Robust molecular micro-capsules for encapsulating and releasing hydrophilic contents

Article abstract of DOI:10.1039/c3cc43803a

The hydrophobic-amphiphilic self-assembly approach has been employed to prepare molecular micro-capsules simply by cooling down an emulsion, in a hot polar solvent medium, of a melted compound having two very well-distinguished units, both with highly non-polar and hydrophobic characteristics. The resulting micro-capsules are very stable and robust both in suspension and under dry conditions. Further, such micro-capsules can effectively encapsulate hydrophilic compounds which can later on be easily released upon the application of UV-light.

Full text of DOI:10.1039/c3cc43803a

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Robust molecular micro-capsules for encapsulating and
releasing hydrophilic contents†
Cite this: Chem. Commun., 2013,
49, 7827
Francisco Vera,a Marta Mas-Torrent,a Civan Avci,a Jordi Arbiol,ab Jordi Esquena,c
Received 20th May 2013,
Accepted 2nd July 2013
a
a
´
Concepcio Rovira and Jaume Veciana*
DOI: 10.1039/c3cc43803a
www.rsc.org/chemcomm
The hydrophobic–amphiphilic self-assembly approach has been solutions owing to their amphiphilic nature forming bi-layered
employed to prepare molecular micro-capsules simply by cooling structures, so-called vesicles. These capsules can be further
down an emulsion, in a hot polar solvent medium, of a melted stabilized with polymerizable groups that give rise to inter-
compound having two very well-distinguished units, both with connections between the molecules via covalent bonds
highly non-polar and hydrophobic characteristics. The resulting and thus stabilize the shell-forming membrane.3 However,
micro-capsules are very stable and robust both in suspension and in the most recent years, the use of macromolecules to
under dry conditions. Further, such micro-capsules can effectively prepare robust capsules has been more extensively explored
encapsulate hydrophilic compounds which can later on be easily employing a variety of techniques such as amphiphilicity
released upon the application of UV-light.
strategy, polyelectrolyte layer-by-layer, phase separation or
polymerization.4,5
A key focus of attention in nanoscience is currently based on
Very recently, the so-called ‘‘hydrophobic–amphiphilic’’ approach
constructing large-scale systems of nano-structured materials that was developed to prepare molecular micro-scale objects with
give rise to assemblies of high technological interest.1 In such unprecedented shapes (i.e., flowers, cones, fibers, etc.).6 This
materials, the properties are mainly driven by the hierarchically method was based on precipitating in a mixture of solvents a
organized assemblies, rather than the individual components. molecule bearing two very well-distinguished units, but both
One particular case of micro-assemblies which raise an increasing highly non-polar and hydrophobic, consisting of a fullerene
significance is hollow spheres, also called capsules. They allow for derivatized with long alkyl chains. The van der Waals forces
the encapsulation of materials to protect them from the environ- between the aliphatic chains and pÁ Á Áp interactions between
mental influences or for the confinement of chemical reactions. the fullerene units determined the final assemblies. Later on,
An unlimited number of examples of encapsulation can be found the method was applied to a different system: a perchloro-
in Nature, and the appeal of micro-capsules is expanded to a wide triphenylmethyl radical (PTM) moiety functionalised with three
range of applications in the pharmaceutical, cosmetic, food, long alkyl chains.7 In this case, the intermolecular ClÁ Á ÁCl
textile, adhesive and agrochemical industries. Especially interest- interactions of the PTM heads together with the CH2Á Á ÁCH2
ing are stimuli-responsive capsules (i.e., smart capsules) that are interactions of the alkyl chains drove the formation of compact
able to release the encapsulated substances triggered by external functional assemblies with unusual shapes.8
stimuli such as a pH change, light or temperature.2
In this communication, we synthesize a new polychloro-
It is well-known that organic-based capsules can be prepared triphenylmethane (aH-PTM) derivative, compound 1, bearing
by self-assembly of (phospho)lipids that aggregate in aqueous only two long alkyl chains at the para and meta positions of the
phenylvinylene ring. This results in the lowering of the melting
point of the compound down to 48 1C, which is abnormal for a
a
`
Institut de Ciencia de Materials de Barcelona (ICMAB-CSIC) and Networking
polychlorinated aromatic derivative, and the possibility of
interdigitation of the two alkyl chains in its supramolecular
assemblies. We show that this hydrophobic molecule forms an
emulsion in hot polar solutions that leads upon cooling to
formation of micro-capsules without the need for carrying out
any additional step. Further, it is demonstrated that such
assemblies are very stable and robust and can be exploited to
encapsulate polar molecules, which can then be neatly released
upon UV irradiation.
Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN),
Campus de la UAB, 08193 Bellaterra, Spain. E-mail: vecianaj@icmab.es;
Fax: +34 935805729; Tel: +34 935801853
b
c
´
Institucio Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona,
Spain
´
Institut de Quımica Avançada de Catalunya (IQAC-CSIC) and Networking Research
Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN),
C./Jordi Girona, 18-26, 08034 Barcelona, Spain
† Electronic supplementary information (ESI) available: Experimental characteri-
zation of compounds and additional data. See DOI: 10.1039/c3cc43803a
c
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Scheme 1 Synthesis of 1.
Fig. 2 (top) The SEM image of the capsules of 1 deposited on a silicon substrate.
(inset) Zoom of the image showing with white arrows hollow capsules damaged by
e-beam. (bottom) The TEM image of the micro-capsules of 1 on a lacey carbon grid.
In order to gain a better understanding of the supramolecular
structure of the micro-scale objects formed by 1 small-angle
X-ray scattering (SAXS) characterization was performed. The
SAXS spectra of the assemblies of 1 at room temperature exhibit
diffraction patterns that are attributed to the reflections (001) to
(00n) with a d spacing value of ca. 5.1 nm that indicates a
lamellar layered structure (Fig. S2, ESI†). Taking into account
Fig. 1 Schematic procedure followed to form capsules of 1 (a) and to encapsu-
late the dye in them (b).
Compound 1 was synthesized in a 61% yield by a Wittig– the approximate length measured for the extended molecules
Horner–Emmons reaction between the corresponding benz- (B42 Å) and the diameter of aH-PTM moieties (B10 Å), for
aldehyde 2 and the aH-PTM phosphonate 39 (Scheme 1).
every layer a complete interdigitation of the alkoxy chains and a
The optimised procedure followed to prepare micro-capsules face-to-face interaction between the aH-PTM moieties are
of 1 consisted of preparing a suspension (1.4 mM) in THF– expected (Fig. S3, ESI†). Therefore, this confirms that the
water (2.5/1) and heating it at 65 1C. This resulted in the ClÁ Á ÁCl and van der Waals interactions between the aliphatic
melting of the suspended compound (mp. 45 1C) and thus chains are the driving forces for the supramolecular ordering of
the formation of an emulsion of melted 1 in such a polar the micro-capsules formed in such a polar solvent medium.
solvent medium. After 5 minutes, the mixture was rapidly
To demonstrate the capability of the capsules of harboring
cooled down to room temperature leading to the final supra- hydrophilic guests, the red dye Rhodamine B or AlexaFluor-568s
molecular assemblies. This procedure is schematically depicted was dissolved in the THF–water mixture (2.5/1) (c = 0.25 mM) in
in Fig. 1a.
the micro-capsule formation process (Fig. 1b). The fabrication
To visualize the resulting supramolecular organizations, process was carried out as before, although an additional
field emission scanning electron microscopy (FE-SEM) as washing step was introduced at the end in order to remove
well as transmission electron microscopy (TEM) images were the non-encapsulated dye.
acquired. Fig. 2 (top) shows the SEM images of the assemblies of
By optical fluorescence microscopy it is possible to observe
1 after being deposited on a silicon substrate, where spherical the capsules and the dye taking advantage of the intrinsic
and regularly distributed hollow capsules can be clearly observed. fluorescence of 1 that shows a strong emission band at
Additionally, the TEM images of the particles deposited on a 465 nm when irradiated at 305 nm (Fig. S4, ESI†), and that of
lacey carbon grid (Fig. 2, bottom) further confirmed their the red dye that emits at 550 nm (in the case of Rhodamine B,
hollow nature. The cortex of capsules has an approximate
l =
exc = 510 nm) or 603 nm (in the case of AlexaFluor-568s, lexc
thickness of 60 nm, which corresponds to around 15 molecular 510 nm). Fig. 3 shows the fluorescence microscope images of
layers as analyzed by the X-ray characterization (see below). the capsules filled with Rhodamine B once deposited on a
The size and distribution of the capsules were estimated by quartz slide. The micro-capsules are visible when using the
light scattering (LS) which gave an average diameter of transmitted white light. Once irradiated with green light
0.7 mm (Fig. S1, ESI†). It is important to highlight here that, (546 nm), the red fluorescence of the dye can be visualized at
in contrast to conventional vesicles that are stable in the the same position where the capsules were seen. Furthermore,
solution where they are produced but collapse immediately the micro-capsules switched to blue when the UV-light
on solid supports after solvent evaporation, the capsules of 1 (305 nm) was employed for 2 seconds due to the emission
once formed are stable and robust even when the mother of 1. These results unambiguously confirmed the presence of the
solution is dried.
