Construction of a pH-driven supramolecular nanovalve

Article abstract of DOI:10.1021/ol0612509

The versatility of supramolecular chemistry has been exploited in constructing nanovalves based on mesoporous silica MCM-41 and the mutual recognition between secondary dialkylammonium ions and dibenzo[24]crown-8 (DB24C8). Naphthalene-containing dialkylam

Full text of DOI:10.1021/ol0612509

ORGANIC
LETTERS
2006
Vol. 8, No. 15
3363-3366
Construction of a pH-Driven
Supramolecular Nanovalve
Thoi D. Nguyen, Ken C.-F. Leung, Monty Liong, Cari D. Pentecost,
J. Fraser Stoddart,* and Jeffrey I. Zink*
California NanoSystems Institute and Department of Chemistry and
Biochemistry, UniVersity of California, Los Angeles, 405 Hilgard AVenue,
Los Angeles, California 90095
stoddart@chem.ucla.edu; zink@chem.ucla.edu
Received May 22, 2006
ABSTRACT
The versatility of supramolecular chemistry has been exploited in constructing nanovalves based on mesoporous silica MCM-41 and the
mutual recognition between secondary dialkylammonium ions and dibenzo[24]crown-8 (DB24C8). Naphthalene-containing dialkylammonium
threads were tethered to the MCM-41, followed by loading with coumarin 460 and capping with DB24C8. Controlled release of coumarin 460
from the pores of MCM-41 was demonstrated using different bases. The rate of release of coumarin 460 from the nanovalves depends on the
size of the base.
One of the toughest challenges today for researchers intent
upon taking chemistry up to the frontiers of nanoscience is
to introduce a rather fine level of control upon nanoscale
devices adorned with molecular machinery1 that has been
designed and self-assembled to fulfill a particular device
function. Prominent among such hybrid systems are su-
pramolecular2 and molecular3 valves with movable elements
that can be grafted onto mesoporous silica reservoirs in such
a manner that the two parts will work together in harmony
to achieve some desirable outcome at the macroscopic level.
Molecules with movable elements, which have been incor-
porated into working devices, include (1) azobenzene
derivatives4a which can be induced to undergo cis-trans
isomerization, (2) coumarin derivatives4b which can be made
to display reversible intermolecular dimerization, (3) deriva-
tized CdS nanoparticles4c that are chemically labile thanks
to the reversibility of the thiol/disulfide redox process, (4)
heat-responsive4d polymers which are extended at high and
collapsed at low temperatures, (5) electrically erodible
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10.1021/ol0612509 CCC: $33.50
© 2006 American Chemical Society
Published on Web 06/27/2006

polymer gel,4e and (6) pH-sensitive copolymeric hydrogels.4f
Other wholly inorganic systems involve5 the electrochemical
corrosion of a gold membrane in microelectromechanical
systems to open the valve. In all cases, the movable elements
operate in response to a single response.
A unique class of molecules with switchable, and hence
movable, elements are the mechanically interlocked ones,
such as bistable catenanes and rotaxanes.6 These compounds
can be designed such that their movable elements can be
controlled7 by external stimuli, such as pH, electricity, or
light. We have recently reported3 that donor-acceptor
bistable [2]rotaxanes can be tethered to porous silica thin
films and MCM-41 to act together as molecular valves. The
analogous situation exists in the supramolecular domain
where [2]pseudorotaxanes act as gatekeepers at the orifices
to the pores. The mode of action of these two valves relies
on the redox switching of the ring in order to move it away
from the entrances to the orifices, thus allowing release of
the contents trapped inside the pores. Herein, we report the
synthesis and operation of a supramolecular valve that relies
on the pH-controllable crown ether/dialkylammonium ion-
based recognition motif8 as the driving force for pseudoro-
taxane formation.
Dibenzo[24]crown-8 (DB24C8) is a sufficiently large
macrocyclic polyether to be able to encircle dialkylammo-
+
nium ion centers (-CH2NH2 CH2-), thus forming [2]-
pseudorotaxanes.8 Since the noncovalent bonding responsible
for the formation of these 1:1 complexes involves, inter alia,
[N-H‚‚‚‚O]+ hydrogen bonds, they can be made to dissociate
in solution on addition of base. In the context of the present
work, that is, constructing pH-driven supramolecular valves
on the surface of mesoporous silica, the naphthalene-
Figure 1. Graphical representations of operating (supra)molecular
valves. The dialkylammonium-tethered porous silica particle MCM-
41 (A) is loaded with coumarin 460 molecules (B). The pores of
coumarin-loaded MCM-41 are capped with DB24C8 by noncova-
lent interactions, followed by washing away the excess of substrates
(C). Coumarin 460 molecules are released by switching off the
noncovalent interactions upon pH stimulation. (D) The porous silica
particle MCM-41 can be reused for the next molecule-releasing
cycle.
containing9 -CH2NH2 CH2- tether, shown in the box in
+
Figure 1, was utilized as the thread. The unthreaded form of
the [2]pseudorotaxane at the high pH values represents the
+
open state of the switch, while threading of the -CH2NH2 -
CH2- with DB24C8 beads closed the valve. Dethreading
can be achieved using a range of bases.
Nanostructured silica, for use as both the solid support
for the molecular machinery comprising the movable ele-
ments, and the containers in which guest molecules are
trapped and then released on demand, is prepared10,11 by
surfactant-directed self-assembly to yield ordered arrays of
channels in sol-gel-derived silica. Using a modification of
Stober’s synthesis of monodispersed silica for which aqueous
ammonia was used as a morphology catalyst,11 the nano-
structured silica obtained consists of near-spherical silica
particles with an average diameter of 600 nm, as verified
(Figure 2) by scanning electron microscopy (SEM). Using
cetyltrimethylammonium bromide as the template, the highly
ordered pores form a two-dimensional hexagonal structure
that has a lattice spacing of 3.6 nm as measured by X-ray
diffraction (indexed as {100}). The surfactant was removed
by calcination for 5 h at 550 °C. N2 adsorption/desorption
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3364
Org. Lett., Vol. 8, No. 15, 2006

