Recent Synthetic Advances on the Use of Diazo Compounds Catalyzed by Metalloporphyrins.

Diazo compounds are organic substances that are often used as precursors in organic synthesis like cyclization reactions, olefinations, cyclopropanations, cyclopropenations, rearrangements, and carbene or metallocarbene insertions into C-H, N-H, O-H, S-H, and Si-H bonds. Typically, reactions from diazo compounds are catalyzed by transition metals with various ligands that modulate the capacity and selectivity of the catalyst. These ligands can modify and enhance chemoselectivity in the substrate, regioselectivity and enantioselectivity by reflecting these preferences in the products. Porphyrins have been used as catalysts in several important reactions for organic synthesis and also in several medicinal applications. In the chemistry of diazo compounds, porphyrins are very efficient as catalysts when complexed with low-cost metals (e.g., Fe and Co) and, therefore, in recent years, this has been the subject of significant research. This review will summarize the advances in the studies involving the field of diazo compounds catalyzed by metalloporphyrins (M-Porph, M = Fe, Ru, Os, Co, Rh, Ir) in the last five years to provide a clear overview and possible opportunities for future applications. Also, at the end of this review, the properties of artificial metalloenzymes and hemoproteins as biocatalysts for a broad range of applications, namely those concerning carbene-transfer reactions, will be considered.

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.

Influence of Ethanol Parametrization on Diffusion Coefficients Using OPLS-AA Force Field.

Molecular dynamics simulations employing the all-atom optimized potential for liquid simulations (OPLS-AA) force field were performed for determining self-diffusion coefficients (D11) of ethanol and tracer diffusion coefficients (D12) of solutes in ethanol at several temperature and pressure conditions. For simulations employing the original OPLS-AA diameter of ethanol's oxygen atom (σOH), calculated and experimental diffusivities of protic solutes differed by more than 25%. To correct this behavior, the σOH was reoptimized using the experimental D12 of quercetin and of gallic acid in liquid ethanol as benchmarks. A substantial improvement of the calculated diffusivities was found by changing σOH from its original value (0.312 nm) to 0.306 nm, with average absolute relative deviations (AARD) of 3.71% and 4.59% for quercetin and gallic acid, respectively. The new σOH value was further tested by computing D12 of ibuprofen and butan-1-ol in liquid ethanol with AARDs of 1.55% and 4.81%, respectively. A significant improvement was also obtained for the D11 of ethanol with AARD = 3.51%. It was also demonstrated that in the case of diffusion coefficients of non-polar solutes in ethanol, the original σOH=0.312 nm should be used for better agreement with experiment. If equilibrium properties such as enthalpy of vaporization and density are estimated, the original diameter should be once again adopted.

Evaluation of the cellular protection by novel spiropyrazole compounds in dopaminergic cell death.

The loss of neurons is strongly correlated with aging and aging-associated disorders. In this study, cell viability assays and mitochondrial function were performed to evaluate the effect of new spiro-pyrazole derivatives, prepared from aldehydes and 3-amino-1-phenyl-2-pyrazolin-5-one, on neuroprotection in an in vitro model of dopaminergic cell death induced by 1-methyl-4-phenylpyridinium (MPP+). The percentages of neuroprotection by derivatives were found between 21.26% and 52.67% at selected concentrations (10-50 µM) with compound 4d exerting the best neuroprotective effect. The results show that the studied spiropyrazolones perform important roles in dopaminergic neuroprotection and can be used for potential new therapies in the treatment of neurodegenerative disorders including Parkinson's disease.

Enhanced preservation of vacuum-packaged Atlantic salmon by hyperbaric storage at room temperature versus refrigeration.

