Hierarchical chiral expression from the nano- to mesoscale in synthetic supramolecular helical fibers of a nonamphiphilic C 3-symmetrical π-functional molecule

Article abstract of DOI:10.1021/ja202211k

The controlled preparation of chiral structures is a contemporary challenge for supramolecular science because of the interesting properties that can arise from the resulting materials, and here we show that a synthetic nonamphiphilic C₃ compound containing π-functional tetrathiafulvalene units can form this kind of object. We describe the synthesis, characterization, and self-assembly properties in solution and in the solid state of the enantiopure materials. Circular dichroism (CD) measurements show optical activity resulting from the presence of twisted stacks of preferential helicity and also reveal the critical importance of fiber nucleation in their formation. Molecular mechanics (MM) and molecular dynamics (MD) simulations combined with CD theoretical calculations demonstrate that the (S) enantiomer provides the (M) helix, which is more stable than the (P) helix for this enantiomer. This relationship is for the first time established in this family of C₃ symmetric compounds. In addition, we show that introduction of the wrong enantiomer in a stack decreases the helical reversal barrier in a nonlinear manner, which very probably accounts for the absence of a majority rules effect. Mesoscopic chiral fibers, which show inverted helicity, i.e. (P) for the (S) enantiomer and (M) for the (R) one, have been obtained upon reprecipitation from dioxane and analyzed by optical and electronic microscopy. The fibers obtained with the racemic mixture present, as a remarkable feature, opposite homochiral domains within the same fiber, separated by points of helical reversal. Their formation can be explained through an oscillating crystallization mechanism. Although C₃ symmetric disk-shaped molecules containing a central benzene core substituted in the 1,3,5 positions with 3,3′-diamido-2,2′-bipyridine based wedges have shown peculiar self-assembly properties for amphiphilic derivatives, the present result shows the benefits of reducing the nonfunctional part of the molecule, in our case with short chiral isopentyl chains. The research reported herein represents an important step toward the preparation of functional mesostructures with controlled helical architectures.

Full text of DOI:10.1021/ja202211k

ARTICLE
pubs.acs.org/JACS
Hierarchical Chiral Expression from the Nano- to Mesoscale in
Synthetic Supramolecular Helical Fibers of a Nonamphiphilic
C3-Symmetrical π-Functional Molecule
Ion Danila,§ Franc-ois Riobꢀe,§,† Flavia Piron,§ Josep Puigmartí-Luis,† John D. Wallis,z Mathieu Linares,‡
Hans Ågren,‡ David Beljonne,# David B. Amabilino,*,† and Narcis Avarvari*,§
§Universitꢀe d'Angers, CNRS, Laboratoire MOLTECH-Anjou, UMR 6200, UFR Sciences, B^at. K, 2 Bd. Lavoisier, 49045 Angers, France
†Institut de Ciꢁencia de Materials de Barcelona (CSIC), Campus Universitari de Bellaterra, 08193 Cerdanyola del Vallꢁes, Catalonia, Spain
zSchool of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, United Kingdom
‡Laboratory of Theoretical Chemistry, Royal Institute of Technology, SE-106 91 Stockholm, Sweden
#Laboratory for Chemistry of Novel Materials, Universitꢀe de Mons, Place du Parc 20, 7000 Mons, Belgium
S Supporting Information
b
ABSTRACT: The controlled preparation of chiral structures is a contemporary
challenge for supramolecular science because of the interesting properties that can
arise from the resulting materials, and here we show that a synthetic nonamphi-
philic C3 compound containing π-functional tetrathiafulvalene units can form this
kind of object. We describe the synthesis, characterization, and self-assembly
properties in solution and in the solid state of the enantiopure materials. Circular
dichroism (CD) measurements show optical activity resulting from the presence of
twisted stacks of preferential helicity and also reveal the critical importance of fiber
nucleation in their formation. Molecular mechanics (MM) and molecular
dynamics (MD) simulations combined with CD theoretical calculations demon-
strate that the (S) enantiomer provides the (M) helix, which is more stable than the (P) helix for this enantiomer. This relationship is
for the first time established in this family of C3 symmetric compounds. In addition, we show that introduction of the “wrong”
enantiomer in a stack decreases the helical reversal barrier in a nonlinear manner, which very probably accounts for the absence of a
“majority rules” effect. Mesoscopic chiral fibers, which show inverted helicity, i.e. (P) for the (S) enantiomer and (M) for the (R)
one, have been obtained upon reprecipitation from dioxane and analyzed by optical and electronic microscopy. The fibers obtained
with the racemic mixture present, as a remarkable feature, opposite homochiral domains within the same fiber, separated by points of
helical reversal. Their formation can be explained through an “oscillating” crystallization mechanism. Although C3 symmetric disk-
shaped molecules containing a central benzene core substituted in the 1,3,5 positions with 3,30-diamido-2,20-bipyridine based
wedges have shown peculiar self-assembly properties for amphiphilic derivatives, the present result shows the benefits of reducing
the nonfunctional part of the molecule, in our case with short chiral isopentyl chains. The research reported herein represents an
important step toward the preparation of functional mesostructures with controlled helical architectures.
