Studies of the Chemical Selectivity of Hapten, Reactivity, and Skin Sensitization Potency. 1. Synthesis and Studies on the Reactivity toward Model Nucleophiles of the¹³C-Labeled Skin Sensitizers Hex-1-ene- and Hexane-1,3-sultones

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.