Free base porphyrin-cyanine dye conjugate: synthesis and optical properties.

The covalent combination of a cyanine dye (IR-783) with a tetraphenyl porphyrin unit through an ether linkage results in a photoactive system capable of producing singlet oxygen. The synthesis, characterization and photophysical properties of the resulting novel free base porphyrin-cyanine conjugate named TPPO-IR-783 (TOI) is reported. Excited state properties were studied in various solvents with differing polarity. The fluorescence is strongly solvent dependent, however this is not the case for singlet oxygen phosphorescence, which is only observed in tetrahydrofuran (THF), when comparing 8 different polar, non-polar and medium-polarity solvents. This novel type of porphyrin-cyanine photosensitizer has the ability to produce singlet oxygen and absorbs light at NIR wavelengths.

Bio-based matrix photocatalysts for photodegradation of antibiotics.

Antibiotics development during the last century permitted unprecedent medical advances. However, it is undeniable that there has been an abuse and misuse of antimicrobials in medicine and cosmetics, food production and food processing, in the last decades. The pay toll for human development and consumism is the emergence of extended antimicrobial resistance and omnipresent contamination of the biosphere. The One Health concept recognizes the interconnection of human, environmental and animal health, being impossible alter one without affecting the others. In this context, antibiotic decontamination from water-sources is of upmost importance, with new and more efficient strategies needed. In this framework, light-driven antibiotic degradation has gained interest in the last few years, strongly relying in semiconductor photocatalysts. To improve the semiconductor properties (i.e., efficiency, recovery, bandgap width, dispersibility, wavelength excitation, etc.), bio-based supporting material as photocatalysts matrices have been thoroughly studied, exploring synergetic effects as operating parameters that could improve the photodegradation of antibiotics. The present work describes some of the most relevant advances of the last 5 years on photodegradation of antibiotics and other antimicrobial molecules. It presents the conjugation of semiconductor photocatalysts to different organic scaffolds (biochar and biopolymers), then to describe hybrid systems based on g-C3N4 and finally addressing the emerging use of organic photocatalysts. These systems were developed for the degradation of several antibiotics and antimicrobials, and tested under different conditions, which are analyzed and thoroughly discussed along the work.

Latest trends on photodynamic disinfection of Gram-negative bacteria: photosensitizer's structure and delivery systems.

Antimicrobial resistance is threatening to overshadow last century's medical advances. Etiological agents of previously eradicated infectious diseases are now resurgent as multidrug-resistant strains, especially for Gram-negative strains. Finding new therapeutic solutions is a real challenge for our society. In this framework, Photodynamic Antimicrobial ChemoTherapy relies on the generation of toxic reactive oxygen species in the presence of light, oxygen, and a photosensitizer molecule. The use of reactive oxygen species is common for disinfection processes, using chemical agents, such as chlorine and hydrogen peroxide, and as they do not have a specific molecular target, it decreases the potential of tolerance to the antimicrobial treatment. However, light-driven generated reactive species result in an interesting alternative, as reactive species generation can be easily tuned with light irradiation and several PSs are known for their low environmental impact. Over the past few years, this topic has been thoroughly studied, exploring strategies based on single-molecule PSs (tetrapyrrolic compounds, dipyrrinate derivatives, metal complexes, etc.) or on conjunction with delivery systems. The present work describes some of the most relevant advances of the last 6 years, focusing on photosensitizers design, formulation, and potentiation, aiming for the disinfection of Gram-negative bacteria.

Prospects for More Efficient Multi-Photon Absorption Photosensitizers Exhibiting Both Reactive Oxygen Species Generation and Luminescence.

