Helical and flat structures from chiral dendronized rectangular oligo(phenylene ethynylene)s

Article abstract of DOI:10.1021/ol101673z

Figure Presented. The synthesis of two chiral amphiphiles and their self-assembling features in solution and onto surfaces is reported. The different degree of interdigitation of the paraffinic substituents has an enormous influence in the chirality of the aggregates. Thus, while oligo(phenylene ethynylene) 1 shows a bisignated Cotton effect in solution and P-type helices onto surfaces, compound 2 lacks in any dichroic response at room temperature and self-assembles into flat ribbons.

Full text of DOI:10.1021/ol101673z

ORGANIC
LETTERS
2010
Vol. 12, No. 19
4264-4267
Helical and Flat Structures from Chiral
Dendronized Rectangular
Oligo(phenylene ethynylene)s
Fa´tima Garc´ıa,† Fa´tima Aparicio,† Marco Marenchino,‡ Ramo´n Campos-Olivas,‡
and Luis Sa´nchez*,†
Departamento de Qu´ımica Orga´nica, Facultad de Ciencias Qu´ımicas, UniVersidad
Complutense de Madrid, Ciudad UniVersitaria s/n. 28040 Madrid, Spain, and
Structural and Computational Biology Programme, Centro Nacional de
InVestigaciones Oncolo´gicas (CNIO), Melchor Ferna´ndez Almagro, 3,
Madrid E-28029, Spain
lusamar@quim.ucm.es
Received July 20, 2010
ABSTRACT
The synthesis of two chiral amphiphiles and their self-assembling features in solution and onto surfaces is reported. The different degree of
interdigitation of the paraffinic substituents has an enormous influence in the chirality of the aggregates. Thus, while oligo(phenylene ethynylene)
1 shows a bisignated Cotton effect in solution and P-type helices onto surfaces, compound 2 lacks in any dichroic response at room temperature
and self-assembles into flat ribbons.
Chirality is a topic of intense debate and study in chemistry,
and particularly, the origin of homochirality is in the forefront
of this research. Big efforts are being devoted to clarify the
process that yielded asymmetric natural products from
original achiral racemates.1 The generation of chirality is
related to an efficient transfer of chiral information from
chiral units to complex supramolecular structures through
noncovalent interactions.
To emulate the natural organization of biomolecules such
as proteins or polysaccharides, a variety of organic systems
(1) (a) Weissbuch, I.; Leiserowitz, L.; Lahav, M. Top. Curr. Chem. 2005,
259, 123–165. (b) Luisi, P. L. The Emergence of Life: From Chemical
Origins to Synthetic Biology; Cambridge University Press: Cambridge, 2006.
(c) Fo¨rster, S.; Plantenberg, T. Angew. Chem., Int. Ed. 2002, 41, 688–714.
(d) Cornelissen, J. J. L. M.; Rowan, A. E.; Nolte, R. J. M.; Sommerdijk,
N. A. J. M. Chem. ReV. 2001, 101, 4039–4070.
† Universidad Complutense de Madrid.
‡ Centro Nacional de Investigaciones Oncolo´gicas.
10.1021/ol101673z  2010 American Chemical Society
Published on Web 09/02/2010

