Improving Fatigue Resistance of Dihydropyrene by Encapsulation within a Coordination Cage

Article abstract of DOI:10.1021/jacs.0c06146

Photochromic molecules undergo reversible isomerization upon irradiation with light at different wavelengths, a process that can alter their physical and chemical properties. For instance, dihydropyrene (DHP) is a deep-colored compound that isomerizes to light-brown cyclophanediene (CPD) upon irradiation with visible light. CPD can then isomerize back to DHP upon irradiation with UV light or thermally in the dark. Conversion between DHP and CPD is thought to proceed via a biradical intermediate; bimolecular events involving this unstable intermediate thus result in rapid decomposition and poor cycling performance. Here, we show that the reversible isomerization of DHP can be stabilized upon confinement within a PdII6L4 coordination cage. By protecting this reactive intermediate using the cage, each isomerization reaction proceeds to higher yield, which significantly decreases the fatigue experienced by the system upon repeated photocycling. Although molecular confinement is known to help stabilize reactive species, this effect is not typically employed to protect reactive intermediates and thus improve reaction yields. We envisage that performing reactions under confinement will not only improve the cyclic performance of photochromic molecules, but may also increase the amount of product obtainable from traditionally low-yielding organic reactions.

Full text of DOI:10.1021/jacs.0c06146

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Article
Improving Fatigue Resistance of Dihydropyrene by Encapsulation
within a Coordination Cage
Martina Canton,∇ Angela B. Grommet,∇ Luca Pesce, Julius Gemen, Shiming Li, Yael Diskin-Posner,
́
Alberto Credi, Giovanni M. Pavan, Joakim Andreasson, and Rafal Klajn*
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ABSTRACT: Photochromic molecules undergo reversible iso-
merization upon irradiation with light at different wavelengths, a
process that can alter their physical and chemical properties. For
instance, dihydropyrene (DHP) is a deep-colored compound that
isomerizes to light-brown cyclophanediene (CPD) upon irradi-
ation with visible light. CPD can then isomerize back to DHP upon
irradiation with UV light or thermally in the dark. Conversion
between DHP and CPD is thought to proceed via a biradical
intermediate; bimolecular events involving this unstable inter-
mediate thus result in rapid decomposition and poor cycling
performance. Here, we show that the reversible isomerization of
DHP can be stabilized upon confinement within a PdII L4
6
coordination cage. By protecting this reactive intermediate using
the cage, each isomerization reaction proceeds to higher yield, which significantly decreases the fatigue experienced by the system
upon repeated photocycling. Although molecular confinement is known to help stabilize reactive species, this effect is not typically
employed to protect reactive intermediates and thus improve reaction yields. We envisage that performing reactions under
confinement will not only improve the cyclic performance of photochromic molecules, but may also increase the amount of product
obtainable from traditionally low-yielding organic reactions.
cage, we hoped to protect the unstable intermediate from
INTRODUCTION
■
oxidation and radical−radical interactions that lead to
Dihydropyrene (DHP) belongs to the family of diarylethene
photoswitches;1,2 this switch consists of a large π-conjugated
system3 that can be converted to the open form cyclo-
phanediene (CPD) using visible light. This isomerization is
reversible, as CPD can be converted back to DHP both
photochemically and thermally.4 Unlike other photochromic
systems, such as azobenzenes and spiropyrans, DHP is a rare
example of a compound where the colored form constitutes
the thermodynamically more stable isomer.5 One disadvantage
of this molecular switch, however, is its instability and poor
fatigue resistance. The observed fatigue is thought to arise from
the reactivity of the biradical intermediate formed as a result of
photocleavage of the central C−C bond in the singlet excited
state of DHP.6,7 To render photoswitching cycles more robust,
we propose stabilizing the reaction under confinement,8,9 by
encapsulating DHP within the cavity of a coordination
cage.10−14
decomposition. Octahedral PdII L4 cage 1 has been previously
6
shown to be highly flexible due to the rotational freedom
around the imidazole−benzene bonds.33 Cage 1 can thus adapt
the shape of its cavity to the geometry of bound guest
molecules. Furthermore, the flexibility of cage 1 allows the
cavity to dynamically adapt in response to the isomerization of
encapsulated spiropyran33 and azobenzene34 photoswitches.
