Ship-in-a-bottle entrapment of molecules in porous nanocapsules

Article abstract of DOI:10.1039/c1cc11526j

Size-selective pores in the shells of hollow polymer nanocapsules enable combined assembly and entrapment of molecules. Small building blocks enter the capsule through the pores. The assembled molecules, which are larger than the pores, remain entrapped i

Full text of DOI:10.1039/c1cc11526j

Chemical Communications
www.rsc.org/chemcomm
Volume 47 | Number 29 | 7 August 2011 | Pages 8177–8444
ISSN 1359-7345
COMMUNICATION
Eugene Pinkhassik et al.
Ship-in-a-bottle entrapment of
molecules in porous nanocapsules
1359-7345(2011)47:29;1-9

Dynamic Article Links
ChemComm
Cite this: Chem. Commun., 2011, 47, 8223–8225
www.rsc.org/chemcomm
COMMUNICATION
Ship-in-a-bottle entrapment of molecules in porous nanocapsulesw
Sergey N. Shmakov, Sergey A. Dergunov and Eugene Pinkhassik*
Received 16th March 2011, Accepted 6th April 2011
DOI: 10.1039/c1cc11526j
Size-selective pores in the shells of hollow polymer nanocapsules
enable combined assembly and entrapment of molecules. Small
building blocks enter the capsule through the pores. The
assembled molecules, which are larger than the pores, remain
entrapped in the nanocapsules. Porous nanometre-thin walls
permit unhindered functionalization of entrapped molecules.
space inside the nanocapsules will permit unhindered inter-
actions with other molecules, such as substrates or analytes.
We chose 5,10,15,20-tetra-p-tolyl-21H,23H-porphine (H2TTP)
for construction within the nanocapsule (Fig. 1A). H2TTP is
an excellent example of a larger molecule (approx. 2 nm in
Entrapment of large and medium sized molecules in porous
nanocapsules can lead to new functional nanodevices, such as
nanoreactors, sensors, or imaging systems.1 A common method
for entrapment is creating the capsule in the presence of the
target molecule.1,2 Many useful molecules are not compatible
with the capsule preparation chemistry. For example, only
water-soluble molecules can be entrapped in liposome-
templated nanocapsules. New methods for entrapment of
molecules will broaden the scope of devices based on nanocapsules.
Here we demonstrate the first example of entrapment of
medium-sized molecules created within a porous nanocapsule
from small building blocks. In this approach, small building
blocks enter hollow nanocapsules through the pores of the
shell and are then assembled into a larger molecule (Fig. 1).
This larger molecule remains entrapped within the nano-
capsule because it is too big to pass through the pores. Hollow
polymer nanocapsules that have shells containing nanopores
with controlled size and narrow size distribution can be
prepared by polymerization in the presence of pore-forming
templates in the interior of liposomal bilayers.2
Previously, a number of molecules were entrapped in porous
materials, such as zeolites or soft porous crystals, where the
molecules are immobilized in highly confined spaces.3 Such
entrapped molecules have been used in catalysis.
The entrapment of molecules in hollow nanocapsules, where
the interior dimensions greatly exceed the size of the entrapped
molecules, is particularly interesting. Entrapped molecules
would stay in a homogeneous environment. Their properties
are not likely to be negatively affected by the shell of the
nanocapsule. Nanometre-thin porous walls will provide ultra-
fast communication with the external environment.2 Sufficient
Fig. 1 (A) Combined assembly and entrapment of 5,10,15,20-tetra-p-
tolyl-21H,23H-porphine (H2TTP) in a porous nanocapsule. The
synthesis of H2TTP was carried out by a 30-minute reflux in acetic
acid. (B) Space-filling models of building blocks pyrrole (PY) and
p-tolyl aldehyde (PTA), pore-forming template glucose pentaacetate
(GPA), and the assembled molecule (H2TTP). Approximate smallest
cross-sections are shown for PTA, PY, and H2TTP. (C) TEM image of
hollow porous nanocapsules used in this work. (D) Average pore
diameter of approx. 0.8 Æ 0.2 nm in the shells of nanocapsules
confirmed by a colored size probe retention assay, where nanocapsules
retain 0.6 nm yellow and 1.1 nm red dyes prior to pore opening (1)
and release 0.6 nm probe but retain the 1.1 nm dye after opening the
pores (2).2a–c
Institute for Nanomaterials Development and Innovation at the
University of Memphis (INDIUM) and Department of Chemistry,
University of Memphis, Memphis, TN 38152, USA.
E-mail: epnkhssk@memphis.edu; Fax: +1 901 678 3447;
Tel: +1 901 678 2621
w Electronic supplementary information (ESI) available: Experimental
details, IR and UV-vis spectra, spectroscopic data for MnTTPCl and
FeTTP. See DOI: 10.1039/c1cc11526j
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 8223–8225 8223

