Catalytic ship-in-a-bottle assembly within hollow porous nanocapusles

Article abstract of DOI:10.1039/c3nj01449e

Large molecules can be assembled from small components exclusively inside hollow nanocapsules with the help of entrapped catalysts. Phenyl isocyanates enter the capsules through nanopores in the capsule shells and form cyclic trimers that remain entrapped

Full text of DOI:10.1039/c3nj01449e

Volume 38 Number 2 February 2014 Pages 457–860
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New Journal of Chemistry
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LETTER
Eugene Pinkhassik et al.
Catalytic ship-in-a-bottle assembly within hollow porous nanocapusles

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Catalytic ship-in-a-bottle assembly within hollow
porous nanocapusles†
Cite this: New J. Chem., 2014,
38, 481
Nasim Ehterami,a Sergey A. Dergunov,a Yenlik Ussipbekova,b Vladimir B. Birmanc
and Eugene Pinkhassik*a
Received (in Montpellier, France)
20th November 2013,
Accepted 4th December 2013
DOI: 10.1039/c3nj01449e
www.rsc.org/njc
Large molecules can be assembled from small components exclusively molecules larger than the pores.10 Various other nano- and
inside hollow nanocapsules with the help of entrapped catalysts. Phenyl microcapsules were previously reported.11–21
isocyanates enter the capsules through nanopores in the capsule shells
In a simple ship-in-a-bottle synthetic approach, the assembly of
and form cyclic trimers that remain entrapped. No assembly happens large molecule occurs both inside and outside hollow nano-
outside the nanocapsules. Further functionalization of trimers produces capsules. Non-entrapped molecules are separated after the
functional hierarchical nanomaterials.
synthesis. A strategy enabling exclusive formation of the molecules
inside the nanocapsules can be highly beneficial for creating
Here we show that synthesis of large molecules from small functional nanodevices and hierarchical nanomaterials. We show
starting materials can be performed exclusively inside hollow here that a catalyst entrapped inside the nanocapsules can
nanocapsules. Hybrid nanostructures containing molecules facilitate the synthesis of large molecules (Fig. 1). In our approach,
entrapped in nanocapsules can be useful for the creation of the reaction occurs only inside the nanocapsules. The pores in the
functional nanodevices, such as nanosensors or nanoreactors. nanocapsule shell are larger than starting materials and smaller
New strategies leading to successful synthesis of such hybrid than the reaction product. Reagents enter the nanocapsules, and
nanostructures are essential for progress in the field.
the reaction product remains entrapped. We used an encapsulated
Previously we reported ship-in-a-bottle assembly of organic Verkade’s superbase, proazaphosphatrane, to show the feasibility
molecules inside hollow porous polymer nanocapsules.1 In this of our approach. Proazaphosphatrane was shown previously to be a
approach, starting materials enter the nanocapsule through versatile catalyst. In particular, it can catalyze the trimerization of
molecular size nanopores. The product of the reaction is larger isocyanates with high yield.22–24
than the pore size; therefore, molecules formed inside the
nanocapsules remain entrapped. A similar non-covalent assembly
can be used to entrap a supramolecular complex assembled from
smaller components.2 Hollow nanocapsules with uniform nano-
pores can be created by forming a crosslinked polymer shell in the
presence of pore-forming templates in the hydrophobic interior of
a lipid bilayer.3,4 We and others used the directed assembly in the
bilayers of vesicles to form nanocapsules and yolk-shell nano-
structures.3–9 These materials showed unusual properties, such as
ultra-fast transport of ions while providing long-term retention of
a Department of Chemistry, Saint Louis University, 3501 Laclede Avenue, St. Louis,
MO 63103, USA. E-mail: epinkhas@slu.edu; Fax: +1 314 977 2521;
Tel: +1 314 977 2845
b Faculty of Chemistry and Chemical Technology, al-Farabi Kazakh National
University, 71 al-Farabi Ave., Almaty, 050040, Kazakhstan
c Department of Chemistry, Washington University in St. Louis, One Brookings
Fig. 1 Catalytic ship-in-a-bottle assembly of tritolyl isocyanurate in a
porous hollow nanocapsule. The synthesis of isocyanurate was carried
out by a 30 minute reaction in benzene or chloroform in the presence of
proazaphosphatrane as catalyst.
Drive, St. Louis, MO 63130, USA
† Electronic supplementary information (ESI) available: Synthesis and character-
ization of compounds, ESI-MS, NMR, spectra. See DOI: 10.1039/c3nj01449e
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Nanocapsules with entrapped catalyst were prepared by
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polymerization of monomers in the hydrophobic interior of a
liposomal bilayer in a similar way to previously reported
procedures.3–5 Liposomes were formed in an aqueous solution
of Verkade’s superbase. Monomers and pore-forming templates
