198 Topics in Current Chemistry Editorial Board: A. de Meijere KN ...

Directional Aspects of Intermolecular Interactions 15
4.3
Hydrogen Bonding
Hydrogen bonds are among the strongest and most directional intermolecular
interactions. They play a crucial role in aligning molecular components of biological
systems [3, 25, 26]. The hydrogen bond, usually characterized as A-H◊◊◊B,
is an interaction between a hydrogen atom covalently bonded to an electronegative
atom A and another atom B that has lone pairs of electrons or polarizable
p electrons, and is fairly electronegative; the proton (H) donor is A and the proton
(H) acceptor is B. The hydrogen bond is formed when the electronegativity
of A relative to H in the covalent AH bond is such as to withdraw electrons and
leave the proton partially unshielded. The acceptor B then interacts with the
exposed proton [3, 26, 27].
The hydrogen bond (A-H◊◊◊B) is mainly electrostatic in character. Its strength
appears to be a complicated balance of various factors [28] which include:
1. the interactions between fractional charges that have developed on A, B, and H,
2. the deformability (polarizability) of the electron cloud around the acceptor
atom B so that it can make its lone pairs available to the proton (the softness
of B),
3. the transfer of electronic charge from B to H (s-bond transfer),
4. the electronic repulsion between A and B,
5. how readily a hydrogen-bond donor atom A will lose its covalently bound
hydrogen atom as H + (related to the electronegativity of A and the strength
of the A-H bond), and
6. how readily the hydrogen bond acceptor B can accept the H + (the electronegativity
of B).
Of these, the important attractive forces are electrostatic (1), polarization effects
(2), and charge-transfer interactions (3). The electrostatic component (in 1) falls
off less rapidly as a function of distance than do the others, and therefore at
longer distances it is the most important. These energy components are balanced
by repulsive forces (4) which become important at short distances.
Hydrogen bonds will be formed wherever possible [3, 27, 29]. If the numbers
of potential hydrogen bond donors and acceptors in a crystal are not equal,
water, which can donate two and accept either one or two hydrogen bonds, can
help settle the balance of donors and acceptors [30]. Hydrophobic groups in a
molecule tend to pack near hydrophobic groups of other molecules in the unit
cell. If a molecule contains both hydrophobic and hydrophilic areas, these will
pack in separate areas in a crystal, as far apart as possible.
The strength of a hydrogen bond lies somewhere between that of a weak covalent
bond and a van der Waals interaction; 48 kcal mol –1 for strong O-H◊◊◊N
hydrogen bonds as in arginine◊◊◊aspartate hydrogen bonds in proteins, and
2–7 kcal mol –1 for weak C-H◊◊◊O hydrogen bonds. Dunitz [31] pointed out that
the energy required to extend a covalent bond by 0.2 Å is of the order of 50 kcal
mol –1 , while that to extend a hydrogen bond the same amount is only 1.2 kcal
mol –1 ; this illustrates the difference in strengths on the two types of bonds. The
more readily the hydrogen is removed as H + from atom A, the stronger is the