Ecotoxicity and photodegradation of Montelukast (a drug to treat asthma) in water.

The present work focuses on the ecotoxicological effects of montelukast sodium (MTL) and its photoproducts, obtained under environmentally-like conditions. Despite of the potential presence in surface waters and the common use of MTL as asthma drug, limited data has been published for its photodegradation, while no information is available for its ecotoxicity. Light-induced degradation is an effective way for drugs to degrade in aquatic environments, and MTL is highly photosensitive, even by exposure to sunlight. In this study, solar-simulated irradiation of the drug in water was investigated. The drug was quickly converted into a series of photoproducts that were spectroscopically characterized. The possible photoreaction pathways were proposed. Ecotoxicity tests were performed on parent compound and mixture of photoproducts towards two bioindicators (Raphidocelis subcapitata and Daphnia magna). Results evidenced that effects of MTL on D. magna (EC50 = 16.4 mg/L) were greater than effects on R. subcapitata (EC50 = 195.7 mg/L). Microscopy observations revealed that MTL had mainly accumulated in the gut of daphnia. Toxicity data on photolysed solutions highlighted the presence of residual toxicity in all samples, evidencing that no complete mineralization occurred. Future research should focus on monitoring of MTL concentrations in the environment and study its effects in bioaccumulation tests.

A One-Pot Approach to Novel Pyridazine C-Nucleosides.

The synthesis of glycosides and modified nucleosides represents a wide research field in organic chemistry. The classical methodology is based on coupling reactions between a glycosyl donor and an acceptor. An alternative strategy for new C-nucleosides is used in this approach, which consists of modifying a pre-existent furyl aglycone. This approach is applied to obtain novel pyridazine C-nucleosides starting with 2- and 3-(ribofuranosyl)furans. It is based on singlet oxygen [4+2] cycloaddition followed by reduction and hydrazine cyclization under neutral conditions. The mild three-step one-pot procedure leads stereoselectively to novel pyridazine C-nucleosides of pharmacological interest. The use of acetyls as protecting groups provides an elegant direct route to a deprotected new pyridazine C-nucleoside.

Synthesis of novel lignan-like compounds and their antimicrobial activity.

Herein we report the preparation of 3,4-dibenzylfurans and some oxidized derivatives with lignan backbone. The compounds were prepared using the Friedel-Crafts reaction with BF3 etherate as catalyst, demethylation with iodocyclohexane, acetylation and oxidation reactions. The antimicrobial activity was evaluated through their capacity to inhibit the growth of Gram positive and Gram negative bacteria, and of the yeast Candida albicans. Among ten products assayed four furans displayed a good antimicrobial activity against Staphylococcus aureus, S. epidermidis and C. albicans; on the contrary, none of the compounds were active against Pseudomonas aeruginosa. One of them inhibited the growth of S. aureus, S. epidermidis (biofilm producer strain) and C. albicans at 16 µg/mL, showing a bactericidal activity already after one hour of treatment. In summary, the results suggest a possible use of these derivatives for general disinfection practices or antimicrobial agents in cosmesis skin-care.

Ecotoxic effects of loratadine and its metabolic and light-induced derivatives.

Loratadine and desloratadine are second-generation antihistaminic drugs. Because of human administration, they are continuously released via excreta into wastewater treatment plants and occur in surface waters as residues and transformation products (TPs). Loratadine and desloratadine residues have been found at very low concentrations (ng/L) in the aquatic environment but their toxic effects are still not well known. Both drugs are light-sensitive even under environmentally simulated conditions and some of the photoproducts have been isolated and characterized. The aim of the present study was to investigate the acute and chronic ecotoxicity of loratadine, desloratadine and their light-induced transformation products in organisms of the aquatic trophic chain. Bioassays were performed in the alga Pseudokirchneriella subcapitata, the rotifer Brachionus calyciflorus and in two crustaceans, Thamnocephalus platyurus and Ceriodaphnia dubia. Loratadine exerted its acute and chronic toxicity especially on Ceriodaphnia dubia (LC50: 600 µg/L, EC50: 28.14 µg/L) while desloratadine showed similar acute toxicity among the organisms tested and it was the most chronically effective compound in Ceriodaphnia dubia and Pseudokirchneriella subcapitata. Generally, transformation products were less active in both acute and chronic assays.

Hands-on synthesis of furanamides and evaluation of their antimicrobial activity.

