The influence of oligo(ethylene glycol) side chains on the self-assembly of benzene-1,3,5-tricarboxamides in the solid state and in solution

Article abstract of DOI:10.1039/b816418e

Substituted benzene-1,3,5-tricarboxamides (BTAs) 1-4 comprising polar tetraethyleneglycol (tetraEG) and/or apolar (R)-3,7-dimethyloctyl side chains were synthesised and their self-assembly in the solid state and in solution was investigated. While BTA 1 (

Full text of DOI:10.1039/b816418e

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PAPER
www.rsc.org/materials | Journal of Materials Chemistry
The influence of oligo(ethylene glycol) side chains on the self-assembly
of benzene-1,3,5-tricarboxamides in the solid state and in solution
*
´ ´
´
Patrick J. M. Stals, Jan F. Haveman, Rafael Martın-Rapun, Carel F. C. Fitie, Anja R. A. Palmans
*
and E. W. Meijer
Received 18th September 2008, Accepted 2nd October 2008
First published as an Advance Article on the web 6th November 2008
DOI: 10.1039/b816418e
Substituted benzene-1,3,5-tricarboxamides (BTAs) 1–4 comprising polar tetraethyleneglycol (tetraEG)
and/or apolar (R)-3,7-dimethyloctyl side chains were synthesised and their self-assembly in the solid
state and in solution was investigated. While BTA 1 (comprising 3 apolar side chains) shows helical
columnar packing via threefold a-helical type intermolecular hydrogen bonding in the solid state and
up to high dilutions in alkane solution (10ꢀ5 M), helical columnar order is only preserved for
asymmetric BTA 2 (comprising 1 polar and 2 apolar side chains) in the solid state and in a concentrated
alkane solution (10ꢀ2 M). The association constant Kass is reduced by a factor of 107 by introducing one
polar tetraEG chain into the BTA. A further increase in the number of polar tetraEG chains attached to
BTA core results in the complete loss of intermolecular hydrogen bond formation in the solid state and
in solution. Moreover, for the polar BTAs 3–4, comprising 2 or 3 polar tetraEG chains, no self-
assembly in water occurs because of the lack of hydrophobic shielding. We propose that tetraEG side
chains interfere with the intermolecular hydrogen bonds, weakening the stacking behaviour of these
asymmetric derivatives and drastically lowering the association constant due to competing
intramolecular hydrogen bonding interactions. In contrast, one methoxyethyl unit does not affect the
stability of the aggregation of BTAs (Kass ¼ 3 ꢁ 107 Mꢀ1) showing that more than one EG unit is
required to disrupt the self-assembly of BTAs.
chains are frequently introduced to render the supramolecular
assembly compatible with water.11 However, when the dominant
interaction of the self-assembling system is hydrogen bonding,
a hydrophobic pocket around the hydrogen bonding units is
required for finding a balance between water compatibility/
solubility and the formation of ordered aggregates. The success
of this approach was illustrated inter alia for bisureas,2e,11a
1. Introduction
The application of intermolecular hydrogen bonding as a direc-
tional and ordering interaction in (macro)organic molecules and
supramolecular polymers has attracted considerable interest
both in academic research and in industry.1 Hydrogen bonding
motifs such as bisureas,2 ureidopyrimidinones,3 cyclohexane-
1,3,5-tricarboxamides4 and benzene-1,3,5-tricarboxamides5 have
been studied in detail as gelators, hard phases in thermoplastic
elastomers, nanostructured materials, and as liquid crystals.
