Meso-substituted cationic 3- and 4-N-Pyridylporphyrins and their Zn(II) derivatives for antibacterial photodynamic therapy

Photodynamic inactivation of microorganisms known as antibacterial photodynamic therapy (APDT) is one of the most promising and innovative approaches for the destruction of pathogenic microorganisms. Among the photosensitizers (PSs), compounds based on cationic porphyrins/ metalloporphyrins are most successfully used to inactivate microorganisms. Series of meso-substituted cationic pyridylporphyrins and metalloporphyrins with various peripheral groups in the third and fourth positions of the pyrrole ring have been synthesized in Armenia. The aim of this work was to determine and test the most effective cationic porphyrins and metalloporphyrins with high photoactivity against Gram negative and Gram positive microorganisms. It was shown that the synthesized cationic pyridylporphyrins/metalloporphyrins exhibit a high degree of phototoxicity towards both types of bacteria, including the methicillin-resistant S. aureus strain. Zinc complexes of porphyrins are more phototoxic than metal-free porphyrin analogs. The effectiveness of these Zn-metalloporphyrins on bacteria is consistent with the level of singlet oxygen generation. It was found that the high antibacterial activity of the studied cationic porphyrins/metalloporphyrins depends on four factors: The presence in the porphyrin macrocycle of a positive charge (+4), a central metal atom (Zn2+) and hydrophobic peripheral functional groups as well as high values of quantum yields of singlet oxygen. The results indicate that meso-substituted cationic pyridylporphyrins/metalloporphyrins can find wider application in photoinactivation of bacteria than anionic or neutral PSs usually used in APD

Photosensitized Singlet Oxygen Luminescence from the Protein Matrix of Zn-Substituted Myoglobin

A nanosecond laser near-infrared spectrometer was used to study singlet oxygen (¹O₂) emission in a protein matrix. Myoglobin in which the intact heme is substituted by Zn-protoporphyrin IX (ZnPP) was employed. Every collision of ground state molecular oxygen with ZnPP in the excited triplet state results in ¹O₂ generation within the protein matrix. The quantum yield of ¹O₂ generation was found to be equal to 0.9 ± 0.1. On the average, six from every 10 ¹O₂ molecules succeed in escaping from the protein matrix into the solvent. A kinetic model for ¹O₂ generation within the protein matrix and for a subsequent ¹O₂ deactivation was introduced and discussed. Rate constants for radiative and nonradiative ¹O₂ deactivation within the protein were determined. The first-order radiative rate constant for ¹O₂ deactivation within the protein was found to be 8.1 ± 1.3 times larger than the one in aqueous solutions, indicating the strong influence of the protein matrix on the radiative ¹O₂ deactivation. Collisions of singlet oxygen with each protein amino acid and ZnPP were assumed to contribute independently to the observed radiative as well as nonradiative rate constants