Activation and detoxication of aminophenols. II. Synthesis and structural elucidation of various thiol addition products of 1,4-benzoquinoneimine and N-acetyl-1,4-benzoquinoneimine.
1. Nine thioethers of 4-aminophenol with beta-hydroxyethylmercaptan, ranging from mono- to tetra-substituted thioadducts, were prepared from synthetic 1,4-benzoquinoneimine and characterized by 1H-n.m.r. and u.v. spectroscopy. For each compound, extinction coefficients and pKa values of the amino group were determined. 2. Five thioethers of 4-aminophenol with glutathione (GSH) were prepared and characterized by 1H-n.m.r. and u.v. spectroscopy with their respective extinction coefficients and pKa values. Two further thioadducts were tentatively assigned by their u.v. spectroscopic properties. 3. Reaction products of 1,4-[U-14C]benzoquinoneimine and GSH were studied, indicating formation of 4-amino-2-(glutathione-S-yl)phenol, 4-amino-2,3,6-tris(glutathione-S-yl)phenol as the main products. Formation of glutathione disulphide (GSSG) was not detected. In contrast, N-acetyl-1,4-[U-14C]benzoquinoneimine was partly reduced by GSH and formed only the 2-substituted thioadduct. 4. Investigation of the product orientation in the reductive addition of GSH to 2-(glutathione-S-yl)-1,4-benzoquinoneimine and 3-(glutathione-S-yl)-1,4-benzoquinoneimine, respectively, showed that the 3-substituted derivative formed mainly the 3,5-di-substituted thioadduct, whereas the 2-substituted compound formed mainly the 2,3,6-tri-substituted thioadduct. 5. Formation of thioadducts which autoxidize markedly faster than the parent aminophenol indicates that thioether formation is not an obligatory detoxication process.
Eckert
K G
KG
Walther-Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, FRG.
Eyer
P
P
Sonnenbichler
J
J
Zetl
I
I
D000627:Aminophenols / Q000138:chemical synthesis*; D016227:Benzoquinones; D005978:Glutathione; D007097:Imines; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011809:Quinones; D013056:Spectrophotometry, Ultraviolet; D013440:Sulfides / Q000138:chemical synthesis*; D015262:Xenobiotics / Q000138:chemical synthesis
D000627:Aminophenols; D016227:Benzoquinones; D007097:Imines; D011809:Quinones; D013440:Sulfides; D015262:Xenobiotics; C064299:1,4-benzoquinoneimine; C028473:N-acetyl-4-benzoquinoneimine; D005978:Glutathione