Mechanism of nucleophilic aromatic substitution of 1-chloro-2, 4-dinitrobenzene by glutathione in the gas phase and in solution. Implications for the mode of action of glutathione S-transferases
- Pacific Northwest National Lab., Richland, WA (United States)
The reaction mechanism of nucleophilic aromatic substitution of 1-chloro-2,4-dinitrobenzene by glutathione (as modeled by a thiomethoxide ion) in the gas phase and in solution was elucidated using ab initio molecular orbital theory in combination with a continuum solvent model at the HF/6-31G*, HF/6-31+G{sup **}, and MP2/6-31+G{sup **} levels of theory. Two ion-molecule complexes were located in the gas phase at the HF level, but only one exits at the MP2/6-31+G{sup **} level, while neither exits in aqueous solution. In aqueous solution, there is a large free energy barrier and C-S bond formation is the rate-determining step, which is in agreement with experimental observation. The calculated free energy barrier (30.2 kcal/mol) and the HF/6-31+G{sup **} level of theory seems to be in good agreement with experiment (23.8 kcal/mol), while the MP2/6-31+G{sup **} barrier is too low, indicating that the MP2/6-31+G{sup **} level of theory probably overestimates the stability of the transition state for C-S bond formation. Implications for the mode of action of gluatathione S-transferases (GSTs) and a related enzyme are discussed in light of the results of the current study. 40 refs., 5 figs., 3 tabs.
- DOE Contract Number:
- AC06-76RL01830
- OSTI ID:
- 458613
- Journal Information:
- Journal of the American Chemical Society, Vol. 119, Issue 4; Other Information: PBD: 29 Jan 1997
- Country of Publication:
- United States
- Language:
- English
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