Reaction of mucochloric and mucobromic acids with adenosine and cytidine: formation of chloro- and bromopropenal derivatives

Mucochloric (MCA) and mucobromic acid (MBA)--bacterial mutagens and water disinfection byproducts--were reacted with adenosine, cytidine, and guanosine in N,N-dimethylformamide (DMF). In the MCA reaction with adenosine and cytidine and in the MBA reaction with adenosine one major product was formed. In the reactions of MBA with cytidine and in the reactions of MCA and MBA with guanosine only trace levels of products could be detected, and these were not further characterized. The products from the adenosine and cytidine reactions were isolated by preparative chromatography on octadecylsilane columns and structurally characterized by UV absorbance, 1H and 13C NMR spectroscopy, and mass spectrometry. The products were identified as 3-(N6-adenosinyl)-2-chloro-2-propenal (MClA), 3-(N6-adenosinyl)-2-bromo-2-propenal (MBrA), and 3-(N4-cytidinyl)-2-chloro-2-propenal (MClC). The yields of MClA, MBrA, and MClC were 19, 4 and 7 mol %, respectively. These halopropenal derivatives were formed also in reactions carried out in aqueous solutions at pH 7.4 and 37 degrees C at low yields, about 5 x 10(-3)%. The mechanism of formation of the halopropenal derivatives and of the previously identified etheno and ethenocarbaldehyde derivatives was elucidated by reacting 13C-3 labeled MCA with adenosine in DMF and in water. The location of the labeled carbon in the products was determined from the 13 C NMR spectra. It was concluded that the halopropenal derivatives were formed by mechanisms that differ completely from the one responsible for the formation of the propenal adducts (M1A and M1C) previously reported to be formed in reactions of malonaldehyde with adenosine and cytidine.