Sonication-induced self-assembly of flexible tris(ureidobenzyl)amine: From dimeric aggregates to supramolecular gels

Article abstract of DOI:10.1039/c2cc33408a

Tris(ureidobenzyl)amine derivatives 1a,b form dimeric aggregates in apolar solution and in the solid state. Specifically, the meta-substituted tris(urea) 1a is able to transform into supramolecular gels in certain solvents via sonication.

Full text of DOI:10.1039/c2cc33408a

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
ChemComm
Cite this: Chem. Commun., 2012, 48, 7973–7975
www.rsc.org/chemcomm
COMMUNICATION
Sonication-induced self-assembly of flexible tris(ureidobenzyl)amine: from
dimeric aggregates to supramolecular gelsw
Chao Deng, Ru Fang, Yangfan Guan, Juli Jiang, Chen Lin and Leyong Wang*
Received 11th May 2012, Accepted 18th June 2012
DOI: 10.1039/c2cc33408a
Tris(ureidobenzyl)amine derivatives 1a,b form dimeric aggregates
in apolar solution and in the solid state. Specifically, the meta-
substituted tris(urea) 1a is able to transform into supramolecular
gels in certain solvents via sonication.
There has been a surge of interest in low molecular weight
gelators (LMWGs),1–3 a class of small organic molecules that
can form gels via supramolecular interactions, such as hydrogen
bonding, pÁ Á Áp stacking etc. Bis(urea) derivatives have been
Fig. 1 Chemical structures of tris(3-ureidobenzyl)amines 1a–e and
proved to be highly effective in forming LMWGs,4–14 and their
model compound 2.
gelation ability depends on hydrogen bonding interactions of
the urea groups that can form a-tape motif aggregates via
dimeric aggregates25,30,31 was also synthesized according to the
reported literature.30
NHÁ Á ÁOQC hydrogen bonding interactions.15 Besides the
bis(urea) motif, the tris(urea) motif has also been applied in a
NMR spectra in different solvents proved to be a powerful
tool for studying dimeric aggregates in solution.25 The averaged
number of effective supramolecular assemblies such as anion
recognition,16–22 dimeric aggregates,23–25 and gelators.26–29 In
particular, Steed and co-workers reported tris(urea) gelators
affording supramolecular gels that are susceptible to fine tuning
by anion binding.28 On the other hand, tripodal tris-urea ligands
were also reported as dimeric aggregates both in apolar solution
and in the solid state by Alajarin and co-workers.25,30–32 However,
to our best knowledge, there has been no report on tripodal
tris(urea) receptors showing tunable transformation between
dimeric capsules and supramolecular gels. Motivated by reported
interesting results that the gelation ability of bis- and tris(urea)
compounds can be dramatically affected by inducing only one
CH2 segment into their structures,10,14,26 we envisioned that subtle
modification of substituent groups of tris(urea) compounds
that could form dimeric aggregates might provide the possibility
of forming supramolecular gels in certain solvents. We herein
designed and synthesized novel meta-substituted ‘‘foot’’ tris-
(3-ureidobenzyl)amine derivatives 1a,b (Fig. 1). As a comparison
with 1a,b, novel para-substituted ‘‘foot’’ tris(3-ureidobenzyl)-
amine derivatives (1c,d) were also prepared, and 1e that was well
known to dimerize both in solid state and in solution to form
C3v symmetries of the monomers of tripodal tris(urea)s 1a,b can
be identified in CD3CN and DMSO-d6, a hydrogen bonding
competitive polar solvent, with the singlet of methylenic protons
of the (ArCH2)3N fragment in 1H NMR (Fig. S1–2w).25,30
1H NMR spectra of tris(urea)s 1a,b in less polar solvent CDCl3
were also investigated (Fig. S1–2w). The results showed that the
1H NMR spectrum of 1b in CDCl3 is much clearer than 1a, due
to the better solubility of 1b in CDCl3. More clearly, the
1H NMR spectrum of 1b in CDCl3 indicated that the signals
of both NH protons were shifted to lower field at 7.93 ppm,
compared to the NH signal (NH d 7.11 ppm) of the single urea
model compound 2 also in CDCl3, indicating the difference
between the urea hydrogen-bonding of tris(urea) 1b and the
single urea model compound in CDCl3. In particular, the signals
of the methylenic protons of (ArCH2)3N fragments were split
into two broad peaks, indicating that these protons experience a
diastereotopic environment. Moreover, the pendant aromatic
groups (C2–H in Fig. 1) of 1b in CDCl3 also experience chemical
shifts 0.9 and 1.1 ppm to higher field than in DMSO-d6 and
CD3CN, respectively, for the reason that the protons are
pointing to the inside of the dimeric species25 (Fig. S2, in
1
Key Laboratory of Mesoscopic Chemistry of MOE,
green, ESIw). In addition, H NMR of 1a, and the tris(urea)s
Center for Multimolecular Chemistry, School of Chemistry and
Chemical Engineering, Nanjing University, Nanjing 210093, China.