Scheme 1. Synthesis of Chiral Amphiphiles 1 and 2
endowed with chiral paraffinic side chains can be found in
the literature.2 These studies demonstrate that the absolute
configuration of the stereogenic centers conditions the handed-
ness of the chiral supramolecular constructs. Considering that
the original homochirality took place in aqueous media, ethylene
oxide chains have been attached to those organic systems to
generate nonionic amphiphiles.3 We have incorporated this class
of side chains to radial oligo(phenylene ethynylene) (OPE)
platforms to construct supramolecular ensembles of modulated
morphology and dimensionality.4
Herein, we report on the synthesis of nonionic amphiphiles
based on a rectangular OPE scaffold peripherally substituted
with chiral side chains of paraffinic or polar nature (com-
pounds 1 and 2 in Scheme 1 and Figure S1 in Supporting
Information). The chiral features of amphiphiles 1 and 2 in
solution and onto surfaces have been investigated, and we
have demonstrated that the interdigitation of the alkyl
substituents exerts an enormous influence on the chirality
of the self-assembled nanostructures.
reogenic centers of absolute configuration S at the paraffinic
chains (1) or at the ethylene oxide substituents (2) by sequential
Sonogashira cross-coupling reactions6 with the corresponding
alkoxyiodobenzenes (4a,b or 7a,b)7 (Scheme 1).
The chemical structure of the new compounds has been
1
confirmed by H NMR, 13C NMR, and FTIR spectroscopy
and MALDI-TOF spectrometry. The symmetry of com-
1
pounds 1 and 2 gives rise to simple H NMR spectra with
only three aromatic resonances at δ ≈ 7.8, 7.6, and 6.9. The
methyl groups attached to the stereogenic centers appear as
doublets at δ ≈ 1.0. The stretching bands corresponding to
the CH2 groups provide valuable information about the
interdigitation degree of the paraffinic chains: while 1 shows
two broad vibrations at ν 2923 and 2869 cm-1, 2 presents
sharper vibrations at 2925 and 2857 cm-1 (Figure S2 in
Supporting Information) diagnostic of more efficient inter-
digitation of the alkyl chains.8
The self-assembly of 1 and 2 was first investigated by
concentration-dependent UV-vis experiments in acetonitrile
(MeCN) as solvent.9 In these experiments, the appearance
of bands at 329 and 360 nm is concomitant with the depletion
of the band at ∼275 nm with increasing concentration, which
implies the π-stacking of these amphiphiles (Figure S3 in
Supporting Information). The variation of the molar fraction
of aggregates (Raggr) with the concentration of OPE is
The synthesis of the target OPEs starts with 1,2-dibromo-
4,5-diiodobenzene,5 which yields chiral amphiphiles with ste-
(2) (a) Rosen, B. M.; Wilson, C. J.; Wilson, D. A.; Peterca, M.; Imam,
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Vijayakumar, C. Angew. Chem., Int. Ed. 2006, 45, 1141–1144. (h) Percec,
V.; Dulcey, A. E.; Balagurusamy, V. S. K.; Miura, Y.; Smidrkal, J.; Peterca,
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Maganov, S. N.; Vinogradov, S. A. Nature 2004, 430, 764–768. (i) George,
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(6) Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang,
P. J., Eds.; Wiley-VCH: New York, 1998.
(7) Compounds 3a, 3b, 4b, and 6a have been prepared by following
previously reported procedures. See ref 4d. For the synthesis of the chiral
dendritic polar chain present in compound 6b, see: (a) Peterca, M.; Percec,
V.; Imam, M. R.; Leowanawat, P.; Morimitsu, K.; Heiney, P. A. J. Am.
Chem. Soc. 2008, 130, 14840–14852. (b) Kim, H.-J.; Zin, W.-C.; Lee, M.
J. Am. Chem. Soc. 2004, 126, 7009–7014.
(3) Ryu, J.-H.; Hong, D.-J.; Lee, M. Chem. Commun. 2008, 1043–1054.
(4) (a) Ferna´ndez, G.; Garc´ıa, F.; Sa´nchez, L. Chem. Commun. 2008,
6567–6569. (b) Garc´ıa, F.; Aparicio, F.; Ferna´ndez, G.; Sa´nchez, L. Org.
Lett. 2009, 11, 2748–2751. (c) Garc´ıa, F.; Ferna´ndez, G.; Sa´nchez, L.
Chem.sEur. J. 2009, 15, 6740–6747. (d) Ferna´ndez, G.; Garc´ıa, F.;
Aparicio, F.; Matesanz, E.; Sa´nchez, L. Chem. Commun. 2009, 7155–7157.
(e) Garc´ıa, F.; Sa´nchez, L. Chem.sEur. J. 2010, 16, 3138–3146.
(8) The asymmetric and symmetric stretching peaks corresponding to
an all-trans conformation appear at 2918 and 2849 cm-1, respectively. See:
Nakanishi, T.; Michinobu, T.; Yoshida, K.; Shirahata, N.; Ariga, K.;
Mo¨hwald, H.; Kurth, D. G. AdV. Mater. 2008, 20, 443–446.
(9) Despite the polar chains incorporated into the aromatic framework
of 1 and 2, it is not possible to solubilize them in polar solvents such as
H2O, butanol, or THF at concentrations higher than 1 × 10-4 M.
Org. Lett., Vol. 12, No. 19, 2010
4265

