Aromatic oligoamide β-sheet foldamers

Article abstract of DOI:10.1021/ja412729s

A rational approach for the construction of multi-stranded artificial β-sheets based not on hydrogen bonding, but rather on π-π aromatic stacking, is presented. Using 4,6-dinitro-1,3-phenylenediamine units, rigid turns were designed that allow face-to-face π-π interactions between appended linear aromatic segments to be strong enough for folding in an organic solvent, but weak enough to prevent aggregation and precipitation. Solution and solid-state studies on a series of turn units showed that the desired degree of rigidity, resulting from hindered bond rotation, could be fine-tuned by the inclusion of additional methyl substituents on the aromatic rings. The high degree of preorganization afforded by these qualities further allowed the facile preparation of macrocyclic sheet structures from their noncyclic precursors. These macrocycles were shown to have slow internal dynamics and defined conformational preferences. Using this background, three- and five-stranded artificial β-sheets were synthesized and their folded conformations extensively characterized in solution by NMR. The solid-state structures of the three- and five-stranded sheets were also elucidated in the solid state by X-ray crystallography and confirmed intramolecular π-π aromatic stacking.

Full text of DOI:10.1021/ja412729s

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Article
Aromatic oligoamide #-sheet foldamers
Laure Sebaoun, Victor Maurizot, Thierry Granier, Brice Kauffmann, and Ivan Huc
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja412729s • Publication Date (Web): 14 Jan 2014
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Aromatic oligoamide β-sheet foldamers
Laure Sebaoun,†,¶ Victor Maurizot,*,†,¶ Thierry Granier,†,¶ Brice Kauffmann,‡,#,§ Ivan Huc*,†,¶
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† Univ. Bordeaux, CBMN (UMR 5248), Institut Européen de Chimie Biologie, 2 rue Escarpit 33600 Pessac, France
¶ CNRS, CBMN (UMR 5248), France.
‡ Univ. Bordeaux, Institut Européen de Chimie Biologie (UMS 3033/US 001), 2 rue Escarpit, 33600 Pessac, France
# CNRS, Institut Européen de Chimie Biologie (UMS 3033), France
§ INSERM, Institut Européen de Chimie Biologie (US 001), France
KEYWORDS: Foldamers, β-Sheets, Macrocycle, Structural Investigation, X-ray Crystallography, NMR
ABSTRACT: A rational approach for the construction of multistranded artificial β-sheets based not on hydrogen bonding,
but on π−π aromatic stacking is presented. Using 4,6-dinitro,3,5-phenylenediamine units, rigid turns were designed that
allow face-to-face π−π interactions between appended linear aromatic segments to be strong enough for folding in an
organic solvent, but weak enough to prevent aggregation and precipitation. Solution and solid state studies on a series of
turn units showed that the desired degree of rigidity, resulting from hindered bond rotation, could be fine tuned by the
inclusion of additional methyl substituents on the aromatic rings. The high degree of preorganization afforded by these
qualities further allowed the facile preparation of macrocyclic sheet structures from their non cyclic precursors. These
macrocycles were shown to have slow internal dynamics and defined conformational preferences. Using this background
three and five-stranded artificial β-sheets were synthesized and their folded conformations extensively characterized in
solution by NMR. The solid state structures of the three and five-stranded sheets were also elucidated in the solid state by
x-ray crystallography and confirmed intramolecular π−π aromatic stacking.
and precipitate. For example, natural peptidic β-sheets
INTRODUCTION
form stable finite well-defined structures in the context
of protein tertiary folds, but polymerize into insoluble
The development of synthetic foldamers has thoroughly
demonstrated that folded conformations do not belong
aggregates when in an isolated form. It follows that
solely to biopolymers, but also occur in a wide variety of
most artificial sheet-like structures possess features that
artificial oligomeric and polymeric backbones that can
prevent extensive aggregation. For instance, sheets
be remote from their natural counterparts.1 Thus, a vast
ly designed to be dimeric10-13 or monomeric,14 which
playground has been opened to chemists with the pro-
spect to create artificial folded architectures with func-
observed.15 It is thus surmised that the rareness of
tions matching and exceeding those of peptides and
nucleic acids. Remarkably, despite the variety of chemi-
based on intermolecular hydrogen-bonding are general-
ensures solubility. Otherwise, infinite assemblies may be
foldamer sheets does not necessarily result from low
cal units used to construct foldamers, a comparably
occurrence, but from the fact that they may be difficult
narrow ensemble of secondary folded motifs has
to track and remain undetected if not designed to be
emerged. Apart from occasional unusual folded struc-
soluble. At the start of this investigation, rationally de-
tures such as pillar-like architectures (stacks of aromatic
signed artificial sheets appeared to be elusive objects
rings),2,3 knots,4 spiral-like objects (‘tail-biters’),5 a few
and their fabrication quite challenging.
