Self-assembling carbohydrate-functionalized oligothiophenes

Article abstract of DOI:10.1021/ol9022694

Carbohydrate-functionalized oligothiophenes have been synthesized applying mild Sonogashira cross-coupling conditions. In an aqueous environment the amphiphilic hybrids self-assemble into chiral superstructures as a result of multiple hydrogen bond intera

Full text of DOI:10.1021/ol9022694

ORGANIC
LETTERS
2009
Vol. 11, No. 22
5098-5101
Self-Assembling Carbohydrate-
Functionalized Oligothiophenes
Sylvia Schmid, Elena Mena-Osteritz, Alexey Kopyshev, and Peter Ba¨uerle*
Institute of Organic Chemistry II and AdVanced Materials, Ulm UniVersity,
Albert-Einstein-Allee 11 89081 Ulm, Germany
peter.baeuerle@uni-ulm.de; sylVia.schmid@uni-ulm.de
Received June 29, 2009
ABSTRACT
Carbohydrate-functionalized oligothiophenes have been synthesized applying mild Sonogashira cross-coupling conditions. In an aqueous
environment the amphiphilic hybrids self-assemble into chiral superstructures as a result of multiple hydrogen bond interactions and the
helicity of the aggregates is controllable by the configuration of the carbohydrate unit. By means of atomic force microscopy highly ordered
layer arrangements on substrates were characterized.
Poly- and oligothiophenes (OTs) are multifunctional materi-
als of great interest for application in organic electronics.1
Because of their excellent semiconducting and optoelectronic
properties they are used in organic light emitting diodes
(OLEDs),2 field-effect transistors (OFETs),3 or solar cells
(OSC).4 OTs have also received attention as ideal models
for polymers:5 they can be isolated in a well-defined form
and consequently reliable structure-property relationships
can be derived in contrast to polydisperse polymeric systems.
An interesting feature of OTs is their ability to self-
assemble,6 which offers a promising approach for building
a wide variety of complex functional nanostructures. A
highly intriguing concept appears by combination of an
artificial π-conjugated system with natural biomolecules.
Thus, molecular recognition can be exploited as a tool to
influence self-assembling processes due to the information
that is present in the biosequence, an important principle
for the construction of biological sensors or electronic
devices. In this respect, some nucleoside7,8 and peptide9-12
functionalized OTs and oligo(p-phenylenevinylenes)13,14
were recently found to act as excellent probes to study self-
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W. J.; Meijer, E. W. J. Am. Chem. Soc. 2000, 122, 1820–1821. (b)
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Chem. Soc. 2006, 128, 5923–5929.
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Ba¨uerle, P. Chem. ReV. 2009, 109, 1141–1278.
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V. AdV. Mater. 1996, 8, 157. (d) Langeveld-Voss, B. M. W.; Janssen,
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Meijer, E. W. J. Am. Chem. Soc. 1996, 118, 4908–4909. (e) Langeveld-
Voss, B. M. W.; Christaans, M. P. T.; Janssen, R. A. J.; Meijer, E. W.
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10.1021/ol9022694 CCC: $40.75
Published on Web 10/21/2009
 2009 American Chemical Society

