Hollow spheres self-assembled by a tetraphenylethylene macrocycle and their transformation to bird nests under ultrasound

Article abstract of DOI:10.1021/ol3035005

A new tetraphenylethylene macrocycle easily self-assembled into both intrinsic pores and extrinsic pores in crystal and hollow spheres in precipitates. The hollow spheres could be transformed into bird nests composed of nanorods under ultrasound, which could be used to load and controllably release anticancer drugs.

Full text of DOI:10.1021/ol3035005

ORGANIC
LETTERS
2013
Vol. 15, No. 4
820–823
Hollow Spheres Self-Assembled by a
Tetraphenylethylene Macrocycle and
Their Transformation to Bird Nests
under Ultrasound
Song Song and Yan-Song Zheng*
School of Chemistry and Chemical Engineering, Huazhong University of Science and
Technology, Wuhan 430074, China
zyansong@hotmail.com
Received December 20, 2012
ABSTRACT
A new tetraphenylethylene macrocycle easily self-assembled into both intrinsic pores and extrinsic pores in crystal and hollow spheres in
precipitates. The hollow spheres could be transformed into bird nests composed of nanorods under ultrasound, which could be used to load and
controllably release anticancer drugs.
Porous materials are attracting increasing interest
because of their importance in separation, storage, and
catalysis. Among the methods for preparation of the porous
materials, using organic macrocycles to self-assemble the
porous materials has special advantages because they can
form both intrinsic porosity and extrinsic porosities.1À21
The inherent cavity of the macrocycle could easily pile into
a porous channel to give intrinsic porosity which could be
modified in diameter, shape, and polarity by the change of
inherent cavity.1À10 In contrast, the extrinsic porosity12À21
from the arrangement of the macrocycles can exist as
(1) Jones, J. T. A.; Hasell, T.; Wu, X.; Bacsa, J.; Jelfs, K. E.;
Schmidtmann, M.; Chong, S. Y.; Adams, D. J.; Trewin, A.; Schiffman,
F.; Cora, F.; Slater, B.; Steiner, A.; Day, G. M.; Cooper, A. I. Nature
2011, 474, 367–371.
(2) Holst, J. R.; Trewin, A.; Cooper, A. I. Nature Chem. 2010, 2, 915–920.
(3) Tozawa, T.; Jones, J. T. A.; Swamy, S. I.; Jiang, S.; Adams, D. J.;
Shakespeare, S.; Clowes, R.; Bradshaw, D.; Hasell, T.; Chong, S. Y.;
Tang, C.; Thompson, S.; Parker, J.; Trewin, A.; Bacsa, J.; Slawin,
A. M. Z.; Steiner, A.; Cooper, A. I. Nat. Mater. 2009, 8, 973–978.
(4) Cooper, A. I. Angew. Chem., Int. Ed. 2012, 51, 2–5.
(5) Che, Y.; Gross, D. E.; Huang, H.; Yang, D.; Yang, X.; Discekici,
E.; Xue, Z.; Zhao, H.; Moore, J. S.; Zang, L. J. Am. Chem. Soc. 2012,
134, 4978–4982.
(6) Nakagaki, T.; Harano, A.; Fuchigami, Y.; Tanaka, E.; Kidoaki,
S.; Okuda, T.; Iwanaga, T.; Goto, K.; Shinmyozu, T. Angew. Chem., Int.
Ed. 2010, 49, 9676–9679.
(7) Dawn, S.; Dewal, M. B.; Sobransingh, D.; Paderes, M. C.;
Wibowo, A. C.; Smith, M. D.; Krause, J. A.; Pellechia, P. J.; Shimizu,
L. S. J. Am. Chem. Soc. 2011, 133, 7025–7032.
(9) Dewal, M. B.; Lufaso, M. W.; Hughes, A. D.; Samuel, S. A.;
Pellechia, P.; Shimizu, L. S. Chem. Mater. 2006, 18, 4855–4864.
(10) (a) Finke, A. D.; Gross, D. E.; Han, A.; Moore, J. S. J. Am.
Chem. Soc. 2011, 133, 14063–14070. (b) Zhou, X.; Liu, G.; Yamato, K.;
et al. Nature Commun. 2012, 3, 949. (c) Barbour, L. J. Chem. Commun.