zig-zag tapes6,7 or non-canonical helices,8 a vast majority
In the following, we report the design, synthesis and
of foldamers are found to adopt the classical motifs
structural characterization of discrete, soluble β-sheet
found in biopolymers, namely helices, linear strands,
foldamers derived from aromatic oligoamides.16 Unlike
turns and sheet-like structures, an observation that
in the few examples of artificial sheets and dimeric tapes
seems to have a theoretical basis.9 Among these second-
mentioned above which rest on hydrogen-bonding,10-13
ary motifs, it is quite remarkable that foldamer helices
the β-sheet foldamers presented here are stabilized by
intramolecular aromatic π-π stacking. Relevant back-
are highly prevalent objects whilst artificial sheets are
rare. A major difference between sheets and helices is
ground to the development of these novel structures
that the latter fulfill their potential for non-covalent
include pillar-like architectures,2,3 some crescent-like
interactions intramolecularly giving rise to discrete and
macrocycles,17 foldamers with cofacial aromatic building
soluble structures, whereas the former tend to aggregate
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blocks,18 zippers based on oligoanthranilamides,19 pyr-
required for the second substitution to reach comple-
tion
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role-imidazole oligoamides that form stacked dimers
upon binding to the minor groove of DNA,20 as well as
extensive work from our group on dimeric,21 trimeric22
and tetrameric23 β-helices, which can be viewed as
strongly bent β-sheets that show the potential of aro-
matic oligomamides to assemble into discrete objects
held by intermolecular aromatic π-π stacking.
Scheme 1. Schematic assembly of the design ele-
ments for building aromatic oligoamide β-sheet
foldamers
The design shown in Scheme 1 involves the combination
of linear flat aromatic segments and of hairpin turns
that would set the linear segments at a distance and
orientation favoring aromatic stacking. A key parameter
was to balance the strength of non-covalent interactions
involved in folding and the level of pre-organization of
the structure. On one hand, strong non-covalent inter-
actions would be expected to result in folding but also in
aggregation and precipitation as these interactions may
occur in both intra and intermolecular fashions. On the
other hand, weak non covalent interactions may not
result in aggregation but may also fail to direct folding
unless the structure is sufficiently preorganized. In the
first generation of designs presented here, folding rests
on aromatic stacking in chloroform, a solvent in which
stacking is weakened by favorable solvent-solute inter-
actions, and on an optimized turn unit that sets the
orientation of aromatic groups so that intramolecular
stacking results in multi-stranded sheet-like structures.
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Chart 1. Study of the influence of substituents of
adjacent rings on the folding of pseudo-β hairpins
RESULTS AND DISCUSSION
Hairpin turn unit design
Aliphatic three atom spacers have been previously found
to be suitable to connect two aryl rings and allow their
face-to-face stacking, but only in the context of DNA
minor groove binders.20 To impart rigidity, sp2 conjugat-
ed spacers have also been used such as tertiary imides
and ureas,3 1,3-phenylene7 and 1,8-diphenylnaphthalene18
groups. Among these, 4,6-dinitro-1,3-phenylenediamine
possesses an attractive feature in that intramolecular
hydrogen bonds between amine and nitro groups are
expected to favor a parallel orientation of aromatic sub-
stituents (see compound 1 Chart 1). However, previous
examples of the use of this moiety in the context of aryl-
amine oligomers showed that rotation about the amine-
phenyl substituent-bond resulted in reduced π-π overlap
between phenyl rings.7 Only in rigid macrocycles was
the overlap found to be significant.24 In order to limit
this bond rotation, we investigated the effect of methyl
groups ortho to the amine on the aryl substituents.
Compound series 1–3 were prepared from 1,3-difluoro-
4,6-dinitrobenzene via aromatic nucleophilic substitu-
tions of the fluorine atoms by aromatic amines.25 For
compounds 1b and 1c, the second substitution is slower
than the first but both take place at room temperature.
