Light-Driven Tetra- and Octa-ß-substituted Cationic Zinc(II) Phthalocyanines for Eradicating Fusarium oxysporum Conidia.

Photodynamic inactivation (PDI) is an emerging therapeutic approach that can effectively inactivate diverse microbial forms, including vegetative forms and spores, while preserving host tissues and avoiding the development of resistance to the photosensitization procedure. This study evaluates the antifungal and sporicidal photodynamic activity of two water-soluble amphiphilic tetra- and octa-ß-substituted zinc(II) phthalocyanine (ZnPc) dyes with dimethylaminopyridinium groups at the periphery (ZnPcs 1, 2) and their quaternized derivatives (ZnPcs 1a, 2a). Tetra(1, 1a)- and octa(2, 2a)-ß-substituted zinc(II) phthalocyanines were prepared and assessed as photosensitizers (PSs) for their effects on Fusarium oxysporum conidia. Antimicrobial photoinactivation experiments were performed with each PS at 0.1, 1, 10, and 20 µM under white light irradiation at an irradiance of 135 mW·cm-2, for 60 min (light dose of 486 J·cm-2). High PDI efficiency was observed for PSs 1a, 2, and 2a (10 µM), corresponding to inactivation until the method's detection limit. PS 1 (20 µM) also achieved a considerable reduction of >5 log10 in the concentration of viable conidia. The quaternized PSs (1a, 2a) showed better PDI performance than the non-quaternized ones (1, 2), even at the low concentration of 1 µM, and a light dose of 486 J·cm-2. These cationic phthalocyanines are potent photodynamic drugs for antifungal applications due to their ability to effectively inactivate resistant forms, like conidia, with low concentrations and reasonable energy doses.

Editorial: Photodynamic Therapy as an Important Tool for Biological Breakthroughs-Photoactive Photosensitizers Applied from Cancer to Microbial Targets.

Photodynamic therapy (PDT) stands as an approved clinical treatment for both oncologic and nononcologic disorders [...].

In Vitro Photoinactivation of Fusarium oxysporum Conidia with Light-Activated Ammonium Phthalocyanines.

Antimicrobial photodynamic therapy (aPDT) has been explored as an innovative therapeutic approach because it can be used to inactivate a variety of microbial forms (vegetative forms and spores) without causing significant damage to host tissues, and without the development of resistance to the photosensitization process. This study assesses the photodynamic antifungal/sporicidal activity of tetra- and octasubstituted phthalocyanine (Pc) dyes with ammonium groups. Tetra- and octasubstituted zinc(II) phthalocyanines (1 and 2) were prepared and tested as photosensitizers (PSs) on Fusarium oxysporum conidia. Photoinactivation (PDI) tests were conducted with photosensitizer (PS) concentrations of 20, 40, and 60 µM under white-light exposure at an irradiance of 135 mW·cm-2, applied during 30 and 60 min (light doses of 243 and 486 J·cm-2). High PDI efficiency corresponding to the inactivation process until the detection limit was observed for both PSs. The tetrasubstituted PS was the most effective, requiring the lowest concentration and the shortest irradiation time for the complete inactivation of conidia (40 µM, 30 min, 243 J·cm-2). Complete inactivation was also achieved with PS 2, but a longer irradiation time and a higher concentration (60 µM, 60 min, 486 J·cm-2) were necessary. Because of the low concentrations and moderate energy doses required to inactivate resistant biological forms such as fungal conidia, these phthalocyanines can be considered potent antifungal photodynamic drugs.

Anti-Viral Photodynamic Inactivation of T4-like Bacteriophage as a Mammalian Virus Model in Blood.

