Metabolism of 1,1,1,2,2-pentafluorohexane and 1,1-difluorocyclohexane by rat liver microsomes in vitro.
Metabolism of 1,1,1,2,2-pentafluorohexane with liver microsomes from phenobarbital-treated rats gave only one metabolite, namely, the 5-hydroxy derivative. Under similar conditions 1,1-difluorocyclohexane was metabolized to give mainly the 3- and 4-hydroxy derivatives in the ratio 1: approximately 5.5. The structures of these metabolites were established by chemical ionization (CI) and/or electron impact (EI) mass spectrometry and confirmed by synthesis in the case of 1,1-difluorocyclohexan-4-ol. Oxidation of 1,1-difluorocyclohexane with lead tetrakis(trifluoroacetate) also gave, inter alia, the 3- and 4-hydroxy derivatives. In saturated hydrocarbons complete replacement of hydrogen by fluorine at one particular carbon will not only block microsomal hydroxylation thereat but will also inhibit hydroxylation at neighbouring hydrogen-bearing carbons, (alpha almost completely, beta markedly, gamma slightly).
D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism*; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010105:Oxygenases / Q000096:biosynthesis; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D005466:Fluorocarbons
D006845:Hydrocarbons, Fluorinated; D010105:Oxygenases; D010634:Phenobarbital; C044231:1,1-difluorocyclohexane; C044230:1,1,1,2,2-pentafluorohexane; D005466:Fluorocarbons