’ INTRODUCTION
organic fibers,11ꢀ13 or organic, when a functional group ap-
pended to the molecular building block possesses a specific
property which can be then replicated and amplified at the nano-
or mesoscale of the chiral aggregate.14ꢀ17 Moreover, collective
properties, not observed in the isolated building blocks, can often
emerge in the supramolecular assemblies. Many of the systems
involved in the formation of chiral fibers consist in π-conjugated
derivatives, such as phenylene-vinylenes,18ꢀ20 oligothiophenes,21,22
and hexabenzocoronenes,23,24 well-known for their semiconduct-
ing behaviors, thus providing twisted or helical wires or ribbons,
with conducting properties.25 The ultimate goal of this approach
is to integrate such fibers in molecular electronic devices.26,27
Supramolecular chirality expressed through the formation of
helical fibres of nano- or meso-scopic size following hierarchical
self-assembly processes is a topic of great current interest in
diverse scientific fields.1ꢀ4 Various applications such as chiral
recognition, when the fibers are entrapped in gels,5 asymmetric
synthesis,6 using silica inorganic helices obtained by replication
of organic helical fibers,7 helical crystallization of biological
macromolecules, when the chiral fibers serve as a template,8,9
biocompatible scaffolds for imaging, tissue engineering, and drug
delivery, in the case of nanofibers decorated with bioactive
molecules,10 have been extensively investigated in the past 15
years. However, probably the most promising applications of
chiral supramolecular structures lie in the field of materials, either
inorganic, prepared upon a transcription process starting from
Received: March 10, 2011
Published: April 25, 2011
r
2011 American Chemical Society
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Figure 1. Schematic model of the self-assembly of twisted stacks of C3 symmetric N,N0,N00-Tris[3(30-carbamoylamino)-2,20-bipyridyl]-benzene-1,3,5-
tricarbonamide derivatives.
It is generally well established that formation of supramolecular
aggregates occurs through a bottom-up process, involving co-
operative intermolecular forces such as πꢀπ stacking and
hydrogen bonding, combined with other weaker and nondirec-
tional interactions,14ꢀ17,26,27 very often leading to fibers posses-
sing complex superstructures. Moreover, it has been emphasized
that the presence of chiral alkyl chains at the periphery of the
molecule which engage in the self-assembly process can trigger
the preferential formation of only one helicity, as an expression of
hierarchical organization at different levels. In this respect, a very
interesting building block provided with C3 symmetry, consisting
of a central aromatic ring functionalized at the 1, 3, and 5
positions with substituted N-monoacylated 3,30-diamino-2,20-
bipyridine units, has been introduced by Meijer and co-workers
(Figure 1).28 Because of the steric hindrance around the central
aromatic core, the three bipyridine wedges, self-rigidified through
intramolecular hydrogen bonding, adopt a propeller-like con-
formation, and furthermore, the interplay of the πꢀπ stacking
interactions lead to the establishment of columnar stacks with a
helical supramolecular architecture.29,30
The substituents (R in Figure 1) attached to the bipyridine
units generally consist of 3,4,5-trialkoxy-benzene fragments
containing solubilizing alkyl28,31,32 or polyether chains.29 More
recently, even desymmetrization of this platform has been
achieved, by the use of two different substituents, two at selected
positions and the other at the remaining one.33 Depending on the
substituents and preparation conditions, discotic liquid
crystals28,33,34 or gels30 have been obtained. In the case of the
aggregates containing chiral side chains, the occurrence of helical
stacks has been proven by circular dichroism (CD) spectroscopic
studies in solution,35 which also emphasized nonlinear effects in
the chiral induction36 according to “sergeants-and-soldiers”31
and “majority rules”32 principles. The peculiar self-assembly
properties of this platform prompted us to attach to its periphery
π-functional tetrathiafulvalene (TTF) units, a well-known elec-
tron rich donor,37,38 in order to take advantage of the propensity
by electron microscopy at the nanoscale. We anticipated that the
presence of chiral alkyl chains on the lateral sulfur atoms would
induce a preferential helicity in the successive levels of hierarch-
ical organization of the supramolecular aggregates of our C3
symmetric derivatives. However, we made the choice to use
rather short chains in order to avoid phase segregation and to
favor intermolecular TTF TTF contacts between the primary
3 3 3
helical stacks with the hope to access higher levels of self-
assembly.
