Current advances on the photocatalytic degradation of fluoroquinolones: photoreaction mechanism and environmental application.

Heterogeneous photocatalysis is one of the most studied and promising techniques for degradation of contaminants of emerging concern, especially pharmaceuticals, and it represents a potential application in wastewater treatment of recalcitrant pollutants, such as fluoroquinolones, which are almost not abated by standard WWTPs. Although photodegradation partially contributes to alleviate their accumulation into the aquatic systems, heterogeneous photocatalysis assures complete sequestration and mineralization of FQs and their photoproducts and offers many advantages with respect to the other advanced oxidation processes (AOPs). The present brief review summarizes the most recent studies regarding the development and application of novel photocatalytic materials to the removal of FQs from contaminated waters. The collected data are arranged relating the mechanistic aspects to specific catalysts' properties, such as adsorption capacity, easy recovery, and reusability, especially under actual conditions.

Glucocorticoids in Freshwaters: Degradation by Solar Light and Environmental Toxicity of the Photoproducts.

The photodegradation process of seven glucocorticoids (GCs), cortisone (CORT), hydrocortisone (HCORT), betamethasone (BETA), dexamethasone (DEXA), prednisone (PRED), prednisolone (PREDLO) and triamcinolone (TRIAM) was studied in tap and river water at a concentration close to the environmental ones. All drugs underwent sunlight degradation according to a pseudo-first-order decay. The kinetic constants ranged from 0.00082 min-1 for CORT to 0.024 min-1 for PRED and PREDLO. The photo-generated products were identified by high-pressure liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The main steps of the degradation pathways were the oxidative cleavage of the chain 17 for CORT, HCORT and the rearrangement of the cyclohexadiene moiety for the other GCs. The acute and chronic toxicity of GCs and of their photoproducts was assessed by the V. fischeri and P.subcapitata inhibition assays. The bioassays revealed no significant differences in toxicity between the parent compounds and their photoproducts, but the two organisms showed different responses. All samples produced a moderate acute toxic effect on V. fisheri and no one in the chronic tests. On the contrary, evident hormesis or eutrophic effect was produced on the algae, especially for long-term contact.

TiO2 and N-TiO2 Sepiolite and Zeolite Composites for Photocatalytic Removal of Ofloxacin from Polluted Water.

TiO2 sepiolite and zeolite composites, as well the corresponding N-doped composites, synthesized through a sol-gel method, were tested for the photocatalytic degradation of a widespread fluoroquinolone antibiotic (ofloxacin) under environmental conditions. The catalysts were characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), and diffuse reflectance spectroscopy (DRS) analyses. A complete drug degradation occurred in 10-15 min in the presence of both TiO2 sepiolite and zeolite catalysts, and in 20-30 min with the N-doped ones. Sepiolite proved to be a better TiO2 support compared to the most common zeolite both in terms of adsorption capacity and photocatalytic efficiency in pollutants degradation. The influence of nitrogen doping (red shift from 3.2 to 3.0 eV) was also investigated. Although it was blurred by a marked increase of the particle dimension and thus a decrease of the specific surface area of the doped catalysts, it allowed a faster drug removal than direct photolysis. The photochemical paths and photoproducts were investigated, too.

g-C3N4-promoted degradation of ofloxacin antibiotic in natural waters under simulated sunlight.

This is the first report on the photodegradation of ofloxacin under simulated solar light and in actual environmental matrices in the presence of a g-C3N4 suspension. The catalyst, prepared from the polymerization of dicyandiamide (650 °C, reaction yield 60%), was characterized by means of powder X-ray diffraction (PXRD), UV-vis diffuse reflectance spectroscopy (DRS), scanning electron microscopy (SEM), and BET surface area measurements. The experiments were carried out in a lab-scale batch reactor at concentrations in the range of micrograms/milligrams per liter. The course of the reaction was monitored by high-pressure liquid chromatography with UV-vis and fluorescence detectors. The g-C3N4-promoted photodegradation occurred at a rate 10 times faster than the direct photolysis and obeyed a first-order kinetics; in addition, the photodegradation kinetics of sonicated g-C3N4 resulted to be of the same order of that caused by P25 TiO2. Finally, the photochemical paths and the photoproducts have been identified and compared to those obtained by using P25 TiO2. From the results of this study, it can be concluded that g-C3N4 is a very attractive photocatalyst compared to P25 TiO2 in view of its ease of preparation, low cost, excellent oxidizing properties, large fraction of solar radiation absorbed, and intrinsically layered structure.

