Three‐Dimensional Potential Energy Surface of Selected Carbohydrates’ CH/π Dispersion Interactions Calculated by High‐Level Quantum Mechanical Methods

Abstract

In this study we present the first systematic computational three-dimensional scan of carbohydrate hydrophobic patches for the ability to interact through CH/π dispersion interactions. The carbohydrates β-d-glucopyranose, β-d-mannopyranose and α-l-fucopyranose were studied in a complex with a benzene molecule, which served as a model of the CH/π interaction in carbohydrate/protein complexes. The 3D relaxed scans were performed at the SCC-DFTB-D level with 3 757 grid points for both carbohydrate hydrophobic sides. The interaction energy of all grid points was recalculated at the DFT-D BP/def2-TZVPP level. The results obtained clearly show highly delimited and separated areas around each CH group, with an interaction energy up to -5.40 kcal mol(-1) . The results also show that with increasing H⋅⋅⋅π distance these delimited areas merge and form one larger region, which covers all hydrogen atoms on that specific carbohydrate side. Simultaneously, the interaction becomes weaker with an energy of -2.5 kcal mol(-1) . All local energy minima were optimized at the DFT-D BP/def2-TZVPP level and the interaction energies of these complexes were refined by use of the high-level ab initio computation at the CCSD(T)/CBS level. Results obtained from the optimization suggest that the CH group hydrogen atoms are not equivalent and the interaction energy at the CCSD(T)/CBS level range from -3.54 to -5.40 kcal mol(-1) . These results also reveal that the optimal H⋅⋅⋅π distance for the CH/π dispersion interaction is approximately (2.310±0.030) Å, and the angle defined as carbon-hydrogen-benzene geometrical centre is (180±30)°. These results reveal that whereas the dispersion interactions with the lowest interaction energies are quite strictly located in space, the slightly higher interaction energy regions adopt a much larger space.

DNA–protein π-interactions in nature: abundance, structure, composition and strength of contacts between aromatic amino acids and DNA nucleobases or deoxyribose sugar

“…Although only π-interactions between the entire sugar face of pyranose and the aromatic amino acid were considered in previous work (61,62,67,76), a range of sugar–π contacts were identified for deoxyribose in the present study, which can involve a single proton, two protons (a bridge), three protons (a face), a lone pair, or both a lone pair and a proton (lone pair–proton; Figures 7B, 8 and 10). As a result, we introduce a classification system for DNA–protein sugar–π interactions based on the sugar edge participating in the contact, which can yield C–H···π and/or lone–pair···π interactions.…”

“…Interestingly, although the strongest interactions occur when a pyranose C–H is directed at the center of the aromatic face (76), the amino acid displays a wide range of locations with respect to the sugar in DNA sugar–π contacts. This implies that the sugar composition plays a large role in determining the preferred geometry of the interaction.…”

Caffeine and Sugars Interact in Aqueous Solutions: A Simulation and NMR Study

“…The absence of these effects might explain the smaller binding energies calculated here compared to the 2.5 – 5.4 kcal/mol estimated from ab initio calculations. 32 Such C-H/π interactions would be present in the experimental systems, but it was not possible to use the NMR results to calculate the binding energies. The binding energies reported here are due primarily to hydration effects resulting from the liberation of structured water molecules.…”

“…However, it has recently been suggested that these types of associations are strengthened by interactions between the C-H bonds and the π-clouds of aromatic rings such those of caffeine. 32–35 Quantum-mechanical studies have been used to estimate the magnitude of this increase in interaction energy that might result from such interactions. While any such effects would of course be present in the NMR experiments reported here, they would appear in the MM simulations only to the extent that they are captured by the force field parameterization, primarily through the choice of atomic partial charges and van der Waals radii.…”

Facial Selectivity between Carbohydrates and Aromatic Amino Acids Explained by a Combination of NCI, NBO and EDA Techniques with NMR Spectroscopy

“…There is an enhancement in the carbohydrate-aromatic stacking with an increase in sugar hydrophobicity through methylation, as observed by Morales and co-workers. 10 The interaction of carbohydrates with model compounds, such as benzene, [11][12][13] toluene, 14 naphthalene, 15 p-hydroxytoluene, 16 and 3-methylindole, 17 has been studied by both theoretical and experimental approaches, and it was determined that the CH-π interaction occurs and is more relevant when three CH bonds of the carbohydrate are oriented toward the aromatic system.…”