Cationic Porphycenes as Potential Photosensitizers for Antimicrobial Photodynamic Therapy

Abstract

Structures of typical photosensitizers used in antimicrobial photodynamic therapy are based on porphyrins, phthalocyanines and phenothiazinium salts, with cationic charges at physiological pH values. However derivatives of the porphycene macrocycle (a structural isomer of porphyrin) have barely been investigated as antimicrobial agents. Therefore, we report the synthesis of the first tricationic water-soluble porphycene and its basic photochemical properties. We successfully tested it for in vitro photoinactivation of different Gram-positive and Gram-negative bacteria, as well as a fungal species (Candida) in a drug-dose and light-dose dependent manner. We also used the cationic porphycene in vivo to treat an infection model comprising mouse 3 rd degree burns infected with a bioluminescent methicillin-resistant Staphylococcus aureus strain. There was a 2.6-log 10 reduction (p < 0.001) of the bacterial bioluminescence for the PDT-treated group after irradiation with 180 J·cm -2 of red light.

In vitro antimicrobial activity of light-activated phthalocyanines

“…Our results with this compound (at a concentration of 8 mg/l and 40 J/cm 2 ) showed only a partial effect on S. aureus (SF 0.0015, i.e., less than 3 logs) and C. albicans (SF 0.33) cultures, and according to the set criterion, we did not consider it as effective. Similar findings were also noted by Ragás et al [11] and Demidova et al [21], where another cationic substance -poly-L-lysine chlorin e6 (conjugate of poly-L-lysine with chlorin e6) was more effective during photodynamic inactivation of E. coli (0.75 μM, 0.2 J/cm 2 ) than during photodynamic inactivation of S. aureus. To achieve similar results during experiments with S. aureus, it was necessary to increase the irradiation dose up to 20 J/cm 2 .…”

“…During photodynamic inactivation of Gram-negative cells, PS with polycationic molecular structures -created naturally or artificially by binding the positively charged chain -have been used. These substances are therefore better able to bind and penetrate through the negatively charged lipopolysaccharide into Gram-negative bacterial cells [10][11][12].…”

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

“…The great advantage of phthalocyanines, chlorins and (iso)bacteriochlorins as PSs is better absorption of red light, which facilitates treatments of deeper infections and deep-seated tumours, but some of the frequent drawbacks often associated with these compounds include a propensity for aggregation and insufficient solubility in water (Mantareva et al 2013;Sharma et al 2013). Recently, porphycene, which is a structural isomer of porphyrin, is receiving more attention as a PS for PACT (Ragàs et al 2010). Cationic amphiphilic PSs can also be prepared by modification of natural porphyrin-related compunds such as the preparation of derivatives of pyropheophorbide-a (Stamati et al 2010).…”

Acid- and hydrogen-bonding-induced switching between 22-π and 18-π electron conjugations in 2-aminothiazolo[4,5-c]porphycenes

“…These macrocycles were first synthesised by , who named them porphycenes since their structure combines features of both porphyrins and acenes. 1 Their isolation and structural characterisation open up new avenues for the research in multiple fields such as photodynamic therapy, [2][3][4][5] organic solar cells, 6-8 catalysis 9,10 and theranostics. 11 Over the last decade, the photophysical properties of symmetric and asymmetric 18-p porphycene derivatives have been studied, revealing specific properties such as the N-H tautomerization 12,13 or nonlinear optical properties [14][15][16] which set them apart from other related 18-p porphyrinoids.…”