The Photodynamic Antibacterial Potential of New Tetracationic Zinc(II) Phthalocyanines Bearing 4-((Diethylmethylammonium)methyl)phenoxy Substituents

Photodynamic inactivation and antimicrobial photodynamic therapy (PDI/APDT) based on the toxic properties of reactive oxygen species (ROS), which are generated by a number of photoexcited dyes, are promising for preventing and treating infections, especially those associated with drug-resistant pathogens. The negatively charged bacterial cell surface attracts polycationic photosensitizers, which contribute to the vulnerability of the bacterial plasma membrane to ROS. The integrity of the plasma membrane is critical for the viability of the bacterial cell. Polycationic phthalocyanines are regarded as promising photosensitizers due to their high quantum yields of ROS generation (mainly singlet oxygen), high extinction coefficients in the far-red spectral range, and low dark toxicity. For application in PDI/APDT, the wide range of possibilities of modifying the chemical structure of phthalocyanines is particularly valuable, especially by introducing various peripheral and non-peripheral substituents into the benzene rings. Depending on the type and location of such substituents, it is possible to obtain photosensitizers with different photophysical properties, photochemical activity, solubility in an aqueous medium, biocompatibility, and tropism for certain structures of photoinactivation targets. In this study, we tested novel water-soluble Zn (II) phthalocyanines bearing four 4-((diethylmethylammonium)methyl)phenoxy substituents with symmetric and asymmetric charge distributions for photodynamic antibacterial activity and compared them with those of water-soluble octacationic zinc octakis(cholinyl)phthalocyanine. The obtained results allow us to conclude that the studied tetracationic aryloxy-substituted Zn(II) phthalocyanines effectively bind to the oppositely charged cell wall of the Gram-negative bacteria <i>E. coli</i>. This finding is supported by data on bacteria's zeta potential neutralization in the presence of phthalocyanine derivatives and fluorescence microscopy images of stained bacterial cells. Asymmetric substitution influences the aggregation and fluorescent characteristics but has little effect on the ability of the studied tetracationic phthalocyanines to sensitize the bioluminescent <i>E. coli</i> K12 TG1 strain. Both symmetric and asymmetric aryloxy-substituted phthalocyanines are no less effective in PDI than the water-soluble zinc octakis(cholinyl)phthalocyanine, a photosensitizer with proven antibacterial activity, and have significant potential for further studies as antibacterial photosensitizers.