Botanical and biological pesticides elicit a similar Induced Systemic Response in tomato (Solanum lycopersicum) secondary metabolism.

Natural pesticides have attracted substantial interest due to the increase in organic agriculture and enhanced attention to environmental pollution. Plant Growth Promoting Bacteria (PGPB) are applied for both disease control and growth enhancement; PGPBs are known to elicit Induced Systemic Response (ISR) in plants. However, less is known about the effect of botanical pesticides, such as the azadirachtin-containing neem extracts, on plant metabolism. This study aimed to investigate the effects of foliar application of the above-mentioned natural pesticides on the metabolic profiling of tomato. Leaf application of Bacillus subtilis fostered Induced Systemic Resistance (ISR) in treated plants via the Jasmonic acid pathway, and enhanced production of secondary metabolites such as flavonoids, phytoalexins and auxins. Changes in sterols and terpenes, as well as an increase in glucosinolates were also observed. Interestingly, azadirachtin-treated tomatoes also showed an increase in ISR and our results revealed that most of the enriched metabolites are shared with a B. subtilis treatment, suggesting conserved biochemical responses. These (un)expected findings indicate that plants are not insensitive to application of natural pesticide and while Azadirachtin is applied as a direct pesticide, it also stimulates a defense response in tomatoes very similar to B. subtilis induced ISR.

Sunlight-induced degradation of fluoroquinolones in wastewater effluent: Photoproducts identification and toxicity.

The photodegradation of Ciprofloxacin (CIP), Enrofloxacin (ENR), Danofloxacin (DAN), Marbofloxacin (MAR) and Levofloxacin (LEV), five widely used fluoroquinolones (FQs), was studied in urban WWTP secondary effluent, under solar light. The degradation profiles and the kinetic constants were determined at the micrograms per litre levels (20-50 µg L(-1)). The photo-generated products were identified by high-pressure liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The toxicity of the photoproducts was assessed by Vibrio fischeri light emission inhibition assay performed on irradiated and not-irradiated FQs solutions, at environmentally significant concentrations. Attention was focused on the evaluation of the photoproducts contribution to the overall biotoxic effect of these emerging pollutants. Data from chronic exposure experiments (24-48 h) were primarily considered. Results confirmed the major usefulness of chronic toxicity data with respect to the acute assay ones and proved the not negligible biotoxicity of the FQs photodegradation products.

Structure-activity relationship and role of oxygen in the potential antitumour activity of fluoroquinolones in human epithelial cancer cells.

The photobehavior of ciprofloxacin, lomefloxacin and ofloxacin fluoroquinolones was investigated using several in vitro methods to assess their cytotoxic, antiproliferative, and genotoxic potential against two human cancer cell lines. We focused our attention on the possible relationship between their chemical structure, O2 partial pressure and photobiological activity on cancer cells. The three molecules share the main features of most fluoroquinolones, a fluorine in 6 and a piperazino group in 7, but differ at the key position 8, unsubstituted in ciprofloxacin, a fluorine in lomefloxacin and an alkoxy group in ofloxacin. Studies in solution show that ofloxacin has a low photoreactivity; lomefloxacin reacts via aryl cation, ciprofloxacin reacts but not via the cation. In our experiments, ciprofloxacin and lomefloxacin showed a high and comparable potential for photodamaging cells and DNA. Lomefloxacin appeared the most efficient molecule in hypoxia, acting mainly against tumour cell proliferation and generating DNA plasmid photocleavage. Although our results do not directly provide evidence that a carbocation is involved in photodamage induced by lomefloxacin, our data strongly support this hypothesis. This may lead to new and more efficient anti-tumour drugs involving a cation in their mechanism of action. This latter acting independently of oxygen, can target hypoxic tumour tissue.