Diverse natural and synthetic furan derivatives have shown biological activity. Here, we describe the preparation of benzyl and arylethyl ß-furanamides with OH or OMe aryl substituents by an adapted sustainable method from a furoic acid using methyl chloroformate. Symmetric and asymmetric ß,ß'-furanamides have instead been prepared using azabenzotriazole based catalyst (HATU). The products have been evaluated for their antimicrobial properties on Gram positive and Gram negative bacteria. Just a minimal not-significant activity has been observed in some derivatives.

Modulation of Antioxidant Compounds in Fruits of Citrus reticulata Blanco Using Postharvest LED Irradiation.

Phlegrean mandarin fruits are already known for health-promoting properties due to the high concentration of phytochemicals in peel, pulp, and seed. Biotic and abiotic factors, including light, may modulate their biosynthesis, metabolism, and accumulation. In this context, light-emitting diodes (LED) have recently been applied to control nutritional traits, ripening process, senescence, fruit shelf-life, and pathogenic microbial spoilage of fruits. This study investigated the effect of the seven-day exposure of Phlegrean mandarin fruits to two LED regimes, white (W) and red-blue (RB), to test the possibility that the storage under specific light wavelengths may be used as green preservation technology that enhances fruit phytochemical properties. To pursue this aim, the antioxidant activity and polyphenolic profile of the pulp and peel of mandarins under W and RB light regimes were evaluated and compared with Control fruits not exposed to LED treatment. Our results indicated that storage under W and RB treatments modulates the antioxidant content in pulp and peel differently. Compared to W, the RB regime increases the ascorbic acid, flavonoid, anthocyanin, and carotenoid concentrations, while the polyphenol profile analysis reveals that the number of important phytochemicals, i.e., quercetin rutinoside, chlorogenic acid, sinensetin, and rutin, are higher under W. The overall data demonstrated that postharvest LED irradiation is a valid tool for modifying fruit phytochemical properties, which also boosts specific bioactive compounds.

Antioxidant Properties of Pulp, Peel and Seeds of Phlegrean Mandarin (Citrus reticulata Blanco) at Different Stages of Fruit Ripening.

In this work, we assess the potential of waste products of Phlegrean mandarin (Citrus reticulata Blanco), namely seeds and peel, to be reutilized as a source of bioactive compounds beneficial for the human diet. Starting from the evidence that the by-products of this specific cultivar are the most powerful sources of antioxidants compared to pulp, we have investigated if and how the bioactive compounds in peel and seeds may be affected by fruit ripening. Three stages of fruit ripening have been considered in our study: unripe fruits = UF, semi-ripe fruits = SRF, ripe fruits = RF. The overall results indicated that RF showed the highest concentration of antioxidants. Among fruit components, peel was the richest in total antioxidant capacity, total polyphenol content, total flavonoids, total chlorophylls and carotenoids, while seeds exhibited the highest concentration of total condensed tannins and ascorbic acid. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay indicates the occurrence, in peel extracts, of 28 phenolic compounds, mainly flavonoids (FLs); in seeds, 34 derivatives were present in the first stage (UF), which diminish to 24 during the ripening process. Our data indicated that the content of phytochemicals in citrus strongly varies among the fruit components and depends on the ripening stage. The higher antioxidant activity of peel and seeds, especially in RF, encourage a potential use of by-products of this specific citrus cultivar for industrial or pharmacological applications. However, to maximize the occurrence of desired bioactive compounds, it is important also to consider the ripening stage at which fruits must be collected.

Investigation on the phototransformation of tadalafil in aqueous media. 6-Epimerization vs. solvent trapping reaction.

Irradiation of tadalafil at lambda > 290 nm in aqueous solutions leads to 6-epimer and/or water adducts depending on concentration and pH. A rationalization of the results involves the heterolytic cleavage of C6-N5 bond via a well-stabilized zwitterionic intermediate. The drug is stable in the dark except under strongly basic conditions where it undergoes C12a-epimerization.

Comparative Studies on Different Citrus Cultivars: A Revaluation of Waste Mandarin Components.

