title: Aromatic substitution reaction of 2-chloropyridines catalyzed by microsomal glutathione S-transferase 1.
abstract: 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.
authors.affiliation: Department of BY Preclinical DMPK, Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Okubo 3, Tsukuba, Ibaraki 300-2611, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Inoue
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ohe
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sagara
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Masato
authors.initials: M
authors.lastname: Chiba
mesh_terms: D000818:Animals; D002722:Chlorobenzenes / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D006841:Hydrocarbons, Aromatic / Q000378:metabolism; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000201:enzymology*; D008968:Molecular Conformation; D009574:Nitro Compounds / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002722:Chlorobenzenes; D006841:Hydrocarbons, Aromatic; D009574:Nitro Compounds; D011725:Pyridines; C083126:2-chloropyridine; D005982:Glutathione Transferase; D005978:Glutathione