The use of two-photon absorption (TPA) for such applications as microscopy, imaging, and photodynamic therapy (PDT) offers several advantages over the usual one-photon excitation. This creates a need for photosensitizers that exhibit both strong two-photon absorption and the highly efficient generation of reactive oxygen species (ROS), as well as, ideally, bright luminescence. This review focuses on different strategies utilized to improve the TPA properties of various multi-photon absorbing species that have the required photophysical properties. Along with well-known families of photosensitizers, including porphyrins, we also describe other promising organic and organometallic structures and more complex systems involving organic and inorganic nanoparticles. We concentrate on the published studies that provide two-photon absorption cross-section values and the singlet oxygen (or other ROS) and luminescence quantum yields, which are crucial for potential use within PDT and diagnostics. We hope that this review will aid in the design and modification of novel TPA photosensitizers, which can help in exploiting the features of nonlinear absorption processes.

Photophysical and Bactericidal Properties of Pyridinium and Imidazolium Porphyrins for Photodynamic Antimicrobial Chemotherapy.

Despite advances achieved over the last decade, infections caused by multi-drug-resistant bacterial strains are increasingly becoming important societal issues that need to be addressed. New approaches have already been developed in order to overcome this problem. Photodynamic antimicrobial chemotherapy (PACT) could provide an alternative to fight infectious bacteria. Many studies have highlighted the value of cationic photosensitizers in order to improve this approach. This study reports the synthesis and the characterization of cationic porphyrins derived from methylimidazolium and phenylimidazolium porphyrins, along with a comparison of their photophysical properties with the well-known N-methylpyridyl (pyridinium) porphyrin family. PACT tests conducted with the tetracationic porphyrins of these three families showed that these new photosensitizers may offer a good alternative to the classical pyridinium porphyrins, especially against S.aureus and E.coli. In addition, they pave the way to new cationic photosensitizers by the means of derivatization through amide bond formation.

Making triplets from photo-generated charges: observations, mechanisms and theory.

Triplet formation by charge recombination is a phenomenon that is encountered in many fields of the photo-sciences and can be a detrimental unwanted side effect, but can also be exploited as a useful triplet generation method, for instance in photodynamic therapy. In this Perspective we describe the various aspects that play a role in the decay of charge separated states into local triplet states. The observations and structures of a selection of (pre-2015) molecular electron donor-acceptor systems in which triplet formation by charge recombination occurs are reported. An overview is given of some more recent systems consisting of BODIPY dimers, and BODIPYs attached to various electron-donor units displaying this same triplet formation process. A selection of polymer-fullerene blends in which triplet formation by (non-geminate) charge recombination has been observed, is presented. Furthermore, in-depth information regarding the mechanistic aspects of triplet formation by charge recombination is given on spin dephasing, through hyperfine interactions, as well as on spin-orbit coupling occurring simultaneously with charge recombination. The limits and constraints of these factors and their role in intersystem crossing are discussed. A pictorial view of the two mechanisms is given and this is correlated to aspects of the selection rules for triplet formation, the so-called El-Sayed rules. It is shown that the timescale of triplet formation by charge recombination is indicative for the mechanism that is responsible for the process. The relatively slow rates (CRkT ∼ 1 × 108 s-1 or slower) can be correlated to proton hyperfine interactions (also called the radical pair mechanism), but substantially faster rates (CRkT ∼ 1 × 109 up to 2.5 × 1010 s-1 or faster) have to be correlated to spin-orbit coupling effects. Several examples of molecular systems showing such fast rates are available and their electron donor and acceptor orbitals display an orthogonal relationship with respect to each other. This orientation of (the nodal planes of) the π-orbitals of the donor and acceptor units is correlated to the mechanisms in photodynamic agents and photovoltaic blends.

Conjugating biomaterials with photosensitizers: advances and perspectives for photodynamic antimicrobial chemotherapy.

