Photocaged Competitor Guests: A General Approach Toward Light-Activated Cargo Release From Cucurbiturils

Article abstract of DOI:10.1002/chem.201702185

A general approach toward the light-induced guest release from cucurbit[7]uril by means of a photoactivatable competitor was devised. An o-nitrobenzyl-caged competitor is photolyzed to generate a competitive guest that can displace cargo from the host macrocycle solely based on considerations of chemical equilibrium. With this method the release of terpene guests from inclusion complexes with cucurbit[7]uril was demonstrated. The binding of the herein investigated terpenes, all being lead fragrant components in essential oils, has been characterized for the first time. They feature binding constants of up to 10⁸ L mol^?1 and a high differential binding selectivity (spanning four orders of magnitude for the binding constants for the particular set of terpenes). By fine-tuning the photoactivatable competitor guest, selective and also sequential release of the terpenes was achieved.

Full text of DOI:10.1002/chem.201702185

A Journal of
Accepted Article
Title: Photocaged Competitor Guests: A General Approach Toward
Light-Activated Cargo Release From Cucurbiturils
Authors: Miguel A. Romero, Nuno Basilio, Artur J. Moro, Mara
Domingues, José A. González-Delgado, Jesús F. Arteaga,
and Uwe Pischel
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To be cited as: Chem. Eur. J. 10.1002/chem.201702185
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Photocaged Competitor Guests: A General Approach Toward
Light-Activated Cargo Release From Cucurbiturils
Miguel A. Romero,[a] Nuno Basílio,*[b] Artur J. Moro,[b] Mara Domingues,[b] José A. González-Delgado,[a]
Jesús F. Arteaga,[a] and Uwe Pischel*[a]
Abstract: A general approach toward the light-induced guest
release from cucurbit[7]uril by means of photoactivatable
an important attribute that could be potentially achieved by
exploiting the differential supramolecular binding of guests
by a certain host type and their competitive displacement by
a photogenerated molecular entity, being only dependent
on considerations of chemical equilibria. In this context
a
competitor was devised. An o-nitrobenzyl-caged competitor is
photolyzed to generate a competitive guest that can displace cargo
from the host macrocycle solely based on considerations of chemical
equilibrium. With this tool the release of terpene guests from
inclusion complexes with cucurbit[7]uril was demonstrated. The
binding of the herein investigated terpenes, all being lead fragrant
components in essential oils, has been characterized for the first
cucurbit[n]urils (CBn) are an emerging family of all-organic
11]
macrocyclic hosts[10,
that feature high guest affinities
(generally in the range of 1051010 M ; exceptionally up to
1
1017 M ) and selective binding of structurally diverse
1
1
time. They feature binding constants of up to 108 M and high
molecules in aqueous solution.[11-14] They are exploited for
example for drug delivery,[15-17] monitoring/control of
biological processes (e.g., enzymatic catalysis),[18-21] and
biomolecule modification,[22-25] but also for the design of
sensors and switches.[26-34]
differential binding selectivity (spanning four orders of magnitude for
the binding constants for the particular set of terpenes). By fine-
tuning of the photoactivatable competitor guest the selective and
also sequential release of the terpenes was achieved.
Introduction
The release of functional molecules by means of
photoactivation is an attractive tool in processes where
spatiotemporal control is an advantage.[1, 2] Often so-called
caged compounds, where the active component is released
by the removal of a light-sensitive protection group, have
been exploited for these purposes. Examples for the light-
induced release of signalling molecules,[3] drugs,[4]
biomolecules,[5] fluorescent dyes,[6, 7] or natural products,[8, 9]
are known. However, the covalent nature of these
constructs requires elevated synthetic efforts, especially
when combinatorial libraries of caged functional molecules
are pretended.
The non-covalent nature of supramolecular interactions
provides an interesting feature for combinatorial assembly,
being an added value especially when light can be used to
achieve the release of guests. Selectivity in photorelease is
Scheme 1. Schematic representation of the release principle, employing the
phototrigger 1. On irradiation the competitor 2 is formed, which in contrast to 1
is able to displace a guest from CB7. Further, the structures of the alternative
phototrigger 3, the competitor guest 4, and CB7 are shown.
