Electric-field triggered controlled release of bioactive volatiles from imine-based liquid crystalline phases

Article abstract of DOI:10.1002/chem.200801782

Application of an electric field to liquid crystalline film forming imines with negative dielectric anisotropy, such as N-(4-methoxybenzylidene)-4- butylaniline (MBBA. 1), results in the expulsion of compounds that do not participate in the formation of t

Full text of DOI:10.1002/chem.200801782

FULL PAPER
DOI: 10.1002/chem.200801782
Electric-Field Triggered Controlled Release of Bioactive Volatiles from
Imine-Based Liquid Crystalline Phases
Andreas Herrmann,[a] Nicolas Giuseppone,[b, c] and Jean-Marie Lehn*[b]
Abstract: Application of an electric
field to liquid crystalline film forming
imines with negative dielectric aniso-
tropy, such as N-(4-methoxybenzyli-
dene)-4-butylaniline (MBBA, 1), re-
sults in the expulsion of compounds
that do not participate in the formation
of the liquid crystalline phase. Further-
more, amines and aromatic aldehydes
undergo component exchange with the
imine by generating constitutional dy-
namic libraries. The strength of the
electric field and the duration of its ap-
plication to the liquid crystalline film
influence the release rate of the ex-
AHCTUNGTRENGNpUN elled compounds and, at the same
time, modulate the equilibration of the
dynamic libraries. The controlled re-
lease of volatile organic molecules with
different chemical functionalities from
the film was quantified by dynamic
headspace analysis. In all cases, higher
headspace concentrations were detect-
ed in the presence of an electric field.
These results point to the possibility of
using imine-based liquid crystalline
films to build devices for the controlled
release of a broad variety of bioactive
volatiles as a direct response to an ex-
ternal electric signal.
Keywords: controlled release
·
dynamic combinatorial chemistry ·
electric fields
crystals
· imines · liquid
Introduction
ceutical applications,[3] but also for the release of flavours
and fragrances in foods or cosmetics.[4,5] In most cases, a dif-
fusion-controlled release of the active compound from the
liquid crystalline phases was reported.
As a consequence of their well-organised structures, liquid
crystals have found numerous applications in display tech-
nology, optical data storage, non-linear optics, high-perform-
ing polymers, and as delivery vehicles for bioactive
matter.[1,2] Depending on the molecular structure and com-
position of the liquid crystalline phase forming materials,
they can exist in various phases that are used as particles,
gels, capsules or waxes for the encapsulation of active sub-
stances into the (lamellar or cubic) liquid crystalline phase.
Liquid crystalline systems, especially those in polymeric
forms, have served for the slow release of drugs in pharma-
Due to rapid evaporation on exposure to air, the percep-
tion of volatile bioactive compounds is quite limited in time.
As the performance of a perfumed or flavoured consumer
article is dependent on the concentration of the respective
compound in the air at a given time, the development of de-
livery systems for the controlled release of volatiles has
become a major area of research in life sciences. Besides de-
livery systems that release compounds slowly over time,[6,7]
there is considerable interest in the development of delivery
systems that can rapidly release active substances using an
external trigger, thus allowing their use as olfactive stimuli-
response materials in air-freshening, insect attractant/repel-
lent or signalling devices. A rapid response to the external
trigger is thus a prerequisite for a well-performing delivery
system of this type. Due to their polarity and/or chemical
nature, only a restricted selection of active materials can be
successfully released from individual capsules or conju-
gates.[6,7] Electric triggers are generally less sensitive towards
the polarity and chemical functionality of bioactive mole-
cules, and are therefore of interest in the release of a broad
variety of compounds from a suitably designed device. The
use of electric fields to release molecules, by inducing a
phase change of polymeric liquid crystalline compounds, has
[a] Dr. A. Herrmann
Firmenich SA, Division Recherche et Dꢀveloppement
1 route des Jeunes, B.P. 239, 1211 Genꢁve 8 (Switzerland)
[b] Prof. Dr. N. Giuseppone, Prof. Dr. J.-M. Lehn
ISIS, Universitꢀ Louis Pasteur, 8 allꢀe Gaspard Monge
B.P. 70028, 67083 Strasbourg Cedex (France)
E-mail: lehn@isis.u-strasbg.fr
[c] Prof. Dr. N. Giuseppone
Present address: SAMS Laboratory, Universitꢀ Louis Pasteur
icFRC and Institut Charles Sadron CNRS—UPR 22
23 rue du Loess, B.P. 84047, 67034 Srasbourg Cedex 2 (France)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200801782.
