Multi-Stimuli-Responsive Interconversion between Bowl- And Capsule-Shaped Self-Assembled Zinc(II) Complexes

Article abstract of DOI:10.1021/jacs.9b11099

Self-assembled metal-organic architectures have great potential to undergo major structural changes into different architectures. Such molecular transformation is widely applicable to responsive systems like drug delivery and allosteric catalysis. A great

Full text of DOI:10.1021/jacs.9b11099

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Article
Multi-Stimuli Responsive Interconversion between Bowl-
and Capsule-Shaped Self-Assembled Zinc(II) Complexes
Kenichi Endo, Hitoshi Ube, and Mitsuhiko Shionoya
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b11099 • Publication Date (Web): 05 Dec 2019
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Multi-Stimuli Responsive Interconversion between Bowl- and Capsule-
Shaped Self-Assembled Zinc(II) Complexes
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Kenichi Endo, Hitoshi Ube, and Mitsuhiko Shionoya*
Department of Chemistry, Graduate School of Science, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-
0033, Japan
Supporting Information
ABSTRACT: Self-assembled metal-organic architectures have great potential to undergo major structural changes into dif-
ferent architectures. Such molecular transformation is widely applicable to responsive systems like drug delivery and allo-
steric catalysis. A great number of metal-organic architectures responsive to a specific stimulus have been reported so far.
However, interconversion between a pair of distinct metal-organic structures in response to multiple stimuli is rarely re-
ported despite its high versatility. Herein we report multi-stimuli responsive interconversion between a bowl-shaped and a
capsule-shaped self-assembled ZnII complexes, [ZnII L3X6] and [ZnII L4], respectively, which were found to form in equilibrium
4
4
from porphyrin-based ligand L and ZnII ions with different stoichiometry. Specifically, this interconversion was induced by
four distinct external stimuli: exogenous ligands, Brønsted base/acid, solvents, and guest molecules. The mechanisms of the
interconversion system are discussed in detail focusing on the species included in the equilibria. Thus, these findings would
provide a helpful clue to design principles for multi-stimuli responsive systems with functional versatility.
though few in number, give different transformation prod-
uctsdepending on the type of stimuli.18 Sofar, there are only
a few examples in which interconversion between a pair of
distinct self-assembled structures can be induced by three
types of stimuli.19 Thus, development of a pair of metal-or-
ganic architectures which can be interconverted in re-
sponse to multiple stimuli would provide a useful insight to
construct new molecular switching systems for various ap-
plications.
■
INTRODUCTION
Cage-shaped discrete supramolecular structures made by
self-assembly of small components often exhibit unique
guest recognition abilities.1 Among them, metal-organic
cages built by ligand coordination to metal ions have been
extensively investigated taking advantage of their synthetic
ease and high designability.2,3 Their application has burst
out in many directions such as catalysis, ion channels, or
drug delivery.2c,4,5 Meanwhile, their structures are intrinsi-
cally dynamic and sometimes can be transformed into other
structures by external stimuli.6 Such molecular transfor-
mation can alter the shape and nature of their inner space,
and enable switching of guest encapsulation7 or catalytic
function.8 This behavior is closely related to natural pro-
teins, which can be dynamically transformed and regulated
in signal transduction.9 Thus, structural transformation of
metal-organic cages has been an attractive research subject
not only to understand the complexity of biological systems
but also to develop materials with a switching function that
works on demand.
To elaborate such multi-stimuli responsive metal-organic
cages, we used a ZnII-porphyrin-based ligand in view of
their high designability and functions. We20 and other
groups21 have previously reported a number of metal-or-
ganic cages constructed from porphyrin-based ligands.