Antimicrobial resistance is threatening to overshadow last century's medical advances. Previously eradicated infectious diseases are now resurgent as multi-drug resistant strains, leading to expensive, toxic and, in some cases, ineffective antimicrobial treatments. Given this outlook, researchers are willing to investigate novel antimicrobial treatments that may be able to deal with antimicrobial resistance, namely photodynamic therapy (PDT). PDT relies on the generation of toxic reactive oxygen species (ROS) in the presence of light and a photosensitizer (PS) molecule. PDT has been known for almost a century, but most of its applications have been directed towards the treatment of cancer and topical diseases. Unlike classical antimicrobial chemotherapy treatments, photodynamic antimicrobial chemotherapy (PACT) has a non-target specific mechanism of action, based on the generation of ROS, working against cellular membranes, walls, proteins, lipids and nucleic acids. This non-specific mechanism diminishes the chances of bacteria developing resistance. However, PSs usually are large molecules, prone to aggregation, diminishing their efficiency. This review will report the development of materials obtained from natural sources, as delivery systems for photosensitizing molecules against microorganisms. The present work emphasizes on the biological results rather than on the synthesis routes to prepare the conjugates. Also, it discusses the current state of the art, providing our perspective on the field.

Crossing the First Threshold: New Insights into the Influence of the Chemical Structure of Anionic Porphyrins on Plant Cell Wall Interactions and Photodynamic Cell Death Induction.

In this study, our fundamental research interest was to understand how negatively charged porphyrins could interact with a plant cell wall and further act inside cells. Thus, three anionic porphyrins differing in their anionic external groups (carboxylates, sulfonates, and phosphonates) were tested. First, the tobacco cell wall was isolated to monitor in vitro its interactions with the three different anionic porphyrins. Unexpectedly, these negatively charged molecules were able to bind to the negatively charged cell wall probably by weak bonds such as hydrogen bonds and/or electrostatic interactions when the tetrapyrrolic core was protonated. Moreover, we showed that at the pH of spent culture medium (4.5), the neutrality of the carboxylated porphyrin (TPPC) facilitated its cell wall crossing while the diffusion of the two other sulfonated (TPPS) or phosphonated (TPPP) porphyrins that remained anionic was delayed. Once inside Tobacco Bright Yellow-2 (TBY-2) cells, TPPC induced higher levels of production of both H2O2 and malondialdehyde compared to TPPS after illumination. That result correlated well with strong cell death induction by photoactivated TPPC. Furthermore, reactive oxygen species-scavenging enzymes such as catalase, peroxidases, and superoxide dismutase were also strongly downmodulated in response to TPPC, while these enzymes were almost unchanged in response to photoactivated TPPS. To the best of our knowledge, this is the first study that took into account the whole story from interactions of porphyrins with a plant cell wall to their photodynamic activity inside the cells.

Novel polycarboxylate porphyrins: synthesis, characterization, photophysical properties and preliminary antimicrobial study against Gram-positive bacteria.

We describe the synthesis, characterization and photophysical properties of two new polycarboxylic photosensitizers. Owing to their structural design, these two compounds show water solubilities larger than natural carboxylic photosensitizers (e.g., protoporphyrin IX, hematoporphyrin, etc.) and also good singlet oxygen quantum yields. These compounds were tested as photo-antimicrobial agents against Staphylococcus aureus and Bacillus cereus strains. Results reveal that their photocytotoxicities are strongly dependent on their amphiphilic character and more precisely the number and position of the carboxylic acid and mesityl substituents.

Development of Phenalenone-Triazolium Salt Derivatives for aPDT: Synthesis and Antibacterial Screening.

The increasing number of hospital-acquired infections demand the development of innovative antimicrobial treatments. Antimicrobial photodynamic therapy (aPDT) is a versatile technique which relies on the production of reactive oxygen species (ROS) generated by light-irradiated photosensitizers (PS) in the presence of oxygen (O2). 1H-Phenalen-1-one is a very efficient photosensitizer known for its high singlet oxygen quantum yield and its antimicrobial potential in aPDT when covalently bound to quaternary ammonium groups. Triazolium salts are stable aromatic quaternary ammonium salts that recently appeared as interesting moieties endowed with antimicrobial activities. The coupling between phenalenone and triazolium groups bearing various substituents was realized by copper-catalyzed azide-alkyne cycloaddition followed by alkylation with methyl iodide or 2-(bromomethyl)-1H-phenalen-1-one. As expected, most of the compounds retained the initial singlet oxygen quantum yield, close to unity. Minimum inhibitory concentrations (MIC) of 14 new phenalenone-triazolium salt derivatives and 2 phenalenone-triazole derivatives were determined against 6 bacterial strains (Gram-negatives and Gram-positives species). Most of these PS showed significant photoinactivation activities, the strongest effects being observed against Gram-positive strains with as low as submicromolar MIC values.

