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.

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.

C-N linked donor type porphyrin derivatives: unrevealed hole-transporting materials for efficient hybrid perovskite solar cells.

A new series of Zn(II) and Cu(II)-based porphyrin complexes 5a and 5b doubly functionalised with carbazole units were developed to be used as hole-transporting materials (HTMs) in perovskite solar cells (PSCs). These complexes were obtained via a nucleophilic substitution reaction mediated by PhI(OAc)2/NaAuCl4·2H2O, or using C-N transition metal-assisted coupling. The hole extraction capability of 5a and 5b was assessed using cyclic voltammetry; this study confirmed the better alignment of the Zn(II) complex 5a with the perovskite valence band level, compared to the Cu(II) complex 5b. The optimised geometry and molecular orbitals of both complexes also corroborate the higher potential of 5a as a HTM. Photoluminescence characterisation showed that the presence of 5a and 5b as HTMs on the perovskite surface resulted in the quenching of the emission, matching the hole transfer phenomenon. The photovoltaic performance was evaluated and compared with those of reference cells made with the standard HTM spiro-OMeTAD. The optimised 5-based devices showed improvements in all photovoltaic characteristics; their open circuit voltage (Voc) reached close to 1 V and short-circuit current density (Jsc) values were 13.79 and 9.14 mA cm-2 for 5a and 5b, respectively, disclosing the effect of the metallic centre. A maximum power conversion efficiency (PCE) of 10.01% was attained for 5a, which is 65% of the PCE generated by using the spiro-OMeTAD reference. This study demonstrates that C-N linked donor-type porphyrin derivatives are promising novel HTMs for developing efficient and reproducible PSCs.

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).

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.

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.

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.

Can Corrole Dimers Be Good Photosensitizers to Kill Bacteria?

Corroles possess key photophysical and photochemical properties to be exploited as therapeutic agents in antimicrobial photodynamic therapy (aPDT). Herein, we present for the first time the antimicrobial efficiency of three corrole dimers and of the corresponding precursor against the Gram(+) bacterium Staphylococcus aureus. Additionally, to explore future clinical applications, the cytotoxicity of the most promising derivatives towards Vero cells was evaluated. The aPDT assays performed under white light irradiation (50 mW/cm2; light dose 450 J/cm2) and at a corrole concentration of 15 µM showed that some dimers were able to reduce 99.9999% of S. aureus strain (decrease of 5 log10 CFU/mL) and their photodynamic efficiency was dependent on position, type of linkage, and aggregation behavior. Under the same light conditions, the corrole precursor 1 demonstrated notable photodynamic efficiency, achieving total photoinactivation (>8.0 log10 CFU/mL reduction) after the same period of irradiation (light dose 450 J/cm2). No cytotoxicity was observed when Vero cells were exposed to corrole 1 and dimer 3 for 24 h according to ISO guidelines (ISO 10993-5) for in vitro cytotoxicity of medical devices. The results show that corrole dimers, dependent on their structures, can be considered good photosensitizers to kill Staphylococcus aureus.

Bioluminescent Models to Evaluate the Efficiency of Light-Based Antibacterial Approaches.

The emergence of microbial resistance to antimicrobials among several common pathogenic microbial strains is an increasing problem worldwide. Thus, it is urgent to develop not only new antimicrobial therapeutics to fight microbial infections, but also new effective, rapid, and inexpensive methods to monitor the efficacy of these new therapeutics. Antimicrobial photodynamic therapy (aPDT) and antimicrobial blue light (aBL) therapy are receiving considerable attention for their antimicrobial potential and represent realistic alternatives to antibiotics. To monitor the photoinactivation process provided by aPDT and aBL, faster and more effective methods are required instead of laborious conventional plating and overnight incubation procedures. Bioluminescent microbial models are very interesting in this context. Light emission from bioluminescent microorganisms is a highly sensitive indication of their metabolic activity and can be used to monitor, in real time, the effects of antimicrobial agents and therapeutics. This chapter reviews the efforts of the scientific community concerning the development of in vitro, ex vivo, and in vivo bioluminescent bacterial models and their potential to evaluate the efficiency of aPDT and aBL in the inactivation of bacteria.

Graphene Oxide and Graphene Quantum Dots as Delivery Systems of Cationic Porphyrins: Photo-Antiproliferative Activity Evaluation towards T24 Human Bladder Cancer Cells.

The development of new photodynamic therapy (PDT) agents designed for bladder cancer (BC) treatments is of utmost importance to prevent its recurrence and progression towards more invasive forms. Here, three different porphyrinic photosensitizers (PS) (TMPyP, Zn-TMPyP, and P1-C5) were non-covalently loaded onto graphene oxide (GO) or graphene quantum dots (GQDs) in a one-step process. The cytotoxic effects of the free PS and of the corresponding hybrids were compared upon blue (BL) and red-light (RL) exposure on T24 human BC cells. In addition, intracellular reactive oxygen species (ROS) and singlet oxygen generation were measured. TMPyP and Zn-TMPyP showed higher efficiency under BL (IC50: 0.42 and 0.22 µm, respectively), while P1-C5 was more active under RL (IC50: 0.14 µm). In general, these PS could induce apoptotic cell death through lysosomes damage. The in vitro photosensitizing activity of the PS was not compromised after their immobilization onto graphene-based nanomaterials, with Zn-TMPyP@GQDs being the most promising hybrid system under RL (IC50: 0.37 µg/mL). Overall, our data confirm that GO and GQDs may represent valid platforms for PS delivery, without altering their performance for PDT on BC cells.