were added to the lipids prior to hydration. Here we used a
1 : 1 : 1 mixture of tert-butyl methacrylate (t-BMA), butyl metha-
crylate (BMA) and ethylene glycol dimethacrylate (EGDMA) as
monomers and a crosslinker, respectively, and glucose pentaacetate
(GPA) as a pore-forming template. We have shown previously
that the polymerization of styrene-based monomers in the
presence of GPA in the bilayer results in the formation of
crosslinked polystyrene shell with uniform nanopores with
approx. 0.8 nm diameter.3,4 These pores are large enough to permit
the diffusion of different para-substituted phenyl isocyanates
(smallest cross-section 0.4 nm), but are too small to allow the
release of a trimer isocyanurate (smallest cross-section 1.2 nm). The
catalyst with the smallest cross-section of 1 nm remains entrapped
in the nanocapsules. After the polymerization, nanocapsules are
treated with a base to facilitate the removal of GPA, precipitated
from an aqueous solution and washed with methanol to remove
lipids and non-entrapped catalyst. After extensive washing, the
supernatant showed no catalytic activity, suggesting that no catalyst
was located outside nanocapsules during the experiments on
trimerization of phenyl isocyanates.
Fig. 2 Cyclotrimerization of p-tolyl isocyanate (A) and partial 1H NMR
spectra (400 MHz, CDCl3, 298 K) of reaction mixture of p-tolyl isocyanate
with nanocapsules containing encapsulated catalyst at t = 0 (B) and after
30 min of reaction (C); peaks of methanol omitted for clarity.
In typical experiments, we added different para-substituted
phenyl isocyanates to a suspension of nanocapsules containing
entrapped Verkade’s superbase. In most experiments, we used
deuterated chloroform as a solvent because it allows monitoring
the reaction with NMR, is compatible with the trimerization
reaction, and disperses polyacrylate nanocapsules well. Reactions
in benzene worked in a similar way to reactions in chloroform.
In chloroform or benzene solutions, isocyanates form trimer
isocyanurates in the presence of Verkade’s superbase catalyst. We
will describe the details of experiments with p-tolyl isocyanate below.
We also performed the reactions with 4-methoxyphenylisocyanate,
4-tert-butylphenyl isocyanate, and 4-acetylphenyl isocyanate
with similar results. NMR spectra taken 30 min after adding
p-tolyl isocyanate to a suspension of nanocapsules containing
entrapped Verkade’s superbase in CDCl3 revealed new peaks at
2.37 and 7.31 ppm in an approx. 1 : 1 ratio (Fig. 2).
These new signals correspond to the trimer, as confirmed in
control experiments performed in the absence of nanocapsules.
In these experiments, the reaction mixture was analyzed by
NMR and mass spectrometry. The NMR spectrum revealed the
same signals as shown in Fig. 2C. When the catalyst is not
encapsulated, mass spectra of the reaction mixture show the
reaction product, starting materials and the catalyst (Fig. 3A)
along with methanol and/or sodium adducts. Methanol was
used here to dilute the reaction mixture to ensure that mass
Fig. 3 (A) Mass spectrum of methanol solution of isocyanurate formation in
the presence of proazaphosphatrane as catalyst. Trimer (Mt, green), catalyst
(Mc, red), and starting isocyanate (Mi, blue) are detected. (B) Mass spectrum
of methanol supernatant after precipitation of nanocapsules following the
reaction of p-tolyl isocyanate in the presence of nanocapsules containing
entrapped proazaphosphatrane, corresponding to the NMR spectrum on
Fig. 2C. Only starting material (blue) is detected in the supernatant.
Since the trimer was present in the NMR spectrum (Fig. 2C)
spectrometry measurements were performed under the same but not in the mass spectrum (Fig. 3B) of the supernatant, we
conditions with and without nanocapsules. We used methanol conclude that the trimerization occurred exclusively inside the
to precipitate nanocapsules from chloroform or benzene before nanocapsules. Lack of catalyst in the supernatant confirmed
MS analysis. The analysis of supernatant from the trimerization that the catalyst remained entrapped in the nanocapsules
of p-tolyl isocyanate in nanocapsules showed only the starting throughout the reaction. In control experiments, we observed
material (Fig. 3B). No trimer or the catalyst was observed.
catalytic activity of the precipitated nanocapsules (see ESI†).
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Fig. 4 Partial 1H NMR spectra (400 MHz, CDCl3, 298 K) of isocyanurate
formed inside nanocapsules.
The trimer was found in the nanocapsules after precipitation,
washing the nanocapsules with methanol, and redispersing
the nanocapsules in chloroform (Fig. 4). This finding further
confirmed that the trimer remained entrapped in the nano-
capsules after formation.
Additional control experiments were performed with 3,5-
di-tert-butylphenyl isocyanate. This compound is too large to
enter nanocapsules through the pores. In the presence of
free proazaphosphatrane, it undergoes a trimerization in
the same way as other phenyl isocyanates used in this