2006, 1163–1168.
(11) Mastalerz, M.; Oppel, I. M. Angew. Chem., Int. Ed. 2012, 51,
5252–5255.
(12) Lim, S.; Kim, H.; Selvapalam, N.; Kim, K.-J.; Cho, S. J.; Seo, G.;
Kim, K. Angew. Chem., Int. Ed. 2008, 47, 3352–3355.
(13) Thallapally, P. K.; McGrail, B. P.; Atwood, J. L.; Gaeta, C.;
Tedesco, C.; Neri, P. Chem. Mater. 2007, 19, 3355–3357.
(14) Tedesco, C.; Erra, L.; Brunelli, M.; Cipolletti, V.; Gaeta, C.; Fitch,
A. N.; Atwood, J. L.; Neri, P. Chem.;Eur. J. 2010, 16, 2371–2374.
(15) Yang, W.-Y.; Ahn, J.-H.; Yoo, Y.-S.; Oh, N.-K.; Lee, M. Nat.
Mater. 2005, 4, 399–402.
(16) Xu, X.-N.; Wang, L.; Li, Z.-T. Chem. Commun. 2009, 6634–6636.
(17) Haridas, V.; Sahu, S.; Sapala, A. R. Chem. Commun. 2012, 48,
3821–3823.
(18) Alfonso, I.; Bru, M.; Burguete, M. I.; Garcia-Verdugo, E.; Luis,
S. V. Chem.;Eur. J. 2010, 16, 1246–1255.
(8) (a) Yang, J.; Dewal, M. B., Jr.; Profeta, S.; Smith, M. D.; Li, Y.;
Shimizu, L. S. J. Am. Chem. Soc. 2008, 130, 612–621. (b) Dawn, S.;
Dewal, M. B.; Sobransingh, D.; Paderes, M. C.; Wibowo, A. C.; Smith,
M. D.; Krause, J. A.; Pellechia, P. J.; Shimizu, L. S. J. Am. Chem. Soc.
2011, 133, 7025–7032.
(19) Li, P.-F.; Chen, C.-F. Chem. Commun. 2011, 47, 12170–12172.
r
10.1021/ol3035005
Published on Web 02/05/2013
2013 American Chemical Society

Figure 1. Structure of macrocyclic molecule 1.
discrete unfilled space, with a hope to form larger size of
pores and encapsulated big guest molecules. However, to
date, no significant amount of research has been done in this
area.
Tetraphenylethylene (TPE) and its derivatives have a
well-known aggregation-induced emission (AIE) effect,
displaying extensive application potential in optoelectro-
nic materials and bio/chemosensors.22,23 Due to repulsive
forces, the four phenyl groups of the TPE molecule are
not completely conjugated with the double bond and make
TPE a twisted molecule. Therefore, no πÀπ stacking
interactions but multiple CHÀπ hydrogen bonds between
TPE molecules or its derivatives exist in crystal struc-
ture,24,25 which is the main reason why they have an AIE
effect. The absence of πÀπ stacking interactions also
suggests that packing of TPE molecules in the aggregate
state is not very close, which gives them the possibility to
form extrinsic void space in solid state.11 It is true that
polymer scaffolds and metalÀorganic frameworks based
on TPE are microporous.26,27 Furthermore, due to sensi-
tivity to the environment, the AIE effect of macrocycles
based on TPE can probably be used as self-signals for
monitoring the process of self-assembly. But macrocyclic
compounds composed of TPE for self-assembling porous
materials have not yet been reported. Here, we report that
a TPE macrocycle could easily self-assemble into hollow
micro-/nanospheres as well as intrinsic and extrinsic por-
ous channels.
Figure 2. Electron microscopy images of a suspension of 1 in
water and THF with different water percentages: (A) TEM
image in 70% water; (B) TEM image in 90% water; (C) TEM
images in 95% water; (D) FE-SEM image in 95% water. [1] =
2.5 Â 10À3 M.
good yield. Solution of 1 in THF did not emit, but the
solid had strong fluorescence. When water was added
into the THF solution and a turbid solution appeared,
the resultant suspension emitted strong fluorescence,
indicating that macrocycle 1 was an AIE compound.
