Correlating the ³¹P NMR Chemical Shielding Tensor and the ²J_P,C Spin–Spin Coupling Constants with Torsion Angles ζ and α in the Backbone of Nucleic Acids

Abstract

Determination of nucleic acid (NA) structure with NMR spectroscopy is limited by the lack of restraints on conformation of NA phosphate. In this work, the (31)P chemical shielding tensor, the Γ(P,C5'H5'1) and Γ(P,C5'H5'2) cross-correlated relaxation rates, and the (2)J(P,C3'), (2)J(P,C5'), and (3)J(P,C4') coupling constants were calculated in dependence on NA backbone torsion angles ζ and α. While the orientation of the (31)P chemical shielding tensor was almost independent of the NA phosphate conformation, the principal tensor components varied by up to ~40 ppm. This variation and the dependence of the phosphate geometry on torsion angles ζ and α had only a minor influence on the calculated Γ(P,C5'H5'1) and Γ(P,C5'H5'2) cross-correlated relaxation rates, and therefore, the so-called rigid tensor approximation was here validated. For the first time, the (2)J(P,C) spin-spin coupling constants were correlated with the conformation of NA phosphate. Although each of the two J-couplings was significantly modulated by both torsions ζ and α, the (2)J(P,C3') coupling could be structurally assigned to torsion ζ and the (2)J(P,C5') coupling to torsion α. We propose qualitative rules for their structural interpretation as loose restraints on torsion angles ζ and α. The (3)J(P,C4') coupling assigned to torsion angle β was found dependent also on torsions ζ and α, implying that the uncertainty in determination of β with standard Karplus curves could be as large as ~25°. The calculations provided a unified picture of NMR parameters applicable for the determination of NA phosphate conformation.

Quantum chemical calculations of31P NMR chemical shifts: scopes and limitations

“…[37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] In several systematic studies it was shown 48-55 that a satisfactory agreement between calculations and experiments is observed when quite a ''heavy'' basis set or high level of theory ‡ was used although deviations and exceptions were also found. In fact, there are relatively few reports on 31 P NMR CS calculations using quantum chemical methods.…”

“…To check this idea, we used 10-ethyl-7,8,9-triphenyl-4-oxa-1,10-diphospatricyclo[5.2.1.02,6]-deca-8-ene-3,5-dione(45) for which several isomeric forms can be realized and for which reliable structural data are available 103 as obtained by an alternative method. To check this idea, we used 10-ethyl-7,8,9-triphenyl-4-oxa-1,10-diphospatricyclo[5.2.1.02,6]-deca-8-ene-3,5-dione(45) for which several isomeric forms can be realized and for which reliable structural data are available 103 as obtained by an alternative method.…”

Recent advances in computational 31P NMR: Part 2. Spin–spin coupling constants

“…In a more theoretical paper from the same group, the 2 J P,C3′ , 2 J P,C5′ , and 3 J P,C4′ coupling constants were calculated in dependence on nucleic acid backbone torsion angles ζ and α , as was specified for a parent nucleic acid 10 and a model ethyl methyl phosphate 11 , both shown in Figure .…”

“…(b) Model ethyl methyl phosphate with atoms and torsion angles defined as in the nucleic acid backbone. Reproduced from Benda et al with the permission of the American Chemical Society…”

“…Two‐dimensional 2 J PC surface of α and ζ torsion angles of the model nucleic acid phosphate. Reproduced from Benda et al with the permission of the American Chemical Society…”