Structure-activity relationships for abiotic thiol reactivity and aquatic toxicity of halo-substituted carbonyl compounds

Using abiotic thiol reactivity (EC50) and Tetrahymena pyriformis toxicity (IGC(50)) data for a group of halo-substituted ketones, esters and amides (i.e. S(N)2 electrophiles) and related compounds a series of structure-activity relationships are illustrated. Only the alpha-halo-carbonyl-containing compounds are observed to be thiol reactive with the order I > Br > Cl > F. Further comparisons disclose alpha-halo-carbonyl compounds to be more reactive than non-ahalo-carbonyl compounds; in addition, the reactivity is reduced when the number of C atoms between the carbonyl and halogen is greater than one. Comparing reactivity among alpha-halocarbonyl-containing compounds with different P-alkyl groups shows the greater the size of the beta-alkyl group the lesser the reactivity. A comparison of reactivity data for 2-bromoacetyl-containing compounds of differing dimensions reveals little difference in reactivity. Regression analysis demonstrates a linear relationship between toxicity and thiol reactivity: log (IGC(50)(-1)) = 0.848 log (EC50-1) + 1.40; n = 19, s = 0.250, r(2) =0.926, r(2) (pred) = 0.905, F= 199, Pr > F=0.0001.