[a]
M. A. Romero, Dr. J. A. González-Delgado, Dr. J. F. Arteaga, Dr. U.
Pischel
CIQSO - Center for Research in Sustainable Chemistry and
Department of Chemistry
University of Huelva
Campus de El Carmen s/n, E-21071 Huelva (Spain)
E-mail: uwe.pischel@diq.uhu.es
As part of our own research program we demonstrated recently
the photorelease of guests from CB7 complexes by light-induced
[b]
Dr. N. Basílio, Dr. A. J. Moro, M. Domingues
Laboratório Associado para a Química Verde (LAQV)
Rede de Química e Tecnologia (REQUIMTE), Departamento de
Química, Faculdade de Ciências e Tecnologia
Universidade NOVA de Lisboa, 2829-516 Caparica (Portugal)
E-mail: nuno.basilio@fct.unl.pt
pH-jump or by coupling of
a (pH-dependent) flavylium
photoswitch to the host-guest equilibrium of a cucurbituril
36]
complex.[35,
However, these approaches required the
implication and strict control of pH conditions and are therefore
limited in their experimental design. This is not ideal for
applications in more realistic contexts.
Supporting information for this article is given via a link at the end of
the document.
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In this work we devise the light-activated photorelease from CB7
by using photoactivatable precursors that generate competitor
guests, based on the photochemistry of the popular o-
of the 1H-NMR signals on addition of CB7 (see Supporting
Information). This very low supramolecular affinity is explained
by (a) the repulsive electrostatic interaction between the
negatively charged carboxylate group and the carbonyl-lined
CB7 portal[20, 50] and (b) the inactivation of the amino group in the
NVOC-protected compound 1.[51] However, upon irradiation of 1
at >280 nm (the photoreaction can be performed at 365 nm but
requires longer irradiation time) phenylalanine (2) is formed. The
now available protonable amino group engages in ion-dipole
interactions with the CB7 portal and offsets the effect of the
nitrobenzyl motif, that can be operated even under physiological
5, 37, 38]
conditions.[1, 2,
This was combined with the differential
binding of guests, inherent to cucurbituril chemistry and leading
to selective as well as sequential release. In addition, our
approach does not require a photoactive host or guest.[27, 33, 39-48]
Both can be photochemically silent, which expands the diversity
spectrum enormously. The potential of this very flexible "plug-
and-play" approach is showcased for the release of fragrant
terpene guests, but could be easily expanded to other functional
guests.
carboxylate. This is translated into
a
more efficient
supramolecular interaction with CB7 (KCB7 = 1.8 × 106 M1)[13]
and resulted in the release of dye 5 (see Figure 1), which was
also independently confirmed by the corresponding competitive
displacement titration with 2 (see Supporting Information). The
absence of binding of 1 and its light-triggered conversion into an
efficient CB7 binder constitute an ideal scenario with view on the
release of a guest, such as dye 5.
Figure 1. UV/vis-absorption spectral changes on irradiation (>280 nm) of a
mixture of phototrigger 1 (500 M), dye 5 (20 M), and CB7 (50 M); pH 7.
The inset shows the temporal development of the photoreaction/displacement.
No spectral changes were observed for the irradiation of a blank control where
no phototrigger 1 was present.
Scheme 2. Structures of the dyes 57 and the terpene guests 813.
Results and Discussion
The NVOC-protected competitor can be varied flexibly, thereby
enabling the displacement of even stronger binding guests. For
this purpose we designed 1-aminoadamantane-NVOC (3) which
is expected to generate the strongly binding 1-
aminoadamantane upon irradiation (4; KCB7 = 1.7 × 1014 M1).[52]
Compound 3 binds to CB7 with a binding constant of KCB7 = 1.4
× 108 M1 (measured by the displacement of 4',6-diamidino-2-
phenylindole dihydrochloride 6 and monitored by fluorescence;
KCB7 = 1.7 × 107 M1; this work).[53] Hence, 3 could be used to
displace guests with affinities in the order of ca. 1091013 M1.