Especially the benzene-1,3,5-tricarboxamide (BTA) unit is of
particular interest; the amide groups are involved in strong,
threefold a-helix type intermolecular hydrogen bonding between
neighbour molecules leading to well-defined, helical, 1D
columnar aggregates.6 These supramolecular polymers behave as
organogels in a variety of solvents7 and are also stable in dilute
alkane solutions (c ¼ 10ꢀ5 M).8
cyclohexane-1,3,5-tricarboxamide
based
hydrogelators,4b,c
ureido-triazines12 and bipyridine based BTAs.13
We recently reported on the impact of attaching oligoEG
chains on the strength of hydrogen bonding interactions in
apolar solvents.14 In ureidopyrimidinones, the dimerisation
constant dropped by a factor of 1000 when an oligoEG chain was
attached while in BTAs the association constant was reduced by
a factor of 107 upon introducing one tetraEG chain. This paper is
a continuation of our work on the effect of oligoEG chains on the
self-assembly of BTAs. Although BTAs directly functionalised
with oligoEG chains are known, their self-assembly in organic
solvents or water was not discussed.15 We here discuss the
synthesis and systematic study of BTAs 1–4 (Scheme 1)
comprising 0, 1, 2 or 3 tetraEG chains. The influence of polar
oligoEG chains on the thermotropic liquid crystallinity of BTAs
is evaluated, as well as the self-assembly of compounds 1–4 in
alkane solvents and in water. As a reference, compound 5 and its
chiral analogue 6 comprising two alkyl and one methoxyethyl
side chain were prepared. A short methoxyethyl unit is selected
for comparison with the tetraEG unit since backfolding of the
oxygen and concomitant interference with the intermolecular
hydrogen bonds is unlikely. In addition, the association constant
Nowadays, supramolecular assemblies that display structure
and properties in water become increasingly important in view of
their potential in biomedical applications such as drug delivery
systems, hydrogels and tissue engineering scaffolds.9 Non-cova-
lent interactions such as hydrogen bonding, p–p stacking or ion
pairing are well known to induce order between molecules in
(aqueous) solution.10 Short oligo(ethylene glycol) (oligoEG)
Laboratory of Macromolecular and Organic Chemistry, Eindhoven
University of Technology, P. O. Box 513, 5600 MB Eindhoven, The
Netherlands. E-mail: e.w.meijer@tue.nl; Fax: +31 (0)40 2451036; Tel:
+31 (0)40 2473101
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with a Linkam THMS 600 heating device, with crossed polar-
isers. The thermal transitions of compounds 1–6 were determined
with a Perkin-Elmer Pyris 1 DSC apparatus under a nitrogen
atmosphere with heating and cooling rates of 10 K/min. The Tg
was determined with heating and cooling rates of 40 K/min.
Simultaneous WAXS and SAXS measurements for compound
2 were performed using an in-house setup with a rotating anode
X-ray generator (Rigaku RU-H300, 18 kW) equipped with two
parabolic multilayer mirrors (Bruker, Karlsruhe), which
produced a highly parallel beam (divergence about 0.012ꢂ) of
monochromatic Cu Ka radiation (l ¼ 0.154 nm). The SAXS
intensity was collected with a two-dimensional gas-filled wire
detector (Bruker Hi-Star). A semitransparent beamstop placed in
front of the area detector allowed monitoring of the intensity of
the direct beam. The WAXS intensity was recorded with a linear
position sensitive detector (PSD-50M, M. Braun, Germany),
which could be rotated around the beam path. The SAXS and
WAXS intensities were corrected by subtracting a background
that was normalized to the intensity of the direct beam. The
powder samples were prepared between two pieces of Kapton
foil (5 mm diameter, 20 mm thickness) spaced with an O-ring
(Viton, 5 ꢁ 1 mm) in a custom made brass sample holder.
A
Linkam THMS600 temperature-controlled system was
employed as sample stage. The glass windows were replaced by
thin Kapton foil (20 mm). The XRD patterns for compound
1 and 5 were obtained with a pinhole camera (Anton-Paar) which
operates with a point-focused Ni-filtered Cu-Ka beam. In this
setup, the samples were held in Lindemann glass capillaries
(0.9 mm diameter). The capillary axis was perpendicular to the
X-ray beam and the pattern was collected on a flat photographic
film perpendicular to the beam. Spacings were obtained via
Bragg’s law. 2-{2-[2-(2-Methoxyethoxy)-ethoxy]-ethoxy}-ethyl
amine was synthesised according to previously described proce-
dures.17 (R)-(+)-Citronellal (95%) was purchased from ABCR
and converted to (R)-3,7-dimethyloctylamine while18
(S)-citronellol was obtained from Takasago and converted to
(S)-3,7-dimethyloctylamine.19 Ethylene glycol dimethyl ether
was distilled prior to use.
Scheme 1 Chemical structures of compounds 1–6.
Kass is determined for compounds 5–6 and compared to the Kass
previously found for compounds 1 and 2.
