Controlled delivery systems using antibody-capped mesoporous nanocontainers

Article abstract of DOI:10.1021/ja904456d

This paper describes the design of new controlled delivery systems consisting of a mesoporous support functionalized on the pore outlets with a certain hapten able to interact with an antibody that acts as a nanoscopic cap. The opening protocol and delive

Full text of DOI:10.1021/ja904456d

Published on Web 09/09/2009
Controlled Delivery Systems Using Antibody-Capped
Mesoporous Nanocontainers
Estela Climent,†,‡ Andrea Bernardos,† Ramo´n Mart´ınez-Ma´n˜ez,*,†,‡
Angel Maquieira,*,† Maria Dolores Marcos,†,‡ Nuria Pastor-Navarro,†
Rosa Puchades,† Fe´lix Sanceno´n,†,‡ Juan Soto,†,‡ and Pedro Amoro´s*,§
Instituto de Reconocimiento Molecular y Desarrollo Tecnolo´gico, Centro Mixto UniVersidad
Polite´cnica de Valencia-UniVersidad de Valencia, Valencia, Spain, Departamento de Qu´ımica,
UniVersidad Polite´cnica de Valencia, Camino de Vera s/n 46022, Valencia, Spain, Centro
InVestigacio´n Biome´dica en Red de Bioingenier´ıa, Biomateriales y Nanomedicina, and Institut de
Cie`ncia del Materials, UniVersitat de Vale`ncia, Post Office Box 2085, E-46071 Vale`ncia, Spain
Received June 3, 2009; E-mail: rmaez@qim.upv.es; amaquieira@qim.upv.es; pedro.amoros@uv.es
Abstract: This paper describes the design of new controlled delivery systems consisting of a mesoporous
support functionalized on the pore outlets with a certain hapten able to interact with an antibody that acts
as a nanoscopic cap. The opening protocol and delivery of the entrapped guest is related by a displacement
reaction involving the presence in the solution of the antigen to which the antibody is selective. As a proof-
of-the-concept, the solid MCM-41 was selected as support and was loaded with the dye [Ru(bipy)3]Cl2.
Then a suitable derivative of the hapten 4-(4-aminobenzenesulfonylamino)benzoic acid was anchored on
the outer surface of the mesoporous support (solid S1). Finally the pores were capped with a polyclonal
antibody for sulfathiazole (solid S1-AB). Delivery of the dye in the presence of a family of sulfonamides
was studied in phosphate-buffered saline (PBS; pH 7.5). A selective uncapping of the pores and dye delivery
was observed for sulfathiazole. This delivery behavior was compared with that shown by other solids that
were prepared as models to assess the effect of the hapten and its interaction with antibody in the dye
delivery control in the presence of the antigen.
Introduction
(SMPS) show unique properties such as large load capacity,
biocompatibility, high thermal stability, homogeneous porosity,
Among the large amount of approximations toward the
development of new smart materials, one particularly tempting
is the possibility to create stimuli-responsive nanosolids able
to react to environmental changes or showing switchable
behaviors.1,2 One appealing application of such systems is the
design of functionalized nanocontainers able to deal with cargo
delivery under controlled conditions via external triggers.3
Traditional delivery systems usually rely on simple diffusion-
controlled processes or degradation of the nanocarrier,4 using
for instance microcapsules,5 micelles,6 vesicles,7 or liposomes.8
As an alternative to these materials, silica mesoporous supports
inertness, and tunable pore sizes with a diameter of ca. 2-10
nm.9 Moreover, it has been recently demonstrated that it is
possible to incorporate in the external surface of SMPS
functional groups able to be opened or closed at will for
functional control release applications. Specifically, it has been
(8) Andresen, T. L.; Jensen, S. S.; Jorgensen, K. Prog. Lipid Res. 2005,
44, 69.
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McCullen, S. B.; Higgins, J. B.; Schlenker, J. L. J. Am. Chem. Soc.
