opp-Dibenzoporphyrin Pyridinium Derivatives as Potential G-Quadruplex DNA Ligands.

Since the occurrence of tumours is closely associated with the telomerase function and oncogene expression, the structure of such enzymes and genes are being recognized as targets for new anticancer drugs. The efficacy of several ligands in telomerase inhibition and in the regulation of genes expression, by an effective stabilisation of G-quadruplexes (G4) DNA structures, is being considered as a promising strategy in cancer therapies. When evaluating the potential of a ligand for telomerase inhibition, the selectivity towards quadruplex versus duplex DNA is a fundamental attribute due to the large amount of double-stranded DNA in the cellular nucleus. This study reports the evaluated efficacy of three tetracationic opp-dibenzoporphyrins, a free base, and the corresponding zinc(II) and nickel(II) complexes, to stabilise G4 structures, namely the telomeric DNA sequence (AG3(T2AG3)3). In order to evaluate the selectivity of these ligands towards G4 structures, their interaction towards DNA calf thymus, as a double-strand DNA sequence, were also studied. The data obtained by using different spectroscopic techniques, such as ultraviolet-visible, fluorescence, and circular dichroism, suggested good affinity of the free-base porphyrin and of its zinc(II) complex for the considered DNA structures, both showing a pattern of selectivity for the telomeric G4 structure. A pattern of aggregation in aqueous solution was detected for both Zn(II) and Ni(II) metallo dibenzoporphyrins and the ability of DNA sequences to induce ligand disaggregation was observed.

A Comparative Evaluation of the Photosensitizing Efficiency of Porphyrins, Chlorins and Isobacteriochlorins toward Melanoma Cancer Cells.

Skin cancer is one of the cancers that registers the highest number of new cases annually. Among all forms of skin cancer, melanoma is the most invasive and deadliest. The resistance of this form of cancer to conventional treatments has led to the employment of alternative/complementary therapeutic approaches. Photodynamic therapy (PDT) appears to be a promising alternative to overcome the resistance of melanoma to conventional therapies. PDT is a non-invasive therapeutic procedure in which highly reactive oxygen species (ROS) are generated upon excitation of a photosensitizer (PS) when subjected to visible light of an adequate wavelength, resulting in the death of cancer cells. In this work, inspired by the efficacy of tetrapyrrolic macrocycles to act as PS against tumor cells, we report the photophysical characterization and biological assays of isobacteriochlorins and their corresponding chlorins and porphyrins against melanoma cancer cells through a photodynamic process. The non-tumoral L929 fibroblast murine cell line was used as the control. The results show that the choice of adequate tetrapyrrolic macrocycle-based PS can be modulated to improve the performance of PDT.

Photodynamic inactivation of microorganisms in different water matrices: The effect of physicochemical parameters on the treatment outcome.

Wastewater (WW) insufficiently treated for the disinfection of microorganisms, including pathogenic ones, is a source of concern and a possible generator of public health problems. Traditional disinfection methods to reduce pathogens concentration (e.g., chlorination, ozonation, UV) are expensive, unsafe, and/or sometimes ineffective, highlighting the need for new disinfection technologies. The promising results of photodynamic inactivation (PDI) treatment to eradicate microorganisms suggest the efficacy of this treatment to improve WW quality. This work aimed to assess if PDI can be successfully extended to real contexts for the microbial inactivation in WW. For the first time, PDI experiments with 9 different water matrices compositions were performed to inquire about the influence of some of their physicochemical parameters on the effectiveness of microbial inactivation. Bacterial photoinactivation was tested in freshwater, aquaculture water, and seawater samples, as well as in influents and effluents samples from domestic, industrial, and a mixture of industrial and domestic WW receiving wastewater treatment plants (WWTPs). Additionally, PDI assays were performed in phosphate-buffered saline isotonic solution (PBS), used as an aqueous comparative matrix. To relate the PDI disinfection efficiency with the physicochemical compositions of the different used water matrices, a series of statistical analysis were performed, in order to support our main conclusions. Overall, the results showed that PDI is an effective and promising alternative to traditionally used WW disinfection methods, with a bacterial reduction of >3.0 log CFU/mL in all the water matrices within the first hour of PDI treatment, but also that the physicochemical composition of the aqueous matrices to be PDI-disinfected must be taken into account since they seem to influence the PDI efficacy, namely the pH, with acidic pH conditions seeming to be associated to a better PDI performance in general.

