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

72 A. Nangia · G.R. Desiraju
ingful. This is because: (1) the crystal structure of any molecule must have a few
intermolecular contacts in the repulsive van der Waals region – a few such forced
contacts can be comfortably accommodated in any crystal structure provided
they are compensated for by the free energy gained from the other numerous
dispersive forces, hydrogen bonds and heteroatom interactions; (2) the
weak, polarisable hydrogen bonds (C-H◊◊◊O, C-H◊◊◊N, C-H◊◊◊X, O-H◊◊◊p) and
other heteroatom interactions (X◊◊◊X, N◊◊◊X, S◊◊◊X) have approach distances and
angle characteristics scattered over a wider range – they are also more susceptible
to the mutually interfering effects in a crystal, effects that can deform considerably
the approach vector from the ideal geometry.
In the statistical approach, such as is possible with the CSD, a large number of
observed interaction geometries cluster in a narrow region. A few outliers are
deformed and may be repulsive in nature. The larger the number of data points,
the greater is the confidence in the intermolecular contact or structural hypothesis
under study. As for the outliers, they could furnish an additional bonus in
that their occurrence is often indicative of an unusual or different chemical
effect.
The utility of the CSD in identifying supramolecular synthons is revealed in
a study of N-H◊◊◊O hydrogen bonding [37]. The patterns of interest are 34 and
35 and the expected precursor urea and imide structures, 30 and 31 (Scheme 6),
were retrieved initially from the April 1997 update. Examination of the two
populations revealed a significant number of common hits, all of which contain
fragment 32. These were excluded from subsequent analysis. Of the 230 remaining
acyclic ureas, there were 44 occurrences of synthon 34 but only one occurrence
of synthon 35 in the 32 acyclic imides. It is clear then that 34 occurs more
frequently in ureas than does 35 in imides. This raises the question as to whether
34 is inherently more stable than 35. Both synthons have three-centre hydrogen
bonds and while 34 contains a bifurcated acceptor, 35 contains a bifurcated
donor. The stabilisation from the urea and imide hydrogen bonded patterns was
calculated (AM1) to be 6.9 and 6.1 kcal mol –1 . It is unlikely that the more
30 31 32 33
34 35
Scheme 6. Hydrogen bonding motifs in ureas 34 and imides 35