Photophysical and Antibacterial Properties of Porphyrins Encapsulated inside Acetylated Lignin Nanoparticles.

Lignin has recently attracted the attention of the scientific community, as a suitable raw material for biomedical applications. In this work, acetylated lignin was used to encapsulate five different porphyrins, aiming to preserve their photophysical properties, and for further use as antibacterial treatment. The obtained nanoparticles were physically characterized, through dynamic light scattering size measurement, polydispersity index and zeta potential values. Additionally, the photophysical properties of the nanoparticles, namely UV-vis absorption, fluorescence emission, singlet oxygen production and photobleaching, were compared with those of the free porphyrins. It was found that all the porphyrins were susceptible to encapsulation, with an observed decrease in their fluorescence quantum yield and singlet oxygen production. These nanoparticles were able to exert an effective photodynamic bactericide effect (blue-LED light, 450-460 nm, 15 J/cm2) on Staphylococcus aureus and Escherichia coli. Furthermore, it was achieved a photodynamic bactericidal activity on an encapsulated lipophillic porphyrin, where the free porphyrin failed to diminish the bacterial survival. In this work it was demonstrated that acetylated lignin encapsulation works as a universal, cheap and green material for the delivery of porphyrins, while preserving their photophysical properties.

Acetylated lignin nanoparticles as a possible vehicle for photosensitizing molecules.

Lignins are underused and abundant bio-sourced polymers with various potential applications. An attractive one is the development of nanoparticles for bioactive compound delivery. Here, we optimized the synthesis of hydrodispersible nanoparticles of acetylated lignin by comparing different lignin sources, degrees of acetylation and preparation methods. The formation of acetylated lignin nanoparticles in various solvents was probed by both experiments and, for the first time, a molecular dynamics simulation. We showed that dialysis is more suitable to obtain these nanoparticles than anti-solvent addition. The encapsulation of hydrophobic photosensitizing porphyrin in these nanoparticles was also demonstrated and rationalized at the molecular level, together with experiments, docking and molecular dynamics simulations. As acetylated lignin has been demonstrated to exhibit photosensitizing activity, the encapsulation of bioactive compounds in lignin nanoparticles opens the doors to a broad range of potential applications.

Porphyrin-Loaded Lignin Nanoparticles Against Bacteria: A Photodynamic Antimicrobial Chemotherapy Application.

The need for alternative strategies to fight bacteria is evident from the emergence of antimicrobial resistance. To that respect, photodynamic antimicrobial chemotherapy steadily rises in bacterial eradication by using light, a photosensitizer and oxygen, which generates reactive oxygen species that may kill bacteria. Herein, we report the encapsulation of 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphyrin into acetylated lignin water-dispersible nanoparticles (THPP@AcLi), with characterization of those systems by standard spectroscopic and microscopic techniques. We observed that THPP@AcLi retained porphyrin's photophysical/photochemical properties, including singlet oxygen generation and fluorescence. Besides, the nanoparticles demonstrated enhanced stability on storage and light bleaching. THPP@AcLi were evaluated as photosensitizers against two Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, and against three Gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis. THPP@AcLi were able to diminish Gram-positive bacterial survival to 0.1% when exposed to low white LED light doses (4.16 J/cm2), requiring concentrations below 5 µM. Nevertheless, the obtained nanoparticles were unable to diminish the survival of Gram-negative bacteria. Through transmission electron microscopy observations, we could demonstrate that nanoparticles did not penetrate inside the bacterial cell, exerting their destructive effect on the bacterial wall; also, a high affinity between acetylated lignin nanoparticles and bacteria was observed, leading to bacterial flocculation. Altogether, these findings allow to establish a photodynamic antimicrobial chemotherapy alternative that can be used effectively against Gram-positive topic infections using the widely available natural polymeric lignin as a drug carrier. Further research, aimed to inhibit the growth and survival of Gram-negative bacteria, is likely to enhance the wideness of acetylated lignin nanoparticle applications.

