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

78 A. Nangia · G.R. Desiraju
2.86–3.18 Å). The more significant observation is that secondary stabilisation is
conferred upon the superstructure by a “T”-shaped C-H◊◊◊p contact between
one of the methylene H-atoms of the 4-carboxybenzyl group and one of the
hydroquinone rings of the BPC34C10 polyether (H◊◊◊p 2.88 Å, C-H◊◊◊p 143°).
The PF 6 – counterion assists in maintaining the co-directionality of the two
carboxyl groups of the [3]pseudorotaxane within the macrocyclic polyether,
possibly through C-H◊◊◊F hydrogen bonds. These three-component complexes
aggregate to generate doubly encircled, six-component organic supermolecules
that are linked by the robust carboxyl dimer supramolecular synthon through
pairs of strong O-H◊◊◊O hydrogen bonds (O◊◊◊O 2.61, 2.68 Å). All this goes to
show that in large and complex supramolecular architectures, numerous strong
and weak hydrogen bonds act in concert to stabilise the crystal structure.
7
Supramolecular Interactions in Biological Systems
7.1
Weak Hydrogen Bonds
The first report on the existence of C-H◊◊◊O hydrogen bonds in organic crystal
structures was published by Sutor in 1962 [52]. The potential of these weak
interactions in nucleotides was emphasised by Rubin et al. in 1972 to explain
conformational preferences in nucleotide bases [53]. They suggested that specific
C-H◊◊◊O interactions between the purine C(8)-H or pyrimidine C(6)-H and
the O(5¢) oxygen are responsible for the anti conformation of these bases. The
existence of weak C-H◊◊◊O hydrogen bonds in proteins has been described by
Derewenda et al. in 1995 [54]. The crystal structures of carbohydrates also exhibit
a large number of short intermolecular C-H◊◊◊O contacts [55]. The traditional
view has been that only hydrogens bonded to oxygen and nitrogen
atoms should be considered in the analysis of crystal structures of biological
macromolecules [42]. There is now convincing evidence that there are a significant
number of weak C-H◊◊◊O and C-H◊◊◊N hydrogen bonds in such structures
which co-exist with the strong O-H◊◊◊O, O-H◊◊◊N and N-H◊◊◊N hydrogen bonds.
A statistical analysis of protein crystal structures shows that the C-H◊◊◊O interactions
exhibit characteristics associated with weak hydrogen bonds: the acidic
C-H groups are more frequent; the acceptor O-atom is of the carbonyl or carboxyl
type, and the median d and q values are about 2.4 Å and 140° . The current
view, expressed by Wahl and Sundaralingam [56], is that weak hydrogen bonds
play a significant role in determining the structure as well as the function of biological
macromolecules like nucleic acids, proteins and carbohydrates.
Watson-Crick (WC)and Hoogsteen (HG) base pairs between adenine and
thymine or uracil have been traditionally constructed with strong hydrogen
bonds. The participation of weak interactions in the recognition between adenine
and thymine or uracil bases leads to the triply hydrogen bonded motif
DAD:ADA consisting of two N-H◊◊◊O and one C-H◊◊◊O hydrogen bonds [57].
The conventional WC and HG hydrogen bonding schemes are strengthened by