Glutathione and N-acetylcysteine inactivations of mutagenic 2(5H)-furanones from the chlorination of humics in water.
The mutagenic 2(5H)-furanones resulting from the chlorination of lignohumic substances in water disinfection and paper pulp bleaching are known to be inactivated by thiols. The objectives of the present study were to characterize the kinetics of an inactivating reaction, isolate and characterize products, and determine their mutagenicity in relation to the starting, mutagenic 2(5H)-furanones. The Salmonella typhimurium (TA100) mutagenicity of mucochloric acid (MCA) had a mean value of 2800 revertants/mumol from four assays and was twice as potent as the C-5 isopropyl ether of MCA (MCA-IPE), whose mutagenicity was determined in the same four assays. A second-order reaction of MCA with GSH at pH 7 was observed. The major product, making up 70% of the total product mixture, was identified as a 1.5:1 mixture of two diastereomers formed by sulfur displacement of the C-4 Cl atom from MCA. The major diastereomer was isolated from the 1.5:1 mixture. Connectivity of GSH to the MCA moiety in the product was established by 2D long-range coupling NMR and fully coupled 13C NMR. On the basis of circular dichroism, the major diastereomer had the S configuration at the hydroxyl-bearing, C-5 ring carbon. MCA-IPE reacted with GSH and N-acetylcysteine (NAC), giving 1:1 mixtures of two diastereomers, again by displacement of the C-4 Cl atom from MCA. A single diastereomer was isolated from the 1:1 MCA-IPE plus NAC reaction. Its structure, determined by X-ray crystallography, had the 5R,8R configuration and was in agreement with the ross structure deduced from the NMR analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
LaLonde
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Department of Chemistry, State University of New York, College of Environmental Science & Forestry, Syracuse 13210-2786.
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D000111:Acetylcysteine / Q000737:chemistry*; D000818:Animals; D002712:Chlorides / Q000737:chemistry; D002855:Chromatography, Thin Layer; D002942:Circular Dichroism; D005663:Furans / Q000737:chemistry* / Q000633:toxicity; D005978:Glutathione / Q000737:chemistry*; D006812:Humic Substances / Q000737:chemistry*; D066298:In Vitro Techniques; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry* / Q000633:toxicity; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013056:Spectrophotometry, Ultraviolet; D014881:Water Supply / Q000032:analysis*; D014961:X-Ray Diffraction
D002712:Chlorides; D005663:Furans; D006812:Humic Substances; D009153:Mutagens; C014117:mucochloric acid; D005978:Glutathione; D000111:Acetylcysteine