Four-Center Hydrogen Bonds

A four-center hydrogen bond is defined as one in which the proton makes three first neighbor contacts to potential hydrogen-bond acceptor atoms in the forward direction with respect to the donor X-H bond. 

The geometrical definition is less rigorous than that for three-center bonds, since it requires only that the X-ft Aj, A2, A3 angles are greater than 90°. 

In the general survey of 1352 NH 0=C bonds [56], the percentage of four-center hydrogen bonds is below 1% and they occur only with N-H as donors. This may be an underestimate caused by the use of arbitrary van der Waals cut-off. 

The geometry of the four-center hydrogen bonds observed in neutron diffraction analyses of the amino acids and of the purines, pyrimidines, nucleosides, 

Metrical Aspects of Three- and Four-Center Hydrogen Bonds 

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Table 8.2. Three- and four-center hydrogen-bond geometries in the paraelectric (room-temperature) form of ammonium sulfate. The transition to the ferroelectric (low temperature) form involves a change to two-centered bonds (nomenclature as in original publication [451]...

Fig. 8.1. The four-center hydrogen bond in the crystal structure of sucrose by neutron diffraction (SUCROS04)...

In contrast to these structures, the methyl-5-thio-a-ribopyranoside [METRBP10] has the 4Ct chair conformation, with no intramolecular hydrogen bonding between the syndiaxial 0(3)H to 0(1)CH3 groups, which are separated by 2.99 A. Instead, there is the four-centered hydrogen bond in which two of the components are intramolecular, as illustrated in Fig. 13.11. The configuration requires a relatively small distortion of the 4Q chair conformation. 

There are three related pattern IT, III and III" involving other three- and four-center hydrogen bonds (Fig. 14.13). IF occurs in L-glutamic acid-HCl [LGLUTA]... 

The 5-amino-l-/ -D-ribofuranosylimidazole-4-carboxamide [ARBIMC10] structure contains both a cyclic trimer and a cyclic pentamer ( Fig. 17.9 a). The amide NH2 group is engaged in a four-centered hydrogen bond with long H- A distances between 2.50 and 2.56 A. There are two intramolecular components indicated by ( ). 

In the crystal structure of netropsin bound to a dodecamer with four A T base pairs in the middle, the four base pairs have high propeller twists [99,100]. As a result, the amino group of adenine is located half-way between the carbonyl groups of two adjacent thymine residues and some three-center hydrogen bonds... 

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