Department of Chemistry, Dermatochemistry and Skin Allergy, University of Gothenburg, Gothenburg, Sweden.
Chem Res Toxicol. 2009 Nov;22(11):1774-81. doi: 10.1021/tx9001435.
The widespread use of scented products causes an increase of allergic contact dermatitis to fragrance compounds in Western countries today. Many fragrance compounds are prone to autoxidation, forming hydroperoxides as their primary oxidation products. Hydroperoxides are known to be strong allergens and to form specific immunogenic complexes. However, the mechanisms for the formation of the immunogenic complexes are largely unknown. We have investigated this mechanism for (5R)-5-isopropenyl-2-methyl-2-cyclohexene-1-hydroperoxide (Lim-2-OOH) by studying the formation of adducts in the reaction between this hydroperoxide and 5,10,15,20-tetraphenyl-21H,23H-porphine iron(III) chloride (Fe(III)TPPCl) in the presence of protected cysteine (NAc-Cys-OMe) or glutathione (GSH). Isolated adducts originate from the addition of the thiol group of NAc-Cys-OMe over the carbon-carbon double bonds of carvone. Furthermore, adducts between NAc-Cys-OMe and carveol as well as between GSH and carvone have been identified. The formation of these adducts most likely proceeds via the radical thiol-ene mechanism. The addition of a terpene moiety to cysteine offers an explanation of the specificity of the immune response to structurally different hydroperoxides. These results also explain the lack of cross-reactivity between carvone and Lim-2-OOH. In conclusion, we propose that immunogenic complexes of olefinic hydroperoxides can be formed via the radical thiol-ene mechanism. These complexes will be specific for the individual olefinic hydroperoxides due to the inclusion of a terpene moiety derived from the hydroperoxide.
如今，在西方国家，香薰产品的广泛使用导致了对香料化合物的过敏接触性皮炎的增加。许多香料化合物容易自动氧化，形成过氧化物作为其主要氧化产物。众所周知，过氧化物是很强的过敏原，并形成特定的免疫原性复合物。然而，形成免疫原性复合物的机制在很大程度上尚不清楚。我们通过研究（5R）-5-异丙烯基-2-甲基-2-环己烯-1-过氧化物（Lim-2-OOH）与 5,10,15,20-四苯基-21H,23H-卟啉铁（III）氯化物（Fe（III）TPPCl）在保护半胱氨酸（NAc-Cys-OMe）或谷胱甘肽（GSH）存在下的反应中形成的加合物，研究了这种机制。分离出的加合物源于 NAc-Cys-OMe 的巯基基团加在香芹酮的碳-碳双键上。此外，还鉴定了 NAc-Cys-OMe 和香芹醇以及 GSH 和香芹酮之间的加合物。这些加合物的形成很可能通过自由基硫醇-烯机制进行。萜烯部分与半胱氨酸的加成解释了对结构不同的过氧化物的免疫反应的特异性。这些结果也解释了香芹酮和 Lim-2-OOH 之间缺乏交叉反应性。总之，我们提出烯烃过氧化物的免疫原性复合物可以通过自由基硫醇-烯机制形成。由于包含了过氧化物衍生的萜烯部分，这些复合物将对单个烯烃过氧化物具有特异性。
