Final effluent samples from 10 southern California (United States) wastewater treatment facilities, employing four distinct treatment schemes, were surveyed for selected pharmaceuticals, personal care products (PPCPs), alkylphenols, and 21 of their halogenated disinfection byproducts. Chlorinated and brominated standards and isotopically labeled internal standards were synthesized and purified to confirm and more accurately quantify selected disinfection byproducts of salicylic acid, bisphenol A, gemfibrozil, naproxen, diclofenac, technical 4-nonylphenol, and 4-tert-octylphenol using high-performance liquid chromatography and tandem mass spectrometry. Concentrations of parent compounds ranged from <10 to 3830 ng/L (gemfibrozil), and those of chloro/bromo byproducts ranged from <4 to 370 ng/L (dibromo nonylphenol). The highest concentrations of parent compounds were measured in effluent that was not subjected to tertiary treatment. The chlorinated and brominated byproduct concentration may be affected by the influent concentration of parent compounds, hydraulic retention times, and chlorine contact times. Salicylic acid was readily halogenated, which is evident from the ratio of halogenated to nonhalogenated species. There were no measured chlorinated byproducts of bisphenol A despite occasionally high concentrations of the parent compound. Not surprisingly, higher concentrations of most brominated species were measured in the treatment plant with the highest bromide concentrations. These results demonstrate the occurrence of novel halogenated byproducts of PPCPs that have limited toxicological data and significant uncertainty with regard to their risk to ecological systems.
The cholesterol-lowering pharmaceutical gemfibrozil is a relevant environmental contaminant because of its frequency of detection in U.S. wastewaters at concentrations which have been shown to disrupt endocrine function in aquatic species. The treatment of gemfibrozil solutions with sodium hypochlorite yielded a 4'-chlorinated gemfibrozil analog (chlorogemfibrozil). In the presence of bromide ion, as is often encountered in municipal wastewater, hypobromous acid generated through a halogen exchange reaction produced an additional 4'-brominated gemfibrozil product (bromogemfibrozil). Standards of chloro- and bromogemfibrozil were synthesized, isolated and characterized using mass spectrometry and NMR spectroscopy. Mass spectrometry was used to follow the in situ halogenation reaction of gemfibrozil in deionized water and wastewater matrices, and to measure levels of gemfibrozil (254 ± 20 ng/L), chlorogemfibrozil (166 ± 121 ng/L), and bromogemfibrozil (50 ± 11 ng/L) in advanced primary wastewater treatment effluent treated by chlorination. Chlorogemfibrozil demonstrated a significant (p < 0.05) reduction in the levels of 11-ketotestosterone at 55.1 μg/L and bromogemfibrozil demonstrated a significant (p < 0.05) reduction in the levels of testosterone at 58.8 μg/L in vivo in Japanese medaka in a 21 day exposure. These results indicated that aqueous exposure to halogenated degradates of gemfibrozil enhanced the antiandrogenicity of the parent compound in a model fish species, demonstrating that chlorination may increase the toxicity of pharmaceutically active compounds in surface water.
Oxygen is an essential participant in the acid-base chemistry that takes place within many enzyme active sites,yet has remained virtually silent as aprobe in NMR spectroscopy. Here,w ed emonstrate the first use of solution-state 17 Oquadrupole central-transition NMR spectroscopyt oc haracterizee nzymatic intermediates under conditions of active catalysis.I nt he 143 kDa pyridoxal-5'-phosphate-dependent enzyme tryptophan synthase,reactions of the a-aminoacrylate intermediate with the nucleophiles indoline and 2-aminophenol correlate with an upfield shift of the substrate carboxylate oxygen resonances.First principles calculations suggest that the increased shieldings for these quinonoid intermediates result from the net increase in the charge density of the substratecofactor p-bonding network, particularly at the adjacent acarbon site.
Oxygen is an essential participant in the acid-base chemistry that takes place within many enzyme active sites, yet has remained virtually silent as a probe in NMR spectroscopy. Here, we demonstrate the first use of solution-state 17O quadrupole central transition NMR spectroscopy to characterize enzymatic intermediates under conditions of active catalysis. In the 143 kDa pyridoxal-5’-phosphate-dependent enzyme tryptophan synthase, reactions of the α-aminoacrylate intermediate with the nucleophiles indoline and 2-aminophenol correlate with an upfield shift of the substrate carboxylate oxygen resonances. First principles calculations suggest that the increased shieldings for these quinonoid intermediates result from the net increase in the charge density of the substrate-cofactor π bonding network, particularly at the adjacent alpha-carbon site.
A method for log D (pH 7.4) measurement was developed using microfluidic liquid-liquid extraction. Values were determined for 26 compounds and compared to results obtained via shake-flask methods. Excellent correlation between the values obtained via both methods was achieved (R(2) = 0.994). The developed methodology is amenable to automation, enabling high-throughput determination of large compound collections.
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