cross section, Fig. 1B) built from smaller building blocks,
pyrrole and p-tolyl aldehyde (0.6 nm each, Fig. 1B). It is easily
observed with spectroscopic methods, and it can serve as a
foundation for creating functional devices. In particular,
metallated porphyrin derivatives have been used as catalysts,4
sensors,5 and oxygen carriers.6
In these experiments, polymer nanocapsules with an average
diameter of 100 nm (Fig. 1C) were obtained by polymerization
of hydrophobic monomers within the interior of lipid bilayers
of liposomes.2 Glucose pentaacetate (GPA) was used as a
pore-forming template leading to the creation of pores with
0.8 Æ 0.2 nm diameter (Fig. 1D).2a–c The pore size was
confirmed with a colored size probe retention assay as
described previously.2a–c Briefly, 1.1 nm and 0.6 nm size
probes were retained within the capsule formed in the absence
of pore-forming templates, and 0.6 nm probe but not the
1.1 nm probe was released when GPA was used in the
synthesis of nanocapsules. Building blocks, pyrrole and p-tolyl
aldehyde, were added to the suspension of nanocapsules in
acetic acid and allowed to diffuse into the nanocapsule inter-
ior. The synthesis of H2TTP was carried out by the reflux for
approximately 30 min.7 The reaction mixture was then cooled,
and nanocapsules were precipitated with methanol.
Unentrapped H2TTP was removed by washing nano-
capsules with a mixture of methanol and chloroform (3 : 5).
Nanocapsules form a gel-like precipitate in this mixture, while
H2TTP is sufficiently soluble. The formation of entrapped
H2TTP is apparent due to the strong coloration of nano-
capsules. Successful synthesis was further confirmed by the
fluorescence spectroscopy (Fig. 2B) that revealed characteristic
emission bands Qx(0,0) at 650 nm and Qx(0,1) at 720 nm
(419 nm excitation wavelength).8 The position and relative
strengths of these bands are identical for free (solid red) and
encapsulated (solid black) H2TTP (Fig. 2B). Light scattering
from nanocapsules was present in UV-vis and fluorescence
spectra of encapsulated porphyrins.
Entrapped H2TTP can rapidly communicate with the
exterior of the nanocapsules. To illustrate this communication,
we carried out the metallation of H2TTP with different metal
salts, zinc acetate, manganese dichloride, and iron acetate
(Fig. 2A).7b Metallation reactions can be easily observed with
fluorescence and UV-vis spectroscopy. By using 419 nm as the
excitation wavelength, we observe the decrease of emission at
650 nm and disappearance of the emission peak at 720 nm
upon addition of zinc acetate to free and entrapped H2TTP
(Fig. 2B, dashed red and dashed black lines show the fluores-
cence spectra of free and encapsulated ZnTTP, respectively).
Similarly, an absorbance peak at 490 nm nearly disappears
immediately upon addition of zinc acetate to entrapped
H2TTP (Fig. 2C; Soret band is shifted to a higher wavelength
due to the sonication of the nanocapsule sample in a
chlorinated solvent).9 Identical behavior of free and entrapped
H2TTP and instantaneous (o1 s) spectral change suggest that
the walls of nanocapsules do not hinder the transport of metal
ions. These results expand our previous observation of
identical protonation and deprotonation rates for entrapped
and free pH-sensitive indicator dyes.2d
Fig. 2 (A) Schematic representation of metallation of entrapped
H2TTP by Zn(OAc)2, MnCl2Á4H2O and Fe(OAc)2. (B) Fluorescence
spectra of free H2TTP (solid red line), entrapped H2TTP (solid black
line), free ZnTTP (dashed red line), and entrapped ZnTTP (dashed
black line). (C) UV spectra of the entrapped porphyrin before (black)
and after (red) addition of Zn(OAc)2. All spectra were recorded in
methylene chloride.
MnTTPCl have been repeatedly washed with methanol, and
no porphyrin was found in the supernatant. The gel-like
precipitate of nanocapsules is colored due to entrapped
porphyrin molecules (Fig. 3, inset). After two months of
standing at ambient conditions, an aliquot of the supernatant
taken from the sample containing entrapped MnTTPCl
showed no trace of MnTTPCl (Fig. 3, black line). For
contrast, a spectrum of free MnTTPCl (Fig. 3, red line) is
shown at the concentration corresponding to the release of
10% of MnTTPCl from the nanocapsules into the supernatant
(0.7 mM). The amount of entrapped MnTTPCl was measured
Entrapped porphyrin molecules are retained within the
nanocapsules. Nanocapsules with entrapped H2TTP and
c
8224 Chem. Commun., 2011, 47, 8223–8225
This journal is The Royal Society of Chemistry 2011

