13C chemical shifts and 1JCH coupling constants of cytidine at different χ dihedrals based on DFT calculations

A molecular dynamic simulation of cytidine reproduced the dominating E-3-endo, the so-called North conformation of the sugar and the anti base orientation with chi = -120 degrees. Taken as starting structures for a geometry optimisation, C-13 chemical shifts and (1)J coupling constants were calculated by DFT [functional: B3LYP, basis set: 6-31G(d,p)]. As for the first time no minimal structural model was used, the results can be interpreted without further approximations except solvent dependence which was not included. The influence of the glycosidic torsion angle was studied. The C-13 chemical shifts correlated with a North conformation of the sugar independent of the base orientation when using an empirically derived coordinate analysis. However, the (1)J(CH) coupling constants and C-13 chemical shifts clearly showed a dependence on the glycosidic torsion which enables the identification of chi. The (1)J(CH) analysis showed that the sugar pucker is not the major determinant for (1)J(C1'H1'). Instead, the base orientation caused major changes, with a maximal difference of 14 Hz. Additionally, (1)J(C2'H2'), (1)J(C3'H3'), and (1)J(C4'H4') are differently influenced by the glycosidic torsion which can be exploited for assigning chi. Analysis of electrostatic and steric effects showed that an isolated view is not able to explain all NMR spectroscopic data but gives some useful ideas. A higher charge on C3' and the (1)J(C6H6) coupling constants were explained by through-space effects. Depending on the glycosidic torsion, the base non-planarity changes substantially. The results clearly show that also for ribonucleotides C-13 chemical shifts and (1)J(CH) coupling constants are dependent on the base orientation which was questioned in the past.