Rosette nanotubes with 1.4 nm inner diameter from a tricyclic variant of the Lehn-Mascal G∧C base

Article abstract of DOI:10.1039/c0cc01859g

A new strategy to access rosette nanotubes with increased inner diameter is presented and demonstrated through the synthesis and self-assembly studies of a tricyclic variant of the Lehn-Mascal G∧C base.

Full text of DOI:10.1039/c0cc01859g

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COMMUNICATION
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Rosette nanotubes with 1.4 nm inner diameter from a tricyclic variant
of the Lehn–Mascal G4C basew
Gabor Borzsonyi,ab Ross S. Johnson,ab Andrew J. Myles,b Jae-Young Cho,b
Takeshi Yamazaki,b Rachel L. Beingessner,b Andriy Kovalenkobc and Hicham Fenniri*ab
Received 12th June 2010, Accepted 15th July 2010
DOI: 10.1039/c0cc01859g
A new strategy to access rosette nanotubes with increased inner
diameter is presented and demonstrated through the synthesis
and self-assembly studies of a tricyclic variant of the Lehn–Mascal
G4C base.
Inspired by molecular organization in biological systems,1
supramolecular synthesis consists in the design and synthesis
of molecules for recognition-directed self-assembly.2 This
approach allows specific functionalities to be expressed in
the self-assembled supramolecular architectures, resulting in
nanostructured materials with tailored physical and biological
properties.3 Based on the self-organization principles of the
guanine (G) and the cytosine (C) base pairs in DNA, Lehn
et al. designed a self-complementary Janus type motif, the
G4C base hybrid, where the hydrogen bonding patterns of
guanine and cytosine are expressed in a single molecule.4
Mascal et al. unequivocally established the self-assembly of
this motif into hexameric rosette supermacrocycles using
single crystal X-ray analysis.5 Later, Fenniri et al. established
the ability of these rosettes to undergo additional levels of
hierarchical organization through p stacking, van der Waals
interactions, and solvophobic effects to form nanotubular
architectures, termed rosette nanotubes (RNTs),6 nanospheroids,7
and superhelices.6d More recently, Perrin et al. added a new
tricyclic member to the G4C family, and established its ability
to self-assemble into tetrameric rosette supermacrocycles.8
Herein we report the synthesis and characterization of a
Fig. 1 Self-assembly of rosette nanotubes with 1 nm and 1.4 nm inner
tricyclic variant of the G4C motif (termed ÂG4C), designed
diameter. Because of the self-complementary H-bonding arrays of
with the aim of assembling RNTs with the largest inner
diameter reported thus far.9 This new construct should
rosettes (B) which in turn self-organizes into a stable tubular stack with
G4C and ÂG4C bases (A) they both self-assemble into hexameric
1.0/3.1 nm and 1.4/3.5 nm inner/outer diameters (C), respectively.w
allow us to develop synthetic strategies to functionalize the
RNTs inner channel. Furthermore, because of its larger outer
diameter (i.e. reduced functional group density), sterically
demanding moieties could be appended to the ÂG4C motif
and displayed on the RNT surface (Fig. 1).
Our synthesis began with barbituric acid, from which
known compound 1 was obtained (Scheme 1).6 Condensation
using malonitrile gave 2, from which compound 3 was obtained
following the procedure of Beck.10 Compound 3 was highly
reactive toward nucleophiles, as it had three electrophilic sites
which are further activated by the appended nitrile group. At
this stage, we investigated the regioselective substitution of the
heterocyclic core of 3 and found that 2 equivalents of allylamine
(1 equivalent nucleophile, 1 equivalent base) at À78 1C - 0 1C
resulted in monosubstitution.
a Department of Chemistry, 11227 Saskatchewan Drive,
University of Alberta, Edmonton, Alberta, T6G2G2, Canada.
E-mail: hicham.fenniri@ualberta.ca; Fax: +1 780-641-1601;
Tel: +1 780-641-1750
b National Institute for Nanotechnology, 11421 Saskatchewan Drive,
University of Alberta, Edmonton, Alberta, T6G2M9, Canada
c Department of Mechanical Engineering, 4–9 Mechanical Engineering
Building, University of Alberta, Edmonton, Alberta, T6G 2G8,
Canada
Single crystal X-ray structure analysisw of the product
showed that the substitution took place at position 4, suggesting
that this is the most electrophilic position. Since our goal was
to place a carbonyl group at position 4, we performed the first
SNAr using one equivalent of benzyl alcohol with one equiva-
lent of triethylamine at À40 1C to afford 4 in 70% yield. Then,
w Electronic supplementary information (ESI) available: Full experi-
mentals for all compounds, molecular modelling and microscopy
preparations and experiments. CCDC 639261. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/
c0cc01859g
c
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Chem. Commun., 2010, 46, 6527–6529 6527