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117

been investigated for polypeptides.[8] Furthermore, it was re-
cently reported that layer-by-layer assembled thin films re-
lease encapsulated compounds by destabilisation of the as-
sembled structure under the effect of an electric field.[9] The
films reacted to small electrochemical potentials and were
found to re-stabilise once the applied potential was re-
moved. However, the layer-by-layer directed self-assembly
requires the incorporated material to possess well-defined
complementary functionalities.
During our investigations on dynamic combinatorial
chemistry (DCC) using reversible covalent reactions to set-
up constitutional dynamic libraries (CDLs),[10] we became
interested in developing adaptive chemical systems that can
be modulated by component exchange as a result of exter-
nal physical parameters (as for example phase transitions[11]
or temperature changes[12]), or by chemical triggers (such as
variations in pH[12,13] or the presence of metal ions[13,14]).
Furthermore, in this context, we recently reported that elec-
tric fields influence the equilibrium mixtures of constitution-
ally related and interconvertible compounds.[15] Application
of an electric field to liquid crystalline type imines with a
negative dielectric anisotropy, such as N-(4-methoxybenzyli-
dene)-4-butylaniline (MBBA, 1) or its ethoxy analogue, re-
sulted in the observation that compounds that do not partic-
ipate in the formation of the nematic phase, as for example
cyclopentanol, are expelled from the liquid crystal in the
presence of an electric field. Compounds that can react with
the liquid crystalline phase forming imines undergo compo-
nent exchange at the isotropic and nematic phase transition,
as illustrated in Scheme 1a for the reaction between 1 and
cyclopentylamine.[15]
lease of amines (Scheme 1a) or carbonyl compounds
(Scheme 1b).
Results and Discussion
Electric field-dependent expulsion of compounds that do
not participate in the liquid crystalline phase formation: To
demonstrate the expulsion of volatile compounds during the
formation of the liquid crystalline phase under the influence
of an electric field, a homogenised mixture of liquid crystal-
line phase-forming imine 1 and cyclopentanol (44 mol%)
was placed as a film between two commercially available
indium tin oxide (ITO) coated glass plates (7.25ꢃ2.5 cm).
To apply high enough voltages while keeping the resistivity
below 6ꢃ107 WcmÀ1 (to avoid decomposition of the com-
pounds by the electric current) ideally the film has to be
very thin.[15] A film of about 21 mm (Æ5%) thickness was
obtained by pipetting 38 mL of the alcohol/imine mixture
onto one of the ITO plates and by slightly pressing another
slide on top of it in such a way to cover most of the surface
between the two glass plates with the film (ca. 17.5 cm2).
The glass plates were each connected at one end to either
one of the poles of a benchtop power supply, which was ad-
justed to generate a tension between 0 and 75 V. The film
was then exposed to a constant voltage (75 V, corresponding
to 3.6ꢃ104 VcmÀ1). Due to the opacity of the nematic phase
formed upon application of the voltage, the isotropic/nemat-
ic phase transition could be observed with the naked eye.[15]
After eight hours the experiment was stopped, and the film
1
was rinsed off the plates with CDCl3. H NMR spectroscopy
Based on the promising results obtained for the pH-de-
pendent controlled release of volatiles from dynamic mix-
tures comprising hydrazones,[16] we now investigated the po-
tential of releasing volatiles from liquid crystalline phase-
forming imines triggered by an electric field. In a first step
we studied the expulsion of compounds that do not partici-
pate in the liquid crystalline phase formation (alcohols,
esters, lactones or nitriles), in a second step we investigated
the possibility of component exchange for the controlled re-
revealed that the amount of remaining cyclopentanol in the
film was 8.5 mol%. If no electric field was applied, the re-
maining amount of cyclopentanol was found to be 37 mol%.
When keeping the mixture in a closed vial no change in the
composition was observed after two hours.