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Soto, J.; Villaescusa, L. A.; Amoro´s, P.; Beltra´n, D.; Guillem, C.;
Latorre, J. J. Am. Chem. Soc. 2004, 126, 8612–8613. (b) Casasu´s, R.;
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J.; Amoro´s, P.; Cano, J.; Ruiz, E. J. Am. Chem. Soc. 2008, 130, 1903–
1917. (c) Bernardos, A.; Aznar, E.; Coll, C.; Mart´ınez-Ma´n˜ez, R.;
Barat, J. M.; Marcos, M. D.; Sanceno´n, F.; Soto, J. J. Controlled
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Org. Chem. 2009, 1669–1673. (i) Park, C.; Oh, K.; Lee, S. C.; Kim,
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† Instituto de Reconocimiento Molecular y Desarrollo Tecnolo´gico,
Centro Mixto Universidad Polite´cnica de Valencia-Universidad de Va-
lencia, and Departamento de Qu´ımica, Universidad Polite´cnica de Valencia.
‡ CIBER de Bioingenier´ıa, Biomateriales, y Nanomedicina.
§ Institut de Cie`ncia dels Materials, Universitat de Vale`ncia.
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9
10.1021/ja904456d CCC: $40.75  2009 American Chemical Society
J. AM. CHEM. SOC. 2009, 131, 14075–14080 14075

A R T I C L E S
Climent et al.
reported that it is possible to design systems able to achieve
zero release, which can be fully opened on command via
external physical or chemical stimuli. Recently, SMPS-based
systems displaying controlled release have been reported that
contain different caps such as nanoparticles, nanovalves, and
supramolecular frameworks that in most cases use changes in
pH,10 temperature,11 redox potential,12,13 or light14 or rely in
the presence of small molecules15 for uncapping the pores.
by certain carbohydrates,17 there is an almost complete lack of
SMPS-based devices designed to trigger cargo release involving
biomolecules. In order to advance in this field and as a proof-
of-the-concept, we were interested in demonstrating that
antibody-antigen interaction could be a powerful switchable
method to develop tailor-made SMPS for controlled delivery
functions. In particular, and as a part of our interest in the use
of inorganic supports for advanced applications,18 we report here
the design of a new controlled delivery system consisting of a
mesoporous support functionalized on the pore outlets with a
certain hapten able to be recognized by an antibody that acts as
a nanoscopic cap. The opening protocol and delivery of the
entrapped guest is related to a highly effective displacement
reaction involving the presence in the solution of the antigen
to which the antibody is selective.
Despite these examples, the use of SMPS equipped with
gatelike scaffoldings for the preparation of real delivery systems
is still in its infancy. Thus, in relation to gated systems, some
examples still show disadvantages for their potential use in
advanced applications such as lack of operational features in
aqueous environments, use of difficult-to-apply or complex
stimuli, etc. In particular, regardless of very recent reported gated
SMPS that can be uncapped by enzymes16 or can be controlled
Results and Discussion
Design and Synthesis of the Gated Material. As stated above,
the incorporation of gatelike ensembles on mesoporous scaffolds
has proved to be a suitable approach for the development of
nanoscopic solids for mass transport control and for studying
the factors that could influence the design of gating functions.
Apart from molecular and supramolecular models used for the
design of gated supports, we were particularly interested in
designing systems where delivery could be governed by
biomolecules. Thus, our attention was focused on the specific
interaction between antibodies and antigens.19
The proposed paradigm is depicted in Scheme 1. In this
approach, the external surface of a suitable SMPS is first
functionalized with a hapten (solid S1) and then the mesopores
are capped with a certain antibody that shows good affinity and
selectivity toward the anchored hapten via suitable interaction
through the two binding IgG regions of the former (solid S1-
AB). It was expected that the typical size of antibodies (ca. 5.5
nm)20 would be enough to cap the mesopores in the SMPS. As
illustrated in Scheme 1, the presence in the solution of the
corresponding antigen (complementary to the antibody) would
induce the uncapping of the pores and release of the entrapped
guest. In order to study the functional open/close protocol of
the gated ensemble, the dye [Ru(bipy)3]2+ was loaded on the
inner mesopores of the MCM-41 solid. Thus, the state of the
gatelike system is easily monitored via the emission band of
the [Ru(bipy)3]2+ dye at λ ) 610 nm (λex ) 453 nm) in the
aqueous phase. Following this procedure, the solid for delivery
studies was prepared with MCM-41 solid as the SMPS and
sulfathiazole (STZ) as the antigen. Polyclonal sera for STZ were
obtained for this target by immunization of female New Zealand
rabbits with bovine serum albumin (BSA)-protein conjugates
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Nanoscopic Hybrid Systems with Gatelike Scaffoldings
A R T I C L E S
Scheme 1. Schematic Representation of Gated Material S1 Capped with Antibody and Structures of Hapten 1, Hapten Derivative 2, and the
Antigen Sulfathiazole (STZ)
containing the hapten 1. The same hapten 1 was made to react
with 3-aminopropyltrimethoxysilane to furnish 2, which was
anchored on the SMPS surface in order to prepare S1 (see
Supporting Information for details).21
This second solid, containing amines, was expected to display
some interaction with the antibody because sulfathiazole (for
which the antibody is selective) also contains an amino group.
