Photodegradation, toxicity and density functional theory study of pharmaceutical metoclopramide and its photoproducts.

Pharmaceuticals as ubiquitous organic pollutants in the aquatic environment represent substances whose knowledge of environmental fate is still limited. One such compound is metoclopramide, whose direct and indirect photolysis and toxicological assessment have been studied for the first time in this study. Experiments were performed under solar radiation, showing metoclopramide as a compound that can easily degrade in different water matrices. The effect of pH-values showed the faster degradation at pH = 7, while the highly alkaline conditions at pH = 11 slowed photolysis. The highest value of quantum yield of metoclopramide photodegradation (ϕ = 43.55·10-4) was obtained at pH = 7. Various organic and inorganic substances (NO3-, Fe(III), HA, Cl-, Br-, HCO3-, SO42-), commonly present in natural water, inhibited the degradation by absorbing light. In all experiments, kinetics followed pseudo-first-order reaction with r2 greater than 0.98. The structures of the photolytic degradation products were tentatively identified, and degradation photoproducts were proposed. The hydroxylation of the aromatic ring and the amino group's dealkylation were two major photoproduct formation mechanisms. Calculated thermochemical quantities are in agreement with the experimentally observed stability of different photoproducts. Reactive sites in metoclopramide were studied with conceptual density functional theory and regions most susceptible to •OH attack were characterized. Metoclopramide and its degradation products were neither genotoxic for bacteria Salmonella typhimurium in the SOS/umuC assay nor acutely toxic for bacteria Vibrio fischeri.

High diversity of natural Dalmatian pyrethrum based on pyrethrin composition at intra- and interpopulation level.

Seeds collected from 10 Dalmatian pyrethrum (Tanacetum cinerariifolium /Trevir./ Sch. Bip. Asteraceae) populations naturally occurring along the Adriatic coast and islands, were used to establish a common garden with the aim of estimating the variation of pyrethrin compounds between and within populations. A recently optimized matrix solid phase dispersion (MSPD) method was used for the extraction of six pyrethrin compounds from dry flower heads of 200 Dalmatian pyrethrum individuals. Separation and quantification of pyrethrin compounds were performed by high performance liquid chromatography with diode array detector (HPLC-DAD). High variability in pyrethrin content and composition was observed within and between populations. Total pyrethrin content in individual samples varied from 0.10% to 1.35% of flower dry weight. On average, the lowest total pyrethrin content was observed in the population of Peljesac (0.22%) and the highest in the island populations of Mali Losinj and Zlarin (0.87%). The population of Mali Losinj had the most favourable pyrethrin profile, including the lowest variability in total pyrethrin content, the highest pyrethrin I (PI) content (up to 60.47%) and PI/PII ratio (up to 5.88), as well as the lowest pyrethrin II (PII) content. In contrast, the populations from Biokovo and Peljesac represented pyrethrin profiles with the lowest content of total pyrethrin, PI and PI/PII ratio. The Biokovo population also had the highest PII content (43.18% on average), while the Peljesac population had the highest jasmolin I (JI) and jasmolin II (JII) content. Four different chemotypes were determined by cluster analysis. Chemotype P1 is the most promising for future breeding programs and is characterized by the highest total pyrethrin content, PI content and PI/PII ratio, as important measures of insecticidal activity. Correlation analysis of each pyrethrin compound with 25 environmental variables and Principal Component Analysis (PCA) were carried out and the importance of optimum temperature and precipitation on pyrethrin quantity and quality was suggested. Total pyrethrin content was significantly correlated with six temperature and five precipitation parameters. Pyrethrin I, PII and cinerin II (CII) were significantly correlated mainly with temperature parameters; JII and cinerin I (CI) with precipitation parameters, while JI was correlated with temperature range and precipitation parameters. The mountainous Biokovo population was an outlier in the PCA analysis, mainly due to the extremely low values of temperature parameters at a higher altitude. Precipitation variables separated the central Adriatic islands inhabiting drier habitats from populations inhabiting habitats with greater precipitation. The high-resolution data from this study provide the opportunity for individual-based selection for breeding plants with the best pyrethrin profiles, as well as for increased adaptation to broader climatic conditions.

