(599f) When Crystals Don’t Grow – the Growth Dead Zone

When crystals don’t grow – the growth dead zone

Yumin Liu^1,2,
Aurora J. Cruz-Cabeza^2,3, Roger J. Davey²

¹ School of Chemical Engineering
and Technology, Collaborative Innovation Centre of Chemical Science and
Chemical Engineering Tianjin
University, Tianjin 300072, P. R. China
² School of Chemical Engineering and Analytical Science, University of Manchester,
Manchester M13 9PL, United Kingdom

³ Astra Zeneca,
Silk Road Business Park, Charter Way Macclesfield SK10 2NA, United Kingdom

There is a region within the metastable zone near the
solubility curve called the growth dead zone, within which a seed crystal is
incapable of either growth or nucleation. On a practical level it is potentially problematic on two
counts. It firstly prevents a crystallizing system from reaching equilibrium,
reducing yields and compromising seeding processes often adopted commercially
and secondly in a polymorphic system it may provide a long lived metastable
state within which a second form may nucleate and grow. Such a crystallization gap was first described by Mullin¹
and its scientific status within the metastable zone was recently re-clarified
by Threlfall and Coles.²In one sense, this growth behaviour
has long been known for certain faces of the polar crystal α-resorcinol^3,4 and has subsequently been recognized in a significant
number of other compounds. It sometimes seems to be an inherent
feature of solution growth in others an impurity is an essential element for
its appearance. But by now, the
mechanisms underlying this particular, general zone of zero growth are too more
phenomenological with relatively few structural examinations.

Figure 1 Dead
zone related with Rugosity  

In this
contribution, we are thoroughly reviewing those previous works and report new
kinetic cases of (R,S)-alanine, β D-mannitol and benzophenone where the effects
of solvent, temperature and additives are considered to explore the underlying
causes of a dead zone in the context of crystal growth mechanisms, solvent
adsorption and surface topology. We thus measured the crystal growth rate for
these three new compounds at different supersaturations from in situ experiments using a growth cell
and an inverted microscope. Confronting the existing and new data with crystal
growth models, we identified that the dead zone cannot be uniquely attributed
to a surface nucleation mechanism. However, the new data do confirm that
temperature, solvent and additives have significant impact on the existence and
extent of dead zone features which taken together suggest a mechanism of
surface site blocking either in the form of solvent adsorption or
self-poisoning. This is further supported by perusal of molecular packing
arrangements which shows that the surfaces along the dead zone directions can
be regarded as corrugated in two dimensions. A simple geometric approach was
used to provide a pragmatic measure of the surface roughness, which reveals
that faces with dead zones are significantly rougher than faces with no dead
zones. A link appears to exist between those facets that exhibit such rugosity and their failure to grow at low supersaturations.

References

1. J. W. Mullin, Crystallization,
4th ed.; Butterworth-Heinemann: Oxford, U.K., 2001.

2. T. L. Threlfall,
S. J. Coles, A perspective on the growth-only zone, the secondary nucleation
threshold and crystal size distribution in solution crystallisation, CrystEngComm. 2016,
18, 369-378.

3. R. J. Davey, B. Milisavljevic, J. R. Bourne, Solvent interactions at
crystal surfaces: the kinetic story of. alpha - resorcinol, J. Phys. Chem. 1988, 92, 2032-2036.

4. A. F. Wells, Abnormal and
modified crystal growth. Introductory paper, Discuss. Faraday Soc. 1949, 5, 197-201.