Identification of adducts formed in reaction of adenosine with 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone, a bacterial mutagen present in chloride disinfected drinking water.
3-Chloro-4-methyl-5-hydroxy-2(5h)-furanone, MCF, a genotoxic hydroxyfuranone present in chlorine disinfected drinking water, was reacted with adenosine, guanosine, and cytidine in aqueous solutions. HPLC analyses of the reaction mixtures showed that only in the reaction of MCF and adenosine clearly detectable products were formed. The two major products were isolated by C18 column chromatography and characterized by UV absorbance, 1H and 13C NMR spectroscopy, and mass spectrometry. The products were identified as 4-(N6-adenosinyl)-3-formyl-3-butenoic acid (I) and 5-(N6-adenosinyl)-3-chloro-4-methyl-2(5H)-furanone (II). The yield of I and II in reactions performed at pH 7.4 and 37 degrees C was 0/8% and 0/5%, respectively. Reaction of adenosine with 13C-3-labeled MCF was employed to elucidate the mechanism of formation of I. It was found that the product was formed by a nucleophilic attack of the exocyclic amino group in adenosine on the carbon in the 4-methyl group of MCF. These adducts appear to be novel and not structurally related to those previously identified in the reaction of adenosine with mucochloric acid, another genotoxic hydroxyfuranone.
Munter
T
T
Department of Organic Chemistry, Abo Akademi University, Turku/Abo, Finland.
Kronberg
L
L
Sjöholm
R
R
D000241:Adenosine / Q000737:chemistry*; D002250:Carbon Radioisotopes; D002713:Chlorine / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D005663:Furans / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009153:Mutagens / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D013997:Time Factors; D014316:Tritium; D018508:Water Purification / Q000379:methods; D014881:Water Supply / Q000592:standards*
D002250:Carbon Radioisotopes; D005663:Furans; D009153:Mutagens; D014316:Tritium; C101818:3-chloro-4-methyl-5-hydroxy-2(5H)-furanone; D002713:Chlorine; D000241:Adenosine