Effects of environmental factors on nitrofurantoin photolysis in water and its acute toxicity assessment.

Pharmaceuticals have special attention of researchers over the world due to their possible effect on the environment and humans. This paper focuses on the photolysis of nitrofurantoin in different water matrices. Nitrofurantoin photodegradation has been indicated as a pseudo-first order photoreaction. The indirect photodegradation rate of nitrofurantoin (river water, k1 = 0.0088 min-1 and synthetic wastewater, k1 = 0.0154 min-1) was slower than its direct photolysis rate (ultrapure water, k1 = 0.0176 min-1). The highest value of quantum yield of nitrofurantoin photodegradation (ϕ = 0.2047) was observed at pH = 4, while at higher pH-values it decreased. Furthermore, the mechanism of nitrofurantoin photodegradation is proposed. Heterocyclic ring opening and further hydrolysis, nucleophilic aromatic photosubstitution and homolytic N-N bond cleavage are suggested as three main initial processes of nitrofurantoin photodegradation. Acute toxicity study of nitrofurantoin and its photoproducts with regard to luminescence inhibition of Vibrio fischeri showed that the toxic effect of nitrofurantoin (EC50 = 4.0 mg L-1) decreases by photolysis.

Titania-Coated Alumina Foam Photocatalyst for Memantine Degradation Derived by Replica Method and Sol-Gel Reaction.

In the present work, alumina (Al2O3) foam was prepared by the replica method where a polyurethane (PU) foam (30 pores per inch (ppi)) template was impregnated with a 60 wt.% Al2O3 suspension. Sintered Al2O3 foam was used as substrate for the deposition of sol-gel derived titania (TiO2) film using dip coating. For the preparation of TiO2 sol, titanium(IV) isopropoxide (Ti-iPrOH) was used as the precursor. The common problem of qualification and quantification of a crystalline coating on a highly porous 3D substrate with an uneven surface was addressed using a combination of different structural characterization methods. Using Powder X-ray Diffraction (PXRD) and synchrotron Grazing Incidence X-ray Diffraction (GIXRD) on bulk and powdered Al2O3 foam and TiO2-coated Al2O3 foam samples, it was determined Al2O3 foam crystallizes to corundum and coating to anatase, which was also confirmed by Fourier Transformed Infrared Spectroscopy (FTIR). Scanning Electron Microscopy with Energy Dispersive X-ray Spectroscopy (SEM/EDS) revealed the structural and microstructural properties of the substrate and coating. Differential Thermal Analysis (DTA) and Thermogravimetric Analysis (TGA) were used to clarify the evolution of the porous microstructure. The Al2O3-TiO2 composite was evaluated as a photocatalyst candidate for the degradation of the micropollutant medication memantine. The degradation rate was monitored using a light-emitting diode (LED) lamp operating at electromagnetic (EM) wavelength of 365 nm. The photocatalytic activity of sol-gel-derived TiO2 film immobilized on the Al2O3 foam was compared with commercially available TiO2 nanoparticles, P25-Degussa, in the form of a suspension. The levels of memantine were monitored by High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS). The efficiency and rate of the memantine photodegradation by suspended TiO2 nanoparticles is higher than the TiO2-coated Al2O3 foam. But, from the practical point of view, TiO2-coated Al2O3 foam is more appropriate as a valuable photocatalytic composite material.

Fate of febantel in the aquatic environment-the role of abiotic elimination processes.

Febantel is widely used anthelmintic drug active against a range of gastrointestinal parasites in animals. Despite the fact that it has been detected in the aquatic environment, there is no information on its environmental fate. Therefore, abiotic elimination processes of febantel in the aquatic environment have been studied. The results of direct and indirect photodegradation experiments showed that febantel was persistent against solar radiation. Kinetics of hydrolytic elimination was pH and temperature dependent with half-lives in the range from 210 min to 99 days. Febantel metabolites, fenbendazole and fenbendazole sulfone, were found as major degradation products using high-resolution mass spectrometry. The proposed hydrolytic degradation pathway consisted of the base catalyzed hydrolysis followed by consecutive oxidative cyclization to the five-membered ring of the benzo-imidazole derivative. Aquatic toxicity of febantel and its hydrolytic mixture were evaluated toward the luminescence bacteria Vibrio fischeri. Investigation of febantel sorption onto river sediments showed that the best agreement was obtained with the linear model (R2 > 0.99), while the rate of sorption is the best described with the kinetic model of pseudo-second order. The organic carbon-normalized sorption coefficient, KOC, ranged from 1490 to 3894 L kg-1 for five sediment samples. The results of this research demonstrate that febantel persist in the natural waters and potentially could travel far from the source.

