Gas-Phase Thermochemical Properties of Pyrimidine Nucleobases

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 Delta H-acid of 335 +/- 4 kcal mol(-1) (Delta G(acid) = 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 Delta H-acid value of 346 +/- 3 kcal mol(-1) (Delta G(acid) = 339 +/- 3 kcal mol(-1)). The proton affinity (PA = Delta H) of thymine is measured to be 211 +/- 3 kcal mol(-1) (GB = Delta G = 203 +/- 3 kcal mol(-1)). Cytosine is known to have several stable tautomers in the gas phase in contrast to ill Solution, where the canonical tautomer predominates. Using, bracketing methods in an FTMS, we measure a Delta H-acid for the more acidic site of 342 +/- 3 kcal mol(-1) (Delta G(acid) = 335 +/- 3 kcal mol(-1)). The Delta H-acid 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 Delta H-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 Delta H-acid of 349 +/- 3 kcal mol(-1) (Delta G(acid) = 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.