We describe here the synthesis and characterization of both
enantiomers of the C3 symmetric tris[3(30-carbamoylamino)-
2,20-bipyridyl]-benzene-1,3,5-tricarbonamide derivatives con-
taining three chiral bis[(R) or (S)-2-methylbutylthio]-tetrathia-
fulvalenyl units at the periphery. Their self-assembly properties
are investigated in solution by variable temperature circular
dichroism (CD) measurements, combined with theoretical cal-
culations, in order to determine the sense of helicity of the
aggregates. The preference for a helical twist over the opposite
one for each enantiomer is strongly supported by unprecedented
molecular mechanics (MM) and molecular dynamics (MD)
simulations in this family of disk shaped compounds, at two
successive hierarchical levels. The mesoscopic size fibers ob-
tained in the solid state from the pure enantiomers, showing
preferential helical coiling and very interesting hierarchical
architectures, are analyzed by optical and electron microscopy.
Moreover, the racemic system, providing fibers with remarkable
morphology which provide key insight into the chiral induction
in this system, is also described.
’ RESULTS AND DISCUSSION
Synthesis and Characterization. For the synthesis of the
enantiomeric disk-shaped compounds 1a (S,S,S,S,S,S) and 1b (R,
R,R,R,R,R) we have applied the convergent procedure described
previously,39 by using the appropriate TTF acid chlorides 2a and
2b, obtained from the corresponding diesters 8a and 8b, contain-
ing chiral 2-methyl-butyl chains introduced in the early stage of
the synthesis (Schemes 1 and 2; see Supporting Information for
details of the synthesis of all the precursors). While for the
preparation of the (S,S) enantiomer 8a the commercially avail-
able (S)-1-bromo-2-methyl-butane was used, the (R,R) enantio-
mer 8b required first the synthesis of (R)-1-bromo-2-methyl-
butane through a six-step procedure48ꢀ50 adapted from literature
(see Supporting Information for experimental details).
of TTF derivatives to engage in intermolecular S S contacts, a
3 3 3
very important feature of their solid state structures. Thus, by the
use of the C3 compound containing three achiral bis(thioethyl)-
TTF fragments, we have recently prepared electroactive nano-
wires from gels, which had shown electric conductivity upon
doping with iodine.39 Several TTF based gelators that give
electroactive fibers upon doping have been described in the past
five years,40ꢀ46 but chiral expression has been only evidenced47
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Scheme 1. Synthesis of the TTFs 2a and 2b
Scheme 2. Synthesis of the C3-Symmetric Enantiopure
Tris(TTF) 1a and 1b
the usual UVꢀvisible range, since the chiral isopentyl chains do
not absorb there, and their influence on the chromophore
transitions (and by inference the conformation of the molecule)
is negligible. This assumption has been verified by the absence of
any bands in the CD spectra of either enantiomer of 1 in
methylene chloride or chloroform, solvents which do not favor
their self-assembly. The UVꢀvisible spectrum of 1 in CH2Cl2
(c = 10ꢀ5 M; see Supporting Information) shows, in the long
wavelength region, absorption bands attributable to both the
bipyridine and TTF chromophores, arising from πꢀπ * transi-
tions. Accordingly, the less energetic absorption that appears as a
broad, weak band, at λmax = 450 nm (ε = 7400 L molꢀ1 cmꢀ1),
can be attributed to a typical πHOMO ꢀπLUMO* transition in
TTF-amides.52 Then, a much more intense and broad band, as a
result of several closely lying transitions, is observed between 400
and 270 nm with a λmax of 296 nm (ε = 74000 L molꢀ1 cmꢀ1).