Both solids will allow assessing the effect that the hapten grafted
onto the MCM-41 pores and its interaction with the antibody
has in the dye delivery control in the presence of antigen. The
procedure to obtain S2 was the same as described for S1 but
without grafting the hapten 2 on the external surface. Addition-
ally S3 was prepared, following literature procedures by reaction
of dye-loaded MCM-41 with 3-[2-(2-aminoethylamino)ethyl-
amino]propyltrimethoxysilane (3) (see Supporting Informa-
tion).15b
Solid S1 should ideally contain the hapten 1 anchored on
the external surface, whereas the dye must be contained in the
mesopore channels. Given that in mesoporous systems the inner
surface is much larger than the external, the preparation of the
solid should be carried out in a programmed fashion. To prepare
the organized hybrid material S1 we made use of a two-step
synthetic procedure that has been used recently by other authors
and by us to develop responsive gating structures containing a
certain cargo in the pores and suitable switchable ensembles
on the pore outlets.15,16c Thus, in a first step, the mesoporous
starting scaffold was added to a solution containing a relatively
high concentration of [Ru(bipy)3]2+ dye in order to achieve
efficient loading of the pores. Then in the same mixture the
hapten derivative 2 was added. This is expected to result in
final solids where 2 is basically placed on the external surface
of the mesoporous silica-based scaffolding because the anchor-
ing reaction of 2 is carried out when the pores are filled with
the ruthenium dye. The final yellow/orange solid (S1) was
filtered, washed with acetonitrile, and dried at 40 °C for 12 h.
For preparation of the final gated material (S1-AB), 400 µg
of the SMPS S1 was suspended in 400 µL of a solution
containing the antibody in phosphate-buffered saline (PBS, pH
7.5; see Supporting Information for the exact composition).
Optimization of the conditions was performed by checking board
titrations with several sera and a range of different serum
dilutions (see Supporting Information). S1-AB was isolated by
centrifugation and washed with PBS to eliminate the residual
dye and the free antibody.
Characterization of Materials. Solid S1 was characterized
by standard procedures. Figure 1 shows powder X-ray diffrac-
tion (PXRD) patterns of the MCM-41 support and the S1
functionalized material. The PXRD of siliceous MCM-41 as
synthesized (curve a) shows four low-angle reflections typical
of a hexagonal array. A significant displacement of the (100)
peak in the PXRD powder of the MCM-41 calcined sample
(curve b) is clearly appreciated due to condensation of silanol
groups during the calcination step. Finally, curve c corresponds
to the S1 PXRD pattern. In this case, all reflections except (100)
are lost, most likely related to a change of contrast due to the
filling of the pore voids with the ruthenium(II) dye. The value
and intensity of the (100) peak in this pattern is strong evidence
that the loading process with the dye and the further function-
alization with hapten have not damaged the mesoporous
scaffolding. The presence of the mesoporous structure in the
MCM-41 calcined sample and final functionalized solids is also
observed by TEM analysis, in which the typical hexagonal
porosity of the MCM-41 matrix can be seen (see Figure 1).
The N2 adsorption-desorption isotherms of the MCM-41
calcined material show a typical type IV isotherm in which the
observed step can be related to the nitrogen condensation inside
the mesopores by capillarity. The absence of a hysteresis loop
in this interval and the narrow pore distribution suggest the
existence of uniform cylindrical mesopores. Application of the
BET model resulted in a value for the total specific surface of
1246 m2/g. The N2 adsorption-desorption isotherm of S1 is
For the sake of comparison, and as control supports, two
additional solids were prepared. One (S2) is a material contain-
ing only the [Ru(bipy)3]2+ dye on the pore voids, whereas the
other (S3) contains [Ru(bipy)3]2+ on the mesopores and
polyamines on the external surface (see Supporting Information).
