Aminopyrazinium-Functionalized Zinc(II) Phthalocyanine as Photosensitizer Against Staphylococcus aureus

Photodynamic inactivation (PDI) has emerged as a powerful approach to tackle drug-resistant microorganisms. Here, we report for the first time the synthesis, characterization, and photophysical properties of two tetra-substituted aminopyrazine and aminopyrazinium zinc(II) phthalocyanines (ZnPcs 1 and 1a , respectively). Due to its superior solubility, ZnPc 1a was selected to evaluate its PDI efficiency against methicillin-resistant Staphylococcus aureus (MRSA) using two photosensitizer (PS) concentrations (5.0 and 10.0 µM) under white light irradiation at 100 mW cm -2 , with exposure times of up to 45 min (total light dose of 0–270 J cm -2 ). Remarkably, ZnPc 1a at 10 µM promoted >8 Log CFU/mL bacterial reduction within only 15 min of irradiation, while at 5 µM it achieved around 6 Log CFU/mL reduction in the same period, reaching complete inactivation to the detection limit after 30 min. Despite the low singlet-oxygen production, effective bacterial photoinactivation mediated by ZnPc 1a was observed. Based on this observation, we propose that the PDI process mediated by ZnPc 1a occurs by the generation of reactive oxygen species (ROS). These results demonstrate high photodynamic efficiency of ZnPc 1a at low concentrations, reinforcing its potential as a potent photosensitizer for antimicrobial photodynamic therapy applications.