Synthesis and Photovoltaic Performance of ß-Amino-Substituted Porphyrin Derivatives.

New ß-amino-substituted porphyrin derivatives bearing carboxy groups were synthesized and their performance as sensitizers in dye-sensitized solar cells (DSSC) was evaluated. The new compounds were obtained in good yields (63-74%) through nucleophilic aromatic substitution reactions with 3-sulfanyl- and 4-sulfanylbenzoic acids. Although the electrochemical studies indicated suitable HOMO and LUMO energy levels for use in DSSC, the devices fabricated with these compounds revealed a low power conversion efficiency (PCE) that is primarily due to the low open-circuit voltage (Voc) and short-circuit current density (Jsc) values.

Porphyrin Photosensitizers Grafted in Cellulose Supports: A Review.

Cellulose is the most abundant natural biopolymer and owing to its compatibility with biological tissues, it is considered a versatile starting material for developing new and sustainable materials from renewable resources. With the advent of drug-resistance among pathogenic microorganisms, recent strategies have focused on the development of novel treatment options and alternative antimicrobial therapies, such as antimicrobial photodynamic therapy (aPDT). This approach encompasses the combination of photoactive dyes and harmless visible light, in the presence of dioxygen, to produce reactive oxygen species that can selectively kill microorganisms. Photosensitizers for aPDT can be adsorbed, entrapped, or linked to cellulose-like supports, providing an increase in the surface area, with improved mechanical strength, barrier, and antimicrobial properties, paving the way to new applications, such as wound disinfection, sterilization of medical materials and surfaces in different contexts (industrial, household and hospital), or prevention of microbial contamination in packaged food. This review will report the development of porphyrinic photosensitizers supported on cellulose/cellulose derivative materials to achieve effective photoinactivation. A brief overview of the efficiency of cellulose based photoactive dyes for cancer, using photodynamic therapy (PDT), will be also discussed. Particular attention will be devoted to the synthetic routes behind the preparation of the photosensitizer-cellulose functional materials.

Efficient Strategies to Use ß-Cationic Porphyrin-Imidazolium Derivatives in the Photoinactivation of Methicillin-Resistant Staphylococcus aureus.

Bacterial resistance to antibiotics is a critical global health issue and the development of alternatives to conventional antibiotics is of the upmost relevance. Antimicrobial photodynamic therapy (aPDT) is considered a promising and innovative approach for the photoinactivation of microorganisms, particularly in cases where traditional antibiotics may be less effective due to resistance or other limitations. In this study, two ß-modified monocharged porphyrin-imidazolium derivatives were efficiently incorporated into polyvinylpyrrolidone (PVP) formulations and supported into graphitic carbon nitride materials. Both porphyrin-imidazolium derivatives displayed remarkable photostability and the ability to generate cytotoxic singlet oxygen. These properties, which have an important impact on achieving an efficient photodynamic effect, were not compromised after incorporation/immobilization. The prepared PVP-porphyrin formulations and the graphitic carbon nitride-based materials displayed excellent performance as photosensitizers to photoinactivate methicillin-resistant Staphylococcus aureus (MRSA) (99.9999% of bacteria) throughout the antimicrobial photodynamic therapy. In each matrix, the most rapid action against S. aureus was observed when using PS 2. The PVP-2 formulation needed 10 min of exposure to white light at 5.0 µm, while the graphitic carbon nitride hybrid GCNM-2 required 20 min at 25.0 µm to achieve a similar level of response. These findings suggest the potential of graphitic carbon nitride-porphyrinic hybrids to be used in the environmental or clinical fields, avoiding the use of organic solvents, and might allow for their recovery after treatment, improving their applicability for bacteria photoinactivation.

Sulfonamide Porphyrins as Potent Photosensitizers against Multidrug-Resistant Staphylococcus aureus (MRSA): The Role of Co-Adjuvants.

Sulfonamides are a conventional class of antibiotics that are well-suited to combat infections. However, their overuse leads to antimicrobial resistance. Porphyrins and analogs have demonstrated excellent photosensitizing properties and have been used as antimicrobial agents to photoinactivate microorganisms, including multiresistant Staphylococcus aureus (MRSA) strains. It is well recognized that the combination of different therapeutic agents might improve the biological outcome. In this present work, a novel meso-arylporphyrin and its Zn(II) complex functionalized with sulfonamide groups were synthesized and characterized and the antibacterial activity towards MRSA with and without the presence of the adjuvant KI was evaluated. For comparison, the studies were also extended to the corresponding sulfonated porphyrin TPP(SO3H)4. Photodynamic studies revealed that all porphyrin derivatives were effective in photoinactivating MRSA (>99.9% of reduction) at a concentration of 5.0 µM upon white light radiation with an irradiance of 25 mW cm-2 and a total light dose of 15 J cm-2. The combination of the porphyrin photosensitizers with the co-adjuvant KI during the photodynamic treatment proved to be very promising allowing a significant reduction in the treatment time and photosensitizer concentration by six times and at least five times, respectively. The combined effect observed for TPP(SO2NHEt)4 and ZnTPP(SO2NHEt)4 with KI seems to be due to the formation of reactive iodine radicals. In the photodynamic studies with TPP(SO3H)4 plus KI, the cooperative action was mainly due to the formation of free iodine (I2).