The laboratorial available methods applied in plasma disinfection can induce damage in other blood components. Antimicrobial photodynamic therapy (aPDT) represents a promising approach and is approved for plasma and platelet disinfection using non-porphyrinic photosensitizers (PSs), such as methylene blue (MB). In this study, the photodynamic action of three cationic porphyrins (Tri-Py(+)-Me, Tetra-Py(+)-Me and Tetra-S-Py(+)-Me) towards viruses was evaluated under white light irradiation at an irradiance of 25 and 150 mW·cm-2, and the results were compared with the efficacy of the approved MB. None of the PSs caused hemolysis at the isotonic conditions, using a T4-like phage as a model of mammalian viruses. All porphyrins were more effective than MB in the photoinactivation of the T4-like phage in plasma. Moreover, the most efficient PS promoted a moderate inactivation rate of the T4-like phage in whole blood. Nevertheless, these porphyrins, such as MB, can be considered promising and safe PSs to photoinactivate viruses in blood plasma.

Phthalocyanines for G-quadruplex aptamers binding.

The G-quadruplex (G4)-forming sequence within the AS1411 derivatives with alternative nucleobases and backbones can improve the chemical and biological properties of AS1411. Zn(II) phthalocyanine (ZnPc) derivatives have potential as high-affinity G4 ligands because they have similar size and shape to the G-quartets. The interactions of four Zn(II) phthalocyanines with the G4 AS1411 aptamer and its derivatives were determined by biophysical techniques, molecular docking and gel electrophoresis. Cell viability assay was carried out to evaluate the antiproliferative effects of Zn(II) phthalocyanines and complexes. CD experiments showed structural changes after addition of ZnPc 4, consistent with multiple binding modes and conformations shown by NMR and gel electrophoresis. CD melting confirmed that ZnPc 2 and ZnPc 4, both containing eight positive charges, are able to stabilize the AT11 G4 structure (ΔTm > 30 °C and 18.5 °C, respectively). Molecular docking studies of ZnPc 3 and ZnPc 4 suggested a preferential binding to the 3'- and 5'-end, respectively, of the AT11 G4. ZnPc 3 and its AT11 and AT11-L0 complexes revealed pronounced cytotoxic effect against cervical cancer cells and no cytotoxicity to normal human cells. Zn(II) phthalocyanines provide the basis for the development of effective therapeutic agents as G4 ligands.

Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures.

The stabilization of G-Quadruplex DNA structures by ligands is a promising strategy for telomerase inhibition in cancer therapy since this enzyme is responsible for the unlimited proliferation of cancer cells. To assess the potential of a compound as a telomerase inhibitor, selectivity for quadruplex over duplex DNA is a fundamental attribute, as the drug must be able to recognize quadruplex DNA in the presence of a large amount of duplex DNA, in the cellular nucleus. By using different spectroscopic techniques, such as ultraviolet-visible, fluorescence and circular dichroism, this work evaluates the potential of a series of multicharged phthalocyanines, bearing four or eight positive charges, as G-Quadruplex stabilizing ligands. This work led us to conclude that the existence of a balance between the number and position of the positive charges in the phthalocyanine structure is a fundamental attribute for its selectivity for G-Quadruplex structures over duplex DNA structures. Two of the studied phthalocyanines, one with four peripheral positive charges (ZnPc1) and the other with less exposed eight positive charges (ZnPc4) showed high selectivity and affinity for G-Quadruplex over duplex DNA structures and were able to accumulate in the nucleus of UM-UC-3 bladder cancer cells.

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 ((1)O2) generation, water solubility and uptake properties.

Unveiling the potent antimicrobial photodynamic therapy in Gram-positive and Gram-negative bacteria - Water remediation with monocharged chlorins.