Design and Working Principle
Our strategy toward light-activated supramolecular release
combines o-nitrobenzyl-caged compounds with the competitive
displacement of a previously bound guest from its cucurbituril
complex by a photogenerated competitor. This principle is
illustrated in Scheme 1 for the example of phototrigger 1, an
NVOC-protected
phenylalanine
(NVOC:
6-
nitroveratryloxycarbonyl). 1 itself does not bind to CB7. This was
deduced experimentally at the micromolar concentration level by
the failure to displace the chalcone charge-transfer dye 5 from
its CB7 complex (KCB7 = 2.3 × 105 M1)[49] by addition of 1,
monitored by UV/vis absorption spectroscopy (see Supporting
Information). At millimolar concentration also no interaction
between CB7 and 1 proceeded, as evidenced by the invariability
However, the insolubility of
3 (limited to ca. 10 μM in
water/methanol 95/5) circumvents the premature release of even
weaker binding guests in experiments that are conducted at the
millimolar concentration level (see below).
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Terpene Binding by CB7
1H-NMR spectroscopy confirmed the notion that the terpene
guests are bound by the CB7 cavity. Gratifyingly, all investigated
guests have various methyl groups and their proton signals are
ideal indicators for gaining information about the binding
situation of the terpenes. Especially the exchange kinetics for
the bicyclic terpenes is slow on the NMR time scale, enabling
the concomitant observation of the free and bound guest. On
addition of CB7 to terpene solutions significant upfield chemical
shift changes apply (Δ ca. 0.51.0 ppm; see 1H-NMR spectra in
Supporting Information). This is indicative of a deep immersion
of the guests into the macrocycle cavity.
As a title of example we have chosen to address the release of
terpene guests from CB7 by means of the above described
mechanism. Eucalyptol (8), geraniol (9), geranylamine (10),
fenchyl alcohol (11), -pinene (12), and borneol (13) were
selected for being representative lead fragrant components of
essential oils (see structures in Scheme 2). First, the binding of
the guests 813 with CB7 was evaluated (see Table 1). Some of
these compounds are highly hydrophobic, which turns this task
into a real experimental challenge.[54] In the case of sufficiently
water soluble guests (8, 10, 11, and 13) isothermal titration
calorimetry (ITC) was employed (see Figure 2(a)), albeit the
binding constant of 13 turned out to be too large to be measured
by direct titration (>5 × 107 M1). The data were contrasted with
those obtained in dye displacement titrations (using the UV/vis-
absorption changes of dye 5 or 6) and were found to be in
satisfactory agreement. For sparingly water-soluble terpenes (9
and 12) and very strong binders (13) dye displacement titrations
were employed for the determination of the 1:1 binding
constants; Figure 2(b). Interestingly, the set of terpenic guests
spans an affinity range of four orders of magnitude (104108 M1).
Geraniol (9) is the weakest binder in the investigated series,
while geranylamine (10) binds two orders of magnitude stronger,
due to the presence of the protonable amino group. The bicyclic
terpenes 12 and 13 are the strongest binders. Interestingly,
small variations of the substituent positions on the
bicyclo[2.2.1]heptane skeleton of the regioisomeric guests 11
and 13 result in rather pronounced differences of the binding
strength. The observed variety of binding constants for the
investigated series gives way to the prediction that the terpenic
guests could be displaced selectively by the action of
phototrigger 1; see below.
Table 1. Binding affinities of the guests 813 with CB7.
1
1
1
[a]
ΔH (kJmol
37.4[b]
)
TΔS (kJmol
)
K (106 M
)
8
0.85[b] [0.34][c]
0.046[c]
3.6[b]
9
10
11
12
13
3.2[b] [1.9][d]
4.8[b] [8.6][c]
≥10[e]
39.7[b]
42.3[b]
2.5[b]
4.1[b]
260[d]
61.7[b,f]
13.7[g]
[a] In square brackets data obtained by alternative methods are shown.
