CH-π Interaction between Carbohydrates and Aromatic Moieties: Electron Density Issue

S. Kozmon^1,2, R. Matuška^1,2, J. Koča^1,2

¹CEITEC – Central-European Institute of Technology, Masaryk University, Kamenice 753/5, 625 00, Brno, Czech Republic

²National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic

Former studies of the CH-π interactions [1,2] between carbohydrates and aromatic moieties were focused on exploration of interaction energies in complexes of selected carbohydrates (β-d-glucopyranose, β-d-mannopyranose and α-l-fucopyranose) with benzene and naphthalene as simplest representatives of aromatic amino acids side chains. These studies provided complex insight into the nature and strength of carbohydrate-aromatic CH-π interaction as well as its additivity with respect to total number of π-electrons interacting it the aromatic system. The next logical step in complex study of CH-π interaction is to study the influence of electron density in the aromatic system to the total interaction energy of the carbohydrate-aromatic complex.

For this reason, we chose established set of selected carbohydrates mentioned above and constructed aromatic systems derivatives with expected increased and decreased electron density in the cycle – namely symmetrical difluoro-, trifluoro- and tetrafluoro-benzene and symmetrical diazine, triazine and tetrazine. All derivatives underwent electron-density evaluation in ring critical points by AIM analysis (MP2/aug‑cc‑pVTZ), which clearly shows decreasing electron density with respect to the degree of derivatization of fluorobenzenes and increasing electron density with respect to the degree of derivatization by nitrogens in the aromatic ring.With this set of molecules, we repeat the semiempirical SCC-DFTB-D potential energy scan with DFT-D BP/def2-TZVPP interaction energy refinement to identify stationary structures of potential energy surface. Their interaction energy is calculated after geometry optimization at DFT-D BP/def2‑TZVPP level. Such level of theory has been previously proved [1] to be sufficient and giving similar results as CCSD(T)/CBS method.

Performed study helps to understand the way how saccharides interact with aromatic amino acid side chains in lectins. More specifically speaking the way, how the substitution of benzene ring in lectins influences the carbohydrate binding potential. Such understanding may be then utilized in tuning the strength of CH-π interaction and also for further glyco-force-field refinements.

This work was funded by the European Community’s Seventh Framework Programme under grant agreement no 205872, the Ministry of Education of the Czech Republic (MSM0021622413, LC06030, MSM6046137305), and the Czech Science Foundation (GD301/09/H004). The project is supported within the SoMoPro programme (project No. 2SGA2747). The research leading to these results obtained financial contribution from the European Union under the Seventh Framework Programme (FP/2007- 2013) by Grant Agreement No. 229603. The research is also co-funded by the South Moravian region. In addition, this work was also supported within the project ‘‘CEITEC-Central European Institute of Technology’’ (CZ.1.05/1.1.00/02.0068) from European Regional Development Fund. Access to the MetaCentrum computing facilities is provided under the research intent MSM6383917201 and is highly appreciated.

[1] Kozmon S., Matuška R., Spiwok V., Koča J.: Chemistry – A European Journal, 2011, 17, 5680-5690.

[2] Kozmon S., Matuška R., Spiwok V., Koča J.: Physical Chemistry Chemical Physics, 2011, 13, 14215-14222.