Gas-Phase Thermochemical Properties of Pyrimidine Nucleobases

Abstract

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 DeltaH(acid) of 335 +/- 4 kcal mol(-1) (DeltaG(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 DeltaH(acid) value of 346 +/- 3 kcal mol(-1) (DeltaG(acid) = 339 +/- 3 kcal mol(-1)). The proton affinity (PA = DeltaH) of thymine is measured to be 211 +/- 3 kcal mol(-1) (GB = DeltaG = 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 DeltaH(acid) for the more acidic site of 342 +/- 3 kcal mol(-1) (DeltaG(acid) = 335 +/- 3 kcal mol(-1)). The DeltaH(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 DeltaH(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 DeltaH(acid) of 349 +/- 3 kcal mol(-1) (DeltaG(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.

Stabilities of nanohydrated thymine radical cations: insights from multiphoton ionization experiments and ab initio calculations

“…Prior to the dry measurement, the nozzle and the carrier gas line were pumped overnight using a scroll pump and then purged for two hours in a flow of argon carrier gas while the powder temperature was increased and stabilized. Water is transparent at 220 nm [30] and thermochemical calculations have shown that proton transfer from T + to T in a dimer cation is exothermic [31]. Therefore, the present TH + signals are attributed to the dissociation of thymine dimer ions (or possibly larger thymine cluster ions), with or without associated water molecules.…”

Dissociative multi-photon ionization of isolated uracil and uracil-adenine complexes

“…was detected strongly in an MPI study of hydrated uracil clusters [11] and electronic structure calculations have shown that the hydrogen-bonded uracil dimer cation relaxes to a proton-transferred form [23]. Similarly, thermochemical calculations have shown that proton transfer from T + to T in a dimer cation is exothermic [24,25]. The (nucleobase ion + 1 mass unit) / (nucleobase ion) signal ratios in Fig.…”

Base-Pairing Energies of Proton-Bound Dimers and Proton Affinities of 1-Methyl-5-Halocytosines: Implications for the Effects of Halogenation on the Stability of the DNAi-Motif

“…The MAD between theory and experiment for the relative N3 PAs is 6.0 ± 7.4 kJ/mol, larger than the AEU in these values, 1.4 ± 0.9 kJ/mol. The B3LYP/def2-TZVPPD calculations indicate that the N3 PAs of 1Me5FC and 1Me5BrC are smaller than C, whereas TCID experiments suggest that the N3 PAs of 1Me5FC and 1Me5BrC exceed that of C. However, both theory and experiment find that the [31] and the PA of C previously determined [29][30][31][32][33][34][35][36][37][38]. The results of these analyses are summarized in Table 2.…”

“…Relative N3 proton affinities (PAs) of the 1-methyl-5-halocytosines are also extracted from the experimental data from competitive analyses of the two primary dissociation pathways that occur in parallel for the proton-bound heterodimers of cytosine and the 1-methyl-5-halocytosines. Absolute N3 PAs of the 1-methyl-5-halocytosines are also obtained using the relative PAs determined here and the PA of C [29,[36][37][38] reported in the literature. The measured values are compared with theoretical results calculated at the B3LYP and MP2(full) levels of theory to evaluate the ability of each level of theory for predicting accurate energetics.…”