sigmoidal in shape and fits to eq 1, corresponding to an
isodesmic model (insets in Figure S3 in Supporting Informa-
tion).10 This analysis sheds values for the binding constant
of ∼5.4 × 105 and 4.2 × 105 M-1 for 1 and 2, respectively.
for 1, turbid dispersions appear above 30 °C, and no CD
response is detected. However, at 10 °C and below, a bisignated
Cotton signal is observed with positive and negative waves at
310 and 340 nm, respectively. This Cotton effect would be
indicative of a left-handed helical columnar stack.
The presence of aggregated species in solution has been
further corroborated by dynamic light scattering (DLS).
CONTIN analysis of the DLS autocorrelation function of
aqueous solutions of 1 (10-4 M) at 90° shows a broad
distribution of hydrodynamic radii (RH) of aggregates
centered at ∼30 nm (Figure S6 in Supporting Information).
However, the similar analysis carried out for aqueous solution
of 2 at the same concentration exhibits an extremely broad
distribution from 10 nm to several micrometers and with
maxima at 30 nm (similarly to 1), 210 nm, and 1.4 µm
(Figure S6 in Supporting Information). In both cases, the
broad distribution of RH could be indicative of a high degree
of polydispersity.14
2Kc + 1 - 2Kc + 1
√
T
T
Raggr ) 1 -
(1)
2(KcT)2
To further corroborate the mechanism experienced by these
compounds to self-assemble, we exploited circular dichroism
(CD) spectroscopy at different conditions of concentra-
tion and temperature (Figures 1, S4, and S5 in Supporting
Finally, we have visualized the supramolecular aggregates
detected in solution by transmission electron microscopy
(TEM). TEM images taken from 1 × 10-4 M aqueous
solutions of chiral OPE 1 show isolated thick rope-like
structures (Figures 2 and S7 in Supporting Information). All
Figure 1
.
CD spectra (a) of 1 and 2 (H2O, 5 × 10-5 M, 5 °C) and
melting curves for 1 (b) and 2 (c) from 5 to 90 °C at intervals of
1 °C/min.
Information).11 In aqueous solution, compound 1 presents a
bisignated Cotton effect with a negative wave at around 300
nm and a positive wave at 340 nm indicative of a right-
handed helical stacking.12 Increasing temperature results in
the desappearence of this CD signal (Figure 1b), and a turbid
dispersion becomes visible. Thus, the dispersion is formed
above the low critical solution temperature transition in
aqueous media. In these conditions, the polar chains are
dehydratated, generating new supramolecular ensembles less
soluble in the aqueous solution.13
Figure 2. TEM images showing the right-handed helical stacks
formed from 1 (∼10-4 M, H2O, 25 °C) onto carbon-coated copper
grids. The insets show a zoom TEM image (down) and the density
profile (top).
Surprisingly, chiral OPE 2 shows no CD signal at room
temperature, despite the fact that it possesses four stereogenic
centers (Figure 1c and S5 in Supporting Information). As occurs
of the helical columnar stacks are right-handed, in very good
agreement with the CD data, and the density profiles indicate
that the pitch of these P-type helices is ∼135 nm. The apolar
nature of the chiral paraffinic chains and the aromatic
skeleton provokes the interdigitation of the chiral paraffinic
chains and the π-stacking. These noncovalent forces produce
chiral self-assembled fibers with a preferred helicity determined
by the stereogenic centers.15 The hydrophobic core of the
aggregated species forces them to coil until forming the thick
filaments that keep the original helical sense (Figure 3).16
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(11) CD spectroscopy has been demonstrated to provide accurate data
on the self-assembly mechanism followed by chiral compounds. For recent
examples, see ref 2a and Jonkheijm, P.; van der Schoot, P.; Schenning,
A. P. H. J.; Meijer, E. W. Science 2006, 313, 80–83.
(12) Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry of Organic
Compounds; Wiley-Interscience: Chichester, U.K., 1994.
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Smith, G. D.; Bedrov, D. J. Phys. Chem. B 2003, 107, 3095–3097. (c)
Aathimanikandan, S. V.; Savariar, E. N.; Thayumanavan, S. J. Am. Chem.
Soc. 2005, 127, 14922–14929. (d) Jia, Z.; Chen, H.; Zhu, X.; Yan, D. J. Am.
Chem. Soc. 2006, 128, 8144–8145. (e) Hirose, T.; Matsuda, K. Chem.
Commun. 2009, 5832–5834.
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4266
Org. Lett., Vol. 12, No. 19, 2010

