Solvophobic effects in the self-assembly of triangular-shape amphiphilic oligo(phenylene ethynylenes)

Article abstract of DOI:10.1021/ol900832e

Triangular-shape OPEs, decorated In their periphery with a variable number of hydrophilic and hydrophobic substituants, have been synthesized to evaluate the Influence of the solvent-solute and solute-solute Interactions Involved In their self-association

Full text of DOI:10.1021/ol900832e

ORGANIC
LETTERS
2009
Vol. 11, No. 13
2748-2751
Solvophobic Effects in the
Self-Assembly of Triangular-Shape
Amphiphilic Oligo(phenylene
ethynylenes)
Fa´tima Garc´ıa, Fa´tima Aparicio, Gustavo Ferna´ndez, and Luis Sa´nchez*
Departamento de Qu´ımica Orga´nica, Facultad de Ciencias Qu´ımicas, Ciudad
UniVersitaria, s/n. 28040 Madrid, Spain
lusamar@quim.ucm.es
Received April 16, 2009
ABSTRACT
Triangular-shape OPEs, decorated in their periphery with a variable number of hydrophilic and hydrophobic substituents, have been synthesized
to evaluate the influence of the solvent-solute and solute-solute interactions involved in their self-association. The similar size and electronic
properties for these radial OPEs allow a direct evaluation of the solvophobic component of the π-π stacking since any preferential Coulombic
or dispersion effect can be discarded. In addition, the formation of aggregates in solution is efficiently transferred to surfaces and the formation
of hollow vesicles can be observed.
The formation of helices from natural biomolecules like proteins
or polynucleotides is guided by the participation of a number
of noncovalent interactions and, significantly, by solvophobic
effects.1 Given that the flat π-surface of aromatic moieties and
the aliphatic chains possess a nonpolar character, polar solvents
favor their stacking to minimize the contact with solvent
molecules, and as a consequence, solvophobic forces play a
pivotal role in the stability and organization of supramolecular
structures with natural1,2 or synthetic3 substrates, many of
them presenting an amphiphilic character.
Nonspecific forces like π-π interactions and, more
specifically its solvophobic component,4 also participate and
control the creation of architectures with different morphol-
ogy and dimensionality from self-assembled amphiphilic
aromatic molecules. Vesicles, micelles, or (helical) fibers can
be obtained from a variety of aromatic amphiphiles in which
the aromatic core is constituted by hexabenzocoronenes,5
perylenebisimides,6 or different classes of π-conjugated
oligomers.7,8 We have recently reported on the formation
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Thompson, J. L.; Moore, J. S. J. Am. Chem. Soc. 2000, 122, 11315–11319.
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5525–5534. (b) Hunter, C. A.; Lawson, K. R.; Perkins, J.; Urch, C. J.
J. Chem. Soc., Perkin Trans. 2 2001, 651–669. (c) Hunter, C. H. Angew.
Chem., Int. Ed. 2004, 43, 5310–5324.
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M.; Scheraga, H. A.; Lifson, S. Biopolymers 1963, 1, 419–429. (c)
Padmanabhan, S.; Baldwin, R. L. J. Mol. Biol. 1994, 241, 706–713. (d)
Saenger, W. Principles of Nucleic Acid Structure; Springer-Verlag: New
York, 1984.
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2260.
10.1021/ol900832e CCC: $40.75
Published on Web 06/01/2009
 2009 American Chemical Society

