DFT-based conformational analysis of negatively-charged cytosine-containing artificial threose nucleic acid (TNA) nucleotides

A conformational analysis was carried out on a negatively charged monomer of the non-natural threonucleic acid (TNA), with a cytosine group at C1’ and a methoxyphosphate group at C3’, at three theory levels: B3LYP/6–31 + G(d, p), B3LYP/6-311 + + G(d, p) and M06-2X/6–31 + G(d, p) in the gas phase. Single-point calculations were also performed using the MP2/aug-cc-pVDZ level to evaluate the DFT results. NBO, AIM and NCI analyses were performed on the two most stable conformers. Calculations were performed in an aqueous environment at the SMD/M06-2X/6–31 + G(d, p) level. The M06-2X functional showed a multicomponent mixture of conformers at equilibrium with two dominant geometries (1 and 3), whereas the B3LYP functional showed conformer 3 to be dominant (> 95%). Conformer 1 is stabilised by set of weak improper H-bond interactions, while conformer 3 is stabilised mainly by a strong H-bond. In the gas phase, conformations 3 E and 2 T 1 were identified for conformers 1 and 3, respectively. Conformer 12 proved to be the most stable in an aqueous environment.