Here, we show that cage 1 encapsulates DHP in quantitative
yield, forming a 1:1 inclusion complex. Upon irradiation with
blue light, encapsulated DHP isomerizes to CPD within the
cage and maintains a similar orientation within the cage cavity
before and after the reaction. Furthermore, the back-reaction
from CPD to DHP was achieved within the cage both upon
irradiation with UV light and in the dark. Using atomistic
molecular dynamics simulations, we show that encapsulated
Reactive species such as radicals15−18 and photo-
chromes19−25 can be stabilized under confinement through a
range of different mechanisms.26−29 Confined spaces can, for
instance, create a hermetic seal around a reactive species,
which prevents or minimizes interactions with the external
environment.30−32 By confining DHP within a coordination
Received: June 7, 2020
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Figure 1. (a) Structural formula of cage 1, including atom numbering scheme used in the NMR spectra. (b) Reversible photoisomerization
between DHP and CPD. (c) Partial 1H NMR spectra (400 MHz, D2O) of empty cage 1, DHP⊂1, and CPD⊂1 (for full-range spectra, see Figures
S2, S7, and S17).
DHP behaves like a molecular gyroscope within the cage
cavity, whereas the movement of encapsulated CPD is
relatively hindered. We found that while confinement within
the cage does not greatly influence the rate of switching, it
significantly increases the fatigue resistance of DHP switching,
as compared to free DHP in solution. To the best of our
knowledge, this work constitutes a unique example in which
stabilization of a reactive intermediate by a coordination cage
is employed as a technique to improve the yield of a reversible
reaction.
respect to those from free DHP in chloroform (Figures S6 and
S8). Furthermore, the methyl peak (H12) from encapsulated
DHP is shifted significantly upfield from −4.24 to −6.44 ppm
upon encapsulation; these effects are due to shielding by the
aromatic panels of the cage. Moreover, integrating signals from
the cage and from encapsulated DHP indicates that the
binding stoichiometry is 1:1.
To confirm the binding stoichiometry of this inclusion
complex, an aqueous solution of the cage in water (0.62 mM)
was titrated using a solution of DHP dissolved in acetonitrile
(6.94 mM) (Supporting Information, section 6). The
formation of the complex was followed by UV/vis absorption
spectroscopy. The absorption signals attributed to encapsu-
lated DHP increased in absorbance until 1 equiv of DHP was
added. Upon further addition of DHP, a plateau in the
absorbance of DHP⊂1 was achieved (Figure S12b).
Furthermore, the baseline was observed to increase, which
indicated that excess DHP was not incorporated within the
cage cavity and thus began to precipitate from solution (Figure
S12a,c). As compared to the UV/vis spectra of free DHP in
acetonitrile (λmax = 336 and 376 nm), pentane (λmax = 336 and
375 nm), and toluene (λmax = 340 and 379 nm), the
wavelengths of maximum absorption from encapsulated DHP
in water (λmax = 346 and 383 nm) are red-shifted by 10 and 7
nm, 10 and 8 nm, and 6 and 4 nm, respectively; this effect is
likely due to differences in the intermolecular interactions
between free DHP and the solvent, and between encapsulated
DHP and the aromatic panels of the cage. We note that there is
no solvent that can dissolve both DHP⊂1 and free DHP,
RESULTS AND DISCUSSION
■
To study the behavior of DHP under confinement, DHP was
first encapsulated within cage 1. To prepare this complex,
excess solid DHP was added to an aqueous solution of 1 (1
mM) and stirred for 24 h at room temperature. Undissolved
DHP was then removed using ultracentrifugation. Despite
DHP being insoluble in water, the resulting supernatant was
observed to be green, which indicated the presence of
encapsulated DHP.