Hyperbaric storage at room temperature (HS/RT: 75 MPa/25 °C) of vacuum-packaged fresh Atlantic salmon (Salmo salar) loins was studied for 30 days and compared to atmospheric pressure at refrigerated temperatures (AP/5 °C, 30 days) and RT (AP/25 °C, 5 days). Most of the fatty acids were not affected by storage conditions, with only a slight decrease of docosahexaenoic acid (DHA) content (n-3 polyunsaturated fatty acid) for AP samples, reflected in the lower polyene index values obtained and higher oxidation extent. For HS, a lower lipid oxidation extension and a slower increase of myofibrillar fragmentation index values were observed, when compared to AP samples. The volatile profile was similar for the HS and fresh samples, with the HS samples retaining fresh-like alcohols and aldehydes components, which disappeared in AP samples, mainly in AP/25 °C samples. The volatile profile for AP samples (5 and 25 °C) revealed mostly spoilage-like compounds due to microbial activity. Drip loss increased progressively during the 30 days of storage under HS, while a slight decrease of water holding capacity after 5 days was observed, increasing further after 30 days. Regarding textural properties, only resilience was affected by HS, decreasing after 30 days. So, HS/RT could represent an interesting extended preservation methodology of fresh salmon loins, since allows retaining important physicochemical properties for at least 15 days, while refrigeration after 5 days showed already volatile spoilage-like compounds due to microbial activity. Furthermore, this methodology allows additional considerable energy savings when compared to refrigeration.

Comparison of the Photodynamic Action of Porphyrin, Chlorin, and Isobacteriochlorin Derivatives toward a Melanotic Cell Line.

Melanoma is the most dangerous form of skin cancer, with an abrupt growth of its incidence over the last years. It is extremely resistant to traditional treatments such as chemotherapy and radiotherapy, but therapies for this cancer are gaining attention. Photodynamic therapy (PDT) is considered an effective modality to treat several types of skin cancers and can offer the possibility to treat one of the most aggressive ones: melanoma. In this work, the effect of PDT on a melanotic cell line (B16F10 cells) was assessed by exposing cultured cells to 5,10,15-tris(pentafluorophenyl)-20-(4-pyridyl)porphyrin (PS1) and to its chlorin (PS2) and isobacteriochlorin (PS3) corresponding derivatives and red LED light (λ = 660 ± 20 nm). The PDT effect in the cells' viability was measured using the MTT assay. The cell apoptosis was quantified by flow cytometry, and the subcellular localization of the photosensitizer was determined by fluorescence microscopy. In addition, the ability of PS2 to generate superoxide radicals was qualitatively assessed by tyrosine nitration. The results show that the efficiency of the PDT process is dependent on the structure of the PS and on their ability to produce singlet oxygen. Besides that, the photoactivation efficiency is highly dependent on the cellular sublocalization of the PS and on its cellular uptake and singlet oxygen production. We also found that the resistant cell line B16F10 has distinctive chlorin, isobacteriochlorin, or porphyrin-specific resistance profiles. Furthermore, it is shown that the highly fluorescent chlorin derivative PS2 can also be considered in imaging diagnostics.

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.

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.

Physicochemical parameters, lipids stability, and volatiles profile of vacuum-packaged fresh Atlantic salmon (Salmo salar) loins preserved by hyperbaric storage at 10 °C.

Lipid stability, physical properties and volatiles profile of vacuum-packaged fresh Atlantic salmon (Salmo salar) loins were evaluated after hyperbaric storage at low temperature (HS/LT: 60 MPa/10 °C) and compared to atmospheric pressure and conventional refrigeration (AP/5 °C) after 5, 15 and 30 days, and at low temperature (AP/10 °C), after 5 and 15 days. No variations in drip loss and water holding capacity were observed for HS/LT samples. Compared to AP, HS/LT caused lower changes on muscle fibres, visible by scanning electron micrographs, and a decrease of resilience property (only after 30 days). In addition, myofibrillar fragmentation index did not change at HS/LT. Fatty acids were generally not affected by the different storage conditions, while the polyene index at HS/LT was similar to fresh samples during the 30 days of storage, confirmed by the lower lipid oxidation state of these samples, compared to AP. According to the volatile profile (SPME-GC/MS), HS samples showed to be more similar to the fresh ones, retaining fresh-like alcohols and aldehydes, generally not detected in AP samples after 15 days, the latter presenting spoilage-related compounds probably derived from microbial activity. According to these results, HS/LT represents a promising preservation methodology for fresh salmon loins (and fish in general), retaining better important physicochemical properties for 30 days, when compared to the conventional refrigeration.

