Conformational preferences of guanine-containing threose nucleic acid building blocks in B3LYP studies

In this paper, detailed and systematic gas-phase B3LYP conformational studies of four monomers of threose nucleic acid (TNA) with guanine attached at the C1' atom and bearing different substituents (OH, OP(=O)OH₂ and OCH₃) in the C2' and C3' positions of the α-l-threofuranose moiety are presented. All exocyclic single-bond (χ, ε and γ) rotations, as well as the ν₀-ν₄ endocyclic torsion angles, were taken into consideration. Three (threoguanosines TG1-TG3) or two (TG4) energy minima were found for the rotation about the χ torsion angle. The syn orientation (the A rotamer family) is strongly privileged in geometries TG1 and TG2, whereas the anti orientation (the C rotamer family) and the syn orientation are observed to be in equilibrium (with populations of 56% and 44%, respectively) for TG3. In the case of TG4, the high-anti orientation (the B rotamer family) turned out to be by far the most favourable, with the contribution exceeding 90% in equilibrium. Such a preference can be attributed to the inability of H-bonding between sugar and nucleobase and possibly because of the steric strains. The low-energy conformers of TG1-TG4 occupy the northeastern (P ∼ 40°) and/or southern (P ∼ 210°) parts of the pseudorotational wheel, which fits the A- and B-type DNA helices quite well. Additionally, in the case of TG4, some relatively stable geometries have the furanoid ring in conformation lying on the northwestern part of the pseudorotational wheel (P ∼ 288°).