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.

Cationic Pyrrolidine/Pyrroline-Substituted Porphyrins as Efficient Photosensitizers against E. coli.

New porphyrin-pyrrolidine/pyrroline conjugates were prepared by revisiting 1,3-dipolar cycloaddition reactions between a porphyrinic azomethine ylide and a series of dipolarophiles. Cationic conjugates obtained by alkylation of the pyrrolidine/pyrroline cycloadducts showed ability to generate singlet oxygen and to produce iodine in presence of KI when irradiated with visible light. Some of the cationic derivatives showed photobactericidal properties towards a Gram-negative bioluminescent E. coli. In all cases, these features were significantly improved using KI as coadjutant, allowing, under the tested conditions, the photoinactivation of the bacterium until the detection limit of the method with a drastic reduction of the required photosensitizer concentration and irradiation time. The obtained results showed a high correlation between the ability of the cationic porphyrin derivative to produce singlet oxygen and iodine and its E. coli photoinactivation profile.

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.

New nitroindazole-porphyrin conjugates: Synthesis, characterization and antibacterial properties.

The synthesis of new porphyrin-indazole hybrids by a Knoevenagel condensation of 2-formyl-5,10,15,20-tetraphenylporphyrin and N-methyl-nitroindazolylacetonitrile derivatives is reported. The target compounds were isolated in moderate to good yields (32-57%) and some of the isolated porphyrin-indazole conjugates showed good performance in the generation of singlet oxygen when irradiated with visible light. Their efficiency as photosensitizers in the photoinactivation of methicillin resistant Staphylococcus aureus-MRSA was evaluated. All derivatives showed to be able to photoinactivate the MRSA bacteria. Compound 3a appears to be the most promising photosensitiser (PS) in the photoinactivation of these bacteria, despite being the least efficient in singlet oxygen generation. The addition of potassium iodide (KI) significantly potentiated the antimicrobial Photodynamic Therapy (aPDT) process mediated by all the analysed porphyrin-indazole conjugates. The combined action of nitroindazole-porphyrins with potassium iodide (KI) action appears to be promising in the photoinactivation of MRSA.

Azides and Porphyrinoids: Synthetic Approaches and Applications. Part 2-Azides, Phthalocyanines, Subphthalocyanines and Porphyrazines.

The reaction between organic azides and alkyne derivatives via the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is an efficient strategy to combine phthalocyanines and analogues with different materials. As examples of such materials, it can be considered the following ones: graphene oxide, carbon nanotubes, silica nanoparticles, gold nanoparticles, and quantum dots. This approach is also being relevant to conjugate phthalocyanines with carbohydrates and to obtain new sophisticated molecules; in such way, new systems with significant potential applications become available. This review highlights recent developments on the synthesis of phthalocyanine, subphthalocyanine, and porphyrazine derivatives where CuAAC reactions are the key synthetic step.

Synthesis, Characterization and Photodynamic Activity against Bladder Cancer Cells of Novel Triazole-Porphyrin Derivatives.

Novel triazole-porphyrin derivatives (TZ-PORs) were synthesized through the Heck reaction and then incorporated into polyvinylpyrrolidone (PVP) micelles. After verifying that this incorporation did not compromise the photophysical and chemical features of TZ-PORs as photosensitizers, the phototoxicity of the formulations towards cancer cells was screened. Biological studies show high photodynamic activity of all PVP-TZ-POR formulations against a bladder cancer cell line with a particular highlight to PVP-TZ-POR 7e and 7f that are able to significantly reduce HT-1376 cell viability, while they had no effect on control ARPE-19 cells.

Azides and Porphyrinoids: Synthetic Approaches and Applications. Part 1-Azides, Porphyrins and Corroles.

Azides and porphyrinoids (such as porphyrin and corrole macrocycles) can give rise to new derivatives with significant biological properties and as new materials' components. Significant synthetic approaches have been studied. A wide range of products (e.g., microporous organic networks, rotaxane and dendritic motifs, dendrimers as liquid crystals, as blood substitutes for transfusions and many others) can now be available and used for several medicinal and industrial purposes.