Environmental photochemistry of fluoroquinolones in soil and in aqueous soil suspensions under solar light.

The photodegradation fate of widely used fluoroquinolone (FQ) drugs has been studied both at the water-soil interface and in soil at actual concentrations (500 ng g(-1)) under natural solar light. Both human and veterinary drugs have been examined, namely ciprofloxacin, danofloxacin, enrofloxacin, levofloxacin, marbofloxacin and moxifloxacin. After spiking and irradiation, samples were submitted to microwave-assisted extraction and analyzed by high-performance liquid chromatography coupled to fluorescence detection (HPLC-FD). FQs degradation was faster in aqueous soil suspension than in neat soil (but lower than in "clean" water). A number of byproducts were identified by HPLC electrospray ionization tandem mass spectrometry after a post-extraction cleanup based on a molecularly imprinted polymer phase, for a more accurate detection. The distribution in the suspension was intermediate between those observed in soils and in aqueous solutions.

A fluorine 1,2-migration via aryl cation/radical/radical anion/radical sequence.

Irradiation of a 7-piperazino-8-fluoroquinolone causes formal 1,2-fluorine migration, piperazine loss and reduction, or nucleophile addition in 8. Product study, laser flash photolysis, and computational modeling support F(-) detachment to yield a triplet 8-quinolyl cation that either inserts intramolecularly or is trapped by Cl(-), Br(-). However, iodide and pyrrole reduce it to the radical that continues the 'redox tour' (aryl cation→ radical→ radical anion→ radical and then again radical or radical anion) leading to the rearranged products.

Photodegradation of fluoroquinolones in surface water and antimicrobial activity of the photoproducts.

The widespread presence of fluoroquinolone antibiotics (FQs) in natural ecosystems is a health hazard for humans and other living organisms. The role of sunlight in degrading FQs present in environmental waters has been studied. In particular, the photodegradation of four largely employed FQs, viz. Ciprofloxacin (CIP), Danofloxacin (DAN), Levofloxacin (LEV) and Moxifloxacin (MOX) has been studied in not tampered river water. Degradation rates have been investigated at ppb levels (20-50 µg L(-1)) under solar light, and the results have been commented critically. The products distribution has been studied by HPLC-ESI-MS/MS analysis and structures have been attributed on the basis of their mass fragmentation spectra. Importantly from the environmental point of view, the (potentially toxic) FQ nucleus remained intact over the early stages of the degradation. Indeed, the photoproducts were proved to possess residual antibacterial activity, as shown from in vitro antibacterial activity tests against different well characterized human and environmental bacterial strains, carried out on the above FQs, as well as for Enrofloxacin (ENR) and Marbofloxacin (MAR).

The resveratrol analog 4,4'-dihydroxy-trans-stilbene suppresses transformation in normal mouse fibroblasts and inhibits proliferation and invasion of human breast cancer cells.

4,4'-dihydroxy-trans-stilbene (DHS) is a synthetic analog of resveratrol, a phytoalexin known for its biological activities. We previously demonstrated that DHS exerts an antiproliferative effect on normal human fibroblasts that is higher than that of the natural parent molecule. No evidence regarding its role in human cancer cell lines has been found thus far. In this study, we investigated the effects of DHS both on chemical-induced transformation of BALB/c 3T3 mouse fibroblasts and on the proliferation and invasion of human breast cancer MCF-7 cells. The results showed that DHS markedly suppresses the two-stage (3-methylcholanthrene plus 12-O-tetradecanoylphorbol-13-acetate) cell transformation. Compared with resveratrol, DHS inhibited both anchorage-dependent and -independent MCF-7 growth more efficiently. In addition, a reduction in the number of cells in S-phase, characterized by a concomitant increase in the levels of p21 and p53 proteins, together with a strong inhibition of pRb protein phosphorylation, was observed in DHS-treated cells. Furthermore, DHS effected a strong reduction in matrix metalloproteinase-2 and -9 activities, concomitantly with a marked inhibition of cell adhesion to the extracellular matrix components as well as inhibition of cell migration and invasion. Importantly, modulation of the adhesion molecule E-cadherin was also found in DHS-treated cells. Taken together, these results demonstrate that the two 4,4'-hydroxyl groups on the stilbenic backbone make DHS a more active molecule than resveratrol in inhibiting neoplastic transformation, cancer cell proliferation and invasion. In conclusion, this study suggests that DHS could be a promising anticancer agent.