That the loss of cyclopentanol observed in the presence of
the electric field was not the result of a variation in temper-
ature was verified by heating the ITO plates in the absence
of the field. Heating, even by tens of degrees, resulted in a
much smaller loss of cyclopen-
tanol than was observed with
the electric field.[15] NMR anal-
ysis showed that the composi-
tion of a solution of 1 and
cyclopentanol in CDCl3, which
was kept between 22.5 and
308C for 2 h, remained un-
changed. Similarly, the applica-
tion of pressure (7 kgcm2) to a
film of 1 and cyclopentylamine
(4:1) had no influence on the
composition of the mixture.[17]
To follow the evaporation of
the volatile compounds in the
presence of the electric field,
we investigated the expulsion
Scheme 1. Principle of constitutional reorganisation by component exchange of MBBA (1) with cyclopentyl-
ACHTUNGTRENNUNGamine (a) or benzaldehyde (b) in the presence of an electric field.
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Controlled Release from Liquid Crystalline Phases
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of the compounds from the liquid crystalline phase as a
function of the applied voltage by dynamic headspace analy-
sis.[18] For practical reasons (especially to avoid displacement
of the glass plates while positioning them inside the head-
space cell) and to increase the amount of compounds to be
placed between the glass slides, two Teflon strips were used
as spacers to ensure a constant distance between the slides.
The thickness of the resulting liquid crystalline film was thus
increased to about 0.1 mm, which allowed the deposition of
100 mL of the mixture.
For the measurements, cyclopentanol was added to
MBBA (1), and the mixture was placed between the coated
sides of two ITO glass slides. The slides were pressed togeth-
er to form a uniform and transparent film covering almost
the entire surface between the slides, before being fixed on
a glass support. The total set-up was then placed inside a
homemade headspace sampling cell (Figure 1) and connect-
Figure 2. Comparison of the average headspace concentrations measured
for the evaporation of cyclopentanol from a liquid crystalline film of 1
after application of 0 V (~), 60 V (*) and 75 V (&).
for all measurements are listed in the Supporting Informa-
tion.
The liquid crystalline film between the two glass slides re-
mained transparent during the measurement, but turned to
a slightly brownish-yellow colour. Small opaque areas, corre-
sponding to the formation of the nematic phase, were
formed along the outer borders of the ITO slides. At the
end of the headspace sampling, the film was dissolved with
CDCl3, analysed by NMR spectroscopy and compared to
the original mixture from the start of the experiment. The
original mixture contained 70 mol% of cyclopentanol,
whose amount at the end of the measurement was deter-
mined to be 41, 33 and 22 mol% after being exposed to a
voltage of 0, 60 and 75 V for 375 min (6.25 h), respectively.
The data (before and after the measurement) show that
with increasing voltage of the applied electric field an in-
creasing amount of cyclopentanol was evaporated from the
film. The film of the reference sample (where no voltage
was applied) remained transparent and did not change its
original colour (slightly yellow).
Figure 1. Set-up of the headspace sampling cell (inner cell volume ca.
625 mL).
No evidence for the formation of degradation products
was observed in the NMR spectra. Nevertheless, it is inter-
esting to note that an arboresque-like, insoluble brownish
film of unknown composition remained at the ITO surface
which was connected to the anode.
ed to the two poles of a benchtop power supply. A constant
flow of air (ca. 206 mLminÀ1) was aspirated through a filter
of activated carbon, a saturated solution of NaCl (to ensure
a constant air humidity of ca. 75%),[19] and then through the
headspace cell. The expelled volatiles were trapped at con-
stant time intervals on Tenax cartridges. During the entire
measurement, the voltage on the power supply was fixed at
either 60 or 75 V, resulting in an electric field of 6000 and
7500 VcmÀ1, respectively. As a control experiment carried
out in parallel, no tension was applied to the slides. Twelve
samples were taken altogether, and the cartridges were ther-
mally desorbed and analysed by GC. Headspace concentra-
tions of cyclopentanol (in ng per litre of air) were deter-
mined by external standard calibration.
The headspace data show that the experiment is quite re-
producible, and similar results were obtained by using either
new or previously used ITO glass plates. Even the insoluble
brownish film seems to have no influence on the experiment
(the slides were re-used in the following experiments).
In similar experiments, mixtures of terpene alcohols (+)-
(R)-citronellol (2), (À)-(1R,2S,5R)-menthol (3) and (Æ)-li-
nalool (4) or benzyl acetate (5), (Æ)-4-octanolide (6), and
(Æ)-2-methyldecanenitrile (7) were added to 1, respectively.