In contrast, heating to 80°C is required for compound 1a
because of the poor nucleophilicity of the 4-nitroaniline
precursor. In the case of the tolyl and xylyl amines in-
volved to prepare series 2 and 3, respectively, harsher
conditions (80°C) and long reaction times (10 days) are
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Figure 1. Part of the 300 MHz H NMR spectra in CDCl3 at
298K of: (A) hairpin turn in the phenyl series 1b; (B) hairpin
turn in the tolyl series 2b; (C) hairpin turn in the xylyl
series 3b; (D) OiBu macrocycle 5a; and (E) OMe macrocycle
5b. Signals of Hext are marked with white circles. Signals of
Hint are marked with full black circles. Stars indicate signals
belonging to an impurity.
(see supporting information) due to the hindrance
caused by the methyl groups.
1H NMR spectra of 1b, 2b, and 3b, which only differ by
the number of methyl groups ortho to the diarylamine
function, show little variations of the chemical shift
value of Hext, the proton ortho to both nitro groups that
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Hint, the
points towards the exterior of the structure (ꢀδ < 0.05
ppm, see Fig. 1A-1C). On the contrary, the resonance of
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Figure 2. Side view (bottom) and front view (top) of the crystal structures of: (A) form 1 of phenyl hairpin turn 1a; (B) form 2 of
phenyl hairpin turn 1a; (C) tolyl hairpin turn 2a; (D) tolyl hairpin turn 2b; (E) xylyl hairpin turn 3a; and (F) xylyl hairpin turn 3b.
Included solvent molecules and –CH3 units of the Boc group in 2b and 3b have been omitted for clarity.
Scheme 2. Two different synthetic pathways to macrocycles 5a and 5ba
aReagents and conditions: a) 6 equiv PyBOP, 6 equiv DIEA, CHCl3, 318K, 7 days, 0.7 mM, yield for 5a =44%; b) 5 equiv NaOH
in THF/MeOH 2:1 vol/vol, 24h, rt then 3 equiv PyBOP, 3 equiv DIEA, CHCl3, 318K, 7 days, 0.7 mM, yield for 5a =25%.
Scheme 3. Synthesis of multi-turn β-sheet foldamers.b
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bReagents and conditions: a) 1.2 equiv EDCI, CH2Cl2, 24h, room temperature, yield = 82%; b) 1 equiv 1,3-difluoro-4,6-
dinitrobenzene, DMSO, 4h, room temperature, yield = 95%; c) 1 equiv tert-butyl-4-amino-3,5-dimethylphenylcarbamate, 1 equiv
DIEA, DMSO, 353K, 3 days, yield = 50%; d), e) see supporting information.
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proton meta to both nitro groups that points towards the
interior of the structure undergoes a major downfield
shift of 1.5 ppm from 1b to 3b. This effect was assigned to
the steric hindrance associated to the methyl groups that
set the tolyl and even more so the xylyl rings in an orien-
tation perpendicular to the dinitrophenyl unit, resulting
in intense ring current effects over Hint. The xylyl series
thus appears to provide a more rigid and better organized
yet easy to prepare hairpin turn.
A crystal structure of 6 clearly shows a C-shaped con-
former in which the amine and ester functions, precursors
of the cyclization step, are brought into close proximity
by sheet-like folding (Fig. 3A, 3B). A direct hydrogen bond
was observed between the amine and ester carbonyl
group (dN-O = 3.3 Å). The distance between the terephthal-
ic rings is 3.5 Å, as expected in aromatic stacks. In solu-
tion, this conformation is presumed to be at equilibrium
with an S-shaped conformer in which the amine and ester
functions are found on opposite sides of the central ter-
ephthalamide unit.
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Further evidence of the effect of methyl groups was gath-
ered in the solid state from the crystal structures of 1a, 2a,
2b, 3a and 3b (Fig. 2). In the two distinct conformers
found in the structure of 1a and in the conformer of 2a
and of 2b the phenyl or tolyl groups are not perpendicular
to the dinitrophenyl unit, and not necessarily parallel to
each other, leading to little π-π face-to-face overlap. On
the contrary, the structures of 3a and 3b show well-
organized conformations with parallel overlapping xylyl
groups. The aryl-aryl distance between the xylyl groups
imparted by the dinitrobenzene unit is 4.8 Å, which is
larger than desired for tight π-π contacts. Nevertheless,
tight π-π contacts were found to take place upon elonga-
tion of the linear segments (see below) and the xylyl hair-
pin turn motif was selected to further develop β-sheet
structures because of its well-controlled geometry.
