Kinetics of the reaction of the first metabolite of fenitropan with some low molecular weight thiols

2-Nitro-I-phenylpropen-3-yl acetate (NPPA), the first metabolite of the fungicide fenitropan, reacted readily with glutathione in aqueous ethanol solutions at room temperature, producing at least two products. The first reaction step, which is believed to be a bimolecular nucleophilic (Michael) addition, had a strongly pH-dependent reaction rate. Second-order rate constants were calculated for the reactions of NPPA at pH 4 with glutathione and with some other low molecular weight thiols. Nucleophilic reactivity of the reacting thiolate anions is linearly related to the pK_a values of the thiols. However, as the concentration of thiolate anion is also determined by the thiol pK_a, there is no simple relationship between second-order rate constants and thiol pK_a. Thus the blocking rate of the various essential sulphydryl groups in fungi by NPPA is determined by the sulphydryl pK_a values and the ambient pH value.