Water pollution is a significant concern worldwide, and it includes contaminants such as antibiotic-resistant pathogens. Antimicrobial photodynamic therapy (aPDT) offers a non-invasive and non-toxic alternative for the inactivation of these microorganisms. So, this study reports the synthesis, structural characterisation, photophysical properties, and aPDT efficacy of cationic free-base and zinc(II) chlorin (Chl) derivatives bearing N,N-dimethylpyrrolydinium groups (H2Chl 1a and ZnChl 1b). The aPDT assays were performed against two bacterial models: Staphylococcus aureus (Gram-(+)) and Escherichia coli (Gram-(-)). The H2Chl 1a and ZnChl 1b distinct's solubility profile, coupled with their ability to generate singlet oxygen (1O2) under light exposure, (H2Chl 1a, Ð¤Δ = 0.58 < TPP, Ð¤Δ = 0.65 < ZnChl 1b, Ð¤Δ = 0.83) opens up their potential application as photosensitizers (PS) in aPDT. The effectiveness of H2Chl 1a and ZnChl 1b at 1.0 and 5.0 µM in aPDT against S. aureus and E. coli at 500 W m-2 (total exposure time: 60-120 min) showed a viability reduction >6.0 log10 CFU mL-1. Additionally, KI was used as a coadjuvant to potentiate the photoinactivation of E. coli, reaching the method's detection limit (>4.0 log10 RLU). As most of the PS developed to inactivate Gram-negative bacteria are cationic with three or more charges, the fact that the H2Chl 1a and ZnChl 1b with only one cationic charge photoinactivate E. coli at low concentrations and with a reduced light dose, it is an importing discovery that deserves further exploration. These monocharged chlorin dyes have the potential for water remediation.

Bacterial Photodynamic Inactivation: Eradication of Staphylococcus aureus and Escherichia coli Mediated by Pyridinium-Pyrazolyl Zinc(II) Phthalocyanines.

Antimicrobial resistance remains an enduring global health issue, manifested when microorganisms, such as bacteria, lack responsiveness to antimicrobial treatments. Photodynamic inactivation (PDI) of microorganisms arises as a noninvasive, nontoxic, and repeatable alternative for the inactivation of a broad range of pathogens. So, this study reports the synthesis, structural characterization, and photophysical properties of a new tetra-ß-substituted pyridinium-pyrazolyl zinc(II) phthalocyanine (ZnPc 1a) that was compared with two previously described pyridinium-pyrazolyl ZnPcs 2a and 3a. The PDI efficacy of these three ZnPcs (1a-3a) against a drug-resistant Gram-positive bacterium (as Staphylococcus aureus) and a Gram-negative bacterium (as Escherichia coli) is also reported. The PDI efficacy toward these bacteria was examined with ZnPcs 1a-3a in the 5.0-10.0 µM range using a white light source with an irradiance of 150 mW/cm2. All ZnPcs displayed a significant PDI activity against S. aureus, with reductions superior to 3 Log CFU/mL. Increasing the treatment time, the E. coli was inactivated until the detection limit of the method (>6.3 Log CFU/mL) using the quaternized ZnPcs 1a-3a (10.0 µM, 120 min) being the inactivation time was reduced when added the KI for ZnPcs 1a and 3a. These findings demonstrate the effective PDI performance of pyridinium-pyrazolyl group-bearing PSs, indicating their potential use as a versatile antimicrobial agent for managing infections induced by Gram-negative and Gram-positive bacteria.

Advances in photocatalytic degradation of organic pollutants in wastewaters: harnessing the power of phthalocyanines and phthalocyanine-containing materials.

Access to clean water is increasingly challenging worldwide due to human activities and climate change. Wastewater treatment and utilization offer a promising solution by reducing the reliance on pure underground water. However, it is crucial to develop efficient and sustainable methods for wastewater purification. Among the emerging wastewater treatment strategies, photocatalysis has gained significant attention for decomposing organic pollutants in water, especially when combined with sunlight and a recoverable photocatalyst. Heterogeneous photocatalysts have distinct advantages, as they can be recovered and reused without significant loss of activity over multiple cycles. Phthalocyanine dyes, with their exceptional photophysical properties, are particularly valuable for homogeneous and heterogeneous photocatalysis. By immobilizing these photosensitizers in various supports, hybrid materials extend their light absorption into the visible spectrum, complementing most supports' limited UV light absorption. The novelty and research importance of this review stems from its discussion of the multifaceted approach to treating contaminated wastewater with phthalocyanines and materials containing phthalocyanines. It highlights key aspects of each study, including photocatalytic efficiency, recyclability characteristics, investigation of the generation of oxygen species responsible for degradation, identification of the major degradation byproducts for each pollutant, and others. Moreover, the review includes tables that illustrate and compare the various phthalocyanines and supporting materials employed in each study for pollutant degradation. Additionally, almost all photocatalysts mentioned in this review could degrade at least 5% of the pollutant, and more than 50 photocatalysts showed photocatalytic rates above 50%. When immobilized in some support, the synergistic effect of the phthalocyanine was visible in the photocatalytic rate of the studied pollutant. However, when performing these types of works, it is necessary to understand the degradation products of each pollutant and their relative toxicities. Along with this, recyclability and stability studies are also necessary. Despite the good results presented in this review, some of the works lack those studies. Moreover, none of the works mentions any study in wastewater.