Macrocyclic β-sheets.
For this proof of concept investigation, simple 2,5-
dialkoxy-terephthalic acid units were selected to consti-
tute linear segments connecting the hairpin turns
(Scheme 1). The 2,5-alkoxy substituents provide hydrogen
bond acceptors that favor coplanar orientation of the aryl
and adjacent amide bonds following principles well estab-
lished for other aromatic amide foldamers.16 Linear, tape-
like, aromatic oligoamides have been described before26
and may be envisaged to replace the terephthalic acid
units and elongate the sheets in future designs. Crescent-
shaped segments may be envisaged as well.17,27
When allowed to polymerize, many aromatic oligoamide
foldamer precursors have a high propensity to form mac-
rocycles instead of long polymeric chains,28,29 as a conse-
quence of the bent shape of short sequences imparted by
folding. Prior to synthesizing long oligomers, we thus
viewed the formation of macrocycles as a simple prelimi-
nary test of the folding propensity of our target sheet
structures. Thus, diamino hairpin turn 3c was reacted
with one equivalent of terephthalic acid having either 2,5-
dimethoxy or 2,5-diisobutoxy subtituents to produce 2+2
macrocycles (Scheme 2). Macrocyle 5a was obtained in
44% (unoptimized) yield. Compound 5a was also ob-
tained in one coupling step from its linear precursor 6
(see below for the preparation of 6). The production and
purification of 5b was complicated by its low solubility
and only 7% of an enriched fraction was isolated.
Figure 3. (A,B) Side view and top view of the crystal struc-
ture of macrocycle precursor 6; (C,D) Side view and top view
of the energy minimized conformation (Maestro version 6.5
using the MM3 force field) of isobutoxy macrocycle 5a as an
anti-parallel conformer; (E, F) Side view and top view of the
energy minimized conformation of isobutoxy macrocycle 5a
as a parallel conformer. Both representations were obtained
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by molecular modeling. Hydrogen atoms have been omitted
The macrocycles thus represent rigid models of two-
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for clarity.
stranded sheets. They are nevertheless subject to internal
dynamics. Indeed, xylylene aromatic protons H3 and H5
(Fig. 4A) appear as a broad singlet at 7.44 ppm in the H
The low solubility of 5b hampered its complete purifica-
tion but was sufficient for H NMR measurements in
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NMR spectrum of 5b, and as two broad signals at 6.54 and
8.10 ppm in the spectrum of 5a (Fig. 4B, 4D). Upon heat-
ing, the two signals of the spectrum of 5a coalesce; upon
cooling to 273K, these signals sharpen. In contrast, cool-
ing a solution of 5b results in a broadening of the signal at
7.44 ppm which eventually disappears into the baseline.
Even at 223 K, its splitting into two signals was not ob-
served.
CDCl3. Compound 5a was highly soluble. The spectra of
5a and 5b were compared to those of 3b (Fig. 1C-1E). They
showed an 0.2 ppm upfield shift of Hint with respect to 3b
which was interpreted as a further stabilization within the
cyclic structure of a sheet-like conformation in which the
linear segments are perpendicular to the dinitrophenyl
turns, and Hint subjected to strong ring current effects
from the xylylenediamine rings. Energy minimized mod-
els of 5a support this view (Fig. 3D, 3F).
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The non equivalence of H3 and H5 reflects the orientation
of the central terephthalamide units with respect to the
xylyl groups. One of the two xylyl protons is exposed to
the amide carbonyl whilst the other faces the amide pro-
ton. Fast rotation of the xylyl units about themselves, or
fast rotation of the terephthalamide units about them-
selves can in principle both result in equivalent H3 and H5
protons. The difference in behavior of 5a and 5b suggests
that we are essentially observing a rotation of the tereph-
thalamide units about themselves, and that the rotation
of the xylyl units is a slower process. Rotation of the ter-
ephthalamides involves passing alkoxy substituents
through the macrocycle cavity, a process that is expected-
ly much faster for the methoxy groups of 5b than for the
isobutoxy groups of 5a. EXSY measurements on 5a al-
lowed the determination of a Gibbs energy of activation
of 62 kJ. mol-1 (see supporting information). No value
could be calculated in the case of 5b.
