Determination of the Complete Correlation Between the Sugar Ring Puckers and 5′-Exocyclic Group Rotamers in Conformationally-Flexible Nucleic Acid Components from NMR Study

Abstract

Inspection of stereochemical models suggests a possible correlation between the proportion (Y_g-/Y_t) of the g^? and t rotamers and the S pucker populations irrespective of the anti-syn conformational composition of the base. Interpretation of the NMR vicinal coupling constants in terms of conformational populations shows a decline of Y_g-/Y_t with X_s approaching zero, consistent with high unfavorability of the Ng^? conformational combination in solution, a result supported by a X-ray crystallographic data survey. Hence, the underlying assumption introduced into the present study is that the g^? rotamer and the N pucker do not coexist together in solution. Therefore, the limiting value of Y_g-/Y_t corresponding to the S pucker could be determined for each compound individually. Finally, populations and relative free energies of all conformational combinations of Ng⁺, Nt, Sg⁺, St and Sg^? (except Ng^? which is not important) have been estimated.

Results of the present study suggest several interesting regularities concerning the syn-anti effect on populations and energies of the conformational combinations in ribo- and deoxyribo-nucleosides. (a) In the anti-type nucleosides, the Ng⁺ conformation is about 2 kJ/mol more stable than Nt, but in the syn-type, the Ng⁺ and Nt have comparable energy, (b) No important changes are observed in the Ng⁺ population comparing the anti-type and syn-type of ribo- and deoxyribo-nucleosides separately, (c) The Nt is considerable stabilized and simultaneously the Sg⁺ is strongly destabilized in the syn-type nucleosides relative to the anti-type, (d) Irrespective of the syn-anti composition the St is always more stable (1–2 kJ/mol) than the Sg^? conformational combination.