Sunlight-induced degradation of soil-adsorbed veterinary antimicrobials Marbofloxacin and Enrofloxacin.

Marbofloxacin (MAR) and Enrofloxacin (ENR), two largely employed veterinary Fluoroquinolones (FQs), were found to be present at the micrograms per kilogram level in agricultural soils of South Lombardy (Italy) several months after manuring. Distribution coefficients (K(d)) from sorption experiments indicated a strong binding to the soil. Soil samples fortified with environmentally significant FQs amounts (0.5 mg kg(-1)) were exposed to solar light that promoted extensive degradation (80%) of both drugs in 60-150 h. Thus, photochemistry could be considered a significant depollution path in the soil, although it was two orders of magnitudes slower than in aqueous solution and a fraction of the drug (ca. 20%) remained unaffected. For MAR the photoprocess was the same as in solution, and involved cleavage of the tetrahydrooxadiazine ring. On the contrary, with ENR only some of the photoproducts determined in water (those arising from a stepwise oxidation of the piperazine side chain) were observed. Substitution of the 6-fluoro by a hydroxyl group and reduction did not occur in the soil, supporting the previous contention that such processes required polar solvation of FQs. Consistently with this rationalization, the irradiation of thin layers of solid drugs led to essentially the same products distribution as in the soil. From the environmental point of view it is important to notice that photodegradation mainly affects the side-chains, while the fluoroquinolone ring, to which the biological effect is associated, is conserved up to the later stages of the degradation.

Fluoroquinolones as potential photochemotherapeutic agents: covalent addition to guanosine monophosphate.

The triplet aryl cation photochemically generated from fluoroquinolones bearing a fluoro atom at position 8 attacks guanosine monophosphate (k(r) > 10(9) M(-1)s(-1)) and forms covalent adducts. The reaction is a model for the implementation of oxygen-independent photochemotherapy.

Photochemical degradation of marbofloxacin and enrofloxacin in natural waters.

The photochemical fate of Marbofloxacin (MAR) and Enrofloxacin (ENR), two Fluoroquinolones (FQs) largely used as veterinary bactericides known to be present in surface waters, was investigated in aqueous solution. The degradation of these pollutants (5-50 microg L(-1) starting concentration) was complete in about 1 h by exposure to solar light (summer) and obeyed a first-order kinetics. The structure of the primary photoproducts was determined. Those from ENR arose through three paths, namely, oxidative degradation of the piperazine side-chain, reductive defluorination, and fluorine solvolysis. More heavily degraded products that had been previously reported were rationalized as secondary photoproducts from the present ones. As for MAR, this underwent homolytic cleavage of the tetrahydrooxadiazine moiety to give two quinolinols. All of the primary products were themselves degraded in about 1 h. The photoreactions rates were scarcely affected by Ca(2+) (200 mg L(-1)), Mg(2+) (30 mg L(-1)), Cl(-) (30 mg L(-1)), and humic acid (1 mg L(-1)), but increased in the presence of phosphate (20 mg L(-1)). The fastest degradation of ENR occurred at pH about 8 where the zwitterionic form was present, while in the case of MAR the cationic form was the most reactive.

Photoarylation of alkenes and heteroaromatics by dibromo-BINOLs in aqueous solution.

The photochemistry of 6,6'-dibromo-BINOL (BINOL = 2,2'-dihydroxy-1,1'-binaphthyl) under mild basic conditions and its methyl and triisopropylsilyl ethers has been investigated in neat and aqueous acetonitrile through product distribution analysis and laser flash photolysis. Arylation and alkylation have been successfully achieved in the presence of allyltrimethylsilane, ethyl vinyl ether, pyrrole, pyridine, thiophene, benzene, and indole. Such a photoreactivity offers a metal and protecting group free synthetic protocol toward mono- and disubstituted 6-aryl/alkyl BINOLs, since the BINOL chirality is preserved in the photoactivation process.