Unique multiphthalocyanine coordination systems: vibrationally hot excited states and charge transfer states that power high energy triplet charge separated states.

Controlling the molecular architecture of well-organized organic building blocks and linking their functionalities with the impact of solar-light converting systems constitutes a grand challenge in materials science. Strong absorption cross-sections across the visible range of the solar spectrum as well as a finely balanced energy- and redox-gradient are all important features that pave the way for either funneling excited state energy or transducing charges. In light of this, we used thiopyridyl-phthalocyanines (PcSPy) and ruthenium (tert-butyl)-phthalocyanines (RuPc) as versatile building blocks and demonstrated the realization of a family of multi-functional PcSPy-RuPc 1-4 by means of axial coordination. Sizeable electronic couplings between the electron donors and acceptors in PcSPy-RuPc 1-4 govern ground-state as well as excited-state reactivity. Time-resolved techniques, in general, and fluorescence and transient absorption spectroscopy, in particular, helped to corroborate a rapid charge separation next to a slow charge recombination. Key to these charge transfer characteristics are higher lying, vibrationally hot states of the singlet excited states in parallel with a charge transfer state and the presence of several heavy atom effects that are provided by ruthenium and sulfur. As such, our advanced investigations confirm that rapid charge separation evolves from both higher lying, vibrationally hot states as well as from a charge transfer state, populating charge separated states, whose energies exceed those of the singlet excited states. Charge recombination involves triplet rather than singlet charge separated states, which delays the charge recombination by one order of magnitude.

The Antimicrobial Photoinactivation Effect on Escherichia coli through the Action of Inverted Cationic Porphyrin-Cyclodextrin Conjugates.

Photodynamic action has been used for diverse biomedical applications, such as treating a broad range of bacterial infections. Based on the combination of light, dioxygen, and photosensitizer (PS), the photodynamic inactivation (PDI) approach led to the formation of reactive oxygen species (ROS) and represented a non-invasive, non-toxic, repeatable procedure for pathogen photoinactivation. To this end, different tetrapyrrolic macrocycles, such as porphyrin (Por) dyes, have been used as PSs for PDI against microorganisms, mainly bacteria. Still, there is significant room for improvement, especially new PS molecules. Herein, unsymmetrical new pyridinone (3−5) and thiopyridyl Pors (7) were prepared with α-, ß-, or γ-cyclodextrin (CD) units, following their quaternization to perform the corresponding free-base Pors (3a−5a and 7a), and were compared with the already-known Pors 6a and 8a, both bearing thiopyridinium and CD units. These water-soluble porphyrins were evaluated as PSs, and their photophysical and photochemical properties and photodynamic effects on E. coli were assessed. The presence of one CD unit and three positive charges on the Por structure (3a−5a and 7a) enhanced their aqueous solubility. The photoactivity of the cationic Pors 3a−5a and 6a−8a ensured their potential against the Gram-negative bacterium E. coli. Within each series of methoxypyridinium vs thiopyridinium dyes, the best PDI efficiency was achieved for 5a with a bacterial viability reduction of 3.5 log10 (50 mW cm−2, 60 min of light irradiation) and for 8a with a total bacterial viability reduction (>8 log10, 25 mW cm−2, 30 min of light irradiation). Here, the presence of the methoxypyridinium units is less effective against E. coli when compared with the thiopyridinium moieties. This study allows for the conclusion that the peripheral charge position, quaternized substituent type/CD unit, and affinity to the outer bacterial structures play an important role in the photoinactivation efficiency of E. coli, evidencing that these features should be further addressed in the pursuit for optimised PS for the antimicrobial PDI of pathogenic microorganisms.

