((15)N(5))-labeled adenine derivatives: synthesis and studies of tautomerism by (15)N NMR spectroscopy and theoretical calculations.
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.
Laxer
A
A
Department of Chemistry, Gonda-Goldschmied Medical Research Center, Bar-Ilan University, Ramat-Gan 52900, Israel.
Major
D T
DT
Gottlieb
H E
HE
Fischer
B
B
D000225:Adenine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008962:Models, Theoretical; D009587:Nitrogen Isotopes
D009587:Nitrogen Isotopes; D000225:Adenine