Cyclic Adenine-, Cytosine-, Thymine-, and Mixed Guanine−Cytosine-Base Tetrads in Nucleic Acids Viewed from a Quantum-Chemical and Force Field Perspective

Abstract

We have carried out a systematic study of hydrogen-bonded cyclic A, C, T, and mixed GCGC tetrads resembling conformations occurring in experimental tetraplex structures, using the B3LYP hybrid density functional (DFT) method and the MMFF and AMBER force fields to determine tetrad structures and interaction energies. The results are compared to G and U tetrads analyzed previously, thereby presenting a comprehensive overview of all cyclic tetrads formed from one base type only, in addition to the GCGC data. The DFT calculations indicate that the C tetrad is planar and the GCGC tetrad is nearly planar and correspond to local minima at C 4 h and C i symmetry, respectively. For A tetrads with N6−H6···N7 and with N6−H6···N1 H-bonds and for T tetrads, nonplanar structures are more stable than the planar ones, and among the nonplanar structures, S 4-symmetric conformations are more stable than C 4 structures. Minima confirmed by frequency calculations are found for the planar C tetrad, the C i -symmetric GCGC tetrad, the C 4-symmetric structure of the A tetrad with N6−H6···N7 H-bonds, and the S 4-symmetric T tetrad, in addition to the already known local minima of the S 4-symmetric structure of the G tetrad and the planar U tetrad with C−H···O hydrogen bonds. The interaction energies (ΔE T) corrected for deformation of the bases in the tetrads range from −69.47 kcal/mol for the GCGC tetrad with three pairs of strong Watson−Crick type hydrogen bonds to −11.09 kcal/mol in the planar A tetrad having only a single N6−H62···N1 interbase hydrogen bond. With more than 18%, the largest cooperativity contribution to ΔE is found for the C and G tetrads. The interaction energies derived from the MMFF and AMBER force field are similar to the DFT data for those tetrads having high interaction energies, whereas the relative deviations are much larger for weakly H-bonded tetrads.

Adenine versus guanine quartets in aqueous solution: dispersion-corrected DFT study on the differences in π-stacking and hydrogen-bonding behavior

“…The hydrogen bond energies for B3LYP have been calculated with the BLYP-D geometries to give a qualitative impression of how B3LYP is unable to reproduce energies for stacked complexes (see Table 4). In accordance with previous work of Meyer et al [18] at the B3LYP level, we find in the gas phase for the G 4 quartet that the difference between the C 4h and the S 4 structures is small, only 0.6 kcal/mol (see Table 4; Fig. 4).…”

“…This is in sharp contrast with previous work [18] at the B3LYP level, where the S 4 structure of A 4 -N1 is only a few Calculations were done with a TZ2P basis set a C 4 starting geometry collapses spontaneously to C 4h structure kilocalorie per mole lower in energy than the C 4 and C 4h structures, and for the A 4 -N7 quartet all symmetric structures are within 0.5 kcal/mol energetically equal. The difference can be ascribed to the difference in the geometries.…”

“…The difference can be ascribed to the difference in the geometries. Our S 4 minima are stacked dimers with hydrogen bonds in between, whereas the B3LYP minima [18] look more like a distorted C 4h structure. For the A 4 -N1 quartet we were able to find a local minimum in the S 4 symmetry at the BLYP-D/TZ2P level (see Fig.…”

“…the three adenine quartets, has been the subject of computational studies [12][13][14][15][16][17][18][19].…”

Interaction of sodium and potassium ions with sandwiched cytosine‐, guanine‐, thymine‐, and uracil‐base tetrads

“…In the following we provide also a comparison between geometries and relative energies of the sandwiched tetrad complexes studied in this work and single-tetrad complexes, of which properties were determined previously at the same theoretical level. 28,36,39 Sandwiched G-Tetrads Previously, G-tetrads have been studied both with and without metal ions. 29,30,[35][36][37][38][39]41 As already noted, there is also one pioneering study for a sandwiched G-tetrad complex.…”