Reaction of Corroles with Sarcosine and Paraformaldehyde: A New Facet of Corrole Chemistry.

Details on the unexpected formation of two new (dimethylamino)methyl corrole isomers from the reaction of 5,10,15-tris(pentafluorophenyl)corrolatogallium(III) with sarcosine and paraformaldehyde are presented. Semi-empirical calculations on possible mechanism pathways seem to indicate that the new compounds are probably formed through a Mannich-type reaction. The extension of the protocol to the free-base 5,10,15-tris(pentafluorophenyl)corrole afforded an unexpected new seven-membered ring corrole derivative, confirming the peculiar behavior of corroles towards known reactions when compared to the well-behaved porphyrin counterparts.

Merging Porphyrins with Gold Nanorods: Self Assembly Construct to High Fluorescent Polyelectrolyte Microcapsules.

Dual probe porphyrin-gold nanorod polyelectrolyte microcapsules were developed to explore the enhancing effects of a plasmonic interface of self-assembled gold nanoparticles in the fluorescence emission from porphyrins loaded into the capsules' core. An analysis of fluorescence lifetime imaging microscopy (FLIM) data reports a notable 105-106-fold increase in the maximum detected photon rates from diffraction-limited spots and an overall six-fold increase in fluorescence as averaged over the whole microcapsule area. Large emission enhancements were correlated with decreases in fluorescence lifetimes. The microcapsule's design proved effective in achieving high fluorescent hybrids and may shed light on new possibilities for advanced materials imaging applications.

Photoinactivation of Phage Phi6 as a SARS-CoV-2 Model in Wastewater: Evidence of Efficacy and Safety.

The last two years have been marked by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This virus is found in the intestinal tract; it reaches wastewater systems and, consequently, the natural receiving water bodies. As such, inefficiently treated wastewater (WW) can be a means of contamination. The currently used methods for the disinfection of WW can lead to the formation of toxic compounds and can be expensive or inefficient. As such, new and alternative approaches must be considered, namely, photodynamic inactivation (PDI). In this work, the bacteriophage φ6 (or, simply, phage φ6), which has been used as a suitable model for enveloped RNA viruses, such as coronaviruses (CoVs), was used as a model of SARS-CoV-2. Firstly, to understand the virus's survival in the environment, phage φ6 was subjected to different laboratory-controlled environmental conditions (temperature, pH, salinity, and solar and UV-B irradiation), and its persistence over time was assessed. Second, to assess the efficiency of PDI towards the virus, assays were performed in both phosphate-buffered saline (PBS), a commonly used aqueous matrix, and a secondarily treated WW (a real WW matrix). Third, as WW is generally discharged into the marine environment after treatment, the safety of PDI-treated WW was assessed through the determination of the viability of native marine water microorganisms after their contact with the PDI-treated effluent. Overall, the results showed that, when used as a surrogate for SARS-CoV-2, phage φ6 remains viable in different environmental conditions for a considerable period. Moreover, PDI proved to be an efficient approach in the inactivation of the viruses, and the PDI-treated effluent showed no toxicity to native aquatic microorganisms under realistic dilution conditions, thus endorsing PDI as an efficient and safe tertiary WW disinfection method. Although all studies were performed with phage φ6, which is considered a suitable model of SARS-CoV-2, further studies using SARS-CoV-2 are necessary; nevertheless, the findings show the potential of PDI for controlling SARS-CoV-2 in WW.

The Interactions of H2TMPyP, Analogues and Its Metal Complexes with DNA G-Quadruplexes-An Overview.

