Activation and detoxication of aminophenols. III. Synthesis and structural elucidation of various glutathione addition products to 1,4-benzoquinone

Abstract

1. Four thioethers of 1,4-hydroquinone with glutathione (GSH) were prepared from 1,4-benzoquinone and characterized by ¹H-n.m.r. and partly by ¹³C-n.m.r. spectroscopy. The structures of three additional thioethers were tentatively assigned by u.v.spectroscopy.

2. The corresponding thioethers of 1,4-benzoquinone with GSH were obtained by oxidation of the corresponding 1,4-hydroquinone thioadducts with PbO₂ or potassium ferricyanide.

3. Relative redox potentials of the hydroquinone/benzoquinone thioethers were estimated by determination of their redox equilibria with benzoquinone/hydroquinone. The redox potential of the mono-substituted derivative was 30 mV lower, and that of the di-substituted derivatives 70 mV lower, than that of the unsubstituted couple, thus explaining the readiness of sequential oxidation and addition reactions of the produced thioethers.

4. By use of 1,4-[U-¹⁴C]benzoquinone the reaction products with GSH were quantified to elucidate the product orientation. As observed with 1,4-benzoquinoneimine and its thioethers, formation of GSSG was not detected at physiological pH.

5. The high susceptibility of particular thioethers of 1,4-hydroquinone towards (aut)oxidation characterizes these products as reactive intermediates rather than as definitive detoxication products.