Antibacterial, antifungal, phytotoxic, and genotoxic properties of two complexes of Ag(I) with sulfachloropyridazine (SCP): X-ray diffraction of [Ag(SCP)]n.

We report the synthesis, characterization, antibacterial and antifungal activities, phytotoxicity, and genotoxicity of two new complexes of silver(I) with sulfachloropyridazine (SCP), one of which is heteroleptic with SCP and SCN(-) ligands (Ag-SCP-SCN), the other of which is homoleptic (Ag-SCP); furthermore, the crystal structure of the homoleptic complex is disclosed. The heterocyclic N atom nearest to the Cl atom and the N(sulfonamide) atom could be coordination sites for the silver ion in the Ag-SCP-SCN complex. The Ag-SCP complex is a polymeric compound with metal-metal bonds, and the heterocyclic and sulfonamide N atoms are points of coordination for Ag(I) . Both complexes showed activity against all the tested bacteria, and in the cases of Escherichia coli and Pseudomonas aeruginosa, the action was better than that of SCP. In all cases, both silver-SCP complexes showed better antifungal activity than SCP, which was inactive against the tested fungi. Notably, the activity against P. aeruginosa, a nosocomial multidrug-resistant pathogen, was better than that of the reference antibiotic cefotaxim. Both silver-sulfa complexes displayed moderate activity against the tested yeast, especially for C. neoformans, which is an important fact considering the incidence of cryptococcosis, mainly in immune-deficient patients. No chromosomal aberrations were observed with the Allium cepa test, which is auspicious for further study of these complexes as potential drugs.

Electrochemical degradation of the antibiotic sulfachloropyridazine by hydroxyl radicals generated at a BDD anode.

The treatment of aqueous solutions of the antibiotic sulfachloropyridazine (SCP) was carried out at the natural pH of the solution (pH 4.5) with hydroxyl radicals (OH) generated at a BDD anode surface by electro-oxidation using an undivided electrochemical cell equipped with a three-dimensional carbon-felt cathode. Hydroxyl radicals are powerful oxidants and react with the antibiotic leading to its overall mineralization. The kinetic study showed that oxidative degradation of SCP follows pseudo first-order reaction kinetics, with a relatively short degradation time. The degree of mineralization of SCP solutions increased with the applied current, being higher than 95% after 8 h of electrolysis at 350 mA or higher current. To determine the degradation pathway upon the action of hydroxyl radicals, the cyclic and aliphatic by-products, as well as the released inorganic ions, were identified and quantified over electrolysis time. The values of the rate constants of reactions between OH and the SCP and its intermediates were determined by the competition kinetics method using p-hydroxybenzoic acid. The absolute rate constant for the OH-mediated degradation of SCP was found to be 1.92 × 10(9)M(-1)s(-1). Toxicity assessment by the Microtox method during the electro-oxidation of SCP solutions revealed the formation of compounds that can be more toxic than the parent molecule, but the overall results confirm the effectiveness of this electrochemical process for the removal of the antibiotic SCP and its by-products from aqueous media.

Electrochemical treatment of the antibiotic sulfachloropyridazine: kinetics, reaction pathways, and toxicity evolution.

The electro-Fenton treatment of sulfachloropyridazine (SCP), a model for sulfonamide antibiotics that are widespread in waters, was performed using cells with a carbon-felt cathode and Pt or boron-doped diamond (BDD) anode, aiming to present an integral assessment of the kinetics, electrodegradation byproducts, and toxicity evolution. H(2)O(2) electrogeneration in the presence of Fe(2+) yielded (•)OH in the solution bulk, which acted concomitantly with (•)OH adsorbed at the anode (BDD((•)OH)) to promote the oxidative degradation of SCP (k(abs,SCP) = (1.58 ± 0.02) × 10(9) M(-1) s(-1)) and its byproducts. A detailed scheme for the complete mineralization was elucidated. On the basis of the action of (•)OH onto four different SCP sites, the pathways leading to total decontamination includes fifteen cyclic byproducts identified by HPLC and GC-MS, five aliphatic carboxylic acids, and a mixture of Cl(-), SO(4)(2-), NH(4)(+), and NO(3)(-) that accounted for 90-100% of initial Cl, S, and N. The time course of byproducts was satisfactorily correlated with the toxicity profiles determined from inhibition of Vibrio fischeri luminescence. 3-Amino-6-chloropyridazine and p-benzoquinone were responsible for the increased toxicity during the first stages. Independent electrolyses revealed that their toxicity trends were close to those of SCP. The formation of the carboxylic acids involved a sharp toxicity decrease, thus ensuring overall detoxification.

Effects of sulfachlorpyridazine in MS.3-arable land: a multispecies soil system for assessing the environmental fate and effects of veterinary medicines.

A multispecies soil system (MS.3) has been used to evaluate the ecological effects of veterinary pharmaceuticals in soil as a result of routine agricultural practices. Different experimental conditions were tested and the variation of the different parameters was evaluated for a final design. A protocol for the MS.3-arable land is presented here. Emergence of seedlings, plant elongation and biomass, earthworm mortality, and soil microbial enzymatic activities have been selected as toxicological endpoints for soil organisms. Toxicity tests were conducted with the leachate on aquatic organisms (in vitro fish cell lines, daphnids, and algae). The system was used for assessing the effects of the antimicrobial sulfachlorpyridazine that was tested in triplicate at concentrations of 0.01, 1, and 100 mg/kg. The chemical was mixed uniformly with a 20-cm depth soil column to resemble the distribution of manure within arable soil. Reversible and nonreversible effects on soil enzymatic activities were observed at 1 and 100 mg/kg, respectively. Earthworms were not affected. Significant reduction of plant elongation and biomass was observed at the highest concentration. Degradation and leaching contributed to the dissipation of sulfachlorpyridazine from the soil column. The undiluted leachate was highly toxic to Daphnia magna. The parent chemical was assumed responsible for the leachate toxicity although the role of mobile metabolites could not be excluded fully. No significant effects were observed for green algae Chlorella vulgaris and for the rainbow trout established cell lines RTG-2 (rainbow trout gonads) and RTL-WI (rainbow trout liver). The MS.3 system offers a cost-effective experimental approach to measure simultaneously fate and effects of chemicals on a realistic soil system under controlled laboratory conditions. The advantages of using MS.3-effect endpoints are discussed.

A lysimeter experiment to investigate the leaching of veterinary antibiotics through a clay soil and comparison with field data.

Pharmaceuticals used in livestock production may be present in manure and slurry as the parent compound and/or metabolites. The environment may therefore be exposed to these substances due to the application of organic fertilisers to agricultural land or deposition by grazing livestock. For other groups of substances that are applied to land (e.g. pesticides), preferential flow in clay soils has been identified as an extremely important mechanism by which surface water pollution can occur. This lysimeter study was therefore performed to investigate the fate of three antibiotics from the sulphonamide, tetracycline and macrolide groups in a clay soil. Only sulphachloropyridazine was detected in leachate and soil analysis at the end of the experiment showed that almost no antibiotic residues remained. These data were analysed alongside field data for the same compounds to show that soil tillage which breaks the connectivity of macropores formed over the summer months, prior to slurry application, significantly reduces chemical mobility.