(21) Langone, J.; van Vunakis, H. Methods Enzymol. 1982, 84, 628–640.
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A R T I C L E S
Climent et al.
Figure 1. (Left) Powder X-ray patterns of the solids (a) MCM-41 as synthesized, (b) calcined MCM-41, and (c) S1 containing the dye [Ru(bipy)3]2+ and
hapten derivative 2. (Right) TEM images of (a) calcined MCM-41 sample and (b) solid S1, showing the typical hexagonal porosity of the MCM-41 mesoporous
matrix.
Table 1. BET Specific Surface Values, Pore Volumes, and Pore
from the typical external surface for a MCM-41 support, this
Sizes Calculated from N2 Adsorption-Desorption Isothermsa for
results in an average distance between antibodies of ca. 7.6 nm,
Selected Materials
a value that is in agreement with the typical effective antibody
pore volumea
(cm3/g)
pore sizea
(nm)
molecular radius of 5.5 nm. Moreover, from the antibody and
hapten contents, a ratio of 86 hapten molecules/antibody
molecules was estimated.
SBET (m2/g)
MCM-41
S1
S3
1246
291
110
0.85
0.22
0.35
2.39
2.31
2.18
Functional Antigen-Driven Controlled Release. As stated
above, we aimed to design delivery systems triggered by a
certain antigen by use of antibody-capped mesoporous scaffolds.
The uncapping protocol, that is, delivery of the Ru complex
from the pore voids to the aqueous solution, was straightfor-
wardly observed via monitoring of the fluorescence band of
[Ru(bipy)3]2+ dye centered at 610 nm (λex ) 453 nm) in the
aqueous phase.
a Volume (V) and diameter (D) of mesopore.
Table 2. Content (R) of Hapten Derivative 2 in S1, Polyamine in
S3, and Dye in Prepared Solids
Rhapten 2
(mmol/g of SiO2)
Rpolyamine
(mmol/g of SiO2)
Rdye
(mmol/g of SiO2)
solid
S1
S1-AB
S2
S3
S3-AB
0.38
0.38
0.66
0.12
0.69
0.60
0.15
To investigate the gating properties, in a typical experiment
250 µL of 1 ppm sulfathiazole in PBS was added to 200 µg of
S1-AB, and the suspension was stirred in order to establish a
competition for the antibody between anchored hapten and free
sulfathiazole. Release of the reporter was also determined for
solutions of S1-AB under similar conditions but in the absence
of sulfathiazole. The difference in emission in the presence and
absence of STZ is displayed in Figure 2, which plots the release
behavior. The figure shows that solid S1-AB displays a poor
release profile versus time (curve a), whereas the same solid in
the presence of 1 ppm STZ (curve b) shows clear delivery of
the dye: 95% of the maximum release of the entrapped guest
was observed after ca. 2 h. Additionally, the figure also shows
how release from the capped system can be triggered on
command by adding sulfathiazole (1 ppm) at a certain time
(curve c). These experiments demonstrate the real possibility
of controlling the cargo delivery in water by use of the antigen
for which the antibody capping the mesopores is selective.
Additionally, delivery from S1-AB as a function of the
concentration of the molecular trigger (sulfathiazole) was
studied, and the results are illustrated in Figure 3. It can be
seen that concentrations as low as 100 ppb sulfathiazole were
able to start to uncap the mesopores. The figure also shows that
the delivered amount of cargo is proportional to the sulfathiazole
concentration, displaying a typical noncompetitive immunoassay
response curve in agreement with an uncapping protocol due
0.40
0.40
typical of mesoporous systems with filled mesopores, and a
significant decrease in the N2 volume adsorbed is observed (see
Supporting Information). In fact, this solid presents relatively
flat curves when compared (at the same scale) to the MCM-41
material, indicating that there is significant pore blocking.
Similar results have been observed for the parent solid S3 and
by us in related systems. BET specific surface values, pore
volumes, and pore sizes calculated from the N2 adsorption-
desorption isotherms for MCM-41 and S1 and S3 are listed in
Table 1 (see Supporting Information for more details).
The content of hapten derivative 2 in S1, polyamine in S3,
and dye in prepared solids, determined by elemental analysis
and thermogravimetric and delivery studies, is shown in Table
2. Further detail for the synthesis and characterization of S3 is
included in Supporting Information.