While the unique structural and electronic features of por-
phyrins can possibly provide functions related to photo-
chemistry or catalysis, their intricate self-assembled struc-
tures have proven to be drastically affected by subtle
changes in chemical surrounding in some cases.20a,c,21b,c
Herein we report a multi-stimuli responsive interconver-
sion system between a bowl-shaped [ZnII L3X6] (1, X = sol-
4
In the last two decades, a great number of examples have
been reported on structural transformations of metal-or-
ganic cages by a variety of contributing factors. Their trans-
formation can be triggered by a change in the metal-ligand
stoichiometry,10 exogenous ligands,10b,11 solvents,12 guest
molecules,13 concentration,12b,14 light,15 and some other
stimuli.16 In general, these transformations can be induced
by a specific kind of stimulus for each case. However, in con-
trast, biomolecules or their self-assembled systems often
exhibit responses to a wide variety of stimuli to achieve
high versatility and functionality.17 Most of previously re-
ported metal-organic cages responsive to multiple stimuli,
vent or counterion) and a capsule-shaped [ZnII L4] (2),
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formed from porphyrin-based ligand L and ZnII (Figure 1).
These two structures can be interconverted not only by al-
tering the metal-ligand stoichiometry but also by other ex-
ternal stimuli such as exogenous ligands, Brønsted
base/acid, solvents, and guest molecules. The difference in
metal-ligand ratios between the two complexes has signifi-
cant influence on their multi-stimuli responsiveness in the
interconversion. Understanding of such a molecular inter-
conversion system responsive to various external stimuli
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would advance the design principles of multi-stimuli re-
sponsive systems with functional versatility.
ter-ligand NOE patterns of both bowls 1 and 1’ were com-
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pletely correlated with the crystal structure of 1’ (Figures
S3 and S10). These results thus suggest that the solution
structure of bowl 1 agrees with the crystal structure of 1’.
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Figure 1. Schematic representation of the multi-stimuli re-
sponsive interconversion between two self-assembled ZnII
complexes examined in this study. The axial ligands bound to
the ZnII porphyrin centers are omitted from the chemical struc-
tures for clarity and for ambiguity in solution.
■
RESULTS AND DISCUSSION
Formation of a Bowl-Shaped Complex [ZnII L3X6] (1).
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We have previously reported that a ZnII-porphyrin-based
ligand L bearing three 2,2’-bipyridin-5-yl (= bpy) groups
self-assembles with CoII ions to form a bowl-shaped CoII
complex, [CoII L3X6] (X = solvent or counterion).20d In this
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Figure 2. The formation of a bowl-shaped complex [ZnII L3X6]
4
study, self-assembly of L with ZnII ions was examined focus-
ing on its geometrically more flexible nature to develop a
molecular responsive system.
(1, X = solvent or counterion).(a) Reaction scheme: L·OTf·3H2O
1
+ Zn(OTf)2 (1.4 eq), CD3CN, [L] = 1.0 mM, 70 °C, 12 h. (b) H
NMR spectrum (500 MHz, 300 K, CD3CN) of bowl 1. Inset shows
the labeling of hydrogen atoms of L. (c) ESI-MS spectrum (pos-
itive, CD3CN) of bowl 1. Inset shows the comparison of the sim-
ulated and experimental isotope distributions of
[Zn4L3(OTf)8]3+.
Firstly, a bowl-shaped complex [ZnII L3X6] (1) was pre-
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pared by mixing L·OTf·3H2O andZn(OTf)2 (1.4 eq) in CD3CN
at 70 °C for 12 h (Figure 2a). 1H NMR study including 1H-1H
COSY and NOESY demonstrated that this reaction produced
one major product in which the ligand moieties are chemi-
cally equivalent while each ligand was desymmetrized from
C2v to C1 symmetry upon complexation (Figure 2b). The ESI-
Based on this finding, we developed a structure model of
bowl 1 optimized by DFT calculation (PBE/DND/COSMO)
(Figure 3, Supporting information for calculation details).