Upon cooling further a solution of 5a, the signals of H3
and H5 broaden again and then both split into two signals
of different intensities, indicating the presence of two
distinct conformers in a ratio of 82:18 (Fig. 4F, 4G). Ex-
change between these different signals is unambiguously
confirmed by a 2D ROESY map (Fig. 4H). This phenome-
non was assigned to the coexistence of parallel and anti-
parallel orientation of the central terephtalamide seg-
ments (compare Fig. 3D and 3F). Because of internal
symmetry elements, each of these conformers possesses
one type of H3 proton, and one type of H5 proton. The fast
rotation of one terephthalamide unit amounts to fast
equilibrium between the two conformers, but the com-
plete coalescence of all H3 and H5 signals requires the fast
rotation of both terephthalamide units. It is reasonable to
hypothesize that the anti-parallel conformer is favored
over the parallel conformer due to electrostatic effects, as
is observed in the crystal structure of 6 (Fig. 3a,3B), thus
reflecting direct interaction between the stacked aromatic
rings.
Figure 4. (A) Allowed rotations (green arrows) and rotation
restricted by hydrogen bonding (red cross) of NH-aryl bonds
in 5a and 5b. H3 and H5 are shown on the structure; Parts of
1
the 400 MHz H NMR spectra in CDCl3 of: (B) 5b at 298 K;
Multi-turn β-sheet structures.
(C) 5a at 313 K; (D) 5a at 298 K; (E) 5a at 273 K; (F) 5a at 248
K; (G) 5a at 223 K. H3 and H5 signals are marked with red and
blue triangles, respectively. H3+H5 fast exchange average
signal is marked by a red-in-blue triangle. Signals belonging
to a second conformer are marked with squares; (H) excerpt
of the 2D ROESY plot (τm = 300 ms) at 223K showing chemi-
cal exchange between protons of the two conformers of mac-
rocycle 5a.
The stepwise synthesis of multiturn sheets was carried
out as outlined in Scheme 3 (see supporting information
for more details). A convergent solution phase approach
was used similar to that developed for helical oligomers.30
Dimeric segment 9 could be prepared by selective cou-
pling of the less hindered amine of xylylene-diamine 8.
Tetrameric building block 11 represents the repeat motif
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of the targeted sequences. It possesses a Boc protected tra. The protocols used for these assignments were similar
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amine and a carboxylic acid protected as an ethyl ester.
Deprotection of the amine of 11 and coupling with one
terephthalic acid unit yielded nonameric three-stranded
sheet 12. During this and other coupling steps, the diaryl
amine of 11 does not require any protection due to hin-
drance and its poor nucleophilicity. Similarly, an octamer
(the Boc protected analogue of octamer amine 6, see
Scheme 2) was prepared from the free acid and the free
amine derivatives of 11, and five-stranded heptadecamer
13 was assembled upon linking two octameric monoam-
ines onto a terephtalic acid unit. For the purpose of facili-
tating NMR assignment, dimethoxy-terephthalamides
were introduced in the central positions of 12 and 13
whereas diisobutoxy-terephthalamides were used at other
positions. Even the longest oligomer 13 was found to be
well soluble (> 8 mM) in chlorinated and aromatic sol-
vents. The scheme was carried out on a 0.2 mmol scale
but is in principle amenable to scaleup29 and it may be
applied to produce even longer structures.
to those described for helical aromatic oligoamides and
critically involve short and long distance proton-carbon
correlations.31 Both indirect and direct evidence of sheet-
like folding in solution could be extracted from these
data. For example, it was noticed that, when going from
12 to 13, the largest upfield shifts concern the central xylyl
protons (ꢀδ > 0.3 ppm), a clear indication of their posi-
tioning at the center of the aromatic stack which expose
them most to ring current effects. A large number of
NOEs were observed that indicate multiturn sheet-like
folding (see the Supporting Information): at every turn
unit, the Hint proton correlate with the adjacent xylyl
methyl protons; most importantly, the central methoxy
protons correlate with aryl protons just above and below
in the sheet. Nevertheless, the sheet-like structure ap-
pears to have much faster internal dynamics than macro-
cycle 5a as far as rotations of the terephthalamide units
about themselves are concerned. Even at low tempera-
ture, all signals remain sharp and no splitting of the xylyl
protons were observed.
