Reactions of Halogenated Hydroperoxides and Peroxyl and Alkoxyl Radicals from Isoflurane in Aqueous Solution

摘要

Model systems,based on aqueous solutions containing isoflurane(CHF2OCHClCF3)as an example,have been studied in the presence and absence of methionine(MetS)to evaluate reactive fates of halogenated hydroperoxides and peroxyl and alkoxyl radicals.Primary peroxyl radicals,CHF2OCH(OO~·)CF3,generated upon 1-e-reduction of isoflurane react quantitatively with MetS via an overall two-electron oxidation mechanism to the corresponding sulfoxide(MetSO).This reaction is accompanied by the formation of oxyl radicals CHF2OCH(O~·)CF3 that quantitatively rearrange by a 1,2-hydrogen shift to CHF2OC~·(OH)CF3.According to quantum-chemical calculations,this reaction is exothermic(DELTA H=-5.1 kcal/mol)in contrast to other potentially possible pathways.These rearranged CHF2OC~·(OH)CF3 radicals react further via either of two pathways:(i)direct addition of oxygen or(ii)deprotonation followed by fluoride elimination resulting in CHF2OC(O)-CF_2~·.Route i yields the corresponding CHF2OC(OO~·)(OH)CF3 peroxyl radicals,which eliminate H~+/O_2~(·-)The resulting ester,CHF2OC(O)CF3,hydrolyzes further,accounting for the formation of HF,trifluoroacetic acid,and formic acid with a contribution of 45% and 80% in air-and oxygen-saturated solutions,respectively.A competitive pathway(ii)involves the reactions of the secondary peroxyl radicals,CHF2OC(O)CF2OO~· The two more stable of the three above mentioned peroxyl radicals can be distinguished through their reaction with MetS.Although the primary CHF2OCH(OO~·)CF3 oxidizes MetS to MetSO in a 2-e step,the majority of the secondarily formed CHF2OC(O)CF2OO~· reacts with MetS via a 1-e transfer mechanism,yielding CHF2OC(O)CF2OO~-,which eventually suffers a total breakup into CHF2O~-+CO2+CF2O.Quantum-chemical calculations show that this reaction is highly exothermic(DELTA H=-81 kcal/mol).In air-saturated solution this pathway accounts for about 35% of the overall isoflurane degradation.Minor products(10% each),namely,oxalic acid and carbon monoxide originate from oxyl radicals,CHF2OC(O)CF2O~· and CHF2-OCH(O~·)CF3.An isoflurane-derived hydroperoxide CHF2OCH(OOH)CF3 in high yield was generated in radiolysis of air-saturated solutions containing isoflurane and formate either via a H-atom abstraction from formate by the isoflurane-derived peroxyl radicals or by their cross-termination reaction with superoxide O_2~(·-).CHF2OCH(OOH)CF3,is an unstable intermediate whose multistep hydrolysis is giving H2O2+2HF+HC(O)OH+CF3CH(OH)2.In the absence of MetS,about 55% of CHF2OCH(OO~·)CF3 undergo termination via the Russell mechanism and 27% are involved in cross-termination with superoxide(O_2~(·-))and peroxyl radicals derived from t-BuOH(used to scavenge ~·OH radicals).The remaining 18% of the primary peroxyl radicals undergo termination via formation of alkoxyl radicals,CHF2OCH(O~·)CF3.