The theoretical hydrodynamic radius of this model (14.8 Å
without counterions) was in good accordance with the ex-
perimental one calculated from the 1H DOSY NMR spectrum
(16.7 Å, Figure S4). In this complex, four ZnII ions and three
ligands L are assembled into an open trigonal bowl. There
exist two types of ZnII centers bound by bpy moieties. The
ZnII center at the bottom is coordinated by three bpy moie-
ties to form a ZnII(bpy)3 motif (Figure 3c). The other three
ZnII centers onthe peripheryare boundbytwo bpymoieties
and have two labile coordination sites ina ZnII(bpy)2X2 fash-
MS measurement indicated the formation of a ZnII L3 com-
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plex (Figure 2c). These results supported the formation of
bowl 1. The yield of bowl 1 was estimated to be 59% from
1H NMR using an internal standard.
The molecular structure of bowl 1 was examined by com-
parisonwith that ofan analogous complex [ZnII L’3X6](bowl
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1’) prepared from a derivative L’ (Scheme S1), as no single
crystals were obtained for 1 despite many trials. The molec-
ular structure of bowl 1’ was determined by XRD analysis
as shown in Figure S19. Its solution-phase structure was
then analyzed by 1H-1H NOESY NMR spectroscopy. The in-
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ion (Figure 3d). Although the ligands X at the labile coordi- a result of a simple extension of bowl 1 but nearly reassem-
bly from ZnII ions and L. The whole structural framework of
2 has an approximately S4 symmetry with minor deviations
attributable to the packing effect. The volume of the intra-
molecular cavity of 2 was estimated to be 393 Å3 (at Con-
nolly radius = 1.6 Å).
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nation sites were modeled as water molecules here accord-
ing to the crystal structure of bowl 1’, they can be other sol-
vent molecules or counterions depending on the chemical
environment. All the centers of both ZnII(bpy)3 and
ZnII(bpy)2X2 show the same handedness (i.e. DDDD or
LLLL) probably due to the stereochemical communication
through the rigid ligand L. The whole structural framework
of bowl 1 has a C3 symmetry.
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Figure 3. A DFT-optimized (PBE/DND/COMSO) structure of
bowl 1 (X = OH2). (a) A ball-stick presentation from the side.
(b) A space-filling presentation down from the C3 axis. (c) The
partial structure around the Zn(bpy)3 center. (d) The partial
structure around one of the ZnII(bpy)2X2 centers. The model
was developed from the crystal structure of an analogous com-
plex, bowl 1’ (Scheme S1). The axial ligands of ZnII-porphyrin
centers were modeled by water molecules coordinated from
inside but are omitted for clarity. No anions are modeled here.
Color code: Zn, orange (at ZnII(bpy)2X2), pink (at ZnII(bpy)3), or
gray (at porphyrin); C, black; N, blue; O, red. Lines are drawn
between Zn(bpy)n centers to guide the eye.
Figure 4. The formation of a capsule-shaped complex [ZnII L4]
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(2). (a) Reaction scheme: L·OTf·3H2O + Zn(OTf)2 (1.0 eq),
CD3CN, 1.0 mM, 70 °C, 16 days. (b–d) A single-crystal XRD
structure of capsule 2: (b) A ball-stick presentation from the
side. (c) A space-filling presentation down from the pseudo-S4
axis; (d) A partial structure around one of the Zn(bpy)3 centers.
The axial ligands at ZnII-porphyrin centers, counterions, and
solvent molecules are omitted for clarity. Color code: Zn, pink
(at the ZnII(bpy)3) or gray (at the porphyrin); C, black; N, blue;
O, red. Lines are drawn between ZnII(bpy)3 centers to guide the
eye.
Formation of a Capsule-Shaped Complex [ZnII L4] (2)
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by Altering Metal-Ligand Stoichiometry. Next, we exam-
ined the effects of metal-ligand stoichiometry onthe self-as-
sembly process. The reaction of L·OTf·3H2O with Zn(OTf)2
(1.0 eq) in CD3CN/D2O = 9:1 at 70 °C yielded a distinct, cap-
sule-shaped complex [ZnII L4] (2) in 90% yield as estimated
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from 1H NMR using an internal standard (Figure 4a, S12).