stirred at a low stirring rate to create a homogeneous solution
at any given time. The release of coumarin 460 molecules
into the solvent was monitored by measuring the lumines-
cence spectrum as a function of time. This task was achieved
by using a charge-coupled device (CCD) detector. This CCD
detector sequentially collects the luminescence spectra once
per second, giving a three-dimensional plot of luminescence
intensity, wavelength, and time, while confirming the identity
of the molecules being released.
The effectiveness of the nanovalve depends on a number
of factors. Its function depends critically on whether the
movable elements associated with the [2]pseudorotaxanes
can effectively prevent the probe molecules from leaking
out. Equally important is the nanovalve’s influence upon how
efficient the opening and releasing of trapped guest molecules
are from the pores. A range of bases with different basicities
and structural dimensions, including hexamethylphosphorus
triamide (HMPT), N,N′-diisopropylethylamine (DIPEA), and
triethylamine (TEA), was employed to effect (Table 1) the
Figure 2. Scanning electron micrograph of the mesoporous silica
particles. Note the 1 µm scale bar.
isotherms at 77 K were used to investigate the porosity of
the material further. The isotherm of the material can be
classified as a type IV isotherm according to IUPAC
nomenclature. The material exhibits high surface area (929.7
m2/g). By employing the Barret-Joyner-Halenda (BJH)
method of calculation, the inner diameter of the pore is
estimated to be 2.0 nm. N2 adsorption/desorption isotherms
also revealed that the pores are empty after calcination such
that they are accessible and suitable for use as molecular
containers (see Supporting Information).
Table 1. Controlled Release Data for Base-Activated Valve
with the Half-Life for the Release Corresponding to Each Base
Base
HMPT
DIPEA
TEA
sizea (nm)
6.2
5.9
5.8
half-life t1/2 (s)
450
300
100
a Obtained from ChemDraw 3D.
The first step in the making of the supramolecular valve
involves derivatizing the silanol functional groups on porous
silica (MCM-41) with isocyanatopropyl-triethoxysilane
(ICPES) to afford12a,b isocyanate-functionalized porous silica.
In contrast to other one-pot syntheses,12c,d this grafting
method for coupling a silane agent to the porous silica yields
material with linkers predominantly situated either close to
the pores’ orifices or outside of the pores.12e,f The dialkyl-
ammonium ion’s â-naphthol unit was then brought into
contact with this surface, and a carbamate was formed,
having, first of all, protected the secondary amine precursor
of the ion with a tert-butoxycarbonyl group. Deprotection
with trifluoroacetic acid produced (Figure 1A) the desired
controlled release of coumarin 460. The slight increase in
the emission intensity (Figure 3) indicates a small amount
of leakage from the closed nanovalve. The release of
coumarin 460 from the pores upon activation by addition of
HMPT (Figure 3A) was characterized by a lag time of 200
s. After this delay, the guest molecules were released at a
much faster rate, as indicated by the much steeper slope.
For HMPT-triggered release,13 t1/2 is 450 ( 30 s. The t1/2
for DIPEA-activated release (Figure 3B) is 300 ( 30 s. With
TEA as the base, no lag time is observed (Figure 3C) and
the t1/2 decreases further to 100 ( 20 s. All three samples
were left to stand overnight, and the emission intensities were
used to define the total (100%) amounts released.
Since all the experimental conditions to trigger the release
of the guest molecules are the same, a direct comparison
between the different release profiles, based on the nature
of the triggering bases, can be made. Comparing the three
bases, the controlled releasesaccording to the deprotonation
mechanismsis governed14 by the basicity and the steric
hindrance of the bases employed. DIPEA and TEA have
similar basicities,15 namely, pKa ) 9.0 and 8.5, respectively,
in Me2SO. The rate of release using DIPEA is lower than
+
naphthalene-containing -CH2NH2 CH2- tethered MCM-
41. The hybrid material was loaded subsequently (Figure 1B)
with coumarin 460, and the pores were capped (Figure 1C)
with DB24C8.
The operation of the nanovalve, that is, the release (Figure
1C,D) of the luminescent probe molecules (coumarin 460),
was studied using luminescence spectroscopy. The loaded
hybrid material was placed as a powder at the bottom of a
spectrophotometric cell containing CH2Cl2, and only the
solvent was exposed to excitation light. The solution was
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(13) The half-life (t1/2) is defined as the time the system takes to release
half of its load.
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Org. Lett., Vol. 8, No. 15, 2006
3365