The shoulders at 380 and 359 nm are assigned to bipyridine
transitions, by comparison with the Eindhoven system,31,32 while
the one at 326 nm very probably arises from the TTF-amide
units. The spectrum in dioxane, a solvent in which the compound
is sufficiently soluble at room temperature to allow accurate
measurements (c = 2ꢀ5 ꢁ 10ꢀ5 M, after moderate heating to
help solubilization), presents the same features, with the maxima
of the absorption bands slightly blue-shifted by a few nanometers.
Nevertheless, strong optical activity is observed in the CD
spectra in this solvent, with the expected mirror image relation-
ship for the two enantiomers (Figure 2). Clearly, in dioxane a
self-assembly process occurs, with formation of supramolecular
aggregates with opposite helicities for the two enantiomers.
The strong bands at λ = 387 and 368 nm are assigned to
bipyridine transitions,31,32 while the very broad signal centered at
λ = 465 nm and the shoulder at λ = 319 nm very probably result
from transitions involving the TTF units. These features demon-
strate not only that the bipyridine units are tilted in the same
sense within the helical stacks but also that the TTF fragments
are twisted preferentially, as a result of the favored helicity
imposed by the homochiral isopentyl chains. The variable
temperature behavior of the CD signal shows that at higher
temperatures the aggregates tend to dissociate. Indeed, when
heating a solution of 1a in dioxane (c = 2 ꢁ 10ꢀ5 M) to 60 °C for
a couple of minutes only, a complete loss of the CD signal is observed
(Figure 3). Nevertheless, not only is the signal recovered upon
cooling the solution back to 20 °C, since an asymptotic growth
The enantiomeric acid chlorides 2aꢀb were selectively re-
acted with 1 equiv of 3,30-diamino-2,20-bipyridine 3,51 to obtain
the monoacylated derivatives 4aꢀb in good isolated yields, with
only traces of the bis(TTF) compounds being separated. Sub-
sequent reaction of 4aꢀb with trimesic chloride 5 afforded 1aꢀb
in 85% yield, as red-brownish powders which are soluble in
chlorinated solvents. For example, viscous solutions are obtained
at high concentrations of compound in methylene chloride, yet
the gel state has not been reached, as was the case with the achiral
ethyl substituents,39 perhaps because of the greater solubility of
1
these new chiral derivatives. Although H NMR spectra show
only broad signals even at high dilutions in CDCl3, yet corre-
sponding to the different functional groups, mass spectrometry
and elemental analysis are in agreement with the proposed
tris(TTF) structure.
Investigation of Aggregation by Circular Dichroism Spec-
troscopy. A very powerful technique to study helical supramo-
lecular aggregates in solution is circular dichroism (CD) spectro-
scopy.35 Our system as an isolated molecule is not CD active in
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Figure 2. CD spectra of the enantiomers (S)-1a and (R)-1b in dioxane (c = 5 ꢁ 10ꢀ5 M) in a rectangular cell with a 2 mm path length.
Figure 3. Temperature dependence of the CD spectra in dioxane of (S)-1a (c = 2 ꢁ 10ꢀ5 M) in a rectangular cell with a 2 mm path length. Inset: Time
dependence of the CD intensity signal at 387 nm after cooling at 20 °C.
with time is observed, but also its intensity becomes much larger
than the initial one, showing that in the final solution the aggregates
are longer or are better organized because of the slow cooling.
We hypothesize that upon heating most of the aggregates were
disassembled, and only a fraction of small optically inactive
aggregates remained, which act as seeds for the growth of the
optically active self-assembled fibers when cooling the solution.
