N-Methylpyridinium Porphyrin Complexes as Sensitizers for Sonodynamic Therapy Against Planktonic and Biofilm-Forming Multidrug-Resistant Microbes

Porphyrins play an extremely important role in both photodynamic (PDT) and sonodynamic therapy (SDT). These techniques, which have a lot in common, are largely based on the interaction between the sensitizer and light or ultrasounds (US), respectively, resulting in the formation of reactive oxygen species (ROS) that have the ability to destroy target cells. SDT requires the use of an appropriate frequency of US waves that are able to excite the chemical compound used. In this study, five porphyrin complexes were used: free-base meso-tetra(N-methyl-pyridinium-4-yl)porphyrin (TMPyP) and its transition metal complexes containing zinc(II), palladium(II), copper(II), and chloride-iron(II). The sonodynamic activity of these compounds was studied in vitro. The obtained results confirm the significant relationship between the chemical structure of the macrocycle and its stability and ability to generate ROS. The highest efficiency in ROS generation and high stability were demonstrated by non-metalated compound and its complex with zinc(II), while complex with copper(II), although less stable, were equally effective in terms of ROS production. Antibacterial activity tests showed the unique properties of the tested compounds, including a reduction in the number of both planktonic and biofilm antibiotic-resistant microorganisms above 5 log, which is rare among sonosensitizers.