Evaluating the effects of the nonplanarity of nucleic acid bases on NMR, IR, and vibrational circular dichroism spectra: a density functional theory computational study

Abstract

The pyramidalizations of N9/1 glycosidic nitrogens in DNA and RNA nucleosides, recently discovered and analyzed in their ultrahigh-resolution X-ray crystal structures (Sychrovsky´; et al. Nucleic Acid Res. 2009, 37, 7321.), were found to have significant effects on the structural interpretation of the 3J(C4/2-H1′) and 3J(C8/ 6-H1′) NMR scalar couplings in purine/pyrimidine nucleosides. The calculated effects on IR and vibrational circular dichroism (VCD) spectra were only minor. The calculated structural deformations in nucleosides, depending on sugar-to-base orientation, gave rise to corrections in the phase shift of the Karplus equations for the 3J(C8/6-H1′) and 3J(C4/2-H1′) couplings ranging from -26° to +25° and from -5.7° to +2.0°, respectively. The sign alternation of this correction in syn and anti nucleosides arises from the stereoinversion of the N9/1 glycosidic nitrogen occurring upon reorientation of the glycosidic torsion. The effect was calculated consistently in the dG, dA, dC, dT, rA, and rG nucleosides. Utilization of the calculated phase-shift corrections in the design of Karplus equations for the 3J couplings was suggested, and the effects on structural interpretation of the experimental couplings were evaluated.