Aromatic substitution reaction of 2-chloropyridines catalyzed by microsomal glutathione S-transferase 1.
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.
Inoue
Kazuko
K
Department of BY Preclinical DMPK, Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Okubo 3, Tsukuba, Ibaraki 300-2611, Japan.
Ohe
Tomoyuki
T
Mori
Kenichi
K
Sagara
Takeshi
T
Ishii
Yasuyuki
Y
Chiba
Masato
M
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
D002722:Chlorobenzenes; D006841:Hydrocarbons, Aromatic; D009574:Nitro Compounds; D011725:Pyridines; C083126:2-chloropyridine; D005982:Glutathione Transferase; D005978:Glutathione