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Fig. 2 Tapping mode atomic force microscopy height (A) and
amplitude (B) images of ÂG4C (0.6 mM in DMF) on mica, and
transmission electron micrographs of (C) ÂG4C (0.3 mM in DMF)
and (D) G4C (1.1 mM in DMF).w
Scheme 1 Synthesis of ÂG4C. (a) POCl3, DMF, reflux, 15 h, 90%;
(b) malonitrile, b-alanine, CH3CN, 30 h, 50%; (c) 180 1C, 48 h, 75%;
(d) BnOH, Et3N, CH2Cl2, À40 1C, 2 h, 70%; (e) allylamine, CH2Cl2,
50 1C, 15 h, 89%; (f) (Boc)2O, Et3N, THF, 24 h, 50%; (g) (Cl3CO)NCO,
CH2Cl2, rt, 6 h; (h) 7 N NH3 in MeOH, rt, 15 h, 90% (2 steps); (i) 4 M
HCl in dioxane, 6 h, 90%.
Tapping mode atomic force microscopy (TM-AFM) and
transmission electron microscopy (TEM) were performed to
obtain direct physical measurements on the ÂG4C RNTs.w
AFM samples were prepared by spin coating DMF solutions
of the ÂG4C (0.6 mM) on mica surfaces. Height measure-
ments were taken using low force TM-AFM (Fig. 2A and B).
Over 400 measurements were obtained and their distribution
was centered around 3.6 Æ 0.3 nm, in excellent agreement with
the predicted diameter of 3.5 nm.w
addition of excess allylamine to 4 in dichloromethane followed
by heating to 50 1C in a sealed tube gave compound 5 in
89% yield. The structure of this key intermediate was also
confirmed using single crystal X-ray analysis.11
For TEM measurements, samples were assembled in DMF
([G4C] = 1.1 mM, [ÂG4C] = 0.3 mM), cast onto TEM
grids and allowed to dry at room temperature.w The samples
were positively stained by exposing the RNTs on the TEM
grids to OsO4 vapor (expected to react with the allyl groups).
For both G4C and ÂG4C, images revealed discrete, high
aspect ratio RNTs. Careful measurementsw revealed that the
G4C RNTs had an outer diameter of 3.1 Æ 0.2 nm, whereas
the ÂG4C RNTs had a larger outer diameter of 3.6 Æ 0.2 nm,
also in excellent agreement with the predicted diameters.
This communication describes briefly the synthesis and
characterization of a heterotricyclic self-complementary molecule,
designed with the aim of assembling rosette nanotubes (RNTs)
with the largest inner diameter reported thus far (i.e. 1.4 nm).
This new construct should allow us to develop synthetic
strategies to functionalize the RNTs’ inner channel for encapsu-
lation and transport processes, and paves the way to the
synthesis of RNTs with an even larger inner diameter (2.0 nm).
Furthermore, because of its increased outer diameter (i.e. reduced
functional group density), sterically demanding moieties could
be expressed on the RNT surface for applications in drug
display/delivery.3c,f–l For instance, recent preliminary studies
suggest that the RNTs could encapsulate drugs such as
The strategy for the third ring formation followed the
previously reported cyclization of the bicyclic G4C motif.6
The allylamine at position 2 of 5 was Boc-protected, and the
resulting compound 6 treated with trichloroacetyl isocyanate.
TLC analysis indicated the total consumption of the starting
material in 5 h, after which 7 M NH3 in methanol was added
to yield compound 7 in 90% yield (2 steps). Global deprotection
using 4 M HCl in 1,4-dioxane resulted in target compound
ÂG4C as the HCl salt in 90% yield, which was subsequently
1
characterized by H-NMR, 13C-NMR, HRMS and elemental
analysis. In our design, we chose allyl moieties on the periphery
of ÂG4C so that subsequent functionalizations may be
carried out.6 The bicyclic diallyl G4C base derivative
(Fig. 1A) was also synthesized as a reference compound for
our characterization experiments (Scheme S1).w
ÂG4C was sparingly soluble in DMF (0.6 mM with heat)
and moderately soluble in DMSO (1.2 mM without heat; 15 mM
with heat). The aggregation behavior of ÂG4C was first
investigated using scanning electron microscopy (SEM) of a
heated DMF solution (0.6 mM) cast onto a TEM grid, which
provided direct visual evidence that ÂG4C self-assembled
into high aspect ratio RNTs.w
c
6528 Chem. Commun., 2010, 46, 6527–6529
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dexamethasone, and induce an enhancement in bone cell
function.12
Biomaterials, 2005, 26, 7304; (d) Y. Yamamoto, T. Fukushima,
Y. Suna, N. Ishii, A. Saeki, S. Seki, S. Tagawa, M. Taniguchi,
T. Kawai and T. Aida, Science, 2006, 314, 1761; (e) R. Chhabra,
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Our next aims are therefore to (a) design water-soluble
versions of ÂG4C for application in drug encapsulation
and delivery, (b) further increase the inner diameter of the
RNTs by synthesizing a tetracyclic variant of the G4C motif
(ÂÂG4C), (c) functionalize the inner and outer surface of the
ÂG4C, and (d) explore the electronic, photonic, and trans-
port properties of the resulting RNTs. This work is currently
in progress in our laboratories.
We acknowledge the support of the National Research
Council of Canada, the Natural Science and Engineering
Research Council of Canada, the University of Alberta, and
the Canada Foundation for Innovation.
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