The Discovery of Intramolecular Stereoelectronic Forces That Drive The Sugar Conformation in Nucleosides and Nucleotides

Abstract

This report summarizes our results8 on how the determination of the thermodynamics of the two-state North (N, C2′-exo-C3′-endo) ⇄ South (S,C2′-endo-C3′-exo) pseudorotational equilibrium in aqueous solution (pD 0.6 - 12.0) basing on vicinal 3JHH extracted from 1H-NMR spectra measured at 500 MHz from 278K to 358K yields an experimental energy inventory of the unique stereoelectronic forces that dictate the conformation of the sugar moiety in β-D-ribonucleosides (rNs), β-D-nucleotides, in the mirror-image β-D- versus β-L-2′-deoxynucleosides (dNs) as well as in α-D- or L- versus β-D- or L-2′-dNs. Our work shows for the first time that the free-energies of the inherent internal flexibilities of β-D- versus β-L-2′-dNs and α-D- versus α-L-2′-dNs are identical, whereas the aglycone promoted tunability of the constituent sugar conformation is grossly affected in the α-nucleosides compared to the β-counterparts.