Meanwhile, when the content of water increased from
65% to 95% (volume percentage, as below), the emission
λ
max increased from 448 to 473 nm (Figure S11, Support-
ing Information). The fluorescence quantum yield of the
suspension of 1 in 70, 90, and 95% water was 9.1, 10, and
15%, respectively, using quinine sulfate as a reference
standard.
Interestingly, not only the fluorescence spectrum but
alsothe morphologyof aggregates of 1 in the mixed solvent
changed with water fraction. It was disclosed by TEM
images that the aggregates were nanorods in a suspension
with 70% water(Figure 2A). Whenthe waterwasincreased
to 90%, the aggregates became solid spheres (Figure 2B).
Surprisingly, hollow spheres were obtained after the water
content was elevated to 95% or more. TEM images re-
vealed that the diameter of the hollow spheres was dis-
tributed from about 1 to 8 μm, and the shell width of the
hollow spheres was in the range of 500 nm to 1 μm
(Figure 2C and Figures S12ÀS13, Supporting Information).
The FE-SEM image disclosed that the suspension of 1 in
95% water was composed of spherical aggregates, and
the surface of many of these was sunken and some of them
were broken, showing that the spheres were truly hollow
(Figure 2D and Figures S14ÀS15, Supporting Information).
The formation of the giant hollow spheres was very reliable
and could be easily repeated as long as water was quickly
added to the solution of 1 in THF until at a percentage of
95% or more. Due to the challenges of obtaining cell-sized
Macrocycle 1 (Figure 1) was synthesized by connecting
two TPE molecules with two triethylene glycol chains in
(20) Atwood, J. L.; Barbour, L. J.; Jerga, A.; Schottel, B. L. Science
2002, 298, 1000–1002.
(21) (a) Thallapally, P. K.; Dobrzanska, L.; Gingrich, T. R.; Wirsig,
T. B.; Barbour, L. J.; Atwood, J. L. Angew. Chem., Int. Ed. 2006, 45,
6506–6509. (b) Tian, J.; Thallapally, P. K.; Dalgarno, S. J.; McGrail,
P. B.; Atwood, J. L. Angew. Chem., Int. Ed. 2009, 48, 5492–5495. (c)
Jiang, S.; Jones, J. T. A.; Hasell, T.; Blythe, C. E.; Adams, D. J.; Trewin,
A.; Cooper, A. I. Nature Commun. 2011, 2, 207.
(22) Hong, Y.; Lam, J. W. Y.; Tang, B. Z. Chem. Soc. Rev. 2011, 40,
5361–5388.
(23) Wang, M.; Zhang, G.; Zhang, D.; Zhu, D.; Tang, B. Z. J. Mater.
Chem. 2010, 20, 1858–1867.
(24) Dong, Y.; Lam, J. W. Y.; Qin, A.; Liu, J.; Li, Z.; Tang, B. Z.;
Sun, J.; Kwok, H. S. Appl. Phys. Lett. 2007, 91, 011111.
(25) Tong, H.; Hong, Y.; Dong, Y.; Ha1ussler, M.; Li, Z.; Lam,
J. W. Y.; Dong, Y.; Sung, H. H.-Y.; Williams, I. D.; Tang, B. Z. J. Phys.
Chem. B 2007, 111, 11817–11823.
(26) Xu, Y.; Chen, L.; Guo, Z.; Nagai, A.; Jiang, D. J. Am. Chem.
Soc. 2011, 133, 17622–17625.
(27) Shustova, N. B.; McCarthy, B. D.; Dinca, M. J. Am. Chem. Soc.
ꢀ
2011, 133, 20126–20129.
Org. Lett., Vol. 15, No. 4, 2013
821

Figure 3. (A) TEM image and (B) FE-SEM image of a suspen-
sion of 1 in 95% water with ultrasonic treatment for 1.5 h. (C)
TEM image with ultrasonic treatment for 45 min. (D) TEM
image with ultrasonic treatment for 4 h. [1] = 2.5 Â 10À3 M.