The solid-state structure of capsule 2 was determined by
single-crystal XRD analysis (Figure 4b–d). Capsule 2 con-
sists of four ZnII ions and four ligands L in the tetrahedron-
capsule shaped structure, in which all the four ZnII centers
adopt a ZnII(bpy)3 motif. Notably, the absolute configura-
tions of the ZnII centers are ΔΔΛΛ (cf. ΔΔΔΔ or ΛΛΛΛ for
bowl 1), demonstrating that the structure ofcapsule 2 is not
The solution-phase characterization of capsule 2 was
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conducted by ESI-MS spectrometry and H and 19F NMR
spectroscopy. The ESI-MS spectrum of a CD3CN solution
n+
showed a set of signals for [Zn4L4(OTf)12-n
]
(n = 3–8),
which suggests that the [ZnII L4] structure was maintained
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in solution (Figure S14). 1H and 19F NMR spectra showed a ZnII/L = 1.4) was further added to this solution. After heat-
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solvent-dependent difference in the anion inclusion behav-
iors. In CD3CN/D2O = 1:1 (v/v), all the signals in the 1HNMR
spectrum were assigned to one type of ligand framework
ing at 70 °C for 13 days, although the conversion was still
ongoing beyond the reaction time, the ratio reached 1:2 =
82:18. Thus, the interconversion between bowl 1 and cap-
sule 2 was thermodynamically induced by altering metal-
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(Figure 5a) based on H-1H COSY and NOESY techniques.
The inter-ligand NOEs observed in the NOESY NMR spec-
trum were consistent with the crystal structure, suggesting
that the crystal structure of capsule 2 is maintained in solu-
tion (Figure S19). On the other hand, when 1H NMR spec-
trum was measured in CD3CN, two sets of signals were ob-
served (Figure 5b). Moreover, 19F NMR spectrum showed
one small signal in a stronger magnetic field compared with
another large signal of coordinatively free TfO− (Figure 5c).
This suggests the inclusion of TfO− ion(s) in the cavity of
capsule 2. The hydrodynamic radius calculated from the 1H
DOSY NMR spectrum (15.6 Å, Figure S14) was in good ac-
cordance with the theoretical one from the crystal structure
(13.3 Å without counterions).
l i g a n d
s t o i c h i o m e t r y .
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Figure 6. The effect of metal-ligand stoichiometry was exam-
ined on the interconversion between bowl 1 and capsule 2. (a)
Reaction scheme. (b–d) 1H NMR spectra (500 MHz, 300 K,
CD3CN): (b) L·OTf·3H2O + Zn(OTf)2 (1.4 eq) in CD3CN (ZnII/L
=1.4), 1.0mM, 70 °C, 12 h; (c)(b) + L·OTf·3H2O (0.40 eq) (ZnII/L
=1.0), 70 °C, 7 days; (d) (c) + Zn(OTf)2 (0.56 eq) (ZnII/L =1.4),
70 °C, 13 days.
ChemicalResponses to Various ExternalStimuli. Next,
we attempted to induce the interconversion between bowl
1 and capsule 2 using various external stimuli. When the
ZnII/L ratio is 1.4, the interconversion between 1 and 2 is
supposed to obey eq (1). As this interconversion is associ-
atedwiththe compositional change between1 and 2, eq (1)
includes [ZnIIX6] species in the right side of the equilibrium.
Accordingly, we expected that the presence of the [ZnIIX6]
species may allow this interconversion between 1 and 2 to
be induced by multiple stimuli without affecting the struc-
tures of 1 and 2.
Figure 5. Solution-phase characterization of capsule 2. (a) 1H
NMR spectrum (500 MHz, 300 K, CD3CN/D2O = 1:1 (v/v)) of 2.
