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

Abstract

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 (Zn[Formula: see text] 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 APDT.

Cationic Porphyrins as Antimicrobial and Antiviral Agents in Photodynamic Therapy

“…In the following work, the authors remarked that the four main criteria for the PSs for APDT efficiency are: (1) the presence of a positive charge in the porphyrin macrocycle (four positive groups); (2) the presence of a central metal atom (Zn(II)); (3) the presence of hydrophobic peripheral functional groups; (4) high values of singlet oxygen quantum yields. A series of PSs with different peripheral substituents in the pyrrole ring were synthesized [108]. A number of TMPyP derivatives with hydrophilic oxyethyl group, hydrophobic butyl or allyl substituents and differing by the presence of zinc atoms in the macrocycle, were obtained.…”

Acquiring of photosensitivity by Mycobacterium tuberculosis in vitro and inside infected macrophages is associated with accumulation of endogenous Zn–porphyrins

“…One of the most effective photosensitizers are porphyrins 4 , among which zinc complexes standout 5 – 11 . Zn–coproporphyrin is considered as a promising compound for PDT of tumors 12 .…”

Acquiring of photosensitivity by Mycobacterium tuberculosis in vitro and inside infected macrophages due to accumulation of endogenous Zn-porphyrins

“…One of the most effective photosensitizers are porphyrins 4 , among which zinc complexes standout [5][6][7][8][9][10][11] .…”