The homogenised clear solutions were deposited as thin
films between two ITO-coated glass slides and analysed
after application of a voltage of 0 (reference) and 75 V as
described above. The data obtained for the release of ter-
pene alcohols 2–4 are shown in Figure 3; those for the ester,
lactone and nitrile 5–7 are depicted in Figure 4.
All experiments were carried out in triplicate. The aver-
age headspace concentrations measured for the release of
cyclopentanol from the liquid crystalline film are illustrated
in Figure 2; the absolute headspace concentration obtained
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J.-M. Lehn et al.
1
Analysis of the H NMR data before and after the experi-
ment (performed only once for each series) confirmed the
trend observed from the headspace measurements. Howev-
er, due to a considerable peak overlap and the small
amounts of volatiles relative to butylaniline derivative 1, the
1H NMR integration data were found to be less precise than
the headspace measurements.
The formation of the brownish film on the slide connected
to the anode of the power supply (see above) was found to
be significantly less pronounced in the experiments with
compounds 2–7, as compared to the previous experiments
with cyclopentanol.
Besides the voltage of the applied electric field, the
amount of volatiles released during the experiment depends
on the vapour pressure (volatility) of the respective com-
pounds. The calculated vapour pressures of 2.25 (2), 2.58
(3), 3.54 (7), 3.96 (6), 11.09 (4) and 24.93 Pa (5)[20] roughly
account for the measured headspace concentrations of the
different compounds, with the highest concentrations of
each series corresponding to the most volatile compound (li-
nalool (4), and benzyl acetate (5)), and the lowest concen-
trations for the least volatile compounds (citronellol (2) and
2-methyldecanenitrile (7)).
Figure 3. Comparison of the average headspace concentrations measured
for the evaporation of alcohols 2 (&, &), 3 (*, *) and 4 (~, ~) from a
liquid crystalline film of 1 in the presence (solid line) or absence (dotted
line) of an applied electric field.
The measurements show that a voltage-dependent release
of bioactive volatiles by expulsion from the liquid crystalline
film is possible, even if compound mixtures are used. Fur-
thermore, with the human olfactory thresholds of fragrances
2–5 being at 46, 269, 347 and 912 ngLÀ1, respectively,[21] the
measured headspace concentrations all lie far above this
threshold value, and the compounds can thus easily be de-
tected by humans for the entire duration of the experiment.
Electric field-dependent expulsion of compounds under-
going component exchange with the liquid crystalline phase-
forming imine: If compounds that react reversibly with the
liquid crystalline phase-forming imine were added (such as
primary and secondary amines), component exchange by
transamination was observed.[15] The composition of the
final mixture was thereby influenced by the presence or ab-
sence of an electric field. For example, a mixture of MBBA
(1) with cyclopentylamine (64 mol%) gave, after equilibra-
tion in a closed vial for 20 h, a mixture containing only
33 mol% of 1. A content of 38 mol% of 1 was obtained
when the mixture was placed between the ITO glass plates
without applying an electric field. However, the presence of
an electric field (3.1ꢃ104 VcmÀ1) shifted the equilibrium to
69 mol% of 1 in the final composition. Similarly, a 2:1 mix-
ture of 1 and benzylamine gave an equilibrium containing
only 6 mol% of 1 after 20 h in a closed vial, 8 mol% when
placed between the ITO plates, but 25 mol% when the elec-
tric field was applied for the same period of time. In both
cases the formation of the liquid crystalline film forming
imine 1 was favoured in the presence of the electric field.
Replacing the liquid crystal by pentaethyleneglycol
(having the same viscosity as 1) and applying the electric
field (3.0ꢃ104 VcmÀ1) on a mixture with cyclopentylamine
for 4 h showed that exactly the same amount of cyclopentyl-
amine was evaporated in the presence or absence of the
Figure 4. Comparison of the average headspace concentrations measured
for the evaporation of compounds 5 (&, &), 6 (*, *) and 7 (~, ~)
from a liquid crystalline film of 1 in the presence (solid line) or absence
(dotted line) of an applied electric field.
The headspace data recorded for the release of 2–7 gener-
ally showed larger standard deviations than in the previous
experiment with cyclopentanol (see the Supporting Informa-
tion). In the case of 2, this may be due to the fact that the
response of the compound at the FID-detector of the GC is
relatively small, resulting in smaller peak areas. Further-
more, in one of the experiments with the terpene alcohols,
the film between the two glass plates was less regularly
spread, thus causing possible slight variations in the film
thickness. Nevertheless, the data were found to be reprodu-
cible and, in all cases, the presence of the electric field in-
creased the amounts of volatiles released from the system.
