Structure-Activity Relationship in Boronic Acid-Functionalized Zinc(II) Phthalocyanines for the Photoinactivation of Gram- Positive Bacteria

The rapid emergence of antimicrobial resistance demands innovative therapeutic strategies, such as antimicrobial photodynamic therapy (aPDT). While zinc(II) phthalocyanine (ZnPc) dyes possess photophysical properties, their efficacy is often harmed by low solubility and aggregation in biological media. To overcome these limitations, we explored the functionalization of ZnPcs with boronic acid groups to enhance solubility and promote interactions with bacterial cells. We report the synthesis, structural characterization, and photophysical evaluation of tetra(1)-, octa(2)-, and octa-fluorinated(3)-substituted ZnPcs.

Their antimicrobial efficacy was evaluated against Staphylococcus aureus under white light irradiation. The results demonstrated that structural variations significantly impact biological outcomes. When tested alone at 5 and 10 µM, the ZnPcs 1 and 2 successfully inactivated S. aureus within 30 to 60 min (light dose 180–270 J cm^-2). However, the ZnPc 3 derivative was ineffective even after extended irradiation times, failing to induce bacterial inactivation (60 min, light dose 360 J cm^-2) .

To potentiate the photodynamic action, potassium iodide (KI) was introduced as a coadjuvant. KI reacts with reactive oxygen species (ROS) to generate highly toxic and persistent reactive iodine species (RIS) in the microenvironment. The addition of KI produced a remarkable synergistic effect, reducing the inactivation times for both ZnPcs 1 and 2 (15–30 min) and enabled complete photoinactivation for the fluorinated ZnPc 3 within 60 min, even at the lowest tested concentrations.

In conclusion, incorporating boronic acid into ZnPcs preserves their photodynamic efficiency, while the synergistic combination with KI successfully overcomes structural limitations. This approach enables highly efficient photoinactivation of Gram-positive bacteria, demonstrating strong potential for aPDT applications.