STRUCTURE-PROPERTY RELATIONSHIPS IN CRYSTAL STRUCTURES OF
MOLECULES
WITH NON-CENTROSYMMETRIC POLYMORPHS
Graham J. Tizzard,* Michael B. Hursthouse, Department of Chemistry, University of Southampton, UK.
Background
There are a number of different attractive forces which determine the packing in molecular crystals and they can be approximately classified as
follows: dispersion or London forces, multipolar forces, hydrogen bonding and charge transfer forces. It is the complex interplay of these forces along with
repulsion energy which can lead to many local minima in the lattice energy of a crystal which can thus result in polymorphism (i.e. the existence of more than
one crystalline form in a substance). In the study of polymorphism, hydrogen bonds, which are the highest energy interactions in molecular crystals and thus
appear to be the most important attractive force. There is clear evidence that multifunctional molecules (e.g. pharmaceuticals) with multiple H-bonding sites
promote polymorphism and that the polymorphism exhibited by these molecules can be ascribed to the different H-bonding topologies. However,
polymorphism also occurs in systems without strong hydrogen bonds (N – H ∙∙∙ X, O – H ∙∙∙ X, S – H ∙∙∙ X; X = N, O, S, F, Cl, Br, I). In these cases, although
H-bonding may still be present in the form of weaker interactions such as C – H ∙∙∙ X and C – H ∙∙∙ П, the overarching importance of hydrogen bonding in
defining polymorphism is greatly reduced.
This project is concerned with making a detailed study of the latter type of the above systems. In these systems electrostatic interactions are expected
to exert a greater influence on the crystal structure adopted. A particular point of interest is the occurrence of polymorphs, in what are essentially achiral
molecules, that have both centrosymmetric and non-centrosymmetric crystal structures. Interest in the second of these is very important for the development
of useful materials with nonlinear optical properties. In this poster we present preliminary results for two small families of compounds, one in which
hydrogen bonding occurs and one in which the hydrogen bonding appears to be weak or non-existent according to normal criteria.
5-nitrouracil
As shown in the table
below, three polymorphs of 5nitrouracil have been identified
from the Cambridge Structural
Database (CSD) [1], of which one
of these is non-centrosymmetric
and is shown in figures 1, 2. and 3
(right). All of the polymorphs of
5-nitrouracil
exhibit
strong
hydrogen bonding.
CSD code
Crystal System
Space Group
(No.)
NIMFOE
NIMFOE01
NIMFOE02
monoclinic
orthorhombic
orthorhombic
P21/n
(14)
Pbca
(61)
P212121
(19)
a/Å
5.873
8.308
5.4342
b/Å
9.693
10.426
9.8406
c/Å
10.4561
13.363
10.3659
α/º
90
90
90
β/º
104.7
90
90
γ/º
90
90
90
577.3769
1157.492
554.3247
4
8
4
1.0
1.0
1.0
Cell Volume / Å3
Z
Z’
Reference
[2]
[3]
[3]
N,N-Dimethyl-8-nitronapthaleneamine
As shown in the table
below, three polymorphs of N,NDimethyl-8-nitro-napthaleneamine
have been identified from the CSD,
of which one of these is noncentrosymmetric and is shown in
figures 4, 5. and 6 (right). None of
the polymorphs of N,N-Dimethyl8-nitro-napthaleneamine
exhibit
strong hydrogen bonding.
CSD code
DIWWEL
DIWWEL01
DIWWEL02
Crystal System
monoclinic
monoclinic
monoclinic
P21/c
(14)
C2/c
(15)
Pn
(7)
Space Group
(No.)
a/Å
8.373
33.150
8.429
b/Å
7.268
8.272
21.053
c/Å
17.311
26.090
10.199
α/º
90
90
90
β/º
96.75
115.22
111.88
γ/º
90
90
90
1046.158
6472.355
1679.735
4
24
6
1.0
3.0
3.0
Cell Volume / Å3
Z
Z’
Reference
[4]
[4]
[4]
Figure 1. This is a view of the packing arrangement of the noncentrosymmetric polymorph (NIMFOE02) along the a-axis. The
H-bonding interactions have been picked out and range from
2.219Å – 2.884Å (donor to acceptor distance).