This process is reproducible and gives mirror image spectra for the
enantiomers, suggesting that any linear dichroism is negligible.
This explanation is supported by the fact that the CD signal is
not recovered after heating at 50ꢀ60 °C for a couple of minutes
for concentrations smaller than 1 ꢁ 10ꢀ5 M, or for 20 min (and
more) for concentrations of 2 ꢁ 10ꢀ5 M, indicating that the critical
concentration for nucleation of the aggregates (i.e., supersatura-
tion) is apparently not reached. So, the aggregates are not formed
in 24 h (or more) after total dissolution. However, when a fresh
concentrated solution (1 ꢁ 10ꢀ4 M) is added to the heated and
cooled 2 ꢁ 10ꢀ5 M solution to reach a final concentration of
3.6 ꢁ 10ꢀ5 M, the CD signal of the resulting mixture is much
more intense than the one due only to the nucleation sites
provided by the new solution. Therefore, it seems that the
existing aggregates from the added solution act as seeds for the
self-assembly of the molecules dispersed in the initially heated
solution (Figure 4).
A solution prepared with a racemic mixture of 1a and 1b does
not show any optical activity, as expected, confirming that the
effects reported above are not a result of linear dichroism. On the
other hand, no clear evidence for a “majority rules” effect could
be observed by CD measurements (vide infra). That is, a straight
line of optical activity versus ratio of enantiomers is obtained.
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This again points to the importance of kinetic effects (nucleation
and growth) in the formation of the fibers of 1.
starting from the C3 core tris[3(30-formylamino)-2,20-bipyridyl]-
benzene-1,3,5-tricarbonamide, and then by adding successively
on the bipyridine wedges TTF, bis(thioethyl)-TTF, and, finally,
(R)-or(S)-2-methylbutylthio-TTF units (Supporting Information).
In each case two helices, one clockwise (CW or P) and the other
counter-clockwise (CCW or M), have been built. While for the
first system the twist of the helices converged to about 12.0°, and
therefore a periodic box of 10 molecules was sufficient to simulate an
infinite stack, when considering the C3 symmetry of our systems,
introduction of TTF units provoked a reduction of the twist to
Molecular Modeling of Simple Stacks. In order to get more
insight into the self-assembly process and to determine the sense
of helicity of the aggregates in solution, molecular mechanics
(MM) and molecular dynamics (MD) calculations were per-
formed, while periodic boundary conditions (PBC) were used to
simulate infinite stacks. The stabilization energy per molecule
arising from stacking interaction is calculated as Estab = (nEisol
ꢀ
Estack)/n, where n is the number of molecules within the stack,
Eisol the energy of an isolated molecule, and Estack the energy of
the stack. Four systems with increasing complexity were studied,
about 8.0°, in order to accommodate TTF TTF interactions.
3 3 3
Consequently, a periodic box of 15 molecules is required to
simulate an infinite stack for the TTF containing systems.
Obviously, the first three compounds are achiral, and thus the
P and M helices have strictly the same energy (Supporting Infor-
mation). The introduction of a chiral group (here the (S)-
methyl-butyl chain) has a drastic influence on the stability, since
the two helices (P and M) are no longer equivalent. Even if the
twist of the helix remains unchanged (about 8°), the intermolecular
distance between the units within the stack is slightly different,
4.01 Å for the P helix and 4.03 Å for the (M) helix. More
importantly, MD simulations show clearly that the M helix is
more stable than the P helix (Supporting Information). By
optimizing several points along the MD trajectory, we were able
to calculate the stabilization energy per molecule at 104.8 ( 0.4
kcal/mol for the P helix and 106.8 ( 0.5 kcal/mol for the M helix,
indicating that the M primary twisted ribbon is the most stable,
very likely thanks to more favorable van der Waals interactions
between the chains, and should be the one responsible for the
chiroptical signals in the CD spectra in solution. Although the
two structures seem similar at first sight, there are clear differ-
ences in the arrangement of the (S)-methyl-butyl groups at the
periphery and also some tiny differences in the hydrogen bond
distances between the amide groups and bipyridine moieties
(Figure 5).
