S-Oxidation of Thiazolidinedione with Hydrogen Peroxide, Peroxynitrous Acid, and C4a-Hydroperoxyflavin: A Theoretical Study
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- 作者：Nikhil Taxak ; Vinod Parmar ; Dhilon S. Patel ; Anuja Kotasthane ; Prasad V. Bharatam
- 刊名：Journal of Physical Chemistry A
- 出版年：2011
- 出版时间：February 10, 2011
- 年：2011
- 卷：115
- 期：5
- 页码：891-898
- 全文大小：954K
- 年卷期：v.115,no.5(February 10, 2011)
- ISSN：1520-5215
文摘
Quantum chemical analysis was carried out to model metabolism of glitazone class of drugs through oxygen transfer process to the sulfur atom of thiazolidinedione ring with different oxidants such as H2O2, HOONO, and C4a-hydroperoxyflavin. Complete optimization (geometric and energy parameters) of all the required structures and transition states on the reaction path was carried out using MP2(full)/6-31+G(d,p). Charge and second-order delocalization analyses of important structures were carried out using the NBO method. The effect of solvent on the oxygen transfer to sulfur of thiazolidinedione was studied by including one, two, or three explicit water molecules. These calculations revealed that explicit solvent (water) effectively contributed in the sulfoxidation of thiazolidinedione and led to remarkable reduction in the energy barrier by 10 kcal/mol as compared to the gas phase. These results were found to be consistent with previously reported S-oxidation of dimethyl sulfide. When explicit water molecules were included, solvent molecules stabilize the charge separation at the transition state via specific interactions, and oxidation occurs via stretching of the O鈭扥 bond of oxidants and gradual formation of S鈭扥 bond. This study is helpful in understanding the metabolite generation due to the S-oxidation process in the glitazone series of antidiabetic drugs under physiological conditions.