Section 22.2.7.1. C—H···O hydrogen bonds

Sutor (1962) first summarized evidence for C—H···O hydrogen bonds following earlier suggestions by Pauling (1960), and current evidence has been nicely summarized in several recent articles (Derewenda et al., 1995; Wahl & Sundaralingam, 1997). The energy of C—H···O hydrogen bonds has been generally estimated as ∼0.5 kcal mol⁻¹ (about 10% of an N—H···O interaction) but may be higher, especially in hydrophobic environments. It also depends on the acidity of the C—H proton, with methylene (CH₂) and methyne (CH) groups being most favourable.

A number of examples of C—H···O hydrogen bonds can be found in nucleic acid structures (Wahl & Sundaralingam, 1997). The best known is that between the backbone O5′ oxygen and a purine C(8)—H or pyrimidine C(6)—H, when the bases are in the anti conformation. Another example is given by a U–U base pair, in which the two bases form a conventional N(3)—H···O(4) hydrogen bond and a C(5)—H···O hydrogen bond.

In proteins, two groups are regarded as being particularly significant (Derewenda et al., 1995). These are the C^ɛH of His side chains and the methylene H atoms of the main-chain α-carbon atoms. C—H···O hydrogen bonds involving His side chains have been found for the active-site His residues of proteins of the lipase/esterase family and in other proteins (Derewenda et al., 1994). The C^αH atoms appear to provide much more widespread C—H···O hydrogen bonding, however, especially in β-sheets, where they are directed towards the `free' lone pairs of the main-chain C=O groups. C—H···O hydrogen bonds may thus play a previously unrecognised role in satisfying the hydrogen-bond potential of C=O groups. In general, Derewenda et al. (1995) find a significant number of C···O contacts that meet the criteria for C—H···O hydrogen bonds; the H···O distance peaks at 2.45 Å (C···O 3.5 Å), which is less than the van der Waals distance of 2.7 Å, and the angles indicate that the H atoms are directed at the acceptor lone-pair orbitals.