Section 22.2.2. Nature of the hydrogen bond

Hydrogen bonds are attractive electrostatic interactions of the type D—H···A, where the H atom is formally attached to a donor atom, D (assumed to be more negative than H), and is directed towards an acceptor, A. The acceptor A is normally an electronegative atom, usually O or N, but occasionally S or Cl, with a full or partial negative charge and a lone pair of electrons directed towards the H atom. Although most of the hydrogen bonds in proteins and nucleic acids are N—H···O or O—H···O (less often, N—H···N), it is important to be aware that other possibilities exist, including N—H···S, O—H···S and C—H···O, and that these can be very important in specific cases (Adman et al., 1975; Derewenda et al., 1995). Likewise, the π-electron clouds of aromatic rings can also act as acceptors for appropriately oriented D—H groups (Legon & Millen, 1987; Mitchell et al., 1994).

In an ideal hydrogen bond, the donor heavy atom, the H atom, the acceptor lone pair and the acceptor heavy atom should all lie in a straight line (Legon & Millen, 1987), as illustrated in Fig. 22.2.2.1(a). The strength of the interaction is also expected to depend on the electronegativities of the atoms involved. Hydrogen bonds are said to be bifurcated when a single D—H group interacts with two acceptors in a three-centred hydrogen bond (Fig. 22.2.2.1b); these hydrogen bonds are necessarily nonlinear and weaker. However, the term bifurcated is also sometimes applied to the quite different situation where a donor atom with two H atoms or an acceptor atom with two lone pairs makes two hydrogen bonds, as in Figs. 22.2.2.1(c) and (d). These interactions can be strong and linear. Some hydrogen-bonding arrangements are said to be cooperative; for example, hydrogen bonding by a peptide C=O group should enhance the polarity of the whole peptide unit and hence the acidity of the amide proton and the strength of its hydrogen bonding (Jeffrey & Saenger, 1991).

Figure 22.2.2.1| top | pdf | Hydrogen-bonding configurations. (a) The standard two-centre hydrogen bond in which an H atom attached to a donor atom, D, is directed towards a lone pair of an acceptor, A. (b) A classic three-centre, or bifurcated, hydrogen bond, with a single H atom shared between the lone pairs of two acceptors. The situations shown in (c) and (d) are not true three-centre hydrogen bonds since they are essentially equivalent to that in (a).