of supramolecular structures of different morphology and
dimensionality (vesicles, toroids, networks or wires) from
simple radial oligo(phenylene ethynylenes) (OPEs).9
Herein, we report on the synthesis, redox properties, and
self-assembling features of a series of triangular-shape
amphiphilic OPEs decorated with a variable number of polar
tryethyleneglycol (TEG) and aliphatic decyl chains in their
periphery. The similar size and electronic properties of the
new amphiphiles reported discard any preferential dispersion
or Coulombic effect in their π-stacking, and therefore, a
direct evaluation of the influence of solvophobic effects in
the self-assembly can be extracted from this type of discrete
amphiphilic systems.
the heptamer (m/z ) 5964) are distinguishable for 1 and 2,
respectively (Figures S1 and S2, Supporting Information).
Similar results have been obtained for the previously reported
congeners S19a and S212 (see the Supporting Information)
bearing three TEG or three decyl chains, respectively (Figure
S3, Supporting Information).
The self-assembly features of 1 and 2 in solution were
first investigated by concentration-dependent 1H NMR
experiments (Figures 1 and S4, Supporting Information).
Compounds 1 and 2, endowed with a variable number of
TEG and decyl chains and, therefore, with a modulated
hydrophilia/hydrophobia relationship, have been readily
obtained by following a one-pot Sonogashira cross-coupling
protocol10 in which the decyloxyphenyl units are first
attached to the central aromatic fragment. Thus, for the
synthesis of 1, endowed with two TEG and only one decyl
chains, 1,3,5-triethynylbenzene (3b)11 was reacted with 1
equiv of the 1-(decyloxy)-4-iodobenzene 4a12 in the presence
of triethylamine, copper iodide, and Pd(PPh3)Cl2 as catalyst.
The reaction was monitored by TLC until all starting
materials 3b and 4a disappeared. After that, an excess of
4b9a was added to the reaction mixture to afford 1 in 26%
yield (Scheme 1). A similar strategy was followed to obtain
1
Figure 1
.
Partial H NMR spectra (CD3CN, 300 MHz) of 1 at
different concentrations (1.5-100 mM).
1
Concentration-dependent H NMR studies of 1 in CD3CN
(300 MHz, 298 K, 1.5-100 mM)13 show slight upfield shifts
of most resonances upon increasing concentration, indicative
of an eclipsed face-to-face π-π stacking (Figure 1).4
However, only the resonance corresponding to the protons
of the central aromatic ring experienced a small shielding
effect with increasing concentration when similar studies
were carried out with 1 and 2 in C6D6 (300 MHz, 298 K,
1.5-100 mM) (Figure S4, Supporting Information), which
can be attributed to a rotated offset π-stacking.4 Plotting the
variation of the chemical shifts versus concentration reveals
the different participation of the aromatic moieties in
Scheme 1. Synthesis of Triangular-Shape Amphiphiles 1 and 2
(6) (a) Ghosh, S.; Li, X.-Q.; Stepanenko, V.; Wu¨rthner, F. Chem.sEur.
J. 2008, 14, 11343–1357. (b) Zhang, X.; Chen, Z.; Wu¨rthner, F. J. Am.
Chem. Soc. 2007, 129, 4886–4887. (c) Xu, B. Q.; Xiao, X.; Yang, X.; Zang,
L.; Tao, N. J. J. Am. Chem. Soc. 2005, 127, 2386–2387.
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T. D.; Glotzer, S. C.; Lee, M. Angew. Chem., Int. Ed. 2009, 48, 1664–
1668. (b) Ryu, J.-H.; Hong, D.-J.; Lee, M. Chem. Commun. 2008, 1043–
1054.
2, which possesses two decyl and one TEG chains, in 33%
yield (Scheme 1). Compounds 1 and 2 have been fully
characterized by NMR, FTIR, and UV-vis spectroscopy and
MALDI-TOF spectrometry (see the Supporting Information).
A first insight into the self-assembly ability of compounds
1 and 2 was obtained from the corresponding MALDI-TOF
spectra. Both amphiphiles show no preferential self-as-
sembling properties in the gas phase since the presence of
aggregated species up to the pentamer (m/z ) 4290) and to
(8) (a) Ajayaghosh, A.; Praveen, V. K. Acc. Chem. Res. 2007, 40, 644–
656. (b) Hoeben, F. J. M.; Shklyarevskiy, I. O.; Pouderoijen, M. J.;
Engelkamp, H.; Schenning, A. P. H. J.; Christiansen, P. C. M.; Maan, J. C.;
Meijer, E. W. Angew. Chem., Int. Ed. 2006, 45, 1232–1236.
(9) (a) Ferna´ndez, G.; Garc´ıa, F.; Sa´nchez, L. Chem. Commun. 2008,
6567–6569. (b) Garc´ıa, F.; Ferna´ndez, G.; Sa´nchez, L. Chem.sEur. J., in
press., DOI: 10.1002/chem.200900303.
(10) Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang,
P. J., Eds.; Wiley-VCH: New York, 1998.
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Jasper, B.; Hepp, A. Organometallics 2007, 26, 2363–2369.
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470.
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Shimomura, T.; Ito, K.; Hashizume, T.; Ishii, N.; Aida, T. Science 2004,
304, 1481–1483. (b) Kastler, M.; Pisula, W.; Wasserfallen, D.; Pakula, T.;
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(13) The scarce solubility of less polar 2 in CD3CN at concentrations
1
above of 10 mM has prevented a concentration-dependent H NMR study
in this solvent.
Org. Lett., Vol. 11, No. 13, 2009
2749