Vine Waste Valorisation: Integrated Approach for the Prospection of Bioactive Lipophilic Phytochemicals.

Substantial amounts of vine wastes are produced during vineyard management, and the chemical profiling of high-value lipophilic phytochemicals is becoming crucial in order to find a complementary route towards their integrated valorisation. The prospection of bioactive phytochemicals from unripe grape, vine shoot, vine cane, stalk and leaf dichloromethane extracts was carried out by gas chromatography-mass spectrometry (GC-MS), analysing samples from a mixture of four red Vitis vinifera L. varieties (Baga, Aragonez, Água Santa and Shiraz), collected at Bairrada Appellation, as a representative case study of typical multi-variety Portuguese vineyards. Vine wastes showed distinct amounts of lipophilic extract, ranging from 0.68% (vine canes) to 13.35% (vine leaves) at dry weight (dw). Thirty-three components were identified, including fatty acids and alcohols, sterols and triterpenoids accounting for amounts from 118.9 mg/100 g dw to 1512.0 mg/100 g dw. The integrated study revealed that unripe grape, stalk and leaf dichloromethane extracts stood out as possible sources of triterpenic compounds (103.2 to 653.5 mg/100 g dw), with lupeol, ursolic and oleanolic acids prevailing. Leaf extract is also reported as an undervalued source of α-tocopherol, as the major component detected in this matrix (300.5 mg/100 g dw). These exploratory results are a relevant contribution for the exploitation of undervalued vine residues as a source of health-promoting components with the potential to be used as supplements or nutraceutical ingredients.

Copper-phthalocyanine coordination polymer as a reusable catechol oxidase biomimetic catalyst.

The development of selective, efficient, and recoverable/reusable catalysts for oxidation reactions has become one of the main challenges of modern chemistry. Considering our interest in efficient catalytic systems based on porphyrin (Por) and phthalocyanine (Pc) coordination polymers, we report here the synthesis, characterization and catalytic activity of a new Pc coordination polymer (coined hereafter as Cu4CuPcSPy). The new Pc material was obtained in excellent yield, from the reaction of H2PcSPy with an excess amount of copper(ii) acetate. The catalytic efficiency of Cu4CuPcSPy was evaluated in the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) in the presence of molecular oxygen from air, with or without the addition of aqueous 30% hydrogen peroxide. The comparison between the homogeneous (CuPcSPy) and the heterogeneous (Cu4CuPcSPy) catalytic systems showed a better performance for the Cu4CuPcSPy material, that can be recovered by filtration and reused, maintaining its activity roughly unchanged during three catalytic cycles. An increment of approximately 30% was also verified in the catalytic activity of the homogeneous and heterogeneous systems by adding aqueous hydrogen peroxide to the catalytic reactions.

New Materials Based on Cationic Porphyrins Conjugated to Chitosan or Titanium Dioxide: Synthesis, Characterization and Antimicrobial Efficacy.

The post-functionalization of 5,10,15-tris(1-methylpyridinium-4-yl)-20-(pentafluorophenyl)porphyrin tri-iodide, known as a highly efficient photosensitizer (PS) for antimicrobial photodynamic therapy (aPDT), in the presence of 3- or 4-mercaptobenzoic acid, afforded two new tricationic porphyrins with adequate carboxylic pending groups to be immobilized on chitosan or titanium oxide. The structural characterization of the newly obtained materials confirmed the success of the porphyrin immobilization on the solid supports. The photophysical properties and the antimicrobial photodynamic efficacy of the non-immobilized porphyrins and of the new conjugates were evaluated. The results showed that the position of the carboxyl group in the mercapto units or the absence of these substituents in the porphyrin core could modulate the action of the photosensitizer towards the bioluminescent Gram-negative Escherichia coli bacterium. The antimicrobial activity was also influenced by the interaction between the photosensitizer and the type of support (chitosan or titanium dioxide). The new cationic porphyrins and some of the materials were shown to be very stable in PBS and effective in the photoinactivation of E. coli bacterium. The physicochemical properties of TiO2 allowed the interaction of the PS with its surface, increasing the absorption profile of TiO2, which enables the use of visible light, inactivating the bacteria more efficiently than the corresponding PS immobilized on chitosan.