142–164; (c) W. Ch. Mak, K. Y. Cheung and D. Trau, Adv. Funct.
Mater., 2008, 18, 2930–2937; (d) M. Germain, S. Grube, V. Carriere,
H. Richard-Foy, M. Winterhalter and D. Fournier, Adv. Mater.,
2006, 18, 2868–2871; (e) G. Baier, A. Musyanovych, M. Dass,
S. Theisinger and K. Landfester, Biomacromolecules, 2010, 11,
960–968; (f) D. Crespy, M. Stark, C. Hoffmann-Richter,
U. Ziener and K. Landfester, Macromolecules, 2007, 40,
3122–3135; (g) K. Y. Kwona, J. Youna, J. H. Kim, Y. Park,
Ch. Jeon, B. Ch. Kim, Y. Kwon, X. Zhao, P. Wang, B. I. Sang,
J. Lee, H. G. Park, H. N. Chang, T. Hyeon, S. Ha, H.-T. Jung and
J. Kim, Biosens. Bioelectron., 2010, 26, 655–660; (h) E. Donath,
G. B. Sukhorukov, F. Caruso, S. A. Davis and H. Mohwald,
¨
Angew. Chem., Int. Ed., 1998, 37, 2201–2205; (i) L. J. De Cock,
S. De Koker, B. G. De Geest, J. Grooten, Ch. Vervaet, J. P. Remon,
G. B. Sukhorukov and M. N. Antipina, Angew. Chem., Int. Ed.,
2010, 49, 6954–6973; (j) M. F. Bedard, B. G. De Geest,
´
A. G. Skirtach, H. Mohwald and G. B. Sukhorukov, Adv. Colloid
¨
Interface Sci., 2010, 158, 2–14.
2 (a) S. A. Dergunov and E. Pinkhassik, Angew. Chem., Int. Ed., 2008,
47, 8264–8267; (b) D. C. Danila, L. T. Banner, E. J. Karimova,
L. Tsurkan, X. Wang and E. Pinkhassik, Angew. Chem., Int. Ed.,
2008, 47, 7036–7039; (c) S. A. Dergunov, K. Kesterson, W. Li,
Z. Wang and E. Pinkhassik, Macromolecules, 2010, 43, 7785–7792;
(d) S. A. Dergunov, B. Miksa, B. Ganus, E. Lindner and
E. Pinkhassik, Chem. Commun., 2010, 46, 1485–1487;
(e) S. N. Shmakov and E. Pinkhassik, Chem. Commun., 2010, 46,
7346–7348.
3 (a) S. Horike, S. Shimomura and S. Kitagawa, Nat. Chem., 2009, 1,
695–704; (b) M. H. Alkordi, Y. Liu, R. W. Larsen, J. F. Eubank and
M. Eddaoudi, J. Am. Chem. Soc., 2008, 130, 12639–12641;
(c) A. D. Price, A. N. Zelikin, K. L. Wark and F. Caruso, Adv.
Mater., 2010, 22, 720–723; (d) K. Mori, K. Kagohara and
H. Yamashita, J. Phys. Chem. C, 2008, 112, 2593–2600;
Fig. 3 Black line: UV-vis spectra of supernatant taken from a sample
containing nanocapsules with entrapped MnTTPCl (inset, sample 3).
Red line: supernatant mixed with free MnTTPCl added in the
concentration corresponding to the release of 10% of entrapped
MnTTPCl (0.7 mM). Inset: blank nanocapsules (1), nanocapsules with
entrapped H2TTP (2), and nanocapsules with entrapped MnTTPCl (3)
in methanol.
by atomic absorption spectroscopy. In similar experiments, no
release of H2TTP, ZnTTP, and FeTTP was observed. Long-
term retention of the entrapped porphyrin molecules confirms
the successful implementation of the underlying idea of this
study, the combined assembly and entrapment of molecules in
porous nanocapsules. The ability to vary the pore size by using
different pore-forming templates, demonstrated previously,2b
will permit tuning the pores for entrapment of different