The characterization of this complex was achieved by
1
performing 1D and a suite of 2D NMR experiments. The H
1
DOSY spectrum indicates that all signals observable by H
NMR diffuse at the same rate (Figure S9); that is, the signals
attributed to DHP and to cage 1 diffuse together through
solution, which confirms the formation of the complex. All
1
1
signals observed by H NMR were fully assigned by H−1H
COSY and H−1H NOESY (Figures S10 and S11). The H
NMR spectrum of DHP⊂1 (Figure 1) shows that the aromatic
peaks from DHP (H9, H10, H11) are shifted upfield with
1
1
B
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1
which renders direct comparison between these two systems
challenging.
encapsulated DHP is observed in the H NMR spectrum, we
infer that this rotation is fast on the NMR timescale.
1H−1H NOESY provided additional information elucidating
the orientation of DHP within the cavity of cage 1. The methyl
groups (H12) from DHP are correlated with the equatorial and
benzene regions of the cage (H4−8), highlighted in purple and
orange in Figure 2a. This result suggests that DHP is oriented
The solution-state structure surmised from NOESY
correlations was confirmed in the solid state upon obtaining
the X-ray crystal structure of DHP⊂1 (Figure 2b,c). Crystals
were obtained by slow evaporation of water from a solution of
DHP⊂1 at room temperature. As suggested by NOESY,
disorder was observed in the orientation of DHP within the
cavity. Upon refinement of the crystal structure, two
orientations of DHP were observed. The major species,
present in approximately 66% composition, contains DHP
oriented roughly vertically within the cavity, while the minor
species (34%) contains DHP oriented horizontally (Figure 2c).
Furthermore, the X-ray crystal structure demonstrates the high
degree of flexibility within the cage, which allows the cavity to
conform to the geometry of DHP. As compared to the crystal
structure of the empty cage, the structure of DHP⊂1 is
distorted along the axial direction; the axial Pd−Pd distance
increases from 16.865 Å in the empty cage34 to 19.552 Å and
19.910 Å in DHP⊂1 (the crystal structure features two
alternating complexes with slightly different structural
parameters), corresponding to 15.9% and 18.0% increases,
respectively. Previously reported crystal structures of inclusion
complexes formed by cage 1 also show a similar effect. The
crystal structure for DHP⊂1, however, is significantly more
distorted than that for any of the seven inclusion complexes of
1 obtained to date,33−36 where the largest increase in the axial
Pd−Pd distance corresponded to 13.3% (Table S1).
Having obtained the crystal structure for DHP⊂1, we
noticed a striking similarity with the structure previously
reported for an encapsulated merocyanine (MC⊂1 in Figure 3;
Figures S13 and S14). In both structures, cage 1 extends axially
to accommodate the guest, and the methyl groups of DHP and
MC are located within the equatorial pockets of the cage.
Furthermore, encapsulated MC is oriented in a vertical fashion
similar to the major species within the structure of DHP⊂1.
Given the parallels between these two structures, we were
interested in whether one of these guests could displace the
other from the cavity of 1 (Figure 3a). To this end, we treated
DHP⊂1 with a mixture of 2 equiv of free DHP and 3 equiv of
MCH (i.e., the nonencapsulated form of MC33) such that the
total amounts of DHP and MCH in the system were the same
(see Supporting Information, section 9). The reaction could
conveniently be followed by UV/vis absorption spectroscopy,
due to the fact that the encapsulated MC is the only species in
the system absorbing at λ > 550 nm. Specifically, we followed
the increase of absorption at the wavelength of MC’s maximum
absorption (600 nm) and found that the exchange proceeded
rapidly, reaching equilibrium within the first 30 min (Figure 3b
and the green trace in Figure 3d, top). The equilibration could
be followed independently by monitoring the fluorescence
intensity at 670 nm (λexc = 550 nm), where encapsulated MC
is the exclusive emitter (Figure S15a and the green trace in
Figure 3d, bottom). In a separate experiment, we prepared
MC⊂1 and mixed it with 2 equiv of free MCH + 3 equiv of
DHP. The reaction was somewhat slower, which could be
attributed to the very low DHP solubility in water; never-
theless, similar compositions of mixtures in both experiments
were reached within the initial 1 h of exchange (Figure 3d).