Figure 4. CD spectra in dioxane of (S)-1a at 20 °C before heating (c= 2 ꢁ
10ꢀ5 M) (black line), after heating at 50 °C for 20 min and then standing
at 20 °C for 12 h (c = 2 ꢁ 10ꢀ5 M) (red line), and after adding fresh
solution (cfinal = 3.6 ꢁ 10ꢀ5 M) (blue line), in a rectangular cell with a 10
mm path length.
Figure 5. Aggregate of (S)-1a. Top view (A), side view (C), and detailed view (E) for the P helix; top view (B), side view (D), and detailed view (F) for
the M helix.
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Figure 6. Excitonic CD spectrum of (S)-1a as averaged over the MD trajectory. The inset shows transition densities for a few relevant molecular
electronic transitions involved in the weak, low-energy broad band (B, blue line) and the strong, high-energy band (A, red line). Note the different scales.
Figure 7. Formation of the coiled superhelix after 100 ps of dynamics.
Note that the calculated diameter of a fiber amounts to 43.3 (
by about 60ꢀ90 nm compared to experiment (likely because
solvent effects were not taken into account in the calculations).
Note that this is the first time in this type of C3 symmetric
systems when the helical conformation (M or P) of the aggre-
gates in solution has been unambiguously determined on the
basis of experimental and theoretical CD combined with MM
and MD simulations. Obviously, the opposite result is obtained
when the simulation is performed with the (R)-methyl-butyl chain,
that is a more stable P conformation by 2 kcal/mol (8.38 kJ/mol)
per molecule. In order to estimate the effect of introducing a
small amount of the “wrong” enantiomer into a stack formed by
the major enantiomer in its preferred helical sense, two M helices
containing either 14 (S)-1a and 1 (R)-1b molecules or 13 (S)-1a
and 2 noninteracting (R)-1b molecules have been optimized. In
the first case the aggregate is 0.3 kcal/mol (1.26 kJ/mol) per
molecule less stable than the all (S) stack, while in the second
case it is already 1 kcal/mol less stable, thus indicating that the
sequential insertion of the opposite enantiomer within a chain of
a major enantiomer does not have a linear effect. This could explain
the nonexistence of a “majority rules” effect in our system, since
for an ee of 73%, corresponding to a stack with 13 (S)-1a and
0.1 Å. The shortest intermolecular S S contacts within the
3 3 3
fibers range between 3.87 and 4.48 Å, at the limit of the van der
Waals interactions, while the dihedral angles between the aro-
matic core and the bipyridine units, and the bipyridine and TTF
units, amount to 49.7° and 139.0°, respectively (see Supporting
Information). Thus, there is clearly an interplay between the
πꢀπ stacking of the aromatic units, TTF TTF interactions,
3 3 3
and hydrogen bonding between the amide groups responsible for
the formation and stability of these primary fibers.
Snapshots extracted along the MD simulations of an (S)-1a
(M) helix were used as input for the calculation of the excitonic
contribution to the CD response (see Experimental Section).
The results reported in Figure 6 show multiple negative CD
bands consistent with a left-handed chiral arrangement of the
chromophores. Transitions with weak optical and CD intensity
are predicted in the range 450ꢀ350 nm that have contributions
from both TTF and bipyridine localized electronic excitations, while
a much stronger bipyridine band is computed at ∼300 nm. This
assignment is consistent with the analysis of the measured absorption
and CD spectra above, yet the calculated transitions are blue-shifted
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Figure 9. SEM image of the P helical fibers with different sizes obtained
from a solution of (S)-1a (2 mg/mL) in dioxane and deposited on gold
on glass, with no coating.
Figure 8. Optical micrographs (above) in reflection mode of the P
helical fibers obtained from a solution of (S)-1a (2 mg/mL) in dioxane
and (below) in transmission with polarizing filters crossed.
