title: Studies of the chemical selectivity of hapten, reactivity, and skin sensitization potency. 1. Synthesis and studies on the reactivity toward model nucleophiles of the (13)C-labeled skin sensitizers hex-1-ene- and hexane-1,3-sultones.
abstract: The potent skin sensitizers hex-1-ene- and hexane-1,3-sultone have been synthesized isotopically labeled with (13)C at reactive sites. The reactivity of 2-[(13)C]- and 3-[(13)C]hex-1-ene-1,3-sultones and of 3-[(13)C]hexane-1,3-sultone toward a series of model nucleophiles for protein amino acid residues, i.e., butylamine, diethylamine, imidazole, propanethiol, and phenol, was followed by (13)C NMR spectroscopy. The reactivity in water of hex-1-ene-1,3-sultone toward model nucleophiles follows the hard and soft acid and base theory with the hard nucleophiles (primary and secondary amine and phenate) mainly reacting at position 3 by S(N) substitution, and the soft nucleophiles (thiolate and imidazole) mainly reacting at position 2 by a Michael addition reaction. Hexane-1,3-sultone reacts with model nucleophiles at position 3 by S(N) substitution. Both saturated and unsaturated sultones are sensitive to hydrolysis when reacted in water.
authors.affiliation: Laboratoire de Dermatochimie associé au CNRS, Université Louis Pasteur, Clinique Dermatologique, CHU, F-67091 Strasbourg Cedex, France.
authors.forename: E
authors.initials: E
authors.lastname: Meschkat
authors.forename: M D
authors.initials: MD
authors.lastname: Barratt
authors.forename: J
authors.initials: J
authors.lastname: Lepoittevin
mesh_terms: D002082:Butylamines / Q000737:chemistry; D002247:Carbon Isotopes; D006241:Haptens / Q000737:chemistry* / Q000276:immunology; D007093:Imidazoles / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009282:Naphthalenesulfonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D019800:Phenol / Q000737:chemistry; D012867:Skin / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D002082:Butylamines; D002247:Carbon Isotopes; D006241:Haptens; D007093:Imidazoles; D009282:Naphthalenesulfonates; D013438:Sulfhydryl Compounds; C030762:propanethiol; D019800:Phenol; C029899:imidazole; C016768:naphthosultone