2. Experimental
2.1 Materials and methods
CD and UV measurements were recorded on a Jasco J-815
spectrometer at room temperature using spectroscopic grade
2.2 Synthesis of compounds 1–4
solvents. Cells with an optical path length of 1 cm (10ꢀ5
M
solutions), 1 mm (10ꢀ4 M solutions), 0.1 mm (10ꢀ3 M solutions)
and 0.01 mm (10ꢀ2 M solutions) were employed. The association
constant Kass of compound 5 was determined by performing
A 100 mL two-necked round bottom flask was charged with
a solution of 2-{2-[2-(2-methoxyethoxy)-ethoxy]-ethoxy}-ethyl
amine (2.505 g, 12.09 mmol), triethyl amine (2.523 g, 24.93
mmol) and (R)-3,7-dimethyl-octylamine (1.915 g, 12.17 mmol)
in 25 mL of dry chloroform (amylene stabilised), and stirred
under inert atmosphere. To this mixture, a solution of 1,3,5-
benzenetricarboxylic acid chloride (1.924 g, 7.247 mmol) in 10
mL of dry chloroform (amylene stabilized), was added dropwise.
After the addition was complete, the reaction mixture was stirred
overnight at room temperature and under inert atmosphere. To
the reaction mixture, 20 mL of chloroform was added, and the
solution was washed with 25 mL 1 M HCl (check for acidity).
The organic layer was collected and evaporated to yield 5.50 g of
the crude product as a yellowish/orange oil, which also contained
solid product. Compounds 1–4 were isolated by gradient column
chromatography. Ethylene glycol dimethyl ether/n-heptane, 3/7,
was applied to afford compound 1. After compound 1 eluted
from the column (checked with TLC), the eluent was changed to
ꢂ
a sergeants-and-soldiers experiment at T ¼ 25 C as previously
described by us.16 To a solution of achiral compound 5, small
aliquots of chiral 6 were added via a syringe and the increase in
CD effect was probed at l ¼ 223 nm. The normalised CD effect
was plotted as a function of chiral 6 added and the best fit was
obtained with Kass ¼ 3 ꢁ 107 Mꢀ1 and s ¼ 60 (see ref. 16 for
1
details). H-NMR measurements were conducted on a Varian
Mercury 200 MHz. Maldi-TOF-MS were acquired using
a Perserptive Biosystem Voyager-DE PRO spectrometer. In all
cases, a-cyano-4-hydroxycinnamic acid was employed as the
matrix material. Elemental analysis was performed on a Perkin
Elmer 2400 series II CHNS/O analyser. IR spectra were recorded
at room temperature on a Perkin Elmer spectrum 1 using
a universal ATR. Polarisation optical microscopy measurements
were done using a Jenaval polarisation microscope equipped
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ethylene glycol dimethyl ether/n-heptane (7/3) to obtain
compound 2 (checked with TLC). After this, compound 3 was
obtained after changing the eluent to THF and the last product
fraction was obtained by flushing the column with THF
(or alternatively with 5% MeOH in THF). The product fractions
6H, CH3). IR n (cmꢀ1) 3234 (N–H stretch), 1639 (C]O), 1557
(amide II). Anal. Calcd for (MW ¼ 489.69 g/mol): C, 68.67; H,
9.67; N, 8.59. Found: C, 68.69; H, 9.91; N, 8.44%. Compound 6:
1H-NMR (CDCl3): d ¼ 8.29 (m, 3H, Ar–H), 6.96 (t, 1H, N–H),
6.62 (t, 2H, N–H), 3.40–3.66 (m, 8H, O–CH2, NH–CH2), 3.37
(s, 3H, O–CH3), 1.29–1.61(m, 20H, CH, CH2), 0.92 (d, 6H, CH3),
0.88 (d, 12H, CH3). IR n (cmꢀ1) 3235 (N–H stretch), 1635
(C]O), 1556 (amide II). Maldi-TOF Calcd. [M + Na+] ¼ 568.42
Da; Obs. [M + Na+] ¼ 568.31 Da.
1
(4.2 g in total) were collected and checked with H-NMR and
Maldi-TOF-MS after evaporation in vacuo.