2 (R)-1b molecules, the chain is already at the halfway point to
the helix reversal in terms of energy (105.8 kcal/mol) when
compared to the pure chain of 15 (S)-1a molecules (106.8 kcal/
mol in M and 104.8 kcal/mol in P conformations). To gain
insight into the upper level of organization of the system, three
primary fibers built out of 45 (S)-1a molecules, in an M con-
formation, have been set next to each other and then left free
to self-assemble with no imposed constraint. MD simulations
(100 ps) clearly show that the three helices wrap spontaneously
one around the other to converge to a coiled superhelix of the
M conformation (Figure 7). The diameter of this secondary helix
is around 6ꢀ7 nm. The estimated shortest S S distance
3 3 3
Figure 10. SEM image of the (M) helical fibers obtained from a solution
of (R)-1b (2 mg/mL) in dioxane and deposited on gold on glass, with no
coating.
between neighboring fibers amounts to about 7.8 Å.
Hierarchical Self-Assembly. As pointed out above, CD
measurements have been performed at concentrations for 1 in
dioxane of 10ꢀ5 M, for which no precipitation occurred. How-
ever, at higher concentrations the compound can be dissolved in
dioxane by heating for a longer time, but upon cooling back to
room temperature a precipitate slowly appears. The analysis of
this precipitate by optical or scanning electronic microscopy
(SEM) reveals the formation of fibers with an exceptionally well-
defined mesoscale helicity, which can be clearly visualized by
these techniques. The best quality fibers were formed for
concentrations in 1aꢀb of 2 mg/mL (1 ꢁ 10ꢀ3 M), and as
can be observed in Figure 8, the fibers, obtained from the (S)
enantiomer 1a, show right-handed (P) helicity. The fibers are as
long as dozens of micrometers, while their height is identical to
their width, amounting to 1.5ꢀ2.0 μm, as proven by changing the
focal plane from the top of the fibers to the middle, and to the
bottom. In addition, the molecules seem to be well ordered in the
fibers, as indicated by the bright contrast seen in transmission
optical micrographs.
Measurement of the sizes of the fibers in the sharpest images
indicates that they have a thickness of about 1.5ꢀ1.6 μm. The
stripes visible on the fibers have a thickness of 1.05ꢀ1.1 μm, form
an angle of 45° with the long axis of the fiber, and repeat with a
pitch of 1.05 μm. It appears thus that the large fiber is formed
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example of the collagen,57ꢀ59 consisting of three left-handed helices
giving rise by self-assembly to a right-handed coiled coil, show
the same type of helical inversion between the different levels of
hierarchical organization, although it is very difficult to rationa-
lize or to predict this behavior. The following image (Figure 9)
shows an area with larger fibers seen very occasionally, which
show a higher order of chiral expression, but of the same sense.
These fibers have a width of 2.5 μm, whereas the majority of
the fibers have a width of 1.5ꢀ2.0 μm. As expected, the (R)
enantiomer 1b provides fibers with the opposite helicity (M) but
the same size range, under the same conditions (Figure 10).
When a racemic mixture of (S)-1a (2 mg/mL) and (R)-1b
(2 mg/mL) is reprecipitated from hot dioxane the pattern of the
fibers is particularly interesting, since within the same fiber there
are several homochiral but opposite domains with points where
helical reversal is clearly observed (Figure 11).
The size of these fibers is similar to that of the enantiopure
ones. The fact that helical reversal is observed in the case of the
racemic mixture can be discussed in terms of a diffusion
controlled process. For example, during the formation of the
fibers from (S)-1a, with (P) helicity, the growth rate is far
superior to the diffusion rate, thus leading to a gradual increase
of the local supersaturation in the opposite enantiomer (R) until
the point when the critical supersaturation is reached. Then the
growth of the fiber continues with the (R) enantiomer which
promotes the opposite helicity (M) after an occurrence of helical
reversal. Thus, the formation of fibers resembles an oscillating
process and can be related to the 2D oscillating crystallization
phenomenon, nicely described by Coquerel et al.60 This idea is
backed up by the observation of much longer but less ordered
fibers upon mechanical stirring during precipitation, very likely
because of the faster kinetics favoring the diffusion process.
Variable ratio mixtures of the two enantiomers did also provide
the same type of fibers showing both helicities, with no indication
of a “majority rules” effect, in agreement with the CD measure-
ments and the MM and MD simulations on the primary fibers.