E-mail: lywang@nju.edu.cn; Tel: +86-25-8359-2529
w Electronic supplementary information (ESI) available: Experimental
procedures and characterization for all new compounds, ROESY,
DOSY concentration-dependent 1H NMR spectroscopy, and solvent-
tuning experiment. CCDC 869084. For ESI and crystallographic data
in CIF or other electronic format see DOI: 10.1039/c2cc33408a
1c, d for comparison and well known 1e25 in CDCl3 showed
similar solution behavior as 1b (Fig. S1, 3–4w), in which the
methylenic protons of their (ArCH2)3N fragments were split
into two doublets (1d, 1e) or broad peaks (1a, 1c), indicating
the feature of dimeric species formation of 1a–d in CDCl3.25,30
The dimeric aggregates of 1a,b in CDCl3 were also indentified,
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 7973–7975 7973

View Article Online
CHCl3 (Fig. S8w), it will form opaque weak gels at 2.0%
weight by sonication in mixed solvents such as CH2Cl2–
MeOH (10 : 1 v/v) and CHCl3–MeOH (10 : 1 v/v) (Fig. 3a).
Compared to 1a, tris-urea 1b formed a white, opaque gel-like
precipitate in CH3CN by sonication and did not form gels in
other solvents (Fig. 3a). In contrast, tris(urea)s 1c–e only
formed white precipitates in CH3CN by long-time sonication,
presumably owing to their very poor solubility in CH3CN even
at elevated temperatures.26
Fig. 2 Crystal structure of the tris(urea) dimer 1aÁ1a with one enclosed
Scanning electronic microscopy (SEM) was usually employed
to study the morphologies of aggregation states. SEM images of
tris(urea) 1a xerogel prepared from the CH3CN gel exhibited a
partially intertwined 3D network structures consisting of very
thin and irregularly twisted 1D nanofibers (Fig. 3b). The thicker
fibers clearly consist of bundles of these very thin fibers. The
fibers in turn fuse and intertwine to form an entangled network.
Supramolecular interactions often play important roles in
the self-assembly of supramolecular gel in bis- and tris(urea)
architectures.15 To investigate the driving forces for the self-
assembly process, 1H NMR experiments of tris(urea) 1a at
various concentrations were carried out in CD3CN in the
concentration range of 1.3–20.1 mg mLÀ1 (Fig. S9w). We
found that the NHa resonance displayed a downfield shift
from 7.62 to 7.65 ppm and the NHb resonance also showed an
obvious downfield shift from 7.35 to 7.43 ppm upon increasing
the concentration from 3.6 to 20.1 mg mLÀ1, which indicated
the existence of hydrogen-bonding interactions among the urea
groups during the formation of supramolecular aggregates.37
The C2–H resonance displayed an obvious upfield shift from
7.67 to 7.56 ppm with the concentration increasing from 1.3 to
20.1 mg mLÀ1. These results indicated that the formation of
supramolecular aggregates of 1a could be driven by hydrogen-
bonding and slight pÁ Á Áp stacking interactions in CD3CN.38
The gel formed by hydrogen-bonding interactions could be
tuned or destroyed by competitive anion or strong polar
solvents. Steed and co-workers reported that the bis- and
tris(urea) supramolecular gels were susceptible to fine tuning by
anion binding.10,13,14,28,39 More recently, Yang and co-workers
have reported platinum–acetylide gels that can be collapsed by
DMF-tuning.37 In our case, a solvent-tuning experiment was
carried out by the addition of DMSO into the gel of 1a in
CH3CN (Fig. S10w), since DMSO is a well known good acceptor
that can form hydrogen bonds with urea groups to disaggregate
the urea a-tape motif aggregates. Interestingly, 28 equivalents of
DMSO to 1a were needed to completely destroy the gel network.