Figure 4. (A) Structures of 1 in single crystal from water and
THF; (B) intrinsic and extrinsic channels packed by 1.
vesicles, these kinds of giant hollow sphere have a potential
to be used as artificial cells.28,29
was decreased to 450 and 437 nm from 473 nm, respec-
tively. Notably, the hollow spheres were not altered under
ultrasonic waves if they were suspended in pure water
without THF. Therefore, the transformation of the aggre-
gates from hollow spheres to nanorods was not a simple
breakage of the spheres, but a change resulting from a
dissolving and reassembling process. In 90% water in
which solid spheres were formed, the solid spheres could
be transformed into nanorods not only by ultrasound but
also by standing at room temperature, corroborating the
dissolving and reassembling process.
X-ray diffraction of a single crystal of 1 obtained from
water and THF30 disclosed that 1had an inherent rectangular
cavity with 1.5 nm length and 0.7 nm width (Figure 4A).
The rectangular cavities of 1 could pack into intrinsic cubic
channels, which were filled with THF molecules (THF/1
2:1) (Figure 4B, pore I). Because of the twisted conjugated
structure of 1, two neighboring macrocyclic molecules
were staggered along the channel direction (axis a) rather
than eclipsed. Between four intrinsic cubic channels, one
extrinsic cubic channel with 1.2 nm length and 0.7 nm
width was formed, which was also filled with THF mole-
cules (THF/1 2:1) (Figure 4B, pore II). It could also be
regarded that the extrinsic cubic channel was formed
through the piling up of rectangles composed of four
molecules of 1. Therefore, the interior of one molecule of
1 made up one part of the intrinsic channel and simulta-
neously the exterior of it became one part of extrinsic
channel. This packing gave a very large exposed molecular
After standing at room temperature for 3 days, the
nanorods in 70% water grew bigger and emitted more
intensivefluorescence, whilethe solid spheresin90% water
converted into nanorods and the emission λmax decreased
from 470 to 450 nm. However, the hollow spheres in 95%
water were very stable and no change in morphology or
fluorescence was observed after they were allowed to stand
for more than two weeks.
However, when treated with ultrasonic waves, the hol-
low sphere reassembled into nanorods which could form
an aggregate just like a bird nest (Figure 3A,B and Figures
S16 and S17, Supporting Information). As ultrasonic time
was increased from 45 min to 1.5 and 4 h, the width of the
nanorods decreased from about 100 to 70 nm and 30 nm,
respectively, while their length was stable at about 600 nm.
Meanwhile, after 45 min of ultrasonic treatment, the
produced nanorods were on the shell of the sphere and
the round aggregate arranged by the nanorods was still
enclosed (Figure 3C). After 1.5 h, the hollow sphere
opened in one direction, but most of the nanorods re-
mained at their original position on the shell, which led to
a bird nest like aggregate (Figure 3A,B). After 4 h, the
nanorods were totally dispersed and no longer arranged
around a cycle while their width was obviously reduced
(Figure 3D). In addition, the emission λmax of the fluores-
cence spectrum of the hollow spheres decreased with
ultrasonic time (Figure S18, Supporting Information).
After 1.5 and 4 h of ultrasonic treatment, the wavelength
(28) Sakaino, H.; Sawayama, J.; Kabashima, S.-i.; Yoshikawa, I.;
Araki, K. J. Am. Chem. Soc. 2012, 134, 15684–15687.
(29) Diguet, A.; Yanagisawa, M.; Liu, Y.-J.; Brun, E.; Abadie, S.;
(30) The crystallographic data have been deposited in the Cambridge
Structural Database as CCDC 907540 for a single crystal from water and
THF and CCDC 907541 for a single crystal from dichloromethane and
methanol.
Rudiuk, S.; Baigl, D. J. Am. Chem. Soc. 2012, 134, 4898–4904.
822
Org. Lett., Vol. 15, No. 4, 2013

than the middle value (45°) between 0° and 90°. Compared
with the nanorod, the spherical aggregate could emit
fluorescence with a longer wavelength (up to a difference
of 36 nm) and also had a larger absorption λmax (a dif-
ference of about 15 nm) in UVÀvis spectrum (Figure S19,
Supporting Information), indicating that the molecule of 1
in spheres had more conjugation, which in turn led to less
dihedral angle and bigger repulsive force. A single crystal
structure30 of 1 from dichloromethane and methanol
emitted blue fluorescence with a wavelength 10 nm shorter
than that of the single crystal from THF and water
(Figure S20, Supporting Information), but had an aver-
age dihedral angle of 54.71° which was 2.8° larger than
that of the later crystal (Figures S21ÀS22, Supporting
Information). Furthermore, the average twisted angle31
(7.97°) of the double bond in the former crystal was also
less than that (11.72°) in the crystal from water and THF.