We have previously demonstrated33 that cage 1 binds MC with
a high association constant of Kassoc > 107 M−1. Unfortunately,
we cannot directly measure Kassoc for DHP⊂1 because DHP is
insoluble in water. Furthermore, upon adding <1 equiv of
1
Figure 2. (a) Partial H−1H NOESY spectrum (500 MHz, D2O) of
DHP⊂1. Signals highlighted in red, orange, and purple originate from
1’s axial imidazole, equatorial imidazole, and benzene rings,
respectively (see Figure 1a). Signals highlighted in green originate
from DHP. (b) Crystal structure of DHP⊂1 (major conformation).
(c) Side-views of the crystal structures of the major and minor
conformers of DHP⊂1 showing the orientation of DHP within cage
1.
within the cage cavity such that the methyl groups are
accommodated within the widest, equatorial region of the cage.
No significant correlations are observed between the aromatic
protons H9−H11 from DHP and the cage. Similarly, no
significant correlations are observed between protons from the
axial region of the cage (H1−3), highlighted in red, and DHP.
The absence of these correlations indicates that DHP may be
spinning within the cavity of cage 1, with the methyl groups
remaining relatively fixed in the equatorial pockets of the cage
cavity. Given that only one set of signals corresponding to
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Figure 3. (a) Dynamic guest exchange involving DHP⊂1 and a sulfonated merocyanine. (b) Evolution of UV/vis absorption spectra upon mixing
DHP⊂1 with an equimolar amount of free MCH. (c) Evolution of UV/vis absorption spectra upon mixing MC⊂1 with an equimolar amount of
free DHP. (d) Following the absorbance at 600 nm (top; replotted from parts b and c) and emission at 670 nm (regions where encapsulated DHP
does not absorb and emit) over time (excitation wavelength, λexc = 550 nm). Purple markers, MC⊂1 + DHP; green markers, DHP⊂1 + MCH.
DHP to a solution of cage 1 in water, all DHP becomes
encapsulated (Supporting Information, section 6), and the
resulting linear titration curve cannot be fit to obtain an
accurate Kassoc value. The competition experiment described
above, however, can be used to estimate the strength of Kassoc
for DHP⊂1. Provided that equimolar amounts of MC and
DHP were used in our experiments, resulting in a ∼1:1
distribution of the two guests inside the cage at equilibrium
(Figure 3d), we conclude that DHP interacts with the cage
with an affinity similar to that of MC. This result arises from
several features shared by these guests; both compounds are
planar, highly conjugated, and they are similar in geometry,
with two methyl groups oriented orthogonally to the aromatic
system. As mentioned above, encapsulation of DHP and MC is
associated with a similar degree of structural rearrangement by
cage 1, which accumulates a similar energetic cost. This cost is
offset in part by similar π−π stacking interactions between the
cage panels and the aromatic guests DHP and MC.
Having extensively characterized the DHP⊂1 complex, we
studied DHP photoisomerization by irradiating an aqueous
solution of DHP⊂1 with blue light at 460 nm. The solution of
DHP⊂1 was observed to change from green to light-brown;
these visual changes were accompanied by changes in the UV/
vis spectra, which show a consistent decrease in the band
centered at 470 nm in the visible region (Figure 4a). We
recorded UV/vis spectra every 30 s and monitored conversion
to CPD⊂1 as a function of irradiation time (Figure 4b). For
comparison, we performed the same experiment under
identical irradiation conditions on free DHP in acetonitrile
(Figure 4c). In both cases, conversion proceeded according to
apparent first-order kinetics, with rate constants of 1.5 × 10−2
and 0.5 × 10−2 s−1 for free and encapsulated DHP,
respectively. From the ratio of these constants, it can be
inferred that the DHP → CPD photoisomerization quantum
yield decreases by a factor of 3 upon encapsulation. At the
same time, we note that CPD requires slightly more space than
does DHP, which likely contributes to the decrease in
isomerization rate that we observe under confinement. Indeed,
these results are consistent with the switching behavior of
diarylethenes confined within highly ordered polymer
martices.37
1
We also followed the reaction by H NMR spectroscopy
(Figure 4d). As the system was irradiated with blue light, the
diagnostic signals from DHP were observed to decrease as the
signals from encapsulated CPD increased. At each data point,
the molar composition of the system was calculated by
integrating the signal corresponding to H12 from DHP (−6.44
ppm) against H16 from CPD (−0.60 ppm) (see also Figure
1c). This analysis allowed us to conclude that the reaction was
near-quantitative, with up to 94% of CPD⊂1 at the
photostationary state (PSS) (obtained within <1 h for the 1
mM solution used for these NMR studies).
