Uracil and Thymine Reactivity in the Gas Phase: The S(N)2 Reaction and Implications for Electron Delocalization in Leaving Groups

Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901, USA.
Journal of the American Chemical Society (Impact Factor: 12.11). 11/2009; 131(51):18376-85. DOI: 10.1021/ja906814d
Source: PubMed


The gas-phase substitution reactions of methyl chloride and 1,3-dimethyluracil (at the N1-CH(3)) are examined computationally and experimentally. It is found that, although hydrochloric acid and 3-methyluracil are similar in acidity, the leaving group abilities of chloride and N1-deprotonated 3-methyluracil are not: chloride is a slightly better leaving group. The reason for this difference is most likely related to the electron delocalization in the N1-deprotonated 3-methyluracil anion, which we explore further herein. The leaving group ability of the N1-deprotonated 3-methyluracil anion relative to the N1-deprotonated 3-methylthymine anion is also examined in the context of an enzymatic reaction that cleaves uracil but not thymine from DNA.

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