When the amount of STZ that induced the observed dye
release is taken into account, and with the assumption that two
molecules of STZ interact with one antibody molecule (if total
occupation is supposed), it can be estimated that S1-AB material
contains 1.74 × 1018 antibody molecules/g of solid. Additionally,
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Nanoscopic Hybrid Systems with Gatelike Scaffoldings
A R T I C L E S
Figure 2. Kinetic release of [Ru(bipy)3]2+ dye from solid S1-AB in the
absence (a) and presence (b) of 1 ppm sulfathiazole in aqueous PBS (pH
7.5). A third curve (c) shows the release profile of [Ru(bipy)3]2+ complex
from S1-AB in PBS (pH 7.5) until t ) 70 min (indicated by the arrow in
the figure), when suddenly sulfathiazole (1 ppm) is added to the solution.
Figure 4. Relative release of [Ru(bipy)3]2+ from S1-AB in the presence
of 1 ppm of certain molecules (sulfonamides) in PBS (pH 7.5) after 2 h of
reaction. From left to right: sulfathiazole (STZ), sulfamethizole (SMT),
sulfamerazine (SMR), sulfisoxazole (SOX), sulfamethoxypyridazine (SMP),
sulfaguanidine (SG), N4-phthalylsulfathiazole (PSTZ), sulfadimethoxine
(SDM), sulfadiazine (SDZ), sulfamethoxazole (SMX), sulfacetamide (SAM),
sulfasalazine (SSZ), and sulfanilamide (SAN). The structures of these
sulfonamides used in the cross-reactivity studies are shown in Supporting
Information.
presence of different sulfonamides. A very selective uncapping
with sulfathiazole was detected, where only the sulfonamides
sulfamethizole (SMT) and sulfamerazine (SMR) show certain
cross-reactivity with S1-AB.23
In addition to these delivery studies with S1-AB, further
control experiments were carried out with solids S2 and S3 in
order to evaluate the effect of the anchored hapten on the
selective delivery process. Both solids S2 and S3 contain the
ruthenium dye in the mesopores. Solid S2 does not have any
additional functionalization; S3 contains amino moieties on the
external surface (see Supporting Information for details). As
stated above, due to the presence also of an amino group in
sulfathiazole, some kind of interaction between the polyamines
anchored on S3 and the antibody was expected.
Aqueous suspensions at pH 7.5 of solids S2 and S3 alone
showed fast dye release; however, dye delivery was strongly
inhibited when S2 was in the presence of the antibody due to
an unspecific adsorption process of the antibody on the surface
of S2, most likely through interactions with the silanol groups
on the SMPS. Most importantly, the addition of sulfathiazole
to this S2-AB material resulted in no cargo delivery even when
large amounts of sulfathiazole were added (up to 50 ppm). In
relation to S3, addition of the antibody to this solid resulted in
the preparation of solid S3-AB (analogous to S1-AB). The
gating properties of this new solid were studied in 250 µL of a
solution containing PBS and 200 µg of S3-AB, and the release
behavior as a function of time in the presence and absence of
STZ is displayed in Figure 5 (left). The figure shows that solid
S3-AB displays a rather important release in the absence of
sulfathiazole (curve a) in contrast with the low delivery of the
dye observed for S1-AB (see Figure 2 curve a). This different
behavior is most likely due to much poorer interaction of the
Figure 3. Relative percentage of released [Ru(bipy)3]2+ dye from S1-AB
as a function of the concentration of sulfathiazole in PBS (pH 7.5) after
2 h of reaction. The amount of released dye was determined through the
emission band (λem ) 610 nm) of the [Ru(bipy)3]2+ dye in the solution (λex
) 453 nm).
to a displacement of the antibody as indicated in Scheme 1.22
Typically the maximum percentage of dye delivery from S1 in
the presence of STZ was over 50-60% of the loaded dye.
Selective Delivery. One of the potential advantages of using
antibodies as capping groups is the development of highly
selective key-in-lock gating systems. For instance, it is well-
known that antibodies can identify and bind only to their unique
antigen in mixtures containing a number of different molecules.
In order to investigate selectivity in the opening protocol, dye
delivery from S1-AB was tested in the presence of other
molecules very similar to sulfathiazole; that is, a set of
sulfonamides (see Supporting Information for the structures).