Synthesis and photodynamic effects of new porphyrin/4-oxoquinoline derivatives in the inactivation of S. aureus.

New porphyrin/4-oxoquinoline conjugates were synthesized from the Heck coupling reaction of a ß-brominated porphyrin with 1-allyl-4-oxoquinoline derivatives, followed by demetallation and deprotection affording the promising photosensitizers 9a-e. Singlet oxygen studies have demonstrated that all the porphyrin/4-oxoquinoline conjugates 9a-e were capable of producing cytotoxic species and found to be excellent photosensitizing agents in the inactivation of S. aureus by the antimicrobial photodynamic therapy (aPDT) protocol.

A Suitable Functionalization of Nitroindazoles with Triazolyl and Pyrazolyl Moieties via Cycloaddition Reactions.

The alkylation of a series of nitroindazole derivatives with 1,2-dibromoethane afforded the corresponding N-(2-bromoethyl)- and N-vinyl-nitro-1H-indazoles. The Cu(I)-catalysed azide- alkyne 1,3-dipolar cycloaddition was selected to substitute the nitroindazole core with 1,4-disubstituted triazole units after converting one of the N-(2-bromoethyl)nitroindazoles into the corresponding azide. The reactivity in 1,3-dipolar cycloaddition reactions with nitrile imines generated in situ from ethyl hydrazono-α-bromoglyoxylates was studied with nitroindazoles bearing a vinyl unit. The corresponding nitroindazole-pyrazoline derivatives were obtained in good to excellent yields.

Photoinactivation of Pseudomonas syringae pv. actinidiae in kiwifruit plants by cationic porphyrins.

MAIN CONCLUSION: The studied cationic porphyrins formulation allows an effective photoinactivation of Pseudomonas syringae pv. actinidiae in kiwifruit leaves under sunlight irradiation, without damaging the plant. Pseudomonas syringae pv. actinidiae (Psa) is a Gram-negative phytopathogenic bacterium responsible for canker on kiwifruit plant. Over the last decade, this bacterium dramatically affected the production of this fruit worldwide, causing significant economic losses. In general, Psa control consists in the application of copper which are toxic and persist in the environment. The application of antimicrobial photodynamic therapy (aPDT) as an alternative to inactivate Psa has already been demonstrated in recent studies that showed a 4 log Psa reduction using the cationic porphyrin Tetra-Py+-Me as photosensitizer (PS) and 3 consecutive cycles of treatment with a light irradiance of 150 mW cm-2. The present work aimed to evaluate the photodynamic efficiency of a new formulation constituted with five cationic porphyrins as PS in Psa inactivation. This new formulation was prepared to have as main component the tri-cationic porphyrin which is considered one of the most efficient photosensitizers in the photoinactivation of microorganisms. The in vitro study with a PS concentration of 5.0 µM and low irradiance, showed a 7.4 log photoinactivation after 60 min. Posteriorly, several assays were performed with the PS at 50 µM on kiwifruit leaves (ex vivo), under different conditions of light and inoculation. The ex vivo assays with artificially contaminated leaves showed a 2.8 and 4.5 log inactivation with low irradiance and sunlight, respectively, after 90 min. After a second treatment with sunlight, a 6.2 log inactivation was achieved. The photoinactivation on naturally contaminated leaves was about 2.3 log after 90 min sunlight irradiation. Ten consecutive cycles of phototreatment in sub-lethal conditions showed that Psa does not develop resistance, nor recover viability. The results suggest that aPDT can be an alternative to the current methods used to control Psa, since it was possible to inactivate this bacterium under sunlight, without damaging the leaves.

Porphyrin-Oligopyridine Triads: Synthesis and Optical Properties.

The synthesis of two triads with two porphyrinyl units linked by oligopyridine derivatives and a new ß-functionalized porphyrin-dihydroazepine is described. One of the porphyrin-oligopyridine triads has a quinquepyridine unit connecting the porphyrins ß-pyrrolic positions, while the other one has an asymmetric quaterpyridine with one of the pyridines fused to the porphyrin. All compounds have fluorescence emission quantum yields in the range of meso-tetraphenylporphyrin (16-22%).

An insight into the photodynamic approach versus copper formulations in the control of Pseudomonas syringae pv. actinidiae in kiwi plants.

