Reaction mechanism of uracil bromination by HBrO: a new way to generate the enol-keto form of 5-bromouracil.
Knowledge on the uracil bromination reaction is helpful for understanding the origin of the mutagenicity of 5-bromouracil (BrU). To get more details about this reaction, we explore the corresponding reaction mechanism by theoretical method. A total of seven pathways were studied for this purpose. The diketo form of BrU is observed as the main product in these pathways, which agrees well with experimental results. The most energy-favorable reaction pathway is found to be that Br and OH attacked the opposite sides of uracil. The reaction intermediate reported in the experiment is predicted to be reasonably stable. In the following step, a dehydration process occurs between H11 and O13-H14 when there are no explicit H(2)O taking part. However, when there are explicit water molecules in the environment, explicit H(2)O will lower the reaction barrier in the formation of reaction intermediates and the final product BrU. A proton-transfer process from C5 to O10 is facilitated by explicit H(2)O, which results in enol-keto form intermediate of this modified base (defined as BrU*). These results indicate a new way to generate the enol-keto form of BrU.
Hu
Xingbang
X
Department of Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.
Li
Haoran
H
Liang
Wanchun
W
D001959:Bromates / Q000737:chemistry*; D001966:Bromine / Q000737:chemistry*; D001976:Bromouracil / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D006900:Hydroxylation; D007536:Isomerism; D007659:Ketones / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure
D001959:Bromates; D007659:Ketones; D001976:Bromouracil; D002244:Carbon; C027664:hypobromous acid; D001966:Bromine