Hoogsteen–Watson–Crick 9-Methyladenine:1-Methylthymine Complex: Charge Density Study in the Context of Crystal Engineering and Nucleic Acid Base Pairing

Abstract

This study provides a detailed charge density distribution analysis supported by comprehensive energetic investigations. The nature of the intermolecular interactions existing in the 9-methyladenine:1-methylthymine cocrystal structure with respect to those specific for the corresponding monocomponent crystals is explored. Charge density topological investigations lead to reliable hydrogen-bond interaction energies consistent with the results of the DFT approach with Grimme dispersion correction applied. The cocrystal structure cohesive energy corresponds with the average stability of its components' crystals. This is in agreement with the experimental observations. Thus, formation of the particularly strong 9-methyladenine:1-methylthymine motif (interaction energy around −70 kJ•mol −1 , DFT(B3LYP)/pVTZ, BSSE and dispersive corrections applied) may constitute the driving force for cocrystal growth. All three systems form molecular layers governed by hydrogen-bond interactions whereas interacting mostly dispersively with each other. The interlayer contacts are found to be significant. Formation of particularly short H•••H contacts is a distinctive feature of the cocrystal lattice. Also, creation of the cis-Hoogsteen−Watson−Crick (cHW) adeninethymine base pair motif (Leontis and Westhof classification), instead of creating the most frequently appearing DNA Watson− Crick base pair (cWW), is remarkable. It occurs that this A:U/T orientation is slightly more stable than the analogous cWW one. Nevertheless, in RNA chains, being more flexible than DNA molecules, the cHW A:U base pairing remains rather rarely encountered, which is probably the effect of the rigidity of nucleic acid chain backbones. In general, the purine-pyrimidine interaction strength is most sensitive to the directionality of the formed hydrogen bonds.

Intermolecular Interactions in Ionic Crystals of Nucleobase Chlorides—Combining Topological Analysis of Electron Densities with Energies of Electrostatic Interactions

“…Despite their overall repulsive interactions, we observed numerous bond critical points (BCP) and bond paths between many nucleobase cations in the studied crystals using topological analysis of crystal electron densities (experimental or theoretical). Properties of BCPs do not differ much from those of neutral base pairs [63] as was observed for other systems [13] as well. Moreover, interaction energies computed from electron densities and their Laplacians at BCPs according to the Espinosa-Molins-Lecomte approach (E EML ) are negative, suggesting attractive interactions between cations.…”

“…This is rather obvious since charge densities of nucleobases are far from being spherical (and point-like) and the closer the distance the more important the actual shape of the charge density of interacting molecules is. Interestingly, after subtracting the electrostatic interaction energy of molecular point charges (E Coul ) from exact E es , the remaining differences are values typical for dimers of neutral nucleobases in their crystals [59,63]. For some of dimers, the origin of the difference between the exact E es and the approximated one (E Coul ) can be explained simply by the fact that higher electric multipole moments of nucleobase molecule(s) (higher than point charge) have important contributions.…”

Synthesis, structural characterization and computational studies of catena-poly[chlorido[μ3-(pyridin-1-ium-3-yl)phosphonato-κ3 O:O′:O′′]zinc(II)]

“…4. The total energy falling on the ASUequivalent fragment of a polymeric chain in the crystal structure of (1) is À205.4 kJ mol À1 and is comparable with the cohesive energy values for molecular crystals of small organic species interacting via hydrogen bonds further stabilized by stacking interactions (Durka et al, 2012;Jarzembska et al, 2013;Kutyła et al, 2016;Price, 2014). N1-H1NÁ Á ÁO33 iii and C6-H6Á Á ÁO31 iv , as well as offset faceto-facestacking interactions.…”

Electrostatic Interactions in Aminoglycoside-RNA Complexes

“…It was also shown that UBDB effectively reproduces the electrostatic interactions in molecular dimers (39), Watson-Crick basepairs (40), and nucleic acid fragments (41).…”