This result confirmed that the molecule of 1 that emitted
shorter wavelength of light had a less repulsive force.
Therefore, spherical aggregates that emitted a longer
wavelength of light were composed of higher energy of 1
and could spontaneously transform into nanorods by
standing and ultrasonic treatment. As the water content
was increased, the large hydrophobic force could make the
molecule of 1 exist in a conformation with higher energy.
Powder X-ray diffraction revealed that nanorods and solid
spheres displayed many strong and sharp peaks, but the
hollow spheres almost exhibited only a weak and broad
peak at low angles (Figures S23ÀS25, Supporting
Information), demonstrating that the precipitating was
so fast that 1 could not form ordered pack in hollow
spheres.24 Treated by ultrasonic waves, the powder X-ray
diffraction pattern gave many strong sharp peaks, indicat-
ing that the amorphous hollow spheres were transformed
into more stable crystalline nanorods.
Figure 5. Schematic illustration for the formation of a hollow
sphere.
surface in the solvated channels of 1 and one molecule of 1
could combine four molecules of THF.
As expected, no πÀπ stacking interactions were found
between macrocycles, but there were many ArHÀπ,
CHÀπ, and ArHÀO hydrogen bonds between aromatic
rings. In addition, between the phenyl rings and solvent
˚
˚
THF, there were ArHÀH (2.288 A), ArHÀO (2.556 A),
˚
and ArHÀC (2.823 A) interactions. These interactions
played a key role in the formation of both intrinsic and
extrinsic porosity.
The reason why porous aggregates of 1 were formed in a
smaller amount of water was probably related to the
precipitating velocity. When a smaller amount of water
was added into the solution of 1 in THF, the molecules of 1
precipitated slowly and could efficiently pack each other so
that no large cavity could be seen by TEM. When water
was increased to 95%, the macrocyclic molecules precipi-
tated too fast to pack efficiently, therefore, hollow spheres
were obtained. It was not difficult to deduce from the
crystal structure of 1 that hollow spheres could be pro-
duced if pore II was composed of more than four macro-
cyclic molecules. These molecules were staggered and,
due to hydrophobic force, could arrange around a cycle
to form a round cavity as shown in Figure 5.
According to structure theory, a small repulsive force
between phenyl groups and a large conjugation of them
with the double bond will make 1 more stable. However,
more conjugation will lead to a smaller dihedral angle
between the phenyl plane and double bond plane, which
would lead to a larger repulsive force. As a result, a balance
between the repulsive force and conjugation effect or
between the dihedral angles of 0À90° for molecule of 1
arrived.25 Because of crowded phenyl groups, a bigger
dihedral angle instead of more conjugation will stabilize
the molecule. Therefore, the average dihedral angle of the
four phenyl rings in the crystal structure of 1 from a mixed
solvent of water and THF was 51.71°, which was larger
The potential for the loading and releasing of guest
molecules by the hollow spheres was demonstrated using
a picric acid salt of the anticancer drug procarbazine (here
abbreviated as picrate) as a representative example. By
UVÀvis measurement of the picrate, the loading amount
of the picrate was calculated to be 5.3 mg per 100 mg of 1.
The release of the picrate was fast under ultrasonic waves.
In 1.5 and 3 h, 57% and 92% of the loaded picrate was
released, respectively (Figure S26, Supporting Information).
If left to stand at room temperature, only 9.8% and 62%
of the picrate were released in 12 and 72 h, respectively
(Figure S27, Supporting Information).
Acknowledgment. This research work was supported
by the National Natural Science Foundation of China (No.
20872040 and 21072067) and the Analytical and Testing
Centre at Huazhong University of Science and Technology.
Supporting Information Available. Experimentaldetails,
XRD patterns, more crystal structures, and images. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(31) Shustova, N. B.; Ong, T.-C.; Cozzolino, A. F.; Michaelis, V. K.;
ꢀ
Griffin, R. G.; Dinca, M. J. Am. Chem. Soc. 2012, 134, 15061–15070.
The authors declare no competing financial interest.
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