1H NMR titration of 1a with DMSO-d6 in CD3CN provides
insight of the structures of gelator-solvent binding (Fig. S11w).
Upon the addition of DMSO-d6, tris(urea) 1a showed a large
downfield shifts of both NHa and NHb protons. It seems that
the addition of DMSO may result in the dissociation of the
intermolecular hydrogen bonding of gels, thereby leading to
disaggregation of the supramolecular assembly, which again
confirms the important role of hydrogen bonding interactions
among the urea groups during the generation of the gels.
The pattern of 1H NMR signals of tris(urea) 1a in CD3CN is
consistent with averaged C3v symmetries characteristic of the
monomers. However, the X-ray analysis of 1a showed the
hydrogen-bonded dimeric aggregate which was entangled by a six-
membered ring of ureas in a head-to-tail fashion. We supposed that
molecule of H2O (yellow sphere): top view (a) and axial view (b).
respectively, on the basis of DOSY measurement33 (Fig. S7w).
The ROESY experiments of 1bÁ1b and 1dÁ1d in CDCl3
34
further confirmed that intermolecular NOE contacts only fit
within a dimeric structure instead of monomer (Fig. S5–6w).
Colorless block crystals of tris(ureidobenzyl)amine 1a for
X-ray diffraction measurement were successfully obtained
from slow evaporation of its CH3CN solution. It is notable
that a six-membered ring of ureas in a head-to-tail fashion
based on hydrogen bonding interactions was observed in the
structure of dimeric aggregate (Fig. 2). This capsule-like
dimeric aggregate consists of two enantiomeric tripods and
exhibits an overall S6 symmetry.25 The distance of N–HÁ Á ÁO
hydrogen bonds between two ureas are 2.932(2) and 3.118(2) A,
implying a rather unsymmetric six-membered hydrogen bonded
ring.30 There are reports that intermolecular CHÁÁÁp interactions
between the aromatic CHs and the aryl rings play an important
role for the thermodynamic and kinetic stability of the capsule,35
and for instance, well known para-substituted ‘‘foot’’ tris(ureido-
benzyl)amines 1eÁ1e shows CHÁ Á Áp interactions between the
pendant aromatic CHs and the tribenzylamine skeleton aryl
rings in the crystalline states.30,31 Therefore, the CHÁ Á Áp
interactions of meta-substituted ‘‘foot’’ tris(urea) 1aÁ1a in
our case might be decreased for the reason that the pendant
aromatic CHs were substituted by oxygen atoms, resulting in
the decreasing of the stability of dimeric aggregate. Further, to
our surprise, the X-ray structure shows that the cavity of
capsule-like 1aÁ1a is filled with one molecule of H2O.
Cooling of a thermally dissolved super-saturated CH3CN
solution of 1a (1.5% by weight) resulted in precipitation.
Surprisingly, an opaque organogel was obtained through
ultrasonication during its cooling process,36 (Fig. 3a) and the
resultant gel was stable at ambient temperatures without
crystallizing or melting. Although tris(urea) 1a cannot form
a perfect gel in apolar solvents by sonication, such as CH2Cl2,
Fig. 3 (a) Gels of 2 wt% 1a in (from left to right) (A) CH3CN,
(B) 10 : 1 (v/v) CH2Cl2–MeOH, (C) 10 : 1 (v/v) CHCl3–MeOH, and as
a comparison, (D) gel-like precipitate of 2 wt% 1b in (right) CH3CN.
(b) SEM micrograph of the xerogel of 1a gel formed in CH3CN
(solvent) showing the thread-like nature of the gel fibres.
c
7974 Chem. Commun., 2012, 48, 7973–7975
This journal is The Royal Society of Chemistry 2012

View Article Online
9 L. S. Reddy, S. Basavoju, V. R. Vangala and A. Nangia, Cryst.
Growth Des., 2006, 6, 161–173.
10 M.-O. M. Piepenbrock, G. O. Lloyd, N. Clarke and J. W. Steed,
Chem. Commun., 2008, 2644–2646.
11 M.-O. M. Piepenbrock, N. Clarke and J. W. Steed, Langmuir,
2009, 25, 8451–8456.