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electric field, and that the expulsion of the compound is in
fact the result of the applied electric field to the liquid crys-
talline phase.
This was also observed when an equimolar mixture of
amines 8-11 (each at 25 mol% with respect to 1) was equili-
brated with imine 1. Transamination gave rise to four addi-
exchange and release of the aldehyde part of the imine was
also possible. The reversible formation of imines requires
the presence of at least trace amounts of water, which could
be present either in the film or result from ambient humidi-
ty. We thus investigated the effect of the electric field on the
evaporation of a series of aromatic aldehydes and ketones
to be exchanged with 1, by dynamic headspace analysis, as
described above. Benzaldehyde (16), 4-ethylbenzaldehyde
(17) and acetophenone (18) were chosen as the volatiles to
be released. If the carbonyl compounds react with the imine
tional imines 12–15, which were quantified by 1H NMR
spectroscopy (in CDCl3) after 18 h of equilibration in a
closed vial, as a film between two ITO glass slides (without
application of an electric field) and between two glass slides
in the presence of an electric field (3.0ꢃ104 VcmÀ1), respec-
tively. The composition of the equilibrated mixtures is given
in Table 1.
by component exchange, 4-methoxybenzaldehyde (19) is ex-
pected to be generated and released into the headspace by
expulsion from the liquid crystalline phase-forming imine.
1H and 13C NMR spectroscopy, as well as GC/MS analysis of
the film after the analysis, combined with a comparison of
GC retention times of the headspace samples, confirmed the
formation of 19, both in the presence and absence of the
electric field. Furthermore, the generation of N-(benzyli-
dene)-4-butylaniline (20) and N-(4-ethylbenzylidene)-4-
butylaniline (21) was demonstrated, whereas the formation
of the corresponding ketone derivative of acetophenone 22
was not observed. The identity of imines 20 and 21 was con-
firmed by synthesis of the reference compounds[22] and com-
parison of their spectroscopic data. The headspace data
measured in the presence and absence of the electric field
(average of two measurements) are illustrated in Figure 5.
In a similar experiment, 16, 18 and 19 were mixed togeth-
er and added to N-(4-ethylbenzylidene)-4-butylaniline (21).
The film of the compound mixture was then exposed to a
Table 1. Composition of an equilibrated mixture of imine 1 with amines
1
8–11 determined by H NMR spectroscopy.
Compound Composition [mol%] after 18 h of equilibration
in a closed vial between ITO plates between ITO plates
without electric field with electric field
(3ꢃ104 VcmÀ1
)
1
27.7
13.6
20.6
16.2
21.9
34.3
8.8
17.8
17.0
22.1
49.9
5.5
7.7
15.6
21.3
12
13
14
15
Depending on the equilibration conditions, mixtures with
a variable content of imines 12–15 were obtained. In the
presence of the electric field the amount of 1 in the equili-
brated mixture remained at 50 mol%, whereas in the ab-
sence of the field it dropped to a value below 35 mol%. The
electric field favours the formation of a liquid crystalline
film of 1, and the resulting electro-rheological effect expels
the amines which do not participate in the formation of the
liquid crystalline film. Interestingly, the amounts of 14 (ca.
16 mol%) and 15 (ca. 22 mol%) remained constant in all
three samples, which is presumably due to the fact that the
corresponding amines 10 and 11 are the least volatile
amines of the series, with vapour pressures of 26.5 and
0.8 Pa, respectively. The more volatile analogues 8 and 9
(257.0 and 44.5 Pa) are expelled first, which decreases the
amount of imines 12 and 13 in the mixture in favour of the
liquid crystalline phase-forming imine 1.
Figure 5. Comparison of the average headspace concentrations measured
for the evaporation of carbonyl compounds 16 (&, &), 17 (*, *), 18
(ꢃ) and 19 (~, ~) from a liquid crystalline film of 1 in the presence
(solid line) or absence (dotted line) of an applied electric field.
Because amines are less interesting as bioactive com-
pounds to be released, we were interested to see whether an
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121

J.-M. Lehn et al.
voltage of 75 V or 0 V (reference) as described above.