[b] Measured by ITC in water at 25 ⁰C. [c] Measured by displacement
of 5 in water (pH 9). [d] Measured by fluorescence monitoring of the
displacement of 6 in water (pH 7). [e] Estimated by displacement of 7 in
10 mM acetate buffer (pH 4). Only a lower limit is given due to a higher
uncertainty caused by the low solubility of 12. [f] Binding constants
1
larger than 5 × 107 M are hard to measure by direct ITC titration.
However, the H value can be measured reliably by ITC. [g] The value
for TS was calculated from G (via K) and H.
The ITC data for the terpenes 8, 10, 11, and 13 reveal that
their complexation is enthalpically driven; see Figure
2(a).[55] This is a typical situation found for the binding of
hydrophobic guests by CB7 and interpreted as the benefit
that results from the release of high-energy water
molecules from the macrocyclic host cavity to the
surrounding bulk water.[55] At the same time there is no
entropic gain associated to the guest binding, pointing to a
much less significant, if existent, contribution of a classical
hydrophobic effect.
A different facet of the binding of terpenes by CB7 is the
capacity of the macrocycle to retain the fragrant guest from
passing to the gas phase. As a title of example we
performed
experiments[56] at constant temperature (24 ⁰C) with an
aqueous eucalyptol solution ([ ] = 50 μM) in the absence or
presence of CB7 (120 μM; corresponding to 98%
complexation degree of ), using a polyacrylate-coated
solid-phase
microextraction
(SPME)
8
8
fused-silica fiber (85 μm coating). The extracted terpene
was subjected to gas chromatography coupled with mass
spectrometric detection, providing relative concentrations of
Figure 2. (a) Isothermal titration calorimetry (ITC) data for the binding of 8 by
CB7 in water; titration of CB7 into 0.4 mM 8. (b) Competitive displacement of 6
([6] = [CB7] = 1 M; KCB7(6) = 1.7 × 107 M1, this work) by 13, monitored by
fluorescence spectroscopy (exc
= 362 nm; isosbestic point in UV/vis
8
in the headspace. Keeping the optimized experimental
absorption spectra).
parameters constant (especially the times for extraction and
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desorption), it was found that CB7 retained guest
8
to a
aqueous solution containing 50 μM 8, 120 μM CB7, and 240 μM
1. The corresponding SPME experiments indicated a 2.5-fold
increase of the headspace concentration of 8 as the result of the
photorelease.
large extent, characterized by a drop to 5% of the initially
measured headspace concentration in the absence of the
host macrocycle. Also the evaporation of the terpene from
its water solution was slowed down by the macrocyclic host:
a half-life of 229 minutes in the absence of CB7 is
contrasted by 679 minutes in the presence of CB7 (see
Figure 3).
Figure 4. 1H-NMR spectra of (a) 8•CB7 host-guest complex (each component
at 1 mM); (b) a mixture of 1 (1 mM), CB7 (125 M), and 8 (100 M) before
irradiation; (c) after 120 min irradiation (>280 nm) of the same mixture as
under (b); (d) only 8; pD 6.5. The signals are assigned with color codes: 8 -
red (complexed - squares, free - dots); 1 - blue dots; free excess 2 - green
dots; NVOC-derived photoproduct - black dots; CB7 - magenta triangles. Note
that 1 was used in large excess and that the exchange rate between free and
complexed 2 is assumed to be intermediate. The 1H-NMR signals of excess
free 2 appear considerably broaden, while the signals of complexed 2 are not
observed. The HOD signal is not shown for the sake of clarity (axis break).
Figure 3. Transfer of 8 (50 M) from aqueous solution (pH 7) to the gas phase,
in the absence (blue data points) and presence of CB7 (120 M, red data
points); quantified by SPME. The normalized concentrations of
8 are
expressed as chromatography peak areas divided by the initial zero-time peak
area for each experiment (see text). The time corresponds to the duration of
leaving the solution-containing vial open to the ambient atmosphere. Each
point was measured after closing the container vial again and re-equilibrating
the solution for 10 min.