Inset shows the labelling of hydrogen atoms of L. (b) 1H NMR
spectrum of 2 in CD3CN. The violet arrows indicate the signals
of the inclusion complex with TfO−. (c) 19F NMR spectrum (471
MHz, 300 K, CD3CN) of 2. The violet arrow indicates the signal
of the encapsulated TfO−.
4[ZnII L3X6] (1) ⇄ 3[ZnII L4] (2) + 4[ZnIIX6]
(1)
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Interconversion between the Bowl- and Capsule-
Shaped ZnII Complexes by Changing Metal-Ligand Stoi-
chiometry. To examine whether these two ZnII complexes
are interconvertible, the metal-ligand stoichiometry was
altered in stages (Figure 6). Firstly, L·OTf·3H2O and
Zn(OTf)2 (1.4 eq, ZnII/L = 1.4) were mixed in CD3CN at 70 °C
for 12 h. The 1H NMR spectrum showed the ratio of bowl 1
to capsule 2 was 98:2. L·OTf·3H2O (0.40 eq to the initial
amount of L, ZnII/L = 1.0) was then added to the solution.
After heating the reaction mixture at 70 °C for 7 days, cap-
sule 2 increased with a decrease in bowl 1, and eventually
the ratio reached 1:2 = 1:99. In contrast to this conversion,
the reverse structural change took place from capsule 2 to
bowl 1 when Zn(OTf)2 (0.56 eq to the initial amount of L,
With this view, we examined the effects of a series of ex-
ternal stimuli on the interconversion between bowl 1 and
capsule 2. As a result of the experiments, we found that a
variety of stimuli induce the interconversion between 1 and
2. Specifically, exogenous ligands, Brønsted base/acid, sol-
vents, and guest molecules have been proven to induce the
reversible structural changes between 1 and 2 as discussed
below.
Interconversion Triggered by Exogenous Ligands.
Firstly, we tested to see if exogenous ligands such as a bi-
dentate ligand, 1,10-phenanthroline (phen), affect the inter-
conversion (Figure 7). A solution of bowl 1 was prepared
from L·OTf·3H2O and ZnII(OTf)2 (1.4 eq) in CD3CN at 70 °C,
and then phen (1.4 eq) was added to this solution at room
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temperature. Its 1H NMR spectrum after 5 min showed the
monodentate (N-methylimidazole, (R)-1-phenylethyla-
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appearance of a new species assigned to 1·(phen)3. When
the reaction mixture was heated at 70 °C for 6 days, the 1H
NMR spectrum further changed and demonstrated the for-
mation of capsule 2 in 83% conversion with simultaneous
presence of [ZnII(phen)3]2+. Therefore, this conversion can
be formulated as eq (2).
mine), and anionic (acetate, thiocyanate, chloride, bromide,
and iodide) ligands indicated a similar tendency of conver-
sion patterns and mechanisms.
The reverse conversion fromcapsule 2 to bowl 1 wasalso
possible in some cases. In the case of bromide anion, for in-
stance, capsule 2 generated was converted back to bowl 1
by the use ofAgOTf (Figure S33). Inthe case of acetate anion,
La(OTf)3, which can trap acetate anions, was effective in a
similar manner (Figure S34). In this way, the interconver-
sion between bowl 1 and capsule 2 was induced by exoge-
nous ligands.
4[ZnII L3(phen)3] (1·(phen)3)
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→ 3[ZnII L4] (2) + 4[ZnII(phen)3]
(2)
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The conversion from bowl 1 to capsule 2 was supposed
to be initiated by the coordination of phen to the three
ZnII(bpy)2X2 moieties of 1 to form 1·(phen)3. Then, further
ligandexchange occurs to form2 and [ZnII(phen)3]2+. Unlike
eq (1), eq (2) contains [ZnII(phen)3]2+ and 1·(phen)3 instead
of [ZnIIX6] and 1, respectively. The formation of
[ZnII(phen)3]2+ would provide higher stabilization than that
of 1·(phen)3 because before addition of phen the
ZnII(bpy)2X2 moieties of 1 are more stabilized by the coor-
dination of two bidentate bpy ligands compared withZnIIX6.