12 M.-O. M. Piepenbrock, N. Clarke and J. W. Steed, Soft Matter,
2010, 6, 3541–3547.
13 M.-O. M. Piepenbrock, N. Clarke, J. A. Foster and J. W. Steed,
Chem. Commun., 2011, 47, 2095–2097.
14 G. O. Lloyd, M.-O. M. Piepenbrock, J. A. Foster, N. Clarke and
J. W. Steed, Soft Matter, 2012, 8, 204–216.
15 J. W. Steed, Chem. Soc. Rev., 2010, 39, 3686–3699.
16 D. A. Jose, D. K. Kumar, B. Ganguly and A. Das, Inorg. Chem.,
2007, 46, 5817–5819.
Fig. 4 Possibility of the tris(urea) 1a related to the transformation
between dimeric capsules and supramolecular gels by sonication.
in terms of 1a, its formed dimeric aggregates in the crystal
might be the most highly ordered aggregation in the solid
state, and its amorphous precipitate resulted from cooling of
its thermally dissolved CH3CN solution is a random aggregation.
The sonication-induced formation of gels may be an intermediate
aggregation between these two above states.40 We presumed that
the belt of six hydrogen-bonded ureas of 1aÁ1a might be biased
by ultrasound, which can drive self-assembly to less ordered
aggregates41 resembling the tris(urea) LMWGs26,28 (Fig. 4),
resulting in the hydrogen bonding of the ureas to form one-
dimensional polymer-like fibrous aggregates (Fig. 3b)
17 P. S. Lakshminarayanan, I. Ravikumar, E. Suresh and P. Ghosh,
Chem. Commun., 2007, 5214–5216.
18 R. Custelcean, P. Remy, P. V. Bonnesen, D.-e. Jiang and
B. A. Moyer, Angew. Chem., Int. Ed., 2008, 47, 1866–1870.
19 B. Wu, J. Liang, J. Yang, C. Jia, X.-J. Yang, H. Zhang, N. Tang
and C. Janiak, Chem. Commun., 2008, 1762–1764.
20 N. Busschaert, P. A. Gale, C. J. E. Haynes, M. E. Light,
S. J. Moore, C. C. Tong, J. T. Davis and J. W. A. Harrell, Chem.
Commun., 2010, 46, 6252–6254.
21 M. Arunachalam and P. Ghosh, Chem. Commun., 2011, 47,
8477–8492.
22 N. Busschaert, M. Wenzel, M. E. Light, P. Iglesias-Herna
R. Perez-Tomas and P. A. Gale, J. Am. Chem. Soc., 2011, 133,
14136–14148.
23 J. J. Gonzalez, R. Ferdani, E. Albertini, J. M. Blasco, A. Arduini,
´
ndez,
´
´
In summary, we have prepared tris(ureidobenzyl)amine
derivatives 1a and 1b which can form dimeric aggregates in
apolar solution. X-Ray analysis of 1a showed the existence of a
hydrogen-bonded dimeric aggregate entangled by a six-membered
ring of ureas in a head-to-tail fashion and the cavity is filled with a
molecule of H2O. Specifically, the tris(urea) 1a would transform
into supramolecular gels in certain solvents via sonication. SEM
was employed to study the morphology of xerogels of 1a, which
shows the thread-like nature of gel nanofibres. Concentration-
dependent 1H NMR spectroscopy and solvent-tuning experiments
confirmed that intermolecular hydrogen bonding plays an essential
role in the formation of supramolecular aggregates. This research
offers an insight of the transformation between dimeric capsules
and supramolecular gels for tripodal tris(urea) receptors.
´
A. Pochini, P. Prados and J. de Mendoza, Chem.–Eur. J., 2000, 6,
73–80.
24 Y. Rudzevich, V. Rudzevich, D. Schollmeyer, I. Thondorf and
V. Bohmer, Org. Lett., 2005, 7, 613–616.
¨
25 M. Alajarin, R.-A. Orenes, J. W. Steed and A. Pastor, Chem.
Commun., 2010, 46, 1394–1403.
26 M. de Loos, Alette G. J. Ligtenbarg, J. van Esch, H. Kooijman,
Anthony L. Spek, R. Hage, Richard M. Kellogg and Ben
L. Feringa, Eur. J. Org. Chem., 2000, 3675–3678.
27 K. J. C. van Bommel, C. van der Pol, I. Muizebelt, A. Friggeri,
A. Heeres, A. Meetsma, B. L. Feringa and J. van Esch, Angew.
Chem., Int. Ed., 2004, 43, 1663–1667.