N,N0,N00-Tri((R)-3,7-dimethyloctyl)benzene-1,3,5-tricarbox-
amide (1). Compound 1 was obtained as a white solid (0.7 g).1H-
NMR (CDCl3): d ¼ 8.34 (s, 3H, Ar–H), 6.44 (t, 3H, N–H), 3.50
(m, 6H, NH–CH2), 1.67–1.13 (m, 36H, CH, CH2), 0.94 (d, 9H,
CH3), 0.86 (d, 18H, 2 ꢁ CH3). IR n (cmꢀ1) 3226 (NH stretch),
1635 (C]O), 1563 (amide II). Maldi-TOF Calcd.
[M + Na+] ¼ 650.53 Da; Obs. [M + Na+] ¼ 650.51 Da. Anal.
Calcd for C39H69N3O6 (MW ¼ 627.97 g/mol): C, 74.59; H, 11.07;
N, 6.69. Found: C, 74.05; H, 11.20; N, 6.46%.
3. Results and discussion
3.1 Synthesis of compounds 1–6
Asymmetric benzene-1,3,5-tricarboxamides (BTAs) that
comprise both apolar and polar side chains (Scheme 1) are easily
prepared via a simple one-pot procedure by reacting benzene-
1,3,5-tricarboxylic acid chloride with a 1/1 mix of polar and
apolar amines followed by purification with column chroma-
tography. We selected 2-{2-[2-(2-methoxyethoxy)-ethoxy]-
ethoxy}-ethyl amine and (R)-3,7-dimethyloctylamine as the
reactants; the latter because its chirality provides a convenient
handle to study the self-assembly of the different derivatives with
circular dichroism (CD) spectroscopy. Both amines are acces-
sible via a straightforward synthesis and ample difference in their
polarity ensures easy separation of compounds 1–4 with gradient
column chromatography. As expected, a statistical mixture was
obtained for compounds 1–4 after column chromatography,
which indicates that both amines displayed similar reactivity.
Reference compounds 5 and 6 were synthesised and isolated in
analogy to compound 2 with the exception that methoxyethyl-
amine and n-octylamine or (S)-3,7-dimethyloctylamine were
employed as the amine mixture. The purity of all compounds
was confirmed with NMR and Maldi-ToF-MS or elemental
analysis.
N-(2-{2-[2-(2-Methoxyethoxy)-ethoxy]-ethoxy}-ethyl)-N0,N00-
di((R)-3,7-dimethyloctyl)benzene-1,3,5-tricarboxamide
(2).
Compound 2 was obtained as a white sticky product (1.4 g).1H-
NMR (CDCl3): d ¼ 8.40 (d, 3H, Ar–H), 7.65 (t, 1H, N–H), 6.67
(t, 2H, N–H), 3.68 -3.58 (m, 14 H, O–CH2), 3.48 (m, 6H,
NH–CH2), 3.21 (s, 3H, O–CH3), 1.67–1.13 (m, 24H, CH, CH2),
0.94 (d, 6H, CH3), 0.86 (d, 12H, CH3). IR n (cmꢀ1) 3238 (NH
stretch), 1637 (C]O), 1556 (amide II). Maldi-TOF Calcd.
[M + Na+] ¼ 700.50 Da; Obs. [M + Na+] ¼ 700.47 Da. Anal.
Calcd for C38H67N3O7 (MW ¼ 677.97 g/mol): C, 67.32; H, 9.96;
N, 6.20. Found: C, 67.34; H, 10.18; N, 6.16%.
N-((R)-3,7-Dimethyloctyl)-N0,N00-di(2-{2-[2-(2-methoxyeth-
oxy)-ethoxy]-ethoxy}-ethyl)benzene-1,3,5-tricarboxamide
(3).
1
Compound 3 was obtained as a colorless oil (1.4 g). H-NMR
(CDCl3): d ¼ 8.44 (m, 3H, Ar–H), 7.26 (t, 2H, N–H), 6.76 (t, 1H,
N–H), 3.68–3.58 (m, 28H, O–CH2), 3.48 (m, 6H, NH–CH2), 3.27
(s, 6H, O–CH3), 1.67–1.13 (m, 12H, CH, CH2) 0.94 (d, 3H, CH3),
0.86 (d, 6H, CH3). IR n (cmꢀ1) 3331 (NH stretch), 1653 (C]O),
1553 (amide II). Maldi-TOF Calcd. [M + Na+] ¼ 750.46 Da; Obs.