Peel, pulp and seed extracts of three mandarin varieties, namely Phlegraean mandarin (Citrus reticulata), Kumquat (Citrus japonica), and Clementine (Citrus clementina) were compared and characterised in terms of photosynthetic pigment content, total polyphenols amount, antioxidant activity and vitamin C to assess the amount of functional compounds for each cultivar. The highest polyphenols content was found in the Phlegraean mandarin, especially in peel and seeds, whereas Kumquat exhibited the highest polyphenols amount in the pulp. The antioxidant activity was higher in the peel of Phlegraean mandarin and clementine compared to Kumquat, which showed the highest value in the pulp. The antioxidant activity peaked in the seeds of Phlegraean mandarin. The vitamin C in the Phlegraean mandarin was the highest in all parts of the fruit, especially in the seeds. Total chlorophyll content was comparable in the peel of different cultivars, in the pulp the highest amount was found in clementine, whereas kumquat seeds showed the greatest values. As regards total carotenoids, peel and pulp of clementine exhibited higher values than the other two cultivars, whereas the kumquat seeds were the richest in carotenoids. Among the analysed cultivars Phlegraean mandarin may be considered the most promising as a source of polyphenols and antioxidants, compared to the clementine and Kumquat, especially for the functional molecules found in the seeds. Moreover, regardless of cultivars this study also highlights important properties in the parts of the fruit generally considered wastes.

Synthesis of 3-benzoyl-4-benzylfurans structural related to furolignans.

Furolignan-type natural products, possessing important biological properties, have been synthesized from a commercially available furan. The elaborated synthetic strategy is based on an innovative Friedel-Crafts reaction starting from an alcohol or a carboxylic acid and triflic anhydride as promoter. Through this synthetic strategy, furolignans having two different aryl groups have been obtained. The products have been evaluated for their antimicrobial properties on Gram positive and Gram negative bacteria, in order to compare their biological activities with those of natural analogues.

Phototransformation products of tamoxifen by sunlight in water. Toxicity of the drug and its derivatives on aquatic organisms.

Transformation of tamoxifen has been observed in water by prolonged sunlight irradiation. The main photoproducts, isolated by chromatographic techniques, have been identified by spectroscopic means. Photoisomerization, photocyclization and, to a lesser extent, photooxygenation appear to be involved in the degradation of the drug. The acute and chronic toxicity of the parent drug and its photoproducts were tested on non-target aquatic organisms (Brachionus calyciflorus, Thamnocephalus platyurus, Daphnia magna and Ceriodaphnia dubia). Exposure to all the compounds induced mainly chronic effects without significant differences among the parental and derivative compounds.

Transformation and ecotoxicity of carbamic pesticides in water.

BACKGROUND: N-methylcarbamate insecticides are widely used chemicals for crop protection. This study examines the hydrolytic and photolytic cleavage of benfuracarb, carbosulfan and carbofuran under natural conditions. Their toxicity and that of the corresponding main degradation products toward aquatic organisms were evaluated. METHODS: Suspensions of benfuracarb, carbosulfan and carbofuran in water were exposed to sunlight, with one set of dark controls, for 6 days, and analyzed by 1H-NMR and HPLC. Acute toxicity tests were performed on Brachionus calyciflorus, Daphnia magna, and Thamnocefalus platyurus. Chronic tests were performed on Pseudokirchneriella subcapitata, and Ceriodaphnia dubia. RESULTS AND DISCUSSION: Under sunlight irradiation, benfuracarb and carbosulfan gave off carbofuran and carbofuran-phenol, while only carbofuran was detected in the dark experiments. The latter was degraded to phenol by exposure to sunlight. Effects of pH, humic acid and KNO3 were evaluated by kinetics on dilute solutions in the dark and by UV irradiation, which evidenced the lability of the pesticide at pH 9. All three pesticides and phenol exhibited acute and higher chronic toxicity towards the aquatic organisms tested. CONCLUSION: Investigation on the hydrolysis and photolysis of benfuracarb and carbosulfan under natural conditions provides evidence concerning the selective decay to carbofuran and/or phenol. Carbofuran is found to be more persistent and toxic. RECOMMENDATIONS AND OUTLOOK: The decay of benfuracarb and carbosulfan to carbofuran and the relative stability of this latter pesticide account for many papers that report the detection of carbofuran in water, fruits and vegetables.

Photochemical fate and eco-genotoxicity assessment of the drug etodolac.

The photochemical behavior of etodolac was investigated under various irradiation conditions. Kinetic data were obtained after irradiation of 10(-4) M aqueous solutions by UVB, UVA and direct exposure to sunlight. The Xenon lamp irradiation was used in order to determine the photodegradation quantum yield under sun-simulated condition (ϕsun). The value was determined to be=0.10±0.01. In order to obtain photoproducts and for mechanistic purposes, experiments were carried out on more concentrated solutions by exposure to sunlight and to UVA and UVB lamps. The drug underwent photooxidative processes following an initial oxygen addition to the double bond of the five membered ring and was mainly converted into a spiro compound and a macrolactam. Ecotoxicity tests were performed on etodolac, its photostable spiro derivative and its sunlight irradiation mixture on two different aquatic trophic levels, plants (algae) and invertebrates (rotifers and crustaceans). Mutagenesis and genotoxicity were detected on bacterial strains. The results showed that only etodolac had long term effects on rotifers although at concentrations far from environmental detection values. A mutagenic and genotoxic potential was found for its derivative.

