Gas-phase thermochemical properties of pyrimidine nucleobases

Min Liu, Tingting Li, F. Sedinam Amegayibor, Daisy S. Cardoso, Yunlin Fu, Jeehiun K. Lee

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(Figure Presented) The gas-phase acidity and proton affinity of thymine, cytosine, and 1-methyl cytosine have been examined using both theoretical (B3LYP/6-31+G*) and experimental (bracketing, Cooks kinetic) methods. This paper represents a comprehensive examination of multiple acidic sites of thymine and cytosine and of the acidity and proton affinity of thymine, cytosine, and 1-methyl cytosine. Thymine exists as the most stable "canonical" tautomer in the gas phase, with a ΔHacid of 335 ± 4 kcal mol-1 (ΔGacid = 328 ± 4 kcal mol-1) for the more acidic N1-H. The acidity of the less acidic N3-H site has not, heretofore, been measured; we bracket a ΔH acid value of 346 ± 3 kcal mol-1 (ΔG acid = 339 ± 3 kcal mol-1). The proton affinity (PA = ΔH) of thymine is measured to be 211 ± 3 kcal mol-1 (GB = ΔG = 203 ± 3 kcal mol-1). Cytosine is known to have several stable tautomers in the gas phase in contrast to in solution, where the canonical tautomer predominates. Using bracketing methods in an FTMS, we measure a ΔHacid for the more acidic site of 342 ± 3 kcal mol-1 (ΔGacid = 335 ± 3 kcal mol -1). The ΔHacid of the less acidic site, previously unknown, is 352 ± 4 kcal mol-1 (345 ± 4 kcal mol -1). The proton affinity is 228 ± 3 kcal mol-1 (GB = 220 ± 3 kcal mol-1). Comparison of these values to calculations indicates that we most likely have a mixture of the canonical tautomer and two enol tautomers and possibly an imine tautomer under our conditions in the gas phase. We also measure the acidity and proton affinity of cytosine using the extended Cooks kinetic method. We form the proton-bound dimers via electrospray of an aqueous solution, which favors cytosine in the canonical form. The acidity of cytosine using this method is ΔH acid = 343 ±3 kcal mol-1, PA = 227 ± 3 kcal mol-1. We also examined 1-methyl cytosine, which has fewer accessible tautomers than cytosine. We measure a ΔHacid of 349 ±3 kcal mol-1 (ΔGacid = 342 ±3 kcal mol -1) and a PA of 230 ± 3 kcal mol-1 (GB = 223 ± 3 kcal mol-1). Our ultimate goal is to understand the intrinsic reactivity of nucleobases; gas-phase acidic and basic properties are of interest for chemical reasons and also possibly for biological purposes because biological media can be quite nonpolar.

Original languageEnglish (US)
Pages (from-to)9283-9291
Number of pages9
JournalJournal of Organic Chemistry
Issue number23
StatePublished - Dec 5 2008

All Science Journal Classification (ASJC) codes

  • Organic Chemistry


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