Effect of High Pressure on Paracoccus denitrificans Growth and Polyhydroxyalkanoates Production from Glycerol.

The performance of fermentation under non-conventional conditions, such as high pressure (HP), is a strategy currently tested for different fermentation processes. In the present work, the purpose was to apply HP (10-50 MPa) to fermentation by Paracoccus denitrificans, a microorganism able to produce polyhydroxyalkanoates (PHA) from glycerol. In general, cell growth and glycerol consumption were both reduced by HP application, more extensively at higher pressure levels, such as 35 or 50 MPa. PHA production and composition was highly dependent on the pressure applied. HP was found to decrease polymer titers, but increase the PHA content in cell dry mass (%), indicating higher ability to accumulate these polymers in the cells. In addition, some levels of HP affected PHA monomeric composition, with the polymer produced at 10 and 35 MPa showing considerable differences relative to the ones obtained at atmospheric pressure. Therefore, it is possible to foresee that the changes in polymer composition may also affect its physical and mechanical properties. Overall, the results of this study demonstrated that HP technology (at specific levels) can be applied to P. denitrificans fermentations without compromising the ability to produce PHA, with potentially interesting effects on polymer composition.

Photodegradation of metoprolol using a porphyrin as photosensitizer under homogeneous and heterogeneous conditions.

Porphyrins are known as effective photosensitizers and can be an interesting key in phototreatment of water contaminated with micropollutants such as pharmaceuticals. They already showed to be efficient photocatalysts for the degradation of dyes, chlorophenols and other pollutants. This work demonstrates the applicability of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (H2TF5PP) as photosensitizer for treatment of water contaminated with metoprolol, a highly prescribed ß-blocker, which is not completely removed in sewage treatment plants. Studies were firstly developed under homogeneous conditions with simulated solar radiation and porphyrin was found to be efficient in the photodegradation of metoprolol, following a pseudo-first order kinetics with ca. 90% metoprolol degradation after 12 h. Experiments in presence of scavengers confirmed the mechanism of degradation via singlet oxygen. Appearance of several new peaks in HPLC chromatograms indicates the formation of products, identified by HPLC-MSn. Furthermore, the porphyrin was immobilized on a silica support and used as heterogeneous photocatalyst in degradation of metoprolol. Experiments using this heterogeneous photocatalyst under real solar irradiation were also performed, and similar results were obtained. Kinetic comparison of metoprolol photodegradation in buffer solution and in real wastewater treatment plant effluent showed that the efficiency of the immobilized porphyrin was not decreased by the complex matrix of the effluent.

Bifunctional Porphyrin-Based Nano-Metal-Organic Frameworks: Catalytic and Chemosensing Studies.

The use of 5,10,15,20-tetrakis( p-phenylphosphonic acid)porphyrin (H10TPPA) as a linker in the preparation of porphyrin-based metal-organic frameworks (Por-MOFs) through coordination to lanthanides cations is reported. The resulting unprecedented materials, formulated as [M(H9TPPA)(H2O) x]Cl2· yH2O [ x + y = 7; M3+ = La3+ (1), Yb3+ (2), and Y3+ (3)], prepared using hydrothermal synthesis, were extensively characterized in the solid-state, for both their structure and thermal robustness, using a myriad of solid-state advanced techniques. Materials were evaluated as heterogeneous catalysts in the oxidation of thioanisole by H2O2 and as chemosensors for detection of nitroaromatic compounds (NACs). Nano-Por-MOFs 1-3 proved to be effective as heterogeneous catalysts in the sulfoxidation of thioanisole, with Por-MOF 1 exhibiting the best catalytic performance with a conversion of thioanisole of 89% in the first cycle and with a high selectivity for the sulfoxide derivative (90%). The catalyst maintained its activity roughly constant in three consecutive runs. Por-MOFs 1-3 can be employed as chemosensors because of a measured fluorescence quenching up to 70% for nitrobenzene, 1,4-dinitrobenzene, 4-nitrophenol, and phenol, with 2,4,6-trinitrophenol exhibiting a peculiar fluorescence profile.