Efficient Singlet Oxygen Photogeneration by Zinc Porphyrin Dimers upon One- and Two-Photon Excitation.

The development of photodynamic therapy (PDT) at depth requires photosensitizers which have both sufficient quantum yield for singlet oxygen generation and strong two-photon absorption. Here, we show that this can be achieved by conjugated linkage of zinc porphyrins to make dimers. We determined the quantum yield of generation of 1O2 , ϕΔ, by measuring emission at 1270 nm using a near-infrared streak camera and found it to increase from 15% for a single porphyrin unit to 27-47% for the dimers with a conjugated linker. Then, we recorded the spectra of two-photon absorption cross section, σ2, by a focus-tunable Z-scan method, which allows for nondestructive investigation of light-sensitive materials. We observed a strong enhancement of the two-photon absorption coefficient in the dimers, especially those with an alkyne linker. These results lead to an excellent figure of merit for two-photon production of singlet oxygen (expressed by the product σ2 × Ï•Δ) in the porphyrin dimers, of around 3700 GM, which is very promising for applications involving treatment of deep tumors by PDT.

Synthesis of perylene-3,4-mono(dicarboximide)--fullerene C60 dyads as new light-harvesting systems.

Fullerene C 60-perylene-3,4-mono(dicarboximide) (C 60-PMI) dyads 1- 3 were synthesized in the search for new light-harvesting systems. The synthetic strategy to the PMI intermediate used a cross-coupling Suzuki reaction for the introduction of a formyl group in the ortho, meta, or para position. Subsequent 1,3-dipolar cycloaddition with C 60 led to the target C 60-PMI dyad. Cyclic voltammetry showed that the first one-electron reduction process unambiguously occurs onto the C 60 moiety and the following two-electron process corresponds to the concomitant second reduction of C 60 and the first reduction of PMI. A quasi-quantitative quenching of fluorescence was shown in dyads 1- 3, and an intramolecular energy transfer was suggested to occur from the PMI to the fullerene moiety. These C 60-PMI dyads constitute good candidates for future photovoltaic applications with expected well-defined roles for both partners, i.e., PMI acting as a light-harvesting antenna and C 60 playing the role of the acceptor in the photoactive layer.

Synergistic enhancement of tolerance mechanisms in response to photoactivation of cationic tetra (N-methylpyridyl) porphyrins in tomato plantlets.

Antimicrobial photodynamic treatment (APDT) is largely used in medical domain and could be envisaged as a farming practice against crop pathogens such as bacteria and fungi that generate drops in agricultural yields. Thus, as a prerequisite for this potential application, we studied the effect of water-soluble anionic (TPPS and Zn-TPPS) and cationic (TMPyP and Zn-TMPyP) porphyrins tested on tomato (Solanum lycopersicum) plantlets grown in vitro under a 16 h photoperiod. First of all, under dark conditions, none of the four porphyrins inhibited germination and induced cytotoxic effects on tomato plantlets as etiolated development was not altered. The consequences of porphyrin long-term photoactivation (14 days) were thus studied on in vitro-grown tomato plantlets at phenotypic and molecular levels. Cationic porphyrins especially Zn-TMPyP were the most efficient photosensitizers and dramatically altered growth without killing plantlets. Indeed, tomato plantlets were rescued after cationic porphyrins treatment. To gain insight, the different molecular ways implied in the plantlet tolerance to photoactivated Zn-TMPyP, lipid peroxidation, antioxidative molecules (total thiols, proline, ascorbate), and ROS detoxification enzymes were evaluated. In parallel to an increase in lipid peroxidation and hydrogen peroxide production, antioxidative molecules and enzymes (guaiacol peroxidase, catalase, and superoxide dismutase) were up-regulated in root apparatus in response to photoactivated Zn-TMPyP. This study showed that tomato plantlets could overcome the pressure triggered by photoactivated cationic porphyrin by activating antioxidative molecule and enzyme arsenal and confining Zn-TMPyP into cell wall and/or apoplasm, suggesting that APDT directed against tomato pathogens could be envisaged in the future.

