demand surface-specific treatment approaches such as photoantimicrobial chemotherapy (PACT). Here, we report two structurally related pyrene-based photosensitizers, PyB and PyP, and evaluate their photophysical properties and blue-light (440 nm) activated antibacterial activity against Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). We demonstrate enhanced singlet oxygen–mediated phototoxicity of PyP compared to PyB due to the presence of a triphenylphosphonium (TPP+) moiety. These results highlight how subtle molecular design modifications can be exploited for developing novel photoinduced antibacterial agents.