Nitrofurantoin hydrolytic degradation in the environment.

Occurrence of pharmaceuticals, especially antibiotics in the environment increased attention to their environmental fate. Hydrolysis is one of two abiotic processes by which compounds are degraded in the environment. According to authors knowledge this is the first study investigating hydrolytic degradation of nitrofurantoin at pH-values normally found in the environment. Nitrofurantoin hydrolytic degradation appeared to be much slower at acidic (pH 4) solution compared to neutral (pH 7) and alkaline (pH 9) solutions at all three investigated temperatures (20 °C, 40 °C and 60 °C). In all cases nitrofurantoin hydrolysis followed the first-order kinetics with half-lives ranged from 0.5 days at pH 9 and 60 °C to 3.9 years at pH 4 and 20 °C. Temperature dependence of the hydrolysis rate constant was quantified by Arrhenius equation; obtained Ea values were as follows: 100.7 kJ mol-1 at pH 4, 111.2 kJ mol-1 at pH 7 and 102.3 kJ mol-1 at pH 9. Increase in hydrolysis rate constants for each 10 °C increase in temperature were 3.4, 3.9 and 3.5 at pH 4, pH 7 and pH 9, respectively. The structures of hydrolytic degradation products were determined and degradation pathways were suggested. Three main processes occurred depending on pH-values: protonation of the nitrofurantoin followed by cleavage of the NN single bond, heterocyclic non-aromatic ring cleavage, and reduction of the non-aromatic heterocyclic ring.

Environmental behavior of sulfadiazine, sulfamethazine, and their metabolites.

Sulfonamides are one of the most frequently used antibiotics worldwide. Therefore, processes that determine their fate in the environment are of great interest. In the present work, biodegradation as biotic process and hydrolysis and photolysis as abiotic processes were investigated. In biodegradation experiments, it was found out that sulfonamides (sulfadiazine and sulfamethazine) and their N 4-acetylated metabolites were not readily biodegradable. The results showed that decrease of concentrations were in the range from 4% for sulfadiazine to 22% for N 4-acetylsulfamethazine. Hydrolytic experiments examined at pH values normally found in the environment also showed their resistance. However, photolysis proved to be significant process for decreasing concentrations of sulfonamides and their metabolites in three various aqueous matrices (Milli-Q water, river water, and synthetic wastewater). In addition, influence of ubiquitous water constituents (Cl-, NO3-, SO42-, PO43-, and humic acids) was also investigated, showing their different impact on photolysis of investigated pharmaceuticals. The results showed that photolysis followed first-order kinetics in all cases. The obtained results are very important for assesing the environmental fate of sulfonamides and their metabolites in the aquatic environment.

UV photolysis of diclofenac in water; kinetics, degradation pathway and environmental aspects.

In this study, the photolysis behavior of commonly used anti-inflammatory drug diclofenac (DCF) was investigated using UV-C and UV-A irradiation. In that purpose, DCF conversion kinetics, mineralization of organic content, biodegradability, and toxicity were monitored and compared. The results showed different kinetics of DCF conversion regarding the type of UV source applied. However, in both cases, the mineralization extent reached upon complete DCF conversion is rather low (≤10 %), suggesting that the majority of DCF was transformed into by-products. Formation/degradation of main degradation by-products was monitored using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS), whereas different profiles were obtained by UV-C and UV-A photolysis. The results of bioassays revealed that biodegradability of DCF solutions remained low through the applied treatments. The toxicity of irradiated DCF solutions was evaluated using Vibrio fischeri. A significant reduction of toxicity, especially in the case of UV-A radiation, was observed upon complete degradation of DCF. In addition to toxicity reduction, calculated Log K OW values of DCF degradation by-products indicate their low potential for bioaccumulation (Log K OW ≤ 3) in comparison to the parent substance.