[M + Na+] ¼ 750.45 Da.
3.2 Properties of compounds 1–6 in the solid state
The physical appearance of compounds 1–6 differs dramatically.
At room temperature, compounds 1, 5 and 6 are solids,
compound 2 is a sticky solid and compounds 3–4 are oils. We
investigated the thermal behaviour of all compounds 1–6 with
polarisation optical microscopy (POM) and differential scanning
calorimetry (DSC). If liquid crystallinity was present, the nature
of the mesophase was confirmed with WAXS and SAXS
measurements. In addition, we measured the infrared (IR)
spectra of compounds 1–6 to assess the presence of intermolec-
ular hydrogen bonding. All data are summarised in Tables 1
and 2.
N,N0,N00-Tri(2-{2-[2-(2-methoxyethoxy)-ethoxy]-ethoxy}-ethyl)-
benzene-1,3,5-tricarboxamide (4). Compound 4 was obtained
as a slightly yellow oil (0.7 g). 1H-NMR (CDCl3): d ¼ 8.47 (s, 3H,
Ar–H), 7.46 (s, 3H, N–H), 3.68–3.58 (m, 42H, O–CH2), 3.50
(m, 6H, NH–CH2), 3.30 (s, 9H, O–CH3). IR n (cmꢀ1) 3334
(NH stretch), 1664 (C]O), 1533 (amide II). Maldi-TOF Calcd.
[M + Na+] ¼ 800.43 Da; Obs. [M + Na+] ¼ 800.41 Da.
Compound 1 was previously reported to be liquid crystalline
(LC) in enantiopure (S)-form between 109 ꢂC (DH ¼ 16 kJ/mol)
and 236 ꢂC (DH ¼ 21 kJ/mol) and the mesophase was tentatively
assigned as a columnar mesophase.8a WAXS and SAXS
measurements on a sample of (R)-1 now unambiguously
2.3 Synthesis of N-(2-methoxyethyl)-N0,N00-di(n-octyl)-
benzene-1,3,5-tricarboxamide (5) and N-(2-methoxyethyl)-
N0,N00-di((S)-3,7-dimethyloctyl)-benzene-1,3,5-tricarboxamide
(6)
The synthesis and isolation of compounds 5 and 6 was done in
analogy to compound 2 using 2-methoxyethylamine and octyl-
amine or (S)-3,7-dimethyloctylamine for 5 and 6, respectively.
Compound 5: 1H-NMR (CDCl3): d ¼ 8.32 (m, 3H, Ar–H), 6.94
(t, 1H, N–H), 6.62 (t, 2H, N–H), 3.43–3.70 (m, 8H, O–CH2, NH–
CH2), 3.39 (s, 3H, O–CH3), 1.29–1.61(m, 24H, CH2), 0.88 (m,
confirm a hexagonally ordered, columnar ꢂmesophase (Colho
)
phase for the compound (Table 2). At 140 C two features are
detected in the wide-angle region: first, a sharp reflection that
˚
corresponds to a distance of 3.5 A and is characteristic of the
stacking of disc-like molecules; second, a broad diffuse halo
˚
associated to a distance of about 4.7 A that arises from short-
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Table 1 IR and DSC data of compounds 1–6
Compound
n (NH) [cmꢀ1
3225
]
n (C]O) [cmꢀ1
1636
]
n (C–N) [cmꢀ1
1563
]
Tg [ꢂC]
—
Tm [ꢂC] DH [kJ/mol]
Tcl [ꢂC] DH [kJ/mol]
1
2
109a
16.0
—
236a
21.0
134
10.2
—
—
145
9.7
3238
1637
1556
—
3
4
5
3331
3334
3234
1655
1656
1639
1533
1537
1557
ꢀ40
—
—
—
—
83
1.9
84
2.4
6
3235
1635
1556
—
181
9.7
a
Data obtained from reference 8a.
Table 2 X-Ray data for compounds 1–2 and 5
Compounds 3 and 4 show no birefringence under crossed
polarizers at room temperature, which is indicative of the
absence of long range ordering. The DSC trace of compound
3 shows a single glass transition temperature at ꢀ40 ꢂC while no
transitions are observed for compound 4 within the measured
temperature range from ꢀ100 ꢂC to room temperature.
