C–H···O interaction

In chemistry, a C–H···O interaction represents a special type of weak hydrogen bond. Although weak, these hydrogen bonds are very important in nature, since they occur in the structures of important biomolecules like amino acids, proteins, sugars, DNA and RNA.^[1] C–H...O interactions represent 20-25% of all hydrogen bonds in proteins.^[2]

History

The C–H···O interaction was discovered in 1937 by Samuel Glasstone. Glasstone studied properties of mixtures of acetone with different halogenated derivatives of hydrocarbons and realized that dipole moments of these mixtures differ from dipole moments of pure substances. He explained this by establishing the concept of C–H···O interactions.

Properties

Two main characteristics of a C–H···O interaction are directionality and interaction energy. Based on directionality it was shown that C–H···O interactions are hydrogen bonds, and not van der Waals interactions.^[3]

The directionality of a C–H···O interaction is usually defined by the angle α between the С, Н and О atoms, and the distance d between the O and H atoms. In a С–Н···О interaction, the angle α is in the range between 90 to 180°, and the distance d is usually smaller than 3.2 Å.^[4] In the case of aromatic C–H donors, C–H···O interactions are not linear due to influence of aromatic ring substituents near the interacting C-H group.^[5][6] The interaction energy of a C–H···O interaction is in the range of 1.0 - 2.0 kcal/mol. However, in the case of very acidic hydrogen atoms, this value could be much higher.

C–H···O interactions can be important in drug design. These interactions influence the structure of therapeutic proteins,^[7] and aromatic amino acids from therapeutic proteins often donate hydrogen atoms and form C–H···O interactions. C–H···O interactions can also strengthen some other type of noncovalent interactions, like O-H...π interactions.^[8] Strong C-H...O interactions are observed in nucleic acids.^[9]

References