2-deoxy-β-D-ribofuranosylamine:: Quantum mechanical calculations of molecular structure and NMR spin-spin coupling constants in nitrogen-containing saccharides

Ab initio molecular orbital (MO) and density functional theory (DFT) calculations using a polarized split-valence basis set have been performed on 2-deoxy-beta-D-ribofuranosylamine (2-deoxy-beta-D-erythropentofuranosylamine) in its unprotonated (3) and protonated (4) forms. Structural data confirm three previously reported factors influencing bond lengths in aldofuranosyl rings, and suggest the existence of a new 1,4-lone pair effect. Conformational energy profiles for 3 and 4 were compared to that described recently for 2-deoxy-beta-D-ribofuranose (2-deoxy-beta-D-erythro-pentofuranose) 5. Results show that preferred conformation and energy barriers to pseudorotation are affected significantly by changes in C1 substitution. N-Protonation of 3 reduces pseudorotational barriers, suggesting a more flexible ring relative to the unprotonated molecule. NMR spin-spin coupling constants involving C1 and H1 were calculated in 3 and 4 using DFT methods described previously (Cloran et al. J. Phys. Chem. 1999, 103, 3783-3795). Trends in computed couplings as a function of ring conformation and C1 substitution confirm prior predictions based on experimental observations in aminosugars and nucleosides. In general, one- and two-bond J(CH) and J(CC) values appear more influenced by O --> N substitution and by N-protonation than vicinal (3)J(CH) and (3)J(CC). These results will be useful in studies of related NMR scalar coupling constants in biologically relevant aminosugars and nucleosides, either free in solution or as components of oligosaccharides and oligonucleotides.