Thus, additionof phen predominantly shiftsthe equilibrium
balance from 1 to 2.
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Interconversion Triggered by Brønsted Base/Acid.
Next, as a more indirect method to trap ZnII ions, the effects
of Brønsted base/acid were examined (Figure 8). To a solu-
tion of bowl 1, prepared from L·OTf·3H2O and Zn(OTf)2 (1.4
eq) in CD3CN, was added N,N-diisopropylethylamine
(iPr2NEt, 0.67 eq) followed by heating at 70 °C for 13 days.
The conversion ratio of bowl 1 to capsule 2 reached 1:2 =
10:90 as shown in the 1H NMR spectra (Figure S33). Then,
trifluoromethanesulfonic acid (TfOH, 0.67 eq) was added to
the solution and heated at 70 °C for 12 days. The acid addi-
tion resulted in the conversion back to bowl 1 with the ratio
of 1:2 = 79:21.
Figure 8. The effect of Brønsted base/acid was examined on
the interconversion between bowl 1 and capsule 2. The mole
fractions of bowl 1 and capsule 2 after the application of each
stimulus were determined by 1H NMR. (i) L·OTf·3H2O +
Zn(OTf)2 (1.4 eq), CD3CN (containing 28 mM H2O), 1.0 mM,
70 °C, 15 h; (ii) (i) + iPr2NEt (0.67 eq), 70 °C, 16 days; (iii) (ii) +
TfOH (0.67 eq), 70 °C, 12 days.
Figure7.Phenanthroline (phen) wastestedasa chemical stim-
ulus to induce conversion from bowl 1 to capsule 2. (a) Reac-
tion schemes. (b–d) 1H NMR spectra (500 MHz, 300 K, CD3CN):
(b) L·OTf·3H2O + Zn(OTf)2 (1.4 eq), CD3CN, 1.0 mM, 70 °C, 16 h;
(c) (b) + phen (1.4 eq); (d) (c) + heating at 70 °C for 6 days.
In the conversion from bowl 1 to capsule 2, quantitative
protonation of iPr2NEt was observed by 1H NMR spectros-
copy (Figure S35). The proton should come from H2O con-
tained inCD3CN (28 mM as determinedby 1H NMR analysis).
Since the amount of iPr2NEt used was two equivalents to 1,
this interconversion can be formulated as eq (3) including
the generation of Zn(OH)2. The formation of Zn(OH)2 can be
regarded as consumption of [ZnX6] in eq (1), which should
shift the equilibrium to the right. This result demonstrates
that addition of Brønsted base/acid is also effective for the
interconversion between bowl 1 and capsule 2.
Chart 1. Exogenous ligands used as chemical stimuli.
4[ZnII L3X6] (1) + 8iPr2NEt + 8H2O
4
→ 3[ZnII L4] (2) + 4Zn(OH)2 + 8[iPr2NHEt] + 24X
(3)
4
Not only phen but also several other ligands shown in
Chart 1 induced the conversion from 1 to 2 (Figures S25–
S32). Neutral bidentate (phen, ethylenediamine), neutral
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complex 4⊂1 in association with the release of guest 3
InterconversionTriggered bySolvents. The stimuli de-
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scribed above were found effective for the interconversion
at the concentrations comparable to those of ligand L. Then,
we turned our attention to a bulk constituent, that is, sol-
vent. Addition of water was firstly examined. D2O was ti-
tratedto a CD3CN solution ofbowl 1 on heating at 70°C until
equilibrium was reached with respect to each addition of
D2O (Figures 9 and S36). Bowl 1 was gradually converted to
capsule 2 with an increase in the proportion of D2O, and the
proportion of 2 reached 87% when the mole fraction of D2O
reached 22%. The reverse conversion was achieved by
evaporation of all the solvents followed by addition of
CD3CN and subsequent heating (Figure S36).
from capsule 2. The inclusion complex 4⊂1 was well-char-
acterized by 1H NMR spectroscopy and ESI-MS (Figures S43
and S44). In this process, the original guest 3 was replaced
by guest 4 because of the strong donor-acceptor stacking
interactions between 4 and the porphyrin rings of 1. Since
guest 4 is too large to be included in the cavity of capsule 2,
the host was again reconfigured to form bowl 1 with an
open cavity including guest 4. This interconversion should
also follow eq (1) representing the formation of [ZnIIX6].
