PT  - JOURNAL ARTICLE
AU  - Kazuko Inoue
AU  - Tomoyuki Ohe
AU  - Kenichi Mori
AU  - Takeshi Sagara
AU  - Yasuyuki Ishii
AU  - Masato Chiba
TI  - Aromatic Substitution Reaction of 2-Chloropyridines Catalyzed by Microsomal Glutathione <em>S</em>-Transferase 1
AID  - 10.1124/dmd.109.027698
DP  - 2009 Sep 01
TA  - Drug Metabolism and Disposition
PG  - 1797--1800
VI  - 37
IP  - 9
4099  - http://dmd.aspetjournals.org/content/37/9/1797.short
4100  - http://dmd.aspetjournals.org/content/37/9/1797.full
SO  - Drug Metab Dispos2009 Sep 01; 37
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.