Three different fluoro- or chloro-substituted 1'-deoxy-1'-phenyl-ß-D-ribofuranoses.

Crystal structures are reported for three fluoro- or chloro-substituted 1'-deoxy-1'-phenyl-ß-D-ribofuranoses, namely 1'-deoxy-1'-(2,4,5-trifluorophenyl)-ß-D-ribofuranose, C11H11F3O4, (I), 1'-deoxy-1'-(2,4,6-trifluorophenyl)-ß-D-ribofuranose, C11H11F3O4, (II), and 1'-(4-chlorophenyl)-1'-deoxy-ß-D-ribofuranose, C11H13ClO4, (III). The five-membered furanose ring of the three compounds has a conformation between a C2'-endo,C3'-exo twist and a C2'-endo envelope. The ribofuranose groups of (I) and (III) are connected by intermolecular O-H···O hydrogen bonds to six symmetry-related molecules to form double layers, while the ribofuranose group of (II) is connected by O-H···O hydrogen bonds to four symmetry-related molecules to form single layers. The O···O contact distance of the O-H···O hydrogen bonds ranges from 2.7172 (15) to 2.8895 (19) Å. Neighbouring double layers of (I) are connected by a very weak intermolecular C-F···π contact. The layers of (II) are connected by one C-H···O and two C-H···F contacts, while the double layers of (III) are connected by a C-H···Cl contact. The conformations of the molecules are compared with those of seven related molecules. The orientation of the benzene ring is coplanar with the H-C1' bond or bisecting the H-C1'-C2' angle, or intermediate between these positions. The orientation of the benzene ring is independent of the substitution pattern of the ring and depends mainly on crystal-packing effects.

C-F...H-C hydrogen bonds in ribonucleic acids.

We report the synthesis of 1'-deoxy-1'-(benzimidazol-1-yl)-beta-D-ribofuranose 7 and 1'-deoxy-1'-phenyl-beta-D-ribofuranose 2. With these two ribonucleoside analogues we have a set of nine different RNA building blocks in hand, which are isostere to the natural bases. Now it is possible to investigate their duplex stabilizing forces. These forces are hydrogen bonds, base stacking, and solvation. The phosphoramidites of all building blocks were incorporated into a 12mer RNA, and the resulting RNA duplexes were investigated by UV- and CD-spectroscopy. We found that some of the RNA analogues are universal bases. The best universal bases with the lowest destabilization and the smallest discrimination between the natural bases are 1 (B) and 9 (E). On the basis of UV measurements we determined the melting points and the thermodynamic data. We were able to show that there are no hydrogen bonds between the natural bases and the RNA analogues. From thermodynamic data we calculated the contributions for base stacking and solvation of all modified building blocks. Comparison of calculated and measured data of double modified base pairs in 12mer RNA duplexes showed a further duplex stabilizing force in base pairs containing fluorine atoms at the Watson-Crick binding site. This stabilizing force can be defined as C-F.H-C hydrogen bond as is observed in crystal structures of 1'-deoxy-1'-(4-fluorophenyl)-beta-D-ribofuranose.