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

Crystalline Polymorphism of Organic Compounds 193
amide (DSC, XRD) [140], paraffins C 26 – C 60 (DTA, thermobarometric analysis)
[141] and tripalmitin (DSC, thermodiffractometry, microcalorimetry) [142].
This list represents a very small selection, merely serving to indicate the variety
of techniques employed.
Several recent developments in the areas of structure determination are
having a significant impact on the study of organic crystal polymorphism and
these are now surveyed, together with examples of applications to specific
systems. In the discussion above, it has been maintained that a knowledge of the
crystal structure of a polymorph provides a sound basis for interpretation of
other analytical data pertaining to that species and is crucial for even a rudimentary
understanding of phase transformations at the molecular level. It is
also well known that many polymorphs of technological interest cannot readily
be obtained as single crystals suitable for X-ray structural elucidation. However,
since the advent of the Rietveld, or “whole-pattern”, refinement technique [143]
which allows crystal structure refinement using X-ray or neutron powder
diffraction data, the status of powder XRD has been elevated from that of a mere
“fingerprinting” technique to one of formidable power as a structure-solving
tool. This power has been significantly enhanced by recent progress in obtaining
trial structural models for Rietveld refinement directly from the diffraction
intensities. Since the powder pattern is a one-dimensional projection (on 2q) of
the three-dimensional single crystal diffraction data, a key problem in this
challenging research area is unravelling the intensities of severely, or exactly,
overlapping reflections. In a recent study, an algorithm for achieving this was
reported [144] and, together with software routines for space group determination
and a fast iterative Patterson squaring routine, this combination led to the
successful ab initio crystal structure determination of an aluminophosphatebased
molecular sieve from X-ray powder data exclusively. It is noteworthy that
as many as 65% of the reflection data used in this analysis suffered from severe
overlap. This approach holds great promise for future structure determination
of polymorphs which hitherto have been obtained in the form of powders only.
More recently, a method using powder diffraction for structure solution was
described in which structural information is not extracted directly from the
intensities; instead, trial structures are generated using a Monte Carlo approach
[145] commencing with a collection of atoms initially randomly placed in the
crystal unit cell. A series of trial structures is then generated by random movement
of the atoms, each trial structure being accepted or rejected depending
on the level of agreement between the calculated and experimental powder
patterns. The Monte Carlo method employed is based on the Metropolis importance
sampling algorithm using the crystallographic R-factor as the basis for
constructing trial models. The best model is then used in a conventional
Rietveld refinement. The structures of two compounds, with eleven and twelve
non-hydrogen atoms in the respective asymmetric units, were solved by this
procedure using high-resolution powder X-ray intensity data measured with a
position-sensitive detector. The novel feature of this method is the use of the
Monte Carlo algorithm for generating trial structures.
Crystal structure prediction based on lattice energy minimisation has already
been discussed and attention has been drawn to the serious drawbacks of this