study. When it was added to a suspension of nanocapsules
containing entrapped proazaphosphatrane, no trimerization
was observed (see ESI†).
We functionalized an entrapped trimer with diaza-18-crown-
6 (DA18C6) to illustrate the possibility of creating hierarchical
nanomaterials (Fig. 5). A conformationally flexible DA18C6
was added to the capsules containing an entrapped trimer
synthesized from 4-acetylphenyl isocyanate. It diffused into
the capsules through the pores2 and was covalently bound to the
trimer via the Mannich reaction (Fig. 5A). Non-reacted reagents
were removed, nanocapsules were mixed with a solution of
Cu(NO3)2 and then washed several times with methanol. Blue
color of precipitated nanocapsules (Fig. 5B, sample 2) indicated
the formation of a complex between copper and entrapped
compound.
In control experiments, DA18C6 was added to the nano-
capsules containing the isocyanurate but the Mannich reaction
was not performed. After removal of unreacted materials,
exposure to Cu(NO3)2 and washing steps, no retention of
copper was observed (Fig. 5B, sample 3). These preliminary
experiments support the feasibility of creating functional
nanostructures using site-specific assembly.
Fig. 5 (A) Attachment of a crown compound to the entrapped trimer via a
Mannich reaction between cyclotrimer and DA18C6; (B) top: schematic
representation of functionalized trimer entrapped in hollow nanocapsule.
Isocyanurate from the scheme above is shown as a grey triangle. Bottom:
(1) blank nanocapsules in methanol; (2) nanocapsules containing trimer
functionalized with DA18C6 after exposure to Cu(NO3)2 and multiple
washing steps; (3) nanocapsules with a non-functionalized trimer after
exposure to Cu(NO3)2 and multiple washing steps.
In conclusion, we have shown a successful reaction exclusively
inside nanocapsules catalyzed by an entrapped proazaphos-
phatrane catalyst. The reaction product is too big to escape from
the capsule. This strategy may be useful for selective synthesis of
hybrid nanostructures or hierarchical nanomaterials.
2,2-dimethoxy-2-phenyl-acetophenone (3 mg, 0.01 mmol) were
added. Chloroform was evaporated using a stream of purified argon
to form a lipid–monomer mixture. Methylene chloride or other
volatile solvents can be used instead of chloroform. The mixture was
further dried in vacuum to remove traces of solvent. Eight ml of the
aqueous solution of Verkade’s superbase (1.5 Â 10À4 M) was
added to the test tube with the lipid–monomer mixture and
Experimental
Preparation of catalyst-loaded nanocapsules
160 mg of DMPC was dissolved in 0.4 mL of chloroform in a incubated at 35 1C for 30 minutes. During the hydration of the
test tube, then t-BMA (32 mL, 0.193 mmol), BMA (32 mL, lipid–monomer mixture, the culture tube was briefly agitated
0.199 mmol), EGDMA (32 mL, 0.166 mmol) and initiator on a Vortexer every 5 min. Five freeze–thaw cycles were done to
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increase encapsulation of catalyst. The suspension was Nanocapsules were then washed with methanol to remove
extruded 12 times at 35 1C through a track-etched polyester unreacted chemicals.
nucleopore membrane (Sterlytech) with 0.2 mm pore size using
Complexation of copper by entrapped crown compounds
a Lipex stainless steel extruder (Northern Lipids).
The sample was irradiated for 1.5 hours with UV light
(l = 254 nm) in a photochemical reactor (10 lamps, 32 W
each; the distance between the lamps and the sample was
10 cm) using a quartz tube with path length of light of
approximately 3 mm.
327 mg of Cu(NO3)2 was dissolved in a mixture of MeOH and
C6H6 (1 : 2). 2 ml of this solution was added to the 2 ml of
nanocapsules solution. After one hour, nanocapsules were
washed three times in methanol to remove non-complexed
copper salt as judged by the clear supernatant.
Following the polymerization, methanol was added to the
reaction mixture to precipitate the nanocapsules. Several
drops of aqueous NaCl solution were added to methanol
solution to increase aggregation of the nanocapsules. The
nanocapsules were separated from the reaction mixture and
purified in repeated centrifugation and resuspension steps
using methanol, water–methanol mixture and water as washing
solutions.
Nanocapsules were suspended in a mixture of 1 ml of
methanol and 1 ml of aqueous 1 M NaOH, and the mixture
was stirred at 75 1C for 1 hour to hydrolyze pore-forming
templates. Hydrolysis was monitored with LC-MS. After the
hydrolysis, the mixture was neutralized with aqueous HCl and
the nanocapsules were precipitated with methanol and washed
with methanol.
Acknowledgements
This work was supported by National Science Foundation
(CHE-0933363, CHE-1012951, and CHE-1316680), Saint Louis
University Presidential Research Fund, and a grant from the
Committee of Science of the Ministry of Education and Science
of Republic of Kazakhstan (No 0547/GF2).
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A suspension of nanocapsules prepared as described above
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