Mutagenic Properties of 5-Halogenuracils: Correlated Quantum Chemical ab Initio Study
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- 作者：Michal Hanus ; Martin Kabelá ;
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- 刊名：Biochemistry
- 出版年：2005
- 出版时间：February 8, 2005
- 年：2005
- 卷：44
- 期：5
- 页码：1701 - 1707
- 全文大小：87K
- 年卷期：v.44,no.5(February 8, 2005)
- ISSN：1520-4995
文摘
The relative stability of all possible 5-bromouracil tautomers was studied theoretically in agas phase, in a microhydrated environment (with one water molecule), and in bulk water. Tautomerstructures were determined by gradient optimization at the correlated ab initio quantum chemical levelwith an extended basis set of atomic orbitals. The role of water was examined by using a self-consistentreaction field method. The relative stabilization and free energies in the gas phase, the microhydratedenvironment, and the bulk water clearly support the preference of the canonical keto form of 5-bromouracilin all mentioned environments. An increased abundance of enol tautomers when passing from uracil to5-bromouracil is not supported by our calculations. Thus, the tautomeric model of the mutagenic activityof 5-bromouracil proposed previously [Hu et al. Biochemistry (2004) 43, 6361] can be refuted. The validityof other mutagenic models was also discussed, and finally a new mechanism for explaining the mutagenicactivity of halogenuracils based on their different behaviors in triplet excited states was suggested.