Light-activated Guest Release
With the binding data at hand we proceeded to the photorelease
of the terpene guests from their complexes at concentrations of
hundreds of micromolar (100400 M) by irradiation in the
presence of 1. The release was monitored by 1H-NMR
spectroscopy; see Figure 4 for the example of eucalyptol (8) and
the Supporting Information for the other terpenes. Under the
specific experimental conditions (see caption of Figure 4) 87% of
8 was bound to CB7 before irradiation, while after two hours of
irradiation (280 nm cut-off filter) 93% of all 8 was unbound.
Hence, effectively 92% of all initially bound 8 was released. The
experiment was repeated under comparable conditions for the
other terpenes, employing optimized concentrations of CB7,
terpene, and phototrigger. For geraniol (9), having the weakest
CB7 affinity in the series, 100% release was obtained. The
stronger binding geranylamine (10) and fenchyl alcohol (11)
were less efficiently released; 45% and 54%, respectively.
Finally, the strongly binding guests -pinene (12) and borneol
(13) are not displaced by the photogenerated phenylalanine (2).
Hence, as anticipated, the variable binding affinity has direct
impact on the efficiency of the photorelease experiment and
thereby its selectivity. The release of guest 8 was also confirmed
by determining the relative headspace concentrations before
and after irradiation (6 hours with a TLC lamp at 365 nm) of an
Figure 5. Photorelease of 13 from CB7 by light irradiation (>300 nm),
monitored by 1H-NMR spectroscopy. Conditions: 1-aminoadamantane-NVOC
(3, 2 mM), CB7 (500 M), and 13 (250 M) in D2O:CD3OD 50:5; pD 6.8. The
spectra were acquired after different irradiation times: 0 min (b) and 240 min
(c). Additionally the spectra of (a) 13 (250 M) in the presence of CB7 (500
M), (d) only 13 (1 mM), and (e) 4 (1 mM) in the presence of CB7 (1 mM) are
shown. Corresponding signals are color-coded: red
- methyl signals of
complexed borneol; green - methyl signals of free borneol (13); blue - signals
of complexed 1-aminoadamantane (4).
As outlined above, the described approach is of general nature
and the light-triggered formation of a stronger competitor should
allow the delivery of 12 or 13. This has been tested with
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phototrigger 3. The photoirradiation yields the competitor 4
which binds sufficiently strong to displace even borneol (13)
quantitatively (see above and Figure 5) during 240 minutes of
irradiation at >300 nm. The insolubility of the phototrigger in the
millimolar concentration range eliminated the risk of a premature
displacement before exposure to light, only forming water-
soluble competitor during the photoreaction.
binding strength and for the selective release of non-
chromophoric guests. To showcase the potential of the
design, terpene guests were employed. The chosen
compounds are lead ingredients of essential oils and their
binding to CB7 was quantified herein for the first time. The
binding constants span a range of four orders of magnitude,
1
reaching values as high as 108 M . These features enabled
In
displacement by photogenerated
irradiating a mixture of CB7 complexes of four terpenes (
11, and 13) and phototrigger (see Figure 6). Under the
a
final experiment the selective and sequential
the selective and also sequential light-induced release of
the terpenes. Noteworthy, the described photofunctionality
can be extended to a wide spectrum of competitors and
guests.
2
was illustrated by
8
,
9
,
1
chosen experimental conditions and in accordance with the
differentiated terpene affinities for the host macrocycle
(Table 1), geraniol (
after 10 minutes of irradiation. After 40 minutes also
eucalyptol ( ) is released in 75%. Fenchyl alcohol (11) is
more resistant and after 120 minutes ca. 25% are non-
complexed. Borneol (13) withstands the displacement by
as already observed in the experiment with the individual
terpene (see above). It should be stressed that this
sequentiality would not be possible for other macrocyclic
nanocontainers, lacking the high binding selectivity
displayed by CB7.[30]
9) is practically quantitatively released
Experimental Section
8
Materials and General Methods
2
,
Phenylalanine-NVOC (1) was synthesized as previously described and
the identity of the sample was confirmed by H-NMR spectroscopy.[57] 1-
1
Aminoadamantane-NVOC (3) was prepared as described below.
