Influence of fluorine substitution on the molecular conformation of 3'-deoxy-3'-fluoro-5-methyluridine.

ABSTRACT

Fluorine substitutions on the furanose ring of nucleosides are known to strongly influence the conformational properties of oligonucleotides. In order to assess the effect of fluorine on the conformation of 3'-deoxy-3'-fluoro-5-methyluridine (RTF), C10H13FN2O5, we studied its stereochemistry in the crystalline state using X-ray crystallography. The compound crystallizes in the chiral orthorhombic space group P212121 and contains two symmetry-independent molecules (A and B) in the asymmetric unit. The furanose ring in molecules A and B adopts conformations between envelope (2E, 2'-endo, P = 162°) and twisted (2T3, 2'-endo and 3'exo, P = 180°), with pseudorotation phase angles (P) of 164.3 and 170.2°, respectively. The maximum puckering amplitudes, νmax, for molecules A and B are 38.8 and 36.1°, respectively. In contrast, for 5-methyluridine (RTOH), the value of P is 21.2°, which is between the 3E (3'-endo, P = 18.0°) and 3T4 (3'-endo and 4'-exo, P = 36°) conformations. The value of νmax for RTOH is 41.29°. Molecules A and B of RTF generate respective helical assemblies across the crystallographic 21-screw axis through classical N-H...O aand O-H...O hydrogen bonds supplemented by C-H...O contacts. Adjacent parallel helices of both molecules are linked to each other via O-H...O and O...π interactions.