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The H NMR spectra of tetramer 11, nonamer 12 and hep-
tadecamer 13 are sharp, concentration independent and
present no indication of aggregation. Upon increasing
oligomer length, most signals undergo upfield shifts (Fig.
5), Hext being a notable exception. In particular, the signal
of Hint in 11 and 12 were found at 4.87 and 4.85 ppm, re-
spectively, values at slightly lower field than macrocycle
5a (4.70 ppm), whereas in 13, the two Hint protons were
found at higher fields (4.69 and 4.63 ppm). This suggests
a cooperative effect of the number of strands in the struc-
ture on its overall stability, due to cooperative interac-
tions within aromatic stacks, resulting in enhanced ring
current effects over Hint.
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Figure 5. Part of the 300 MHz H NMR spectra in CDCl3 at
298K of: (A) tetramer 11; (B) nonamer 12; and (C) heptade-
camer 13. Signals of Hext are marked with white circles. Sig-
nals of Hint are marked with full black circles.
A series of multidimensional NMR experiments (HSQC,
HMBC, TOCSY and ROESY) allowed us to carry out the
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full assignment of the H NMR spectra of 12 and 13, and
13
the assignment of the largest part of their C NMR spec-
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other. This may correspond to more favorable π-π interac-
tions.32 It may also reflect steric hindrance between isobu-
toxy side chains at the center of the sheets, or between
nitro groups of dinitrophenyl moieties that come close in
space upon folding. As in the structure of 6 (Fig. 3A, 3B),
adjacent terephthalamides are in an anti-parallel orienta-
tion in both 12 and 13, supporting a more stable confor-
mation of this arrangement, and again reflecting direct
interactions between the stacked linear segments. These
two structures suggest that the sheet motif may be elon-
gated indefinitely, though elongation may require slight
distortions as often observed in peptidic β-sheets which
often adopt bent shapes.
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CONCLUSION
We have introduced a rational approach for the construc-
tion of multistranded artificial β-sheets based not on
hydrogen bonding, but on aromatic π−π stacking. Rigid
turn units were designed that allow π−π interactions be-
tween linear aromatic segments to be strong enough for
folding in organic solvents, but weak enough to prevent
aggregation and precipitation. Structural investigation
both in solution and in the solid state show that cyclic
and non-cyclic oligomers adopt the expected sheet struc-
tures. The design principles reported here may be extend-
ed to a variety of patterns using diverse linear or bent
segments connected by the turn units, giving rise to novel
layered aromatic architectures of controlled size and
shape. Research along these lines is currently in progress
and will be reported in due course.
ASSOCIATED CONTENT
Supporting Information
Synthetic schemes, experimental procedures, full characteri-
zation of new compounds, crystallographic data, detailed
1
NMR investigations including complete H NMR assignment
and solution structure elucidation of 12 and 13. This material
is available free of charge via the Internet at
http://pubs.acs.org.
Figure 6. (A, B) Side view and top view of the crystal struc-
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AUTHOR INFORMATION
Corresponding Authors
ture of nonamer 12. (C, D, E) Side view, top view, and front
view of the crystal structure of heptadecamer 13. Hydrogen
atoms and included solvent molecules have been omitted for
clarity.
* E-mail: v.maurizot@u-bordeaux.fr, i.huc@iecb.u-
bordeaux.fr
Notes
The multistranded sheet-like structures were further
evidenced in the solid state by the crystal structures of
both nonamer 12 and heptadecamer 13 (Fig. 6) which
show similar patterns. The three-stranded (two turns)
conformation of 12 and five-stranded (four turns) con-
formation of 13 possess the expected shape, with the xylyl
groups perpendicular to the dinitrophenyl moieties. The
central part of each sheet consists of a face-to-face stack
of three or five terephthalamide groups at a ca 3.5 Å dis-
tance for 12 and 13, respectively, despite the fact that the
aryl-aryl distance between the xylyl groups imparted by
the dinitrobenzene unit is 4.8 Å, and thus reflecting at-
tractive interactions between stacked linear segments.
The terephthalamide rings are slightly offset from each
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was supported by the French Ministry of Research
(predoctoral fellowship to LS) and by the European Research
Council under the European Union's Seventh Framework
Programme (Grant Agreement No. ERC-2012-AdG-320892).
The authors thank Dr. Michael Singleton for proof reading
the manuscript.
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