The evidence that telomerase is overexpressed in almost 90% of human cancers justifies the proposal of this enzyme as a potential target for anticancer drug design. The inhibition of telomerase by quadruplex stabilizing ligands is being considered a useful approach in anticancer drug design proposals. Several aromatic ligands, including porphyrins, were exploited for telomerase inhibition by adduct formation with G-Quadruplex (GQ). 5,10,15,20-Tetrakis(N-methyl-4-pyridinium)porphyrin (H2TMPyP) is one of the most studied porphyrins in this field, and although reported as presenting high affinity to GQ, its poor selectivity for GQ over duplex structures is recognized. To increase the desired selectivity, porphyrin modifications either at the peripheral positions or at the inner core through the coordination with different metals have been handled. Herein, studies involving the interactions of TMPyP and analogs with different DNA sequences able to form GQ and duplex structures using different experimental conditions and approaches are reviewed. Some considerations concerning the structural diversity and recognition modes of G-quadruplexes will be presented first to facilitate the comprehension of the studies reviewed. Additionally, considering the diversity of experimental conditions reported, we decided to complement this review with a screening where the behavior of H2TMPyP and of some of the reviewed metal complexes were evaluated under the same experimental conditions and using the same DNA sequences. In this comparison under unified conditions, we also evaluated, for the first time, the behavior of the AgII complex of H2TMPyP. In general, all derivatives showed good affinity for GQ DNA structures with binding constants in the range of 106-107 M-1 and ligand-GQ stoichiometric ratios of 3:1 and 4:1. A promising pattern of selectivity was also identified for the new AgII derivative.

The Role of Porphyrinoid Photosensitizers for Skin Wound Healing.

Microorganisms, usually bacteria and fungi, grow and spread in skin wounds, causing infections. These infections trigger the immune system and cause inflammation and tissue damage within the skin or wound, slowing down the healing process. The use of photodynamic therapy (PDT) to eradicate microorganisms has been regarded as a promising alternative to anti-infective therapies, such as those based on antibiotics, and more recently, is being considered for skin wound-healing, namely for infected wounds. Among the several molecules exploited as photosensitizers (PS), porphyrinoids exhibit suitable features for achieving those goals efficiently. The capability that these macrocycles display to generate reactive oxygen species (ROS) gives a significant contribution to the regenerative process. ROS are responsible for avoiding the development of infections by inactivating microorganisms such as bacteria but also by promoting cell proliferation through the activation of stem cells which regulates inflammatory factors and collagen remodeling. The PS can act solo or combined with several materials, such as polymers, hydrogels, nanotubes, or metal-organic frameworks (MOF), keeping both the microbial photoinactivation and healing/regenerative processes' effectiveness. This review highlights the developments on the combination of PDT approach and skin wound healing using natural and synthetic porphyrinoids, such as porphyrins, chlorins and phthalocyanines, as PS, as well as the prodrug 5-aminolevulinic acid (5-ALA), the natural precursor of protoporphyrin-IX (PP-IX).

An Insight into the Role of Non-Porphyrinoid Photosensitizers for Skin Wound Healing.

The concept behind photodynamic therapy (PDT) is being successfully applied in different biomedical contexts such as cancer diseases, inactivation of microorganisms and, more recently, to improve wound healing and tissue regeneration. The effectiveness of PDT in skin treatments is associated with the role of reactive oxygen species (ROS) produced by a photosensitizer (PS), which acts as a "double agent". The release of ROS must be high enough to prevent microbial growth and, simultaneously, to accelerate the immune system response by recruiting important regenerative agents to the wound site. The growing interest in this subject is reflected by the increasing number of studies concerning the optimization of relevant experimental parameters for wound healing via PDT, namely, light features, the structure and concentration of the PS, and the wound type and location. Considering the importance of developing PSs with suitable features for this emergent topic concerning skin wound healing, in this review, a special focus on the achievements attained for each PS class, namely, of the non-porphyrinoid type, is given.

Photodynamic treatment of melanoma cells using aza-dipyrromethenes as photosensitizers.

In this study, we report for the first time the use of four aza-dipyrromethenes (ADPMs) as photosensitizers for cancer PDT. The synthesis and characterization of the ADPMs and their photodynamic action against B16F10 melanoma cells were assessed. ADPM 2 is the best singlet oxygen generator and the most phototoxic (at 2.5 µM) towards B16F10 cells.

Tetrapyrrolic Macrocycles: Synthesis, Functionalization and Applications 2018.