Phototransformation of carboxin in water. Toxicity of the pesticide and its sulfoxide to aquatic organisms.

Sunlight exposure of aqueous suspensions of carboxin (1) causes its phototransformation to sulfoxide 2 and minor components. Similar effects are observed in the presence of humic acid or nitrate or at different pH values. Photoproducts 2-9 were isolated by chromatographic techniques and/or identified by spectroscopic means. Carboxin 1 and its main photoproduct sulfoxide 2 were tested to evaluate acute toxicity to primary consumers typical of the aquatic environment: the rotifer Brachionus calyciflorus and two crustaceans, Daphnia magna and Thamnocephalus platyurus. Chronic tests comprised a producer, the alga Pseudokirchneriella subcapitata, and a consumer, the crustacean Ceriodaphnia dubia.

Effects of sensitizers on the photodegradation of the systemic fungicide triadimenol.

The photochemical behaviour of triadimenol (1) under various conditions has been examined. Significant degradation is obtained only in the presence of electron-acceptor sensitizers as 9,10-dicyanoanthracene or 2,4,6-triphenylpyrylium tetrafluoroborate, and long irradiation times are required. 1H-1,2,4-Triazole (2), 4-chlorophenyl formate (3), 4-chlorophenol (4), 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one (5), 4-chlorophenyl 2,2-dimethylpropanoate (6) and 4-chlorobenzoic acid (7) were identified as photoproducts by NMR and GC-MS.

Identification of phototransformation products of prednisone by sunlight: toxicity of the drug and its derivatives on aquatic organisms.

Solar simulator irradiation of an aqueous suspension of prednisone, a widely prescribed drug, produces seven photochemical derivatives. The compounds have been identified on the basis of their physical features. All the chemicals have been tested to evaluate their toxic effects on freshwater organisms from different trophic levels. The rotifer Brachionus calyciflorus and two crustaceans, the cladoceran Daphnia magna and the anostracan Thamnocephalus platyurus, were used to perform acute toxicity tests. Chronic toxicity tests have been performed on the alga Pseudokirchneriella subcapitata (formerly known as Selenastrum capricornutum) and the crustacean Ceriodaphnia dubia. The results showed low acute and chronic toxicity of prednisone. Some of the photoproducts had high toxic effects on C. dubia.

Sensitized photooxygenation of the fungicide furalaxyl.

BACKGROUND: The photolysis of pesticides is of high current interest since light is one of the most important abiotic factors which are responsible for the environmental fate of these substances and may induce their conversion into noxious products. The action of light can also be mediated by oxygen and synthetic or naturally occurring substances which act as sensitizers. Our objective in this study was to investigate the photochemical behaviour of the systemic fungicide furalaxyl in the presence of oxygen and various sensitizers, and to compare the toxicity of the main photoproduct(s) to that of the parent compound. Previous reports on the direct photolysis of the pesticide demonstrated a very slow degradation and the only identified photoproducts were N-2,6-xylyl-D,L-alaninare and 2,6-dimethylaniline. METHODS: Solutions of furalaxyl in CH3CN were photooxygenate using a 500W high-pressure mercury lamp (through a Pyrex glass filter, lambda>300 nm) or a 650W halogen lamp or sunlight and the proper sensitizer. When sunlight was used, aqueous solutions were employed. The photodegradation was checked by NMR and/or GC-MS. The photoproducts were spectroscopically evidenced and, when possible, isolated chromatographically. Acute toxicity tests were performed on the rotifer Brachionus calyciflorus, the crustacean cladoceran Daphnia magna and the anostracan Thamnocephalus platyurus, while chronic toxicity tests (sublethal endpoints) comprised a producer, the alga Pseudokirchneriella subcapitata and the crustacean Ceriodaphnia dubia, as a consumer. RESULTS AND DISCUSSION: In the presence of both oxygen and sensitizer, furalaxyl underwent rapid photochemical transformations mainly to N-disubstituted formamide, maleic anhydride and a 2(5H)-furanone derivative. The formation of these products was rationalized in terms of a furan endoperoxide intermediate derived from the reaction of furalaxyl with active dioxygenated species (singlet oxygen, superoxide anion or ground state oxygen). The 2(5H)-furanone exhibited a higher toxicity than the parent compound. CONCLUSION: This work reports the first data on the photosensitized oxygenation of furalaxyl with evidence of the high tendency of the pesticide to undergo photodegradation under these conditions leading, among other things, to a 2(5H)-furanone, which is more toxic than the starting furalaxyl towards aquatic organisms. RECOMMENDATIONS AND OUTLOOK: Investigation highlights that the photolytic fate of a pesticide, although quite stable to direct photoreaction due to its low absorption of solar radiation at ground level, can be significantly influenced in the environment by the presence of substances with energy or electron-transfer properties as natural dyes, e.g. chlorophyll, or synthetic pollutants, e.g. polycyclic aromatic hydrocarbons (PAH).