Tetracationic porphyrin derivatives against human breast cancer.

Photodynamic therapy (PDT) is an approved therapeutic approach and an alternative to conventional chemotherapy for the treatment of several types of cancer with the advantages of reducing the side effects and developing resistance mechanisms. Here, was evaluated the photosensitization capabilities of 5,10,15,20-tetrakis[4-(pyridinium-1-yl-methyl)phenyl]porphyrin (3), its N-confused isomer (4) and of the neutral precursors (1) and (2) and the results were compared with the ones obtained with the cationic 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP). Both regular porphyrin derivatives 1 and 3 showed higher efficiency to generate singlet oxygen than TMPyP. The PDT assays towards MCF-7 cells under red light irradiation (λ > 640 nm, 23.7 mW cm-2) demonstrated that the cationic porphyrin 3 is an efficient photosensitizer to kill MCF-7 breast cancer cells. The study of the cell death mechanisms induced by the photodynamic process showed that the studied porphyrin 3 and TMPyP caused cell death by autophagic flux and necrosis.

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.

Antimicrobial photodynamic treatment as an alternative approach for Alicyclobacillus acidoterrestris inactivation.

Alicyclobacillus acidoterrestris is a cause of major concern for the orange juice industry due to its thermal and chemical resistance, as well as its spoilage potential. A. acidoterrestris spoilage of orange juice is due to off-flavor taints from guaiacol production and some halophenols. The present study aimed to evaluate the effectiveness of antimicrobial Photodynamic Treatment (aPDT) as an emerging technology to inactivate the spores of A. acidoterrestris. The aPDT efficiency towards A. acidoterrestris was evaluated using as photosensitizers the tetracationic porphyrin (Tetra-Py+-Me) and the phenothiazinium dye new methylene blue (NMB) in combination with white light-emitting diode (LED; 400-740 nm; 65-140 mW/cm2). The spores of A. acidoterrestris were cultured on YSG agar plates (pH 3.7 ± 0.1) at 45 °C for 28 days and submitted to the aPDT with Tetra-Py+-Me and NMB at 10 µM in phosphate-buffered saline (PBS) in combination with white light (140 mW/cm2). The use of Tetra-Py+-Me at 10 µM resulted in a 7.3 ± 0.04 log reduction of the viability of A. acidoterrestris spores. No reductions in the viability of this bacterium were observed with NMB at 10 µM. Then, the aPDT with Tetra-Py+-Me and NMB at 10 µM in orange juice (UHT; pH 3.9; 11°Brix) alone and combined with potassium iodide (KI) was evaluated. The presence of KI was able to potentiate the aPDT process in orange juice, promoting the inactivation of 5 log CFU/mL of A. acidoterrestris spores after 10 h of white light exposition (140 mW/cm2). However, in the absence of KI, both photosensitizers did not promote a significant reduction in the spore viability. The inactivation of A. acidoterrestris spores artificially inoculated in orange peels (105 spores/mL) was also assessed using Tetra-Py+-Me at 10 and 50 µM in the presence and absence of KI in combination with white light (65 mW/cm2). No significant reductions were observed (p < .05) when Tetra-Py+-Me was used at 10 µM, however at the highest concentration (50 µM) a significant spore reduction (≈ 2.8 log CFU/mL reductions) in orange peels was observed after 6 h of sunlight exposition (65 mW/cm2). Although the color, total phenolic content (TPC), and antioxidant capacity of orange juice and peel (only color evaluation) seem to have been affected by light exposition, the impact on the visual and nutritional characteristics of the products remains inconclusive so far. Besides that, the results found suggest that aPDT can be a potential method for the reduction of A. acidoterrestris spores on orange groves.

Antimicrobial Photodynamic Therapy in the Control of COVID-19.

Antimicrobial photodynamic therapy (aPDT), using well known, safe and cost-effective photosensitizers, such as phenothiazines, e.g., methylene blue (MB), or porphyrins, e.g., protoporphyrin-IX (PP-IX), might help to mitigate the COVID-19 either to prevent infections or to develop photoactive fabrics (e.g., masks, suits, gloves) to disinfect surfaces, air and wastewater, under artificial light and/or natural sunlight.

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.

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.

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.

Photodynamic Inactivation of Candida albicans in Blood Plasma and Whole Blood.

The few approved disinfection techniques for blood derivatives promote damage in the blood components, representing risks for the transfusion receptor. Antimicrobial photodynamic therapy (aPDT) seems to be a promising approach for the photoinactivation of pathogens in blood, but only three photosensitizers (PSs) have been approved, methylene blue (MB) for plasma and riboflavin and amotosalen for plasma and platelets. In this study, the efficiency of the porphyrinic photosensitizer Tri-Py(+)-Me and of the porphyrinic formulation FORM was studied in the photoinactivation of Candida albicans in plasma and in whole blood and the results were compared to the ones obtained with the already approved PS MB. The results show that FORM and Tri-Py(+)-Me are promising PSs to inactivate C. albicans in plasma. Although in whole blood the inactivation rates obtained were higher than the ones obtained with MB, further improvements are required. None of these PSs had promoted hemolysis at the isotonic conditions when hemolysis was evaluated in whole blood and after the addition of treated plasma with these PSs to concentrates of red blood cells.