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The effect of singlet oxygen production and lipophilicity of the photosensitizer in photodynamic activity of N-methylated and N- oxidized pyridylporphyrins

Photodynamic therapy (PDT) is based on cytotoxic action of singlet oxygen (1O2) and other reactive oxygen species (ROS), produced upon the visible light-excitation of a photosensitiser (PS), against cancer cells and pathogenic microorganisms.[1, 2] Intracellular localisation of the PS is important for PDT efficiency, due to short lifetime (µs) and “working” distance (nm) of 1O2, and molecules that can easily penetrate into the cell are potentially better PSs.[3] We have recently synthesised a series of N- methylated and N-oxidised tetra- and tripyridylporphyrins bearing 3- and 4-pyridyl groups, and we studied the effect of a long alkyl chain on their PDT activity. Photophysical characteristics proved to be very similar for all the compounds, as well as their ability to produce 1O2 using 9, 10- dimethylantracen (DMA) photodegradation study. [4] A further study of the decrease of the absorption and fluorescence of 1, 3- diphenylisobenzofuran (DBF), in the presence of the photo-activated PSs, as a measure of 1O2 production will be described and compared to the relative method with DMA. In contrast to their 1O2 production, the presence of a long alkyl chain and amphiphilicity of the PSs proved to be crucial for high PDT activity against five cancer cell lines. Furthermore, N-methylated tripyridylporphyrins were generally more PDT efficient than their N-oxidised analogues, and those with 3-pyridyl groups (TMPyP3-C17H35 and TMPyP3-C17H33) were shown to be better PSs than those with 4-pyridyl groups.[4] Cationic PSs can target Gram-negative bacteria due to electrostatic interactions, 5 however, the possible effect of a lipophilic chain is somewhat less investigated. Therefore, we compared the activity of amphiphilic TMPyP3- C17H35 against Legionella pneumophila with the activities of two hydrophilic PSs, TMPyP3 and TMPyP3-CH3. The minimum inhibitory concentration (MIC) and minimum effective (MEC) values were determined in broth, and MEC in tap water, by the microdilution method. Violet and red light with different fluence rates and total doses were used for the activation of the PSs. The most efficient compound in all studies was amphiphilic PS while the activities of the hydrophilic PSs were significantly lower, though tetracationic TMPyP3 was slightly more efficient than tricationic TMPyP3-CH3. The complete inactivation of Legionella in sterile tap water was achieved with nanomolar concentration (0.024 μM) of TMPyP3-C17H35, and the photosensitiser uptake assay has shown that this PS binds to the bacterial cell, already after 10 minutes of incubation in the dark.

Porphyrin ; Photodynamic therapy ; Cancer ; Legionella

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