The resulting CPD⊂1 complex was characterized using 1D
and 2D NMR spectroscopy. The chemical shifts of CPD
protons H13−H15 were shifted upfield by 1.19−1.36 ppm,
whereas the methyl group (H16) experienced the largest shift,
from 1.52 ppm38 to −0.60 ppm (Figure S17). Similarly, the 1H
DOSY spectrum indicates that CPD and cage 1 diffuse at the
same rate, which confirms the formation of an inclusion
complex (Figure S18). Furthermore, 1H−1H COSY and
1H−1H NOESY spectra were used to assign all signals and
confirm that 1:1 binding stoichiometry is maintained after
isomerization (Figures S19 and S20). The NOESY correlations
observed for CPD’s methyl groups within CPD⊂1 were very
similar to those for DHP⊂1, which lead us to infer that they
reside within the edges of the cage identified by the equatorial
Pd atoms. In contrast to DHP⊂1, however, we found
additional host−guest correlations, which involved all CPD
protons (Figure S21).
Interestingly, H13 and H14 are correlated with H4 and H7
from the benzene and equatorial-imidazole regions of the cage.
This observation suggests that the guest assumes a well-defined
D
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which can be quantified by two parameters: d1, the distance
between the axial Pd atoms, and d2, the distance between the
midpoints of opposite edges of the cage identified by the
equatorial Pd atoms (see Figure 5a, inset). Figure 5a shows the
Figure 5. (a) Conformational free-energy landscape of empty cage 1,
mapped as a function of the distance between the axial Pd atoms (d1)
and the distance between the midpoints of opposite edges of the cage
identified by the equatorial Pd atoms (d2; see inset).39 The position of
the minimum-free-energy configuration of empty 1 is indicated with a
gray point; the dash-dotted line identifies the region within 0.5 kcal/
mol of the global minimum. Projected on the free-energy surface of 1
are energy minima (colored points) and regions within 0.5 kcal/mol
of the minima (lines) of DHP⊂1, CPD⊂1, and four other,
representative inclusion complexes involving photochromic guests.
(b) Side-views of DHP⊂1 and CPD⊂1 with isosurfaces of the density
of guest’s orientation (shown in orange). (c) Normalized distributions
of guest orientations within DHP⊂1 and CPD⊂1.
Figure 4. (a) A series of UV/vis absorption spectra of DHP⊂1
accompanying irradiation with 460 nm light. (b) Kinetics of
photoisomerization of DHP⊂1 to CPD⊂1 in water at 20 °C. (c)
Kinetics of photoisomerization of DHP to CPD in acetonitrile at 20
°C. Experiments in (b) and (c) were performed with the same
irradiation setup (λirr = 460 nm) under a pseudo-first-order regime
(A460 ≪ 1).47 Both time profiles were fitted with a first-order model
(gray lines), and apparent first-order rate constants are reported. (d)
1
Partial H NMR spectra (400 MHz, D2O) of DHP⊂1 recorded after
different times of irradiation with 460 nm light. Signals highlighted in
green and gray originate from DHP and CPD, respectively.
conformational free-energy surface (FES) of empty 1,39 where
the gray dash-dotted line identifies the region within 0.5 kcal/
mol from the global-minimum free-energy configuration of the
empty cage, denoted with a gray dot in the dark region of the
FES. The green and cyan dots denote free-energy minima of
the cage encapsulating DHP and CPD (i.e., DHP⊂1 and
CPD⊂1), respectively. As we have recently demonstrated, such
analysis of cage models provides information on the free-
energy cost associated with cage deformation upon guest
encapsulation.39 In this case, our results suggest that this free-
energy cost amounts to ∼6 kcal/mol for both DHP⊂1 and
CPD⊂1 (this cost is compensated by more favorable host−
guest interactions, which lead to guest encapsulation).
