1-(2,3-Dideoxy-erythro-<tex>$\beta$</tex>-D-hexopyranosyl)cytosine : an example of the conformational and stacking properties of pyranosyl pyrimidine nucleosides. A crystallographic and computational approach
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Acta crystallographica: section B: structural science. - Copenhagen
, p. 95-103
C10H15N3O4, M(r) = 241.25, orthorhombic, P2(1)2(1)2(1), a = 7.4013 (4), b = 8.7563 (5), c = 17.392 (1) angstrom, V = 1127.1 (1) angstrom 3, Z = 4, D(m) = 1.42, D(x) = 1.422 Mg m-3, Ni-filtered Cu K-alpha radiation, lambda = 1.54178 angstrom, mu = 0.895 mm-1, F(000) = 512, T = 293 K, final R = 0.044 for 1024 unique observed [F greater-than-or-equal-to 6-sigma(F)] reflections. The conformational parameters are in accordance with the IUPAC-IUB Joint Commission on Biochemical Nomenclature [Pure Appl. Chem. (1983), 55, 1273-1280] guidelines. In order to assess the possible use of pyranosyl-modified pyrimidine nucleosides in the design of new synthetic oligo-nucleotides, the conformational and packing properties of 13 structures were examined. From this study, it becomes clear that the pyrimidine-base geometry is independent of the sugar ring type (furanosyl- or pyranosyl-like). The bases are always positioned in an equatorial orientation on the pyranoside sugar, which means that the sugar adopts a 4C1 conformation in alpha- and 4C1 in beta-enantiomers. As a result of the anomeric effect the O5'-C1' bond length is 0.020 (4) angstrom shorter than the C5'-O5' distance (C1' is the anomeric C atom). The O5'-C1'-N1-C2 torsion angle chi in the 13 nucleosides is centered around 244 (8)-degrees and varies from 196.4(3) to 287.0(2)-degrees. Molecular-mechanics calculations on uncharged pyranosyl nucleosides are found to be less accurate compared with semi-empirical quantum-chemical methods or molecular-mechanics calculations on charged molecules. It is also shown that, aside from steric forces, electrostatic interactions are important in the orientation of the base with respect to the sugar ring. Crystal-packing analysis reveals that the pyranosyl nucleosides show a similar tendency for base stacking to that observed for the corresponding furanosyl nucleosides.