title: alpha-chloroepoxides. 2. Mutagenicity of 1-chlorocyclohexene oxide and its thermal isomerization product, 2-chlorocyclohexanone.
abstract: The pseudo-first-order hydrolysis rate constants in pH 7.4 buffer-acetone solution are reported for 1-chlorocyclohexene oxide and 2-chlorocyclohexanone at 0, 25 and 37 degrees C. The rate constants, in conjunction with product studies, demonstrate that the hydrolysis of 1-chlorocyclohexane oxide quantitatively affords 2-hydroxycyclohexanone and that there is no significant isomerization of 1-chlorocyclohexene oxide to 2-chlorocyclohexanone during the hydrolysis. Both 1-chlorocyclohexene oxide and 2-chlorocyclohexanone were reacted with 2-aminopyridine, a model for adenine, to yield the same product, N-(2'-pyridyl)-2-aminocyclohexanone. The mutagenicity of 1-chlorocyclohexene oxide and 2-chlorocyclohexanone in the Ames liquid incubation assay using TA100 shows 2-chlorocyclohexanone to be slightly more active than 1-chlorocyclohexene oxide, in spite of the finding that 1-chlorocyclohexene oxide is clearly a more reactive electrophile than 2-chlorocyclohexanone. These results are interpreted to indicate the important role that hydrolysis (detoxification) plays in the in vitro evaluation of the proposed ultimate electrophilic metabolites of chloroolefins.
mesh_terms: D055598:Chemical Phenomena; D002621:Chemistry; D003510:Cyclohexanes / Q000633:toxicity*; D003512:Cyclohexanones / Q000633:toxicity*; D006868:Hydrolysis; D007700:Kinetics; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D003510:Cyclohexanes; D003512:Cyclohexanones; D009153:Mutagens; C039058:1-chlorocyclohexene oxide; C039057:2-chlorocyclohexanone