Solar photo-Fenton degradation of nalidixic acid in waters and wastewaters of different composition. Analytical assessment by LC-TOF-MS.

This work assessed the solar photo-Fenton degradation of nalidixic acid (NXA), a quinolone antibacterial agent, in several different aqueous solutions. It has been proven that the composition of the water clearly affects the efficiency of the photo-Fenton process. The presence of chlorine ions induces the concurrence of different mechanisms involving Cl() and Cl(2)(-) radicals, which slow down the process. Up to 35 transformation products (TPs) were identified and their structures characterized by accurate LC-TOF-MS mass measurements during treatment of the different model waters. Photocatalytic degradation was thus observed to proceed mainly through the attack of the hydroxyl radicals on the double bond C((2))C((3)) which induce further ring opening. All the TPs identified persisted after total degradation of NXA. NXA in real pharmaceutical effluent was treated by photo-Fenton as a first stage before biological treatment. As NXA has been demonstrated to be recalcitrant to biological treatment, photo-Fenton treatment of the effluent was continued until its total degradation. Although NXA was efficiently degraded, LC-MS analyses demonstrated that some of the TPs identified after the photo-Fenton treatment were also recalcitrant to biological treatment, persisting after the combined treatment. These results show that analytical assessment of photocatalytic water treatments is essential to assure they are functioning as intended.

Studies on molecular interactions between nalidixic acid and liposomes.

The interaction between nalidixic acid sodium salt (NANa) and liposomes prepared from alpha-L-dipalmitoyl-phosphatidylcholine (DPPC) or from its binary mixture with dioleoyl-phosphatidylcholine (DOPC) was studied with differential scanning calorimetry (DSC) and electron paramagnetic resonance (EPR) spectroscopy. We evaluated the role of broadband ultraviolet-B (UV-B) irradiation on the molecular interactions between the lipids and the NANa, and determined the decay-kinetics of the incorporated spin labeled fatty-acid free radicals. Multilamellar and unilamellar vesicles were prepared by sonication and extrusion. The entrapment efficiencies were determined spectrophotometrically. The size-distribution of the liposomes and its change in time was checked by dynamic light scattering (DLS). Our results indicate that NANa mainly interacts with lipid head groups. However, its effect and presumably the formation of the free radicals, induced by broadband ultraviolet-B, is not localized only to the head group region of the lipid molecules. Depending on DOPC content, interaction between the NANa and the lipids modifies the phase-transition parameters of the liposome dispersions.

Pérdida de la actividad antibacteriana de quinolonas por efecto de la radiación UVA / UVA-induced loss of quinolone antibacterial activity

Se investiga la actividad antibacteriana de soluciones de las quinolonas ácido nalidíxico, ciprofloxacino y levofloxacino irradiadas mediante luz UVA. La fotólisis de las quinolonas produce una disminución de la actividad antibacteriana en cepas de E.coli y de S.aureus, evidenciándose un aumento de la concentración mínima inhibitoria de un 50 por ciento frente a las cepas ensayadas, en relación a las quinolonas no irradiadas. Se postula un mecanismo fotolítico radicalario con la consecuente fotodegradación de la porción gamma-piridona-beta-carboxílica responsable de la actividad antibacteriana (AU)

Quantitative in vitro assessment of phototoxicity by a fibroblast-neutral red assay.

We have adapted the neutral red uptake assay for quantitative assessment of injury to fibroblast cultures by potential phototoxins. Tetracycline derivatives, quinolone derivatives, and chlorpromazine were used as model compounds for development of the assay. Human fibroblasts were incubated with potential phototoxins, the cell cultures irradiated with UV, and the capacity for neutral red uptake determined. Demeclocycline and doxycycline, two known photosensitizers, showed a 94% and 95% decrease of neutral red uptake, respectively, indicating photo-induced cytotoxicity. Minocycline, a non-photosensitizing tetracycline derivative, showed no decrease in uptake. Tetracycline, a weak phototoxin, showed minor (10%) decrease at equivalent concentrations (20 micrograms/ml). Microscopic observation of neutral red uptake and cell damage paralleled the spectrophotometric findings. Chlorpromazine, a non-tetracycline phototoxin, showed 91% decrease. An additional group of phototoxic drugs, quinolone antibacterials, were studied. Nalidixic acid, ofloxacin, ciprofloxacin, and norfloxacin all demonstrated phototoxicity, with nalidixic acid showing the greatest decrease in neutral red uptake. This methodology may provide a useful rapid method to quantify phototoxic potential of new drugs or suspected phototoxins.

Photodegradation of nalidixic and tiaprofenic acids and nifedipine in aerobic conditions.

Since nalidixic acid had been previously studied in acidic and basic media, nifedipine had been investigated in anaerobic conditions and under ultraviolet light and tiaprofenic acid had not been studied at all, their photodegradation was carried out in this laboratory under milder conditions, with methanol as the solvent and using visible light. The role of oxygen was demonstrated and the photoproducts were isolated and identified spectroscopically.