Intramolecular hydrogen bonds in canonical 2'-deoxyribonucleotides: an atoms in molecules study.

The molecular structure and relative stability of different conformers of isolated canonical 2'-deoxyribonucleotides thymidine-5'-phosphate (pdT), 2-deoxycytidine-5'-phosphate (pdC), 2-deoxyadenosine-5'-phosphate (pdA), and 2'-deoxyguanosine-5'-phosphate (pdG) were calculated using the B3LYP/6-31++G(d,p) level of theory. The results of the calculations reveal that, for all nucleotides except pdG, conformers with a syn orientation of the base do not correspond to a minimum on the potential energy surface. In the case of pdA and pdC, conformers with an orthogonal orientation of the nucleobase are located instead, north/syn conformers. These conformers as well as syn conformers of pdG are stabilized by intramolecular N-H...O hydrogen bonds. Analysis of the electron density distribution within the atoms in molecules theory reveals the presence of numerous C-H...O hydrogen bonds in the nucleotides. However, a more detailed consideration of the properties of these bonds demonstrates that many of them should be considered as strong attractive electrostatic interactions rather than true hydrogen bonds. True hydrogen bonds are represented mainly by C6/ C8-H...O5'/O-P in anti conformers and the N-H...O-P bonds in syn conformers. It is demonstrated that the values of ellipticity of the electron density at the bond critical point (BCP) and the distance between BCP and ring critical point are the most reliable indicators for determining the true intramolecular hydrogen bonds.