Again, the headspace concentrations of 16, 18, and 19 con-
tinuously decreased during the experiment and an increasing
amount of 4-ethylbenzaldehyde (17) was formed over time
by component exchange (Figure 6), thus illustrating the gen-
eral nature of the principle. In all cases, the presence of the
electric field afforded higher headspace concentrations than
the reference sample without an electric field, and the head-
space concentrations still correlated with the vapour pres-
sures of the volatiles (16: 134.6 Pa, 18: 43.5 Pa, 17: 16.6 Pa
and 19: 4.0 Pa).[20]
imines,[23] and volatile compounds are more readily expelled
from the liquid crystalline film than non-volatiles. Liquid
crystalline forming imines are therefore suitable materials to
modulate controlled release of volatile organic compounds
by application of an electric field and point to the possibility
of constructing electric devices that allow fine-tuning of the
release rates of individual compounds and compound mix-
tures as a direct response to an electric signal.
In “classical” delivery systems, the release rates of the
active compounds are defined by structural aspects that
define the diffusion rates of the compounds from an encap-
sulating matrix or capsule[6] or the kinetics of a given cova-
lent bond cleavage,[7] as well as by external parameters such
as temperature or pH. The use of an electric field as the
trigger allows the design of delivery systems that are inde-
pendent of the chemical functionalities of the compounds to
be released. Other parameters, such as a change in tempera-
ture, were found to present much weaker effects than the
application of an electric field. The strength of the electric
field and the duration of its application directly modulate
the release of the active compounds as a function of their
vapour pressures. Such a feature is of major interest for the
efficient release of a broad variety of biologically active
compounds in the area of life sciences.[24]
Figure 6. Comparison of the average headspace concentrations measured
for the evaporation of carbonyl compounds 16 (&, &), 17 (*, *), 18
(ꢃ) and 19 (~, ~) from a liquid crystalline film of 21 in the presence
(solid line) or absence (dotted line) of an applied electric field (single
measurement).
Experimental Section
General: If not stated otherwise, commercially available reagents and
solvents were used without further purification. Reactions were carried
out in standard glassware under N2, and yields were not optimised. ITO
coated glass slides were purchased from Aldrich (ca. 7.0ꢃ2.5 cm, 70–
100 ohm resistance, ref. 576352). Electric fields were generated with a
Thurlby Thandar Instruments (TTi) EX752M 75 V/150 V multimode
benchtop power supply, operated between 0 and 75 V. UV/Vis spectra
were recorded on a Perkin–Elmer Lambda 14 spectrometer, l in nm (e),
1H NMR analysis of the film before and after the experi-
ment correlated with the headspace data, with the exception
of acetophenone, where a higher concentration was mea-
sured after the headspace sampling. As the component ex-
change also takes place in the absence of the electric field, it
should be noted that no absolute values corresponding to
the mixture at the beginning of the measurement could be
obtained by NMR spectroscopy, as component exchange in
the NMR tube could not be excluded.
With the human olfactory thresholds of 16 and 18 being
at 186 and 1820 ngLÀ1, respectively,[21] the measured head-
space concentrations lie far above these threshold values,
and the compounds can thus easily be detected by humans
for the entire duration of the experiment.
IR spectra on a Spectrum One FTIR spectrometer, n˜ in cmÀ1 1H and
.
13C NMR spectra were recorded at 258C on a Bruker 400 MHz DPX or
Avance spectrometer, d in ppm downfield from Me4Si as internal stan-
dard, J in Hz. GC-MS (EI) measurements were performed on a Hewlett
Packard HP 5890 or 6890 GC System equipped with a Supelco SPB-1 ca-
pillary column (30 m, 0.25 mm i.d.) at 708C for 10 min then to 2608C
(108CminÀ1), helium flow about 1 mLminÀ1, coupled to a HP MSD 5972
or 5973 quadrupole mass spectrometer, electron energy about 70 eV,
fragment ions m/z (rel. int. in% of the base peak).