This result demonstrates that the interconversion between
bowl 1 and capsule 2 can be triggered by guest molecules
as well.
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Figure 9. The effect of the mole fraction of D2O to CD3CN was
examined on the interconversion between bowl 1 and capsule
2. The mole fractions of 1 and 2 against that of D2O to CD3CN
were determined by 1H NMR. To a solution of L·OTf·3H2O (0.78
mM) containing Zn(OTf)2 (1.4 eq), after heating at 70 °C for 17
h, D2O wasadded portionwise to the solution, followed by heat-
ing at 70 °C until the equilibrium was reached for each point.
Lines are drawn to guide the eye.
Some other solvents other than D2O also led to solvent-
specific ratios of bowl 1 to capsule 2 (Figures S37–40). For
example, addition of DMSO-d6 in the mole fraction of 2.2%
resulted in the ratio of 1:2 = 30:70. The relationship be-
tween the solvent parameters and the resultant ratios re-
mains unclear, but the coordinating ability of the solvent to
the [ZnIIX6] species in eq (1) and the outer-sphere solvation
energy of each species are possible factors affecting the in-
terconversion between 1 and 2.
Figure 10. Interconversion between bowl 1 and capsule 2 in-
duced by guest molecules 3 and 4. (a) Reaction scheme of this
interconversion. (b–d) 1H NMR spectra (500 MHz, 300 K,
CD3OD/D2O = 1:1); (b) L·OTf·3H2O + Zn(OTf)2 (1.4 eq), CD3CN,
1.0 mM, 70 °C, 14 h; (c) (b) + guest 3 (saturated), 70 °C, 13 h;
(d) (c) + guest 4 (0.42 eq), 70 °C, 4 h.
Interconversion Triggered by Orthogonal Guest
Binding. Finally, we examined the effect of guest inclusion
in bowl 1 and capsule 2 on their interconversion in
CD3OD/D2O = 1:1 (Figure 10). To a solution of bowl 1 in the
mixed solvent was added a saturating amount of adaman-
tane (3). After heating at 70 °C for 13 h, the 1H NMR spec-
trum showed the conversion from bowl 1 to capsule 2 (1:2
= 41:59) in association with the appearance of signals in a
higher field attributable to encapsulated 3 in capsule 2 This
inclusion complex 3⊂2 was also characterized by ESI-MS
(Figure S42). This conversion can be interpreted as an “in-
duced-fit” phenomenon,2a since the cavity of capsule 2 gives
a better isolated environment from bulk solvent for 3 than
that of bowl 1.
Inclusion of Guest Anions Induced by Structural Con-
version. To extend the utility of the structural conversion,
we examineda switching function of guest inclusion. Firstly,
we paid attention to TfO− ion originally included in this sys-
tem as the counterion. The 1H and 19F NMR spectra of bowl
1 in CD3CN showed only one set of signals, indicating the
exchange of TfO− between inside and outside the cavity, if
any, was faster than the NMR timescale (Figures 2b and S5).