28 C. E. Stanley, N. Clarke, K. M. Anderson, J. A. Elder,
J. T. Lenthall and J. W. Steed, Chem. Commun., 2006, 3199–3201.
29 M. Yamanaka, T. Nakamura, T. Nakagawa and H. Itagaki,
Tetrahedron Lett., 2007, 48, 8990–8993.
´
30 M. Alajarı
Chem., 2002, 67, 7091–7095.
31 M. Alajarın, A. Pastor, R.-A. Orenes, E. Martı
´
n, A. Pastor, R.-A. Orenes and J. W. Steed, J. Org.
We gratefully thank the financial support of National Natural
Science Foundation of China (No. 20932004, 21072093), National
Basic Research Program of China (2011CB808600), The Doctoral
Fund of Ministry of Education of China (20090091110017),
and The Natural Science Foundation of Jiangsu (BK2011055,
BK2011551).
´
´
nez-Viviente,
H. Ruegger and P. S. Pregosin, Chem.–Eur. J., 2007, 13,
¨
1559–1569.
32 M. Alajarin, A. Pastor, R.-A. Orenes, A. E. Goeta and J. W. Steed,
Chem. Commun., 2008, 3992–3994.
33 The diffusion coefficient of the aggregate of 1a, b was found to be
slightly lower than the internal reference, heptakis(2,3,6-tri-
O-methyl)-b-cyclodextrin (M = 1429 g molÀ1), indicating a
dimeric size (M1a@1a = 2028 g molÀ1 and M1b@1b = 2245 g molÀ1);
see: B. J. B. Folmer, R. P. Sijbesma and E. W. Meijer, J. Am. Chem.
Soc., 2001, 123, 2093–2094.
34 The ROESY experiment of 1a and 1c in CDCl3 could not be
obtained due to their poor solubility.
´
35 M. Chas, G. n. Gil-Ramirez, E. C. Escudero-Adan, J. Benet-
Buchholz and P. Ballester, Org. Lett., 2010, 12, 1740–1743.
36 Y. Li, T. Wang and M. Liu, Tetrahedron, 2007, 63, 7468–7473.
37 X.-D. Xu, J. Zhang, L.-J. Chen, X.-L. Zhao, D.-X. Wang and
H.-B. Yang, Chem.–Eur. J., 2012, 18, 1659–1667.
38 Y. Li and A. H. Flood, J. Am. Chem. Soc., 2008, 130,
12111–12122.
39 G. O. Lloyd and J. W. Steed, Nat. Chem., 2009, 1, 437–442.
40 N. M. Sangeetha and U. Maitra, Chem. Soc. Rev., 2005, 34,
821–836.
Notes and references
1 P. Terech and R. G. Weiss, Chem. Rev., 1997, 97, 3133–3160.
2 L. A. Estroff and A. D. Hamilton, Chem. Rev., 2004, 104, 1201–1218.
3 M.-O. M. Piepenbrock, G. O. Lloyd, N. Clarke and J. W. Steed,
Chem. Rev., 2010, 110, 1960–2004.
4 J. H. van Esch, F. Schoonbeek, M. de Loos, H. Kooijman, A. L. Spek,
R. M. Kellogg and B. L. Feringa, Chem.–Eur. J., 1999, 5, 937–950.
5 J. Brinksma, B. L. Feringa, R. M. Kellogg, R. Vreeker and J. van
Esch, Langmuir, 2000, 16, 9249–9255.
6 F. S. Schoonbeek, J. H. van Esch, R. Hulst, R. M. Kellogg and
B. L. Feringa, Chem.–Eur. J., 2000, 6, 2633–2643.
7 L. Applegarth, N. Clark, A. C. Richardson, A. D. M. Parker,
I. Radosavljevic-Evans, A. E. Goeta, J. A. K. Howard and
J. W. Steed, Chem. Commun., 2005, 5423–5425.
8 Y. Jeong, K. Hanabusa, H. Masunaga, I. Akiba, K. Miyoshi,
S. Sakurai and K. Sakurai, Langmuir, 2005, 21, 586–594.
41 D. Bardelang, Soft Matter, 2009, 5, 1969–1971.
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 7973–7975 7975