PMR-relaxation and steric computations give unequivocal nucleoside conformations.
The configuration and the conformation of alpha and beta anomers of pyrazomycin, cytidine and pseudouridine in aqueous solution have been investigated by 1H-NMR at 250 MHz. T1 proton relaxation measurements are an excellent method to determine the conformation of the base around the glycosidic linkage. Frequently, steric hindrance considerations can help to decide which conformations are possible in nucleoside anomer pairs. The proton-proton coupling constants indicate that the N conformer is largely predominant in the alpha anomers while the S conformer is particularly abundant in beta-pyrazomycin. The steric hindrance is much larger for alpha than for beta-nucleosides and change of a C-C to a C-N glycosidic bond reduces considerably the rotational possibilities of the base. The relaxation data show that alpha-cytidine adopts the anti conformation with gamma = 200 degrees in good agreement with the crystal structure and with the sterical computations. In the other case, when the syn and anti conformations are sterically accessible, the orientation of the base may be completely different from one nucleoside to the other. It can be predicted neither from the crystal structure nor from comparisons with similar compounds. For alpha-pseudo-uridine the predominant orientation of the base (gamma = 120 degrees) is in the boundary of the syn-anti regions; for beta-cytidine the syn (gamma = 65 degrees) and anti (gamma = 215 degrees) conformations are equiprobable at room temperature while beta-pseudouridine shows the syn conformation with gamma = 40 degrees, the smallest angle observed until now. There is no correlation between the N/S and syn-anti ratios.
D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D011741:Pyrimidine Nucleosides; D013329:Structure-Activity Relationship
D011741:Pyrimidine Nucleosides