Standard compound expulsion and crossover experiments: In a typical
protocol the compounds were mixed in a closed vial, the mixture was
heated up to 608C for 5 min, then cooled to room temperature and left
for 2 h. A total of 38 mL (Æ5%) of the neat mixture was then placed be-
tween the coated sides of two ITO glass slides using a microsyringe. The
slides were gently pressed together to obtain a thin film (21 mm, Æ5%)
covering the entire surface (ca. 18.1 cm2). The slides were then thermo-
statted and connected to the different poles of the power supply. The
electric field was applied with values between 0 and 75 V (for an applied
field of 75 V, the experimental error led to a value of 3.5ꢃ104 VcmÀ1
(Æ0.15ꢃ104 VcmÀ1, Æ5%). After a given time, the electric field was shut
off, and the mixture between the two ITO slides dissolved in CDCl3
(2 mL). 1H NMR measurements were carried out within 5 min after dis-
solution of the film. For experiments with both fields and the thermostat-
ted control experiment (without field and set up using the same initial
Conclusions
Application of an electric field to liquid crystalline film-
forming imines with negative dielectric anisotropy results in
the expulsion of compounds that do not participate in the
formation of the liquid crystalline phase. If these compounds
can reversibly react with the imine by component exchange,
the field influences the equilibrium state of constitutional
dynamic mixtures of imines. Both amines and aldehydes are
exchanged upon formation of a CDL of the corresponding
1
mixture), H NMR spectra were recorded until stabilisation of the equili-
bria. The values for the changes in sample composition were obtained
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Controlled Release from Liquid Crystalline Phases
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from comparison of the spectra for the two corresponding experiments
after the same time of equilibration in solution.
nol): l (e)=324 (11700), 264 (18000), 241 (12400), 232 (sh, 13100),
224 nm (14900); MS (EI): m/z (%): 238 ([M+1]+, 7), 237 ([M]+, 37),
195 (16), 194 (100), 193 (3), 91 (3), 90 (6), 89 (6), 77 (3).
Headspace measurements: The liquid crystalline phase mixture was pre-
pared by adding 20 mL of the volatiles to 200 mL of 1. A total of 100 mL
of the homogenised mixture was then placed onto the coated side of an
ITO-coated glass slide. To keep a constant distance between the two
slides, a Teflon film (0.1 mm thickness) was placed at each end of the
glass slide. The ITO glass slide was then covered with a second slide in
such a way that the coated side was in contact with the solution, and that
the slides were not completely superimposed on their smaller side (so as
to fix a crocodile clamp on opposite sides of each glass slide). The slides
were then pressed together to form a uniform and transparent film cover-
ing almost the whole surface between the slides. The set-up was taped to
a glass support and placed inside a home-made headspace sampling cell
(average volume ca. 625 mL) with the cables to the power supply passing
through a Teflon stopper at the top of the cell, allowing a gas-tight fixing
of the cables to the power supply. During the measurements, a constant
flow of air was aspirated through a set-up composed of a filter of activat-
ed carbon (Norit RB 1 0.6, pellets), a wash bottle containing a saturated
solution of NaCl (humidity of the air ca. 75%),[19] a second, empty wash
bottle, the headspace cell, and a Tenax cartridge containing 100 mg of
Tenax-TA (Varian). For the headspace sampling, a Gilian dual mode low
flow sampler pump was used, which was calibrated at a flow rate of
about 206 mLminÀ1. All measurements were carried out in triplicate, if
not stated otherwise, with the voltage on the power supply fixed at 60 or
75 V, respectively. The measurements were started by switching on the
pump and, after 1 min, the voltage. No current was measured on the
power supply during the experiment. The system was equilibrated for
10 min while sampling on a waste Tenax cartridge. After 10 min, the
waste cartridge was replaced with a clean one, and the volatiles were
trapped for 1 (cyclopentanol) or 2 min (all other compounds) onto a
clean cartridge. Then the waste cartridge was replaced. In each case a
control experiment was carried out in parallel under the same conditions,
without however applying any voltage to the ITO plates. Altogether 12
samples were taken. In the experiment with cyclopentanol, the sampling
was repeated every 29 min during 1 min, in all other experiments the
sampling was repeated every 28 min during 2 min. The cartridges were
thermally desorbed on a Perkin–Elmer TurboMatrix ATD desorber and
analysed on a Carlo Erba MFC 500 gas chromatograph equipped with a
I&W Scientific DB1 capillary column (30 m, i.d. 0.45 mm, film 0.42 mm)
and FID detector. The volatiles were analysed using a two-step tempera-
ture gradient starting from 708C to 1308C at 38CminÀ1 and then rising to
2608C at 258CminÀ1. The detector temperature was at 2608C. Headspace
concentrations (in ng per litre of air) were determined by external stan-
dard calibration. The calibrations were effected by using acetone solu-
tions at eight different concentrations; 0.4 mL of each calibration solution
were injected onto a clean Tenax cartridge. All the cartridges were desor-
bed immediately with increasing concentration under the same conditions
as those resulting from the headspace sampling. Plotting the concentra-
tions (in ngLÀ1) against the peak areas gave straight lines with a correla-
tion coefficient of r2 >0.992.