assembly mechanisms. Several dye-carbohydrate conjugates
are known15,16 and various conjugated polymer-carbohydrate
hybrids comprising poly(arylene-ethynylenes),17 poly(phe-
nylene-vinylenes),18 poly(p-phenylene-ethynylenes),19 or poly-
thiophenes20 for mainly sensing applications have been
reported.
functions extend the π-conjugated system of the OT
whereas the lateral dodecyl chains enhance solubility in
lipophilic solvents. By applying Zemplen conditions and
using a catalytic amount of sodium methanolate in a
methanol/tetrahydrofuran (THF) mixture, the ester func-
tions of 4a were removed resulting in OT-carbohydrate
hybrid 4b D-(+)-ManOH-4T in 93% yield. L-(-)-Enan-
tiomeric counterparts 5a L-(-)-ManOAc-4T and 5b L-(-)-
ManOH-4T were accessible in appropriate yields (62%,
97%) following the route described above, but starting
with L-(-)-mannose. As a reference, trimethylsilyl (TMS)-
protected bisethynylated quaterthiophene 6 without car-
bohydrate units was synthesized in 78% yield from
diiodoquaterthiophene 1 and TMS-acetylene according to
a literature protocol.12
Photophysical characterization of OT-hybrids 4a, 4b, 5a,
and 5b and parent compound 6 in THF (see Supporting
Information) resulted in almost identical absorption spectra
with two broad bands peaking at 263-280 and 398-406
nm. The latter band is unequivocally assigned to the typical
π-π* transition of the OT backbone. Fluorescence spectra
showed vibronically fine structure bands at 483-487 nm
indicative of an increased planarization of the OT-backbone
in the excited state.
Herein, we describe first examples of R,ω-carbohydrate-
functionalized OTs, which were accessible by connecting
a semiconducting quaterthiophene (4T) building block and
ester-protected propargylglycosides,22 using Sonogashira
cross-coupling.21 Removal of the ester groups resulted in
biohybrids with highly amphiphilic character. The pres-
ence of various functional groups should qualify the hybrid
compounds to interact via an ensemble of noncovalent
forces, such as π-stacking, van der Waals interaction, or
H-bonding, to benefit under appropriate conditions self-
assembly in solution and in the solid state. Ester-protected
D-(+)-mannose-linked 4T derivative 4a (D-(+)-ManOAc-
4T) was obtained anomerically pure in good yield (75%)
by Pd0-catalyzed coupling of bis-iodinated 3,3′′′-didode-
cylquaterthiophene (4T) 112 and 2 equiv of acetyl-pro-
tected propargyl-R-D-(+)-mannoside 2 (Scheme 1). Lewis
In contrast to 4a, 5a, and 6, solubility of the deprotected
compounds 4b and 5b improves in more polar solvents.
Absorption spectra of the freshly deprotected enantiomeric
hybrids 4b and 5b dissolved in MeOH or MeOH:H2O (1:1)
displayed absorption bands which are hypsochromically
shifted with respect to the THF measurements. In Figure 1,
Scheme 1
Figure 1. Absorption and emission spectra of OT-mannoside 4b
(D-(+)-ManOH-4T) in MeOH (black lines) and in MeOH/H2O (1:
1) mixture (red line). The arrows underline the asymmetric shift
of the absorption in the solvent mixture.
acid-catalyzed glycosylation of peracetylated D-(+)-man-
nose with propargyl alcohol provided R-anomeric pure
sugar-alkyne component23 2 as a suitable starting material
(see Supporting Information). Novel amphiphilic system
4a comprises a variety of functionalities, i.e. a rod-like
hydrophobic quaterthiophene backbone combined with
polar, acetyl-protected monosaccharides. The ethynyl
absorption and emission spectra of OT-mannoside 4b in
MeOH are shown as well as the absorption spectra in MeOH:
H2O (1:1). In the latter more polar mixture the absorption
band indicates an asymmetric shape, including a hypsochro-
mic shift of the maximum to 389 nm and a broadening
extending up to 550 nm (Figure 1, black arrows) suggesting
the formation of H-aggregates.24
(10) Klok, H.-A.; Ro¨sler, A.; Go¨tz, G.; Mena-Osteritz, E.; Ba¨uerle, P.
Org. Biomol. Chem. 2004, 2, 3541–3544.
Org. Lett., Vol. 11, No. 22, 2009
5099

To analyze in detail the nature of aggregates of 4b D-(+)-
ManOH-4T and 5b L-(-)-ManOH-4T circular dichroism
(CD) spectra were taken in MeOH:H2O (1:1) mixture and
are shown in Figure 2. A bisignate Cotton effect can be
square wave voltammetry in dimethylformamide, using
tetrabutylammonium hexafluorophosphate (0.1 M) as elec-
trolyte. In the CVs of the hybrids, two reversible oxidation
waves indicate the formation of stable OT radical cations
(E°1 ) 0.57 V) and dications (E°2 ) 0.67 V). Due to the
electron-withdrawing effect of the O-glycoside unit the redox
potentials of the OT hybrids were higher than those of TMS-
protected parent compound 6 (E°1 ) 0.48 V, E°2 ) 0.60 V)
(see Supporting Information).
Solid state morphologies of adsorbates of ester-protected
OT-carbohydrate hybrid 4a and deprotected 4b on mica were
studied using tapping mode atomic force microscopy (AFM).
Amphiphilic derivative 4a adsorbed in a terrace-like multi-
layered structure with up to 84% coverage of the surface,
indicating a Volmer-Weber growth-mode.25 The number
of layers increased with longer delay time (Td) between
deposition of the solution and start of the spin-coating
process. The well-defined layered structure was not found
in the case of the parent compound 6, which undergoes
cluster formation under identical conditions. In contrast, 4a
exhibited very uniform and stable layers whose thicknesses
(3.5 ( 0.2 nm) perfectly correlated with the calculated length
of the molecule (Figure 3a,b). Modifying the deposition
Figure 2. CD data of OT-mannosides 4b (D-(+)-ManOH-4T, black
curve) and 5b (L-(-)-ManOH-4T, red curve) in MeOH:H2O (1:1)
mixture.
observed at the π-π* transition band with a zero-crossing
of the CD signal located at the absorption maximum of the
chromophore. Bisignate CD curves typically indicate exci-
tonic coupling as a result of chiral aggregation. The shape
of the CD curve for D-(+)4b (Figure 2, black curve: negative
θ at 406 nm; positive θ at 366 nm) indicates self-assembly
of the OT backbones into left-handed supramolecular stacks
induced by the chiral carbohydrate moieties. The L-manno-
sidic counterpart L-(-)-5b displayed an almost perfect mirror
image behavior (Figure 2, red curve), confirming the forma-
tion of well-ordered aggregates with opposite, right-handed
helicity. Thus, the handedness of the observed superstructures
of the π-conjugated oligomer stacks could obviously be tuned
by the introduction of suitable D-(+)- or L-(-)-mannosidic
building blocks. The formation of chiral aggregates is
rationalized as a result of the “free” OH-groups in 4b and
5b being capable of forming intermolecular hydrogen bond-
ing, forcing the π-systems into well-ordered helical as-
semblies. This conclusion found evidence by the study of
optical properties of the protected OT-hybrids 4a and 5a and
the parent compound 6, which undergo conventional positive
solvatochromism and did not show clear CD effects pointing
to chiral aggregation phenomena.
The specific optical rotations [R]D of protected hybrids
D-(+)-ManOAc-4T 4a [+42.5° (c ) 0.12 g/dL)] and L-(-)-
ManOAc-4T 5a [-48° (c ) 0.15 g/dL)] were measured in
dichloromethane. With respect to sign and magnitude, these
values correspond well to those of tetraacetylated O-
propargylmannoside building blocks 2 [+57.8° (c ) 0.27
g/dL)]21c,22a and 3 [-59.6° (c ) 0.27 g/dL)] characterized
as well in this work. These results corroborate the rationale
that the chirality of the carbohydrate units is preserved in
the hybrid systems.
Figure 3. AFM micrographs of 4a and 4b absorbed on mica. (a)
Height image of 4a spin-coated from dichloromethane, 5 × 5 µm2
(bottom: corresponding cross-section, ∆z ) 10 nm). Inset: Struc-
tures after dip-coating setup, 5 × 5 µm2. (b) Calculated geometry
of compound 4a and molecular model of the adsorption geometry.
(c) Amplitude image of 4b deposited from MeOH, 1.5 × 1.5 µm2
(bottom: corresponding cross-section, ∆z ) 5 nm). (d) Calculated
model of 4b and detailed view of the intermolecular H-bonding.
procedure to a dip-coating process and subsequent evapora-
tion of the solvent resulted in the formation of circular
structures (insert in Figure 3a) formed by molecules arranged
in up to four terraces of exactly the same height as in the
former case. Semiempirical calculations for 4a D-(+)-
OT-carbohydrate derivatives 4a and 4b and reference
compound 6 were further characterized by cyclic (CV) and
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Org. Lett., Vol. 11, No. 22, 2009

