RT Journal Article
SR Electronic
T1 Solvolytic formation of 1,2-dichloro-3,4-epoxybutane from butadiene monoxide under physiological conditions.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 206
OP 210
VO 22
IS 2
A1 X Cheng
A1 C Maniglier-Poulet
A1 D Ross
A1 J A Ruth
YR 1994
UL http://dmd.aspetjournals.org/content/22/2/206.abstract
AB Butadiene monoxide, a presumed carcinogenic metabolite of butadiene, is stable in water or phosphate buffer, but was found to rapidly disappear from the headspace of solutions (10(-6) to 10(-4) M) in phosphate-buffered saline incubated at 37 degrees C. The process was first order with respect to monoxide concentration, with an apparent rate constant of 6.6 x 10(-4) sec-1. Mass spectrometric examination of the major product formed indicated it to be 1,2-dichloro-3,4-epoxybutane, which was confirmed by synthesis. Formation of the dichloro epoxide was linearly dependent on chloride ion concentration of the medium, but independent of dissolved oxygen. The formation of the dichloro epoxide is explained by slow solvolytic formation of a chloronium ion from butadiene monoxide, which is followed by attack of chloride ion to generate chlorine and butadiene. The chlorine is than rapidly trapped by second molecule of butadiene monoxide. This was confirmed by competitive trapping of generated chlorine by inclusion of crotyl alcohol in the incubation. A similar pathway has recently been demonstrated for reversible formation of bromine from solvolytically generated bromonium ions. The facile formation of dichloroepoxybutane under physiological conditions may be of significance in the toxicity of butadiene.