molecules. This approach is likely to be broadly applicable
to various molecules assembled from small building blocks,
including organometallic complexes, macrocycles, etc.
¨
(e) T. Doussineau, M. Smaıhi, S. Balme and J.-M. Janot,
ChemPhysChem, 2006, 7, 583–589; (f) M. Silva, M. E. Azenha,
M. M. Pereira, H. D. Burrows, M. Sarakha, C. Forano,
M. F. Ribeiro and A. Fernandes, Appl. Catal. B: Environ., 2010,
100, 1–9; (g) E. Kockrick, T. Lescouet, E. V. Kudrik, A. B. Sorokin
and D. Farrusseng, Chem. Commun., 2011, 47, 1562–1564.
4 (a) P. Battioni, J. P. Renaud, J. F. Bartoli, M. Reina-Artiles,
M. Fort and D. Mansuy, J. Am. Chem. Soc., 1988, 110,
8462–8470; (b) C.-M. Che and J.-S. Huang, Chem. Commun.,
2009, 3996–4015; (c) S. Sakaki, T. Sagara, T. Arai, T. Kojima,
T. Ogata and K. Ohkubo, J. Mol. Catal., 1992, 75, L33–L37;
(d) R. Naik, P. Joshi, S. Umbarkar and R. K. Deshpande, Catal.
Commun., 2005, 6, 125–129.
In summary, we showed that the size-selective pores in the
walls of hollow nanocapsules enable simultaneous assembly
and entrapment of molecules. In this approach, building
blocks that are smaller than the pore size enter the nano-
capsule and assemble into a molecule with the cross section
exceeding the pore size. This newly assembled molecule
remains entrapped within the nanocapsule. Porous walls
permit unhindered communication of entrapped molecules
with external components that are smaller than the pores.
This work was supported by NSF (CHE-1012951) and a
FedEx Institute of Technology Innovation Award.
5 (a) X.-B. Zhang, C.-C. Guo, Z.-Z. Li, G.-L. Shen and R.-Q. Yu,
Anal. Chem., 2002, 74, 821–825; (b) B.-H. Han, I. Manners and
M. A. Winnik, Chem. Mater., 2005, 17, 3160–3171.
6 (a) L. J. Twyman and Yi Ge, Chem. Commun., 2006, 1658–1660;
(b) D.-L. Jiang and T. Aida, Chem. Commun., 1996, 1523–1524.
7 (a) A. D. Adler, F. R. Longo, J. D. Finarelli, J. Goldmacher,
J. Assour and L. Korsakoff, J. Org. Chem., 1967, 32, 476;
(b) K. M. Kadish, K. M. Smith and R. Guilard, The Porphyrin
Handbook, Academic Press, San Diego, 2000; (c) P. Rothemund and
A. R. Menotti, J. Am. Chem. Soc., 1948, 70, 1808–1812;
(d) E. B. Fleischer, J. M. Palmer, T. S. Srivastava and
A. Chatterjee, J. Am. Chem. Soc., 1971, 93, 3162–3167.
8 G. D. Dorough, J. R. Miller and F. M. Huennekens, J. Am. Chem.
Soc., 1951, 73, 4315.
9 (a) E. M. Mhuircheartaigh, W. J. Blau, M. Prato and S. Giordani,
Phys. Status Solidi B, 2007, 244(11), 4227–4230; (b) E. M.
Mhuircheartaigh, W. J. Blau, M. Prato and S. Giordani, Carbon,
2007, 45, 2665–2671.
Notes and references
1 (a) T. S. Koblenz, J. Wassenaar and J. N. H. Reek, Chem. Soc. Rev.,
2008, 37, 247–262; (b) W. J. M. Mulder, G. J. Strijkers, G. A. F. van
Tilborg, A. W. Griffioen and K. Nicolay, NMR Biomed., 2006, 19,
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 8223–8225 8225