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.
Footnotes
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.109.027698.
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ABBREVIATIONS: GST, glutathione S-transferase; GSH, glutathione; MGST1, microsomal GST 1; CDNB, 1-chloro-3,4-dinitrobenzene; QSAR, quantitative structure-activity relationship.
- Accepted June 17, 2009.
- Received March 24, 2009.
- The American Society for Pharmacology and Experimental Therapeutics
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