Oligomeric tetrathiafulvalenes: a new route toward conjugated TTF dimers and trimers.

The synthesis of bis-TTF 1 and tris-TTF 2, linked by an ethenyl spacer, is described using new useful Wittig-type reagents with the introduction of phosphonate functionality on 1,3-dithiole and TTF frameworks. Electrochemical and spectroscopic studies show intramolecular electronic interactions between conjugated TTF units.

Synthesis and photobiocidal properties of cationic porphyrin-grafted paper.

We report on the synthesis of cellulose paper bearing a cationic porphyrin, designed for antimicrobial applications. Tricationic porphyrin has been covalently grafted on paper, without previous chemical modification of the cellulosic support, using 1,3,5-triazine derivative as linker. The obtained porphyrin-grafted paper was characterized by infrared (ATR-FTIR), UV-visible and diffuse reflectance UV-vis (DRUV) spectroscopies to confirm the triazine linkage. Thermogravimetric analysis (TGA) was used to investigate thermal properties of grafted paper. Antimicrobial activity of porphyrin-cellulose material was tested under visible light irradiation against Staphylococcus aureus and Escherichia coli. The two bacterial strains deposited on the resulting photosensitizing filter paper are efficiently killed after illumination.

Fullerene C60-perylene-3,4:9,10-bis(dicarboximide) light-harvesting dyads: spacer-length and bay-substituent effects on intramolecular singlet and triplet energy transfer.

Novel covalent fullerene C(60)-perylene-3,4:9,10-bis(dicarboximide) (C(60)-PDI) dyads (1-4) were synthesized and characterized. Their electrochemical and photophysical properties were investigated. Electrochemical studies show that the reduction potential of PDI can be tuned relative to C(60) by molecular engineering through altering the substituents on the PDI bay region. It was demonstrated using steady-state and time-resolved spectroscopy that a quantitative, photoinduced energy transfer takes place from the PDI moiety, acting as a light-harvesting antenna, to the C(60) unit, playing the role of energy acceptor. The bay-substitution (tetrachloro [1 and 2] or tetra-tert-butylphenoxy [3 and 4]) of the PDI antenna and the linkage length (C(2) [1 and 3] or C(5) [2 and 4]) to the C(60) acceptor are important parameters in the kinetics of energy transfer. Femtosecond transient absorption spectroscopy indicates singlet-singlet energy-transfer times (from the PDI to the C(60) unit) of 0.4 and 5 ps (1), 4.5 and 27 ps (2), 0.8 and 12 ps (3), and 7 and 50 ps (4), these values being ascribed to two different conformers for each C(60)-PDI system. Subsequent triplet-triplet energy-transfer times (from the C(60) unit to the PDI) are slower and in the order of 0.8 ns (1), 6.2 ns (2), 2.7 ns (3), and 9 ns (4). Nanosecond transient absorption spectroscopy of final PDI triplet states show a marked influence of the bay substitution (tetrachloro- or tetra-tert-butylphenoxy), and triplet-state lifetimes (10-20 micros) and the PDI triplet quantum yields (0.75-0.52) were estimated. The spectroscopy showed no substantial solvent effect upon comparing toluene (non-polar) to benzonitrile (polar), indicating that no electron transfer is occurring in these systems.

Superabsorbing fullerenes: spectral and kinetic characterization of photoinduced interactions in perylenediimide-fullerene-C60 dyads.

Two n-type molecular materials are covalently combined into a new photovoltaic component for polymer solar cells. Light harvesting by the perylenediimide results in very fast energy transfer to the fullerene unit, as shown with femtosecond transient absorption spectroscopy in toluene solution. Two energy transfer rates are observed of 2.5 x 10(12) s-1 (53%) and 2 x 10(11) s-1 (47%), attributed to two conformations. The final excited state that is populated is a perylenediimide-based triplet state that is formed on the nanosecond time scale with a high yield.