comparison with the peripheral chains in the self-assembly
process of 1 and 2 (Figure S4, Supporting Information).
The small variation of the chemical shifts observed upon
increasing concentration impedes the calculation of an
accurate value for the association constant (Ka). Thus, in
order to attain the value of Ka and also to evaluate the
influence of the solvent on this thermodynamical parameter,
we have carried out concentration-dependent UV-vis in-
vestigations in a number of solvents of increasing polarity
(Figures S5-8 and Table S1, Supporting Information).
The concentration-dependent UV-vis experiments carried
out for 1 and 2 show identical spectroscopical features. As
occurs in our previous described amphiphilic OPEs,9 the
appearance of bands of low energy is accompanied by the
depletion of the higher energetic band at ∼260 nm. These
features are diagnostic of the π-stacking of these amphiphiles
to form supramolecular structures. In addition, we have
calculated the Ka values for 1 and 2 and also for S1 and S2
by applying the isodesmic model14 to the molar extinction
coefficient (Figures S5-8 and Table S1, Supporting Infor-
mation).9,15
kcal/mol)17 reveals that this thermodynamic parameter
decreases linearly with the increasing number of alkyl chains
(Table S1 (Supporting Information) and Figure 3). As
Figure 3. Plot of the variation of the calculated Ka (UV-vis, 298
K) values in solvents of different polarity. Error bars are associated
with an estimated maximum error of ( 5%.
The calculation of the molar fraction of n-mer aggregates
(Rn) corroborates the applicability of the isodesmic mecha-
nism for the self-assembly of the studied compounds (Figures
2 and S9, Supporting Information).14-16 As expected, the
expected, the opposite trend is observed for the Ka values
determined for nonpolar solvents like benzene (ε ) 2.3, ET(30)
) 34.3 kcal/mol)17 or methylcyclohexane (MCH) (ε ) 2,
ET(30) ) 30.9 kcal/mol),17 in which the Ka values increase
linearly from compound S2, endowed with three aliphatic
chains, to S1 that bears three TEG substituents. Using a
solvent of intermediate polarity as CH2Cl2 (ε ) 9.1, ET(30)
) 40.7 kcal/mol)17 results in nearly identical Ka values
regardless of the number of hydrophilic and hydrophobic
chains. It is well-stablished that chlorinated compounds are
“bad” solvents for favoring π-π interactions which accounts
for the low binding constants observed in CH2Cl2.3
Interestingly, when 2-propanol (ε ) 18, ET(30) ) 48.4 kcal/
mol)17 is utilized to perform the concentration-dependent
UV-vis investigations, the Ka values follow a parabolic trend
(Figure 3) with a maximum value for the binding constant
of compound 1 (∼5 × 105 M-1) and a significant Ka value
for compound 2 of ∼3.5 × 105 M-1, higher than that
determined for S1 that possesses three peripheral polar
chains. Under these conditions, solvent-solvent interactions
are energetically favorable and give rise to a solvent cage
that surrounds the arrays formed by positive solute-solute
solvophobic interactions among the nonpolar aromatic
moieties and the coiled decyl chains. These solvent-solvent
and solute-solute interactions enhance the global π-stacking
of the aromatic rings and increase the Ka values.3,4
Figure 2. Molar fraction of n-mer aggregates (Rn) of 1 (left) and
2 (right) as a function of concentration in different solvents.
increase of Rn for those amphiphiles bearing polar TEG
chains (S1, 1, and 2) starts at lower concentration for polar
solvents, which is diagnostic of their strong propensity to
stack.
A detailed inspection on the Ka values calculated for the
studied compounds in polar CH3CN (ε ) 37, ET(30) ) 45.6
The exothermicity of the self-assembly of amphiphile 1
in isopropanol has been studied by the van’t Hoff analysis
of the Ka values determined by concentration-dependent
UV-vis experiments at different temperatures (Figure S10).
The obtained thermodynamic parameters are ∆H ) -27.07
(14) (a) Martin, R. B. Chem. ReV. 1996, 96, 3043–3064. (b) Zhao, D.;
Moore, J. S. Org. Biomol. Chem. 2003, 1, 3471–3491. (c) Chen, Z.; Lohr,
A.; Saha-Mo¨ller, C. R.; Wu¨rthner, F. Chem. Soc. ReV. 2009, 38, 564–584.
(15) Wu¨rthner, F.; Thalacker, C.; Diele, S.; Tschierske, C. Chem.sEur.
J. 2001, 7, 2245–2253
.
(16) Chen, Z.; Stepanenko, V.; Dehm, V.; Prins, P.; Siebbeles, L. D. A.;
Seibt, J.; Marquetand, P.; Engel, V.; Wu¨rthner, F. Chem.sEur. J. 2007,
(17) SolVents and SolVent Effects in Organic Chemistry; Reichardt, C.,
Ed.; Wiley-VCH: Weinheim, 2003.
13, 436–449
.
2750
Org. Lett., Vol. 11, No. 13, 2009

