REACTION OF THE POTENT BACTERIAL MUTAGEN CHLORO-4-(DICHLOROMETHYL)-5-HYDROXY-2(5H)-FURANONE (MX) WITH 2'-DEOXYADENOSINE AND CALF THYMUS DNA- IDENTIFICATION OF FLUORESCENT PROPENOFORMYL DERIVATIVES

The potent bacterial mutagen and drinking water disinfection byproduct chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was reacted w ith 2'-deoxyadenosine and calf thymus DNA in aqueous solutions at neut ral conditions. HPLC analyses of the 2'-deoxyadenosine reaction mixtur es showed that two previously unidentified products were formed. The p roducts were isolated by preparative C18 chromatography, and their str uctures were characterized by UV absorbance, fluorescence emission, H- 1 and C-13 NMR spectroscopy, and mass spectrometry. It was concluded t hat in both products a propeno bridge had been incorporated between N- 1 and N-6 Of the adenine unit. In one of the products, the propeno bri dge carried a formyl group -D-ribofuranosyl)-7H-8-formyl[2,1-i]pyrimid opurine (pfA-dR)], and in the other the substituents consisted of a fo rmyl group and a chlorine atom ranosyl)-7H-8-formyl-9-chloro[2,1-i]pyr imidopurine (Cl-pfA-dR)]. These novel adducts exhibited fluorescence i n the visible region with emission maxima around 460 nm. The yields of the products in reactions performed at pH 7.4 and 37 degrees C were a bout 0.03 mol %. In reaction of MX with calf thymus DNA, the adduct pf A-dR was formed and its yield was about 0.6 adduct/10(5) nucleotides.