Reverse micelles as a catalyst for the nucleophilic aromatic substitution between glutathione and 2,4-dinitrochlorobenzene

Abstract

The nucleophilic aromatic substitution (S_NAr) between GSH and 2,4-dinitrochlorobenzene was studied in reverse micellar systems composed of limited amounts of water, a surfactant with a polar head and a nonpolar tail, and the organic solvent 2,2,4-trimethylpentane. When the surfactant was positively charged and contained an aromatic ring in the polar head, the second-order rate constant was increased by approximately two orders of magnitude as compared to that in aqueous solution. The rate enhancement could be attributed to the stabilization of the negatively charged Meisenheimer σ-complex by the positively charged polar head and the weak aromatic ring’s electric quadrupole interactions of the surfactant. The reaction rate in reverse micelles composed of neutral polar head groups (Triton X-100) was increased by 3-fold, which may be explained by the interactions of the hydroxy groups of Triton molecules with the π-system of the Meisenheimer complex. An inverse relationship between the molar concentration [H₂O]/[surfactant] ratio, which reflects the inclusive volume of the reverse micellar particle, and the rate enhancement was observed for positively charged or hydroxy-containing reverse micelles, but opposite results were obtained with negatively charged reverse micelles. These reverse micellar systems thus mimic the active site of a detoxification enzyme, glutathione transferase, in which stabilization of the Meisenheimer complex by a positively charged arginine residue, on-edge quadrupole interactions of aromatic amino acids, and the hydroxy group of tyrosine or threonine have been proposed in the enzyme-catalysed S_NAr conjugation.

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