kJ mol-1 and ∆S ) -14.21 J mol-1. These negative
thermodynamical values demonstrate that the enthalpy is the
driving force in the aggregation of 1 in this solvent.18
The redox characteristics of amphiphilic compounds 1, 2,
and S119 have been examined by cyclic voltammetry in
acetonitrile at room temperature (Figure 4). The similar
Figure 5
.
SEM image (298 K) of a drop-cast of a ∼10-4 M solution
of 1 in MeCN on a mica plate. The inset shows the TEM image,
stained with uranyl acetate, of a hollow vesicle of 1 under the same
experimental conditions.
antees the maximum contact for the polar chains with the
polar environment remaining the apolar aromatic frameworks
and decyl tails occult.
Figure 4
. Cyclic voltammograms of amphiphiles 1, 2, and S1 in
acetonitrile (0.5 mM) at room temperature and at 100 mV s-1
.
In conclusion, we have reported on the synthesis and self-
assembling features of a series of triangular-shaped OPEs
decorated in the periphery with a variable number of polar
TEG and apolar decyl chains. The calculated Ka values for
these compounds in a number of solvents (MeCN, CH2Cl2,
benzene, and MCH) present a linear correlation between the
number and nature of the peripheral substituents and the
polarity of the solvent due to the input of π-π and van der
Waals interactions. Unexpectedly, this trend fails for the case
of protic 2-propanol, in which the solvophobic contribution,
not only between the aromatic frameworks but also between
the decyl tails, raises the Ka value for 1 and 2, despite the
fact that all of the studied OPEs present a similar electronic
character. van’t Hoff analysis for compound 1 in this solvent
demonstrates that the exothermicity of the self-assembly
process is enthalpy-driven. Finally, the solvophobic effects
experienced by the aromatic frameworks and the decyl chains
of compound 1 result in the formation of hollow vesicles
with a membrane thickness of ∼8 nm.
electrochemical behaviorscharacterized by the appearance
of two broad irreversible oxidation waves at ∼1.3 and ∼1.7
V20sdiscard any preferential Coulombic factor in the self-
association features of the studied compounds.
Finally, we have also investigated the formation of
organized supramolecular architectures onto surfaces for the
case of amphiphile 1 in polar acetonitrile. Scanning electron
microscopy (SEM) images of 1 on mica plates (∼10-4 M,
298 K) reveal the formation of flattened spherical objects
with diameters in the range of ∼200 nm (Figure 5). The
vesicular character of these structures has been confirmed
by transmission electron microscopy (TEM). The vesicles
observed in TEM images present a membrane thickness of
around 8 nm (inset in Figure 5) in good correlation with the
previous results observed for amphiphile S1.9a These dimen-
sions could imply the interaction between the hydrophobic
decyl chains of two arrays of molecules of 1 pointing the
corresponding hydrophilic TEG chains toward the interior
and the exterior of the membrane. This arrangement guar-
Acknowledgment. This work has been supported by UCM
(UCM-SCH-PR34/07-15826). G.F. is indebted to MEC for
a FPU grant. We gratefully acknowledge Prof. G. Orellana,
Dr. J. Lo´pez, and Prof. N. Mart´ın (Departamento de Qu´ımica
Orga´nica, UCM).
(18) (a) Smulders, M. M. J.; Schenning, A. P. H. J.; Meijer, E. W. J. Am.
Chem. Soc. 2008, 130, 606–611. (b) Garc´ıa-Frutos, E. M.; Go´mez-Lor, B.
J. Am. Chem. Soc. 2008, 130, 9173–9177.
(19) The insufficient solubility of compound S2 in the experimental
conditions has impeded the study of its redox properties.
(20) The oxidation of π-conjugated oligomers usually results in the
apparition of irreversible waves. For recent examples, see: (a) Ferna´ndez,
G.; Sa´nchez, L.; Veldman, D.; Wienk, M. M.; Atienza, C.; Guldi, D. M.;
Janssen, R. A. J.; Mart´ın, N. J. Org. Chem. 2008, 73, 3189–3196. (b)
Atienza, C. M.; Ferna´ndez, G; Sa´nchez, L.; Mart´ın, N.; Sa´ Dantas, I.; Wienk,
M. M.; Janssen, R. A. J.; Rahman, G. M. A.; Guldi, D. M. Chem. Commun.
2006, 51, 4–516.
Supporting Information Available: Experimental details
and supplementary figures. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL900832E
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2751