Antimicrobial resistance has emerged as a global threat to the treatment of infectious diseases. Antibacterial photodynamic therapy (aPDT) is a promising alternative approach and is highly suitable for the treatment of cutaneous bacterial infections through topical applications. aPDT relies on light-responsive compounds called photosensitizer (PS) dyes, which generate reactive oxygen species (ROS) when induced by light, thereby killing bacterial cells. Despite several previous studies in this area, the molecular details of targeting and cell death mediated by PS dyes are poorly understood. In this study, we further investigate the antibacterial properties of two water-soluble Sn(IV) tetrapyridylporphyrins that were quaternized with methyl and hexyl groups (1 and 2). In this follow-up study, we demonstrate that Sn(IV)-porphyrins can be photoexcited by blue light (a 427 nm LED) and exhibit various levels of bactericidal activity against both Gram-(+) and Gram-(?) strains of bacteria. Using localization studies through fluorescence microscopy, we show that 2 targets the bacterial membrane more effectively than 1 and exhibits comparatively higher aPDT activity. Using multiple fluorescence reporters, we demonstrate that photoactivation of 1 and 2 results in extensive collateral damage to the bacterial cells including DNA cleavage, membrane damage, and delocalization of central systems necessary for bacterial growth and division. In summary, this investigation provides deep insights into the mechanism of bacterial killing mediated by the Sn(IV)-porphyrins. Moreover, our approach offers a new method for evaluating the activity of PS, which may inspire the discovery of new PS with enhanced aPDT activity.

A series of Sn(IV) porphyrins with 4-methoxy-(1-SnPor), 3-methoxy-(2-SnPor), 4-hydroxy-(3-SnPor) and 3-methoxy-4-hydroxyphenyl (4-SnPor) meso-aryl rings have been synthesized and characterized. 1-4-SnPor have relatively high singlet oxygen quantum yields in the 0.65-0.68 range in DMSO due to the heavy atom effect of the Sn(IV) ion. The lowest energy Q bands of the complexes lie at 612, 602, 615 and 620 nm, respectively. In the context of 4-SnPor, this represents an 18 nm red shift relative to the spectra of Sn(IV) tetraphenylporphyrin and 2-SnPor, which has methoxy groups at a meta-position. The in vitro photodynamic therapy (PDT) activities of 1-4-SnPor were determined against MCF-7 breast cancer cells through illumination for 20 min with a Thorlabs M625L3 (240 mW.cm-2) light emitting diode (LED) that has an output maximum at 625 nm and a Modulight illumination kit providing a dose of 1.7 J.cm-2 at the well-plate. The IC50 value of 7.1 ?M for 4-SnPor is significantly lower than the values of 14.7, 16.5 and 11.2 ?M for 1-3-SnPor, respectively, due to the significant red shift of its Q00 band that results in a better match with the output maximum of the LED. 1-4-SnPor were found to have relatively high photodynamic antimicrobial activity against planktonic Gram-(+) Staphylococcus aureus (S. aureus) and exhibited moderate activity against Gram-(-) Escherichia coli (E. coli) bacteria upon illumination with the Thorlabs M625L3 LED for 75 min providing a dose of 6.5 J.cm-2 at the well-plate. Log10 reduction values of 7.62 and > 2.40-2.94 were obtained with 1 and 5 ?M solutions in 1% DMSO/PBS, respectively. The photodynamic antimicrobial activities were also investigated against S. aureus and E. coli biofilms. © 2024 World Scientific Publishing Company.

Photodynamic therapy (PDT) is a mode of treatment for different types of cancers, which involves a nontoxic photosensitizer (PS), a light source to activate the PS, and ground-state molecular oxygen (O). Light activation of the PS leads to the generation of reactive oxygen species (ROS), which initiates a toxic effect on the surrounding cellular substrates, thereby destroying the cancerous cells. The commercially used PDT drug Photofrin which is a tetrapyrrolic porphyrin-based photosensitizer has drawbacks such as aggregation in water, prolonged skin photosensitivity, variability in chemical compositions, and minimal absorbance in the red-light region. Metallation of the porphyrin core with diamagnetic metal ions aids the photogeneration of singlet oxygen (ROS). Metalating with Sn(iv) provides a six-coordination octahedral geometry with trans-diaxial ligands. This approach suppresses aggregation in aqueous media and increases ROS generation upon light exposure due to the heavy atom effect. Bulky trans-diaxial ligation hinders the approach of the Sn(iv) porphyrins, thereby suppressing aggregation effects. In this review, we document the recently reported Sn(iv) porphyrinoids and their photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) activity properties. In a similar manner to PDT, the photosensitizer is used to kill the bacteria upon irradiation with light during PACT. Often, bacteria develop resistance against conventional chemotherapeutic drugs over time, decreasing their antibacterial properties. However, in the case of PACT, it is difficult to generate resistance against singlet oxygen produced by the photosensitizer.