dye which was located in the same place as the micro-capsules.
c
7828 Chem. Commun., 2013, 49, 7827--7829
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In summary, it has been shown that the supramolecular
hydrophobic–amphiphilic approach can be applied to fabricate
robust molecular micro-capsules following a very simple pro-
cess based on forming an emulsion of the melted compound 1
and solidifying it in a polar solvent medium by lowering the
temperature. Such micro-capsules can effectively encapsulate
hydrophilic compounds which can later on be easily released
upon the application of UV-light that shatters the micro-
capsules due to the disassembling of molecules. The fabrica-
Fig. 3 Microscope images of micro-capsules of 1 deposited on a quartz slide
with: (a) transmitted white light, (b) irradiation with green light (mercury lamp, tion of stable smart capsules based on molecules with the
546 nm), (c) irradiation with UV light (mercury lamp, 305 nm) for 2 seconds and
hydrophobic–amphiphilic approach offers an elegant alter-
native to the most common strategies currently used for
(d) transmitted white light upon irradiation for 10 s at 305 nm.
preparing organic capsules which employs polymers or poly-
merizable monomers as building blocks, and thus brings novel
perspectives to this field.
We thank the Networking Research Center on Bioengineering,
Biomaterials and Nanomedicine (CIBER-BBN); the DGI (Spain)
with project POMAS CTQ2010–19501/BQU, and the Generalitat
de Catalunya (grant 2009SGR00516). We also thank the European
´
´
project ERC StG 2012-306826 e-GAMES and Monica Roldan
(Servei Microscopia, UAB) for the confocal microscopy experi-
´
ments and Amable Bernabe (ICMAB) for LS measurements.
Fig. 4 Superposition of image captures of some cross-sections of micro-capsules
of 1 (blue) with AlexaFluor-568s in their lumen acquired with two channels: the
red channel (lexc = 561 nm; lem = 585–670 nm) where the dye emits; the blue
channel (lexc = 476 nm; lem = 500–550 nm) where the micro-capsules of 1 emit.
Notes and references
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are shattered due to the disassembling of the molecular units
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phenanthrene derivative;10 as indicated by MALDI-ToF analysis
and UV-Vis measurements (Fig. S5, ESI†).11 As seen in the
image taken after a longer UV-irradiation (Fig. 3d) the capsules
are not structured anymore although some material is observed
at the same positions where the original capsules were located.
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lumen of the micro-capsules and was not deposited around
them, confocal microscopy experiments were carried out. These
experiments were performed using AlexaFluor-568s due to its
enhanced photostability. Fig. 4 shows the confocal microscope
images acquired at different planes separated by 0.04 mm using
two – red and blue – channels. In this figure, images acquired
using the red channel (lexc = 561 nm; lem = 575–670 nm) and
the blue channel (lexc = 476 nm; lem = 500–550 nm) are found to
overlap. Note that irradiating the sample at 476 nm did not
damage the assemblies since compound 1 does not absorb at
this wavelength. These images clearly demonstrate that capsules
have been successfully filled within their lumen with a solution
of the polar dye.
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were also performed. The absorption and fluorescence spectra
of the solvent from a suspension of micro-capsules of 1 filled
with AlexaFluor-568s were registered before and after 10 seconds
of UV irradiation at 305 nm. It was found that only after light
irradiation the optical characteristics of the dye were detectable
in the solvent media, confirming that it had been liberated
(Fig. S6 and S7, ESI†).
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11 A peak corresponding to [MÀHCl]+ appeared in the MALDI-ToF
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phenanthrenes, was observed in the UV-Vis spectra.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 7827--7829 7829