Uracil and thymine reactivity in the gas phase: the S(N)2 reaction and implications for electron delocalization in leaving groups.
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.
Zhachkina
Anna
A
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901, USA.
Lee
Jeehiun K
JK
D002712:Chlorides; D004247:DNA / Q000378:metabolism; D045647:DNA Glycosylases / Q000378:metabolism; D004583:Electrons; D005740:Gases; D055601:Organic Chemistry Phenomena; D013941:Thymine / Q000031:analogs & derivatives / Q000737:chemistry*; D014498:Uracil / Q000031:analogs & derivatives / Q000737:chemistry*
D002712:Chlorides; D005740:Gases; D014498:Uracil; C055991:3-methyluracil; C002451:1,3-dimethyluracil; D004247:DNA; D045647:DNA Glycosylases; D013941:Thymine; C002347:3-methylthymine