Phenylalanine (2), 1-aminoadamantane (4), 6-nitroveratryloxycarbonyl
chloride, 4',6-diamidino-2-phenylindole dihydrochloride (6), and the
terpenes 813 are commercially available from Aldrich in highest purity
and were used as received. Cucurbit[7]uril, the trans-chalcone dye 5, and
p-N,N-dimethylaminophenyltropylium perchlorate (7) were available from
previous studies.[35, 49]
The pH of the solutions was adjusted with HCl or NaOH and measured
with a Crison basic 20+ pH meter. UV/vis absorption spectra were
recorded using
a Varian Cary 100 Bio or a Shimadzu UV-1603
spectrophotometer. Fluorescence spectra were measured with a Varian
Eclipse fluorimeter. Indicator dye displacement assays were conducted
with constant concentrations of dye and CB7. The solutions were allowed
to equilibrate after addition of the terpene until no changes were
observed in absorption or emission as a function of time. In the case of
less water-soluble terpenes up to 0.4 vol% ethanol was employed as co-
solvent.
Synthesis of 1-aminoadamantane-NVOC (3)
1-Aminoadamantane (100 mg, 0.66 mmol) and sodium carbonate (69.96
mg, 0.66 mmol) were dissolved in 2.2 mL water (milli-Q quality). 6-
Nitroveratryloxycarbonyl chloride (NVOC-Cl, 182 mg, 0.66 mmol),
dissolved in 2.2 mL 1,4-dioxane, was then added slowly under stirring to
the aqueous solution. After stirring at room temperature for 2 hours, the
reaction solution was diluted with 20 mL dichloromethane, followed by
the addition of 20 mL 1 N aqueous sodium bisulfate solution. The organic
phase was separated and the aqueous phase was extracted with fresh
dichloromethane. The combined organic extracts were dried over
anhydrous sodium sulfate and then concentrated in vacuo to give a
yellow solid as crude. Purification by silica gel chromatography with n-
hexane/t-butylmethylether (2:1) as the eluent provided 122 mg (47%
yield) of 3 as a slightly yellow solid. 1H-NMR (400 MHz, CDCl3)  7.71 (s,
1H), 6.98 (s, 1H), 5.44 (s, 2H), 4.74 (s, 1H), 3.98 (s, 3H), 3.95 (s, 3H),
2.09 (s, 3H), 1.95 (d, J = 2.7 Hz, 6H), 1.67 (s, 6H) ppm. 13C-NMR (100
MHz, CDCl3)  153.61, 148.08, 139.86, 128.88, 110.09, 108.26, 62.95,
56.55, 51.14, 41.94, 36.36, 29.54 ppm. Note: (NH)(O)C=O was not
observed. HRMS (ESI) Calcd for C20H27N2O6 [M + H]+ 391.1869. Found
391.1866.
Figure 6. (a) Mixture of 8, 9, 11, and 13 with CB7 (600 M) and 1 (1 mM) in
D2O:CD3OD 60:1; pD 6.5. Each terpene was used in a concentration of 150
M. (b)-(e) The same mixture, as under (a), after 10 min, 20 min, 40 min, and
120 min irradiation time, respectively. Characteristic signals of complexed
(marked with squares) and released terpenes (marked with dots) are color-
coded: 8 - purple, 9 - red, 11 - green, 13 - blue. In the initial spectrum (a) the
colored squares correspond to terpene-CB7 complexes. The colored dots in
the spectra (b), (d), and (e) indicate the appearance of released terpenes. For
the sake of clarity, they have been solely marked in the corresponding
spectrum where their release arrived at the maximum level under the
employed conditions (see text). Note that complexed borneol [13, blue
squares in spectrum (a)] is not released at all.