Interfacial assembly of zinc(II) phthalocyanines on graphene oxide (GO): Stable "turn-off-on" nanoplatforms to detect G-quadruplexes (G4).

HYPOTHESIS: The aggregation of phthalocyanines (Pcs) enfeebles their suitability as G-quadruplex (G4) ligands over time. It is hypothesized that the interfacial assembly of Pcs on graphene oxide (GO) influences intermolecular interactions, thereby affecting their physicochemical properties and inducing stabilization of Pcs in solution. Hence, the stacking of Pcs on GO could be tuned to create nanosystems with the ability to detect G4 for longer periods through a slow release of Pcs. EXPERIMENTS: Four cationic structurally-related zinc(II) phthalocyanines (ZnPc) were non-covalently assembled on GO by ultrasonic exfoliation. A comprehensive characterization of ZnPcs@GO was carried out by spectroscopic techniques and electron microscopy to understand the organization of ZnPcs on GO. The fluorescence of ZnPcs@GO was studied in the presence of G4 (T2G5T)4 and duplex ds26 through spectrofluorimetric titrations and monitored along time. FINDINGS: GO induced a re-organization of the ZnPcs mostly to J-aggregates and quenched their original fluorescence up to 98 % ("turn-off"). In general, ZnPcs@GO recovered their fluorescence ("turn-on") after the titrations and showed affinity to G4 (KD up to 1.92 µM). This is the first report that highlights the contribution of GO interfaces to assemble ZnPcs and allow their slow and controlled release to detect G4 over longer periods.

Graphene Quantum Dots and Phthalocyanines Turn-OFF-ON Photoluminescence Nanosensor for ds-DNA.

Supramolecular hybrids of graphene quantum dots (GQDs) and phthalocyanine (Pc) dyes were studied as turn-OFF-ON photoluminescence nanosensors for detection of ds-DNA. Pcs with four (Pc4) and eight (Pc8) positive charges were selected to interact with negatively charged GQDs. The photoluminescence of the GQDs was quenched upon interaction with the Pcs, due to the formation of non-emissive complexes. In the presence of ds-DNA, the Pcs interacted preferentially with the negatively charged ds-DNA, lifting the quenching effect over the photoluminescence of the GQDs and restoring their emission intensity. The best performance as a sensor of ds-DNA was registered for the GQD-Pc8, with a limit of detection (LOD) in the picomolar range. The LOD for GQD-Pc8 was more than one order of magnitude lower and its sensitivity was about a factor of three higher than that of the analogue GQD-Pc4 nanosensor. The sensitivity and selectivity of this simple GQD-Pc8 nanosensor is comparable to those of the more sophisticated carbon-based nanosensors for DNA reported previously.

The Surprisingly Positive Effect of Zinc-Phthalocyanines With High Photodynamic Therapy Efficacy of Melanoma Cancer.

Phthalocyanine (Pc) dyes are photoactive molecules that can absorb and emit light in the visible spectrum, especially in the red region of the spectrum, with great potential for biological scopes. For this target, it is important to guarantee a high Pc solubility, and the use of suitable pyridinium units on their structure can be a good strategy to use effective photosensitizers (PSs) for photodynamic therapy (PDT) against cancer cells. Zn(II) phthalocyanines (ZnPcs) conjugated with thiopyridinium units (1-3) were evaluated as PS drugs against B16F10 melanoma cells, and their photophysical, photochemical, and in vitro photobiological properties were determined. The photodynamic efficiency of the tetra- and octa-cationic ZnPcs 1-3 was studied and compared at 1, 2, 5, 10, and 20 µM. The different number of charge units, and the presence/absence of a-F atoms on the Pc structure, contributes for their PDT efficacy. The 3-(4',5'-dimethylthiazol-2'-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays on B16F10 melanoma cells show a moderate to high capacity to be photoinactivated by ZnPcs 1-3 (ZnPc 1 > ZnPc 2 > ZnPc 3). The best PDT conditions were found at a Pc concentration of 20 µM, under red light (λ = 660 ± 20 nm) at an irradiance of 4.5 mW/cm2 for 667 s (light dose of 3 J/cm2). In these conditions, it is noteworthy that the cationic ZnPc 1 shows a promising photoinactivation ratio, reaching the detection limit of the MTT method. Moreover, these results are comparable to the better ones in the literature.