˚
Spacings (A)
hkl
compound 1a
compound 2b
compound 5c
100
110
200
halo
interdisc distance
intercolumnar
distance
17.2
9.9
8.6
4.7
3.5
19.9
17.0
9.9
—
4.7
3.5
19.6
14.6
8.5
—
4.9
3.5
16.9
Compounds 5 and 6 (Scheme 1) are both obtained as solid
compounds at room temperature and show solid state properties
that closely resemble those of compounds 1 and 2. An LC phase
is observed between 83 and 145 ꢂC for 5 and the textures grown
for the mesophase suggest a Colho phase (Fig. 1B). More
evidence for the presence of a Colho phase in 5 was obtained from
SAXS and WAXS measurements (Table 2). The intercolumnar
Measured at 140 ꢂC. b Measured at 100 ꢂC. c Measured at 120 ꢂC.
a
˚
distance in this case is 16.9 A. For compound 6, the temperature
range interactions between the aliphatic chains as is typically
observed in liquid crystalline phases. In the small-angle region,
a set of three reflections with spacings in the reciprocal ratio
1:O3:2 is consistent with a hexagonal packing of the columns.
From these maxima we can deduce an intercolumnar distance of
range in which LC behaviour is observed ranges from 84 to
181 ꢂC (Table 1). Upon cooling from the isotropic melt, textures
are obtained that are indicative for a Colho phase.
Evidently, replacing one alkyl chain by one tetraEG chain
drastically lowers the stability of the mesophase as evidenced by
the lowering of the clearing temperature from 236 ꢂC in
compound 1 to 134 ꢂC in compound 2. Also in compounds 5 and
6 the clearing temperatures are reduced by ꢃ50 ꢂC compared to
those of the symmetrical analogues (the corresponding N,N0,N00-
trioctylbenzene-1,3,5-tricarboxamide has a clearing temperature
of 204 ꢂC).5a The reduction of the clearing temperature upon the
introduction of EG chains to discotic compounds has been
observed previously and is related to the greater conformational
flexibility of EG chains compared to alkyl chains.20
˚
19.9 A.
Under crossed polarisers, compound 2 shows a birefringent
texture at room temperature and becomes isotropic at around
140 ꢂC. Slow cooling induces the growth of a pseudo-focal-conic
texture with large homeotropic areas, which points to a Colho
mesophase (Fig. 1A). The DSC trace of compound 2 shows only
one large transition at 134 ꢂC (DH ¼ 10.2 kJ/mol) in agreement
with POM observations. The assignment of the mesophase is
confirmed by performing SAXS and WAXS measurements
(Table 2): the pattern is analogous to that of 1, and is consistent
The influence of the polar side chains on the a-helix type
intermolecular hydrogen bonding was further investigated by
infrared (IR) spectroscopy. Brunsveld et al. reported that the
N–H stretch vibration of (S)-1 in the solid state occurred at
˚
with a Colho mesophase with 19.6 A intercolumnar distance.
3223 cmꢀ1 and the C]O stretch at 1640 cmꢀ1 8a
These values
.
were attributed to the intermolecular hydrogen bonds between
N–H and C]O. In tetrachloromethane, where (S)-1 is molec-
ularly dissolved and no intermolecular hydrogen bonding is
present, the values for the N–H and C]O stretch shifted to
3458 cmꢀ1 and 1665 cmꢀ1, respectively.
Fig. 2 shows the solid state IR spectra of compounds 1–4
measured at room temperature, the data are collected in Table 1.
For compound (R)-1, we observe the N–H stretch vibration at
3225 cmꢀ1 and a C]O stretch at 1636 cmꢀ1 which is in good
agreement with the reported values.8a The positions of the N–H
stretch at 3238 cmꢀ1 and C]O stretch at 1637 cmꢀ1 in compound
Fig. 1 POM images under crossed polarisers of the texture of compound
2 at 138 ꢂC (A) and of the texture of compound 5 growing from the
isotropic liquid (B).