Solid-phase extraction and HPLC determination of fluoroquinolones in surface waters.

An investigation on filtration procedures and SPE sorbents used for the determination of traces of the most common veterinary fluoroquinolones (FQs), marbofloxacin (MAR) and enrofloxacin (ENR) used as antibacterial agents in cattle and swine farms in the province of Pavia (Italy), was performed in natural waters. The filter composition and the sorbent used in the SPE strongly influence the correct recovery, both in terms of total and dissolved FQs concentration. An accurate comparison among different filters and SPE sorbents showed that a full determination of analytes was possible on nylon filters followed by anionic (WAX) and hydrophilic-lipophilic balance (HLB) resins as SPE. Quantitative analysis was done by chromatography with fluorescence detection (HPLC-FD). Fluoroquinolones recovery was between 90 and 116% with RSD not greater than 10% (sample volume 250 mL). The developed method allowed to determine both dissolved and NOM-absorbed fractions of FQs, therefore a full determination of the analytes was possible. Limits of detection (LOD) and quantification (LOQ) were, respectively, 0.7 and 2.2 ng/L for ENR and 2 and 6 ng/L for MAR. The kinetics of degradation under solar light was explored.

Inter- and intramolecular photochemical reactions of fleroxacin.

In the cation formed by photoinduced C-F bond cleavage in fleroxacin, intramolecular reaction with the N-ethyl chain is prevented by the electron-withdrawing effect of fluorine and intermolecular attack by nucleophiles is facilitated.

Photoarylation/alkylation of bromonaphthols.

The photochemistry of 6-bromo-2-naphthols has been studied in acetonitrile, aqueous acetonitrile, and isopropyl alcohol in the absence and in the presence of triethylamine by product distribution analysis, laser flash photolysis (LFP), fluorescence, phosphorescence, electrochemical measurements, and DFT calculations. Hydrobromic acid loss in the presence of Et(3)N occurs from the triplet state of 6-bromo-2-naphthol, generating an electrophilic carbene intermediate, which has been successfully trapped by oxygen, allyltrimethylsilane, 2,3-dimethylbut-2-ene, pyrrole, acrylonitrile, 1,4-dimethoxybenzene, and also pyridine. The generation and the reactivity of a triplet carbene intermediate has been supported by LFP, with the detection of 2,6-naphthoquinone-O-oxide (530 < lambda < 650 nm) in the presence of O(2). The electrophilic diradical character of the carbene has been supported by DFT calculations, using the B3LYP, PBE0, and MPWB1K functionals, with the 6-31+G(d,p) basis set and PCM solvation model.

Prebiotic chemistry: chemical evolution of organics on the primitive Earth under simulated prebiotic conditions.

A series of prebiotic mixtures of simple molecules, sources of C, H, N, and O, were examined under conditions that may have prevailed during the Hadean eon (4.6-3.8 billion years), namely an oxygen-free atmosphere and a significant UV radiation flux over a large wavelength range due to the absence of an ozone layer. Mixtures contained a C source (methanol, acetone or other ketones), a N source (ammonia or methylamine), and an O source (water) at various molar ratios of C : H : N : O. When subjected to UV light or heated for periods of 7 to 45 days under an argon atmosphere, they yielded a narrow product distribution of a few principal compounds. Different initial conditions produced different distributions. The nature of the products was ascertained by gas chromatographic-mass spectral analysis (GC-MS). UVC irradiation of an aqueous methanol-ammonia-water prebiotic mixture for 14 days under low UV dose (6 x 10(-2) Einstein) produced methylisourea, hexamethylenetetramine (HMT), methyl-HMT and hydroxy-HMT, whereas under high UV dose (45 days; 1.9 x 10(-1) Einstein) yielded only HMT. By contrast, the prebiotic mixture composed of acetone-ammonia-water produced five principal species with acetamide as the major component; thermally the same mixture produced a different product distribution of four principal species. UVC irradiation of the CH(3)CN-NH(3)-H(2)O prebiotic mixture for 7 days gave mostly trimethyl-s-triazine, whereas in the presence of two metal oxides (TiO(2) or Fe(2)O(3)) also produced some HMT; the thermal process yielded only acetamide.