by the π-stacking of the aromatic framework and the van
der Waals interactions of the decyl side chains. This
hydrophobic structure constitutes the core of the aggregate
being the hydrophilic dendritic chains pointing outward. The
aggregated species thus formed are intrinsically achiral due
to the presence of a symmetry plane in the basic dimeric
unit that frustates a helical organization (Figure 3). Similarly
to amphiphile 1, the hydrophobic core of the aggregates
avoids contacting with the polar environment by the interac-
tion of the dendritic polar wedges forming a dense packing
of tapes and the final thick ribbons appear.
The visualization of isolated self-assembled bilayer ribbons
from 2 has been achieved by using the apolar methylcylco-
hexane (MCH) as solvent to prepare the samples for TEM
imaging. In these conditions, the aromatic skeletons are
interacting by π-stacking, the paraffinic chains would be
entangled to a lesser extent and the polar dendritic wedges
could be slightly coiled. All of these supramolecular forces
direct the formation of long ribbons with typical diameters
of ∼7 nm diagnostic of the formation of a bilayered ribbon
(Figures 4b and S9 in Supporting Information). In addition,
some regions of the long ribbons present diameters of ∼5
nm (red line and inset in Figure 4b). This value is too large
for a single molecule and implies (1) the interaction of 2
forming a bilayer and (2) the formation of slightly twisted
tapes with folded edges generated to avoid the steric
constrains imposed in the columnar stacks by the dendritic
polar wedges to avoid their steric hindrance.4d,17
Figure 3. Schematic illustration of the dimers (represented as blue
tablets) formed upon interdigitation of 1 and 2 and the subsequent
aggregation. The plane of symmetry of the dimer of 2 is shown in
light blue.
TEM images of aqueous solutions (1 × 10-4 M) of
compound 2 demonstrate that this rectangular OPE does not
form chiral nanostructures (Figures 4a and S8 in Supporting
In conclusion, we have synthesized two nonionic chiral
amphiphiles that present opposite chiral features upon
association. The presence of stereogenic centers at the alkyl
chains impedes their efficient interdigitation. Thus, CD and
TEM images demonstrate the formation of right-handed
helices. Contrary to that, when chiral dendritic polar side
chains and linear decyl substituents decorate the periphery
of the aromatic framework, no CD response appears at room
temperature and the aggregation of this chiral OPE forms
achiral ribbons. These studies, which are opposite to those
previously reported for referable chiral hexa-peri-bencoron-
nenes,18 provide valuable information about the structural
requirements participating in the translation of point chiral
information from the molecular to the supramolecular level.
Figure 4. TEM images of amphiphilic OPE 2 in aqueous solution
(∼10-4 M, 25 °C) (a) and in MCH (∼10-4 M) solution (b) onto
carbon-coated copper grids. The insets in (a) and (b) shows the
density profiles along the red lines.
Acknowledgment. This work has been supported by UCM
(UCM-SCH-PR34/07-15826). The MICINN of Spain is
thanked by F.G. for a FPU research grant. The authors are
gratefully acknowledged to Prof. N. Mart´ın (UCM, Spain)
for the generous help.
Information). In contrast, ribbons with a uniform diameter
of ∼67 nm are observed. As indicated by the CD experiments
at room temperature, the lack of chirality in solution is fairly
translated to the surface. Considering the FTIR data, the
aggregation of 2 involves an efficient interdigitation of the
decyl chains that gives rise to self-assembled achiral bilay-
ered fibers whose basic constitutive unit would be a sym-
metric dimer (Figure 3). These fibers would be stabilized
Supporting Information Available: Experimental details
and supplementary figures. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL101673Z
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