activated by TEA does not. The lag time observed for HMPT
is longer than that for DIPEA, signifying a stronger impact
on the part of steric hindrance. The variation of the bases
having different steric factors and basicities, as a result,
manifests itself in the three different release rates such that
TEA > DIPEA > HMPT.
An alternative interpretation of the activation by TEA
(Et3N) is that the nanovalve’s operation is induced by a
competitive binding mechanism involving DB24C8 and the
tertiary trialkylammonium ion. However, when binding
-
studies between DB24C8 and TEA and Et3NH+‚CF3CO2
were performed, no interaction was observed, at least judging
from 1H NMR spectroscopic data.17 These results reveal that
+
TEA acts as a base to deprotonate the -CH2NH2 CH2- ion
center, hence releasing DB24C8 from the nanovalve. Extrac-
tion of the crown ether by a competitive binding mechanism
is not happening.
The motion of the movable elements in the [2]pseudoro-
taxane tethered to a well-defined mesoporous nanostructure
constitutes the open and closed configurations of this
nanovalve system. The steric bulk of the bases plays a vital
role in the functioning of the nanovalve and results in systems
that can release guest molecules at different rates. Moreover,
the diversity provided by different activating agents greatly
improves the flexibility and applicability of this class of
nanovalve. In principle, nanovalves having even larger pores
could be mixed and matched with suitable [2]pseudorotax-
anes to perform precise functions, such as targeted, acid-
base-controlled drug delivery.
Figure 3. Controlled release of coumarin 460 from the dialkyl-
ammonium-DB24C8-MCM-41 nanovalve in CH2Cl2 activated by
(A) hexamethylphosphorus triamide, (B) N,N′-diisopropylethyl-
amine, and (C) triethylamine, as monitored by luminescence
spectroscopy over time. The arrow indicates the triggering time
corresponding to 240 s.
Acknowledgment. The research was conducted as part
of an NSF-NIRT program and DMR 0346610. T.D.N.
acknowledges support from the UCLA Dissertation Year
Fellowship as well as assistance early on from Erik Johansson
and Paul Sierocki.
that when using TEA. This result indicates that the more
bulky DIPEAsdespite being the stronger basesslows down
the deprotonation of the complex tethered to the silica
particles, thus affecting the rate of nanovalve operation (Table
1). When an even more bulky and weaker base (HMPT) is
used,16 the rate of release is even slower. HMPT- and
DIPEA-activated releases exhibit lag times, whereas release
Supporting Information Available: Preparative proce-
dures of all precursor compounds and the nanovalve as well
as the characterization data from NMR spectroscopy, XRD
pattern, and N2 adsorption/desorption isotherm. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL0612509
(16) Bunten, K. A.; Moreno, C.; Poe¨, A. J. Dalton Trans. 2005, 1416-
1421.
(17) See Supporting Information.
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Org. Lett., Vol. 8, No. 15, 2006