’ CONCLUSIONS
Enantiopure C3 symmetric disk-shaped molecules containing
electroactive TTF units decorated with short chiral isopentyl
chains can be synthesized effectively, and they self-assemble into
helical aggregates showing a preferential helicity twist over
several length scales. In solution, the formation of primary helices
as twisted stacks is investigated by CD measurements combined
with theoretical calculations. The CD investigations show that
the chiral expression can be improved by thermal dissociation
and reformation on a nucleus in the solution and that the growth
of the fibers is controlled by the nucleation event. The relative
stability of the (P) and (M) conformations of the stacks has been
evaluated by MM and MD simulations, which clearly indicate
that the (S)-1a enantiomer provides the M helix, more stable by 2
kcal/mol per molecule than the P helix, in agreement with the
optical activity observed in CD spectra. Also, a simulation of a
stack containing a large majority of one enantiomer and one or
two molecules of the opposite enantiomer shows that the
insertion of the “wrong” enantiomer in the helix is unfavorable
for the observation of the “majority rules” effect, in the sense that
the energy difference between the two helical twists becomes
much smaller. For higher concentrations of the compound
mesoscopic size chiral fibers have been obtained, their formation
being clearly dependent on seeding nucleation and diffusion rate.
Figure 11. SEM images of helical fibres obtained from a sample of 1:1
(S)-1a/(R)-1b (2 mg/mL each) in dioxane and deposited on gold on
glass, with no coating.
from two smaller ones that twist around each other. When
considering the computed diameter (∼4.3 nm) of a primary
fiber it appears that (at least) approximately 250 primary helices
could fit side by side in one of these smaller fibers visible as stripes
on the big fiber, yet this number should be much larger since the
single fibers twist around each other when put close together, as
observed in the simulation with three of them. The fibers are
bright in the polarized transmission optical micrographs, indicat-
ing a highly ordered and periodic superstructure. At first sight,
the inversion of helicity between the primary twisted stacks or
secondary helical aggregates of M conformation in solution and
the solid fibers, which can be seen as superhelices or supercoiled
coils formed upon hierarchical self-assembling at successive
levels of organization, seems surprising. Nevertheless, various
examples of helical architectures, either synthetic, as those
described by Nolte et al.,53ꢀ56 or from nature, such as the famous
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Optical and electron microscopy studies show that the solid
fibers, comprised of multiple fibers, have opposite chirality with
respect to the helicity of the single strand fibers in solution.
Remarkable morphologies are observed for the fibers obtained
with the racemic mixture, since homochiral domains together
with helical reversal points are present within the same fiber.
Thus, these TTF-containing C3 symmetric compounds allowed
the achievement of an unprecedented hierarchical chiral self-assembly
in a nonamphiphilic system, very likely thanks to the propensity
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’ ASSOCIATED CONTENT
S
Supporting Information. Full experimental section in-
b
cluding description of the synthesis and characterization of all
new materials and all the techniques employed in the research
reported here. This material is available free of charge via the
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’ AUTHOR INFORMATION
Corresponding Author
amabilino@icmab.es; narcis.avarvari@univ-angers.fr
(25) Hasegawa, M.; Iyoda, M. Chem. Soc. Rev. 2010, 39, 2420–2427.
(26) Schenning, A. P. H. J.; Meijer, E. W. Chem. Commun.
2005, 3245–3258.
’ ACKNOWLEDGMENT
(27) Hoeben, F. J. M.; Jonkheijm, P.; Meijer, E. W.; Schenning, A. P.
H. J. Chem. Rev. 2005, 105, 1491–1546.
This work was supported in France by the Ministry of
Education and Research (grants to I.D. and F.R.), the National
Agency for Research (ANR, Project 09-BLAN-0045-01), and the
CNRS, in Spain by the DGI-Spain (Project CTQ2010-16339),
DGR, Catalonia (Project 2009 SGR 158), and the European
Community0s Seventh Framework Programme under Grant
Agreement No. NMP4-SL-2008-214340, Project RESOLVE.
Financial support from the COST Action D35 is also gratefully
acknowledged. The work in Mons is partly supported by the
Interuniversity Attraction Pole IAP 6/27 of the Belgian Federal
Government and the Belgian National Fund for Scientific
Research (FNRS/FRFC). D.B. is a FNRS Research Director.
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