The uncapping ability of these closely related molecules (at 1
ppm concentration) is shown in Figure 4, which plots the
fluorescence of the dye released from the SMPS S1-AB in the
(22) Additionally, although this report deals primarily with the demonstra-
tion that it is possible to develop controlled delivery systems using
antibody-capped mesoporous nanocontainers, the fact that cargo
delivery is proportional to sulfathiazole (antigen) concentration opens
the possibility of developing novel label-free immunoassay paradigms
where the properties of the reporter (the cargo) could easily be selected
at will. Using this concept, further analytical-oriented studies will be
carried out in due course. Also the development of displacement one-
step analytical formats is very promising because this immunoassay
type usually shows higher sensitivity than the corresponding competi-
tive format. See, for instance, Gonza´lez-Techera, A.; Vanrell, L.; Last,
J.; Hammock, B. D.; Gonza´lez-Sapienza, G. Anal. Chem. 2007, 79,
7799–7806.
(23) Although this first example shows a relatively high selective trigger
of the cargo delivery, it is important to note that even more selective
systems could be prepared using monoclonal antibodies or genetically
engineered antibodies. See, for instance, Liddell, E. Antibodies.
Chapter 8 in The Immunoassay Handbook, 3th ed.; Elsevier: Amster-
dam, 2005.
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A R T I C L E S
Climent et al.
Figure 5. (Left) Kinetic release of [Ru(bipy)3]2+ dye from solid S3-AB in the absence (a) and presence (b) of 1 ppm sulfathiazole in PBS (pH 7.5). (Right)
Relative release of [Ru(bipy)3]2+ from S3-AB in the presence of 0.5 ppm of certain sulfonamides (see Supporting Information for structures) in PBS (pH 7.5)
after 2 h of reaction.
antibody with the polyamines in S3-AB than with the hapten
anchored on S1-AB. Additionally, from Figure 5 (left) it is also
apparent that the presence of sulfathiazole (1 ppm) enhances
the delivery of the dye from the S3-AB solid (curve b). Much
more important in terms of selectivity are the results observed
when solid S3-AB is tested in the presence of a family of
sulfonamides. Figure 5 (right) shows the relative release (with
respect to STZ) of the dye from S3-AB in the presence of a
concentration of 0.5 ppm of these chemicals in PBS (pH 7.5).
A clear unselective uncapping process, as effective in many
cases as that found with sulfathiazole, was observed for most
of the molecules tested.24 This behavior heavily contrasts with
that found under similar conditions with the hapten-containing
solid S1-AB (see Figure 4). The behavior shown by S2 and S3
draws attention to the role played by the anchored hapten groups
in the gating mechanism; that is, the hapten in S1 inhibits the
unspecific attachment of the antibody on the mesoporous surface
(as occurs in S2) and allows at the same time a very selective
uncapping protocol to take place in the presence of the target
antigen (in contrast with S3).
entrapped guests in the presence of target molecules (antigen)
to which the antibody binds selectively. It is advisible to note
that this paradigm relies on a different approach, not previously
used, and therefore it displays new possibilities for modulation
that cannot be considered in other systems. In particular, we
believe that gated SMPS based on the use of antibodies may
be a promising route for the development of custom-made
controlled-delivery nanodevices specifically triggered by target
molecular guests. The possibility of including this antibody
gating protocol on diverse supports, the potential delivery of
different cargos, and the opportunity to select antibodies or
similar bioreceptors for a countless amount of possible antigens
makes this approach highly appealing for a very wide range of
delivery applications in different fields.
Experimental Section
See Supporting Information.
Acknowledgment. We express our gratitude to the Spanish
Ministerio de Ciencia y Tecnolog´ıa (Projects CTQ2006-15456-C04-
01, CB07/01/2012, CTQ2007-64735-AR07, and MAT2009-14564-
C04-01) for their support. E.C. and A. B. are grateful to the Spanish
Ministerio de Ciencia e Innovacio´n and to the Polytechnic
University of Valencia for a grant.
Conclusions
In conclusion, we have demonstrated, as a proof-of-the-
concept and for the first time, that the use of antibodies as
gatekeepers on the surface of SMPS provides a suitable method
for the design of delivery systems able to selectively release
Supporting Information Available: Details of the synthesis
and characterization of materials. This material is available free
of charge via the Internet at http://pubs.acs.org.
(24) It might be important to note that S3-AB or similar systems could be
suitable for the development of gating systems that could be opened
by similar species such as a set of sulfonamides.
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