Photochemical behaviour of the systemic fungicide carboxin.

Irradiation of carboxin (1) with a 500 W UV lamp (filter Pyrex) in CH3CN leads to the products 3, 5-8, 12-14 depending upon the reaction conditions. All photo-products were isolated and characterized. Photooxidation occurred even if unsensitized, while photoalteration was very slow in the absence of oxygen. The main oxygenated-products 3 and 13 were also recovered under biomimetic conditions by exposure of an aqueous solution of 1 to sunlight.

Photoenhanced transformation of nicotine in aquatic environments: involvement of naturally occurring radical sources.

This work investigated the fate of nicotine (Nico) in aqueous solution upon reaction with singlet oxygen ((1)O2) and hydroxyl radical (HO·). The second-order rate constants of Nico with (1)O2 (k(Nico,(1)O(2)) = (3.38 ± 0.14) × 10(6) M(-1) s(-1)) and HO· (kNico,·OH = (1.08 ± 0.10) × 10(9) M(-1) s(-1)) were determined using competition kinetics. Photochemical modelling showed that the reaction of Nico with HO· would prevail over that with (1)O2 in surface waters transformation pathway. The Nico photochemical half-life time could be accounted for by the two reactions. This value would vary in the month-year range depending on the environmental conditions: phototransformation would be favoured in shallow water poor in organic matter and rich in nitrate and nitrite. Irradiation experiments of Nico with nitrite suggested that transformation could not be accounted for by HO· reaction alone. Indeed, a variable fraction of Nico transformation (30-80% depending on the conditions) would take place upon reaction with additional transients, photogenerated NOx being possible candidates. The chemical structures of the transformation intermediates were derived by means of HPLC-MS. The detection of nitroderivatives upon irradiation of Nico with nitrite suggests the involvement of nitrogen dioxide in the relevant photoprocesses.

Chlorpropham and phenisopham: phototransformation and ecotoxicity of carbamates in the aquatic environment.

In this study, a comparison of two carbamic pesticides, chlorpropham and phenisopham, was carried out in terms of both photodegradability and ecotoxicity. The photochemical behaviour of the two pesticides was investigated under environmental-like conditions (aqueous media, UVB or solar irradiation). The photochemical kinetic parameters were calculated by irradiating 5 × 10(-5) M solutions (H2O-CH3CN, 9 : 1 v/v) using UVB lamps. For chlorpropham and phenisopham similar half-life times (39.0 and 55.0 min) were determined. Irradiation by sunlight leads to longer degradation half-life times (about 3 months), while it is possible to observe the formation of the same photoproducts. The well-known dechlorination reaction to a hydroxyphenylcarbamate was observed for chlorpropham. Phenisopham undergoes photo-Fries reaction to give rearranged products (hydroxybenzamides) and fragmentation products (hydroxyphenylcarbamate and N-ethylaniline). Acute and chronic toxicity tests of pesticides and their photoproducts were performed on organisms from two levels of the freshwater aquatic chain, the anostraca crustacean Thamnocephalus platyurus, the rotifer Brachionus calyciflorus and the alga Pseudokirchneriella subcapitata. The acute results showed that chlorpropham had median lethal concentrations for the crustacean T. platyurus and the rotifer B. calyciflorus of 10.16 and 35.19 mg L(-1), respectively, and phenisopham did not show any acute toxicity as the derivatives up to 10 mg L(-1). The only exception was N-ethylaniline which exhibited an acute LC50 value of 0.46 mg L(-1). Phenisopham was the most toxic in the long term exposure while its five derivatives showed lower chronic potential for rotifers and algae. The same trend was observed for chlorpropham except for rotifers.