Studies of the chemical selectivity of hapten, reactivity, and skin sensitization potency. 2. NMR studies of the covalent binding of the C-13-labeledskin sensitizers 2-[C-13]- and 3-[C-13]hex-1-ene- and 3-[C-13]hexane-1,3-sultones to human serum albumin

3-[C-13]- and 2-[C-13]hex-1-ene-1,3-sultones (1a and 1b, respectively) and 3-[C-13]hex-1-ene-1,3-sultone 2a were incubated with human serum albumin in phosphate buffer at pH 8.1. In both cases, the main reaction was a hydroly sis via an S-N reaction at position 3, but several adducts were also formed . Hex-1-ene-1,3 -sultone, which is a strong skin sensitizer, appears also t o be a strongly oxophilic molecule reacting mainly at position 3 through an S-N reaction to give adducts on tyrosines. This sultone was also able to r eact with a single lysine residue, also via an initial S-N reaction at posi tion 3, followed by an intramolecular Michael addition at position 2 to for m a mixture of aziridinium intermediates which were subsequently hydrolyzed to give an amino alcohol derivative as the final product. The same reactio n carried out on acetylated human serum albumin seems to indicate that the target lysine could be Lys199, which is known to be easily acetylated. Hexa ne-1,3-sultone, which is a weak sensitizer, appears to be an even more oxop hilic molecule, making adducts on tyrosines through an S-N reaction at posi tion 3. No reaction was observed on Lys199. The difference in skin sensitiz ation potential seems therefore to be more related to the selective ability of modifying lysine residues than to the more general ability to modify ty rosine residues.