Roman Flyunt1, Oksana Makogon2, Christian Schoneich3, Klaus-Dieter Asmus4
1 MPI-Strahlenchemie, Postfach 101365, D-45413 Mulheim an der Ruhr, Germany,
2 Institute of Physico-Chemistry, National Academy of Sciences of the Ukraine, Naukova Street 3a, 290053, Lvov, Ukraine,
3 Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66045, USA,
4 Radiation Laboratory and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
It was established that peroxyl radicals (CF3CHClOO·) derived from halothane (CF3CHClBr) quantitatively react with methionine (MetS) to the corresponding sulfoxide (MetSO). This reaction was accompanied by the formation of oxyl radicals (CF3CHClO·), which, in a first step, appear to rearrange by 1,2-hydrogen shift to CF3C·(OH)Cl. The latter may react via one of two pathways: direct addition of oxygen or immediate elimination of hydrochloric acid (HCl) from CF3C·(OH)Cl. Direct addition of oxygen yields the corresponding peroxyl radical, which, upon H+/O2·- elimination and subsequent hydrolysis of CF3COCl, could account for the formation of trifluoroacetic acid (TFA), one of the major observed products. An alternative and, based on the combined evidence of our data, probably more favorable route is based on immediate elimination of HCl from CF3C·(OH)Cl, which generates CF3C·(OH)2 upon hydrolysis. Subsequent reaction of this radical with O2 yields CF3C(OO·)(OH)2, followed by H+/O2·- elimination, which also leads to CF3CO2H. This route accounts for approximately 41% of the initial CF3CHClOO· radicals. To accommodate the high yields of fluoride ions and carbon dioxide, which indicate a complete breakdown of the halothane molecule, a competing reaction pathway of the CF3C·(OH)2 radicals is proposed. In its first step elimination of one fluoride ion to yield ·CF2CO2- is envisaged (possibly involving a deprotonated form of CF3C·(OH)2). The peroxyl radicals ·OOCF2CO2-, formed upon oxygen addition to ·CF2CO2-, are suggested to react with MetS, yielding MetSO and alkohol radicals (·OCF2CO2-). It is proposed that the latter decompose via carbon-carbon bond cleavage to COF2, and CO2·-. This pathway, which leads to complete halogen release (as halide ions), accounts for approximately 53% of the initially formed CF3CHClOO· radicals. The observed high MetSO yields, G=(5.6), are explained by oxidation of MetS by CF3CHClOO· and ·OOCF2CO2- via 2-electron transfer mechanisms. A detailed reaction scheme and quantitative material balance is provided on the basis of the measured yields of CF3CO2H, Br-, Cl-, F- and CO2 as major components and carbon monoxide (CO) and oxalate as minor components.