A series of tetraarylchlorins with 3-methoxy-, 4-hydroxy- and 3-methoxy-4-hydroxyphenyl meso-aryl rings (1-3-Chl) and their Sn(IV) complexes (1-3-SnChl) were synthesized and characterized so that their potential utility as photosensitizer dyes for use in photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) can be assessed. The photophysicochemical properties of the dyes were assessed prior to in vitro PDT activity studies against MCF-7 breast cancer cells through irradiation with Thorlabs 625 or 660 nm LED for 20 min (240 or 280 mW·cm). PACT activity studies were performed against both planktonic bacteria and biofilms of Gram-(+) S. aureus and Gram-(?) E. coli upon irradiation with Thorlabs 625 and 660 nm LEDs for 75 min. The heavy atom effect of the Sn(IV) ion results in relatively high singlet oxygen quantum yield values of 0.69?0.71 for 1-3-SnChl. Relatively low IC values between 1.1?4.1 and 3.8?9.4 µM were obtained for the 1-3-SnChl series with the Thorlabs 660 and 625 nm LEDs, respectively, during the PDT activity studies. 1-3-SnChl were also found to exhibit significant PACT activity against planktonic S. aureus and E. coli with Log reduction values of 7.65 and >3.0, respectively. The results demonstrate that the Sn(IV) complexes of tetraarylchlorins merit further in depth study as photosensitizers in biomedical applications.

A Sn(IV) meso-tetra(4-methylthiolphenyl) N-confused porphyrin (4-Sn) complex was prepared to facilitate a comparison of the photophysicochemical and singlet oxygen photosensitiser properties of a series of Sn(IV) complexes of meso-4-methylthiolphenyl-substituted porphyrin, corrole, chlorin, and N-confused porphyrin. 4-Sn has an unusually high singlet oxygen quantum (?) yield of 0.88, markedly higher than the ? values of the other complexes in this series. A Thorlabs M660L4 LED (280 mW · cm) was used to study the photodynamic activity of Sn-4 against the MCF-7 cancer cell line through irradiation at 660 nm for 30 min. The IC value was calculated to be 1.4 (± 0.8) µM, markedly lower than the previously reported values for the rest of the series. Photodynamic antimicrobial activity was also determined against Staphylococcus aureus and Escherichia coli, and 4-Sn was found to deactivate both Gram-(+) and Gram-(?) bacteria despite the absence of cationic charges on the ligand structure.

A series of tetraarylporphyrin, -chlorin and N-confused porphyrin dyes with 4?methoxy? meso -aryl rings ( 1 -Por, 1 -Chl and 1 -NCP) and their Sn(IV) complexes ( 1 -SnPor, 1 -SnChl and 1 -SnNCP) have been synthesized and characterized. The heavy atom effect of the Sn(IV) ion results in relatively high singlet oxygen quantum yield values of 0.67, 0.71 and 0.85 for 1 -SnPor, 1 -SnChl and 1 -SnNCP, respectively. The photodynamic activities of 1 -Por, 1 -Chl, 1 -NCP, 1 -SnPor, 1 -SnChl and 1 -SnNCP were determined against MCF-7 breast cancer cells through illumination with Thorlabs 625 or 660 nm (240 or 280 mW.cm ?2 ) light emitting diodes (LEDs) for 20 min. The IC 50 values for 1 -SnChl and 1 -SnNCP lie between 1.4 ? 6.1 and 1.6 ? 4.8 µM upon photoirradiation with the 660 and 625 nm LEDs, respectively, while higher values of >10 µM were obtained for 1 -SnPor and the free base dyes. In a similar manner, 1 -SnChl and 1 -SnNCP were found to also have significantly higher photodynamic antimicrobial activity against planktonic Gram-(+) Staphylococcus aureus and Gram-(?) Escherichia coli bacteria than the other dyes studied. Upon illumination with Thorlabs 625 and 660 nm LEDs for 75 min, Log 10 reduction values of 7.62 and > 2.40?3.69 were obtained with 1 and 5 µM solutions, respectively.