Photodynamic inactivation of pathogenic Gram-negative and Gram-positive bacteria mediated by Si(IV) phthalocyanines bearing axial ammonium units.

The photodynamic inactivation (PDI) of microorganisms has gained interest as an efficient option for conventional antibiotic treatments. Recently, Si(IV) phthalocyanines (SiPcs) have been highlighted as promising photosensitizers (PSs) to the PDI of microorganisms due to their remarkable absorption and emission features. To increase the potential of cationic SiPcs as PS drugs, one novel (1a) and two previously described (2a and 3a) axially substituted PSs with di-, tetra-, and hexa-ammonium units, respectively, were synthesized and characterized. Their PDI effect was evaluated for the first time against Escherichia coli and Staphylococcus aureus, a Gram-negative and a Gram-positive bacterium, respectively. The photodynamic treatments were conducted with PS concentrations of 3.0 and 6.0 µM under 60 min of white light irradiation (150 mW.cm-2). The biological results show high photodynamic efficiency for di- and tetra-cationic PSs 1a and 2a (6.0 µM), reducing the E. coli viability in 5.2 and 3.9 log, respectively (after 15 min of dark incubation before irradiation). For PS 3a, a similar bacterial reduction (3.6 log) was achieved but only with an extended dark incubation period (30 min). Under the same experimental conditions, the photodynamic effect of cationic PSs 1a-3a on S. aureus was even more promising, with abundance reductions of ca. 8.0 log after 45-60 min of PDI treatment. These results reveal the high PDI efficiency of PSs bearing ammonium groups and suggest their promising application as a broad-spectrum antimicrobial to control infections caused by Gram-negative and Gram-positive bacteria.

Thiopyridinium phthalocyanine for improved photodynamic efficiency against pathogenic fungi.

The emergence of opportunistic pathogens and the selection of resistant strains have created a grim scenario for conventional antimicrobials. Consequently, there is an ongoing search for alternative techniques to control these microorganisms. One such technique is antimicrobial photodynamic therapy (aPDT), which combines photosensitizers, light, and molecular oxygen to produce reactive oxygen species and kill the target pathogen. Here, the in vitro susceptibilities of three fungal pathogens, namely Candida albicans, Aspergillus nidulans, and Colletotrichum abscissum to aPDT with zinc(II) phthalocyanine (ZnPc) derivative complexes were investigated. Three ZnPc bearing thiopyridinium substituents were synthesized and characterized by several spectroscopic techniques. The Q-band showed sensitivity to the substituent with high absorptivity coefficient in the 680-720 nm region. Derivatization and position of the rings with thiopyridinium units led to high antifungal efficiency of the cationic phthalocyanines, which could be correlated with singlet oxygen quantum yield, subcellular localization, and cellular uptake. The minimum inhibitory concentrations (MIC) of the investigated ZnPc-R complexes against the studied microorganisms were 2.5 µM (C. albicans) and 5 µM (A. nidulans and C. abscissum). One ZnPc derivative achieved complete photokilling of C. albicans and, furthermore, yielded low MIC values when used against the tolerant plant-pathogen C. abscissum. Our results show that chemical modification is an important step in producing better photosensitizers for aPDT against fungal pathogens.

5,10,15,20-Tetra-kis(1-methyl-pyridinium-4-yl)porphyrin tetra-iodide tetra-hydrate.