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Fig. 3 (A) UV and (B) CD spectra of compounds 1–3 in n-heptane; c ¼
6.5 ꢁ 10ꢀ5 M.
concentrations is a direct consequence of the low Kass of 2 in
alkane solvents. Since compound 3 shows no thermotropic LC
behaviour, increasing its concentration in decalin was not
expected to induce aggregation. As a result, we can conclude that
compounds 2 and 3 are molecularly dissolved at the concentra-
tion of 6.5 ꢁ 10ꢀ5 M.
Fig. 2 IR spectra of compounds 1–4 taken at room temperature.
2 indicate that the intermolecular hydrogen bonds are retained,
despite the presence of one polar side chain. In contrast, the N–H
stretch at 3331 and 3334 cmꢀ1 and C]O stretch at 1655 and
1656 cmꢀ1 for compounds 3 and 4, respectively, suggests the loss
of the threefold a-helical type intermolecular hydrogen bonds in
compounds 3 and 4 in the bulk; this observation explains the lack
of mesophase order in these compounds at room temperature.
The IR spectra of compounds 5 and 6 show vibrations at posi-
tions characteristic for a threefold, intermolecularly hydrogen
bonded structure (Table 1).
In contrast, the UV and CD spectra of compound 6 measured
in methylcyclohexane at a 3 ꢁ 10ꢀ5 M (D3 ¼ ꢀ48 L.molꢀ1.cmꢀ1 at
l ¼ 223 nm) closely resemble those of 1. Since the configurations
of the alkyl side chains differ, the CD spectra of 1 and 6 are, as
expected, mirror images of each other (Fig. 4A). This suggests
that one methoxyethyl unit does not dramatically affect the
strength of association in BTAs. Performing a ‘‘sergeants-and-
soldiers’’ experiment using chiral analogue 6 as the sergeant
allowed us to determine a Kass of 3 ꢁ 107 Mꢀ1 in methyl-
cyclohexane at 25 ꢂC. Fig. 4B clearly shows the non-linearity
when the normalized CD effect is plotted as a function of the
amount of chiral 6 added to a solution of achiral 5. Although Kass
for compounds 5–6 is a factor of 10 lower than the Kass of 5 ꢁ 108
Mꢀ1 reported for compound 1, it clearly shows that one
methoxyethyl unit does not have a significant impact on the self-
assembly of BTAs.
3.3 Self-assembly of compounds 1–6 in alkanes and water
The influence of polar side chains on the self-assembly of BTAs
in solution was investigated by UV and CD measurements in
n-heptane or methylcyclohexane. Compound 1 is known to
helically stack in diluted alkane solvents; this is reflected by
a lmax at 193 nm in UV and a strong CD effect at 223 nm (D3 ¼
44 L.molꢀ1.cmꢀ1).8 In polar solvents such as acetonitrile, the CD
effect of 1 disappears and in UV the lmax shifts to 208 nm,
indicative of molecularly dissolved species.8b We recently showed
that concentrated solutions of compound 2 in decalin also exhibit
a CD effect (c ¼ 48 mM, D3 ¼ 37 L.molꢀ1.cmꢀ1 at l ¼ 225 nm).14
The Havinga model,16 derived for bipyridine based BTAs,
allowed for the estimation of Kass for compounds 1 and 2 in
alkane solvents. In this model, chiral and achiral derivatives are
mixed in different ratios (the ‘‘sergeants-and-soldiers’’ experi-
ment21) and the chiroptical response is measured by CD spec-
troscopy as a function of the amount of chiral compound added.
If amplification of chirality is present, a non-linear relationship is
observed between the chiroptical response and the amount of
chiral compound added. Comparing the measured data to values
Finally, we evaluated the aggregation of compounds 1–6 in
water. Compounds 1, 2, 5 and 6 are, unsurprisingly, not
compatible with water. Compounds 3 and 4, on the other hand,
are. We measured the CD and UV spectra of 3 in water in
concentrations from 10ꢀ4 to 10ꢀ2 M. None of the investigated
concentrations show a CD effect and all UV spectra (Fig. 5)
suggest that 3 is molecularly dissolved in water, even at high
concentrations. Also compound 4, even more hydrophilic, is
completely soluble in water at all concentrations investigated.
predicted by the Havinga model allows for an estimation of Kass
.
