Gas-phase acidity studies of multiple sites of adenine and adenine derivatives

Seema Sharma, Jeehiun K. Lee

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38 Scopus citations


The acidities of multiple sites in the purine nucleobase adenine (1) and adenine alkyl derivatives 9-ethyladenine (2), 3-methyladenine (3), 1-methyladenine (4), and N,N-dimethylademne (5) have been investigated for the first time, using computational and experimental methods to provide an understanding of adenine reactivity. We have previously measured two acidic sites on adenine, with the N9 site being 19 kcal mol-1 more acidic than the N10 site (333 ± 2 versus 352 ± 4 kcal mol-1, respectively). In this work, we have established that 9-ethyladenine has two sites more acidic than water: the N10 (352 ± 4 kcal mol-1) and the C8 (374 ± 2 kcal mol-1). We have likewise measured two acidities for 3-methyladenine, the N10 (347 ± 4 kcal mol-1) and the C2 (370 ± 3 kcal mol-1). For 1-methyladenine and N,N-dimethyladenine, we measure the N9H acidity to be 331 ± 2 and 333 ± 2 kcal mol-1, respectively. We believe that the bracketing of only one site for the latter species is a kinetic effect, which we discuss further in the paper. Computationally, we have found the interesting result that some of the vinylic C-H sites in these purine bases are predicted to be much more acidic than water (ΔHacid = 390.7 kcal mol-1) in the gas phase, on the order of 373 kcal mol-1. The acidic vinylic C-H sites are always adjacent to an N-R group, and this pattern is maintained regardless of whether the site is on the five- or six-membered ring of the purine. Vinylic C-H sites elsewhere on the purine have calculated acidities of about 400 kcal mol-1. The differing acidities are interpreted through electrostatic potential calculations. We also relate our results to the intriguing biochemical decarboxylation of orotate ribose monophosphate, which involves a vinylic anion adjacent to an N-R group; this decarboxylation is the last step in the de novo biosynthesis of pyrimidine nucleotides, and the enzyme that catalyzes the reaction, orotate ribose monophosphate decarboxylase, has been the subject of intense study recently, as its mechanism remains elusive.

Original languageEnglish (US)
Pages (from-to)7018-7025
Number of pages8
JournalJournal of Organic Chemistry
Issue number21
StatePublished - Oct 15 2004

All Science Journal Classification (ASJC) codes

  • Organic Chemistry


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