Direct functionalization of self-assembled nanotubes overcomes unfavorable self-assembling processes

Article abstract of DOI:10.1039/b903797g

Diamides containing alkyne and azido were self-assembled into nanotubes and were reacted under their self-assembled state with small molecules by "click chemistry"; the resulting compounds remain self-assembled into new nanotubes that cannot be formed by

Full text of DOI:10.1039/b903797g

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Direct functionalization of self-assembled nanotubes overcomes
unfavorable self-assembling processesw
´
Thi-Thanh-Tam Nguyen, Franc¸ ois-Xavier Simon, Marc Schmutz and Philippe J. Mesini*
Received (in Cambridge, UK) 23rd February 2009, Accepted 8th April 2009
First published as an Advance Article on the web 7th May 2009
DOI: 10.1039/b903797g
Diamides containing alkyne and azido were self-assembled into
nanotubes and were reacted under their self-assembled state with
small molecules by ‘‘click chemistry’’; the resulting compounds
remain self-assembled into new nanotubes that cannot be formed
by simple self-assembly of the constituting molecules.
a bulky or polar group in this compound yields compounds
unable to form nanotubes. We have surmised that the small
and non-polar alkyne and azide groups would preserve the
self-assembling pattern. Therefore, the analogues 2 and 3
bearing, respectively, an alkyne and an azide function,
were prepared with good yield at the scale of the gram (see
electronic supplementary informationw) according to methods
developed for other analogues.24–26 The compounds 2 and 3
form gels in cyclohexane for a concentration of 1 wt%.
Examination of the gels was performed by TEM after
cryofracture of the gels. This technique, first developed in
aqueous systems, has been implemented successfully to study
self-assembled systems in organic solvents.23,25–27 The
micrographs show that 2 and 3 self-assemble into nanotubes
(Fig. 1b and c) with diameters of 25.3 Æ 3.6 nm and
27.2 Æ 5.0 nm, respectively, and polydisperse lengths of the
order of the micrometer.
The recent development of carbon nanotubes1–3 shows that
many of their applications result not only from their unique
shape and electronic properties but also from chemical
functionalization of their surface.4–6 This step requires
elaborate chemistry due to the difficulty to solubilize or to
purify them.7 These drawbacks have aroused interest in
nanotubes resulting from the self-assembly of small molecules.8
These nano-objects are attractive owing to their high purity,
ease of formation and high processability. They are formed
through non-covalent interactions, such as van der Waals
interactions or H-bonds between specific groups.9–13 But the
assembling molecules can bear side groups, yielding new
functions for applications such as support for 2D crystal-
lization of proteins,14,15 for cell growth16,17 or chiral recognition.18
In principle, the possibility of tuning their properties by
adding functional groups in the constituting compounds can
be easily addressed by synthesis. But very often, the mere
introduction of a functional group results in the loss of their
self-assembling pattern. For this reason, direct modification of
the self-assembled nanotubes remains very rare. The recent
development of copper catalyzed cycloaddition of alkyne and
azides19–21 (CuAAC) allows one to tackle such derivatization.
Indeed, this highly specific reaction does not interfere with
groups responsible for the self-assembly; then, the introduction
of a small group like azide or alkyne in a molecule can be done
without changing its self-assembling properties. It has been
shown that this reaction can be carried out with supramolecular
assemblies like gelator fibrils, and moreover in heterogeneous
conditions or in high viscosity media such as gels.22
The new nanotubes of 2 and 3 form in alkanes, thus we were
lead to use (PPh3)3CuBr as the catalyst,28,29 since it is soluble
(although only slightly) in those solvents. Nanotubes of 2 were
formed in cyclohexane at a concentration of 2 wt%, which
resulted in the formation of a gel. A solution containing
azidodecane or azidodecanol in excess and the catalyst was
layered on top of the gel and allowed to diffuse (Fig. 2A). The
diffusion of the catalyst through the gel resulted in staining of
the gel into a dark brown color. The reacting solution was
removed when the color frontline had reached the bottom of
the gel. The top solution was removed and replaced by
cyclohexane to remove the excess reagents. The rinsing
solution contained the unreacted reagent and small amounts
of compounds 2. Acetylacetone (acac) was also added in
the rinsing solution in order to extract all remaining
copper-containing products of the reaction.
The diffusion of the rinsing solution resulted in the
progressive bleaching of the lower phase. After the reaction,
the resulting nanotubes could be dissociated in CHCl3 and
analyzed by NMR and HPLC. Compounds 4, 5 and 6 were
synthesized independently in solution (ESIw), and were used as
