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

• Published in: Chemical research in toxicology Vol. 14; no. 1; pp. 110 - 117
• Main Authors: Meschkat, E, Barratt, M D, Lepoittevin, J
• Format: Journal Article
• Language: English
• Published: United States 01.01.2001
• Subjects: Butylamines - chemistry; Carbon Isotopes; Haptens - chemistry; Haptens - immunology; Imidazoles - chemistry; Isotope Labeling - methods; Magnetic Resonance Spectroscopy - methods; Naphthalenesulfonates - chemical synthesis; Naphthalenesulfonates - chemistry; Naphthalenesulfonates - immunology; Phenol - chemistry; Skin - drug effects; Sulfhydryl Compounds - chemistry
• DOI: 10.1021/tx000225n
• ISSN: 0893-228X

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.