Figure 4. This is a view of the packing arrangement of the
non-centrosymmetric polymorph (DIWWEL02) along the aaxis. There are no strong H-bonding interactions in this
structure however, the molecules are functionalised and so we
may expect a particular charge distribution to influence
assembly. Short-contact distances (sum of VdW radii) have
been picked out and range from 2.101Å – 2.816Å.
Figure 2. The electrostatic potential map of 5-nitrouracil has
been calculated using a Hartree-Fock quantum mechanical
model with a 6-31G(*) basis set. The regions of the map range
from red (high electronegativity) through green to blue (high
electropositivity).
Figure 5. The electrostatic potential map of N,N-Dimethyl-8nitro-napthaleneamine has been calculated in the same way as
5-nitrouracil (fig. 2). It should be noted that for both
molecules single-point energy calculations were carried out
using coordinates from the CSD. The calculations were
carried out using the Spartan’02 for Windows molecular
modelling package [5].
Figure 3. This is the same view as above (fig. 1) but with the
atoms colour-coded as to their electrostatic potential (fig. 2).
Some short-contact distances (sum of VdW radii – 0.4Å) are
shown. The H-bond distances are shown (1.800Å – 1.841Å; H
to acceptor distance) and from the model appears to have an
electrostatic component as expected. Another contact between
the nitro O and carbonyl C (2.777Å) also appears to be
electrostatic in nature, again as expected.
Figure 6. This is the same view as above (fig. 4) but with the
atoms colour-coded as to their electrostatic potential (fig. 5).
The network of short-contact distances (sum of VdW radii) is
shown, although no measurements are shown as they are
identical to those above (fig. 4). As can be seen electrostatic
attraction can account for the interactions between the nitro O
and methyl groups and napthalene ‘edge’. However one of
the shortest contacts (2.101Å) is between the intermolecular
methyl groups and this cannot be accounted for by
electrostatic interactions in this model.
Comment
From the above work several points are worth noting. Generally, as expected, the short contact distances are significantly less in the hydrogen
bonding, 5-uracil structures than in the non-hydrogen bonding N,N-dimethyl-8-nitro-napthaleneamine. More specifically, this method of modelling appears
useful at highlighting areas of a crystal structure where electrostatic interactions are important (including H-bonding) and those where it is not, e.g. the
intermolecular amino methyl interactions of N,N-dimethyl-8-nitro-napthaleneamine, where perhaps steric considerations may dominate. Further work is at
present being carried-out using this method and other more quantitive techniques with a series of polymorphic families.
The major ‘bottlenecks’ throughout this project have been workflow related through the transfer of data from one application to another and also from
‘driving’ the applications to obtain the data. Methods of automation are being investigated including the use of Perl to write data-transfer scripts and
spreadsheets to automate calculations. This is with the ultimate aim of providing a complete analysis of the electrostatic interactions of a molecule in the
context of its crystal packing as a single callable process.
Acknowledgements
References
We gratefully acknowledge the support of the EPSRC e-Science
programme (GR/R67729, Combechem).
[1] F. H. Allen, O. Kennard; Chem. Des. Autom. News; 8; 31; 1993.
[2] A. R. Kennedy, M. O. Okoth, D. B. Sheen, J. N. Sherwood, R. M. Vrcelj;
Acta. Cryst. C; 54; 547; 1998.
[3] R. S. Gopalan, G. U. Kulkarni, C. N. R. Rao; ChemPhysChem; 1; 127; 2000.
[4] M. Egli, J. D.
Wallis, J. D. Dunitz; Helv Chim Acta; 69; 255; 1986.
[5] Spartan’02; Wavefunction, Inc.; Irvine, CA, USA.