Studies of the chemical selectivity of hapten, reactivity, and skin sensitization potency. 1. Synthesis and studies on the reactivity toward model nucleophiles of the C-13-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 syn thesized isotspically labeled with C-13 at reactive sites. The reactivity o f 2-[C-13]- and 3-[C-13]hex-1-ene-1,3-sultones and of 3-[C-13]hexane-1,3-su ltone 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 nucleophil es (thiolate and imidazole) mainly reacting at position 2 by a Michael addi tion reaction. Hexane-1,3-sultone reacts with model nucleophiles at positio n 3 by S-N substitution. Both saturated and unsaturated sultones are sensit ive to hydrolysis when reacted in water.