Charge effect on the photoinactivation of Gram-negative and Gram-positive bacteria by cationic meso-substituted porphyrins

<p>Abstract</p> <p>Background</p> <p>In recent times photodynamic antimicrobial therapy has been used to efficiently destroy Gram (+) and Gram (-) bacteria using cationic porphyrins as photosensitizers. There is an increasing interest in this approach, namely in the search of photosensitizers with adequate structural features for an efficient photoinactivation process. In this study we propose to compare the efficiency of seven cationic porphyrins differing in <it>meso</it>-substituent groups, charge number and charge distribution, on the photodynamic inactivation of a Gram (+) bacterium (<it>Enterococcus faecalis</it>) and of a Gram (-) bacterium (<it>Escherichia coli</it>). The present study complements our previous work on the search for photosensitizers that might be considered good candidates for the photoinactivation of a large spectrum of environmental microorganisms.</p> <p>Results</p> <p>Bacterial suspension (10⁷CFU mL^-1) treated with different photosensitizers concentrations (0.5, 1.0 and 5.0 μM) were exposed to white light (40 W m^-2) for a total light dose of 64.8 J cm^-2. The most effective photosensitizers against both bacterial strains were the Tri-Py⁺-Me-PF and Tri-Py⁺-Me-CO₂Me at 5.0 μM with a light fluence of 64.8 J cm^-2, leading to > 7.0 log (> 99,999%) of photoinactivation. The tetracationic porphyrin also proved to be a good photosensitizer against both bacterial strains. Both di-cationic and the monocationic porphyrins were the least effective ones.</p> <p>Conclusion</p> <p>The number of positive charges, the charge distribution in the porphyrins' structure and the <it>meso</it>-substituent groups seem to have different effects on the photoinactivation of both bacteria. As the Tri-Py⁺-Me-PF porphyrin provides the highest log reduction using lower light doses, this photosensitizer can efficiently photoinactivate a large spectrum of environmental bacteria. The complete inactivation of both bacterial strains with low light fluence (40 W m^-2) means that the photodynamic approach can be applied to wastewater treatment under natural light conditions which makes this technology cheap and feasible in terms of the light source.</p

An insight on bacterial cellular targets of photodynamic inactivation

The emergence of microbial resistance is becoming a global problem in clinical and environmental areas. As such, the development of drugs with novel modes of action will be vital to meet the threats created by the rise in microbial resistance. Microbial photodynamic inactivation is receiving considerable attention for its potentialities as a new antimicrobial treatment. This review addresses the interactions between photosensitizers and bacterial cells (binding site and cellular localization), the ultrastructural, morphological and functional changes observed at initial stages and during the course of photodynamic inactivation, the oxidative alterations in specific molecular targets, and a possible development of resistance

Noncovalent functionalization of thiopyridyl porphyrins with ruthenium phthalocyanines

Preconditions for the design of efficient organic solar-light-converting systems are strong absorptions across the visible region, the capacity to funnel excited state energy by intermolecular energy transfer, and alternative association processes in the photoinduced electron transfer. In this context, thiopyridyl porphyrins (PorSPy) and ruthenium phthalocyanines (RuPcs) proved to be versatile building blocks for the construction of novel supramolecular Por-Pc hybrid systems (PorSPy-RuPc) by axial coordination at ruthenium. The thiopyridyl groups placed at the bay region of the porphyrins coordinate the RuPc dye. A notable redistribution of the electron density in the new heterochromophore structures evidences the electron-donating/-accepting communication between the two dyes in the supramolecular hybrids. These structural hybrids were investigated physicochemically by means of their ground and excited state reactivities. Photophysical investigation by time-resolved transient absorption, mainly fluorescence and femtosecond spectroscopy, evidenced efficient intermolecular energy transfer from the photoexcited central porphyrin to the peripheral phthalocyanines in the supramolecular multichromophore ensembles. The findings may give impetus for the design of interesting materials for solar-light-converting systems

Inverted methoxypyridinium phthalocyanines for PDI of pathogenic bacteria

Phthalocyanines (Pc) are photoactive molecules that can absorb and emit light in a large range of the UV-Vis spectrum with recognized potential for medical applications. Considering the biomedical applications an important limitation of these compounds is their low solubility in water. The use of suitable pyridinium groups on Pc is a good strategy to solve this drawback and to make them more effective to photoinactivate Gram-negative bacteria via a photodynamic inactivation (PDI) approach. Herein, an easy synthetic access to obtain inverted tetra-and octa-methoxypyridinium phthalocyanines (compounds 5 and 6) and also their efficiency to photoinactivate a recombinant bioluminescent strain of Escherichia coli is described. The obtained results were compared with the ones obtained when more conventional thiopyridinium phthalocyanines (compounds 7 and 8) were used. This innovative study comparing thiopyridinium and inverted methoxypyridinium moieties on cationic Pc is reported for the first time taking into account the efficiency of singlet oxygen (O-1(2)) generation, water solubility and uptake properties

Synthesis, characterization and biomolecule-binding properties of novel tetra-platinum(II)-thiopyridylporphyrins

The new complexes tetra-platinum(II)-thiopyridylporphyrin 3 and tetra-platinum(II)-thiopyridylporphyrinato Zn(II) 4 were obtained by coordination of the peripheral thiopyridyl units of the free-base 5,10,15,20-tetrakis[2,3,5,6-tetrafluoro-4-(4-pyridylsulfanyl) phenyl] porphyrin 1 or their corresponding zinc complex 2, respectively, with four chloro(2,2'-bipyridine) platinum(II) [Pt(bpy)Cl](+) units. Both compounds were characterized by several spectroscopic techniques demonstrating a particular behaviour in the emission spectra due to the absence or presence of zinc. The tetra-platinum(II)-thiopyridylporphyrins exhibited an increase in the emission quantum yield when compared with the starting thiopyridylporphyrins 1 and 2. Spectroscopic studies of both platinum derivatives reveal their ability to interact unequivocally with DNA from calf thymus and DNA of low molecular weight from salmon sperms, and also with the most abundant protein in human blood plasma, human serum albumin (HSA). Herein, both tetra-platinum(II)-thiopyridylporphyrins 3 and 4 exhibit electrostatic surface binding with the negative phosphate groups of DNA. Similar to cationic-anionic binding with DNA, tetra-platinum(II)-thiopyridylporphyrinato zinc(II) demonstrates a particular binding intercalation mode with DNA. Photophysical studies demonstrated that both porphyrins are photostable and able to generate singlet oxygen (O-1(2)) after light irradiation. Exposure of pMT123 plasmid DNA to tetra-platinum(II)-thiopyridylporphyrins and irradiation with light lead to single-strand breakage as determined by the conversion of the supercoiled form of the plasmid (form I) into the nicked circular form (form II). The tetra-platinum(II)-thiopyridylporphyrinato Zn(II) demonstrates a particular intercalation binding mode with DNA and an ability to cleave DNA after photo-excitation

New platinum(II)-bipyridyl corrole complexes: synthesis, characterization and binding studies with DNA and HSA

A

Amphiphilic phthalocyanine-cyclodextrin conjugates for cancer photodynamic therapy

Three phthalocyanines (Pcs) conjugated with alpha-, beta- and gamma-cyclodextrins (CDs) were prepared and their application as photosensitizer (PS) agents was assessed by photophysical, photochemical and in vitro photobiological studies. The photoactivity of Pc-alpha-CD and Pc-gamma-CD ensures their potential as PDT drugs against UM-UC-3 human bladder cancer cells