In the last decade, the worldwide production of kiwi fruit has been highly affected by Pseudomonas syringae pv. actinidiae (Psa), a phytopathogenic bacterium; this has led to severe economic losses that are seriously affecting the kiwi fruit trade. The available treatments for this disease are still scarce, with the most common involving frequently spraying the orchards with copper derivatives, in particular cuprous oxide (Cu2O). However, these copper formulations should be avoided due to their high toxicity; therefore, it is essential to search for new approaches for controlling Psa. Antimicrobial photodynamic therapy (aPDT) may be an alternative approach to inactivate Psa. aPDT consists in the use of a photosensitizer molecule (PS) that absorbs light and by transference of the excess of energy or electrons to molecular oxygen forms highly reactive oxygen species (ROS) that can affect different molecular targets, thus being very unlikely to lead to the development of microbe resistance. The aim of the present study was to evaluate the effectiveness of aPDT to photoinactivate Psa, using the porphyrin Tetra-Py+-Me and different light intensities. The degree of inactivation of Psa was assessed using the PS at 5.0 µM under low irradiance (4.0 mW cm-2). Afterward, ex vivo experiments, using artificially contaminated kiwi leaves, were conducted with a PS at 50 µM under 150 mW cm-2 and sunlight irradiation. A reduction of 6 log in the in vitro assays after 90 min of irradiation was observed. In the ex vivo tests, the decrease was lower, approximately 1.8 log reduction at an irradiance of 150 mW cm-2, 1.2 log at 4.0 mW cm-2, and 1.5 log under solar radiation. However, after three successive cycles of treatment under 150 mW cm-2, a 4 log inactivation was achieved. No negative effects were observed on leaves after treatment. Assays using Cu2O were also performed at the recommended concentration by law (50 g h L-1) and at concentrations 10 times lower, in which at both concentrations, Psa was efficiently inactivated (5 log inactivation) after a few minutes of treatment, but negative effects were observed on the leaves after treatment.

Cancer, Photodynamic Therapy and Porphyrin-Type Derivatives.

This review has two parts. The first one gives an approach to interdisciplinary studies against cancer carried out by many scientists using porphyrin-type substrates as photosensitizers in PDT. Intensive studies were performed for almost six decades. The successes really started in 1993 with the first formulation patented under the trade name Photofrin, which was immediately approved in several countries to treat certain types of cancer. Photofrin is still used although certain negative features soon became well known. That has motivated the search for better new photosensitizers. Several ones were developed, evaluated and a few of them had clinical approval. This group includes porphyrin derivatives and pro-drugs (aminolevulinic acid and its alkyl esters). Oncological, dermatological and ophthalmic applications are now taking place for the benefit of mankind. The second part of this review is related with the work carried out in Aveiro at the authors University on the synthesis and biological evaluation of several potential PDT photosensitizers. Not only new synthetic methodologies mainly for porphyrins and chlorins were developed but also other related macrocycles of the phthalocyanine and corrole types have entered in the same "pipeline". In vivo and in vitro biological evaluations also took place under interdisciplinary studies.

An insight on the role of photosensitizer nanocarriers for Photodynamic Therapy.

Photodynamic therapy (PDT) is a modality of cancer treatment in which tumor cells are destroyed by reactive oxygen species (ROS) produced by photosensitizers following its activation with visible or near infrared light. The PDT success is dependent on different factors namely on the efficiency of the photosensitizer deliver and targeting ability. In this review a special attention will be given to the role of some drug delivery systems to improve the efficiency of tetrapyrrolic photosensitizers to this type of treatment.

N-Confused Porphyrin Immobilized on Solid Supports: Synthesis and Metal Ions Sensing Efficacy.

In this work, the N-confused porphyrin 5,10,15,20-tetraphenyl-2-aza-21-carbaporphyrin (NCTPP) was immobilized on neutral or cationic supports based on silica and on Merrifield resin. The new materials were characterized by appropriate techniques (UV-Vis spectroscopy, SEM, and zeta potential analysis). Piezoelectric quartz crystal gold electrodes were coated with the different hybrids and their ability to interact with heavy metals was evaluated. The preliminary results obtained showed that the new materials can be explored for metal cations detection and the modification of the material surface is a key factor in tuning the metal selectivity.

Carbene Transfer Reactions Catalysed by Dyes of the Metalloporphyrin Group.

Carbene transfer reactions are very important transformations in organic synthesis, allowing the generation of structurally challenging products by catalysed cyclopropanation, cyclopropenation, carbene C-H, N-H, O-H, S-H, and Si-H insertion, and olefination of carbonyl compounds. In particular, chiral and achiral metalloporphyrins have been successfully explored as biomimetic catalysts for these carbene transfer reactions under both homogeneous and heterogeneous conditions. In this work the use of synthetic metalloporphyrins (MPorph, M = Fe, Ru, Os, Co, Rh, Ir, Sn) as homogeneous or heterogeneous catalysts for carbene transfer reactions in the last years is reviewed, almost exclusively focused on the literature since the year 2010, except when reference to older publications was deemed to be crucial.