title: ((15)N(5))-labeled adenine derivatives: synthesis and studies of tautomerism by (15)N NMR spectroscopy and theoretical calculations.
abstract: Since the nitrogens of nucleosides and nucleotides play an important role in the molecular recognition of these compounds, (15)N NMR became a method of choice in this field. Fully (15)N-labeled adenine, required in the latter studies, was obtained in four synthetic steps, in a good yield. Likewise, ((15)N(5))-2-hexylthioether-adenine and ((15)N(5))-8-Br-adenine were obtained in five synthetic steps from the relatively inexpensive (15)N sources: (15)N-NH(4)Cl, (15)N-NH(4)OH, (15)N-NaNO(2). Full (15)N labeling of these adenine prototypes enabled to obtain high-resolution (15)N NMR spectra of these bases at 60.8 MHz. Furthermore, the spectra suggested the existence of the N3-H species in the tautomeric mixtures of these compounds in solution, in addition to the well-reported N9-H (major) and N7-H (minor) tautomers. These observations were also supported by quantum mechanical calculations of the tautomeric equilibria in the gas phase and in solution of the above-mentioned adenine compounds. The gas-phase tautomeric equilibria were estimated using density functional theory and second-order perturbation theory methods. Solvent effects were included by means of both continuum and discrete solvation models. The observation of the existence of the N3-H tautomer has a clear impact on the possible H-bonding patterns of these adenine prototypes and on their molecular recognition by various biological macromolecules. The above(15)N-labeled analogues are expected to find use as (15)N NMR probes for numerous biochemical studies.
authors.affiliation: Department of Chemistry, Gonda-Goldschmied Medical Research Center, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Laxer
authors.forename: D T
authors.initials: DT
authors.lastname: Major
authors.forename: H E
authors.initials: HE
authors.lastname: Gottlieb
authors.forename: B
authors.initials: B
authors.lastname: Fischer
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008962:Models, Theoretical; D009587:Nitrogen Isotopes
chemical_list: D009587:Nitrogen Isotopes; D000225:Adenine