Studies of the chemical selectivity of hapten, reactivity, and skin sensitization potency.: 1.: Synthesis and studies on the reactivity toward model nucleophiles of the 13C-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 isotspically labeled with C-13 at reactive sites. The reactivity of 2-[C-13]- and 3-[C-13]hex-1-ene-1,3-sultones and of 3-[C-13]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 C-13 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.