Synthesis of 4-butyl-N-[(1E)-(4-ethylphenyl)methylene]aniline (21): As
described for 20 with 4-ethylbenzaldehyde (17, 1.74 g, 13.0 mmol and
0.35 g, 2.6 mmol) to give
a
brownish oil (3.92 g (quant.)). 1H NMR
(400 MHz, CDCl3): d=8.44 (s, 1H), 7.81 (d, J=7.6 Hz, 2H), 7.29 (d, J=
8.2 Hz, 2H), 7.22–7.10 (m, 4H), 2.71 (q, J=7.5 Hz, 2H), 2.62 (t, J=
7.7 Hz, 2H), 1.67–1.56 (m, 2H), 1.37 (hex., J=7.5 Hz, 2H), 1.27 (t, J=
7.4 Hz, 3H), 0.94 ppm (t, J=7.4 Hz, 3H); 13C NMR (100.6 MHz, CDCl3):
d=159.59 (d), 149.83 (s), 147.93 (d), 140.66 (s), 134.06 (s), 129.08 (d),
128.81 (d), 128.30 (d), 120.78 (d), 35.19 (t), 33.72 (t), 28.95 (t), 22.35 (t),
15.39 (q), 13.98 ppm (q); IR (neat): n˜ =3049w, 3023w, 2959m, 2927m,
2871m, 2856m, 2730w, 1912w, 1898w, 1803w, 1772w, 1703w, 1626s,
1598m, 1568m, 1511m, 1502m, 1455m, 1417m, 1376w, 1363w, 1306w,
1260w, 1240w, 1192m, 1168s, 1112m, 1059m, 1050m, 1016m, 975m,
942w, 928w, 885m, 832s, 800m, 748m, 728m, 699w, 660w, 642w, 637w
cmÀ1; UV/Vis (ethanol): l (e)=319 (13600), 270 (19000), 226 (15000),
203 nm (28500); MS (EI): m/z (%): 266 ([M+1]+, 9), 265 ([M]+, 40),
223 (19), 222 (100), 207 (8), 206 (5), 91 (8), 90 (5), 89 (3), 77 (3).
Acknowledgements
We thank Dr. J.-Y. de Saint Laumer for the calculation of the vapour
pressures, B. Levrand for the preparation of compounds 20 and 21, and
Dr. Roger Snowden for constructive comments on the manuscript.
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Synthesis of 4-butyl-N-[(1E)-phenylmethylene]aniline (20): A solution of
4-butylaniline (2.0 g, 13.4 mmol) and benzaldehyde (16, techn., contain-
ing benzoic acid, 1.42 g, 13.4 mmol) in ethanol (150 mL) was heated
under reflux for 42–44 h. Then more 16 (0.71 g, 6.7 mmol) was added and
the mixture was left stirring under reflux overnight. After cooling to
room temperature, the reaction mixture was concentrated and the re-
maining volatiles were removed by bulb-to-bulb distillation to give a
brownish oil (3.47 g (quant.)). 1H NMR (400 MHz, CDCl3): d=8.47 (s,
1H), 7.92–7.85 (m, 2H), 7.49–7.42 (m, 3H), 7.23–7.12 (m, 4H), 2.63 (t,
J=7.9 Hz, 2H), 1.67-1.56 (m, 2H), 1.43–1.31 (m, 2H), 0.94 ppm (t, J=
7.4 Hz, 3H); 13C NMR (100.6 MHz, CDCl3): d=159.56 (d), 149.61 (s),
140.89 (s), 136.39 (s), 131.17 (d), 129.11 (d), 128.72 (d), 128.71 (d), 120.80
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1813w, 1759w, 1704w, 1627m, 1598m, 1577m, 1504m, 1464m, 1450m,
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1113m, 1071m, 1024w, 1015w, 1000w, 986w, 971m 927w, 916w, 882m,
781w, 754s, 727m, 689s, 667w, 652w, 638m, 626w cmÀ1; UV/Vis (etha-
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Received: August 29, 2008
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