Control of Crystallization Pathways by Electric Fields
165
Indications that static external electric fields could affect the crystallization
process had been reported previously [28–30]. For example, relatively small electric fields of 2-8 kV cm
−1 applied during the crystallization of proteins increased
the nucleation and growth rate [31–33]. Electric fields have also been made responsible for shifting preference towards one polymorphic form of glycine over another
when crystallized from solution [34, 35]. In terms of the origin of these field-induced
effects, contributions from field-dependent thermodynamic potentials [6–8] as well
as field-induced orientations have been discussed [36, 37]. In general, the detailed
mechanism involved in such field effects on crystallization have not been identified
[38].
In the case of crystallization from solution, e.g., water, the field effect may be
indirect through structural changes in the solvent. In the present case of VEC, the
situation is simpler as this is a pure substance with no significant tendency to form
supermolecular structures by directional bonding (such as hydrogen bonds). VEC
is a simple liquid in the sense that its high dielectric constant of about 79 (at T =
183 K) [39] is largely determined by the high molecular dipole moment of μ =
4.76 D [40], with no indication of strong orientational dipole correlation that leads
to effective dipoles larger than μ. This means that using μ = 4.76 D, E = 200 kV
cm
−1 , and T = 200 K as parameters, the value of μE/k B T will not exceed 0.1 for the
experiments on VEC. Therefore, strong overall molecular orientation is not expected.
The connection between net orientation, cosθ , and field E is the Langevin relation
which is approximately cosθ = a/3 for a dipole gas, with a = μE/k B T. Regardless
of these considerations, even fields as small as 37 kV cm
−1 give rise to substantial
changes in the crystallization rates and outcomes, see Fig. 7.
It is a reasonable question to ask whether the observations shown here are specific
to VEC or possibly of a more general nature. VEC is a compound of a family of
derivatives of propylene carbonate (PC), which are highly polar materials [41]. PC
itself is a simple liquid in the sense that the Kirkwood correlation factor is near unity
in the viscous regime [42], and similar behavior may be expected for its vinyl derivative VEC. Therefore, in the absence of properties that are highly particular for VEC
apart from a considerable polarity, it is likely that the field effects outlined here may
be found in numerous other substances. Many pharmaceutical materials have similarly high dielectric constants, and field-induced alternative crystal structures may
provide materials with the same chemistry but improved shelf-life, bioavailability,
and solubility [43, 44].
Other systems for which static electric fields are expected to impact crystallization
outcomes and generate new polymorphs are those that already show more that one
crystal structure [45] in the absence of a field. A prime example of such a case is
ROY, a pharmaceutical precursor compound, 5-methyl-2-[(2-nitrophenyl)amino]-3thiophenecarbonitrile, that is named for its red, orange, and yellow crystals. ROY is
known to form 10 different crystal structures under ambient conditions [46]. Computationally, many more stable structures have been predicted [47], and chances are that
some of these might be found by crystallization under the influence of static electric
fields.
165
Indications that static external electric fields could affect the crystallization
process had been reported previously [28–30]. For example, relatively small electric fields of 2-8 kV cm
−1 applied during the crystallization of proteins increased
the nucleation and growth rate [31–33]. Electric fields have also been made responsible for shifting preference towards one polymorphic form of glycine over another
when crystallized from solution [34, 35]. In terms of the origin of these field-induced
effects, contributions from field-dependent thermodynamic potentials [6–8] as well
as field-induced orientations have been discussed [36, 37]. In general, the detailed
mechanism involved in such field effects on crystallization have not been identified
[38].
In the case of crystallization from solution, e.g., water, the field effect may be
indirect through structural changes in the solvent. In the present case of VEC, the
situation is simpler as this is a pure substance with no significant tendency to form
supermolecular structures by directional bonding (such as hydrogen bonds). VEC
is a simple liquid in the sense that its high dielectric constant of about 79 (at T =
183 K) [39] is largely determined by the high molecular dipole moment of μ =
4.76 D [40], with no indication of strong orientational dipole correlation that leads
to effective dipoles larger than μ. This means that using μ = 4.76 D, E = 200 kV
cm
−1 , and T = 200 K as parameters, the value of μE/k B T will not exceed 0.1 for the
experiments on VEC. Therefore, strong overall molecular orientation is not expected.
The connection between net orientation, cosθ , and field E is the Langevin relation
which is approximately cosθ = a/3 for a dipole gas, with a = μE/k B T. Regardless
of these considerations, even fields as small as 37 kV cm
−1 give rise to substantial
changes in the crystallization rates and outcomes, see Fig. 7.
It is a reasonable question to ask whether the observations shown here are specific
to VEC or possibly of a more general nature. VEC is a compound of a family of
derivatives of propylene carbonate (PC), which are highly polar materials [41]. PC
itself is a simple liquid in the sense that the Kirkwood correlation factor is near unity
in the viscous regime [42], and similar behavior may be expected for its vinyl derivative VEC. Therefore, in the absence of properties that are highly particular for VEC
apart from a considerable polarity, it is likely that the field effects outlined here may
be found in numerous other substances. Many pharmaceutical materials have similarly high dielectric constants, and field-induced alternative crystal structures may
provide materials with the same chemistry but improved shelf-life, bioavailability,
and solubility [43, 44].
Other systems for which static electric fields are expected to impact crystallization
outcomes and generate new polymorphs are those that already show more that one
crystal structure [45] in the absence of a field. A prime example of such a case is
ROY, a pharmaceutical precursor compound, 5-methyl-2-[(2-nitrophenyl)amino]-3thiophenecarbonitrile, that is named for its red, orange, and yellow crystals. ROY is
known to form 10 different crystal structures under ambient conditions [46]. Computationally, many more stable structures have been predicted [47], and chances are that
some of these might be found by crystallization under the influence of static electric
fields.