references to measure the yields of each species by HPLC
(ESIw). These analyses showed that the CuAAC reaction
We have shown23 that diamide 1 (Scheme 1) self-assembles
in alkanes through H-bonds between the amide groups and
p–p stacking between the aromatic parts to form nanotubes
with outer diameters of 29 nm and lengths of several micro-
metres (Fig. 1a). The formation of these tubes results, at
the macroscopic level, in the gelification of the solvent for
concentrations greater than 0.4 wt%. Usually, introduction of
Institut Charles Sadron, CNRS, 23 rue du Loess, BP 84047,
67034 Strasbourg Cedex 2, France. E-mail: mesini@ics.u-strasbg.fr;
Fax: 33 (0)388 41 40 99; Tel: 33 (0)388 41 40 70
w Electronic supplementary information (ESI) available: Experi-
mental, electron micrograph of gels not treated with acac. See DOI:
10.1039/b903797g
Scheme 1 Structure of the self-assembling compounds.
Chem. Commun., 2009, 3457–3459 | 3457
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Fig. 1 Freeze fracture TEM of gels of 1 (a), 2 (b) and 3 (c) in
Fig. 3 Freeze fracture-TEM of the gels of nanotubes after reaction;
cyclohexane (2 wt%).
(a)
2 and N3–C10H21; (b) 2 and N3–C10H20–OH; (c) 3 and
R–C9H18–OH.
do not dissolve or segregate from the tubes formed from 2 or 3.
When acac is omitted in the rinsing step, the reactions have
similar yields, but examination of the resulting suspensions by
electron microscopy shows nanoparticles scattered throughout
the samples along with the tubes (ESI, Fig. S1w). Their angular
edges and layered structure suggests they are nanocrystallites
that are probably particles of copper side-products. The
diffusion of the catalyst and the reagent limits the reaction
rate therefore we checked if it induces heterogeneities in the
resulting gel. The gels were analyzed at different distances
from the top. Chromatography measurements showed similar
yields close to the top or close to the bottom. Electron
microscopy also showed no significant differences between
the different spots.
The conversions of the functional groups in solution is
between 70 and 89% (ESIw). The same conversion rates in
the gels are lower, between 55% and 61%. These lower yields
may be explained by the heterogeneous conditions of the
reaction or by the possible orientation of part of the reactive
groups toward the inner cavity of the tubes where the catalyst
diffusion is expected to be reduced.
Pure 4 forms gels for concentrations greater than 0.8 wt%,
and the micrographs of these gels show they are composed of
nanotubes like in the reacted gel, but with a larger diameter
(31.6 Æ 4.3 nm). There is a gap between the objects resulting
from the reaction of tubes of 2 and the ones resulting from the
spontaneous self-assembly of 4. The difference is even stronger
for compound 5, since it does not form tubes at all. When pure
5 is mixed in cyclohexane and heated, it does not dissolve but
melts in a separate phase, and recrystallizes upon cooling.
We also checked whether mixtures of 5 and 2 in the same
proportions as in the nanotubes after reaction (82/18) can
reform the same nanotubes: one observes precipitation of 5,
and gelation upon cooling of the supernatant containing 2.
The same result was also obtained when the product mixture
from the reaction with gel was dissolved in CHCl3 and
tentatively re-assembled in cyclohexane. These observations
are summarized on Scheme 2. They indicate that the nanotubes
resulting from reactions of tubes by click chemistry, when they
Fig. 2 (A) Schematic set-up of the reaction. (B) Structure of the
compounds formed during the reaction with nanotubes.
between the nanotubes of
2 and azidodecane yielded
compound 4 according to Fig. 2, and unreacted 2 in a
proportion 4/2 of 67/33 (yield of 4 + 2: 91%). Only small
amounts of catalysts phosphines and azidodecane were
detected. Similar results were obtained when the nanotubes
of 2 were reacted with azidodecanol or when nanotubes of 3
were reacted with undecynol. (5/2: 82/18; 6/3: 72/28).
Cryofracture of the gels showed that the tubular shape of
the self-assemblies was preserved after the reaction (Fig. 3).
The diameters of the tubes in the gels containing 4, 5 and 6
are the same as those of the starting nanotubes within the
uncertainty of the measurements (resp. 24.6 Æ 4.1, 23.6 Æ 3.6,
27.9 Æ 4.4 nm). The density of the tubes is the same as in the
initial one, which shows that the final compounds 4, 5 or 6
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3458 | Chem. Commun., 2009, 3457–3459

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the Re
´
gion Alsace (T.-T.-T. N). We thank Dr P. Baxter for
fruitful discussions, A. Rameau and C. Foussat for the
chromatography experiments, and Dr P. Schultz, IGBMC,
Illkirch, for the use of the cryofracturing apparatus.
Notes and references
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This work was supported by a PhD fellowship from the
Ministere de l’Education (F.-X. S.) and by a fellowship from
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