Studies on nucleosides and nucleotides. LXXXI. Carbon-13 magnetic resonance spectra of 8-substituted purine nucleotides. Effects of various phosphate groups on the chemical shifts and conformation of nucleotides.

Abstract

Carbon-13 magnetic resonance spectra of 8-substituted purine nucleotides and the corresponding parent nucleotides were measured. The 8-substituted derivatives included the 2'-, 3'-, 2', 3'-cyclic, 5'-and 3', 5'-cyclic phosphates of 8-bromoadenosine and the 5'-phosphates of 8-bromoguanosine, 8-methylinosine and 2-methylthio-8-methylinosine. All the 8-substituted nucleotides showed a characteristic upfield shift (-0.9 to -3.7 ppm) of the 2'-carbon with respect to the corresponding parent nucleotides. These results show that they take a syn conformation in aqueous solution to some extent. It was concluded from consideration of the sugar puckerings in the published PMR data that the 5'-phosphate of 8-bromoadenosine takes a more rigid syn conformation than the 2'-, 3'-and 2', 3'-cyclic phosphates. It is also suggested that 8-bromoadenosine has flexible glycosidic conformation similar to those for the latter compounds in water while in DMSO it adopts a more rigid conformation. The 5'-phosphates of the other 8-substituted nucleosides were also assumed to adopt a rigid syn conformation. The influences of various types of phosphate groups on the carbon chemical shifts are also discussed. Relatively large upfield shifts were observed for the C (4') signal of the 8-substituted 5'-nucleotides which has been assumed to be a reflection of a high population of non-gg conformations about the C (4')-C (5') bond.