Are C–H⋯O interactions linear? The case of aromatic CH donors

Abstract

The angular distribution of the C–H⋯O interactions of aromatic C–H donors was studied by analyzing data in the Cambridge Structural Database (CSD) and by ab initio calculations. The analysis of the C–H⋯O interactions in the crystal structures from the CSD indicate that aromatic C–H donors do not show strong preference for linear contacts and that the preference depends on the type of the atom or group in the o-position to the interacting C–H group. Namely, the acceptor oxygen atom has possibility for simultaneous C–H⋯O interactions with the hydrogen atom in the o-position to the interacting C–H group. The C–H⋯O interactions of aromatic molecules with two hydrogen atoms in the o-positions do not show preference for linear contacts. Bifurcated interactions are observed in a substantial number of structures. Moreover, in the structures with a substituent in the o-position there is possibility for simultaneous interactions, depending on the nature of the substituent. The results of the ab initio calculations are in accord with the CSD data and show that the stabilization energy is larger for bifurcated than for linear interactions. The calculated energies at the MP2/cc-pVTZ level for linear C–H⋯O interactions of benzene with water, methanol, and acetone are 1.28, 1.47, 1.45 kcal mol⁻¹; while for bifurcated interactions are 1.38, 1.63, and 1.70 kcal mol⁻¹, respectively. Analysis of the data in the CSD and the ab initio calculations indicate that the vicinity of the other possible hydrogen donors in the aromatic molecules causes a small tendency for linear contact in the C–H⋯O interactions. The result that nonlinear interactions are not energetically disfavoured, because of the possibility for simultaneous interactions, can be very important for recognizing C–H⋯O interactions in biomolecules containing aromatic groups, like proteins.