ManOAc-4T suggest an all-trans conformation of the qua-
terthiophene backbone and carbohydrates stretched following
the molecular axis (Figure 3b).
drates. The observed small fibers (Figure 3c) have a uniform
height of about 3.4 nm being in accordance with the width
of the molecule, considering that hydrogen bond formation
of the carbohydrate-functionalized termini took place parallel
to the surface (Figure 3d). In the calculated model, the OT
backbones are separated to 0.6 nm leading to less efficient
π-π stacking.
Due to the amphiphilic character of the molecules the
aggregation model should take into account stabilization due
to phase separation. The semiempirical calculated model
presented in Figure 3b considers not only the intermolecular
phase separation, but also the preferred interaction between
the hydrophilic substrate and the polar part of the molecule.
The monolayer formed in this model is additionally stabilized
by π-π interaction of the conjugated backbones and by van
der Waals interactions of the alkyl chains.
Deprotected hybrid 4b adsorbed from methanol on mica
at Td ) 0 (instantaneous coating) in a monolayer structure
covered by small clusters. With an increase in the delay time,
fiber-like structures (Td ) 20 s, Figure 3c) and finally large
clusters (Td ) 60 s) appeared. The monolayer formed at Td
) 0 evidenced instabilities and a height of only 0.7 nm,
suggesting that the molecules were lying on the mica surface.
The lack of a stable and compact monolayer structure as
well as the dependence of the size of the aggregates on Td
implies strong molecule-molecule interactions, as a result
of H-bonding induced by the deprotection of the carbohy-
In conclusion, an efficient and convenient protocol based
on Sonogashira cross-coupling for the construction of novel
R,ω-end-capped R-D-(+)- and R-L-(-)mannose oligothio-
phene hybrids has been developed. Investigation on optical
properties of amphiphilic deprotected hybrids 4b and 5b in
polar solvents revealed self-assembly into chiral superstruc-
tures of the π-conjugated oligomer blocks whose handedness
depend on the stereochemistry of the pending mannosidic
bioblocks. Characterization of the self-assembly behavior of
R-D-(+)mannosidic hybrids 4a and 4b in the solid state on
mica resulted in a highly ordered layer arrangement.
These findings now allow that the developed synthetic
strategy can be exploited to rationally design novel biocom-
patible and self-assembling (semi)conducting materials by
a combination of miscellaneous ethynylated saccharides and
halogenated π-conjugated building blocks. Thus, self-as-
sembly of these materials into chiral superstructures can be
tuned by the choice of saccharidic building blocks with
suitable stereochemistry.
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Acknowledgment. The authors gratefully acknowledge
helpful discussions with Prof. Dr. V. Austel and financial
support from the German Research Foundation (DFG) in the
frame of Collaborative Research Center SFB 569 and the
Fonds der Chemischen Industrie.
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