RT Journal Article SR Electronic T1 Aromatic Substitution Reaction of 2-Chloropyridines Catalyzed by Microsomal Glutathione S-Transferase 1 JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 1797 OP 1800 DO 10.1124/dmd.109.027698 VO 37 IS 9 A1 Kazuko Inoue A1 Tomoyuki Ohe A1 Kenichi Mori A1 Takeshi Sagara A1 Yasuyuki Ishii A1 Masato Chiba YR 2009 UL http://dmd.aspetjournals.org/content/37/9/1797.abstract AB We investigated the substitution reaction of a series of 2-chloropyridine derivatives catalyzed by rat liver microsomal glutathione S-transferase 1. Various 2-chloropyridine derivatives were metabolized to the corresponding substituted glutathione conjugates via displacement of chlorine atom with glutathione. The reaction was affected by the electron-withdrawing strength and position of the substituents. Molecular orbital calculations on the change in Gibbs free energy between the initial and transition states verified the presence of a Meisenheimer complex and its influence on the reaction rate.