Remarkably, both the energy minima and the regions within
orientation, with protons H13 and H14 located within the open
windows of the cage. Unfortunately, despite extensive efforts,
we did not succeed in obtaining single crystals of CPD⊂1.
However, because of the remarkable agreement between the
NOESY and X-ray data for DHP⊂1, we anticipate that the
crystal structure of CPD⊂1 would similarly reflect the
solution-state structure determined by NMR.
To obtain further insight into the structures of DHP⊂1 and
CPD⊂1, we studied both inclusion complexes by atomistic
molecular dynamics (MD) simulations in explicit water.39
Upon binding guests, cage 1 undergoes structural deformation,
E
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0.5 kcal/mol of the minima were found to be very similar for
DHP⊂1 and CPD⊂1. This finding can be explained by the
relatively minor conformational change associated with the
isomerization of DHP to CPD. In sharp contrast, isomerization
of other photochromic systems, such as arylazopyrazole (dark-
blue) and tetra-o-methoxyazobenzene (violet), was accom-
panied by large changes in both d1 and d2 (Figure 5a),39 in
agreement with the large structural difference between the
trans and cis isomers of these compounds.
Next, we used MD simulations to study the orientation and
mobility of DHP and CPD guests inside cage 1. The orange
areas in Figure 5b describe the trajectories of the tips of the
orange arrows identifying the long axes of DHP and CPD (i.e.,
the lines connecting the two most distant carbon atoms of each
guest). The larger is the orange area, the higher is the mobility
of the guest within the cage during the equilibrium MD run.
The orange ring in Figure 5b, left, means that the DHP guest
can freely rotate inside the cage in a gyroscope-like
fashion,40−43 with its two methyl groups interacting stably
with the equatorial region of the cage. The facile rotation of
DHP within 1 can be explained by the guest’s structure, where
the methyl groups protrude perpendicular with respect to the
aromatic system. The interactions of these methyl groups with
the equatorial region of the cage position the aromatic system
of DHP precisely along the long axis of the cage (defined as
the black dotted line connecting two axial Pd atoms in Figure
5b), whereas the planarity of the aromatic system poses limited
steric hindrance to rotation. In contrast, the CPD guest
appears to be significantly more constrained in quasi-vertical
configuration (in the MD regime), with the orange trajectories
populated by its main axis located within ∼30° of the long axis
of the cage (Figure 5b, right). Analysis of a minimum-free-
energy configuration (Figure S24b) reveals that CPD’s methyl
groups interact with cage 1’s edges and its benzene rings
interact with the benzene rings of 1’s imidazole panels. These
interactions “lock” the CPD guest within the cage, which
explains the NOESY correlations involving cage 1 with all
protons from CPD (Figure S21).
The most favorable orientations of DHP and CPD within
the cage were quantified by calculating the distributions of
guest orientations, defined by the angle between the long axis
of the guest (orange arrows in Figure 5b) and the long axis of
the cage (black dotted line). The two maxima at ∼10° and
∼170° in the green curve in Figure 5c indicate that DHP
preferentially assumes a quasi-vertical orientation within the
cage. A smaller maximum at ∼90° suggests that a horizontal
orientation is also plausible. Remarkably, both of these guest
configurations have also been identified in the crystal structure
of DHP⊂1 (Figure 2c, left and right, respectively). On the
other hand, the calculated orientation distributions for the
CPD isomer (Figure 5c, blue line) confirm that it resides inside
the cage exclusively in a near-vertical orientation.