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.

Effects of the Inoculant Strain Pseudomonas sp. SPN31 nah + and of 2-Methylnaphthalene Contamination on the Rhizosphere and Endosphere Bacterial Communities of Halimione portulacoides.

The aim of this study is to evaluate the effects of the inoculation of the saltmarsh plant (Halimione portulacoides) with Pseudomonas sp. SPN31 nah+ combined with exposure to 2-methylnaphthalene (2-MtN) on the plant rhizosphere and endosphere bacterial communities as well as on plant health. To achieve this goal, microcosm experiments were set up. Denaturing gradient gel electrophoresis (DGGE) profiles and statistical analysis showed that rhizosphere and endosphere bacterial communities had distinct responses to plant inoculation and/or exposure to 2-MtN. PCR-sequencing analysis of nah genes encoding for 2-MtN degrading enzymes suggested the presence of Pseudomonas sp. SPN31 nah+ in the endosphere of H. portulacoides with 2-MtN contamination. Moreover, a significant effect in the photosynthetic performance of inoculated plants was detected. To conclude, despite the potential beneficial effect of plant inoculation with Pseudomonas sp. SPN31 nah+ endophytic bacteria may have on plant health, no significant effect on the removal of MtN was detected for the level of contamination used in the study.

Efficient Catalytic Oxidation of 3-Arylthio- and 3-Cyclohexylthio-lapachone Derivatives to New Sulfonyl Derivatives and Evaluation of Their Antibacterial Activities.

New sulfonyl-lapachones were efficiently obtained through the catalytic oxidation of arylthio- and cyclohexylthio-lapachone derivatives with hydrogen peroxide in the presence of a Mn(III) porphyrin complex. The antibacterial activities of the non-oxidized and oxidized lapachone derivatives against the Gram-negative bacteria Escherichia coli and the Gram-positive bacteria Staphylococcus aureus were evaluated after their incorporation into polyvinylpyrrolidone (PVP) micelles. The obtained results show that the PVP-formulations of the lapachones 4b-g and of the sulfonyl-lapachones 7e and 7g reduced the growth of S. aureus.

Identification and characterization of photodegradation products of metoprolol in the presence of natural fulvic acid by HPLC-UV-MSn.

Metoprolol is a ß-blocker highly prescribed for the treatment of heart diseases. It is not efficiently removed in wastewater treatment plants and it has been detected not only in the treated effluents, but also in natural waters. Thus, the knowledge of its fate in the environment is an important issue, and photodegradation is an important degradation pathway. While direct photodegradation of metoprolol by solar light is not relevant, there is evidence in the literature that it suffers indirect photodegradation and a few studies have been published showing the important role of dissolved humic matter as photo-sensitizer. However, the identification of the photoproducts formed in the presence of humic matter is very poor, since only 2 photoproducts had been identified. This study investigated the degradation of metoprolol under simulated solar radiation and in the presence of fulvic acids (FA) extracted from a river. During the photodegradation experiments we observed the formation of new compounds which were separated and tentatively identified by HPLC-UV-ESI-MSn. At least 16 compounds were tentatively identified, including the 2 compounds previously identified in the literature and 4 new compounds which had not been detected by other authors as degradation products of metoprolol, even when submitted to artificial degradation processes.

Porphyrin-Based Metal-Organic Frameworks as Heterogeneous Catalysts in Oxidation Reactions.

Porphyrin-based Metal-Organic Frameworks (Por-MOFs) constitute a special branch of the wide MOF family that has proven its own value and high potential in different applications. In this mini-review the application of these materials as catalysts in oxidation reactions is highlighted.