Conclusions
A new approach for the light-induced release of guests from
their cucurbituril complexes by means of the
photodeprotection of o-nitrobenzyl-tagged competitor
guests was developed. The experimental design is very
flexible, allowing for the fine-tuning of the competitor
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Isothermal Titration Calorimetry
Junta de Andalucía (P12-FQM-2140 for U.P. and PhD
contract for M.A.R.), and the Associated Laboratory for
Sustainable Chemistry-Clean Processes and Technologies-
LAQV is acknowledged. The latter is financed by national
funds from FCT/MEC (UID/QUI/50006/2013) and co-
financed by the ERDF under the PT2020 Partnership
Isothermal Titration Calorimetry (ITC) measurements were performed on
a Nano ITC (TA Instruments) with standard volumes. The solutions were
thoroughly degassed before use by stirring under vacuum. The sample
cell was loaded with the terpene solution and a 250 µl autopipette was
filled with the CB7 solution. The guests were titrated in a sequence of 50
injections of 5 µl after achievement of baseline stability.
Agreement
Portuguese FCT/MEC is also acknowledged through the
National Portuguese NMR Network (RECI/BBB-
BQB/0230/2012). N.B. and A.J.M. are recipients of FCT
postdoctoral grants (SFRH/BPD/84805/2012 and
(POCI-01-0145-FEDER-007265).
The
Photorelease Experiments
The photorelease was followed in NMR experiments that were run on a
Bruker AMX 400 or an Agilent 400 MR instrument, operating at 400 MHz
(1H) or 100 MHz (13C). The solutions for NMR were prepared in D2O (in
some cases with CD3OD as co-solvent) and the pD was adjusted with
DCl or NaOD. Corrections due to isotope effects were applied using the
equation pD = pH* + 0.4, where pH* is the reading taken from the pH
meter.[58]
SFRH/BPD/69210/2010). We are grateful to Dr. S. Pauleta
(Lisbon) for providing access to the ITC equipment (FCT-
ANR/BBB-MET/0023/2012) and to Dr. C. Bonifácio (Lisbon)
for technical assistance. We thank Prof. M. A. Fernández
Recamales (Huelva) for making the SPME setup available.
Keywords: photochemistry • supramolecular chemistry •
cucurbiturils • release • terpenes
Light-irradiation experiments were conducted with a 200 W Hg-Xe lamp
using a 280 nm cut-off filter or with a 150 W Xe lamp. Experiments with
phototrigger 3 were done in a suspension, because of its insolubility in
water. Compound 3 was pre-solubilized in CD3OD and then diluted to the
final concentration. This re-precipitation assured reproducible conditions
and the irradiation time until the completion of the photoreaction,
indicated by the solubilization of all photoproducts, was rather constant
between different experiments. In a mixture of water/methanol (95/5)
compound 3 has a maximum solubility of 200 M. It is assumed that the
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The relative concentrations of phototrigger and terpene•CB7 complex
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8 and 11 in Supporting Information). The same is true for the pD value.
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with a protonable amino group. However, even under less acidic or
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Acknowledgements
The financial support by the Spanish MINECO (CTQ2011-
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peptides that contain phenylalanine at the C-terminus, where a similar
electronic situation is found. Noteworthy, peptides with phenylalanine at
the N-terminus bind even stronger than phenylalanine itself, because
the carboxylate is replaced by an amide; see for example refs. 20 and
50.
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Entry for the Table of Contents
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The competition is on: The
phototriggered generation of
Miguel A. Romero, Nuno Basílio,* Artur
J. Moro, Mara Domingues, José A.
González-Delgado, Jesús F. Arteaga,
Uwe Pischel*
competitor guests from o-nitrobenzyl-
caged precursors can be used to
displace functional guests from the
cucurbit[7]uril cavity. This general
approach was harnessed for the light-
triggered supramolecular release of
terpene fragrances in a selective and
also sequential manner.
Page No. – Page No.
Photocaged Competitor Guests: A
General Approach Toward Light-
Activated Cargo Release From
Cucurbiturils
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