The asymmetric unit of the title compound, C(44)H(38)N(8) (2+)·4I(-)·4H(2)O, comprises two halves of non-equivalent cations of 5,10,15,20-tetra-kis-(1-methyl-pyridinium)porphyrin (with the full mol-ecule of each completed by the application of inversion symmetry), four charge balancing iodide anions and four water mol-ecules of crystallization (two water mol-ecules are fully occupied and four mol-ecules have a site occupancy of 50%). The porphyrin cations are arranged into supramolecular columns parallel to the b axis, mediated by π-π [centroid-centroid distance = 3.762 (4) Å] and C-H⋯π supra-molecular inter-actions [C⋯centroid distance = 3.522 (7) Å, C-H⋯centroid = 128°], leading to the formation of columns parallel to the b axis. The close packing leads to the presence of a one-dimensional channel filled with partially occupied water mol-ecules engaged in O-H⋯O and O-H⋯I hydrogen bonds.

Photoinactivation of Escherichia coli with Water-Soluble Ammonium-Substituted Phthalocyanines.

Zinc(II) phthalocyanines (Pcs) peripherally decorated with 2,4,6-tris(dimethylaminomethyl)phenoxy groups (Pcs 1 and 3) and the corresponding quaternized derivatives (Pcs 2 and 4) were synthesized and their photodynamic inactivation (PDI) efficiency against recombinant bioluminescent Escherichia coli was examined. The photophysical data revealed that the presence of the ammonium units on the Pc structures promotes a redshift of the absorption bands when compared with the corresponding nonquaternized ones. The ammonium-substituted Pcs 2 and 4 showed excellent stability in dimethylformamide, moderate photostability, and increased efficiency to generate singlet oxygen (1O2). The water-soluble photosensitizers 2 and 4 at 5.0 µM exhibited a high photodynamic inactivation (PDI) efficiency against planktonic bioluminescent E. coli, reaching the detection limit of the methodology (a decrease of ∼4 log in the bioluminescence signal) after 210 min and 150 min under red light, delivered at a fluence rate of 135 mW·cm-2, respectively. Moreover, for the first time, it was accessed with the combined action of KI with ammonium-substituted Pcs. The addition of potassium iodide significantly improved the efficacy of Pc 2, which could reach the same inactivation rate after a short period of 5 min under the same irradiation conditions. The use of KI potentiates the PDI efficacy probably because of the generation of additional highly cytotoxic species during the photodynamic process which begins with the reaction of 1O2 with KI producing peroxyiodide species. The results of this work show that Pcs 2 and 4, with or without KI, can be considered as promising Pc dyes for the PDI of Gram-negative bacteria.

Unsymmetrical cationic porphyrin-cyclodextrin bioconjugates for photoinactivation of Escherichia coli.

Photodynamic inactivation (PDI) of microorganisms has been used for the treatment of bacterial infection. PDI is based on the combination of three non-toxic elements: a photosensitizer (PS), light and molecular oxygen, which lead to the formation of reactive oxygen species (ROS) that cause lethal oxidative damage into the target pathogenic bacteria. For that, clinical approved tetrapyrrolic macrocycles, with particular emphasis on photoactive porphyrin (Por) dyes, have been used as PS in PDI for different biomedical applications. Two novel unsymmetrical free-base thiopyridyl Pors conjugated with α- or γ-CD units (Pors 2 and 3) were prepared and the corresponding cationic ones (Pors 2a and 3a) were assessed as water-soluble photosensitizer (PS) agents by photophysical, photochemical and E. coli photobiological studies. The presence of the CD unit and the positive charges on the Por periphery (2a and 3a) enhance their solubility in aqueous media. The photoactivity of the two cationic Pors 2a and 3a ensures their potential as PDI drugs against Gram-negative bacteria model, a bioluminescent E. coli, which the best PDI efficiency was determined for Por 3a that achieved the highest bacterial reduction of 4.0 log10 (ANOVA, p < 0.0001), reaching the detection limit of the method after 15 min.