Photodynamic inactivation of Escherichia coli with cationic ammonium Zn(ii) phthalocyanines

Abstract

The aim of this work was the development of a family of novel water soluble Zinc(II) phthalocyanines (Pc) for the photodynamic inactivation of Gram-negative bacteria. Pc derivatives 1a, 2a and 3a containing trimethylammonium groups with varied number and nature of the groups at peripheral positions were synthesized by cyclotetramerization of dimethyl amino substituted phthalonitriles in the presence of zinc powder, using 1-chloronaphthalene as a solvent, followed by cationization using dimethyl sulfate. The solubility, singlet oxygen generation ((1)O2) and stability/photostability of each Pc were evaluated as well as the affinity to bacterial cells and their photosensitizing potential against a recombinant bioluminescent Escherichia coli strain, used as a biological model for Gram negative bacteria. The efficiency of photodynamic inactivation was assessed under white and red light at an irradiance of 150 mW cm(-2). All Pc were soluble in phosphate buffer saline and in dimethyl sulfoxide and demonstrated good stability/photostability. The photochemical parameters reveal that Pc 2a and 3a are more efficient singlet oxygen producers than Pc 1a, for which singlet oxygen generation could not be demonstrated. Pc 2a and 3a caused photosensitization in E. coli. The inactivation factors attained with red light were, however, generally higher than those with white light. Under red light Pc 3a and 2a caused, respectively, 5.6 and 4.9 log reduction in the bioluminescence of the E. coli while, with white light, the corresponding inactivation factors were 2.5 and 0.5 log. The order of the PDI efficiency (3a > 2a ⋙ 1a) was determined by the combined effect of solubility, singlet oxygen generation ability and affinity to bacterial cells. Ammonium phthalocyanines with eight charges or containing halogen atoms such as chlorine, when irradiated with red light can, therefore, be regarded as promising photosensitizers for the inactivation of Gram-negative bacteria.

Photoinactivation of Planktonic and Biofilm Forms of Escherichia coli through the Action of Cationic Zinc(II) Phthalocyanines

“…As hypothesised, the ammonium groups of the ZnPc 1 a – 2 a improves the photoinactivation rate and may have led to an increase in the PDI efficiency due to their ability to interact electrostatically through the peripheral positive charge of the PS and the cell‐wall of Gram‐negative bacterium. Also, an increase in the number of ammonium groups, can enhance electrostatic repulsion between these molecules (avoiding aggregation behaviour) and, at the same time, it influences their cell target sites, which altogether can contribute to improve the PDI efficiency ,,…”

“…The cellular localization and preferential binding sites are strongly influenced by the molecular structure as well as the nature, number and distribution of charges on the PS. A recent study of our research group revealed that an increase in the number of ammonium groups on ZnPc improves the photoinactivation rate of these derivatives towards Gram‐negative bacteria ,. Following our interest in the development of efficient PDI photosensitizers, we hypothesise that this can exhibit strong influence in the production of 1 O 2 and PDI efficiency.…”

Turning Photons into Drugs: Phthalocyanine‐Based Photosensitizers as Efficient Photoantimicrobials

“…ZnPc derivatives containing trimethylammonium groups with a varied number and nature of the groups at peripheral positions were described by the Tomé group [43] . The photosensitizing potential of these compounds against a recombinant bioluminescent E. coli strain was shown to be dependent on the nature of the neighbouring group.…”

Antimicrobial photodynamic therapy against Staphylococcus aureus using zinc phthalocyanine and zinc phthalocyanine-integrated TiO2 nanoparticles

“…Also, antimicrobial efficiency of ZnPcs has been tested as in vivo animal models for clinical trials [35,36]. In our previous studies it is observed that synthesized ZnPc has highly promising PDT agent for cancer treatment [23,35,[37][38][39]. For this reason, we have examined APDT efficiency of synthesized ZnPc and ZnPc-TiO 2 in this article.…”

“…Studies in the literature have shown that cationic charges of PSs are more effective [21][22][23]. In addition, this accumulation occurs faster in microbial cells and could selectively bind to these microorganisms while PS accumulation is slow in normal mammalian cells [24].…”