Figure 6. (a) Molar composition of the DHP⊂1/CPD⊂1 mixture
(green and empty markers, respectively) as a function of 460 and 254
nm irradiation time. The data are extracted from NMR spectra
recorded immediately after irradiation (for the original spectra, see
Figure S22). (b) Kinetics of the thermal back-isomerization of
CPD⊂1 to DHP⊂1 in water at 20 °C. (c) Kinetics of the thermal
back-isomerization of CPD to DHP in acetonitrile at 20 °C. The data
in both (b) and (c) are consistent with first-order kinetics, as
indicated by the gray lines (data fitting).
UV light. These results indicate that the photoswitching is
near-quantitative in both directions (Figure 6a). Although even
higher conversions can be achieved for nonencapsulated DHP
in acetonitrile, the reaction cycle is accompanied by a
significant degree of decomposition (Figure S25).
The ring-closing reaction (CPD → DHP) not only occurs
upon irradiation with UV light but also spontaneously in the
dark. To investigate the rate of this back-reaction, we followed
the conversion of CPD⊂1 to DHP⊂1 in the dark by UV/vis
spectroscopy over time (Figure 6b); by comparing the spectral
changes for solutions of CPD⊂1 in water and free CPD in
acetonitrile (Figure 6c), we found that the reaction in both
cases obeyed first-order kinetics, with kinetic constants of 2.0 ×
10−6 and 2.3 × 10−6 s−1, respectively. The negligible difference
between these two values suggests that confinement within
cage 1 does not significantly influence the rate of back-
isomerization. This finding is in agreement with our MD
simulations, which suggest that the structural changes
associated with isomerization from CPD to DHP can be
readily accommodated within the cavity of cage 1.
Having extensively characterized the 1:1 inclusion com-
plexes DHP⊂1 and CPD⊂1, we investigated the reversibility
Because DHP isomerization is thought to proceed through a
biradical species,6,7 the fatigue resistance of this process may be
compromised by oxidative and radical−radical decomposition
pathways. To determine if confinement within cage 1 would
contribute additional stabilization to this reaction, we
compared the fatigue experienced by encapsulated and free
DHP over 10 isomerization cycles (Figure 7). Because DHP is
insoluble in water, we chose to compare the behavior of
aqueous DHP⊂1 with that of free DHP dissolved in pentane,
which is stable under the conditions used for the cycling
experiment and does not readily react with radical species. To
1
of photoisomerization by H NMR and UV/vis absorption
spectroscopy (Figure 6). The back-isomerization reaction can
be induced by irradiation with UV light at 254 nm. Indeed, by
exposing a solution of CPD⊂1 to 254 nm, the signals
corresponding to DHP were observed to re-emerge, and a new
PSS comprising as much as ∼98% of DHP⊂1 was reached
within 40 min (for the 1 mM solution used in the NMR
studies). Remarkably, we observed negligible cage decom-
position, despite prolonged irradiation with highly energetic
F
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allows the cavity to adapt in response to guest isomerization.
Consequently, confinement within the cage does not
significantly impact conversion between DHP and CPD,
which could be realized with very high yields in both
directions. Instead, confinement within cage 1 serves as a
protective environment for the reactive intermediate involved
in this reaction, minimizing bimolecular events and improving
fatigue resistance during photoswitching cycles. In short, the
cage protects DHP from photodegradation without compro-
mising efficient photoswitching. The degree of stabilization is
remarkable given the open structure of the cage and rapid
exchange kinetics found for a structurally similar guest
(sulfonated merocyanine). While confinement is known to
contribute to stabilizing reactive species, previous examples
typically utilize this effect for accelerating reactions or for
trapping and visualizing transient species.44−46 Significantly,
this work introduces the idea that stabilization within confined
spaces can improve the yield of a reaction by preserving an
unstable intermediate from degradation. While this particular
system is limited to water, which drives encapsulation of DHP
due to the hydrophobic effect (Supporting Information,
section 14), this strategy can in principle be extended to
confined environments in a wide variety of solvents. We
envisage that confinement of DHP may improve its utility for
applications requiring high-performance photoswitches. Fur-
thermore, we anticipate that this approach is extensible to
improving the yield of other reactions. In traditional organic
chemistry, side-products are often generated due to undesir-
able reactions involving a reactive intermediate. When an inert
environment is provided for such intermediates, confinement
could thus provide a means to minimize side-products and
improve reaction yield.