Natural and synthetic macrocycles like porphyrins, corroles and phthalocyanines are considered strong candidates to be used in different fields, such as catalysis, sensing, medicine, materials science, or in the development of advanced biomimetic models. All these applications are strongly dependent on the availability of compounds with adequate and specific structural features. This Special Issue has collected 13 contributions which consolidate and expand our knowledge on the application of these macrocycles in different fields accompanied by innovative synthetic methodologies to afford and to functionalize this type of compounds.

Selective two-photon absorption in carbon dots: a piece of the photoluminescence emission puzzle.

Carbon nanodots (Cdots) are now emerging as promising nonlinear fluorophores for applications in biological environments. A thorough and systematic approach to the two-photon induced emission of Cdots that could provide design guidelines to control their nonlinear emission properties is still missing. In this work, we address the nonlinear optical spectroscopy of Cdots prepared by controlled chemical cutting of graphene oxide (GO). The two-photon absorption in the 700-1000 nm region and the corresponding emission spectrum are carefully investigated. The highest two-photon absorption cross-section estimated was 130 GM at 720 nm. This value is comparable with the one reported for graphene nanoribbons with push-pull architecture. The emission spectrum depends on the excitation mode. At the same excitation energy, nonlinear excitation results in excitation-wavelength independent emission, while upon linear excitation the emission is excitation-wavelength dependent. The biphotonic interaction seems to be selective towards sp2 clusters bearing electron donor and acceptor groups found in push-pull architectures. Both linear and nonlinear emission can be understood based on the existence of isolated sp2 clusters involved in π-π stacking interactions with clusters in adjacent layers.

Evaluation of meso-substituted cationic corroles as potential antibacterial agents.

Cationic derivatives of 5,10,15-tris[4-(pyridin-4-ylsulphanyl)-2,3,5,6-tetrafluorophenyl]-corrolategallium(III)pyridine and 5,10,15-tris[4-(pyridin-2-ylsulfanyl)-2,3,5,6-tetrafluorophenyl]-correlategallium(III)pyridine were synthesized and their photosensitizing properties against the naturally bioluminescent Gram-negative bacterium Allivibrio fischeri were evaluated. The cationic corrole derivatives exhibited antibacterial activity at micromolar concentrations against this Gram-negative bacterium strain.

Fluorescent Bioactive Corrole Grafted-Chitosan Films.

Transparent corrole grafted-chitosan films were prepared by chemical modification of chitosan with a corrole macrocycle, namely, 5,10,15-tris(pentafluorophenyl)corrole (TPFC), followed by solvent casting. The obtained films were characterized in terms of absorption spectra (UV-vis), FLIM (fluorescence lifetime imaging microscopy), structure (FTIR, XPS), thermal stability (TGA), thermomechanical properties (DMA), and antibacterial activity. The results showed that the chemical grafting of chitosan with corrole units did not affect its film-forming ability and that the grafting yield increased with the reaction time. The obtained transparent films presented fluorescence which increases with the amount of grafted corrole units. Additionally, all films showed bacteriostatic effect against S. aureus, as well as good thermomechanical properties and thermal stability. Considering these features, promising applications may be envisaged for these corrole-chitosan films, such as biosensors, bioimaging agents, and bioactive optical devices.

Photodynamic inactivation of mammalian viruses and bacteriophages.

Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

Bioluminescence and its application in the monitoring of antimicrobial photodynamic therapy.

Light output from bioluminescent microorganisms is a highly sensitive reporter of their metabolic activity and therefore can be used to monitor in real time the effects of antimicrobials. Antimicrobial photodynamic therapy (aPDT) is receiving considerable attention for its potentialities as a new antimicrobial treatment modality. This therapy combines oxygen, a nontoxic photoactive photosensitizer, and visible light to generate reactive oxygen species (singlet oxygen and free radicals) that efficiently destroy microorganisms. To monitor this photoinactivation process, faster methods are required instead of laborious conventional plating and overnight incubation procedures. The bioluminescence method is a very interesting approach to achieve this goal. This review covers recent developments on the use of microbial bioluminescence in aPDT in the clinical and environmental areas.