TY - JOUR T1 - Aromatic Substitution Reaction of 2-Chloropyridines Catalyzed by Microsomal Glutathione <em>S</em>-Transferase 1 JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1797 LP - 1800 DO - 10.1124/dmd.109.027698 VL - 37 IS - 9 AU - Kazuko Inoue AU - Tomoyuki Ohe AU - Kenichi Mori AU - Takeshi Sagara AU - Yasuyuki Ishii AU - Masato Chiba Y1 - 2009/09/01 UR - http://dmd.aspetjournals.org/content/37/9/1797.abstract N2 - 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. ER -