Figure 7. (a) Poor fatigue resistance of free DHP in pentane solution
over 10 switching cycles. (b) Improved fatigue resistance of DHP⊂1
in water over 10 switching cycles. Deoxygenated solvents were used.
In each cycle, the samples were exposed to 10 min of blue light (λ =
460 nm) followed by 10 min of UV light (λ = 254 nm).
ASSOCIATED CONTENT
■
sı
* Supporting Information
avoid the interference of oxygen in the switching process, the
solvents were deoxygenated by bubbling N2.
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.0c06146.
Deoxygenated solutions of DHP⊂1 in water and DHP in
pentane (at concentrations in the micromolar range) were
prepared, and cyclic isomerization of the two solutions was
achieved in parallel by irradiating both samples with blue light
at 460 nm (10 min), then UV light at 254 nm (10 min); this
process was followed by UV/vis spectroscopy. After 10 cycles,
we calculated that 28% of free DHP in pentane was lost due to
fatigue (Figure 7a). As anticipated, however, confinement
within cage 1 contributed significantly to stabilizing the
photochemical conversion between DHP and CPD. Only 8%
of encapsulated DHP was observed to decompose after
completion of this experiment (Figure 7b). When the above
experiment was repeated in water that had not previously been
deoxygenated, 13% of DHP was observed to decompose after
10 irradiation cycles under otherwise identical conditions. The
additional decomposition experienced by DHP in the presence
of oxygen is unsurprising given the large open windows within
the cage framework, which allow oxygen to easily access
encapsulated photoswitch (Figure S26). Significantly, the
fatigue experienced by DHP in this experiment remains far
lower than the fatigue experienced by free DHP in
deoxygenated pentane.
General information, synthesis and characterization of
triimidazole ligand, synthesis and characterization of
cage 1, synthesis and characterization of DHP, formation
and characterization of DHP⊂1, UV/vis titration of cage
1 with DHP, X-ray data collection and structure
refinement of DHP⊂1, comparison of the crystal
structures of DHP⊂1 and MC⊂1, guest exchange
experiments, formation and characterization of
CPD⊂1, molecular dynamics simulations, photoisome-
rization study of free DHP in acetonitrile, photo-
isomerization study of DHP⊂1 in nondeoxygenated
water, study of release of DHP from cage 1 using
acetonitrile, and supplementary references (PDF)
X-ray crystal structure of DHP⊂1 (CIF)
AUTHOR INFORMATION
Corresponding Author
■
Rafal Klajn − Department of Organic Chemistry, Weizmann
Institute of Science, Rehovot 76100, Israel; orcid.org/0000-
0002-6320-8875; Email: rafal.klajn@weizmann.ac.il
Authors
CONCLUSIONS
Martina Canton − Department of Organic Chemistry,
Weizmann Institute of Science, Rehovot 76100, Israel; Center
for Light-Activated Nanostructures (CLAN) and Dipartimento
■
In this work, we have shown that DHP and CPD form 1:1
inclusion complexes with cage 1, and the flexibility of the cage
G
https://dx.doi.org/10.1021/jacs.0c06146
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Joakim Andreasson − Department of Chemistry and Chemical
Engineering, Chalmers University of Technology, Goteborg
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge funding from the European Union’s Horizon
2020 research and innovation program under the European
Research Council (ERC) grant agreements 820008 (to R.K.),
818776 (to G.M.P.), and 692981 (to A.C.) and the Marie
Skłodowska-Curie grant agreement no. 812868 (to J.G.), the
Swedish Research Council VR (grant agreement 2016-03601
to J.A.), the Swiss National Science Foundation (grant
agreement 200021_175735 to G.M.P.), and the Minerva
Foundation with funding from the Federal German Ministry
for Education and Research (R.K.). L.P. and G.M.P.
acknowledge the computational resources provided by the
Swiss National Supercomputing Center (CSCS). A.B.G.
acknowledges funding from the Zuckerman STEM Leadership
Program.
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