In this way, we previously estimated a Kass of 5 ꢁ 108 Mꢀ1 for
compound 1 in n-heptane at 20 ꢂC.22 For compound 2 a Kass of 21
Mꢀ1 was estimated in decalin at 20 C.23
ꢂ
We prepared solutions of compounds 1–3 in n-heptane at
a concentration of 6.5 ꢁ 10ꢀ5 M and measured the UV and CD
Fig. 4 (A) CD spectra of compound (R)-1 (open circles) in heptane
(c ¼ 6.5 ꢁ 10ꢀ5 M) and (S)-6 (closed circles) in methylcyclohexane (c ¼ 3
ꢁ 10ꢀ5 M). (B) Development of the normalised CD effect as a function of
chiral 6 added to a solution of achiral 5 (c ¼ 3 ꢁ 10ꢀ5 M in methyl-
cyclohexane, T ¼ 25 ꢂC). The dotted line represents the best fit of the data
spectra at 20 C (Fig. 3).24 Fig. 3A shows that the lmax in UV
ꢂ
shifts to 208 nm upon introduction of one tetraEG moiety, which
is indicative of molecularly dissolved species. In addition, the CD
effect at 225 nm collapses when going from compound 1 to 2 and
3, respectively (Fig. 3B). The loss of the CD effect of 2 at lower
to the model where Kass ¼ 3 ꢁ 107 Mꢀ1
.
128 | J. Mater. Chem., 2009, 19, 124–130
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View Article Online
these asymmetric derivatives and drastically lowering the asso-
ciation constant due to competing interactions. In contrast, one
methoxyethyl unit does not affect the stability of the aggregation
of BTAs suggesting that more than one EG unit is required. The
polar BTAs 3 and 4 do not show self-assembly in water because
of the lack of hydrophobic shielding.
The possibility of backfolding of oligoEG chains and resulting
competitive hydrogen bonds may also be responsible for low
association constants in other supramolecular systems after
introducing oligoEG residues. Therefore, when preparing water-
compatible small molecules programmed to self-assemble into
complex structures, care should be taken when designing the
molecules: hydrogen bonding groups must be shielded from the
oligoEG units by linker units and sufficiently strong hydro-
phobic, p–p stacking or other non-covalent interactions must be
built into the system. Eventually, we aim to elucidate the struc-
ture–properties relationships in molecules intended to self-
assemble in water in order to achieve our goal of design driven
non-covalent synthesis of complex, functional supramolecular
assemblies.
Fig. 5 UV spectrum of compound 3 in water; c ¼ 60 mM.
Fig. 6 Proposed folding back of ethylene glycol residues in compounds
2 and 5.
3.4 Influence of oligoEG chains on intermolecular hydrogen
bonding in BTAs in the solid state and in solution
Acknowledgements
R.M.-R. acknowledges support from an EU Marie Curie Intra-
European Fellowship (Project MEIF-CT-2006-042044) within
the EC Sixth Framework Programme. The authors would like to
thank Ivo Filot for providing the art work, NWO for funding
and Dr Dmytro Byelov of AMOLF in Amsterdam for his help
The introduction of one polar oligoEG side chain impacts the
strength of association in BTAs as evidenced by the significant
reduction of Kass from 5 ꢁ 108 Mꢀ1 in 1 to 21 Mꢀ1 in 2. Such
a large reduction in Kass is not observed in the case of
a methoxyethyl unit (compounds 5–6) where Kass ¼ 3 ꢁ 107 Mꢀ1
.
´
with the SAXS/WAXS measurements. Dr J. Barbera is gratefully
Also in the solid state, oligoEG side chains eventually lead to loss
of columnar order.
acknowledged for providing us access to the powder X-ray
diffraction equipment at the University of Zaragoza (ES).
We propose that the reduction of Kass in 2 results from folding
back of the ethylene glycol residues. Competitive hydrogen
bonding interactions between the EG oxygen and the amide N–H
of the tricarboxamide core are possible as tentatively depicted in
Fig. 6. In compounds 5 and 6 on the other hand, a 5-membered
ring is required for intramolecular hydrogen bonding between
the EG oxygen an the amide N–H which is less likely to form.
Interestingly, at high concentrations and in bulk the threefold
a-helical type hydrogen bonding in 2 is present as evidenced by
IR spectroscopy.14
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