title: Experimental and theoretical investigations of the autoxidation of geranial: a dioxolane hydroperoxide identified as a skin sensitizer.
abstract: The autoxidation of geranial with O(2) was studied both experimentally and using density functional theory. Computational results were used to interpret experimentally observed product ratios. Geranial was found to autoxidize, forming 6,7-epoxygeranial as the main oxidation product. Hydroperoxides corresponding to those identified as important skin sensitizers in previous studies of fragrance terpenes could not be detected. Instead, a dioxolan derivative and its corresponding hydroperoxide were identified and detected in high concentrations. The distribution of products in autoxidation generally depends on the stabilities of the intermediate peroxyl radicals. In this study, the formation of a peracyl radical was found to be highly favored. This radical forms peracid which epoxidizes geranial. The epoxide thus produced can react with acyl radical to yield the dioxolan hydroperoxide. The dioxolan derivative is believed to form in an acid catalyzed closed shell reaction between 6,7-epoxygeranial and geranial. The dioxolan hydroperoxide and 6,7-epoxygeranial are strong sensitizers and are considered to be the compounds mainly responsible for the skin sensitization potency of air-exposed geranial.
authors.affiliation: Dermatochemistry and Skin Allergy, Department of Chemistry, University of Gothenburg, SE-412 96 Gothenburg, Sweden. lina.hagvall@gu.se
authors.forename: Lina
authors.initials: L
authors.lastname: Hagvall
authors.forename: Carina
authors.initials: C
authors.lastname: Bäcktorp
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Norrby
authors.forename: Ann-Therese
authors.initials: AT
authors.lastname: Karlberg
authors.forename: Anna
authors.initials: A
authors.lastname: Börje
mesh_terms: D000080462:Acyclic Monoterpenes; D000485:Allergens / Q000009:adverse effects / Q000737:chemistry*; D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D004148:Dioxolanes / Q000009:adverse effects / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000009:adverse effects / Q000737:chemistry*; D023441:Local Lymph Node Assay; D051379:Mice; D039821:Monoterpenes / Q000009:adverse effects / Q000737:chemistry*; D010084:Oxidation-Reduction; D012867:Skin / Q000187:drug effects
chemical_list: D000080462:Acyclic Monoterpenes; D000485:Allergens; D004148:Dioxolanes; D039821:Monoterpenes; D006861:Hydrogen Peroxide; C007076:citral