On the other hand, those of capsule 2 in CD3CN showed two
sets of signals corresponding to TfO−⊂2 and free 2 or TfO−,
respectively, indicating the inclusion of TfO− inside the cap-
sule in a slow exchange (Figure 5). This difference reflects
the open and closed shapes of bowl 1 and capsule 2, respec-
tively. In the interconversion experiments by metal-ligand
stoichiometry, exogenous ligands, and Brønsted base/acid,
Further addition of a sulfonamide derivative 4 to this so-
lution and subsequent heating resulted in the conversion of
capsule 2 back to bowl 1 (1:2 = 89:11) as another inclusion
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the 1H NMR signals of each complex showed the same pat- 1 to capsule 2 occurred even though the ZnII/L stoichiome-
try was kept constant at ZnII/L = 1.4. In these cases, [ZnIIX6]
species as well as 1 and 2 must be considered stoichiomet-
rically in the equilibrium (Figure 12). Interestingly, when
ligand X was replaced with a strong ligand, it works as trap-
ping of ZnII to shift the equilibrium in a waythat is favorable
for the formation of capsule 2, as described above for the
effects of exogenous ligands.
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3
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tern as bowl 1 or one set of signals for capsule 2 with and
without TfO− inside (e.g. Figure 6). These results suggest
that a TfO− ion can be included or released in response to
external stimuli resulting in the interconversion between
bowl 1 and capsule 2.
Based on this result, methanesulfonate (MsO−) was exam-
ined as another guest ion. In contrast to TfO−, MsO− was
found almost quantitatively included inside capsule 2 (Fig-
ure S45). To achieve switching of inclusion, we employed Cl
− as an exogenous ligand to induce transformation (Figure
11). First, nBu4N·OMs (0.25 eq) was added to a solution of
bowl 1, prepared from L·OTf·3H2O and Zn(OTf)2 (1.6 eq) in
The equilibrium balance can be affected in part by the lig-
and deformation. The ligand L is far more distorted in cap-
sule 2 than in bowl 1, as estimated by their DFT-optimized
models (PBE/DND/COSMO, Figure 12). This ligand defor-
mation, possibly along with solvation effects, favors the left
side in this equilibrium in the absence of specific stimuli.
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1
CD3CN. As the H NMR spectrum of bowl 1 remained un-
changed, MsO− was not included inside bowl 1. nBu4N·Cl
(1.6 eq) was then added to this solution asan exogenous lig-
and to induce conversion. After heating at 70 °C for 2 days,
the 1H NMR spectrum showed the conversion from bowl 1
to MsO−⊂2 (1:MsO−⊂2 = 30:70). This result suggests that
For kinetic consideration, the conversion from bowl 1 to
capsule 2 looks as if one more ligand L is added as a “lid” to
bowl 1. However, the actual mechanism is supposed to be
rather complicated as suggested by their structures. In the
unsymmetrical ligand L, there are two difficult types of bpy
moieties: (α) a bpy moiety in the trans position to the N-
methylpyridinium group and (β) two bpy moieties in the cis
position to the N-methylpyridinium group on the porphyrin
ring. In bowl 1, every neighboring pair of ligand L is con-
nected by two ZnII centers in an αα-ββ mode, while in cap-
sule 2 they are connected in an αβ-βα and an αβ-ββ modes
(Figure S47). This suggests that the interconversion be-
tweenbowl 1 andcapsule 2 should require dissociationand
reconstruction processes for every edge connection. Nota-
bly, their conversion was indeed very slow, despite the typ-
ically labile nature of ZnII, and therefore required heating
for a couple of days at 70 °C in some cases. In particular
cases, the interconversion did not reach equilibrium in the
given reaction times (e.g. Figure 6). This is probably due to
theactive structure conversion processes mentioned above.
the inclusion of MsO− was associated with the conversion
from bowl 1 to capsule 2. So far, only a limited number of
examples of guest inclusion in metal-organic cages with
structural conversion have been reported.14 This
open/closed interconversion between bowl 1 and capsule
2 is intriguing from a viewpoint of dynamic host-guest
chemistry.
Figure 11. Chloride ion-induced inclusion of a MsO− ion with
the conversion from bowl 1 to capsule 2. (a) Reaction scheme.
(b,c) 1H NMR spectra (500 MHz, 300 K, CD3CN); (b) L·OTf·3H2O
n
+ Zn(OTf)2 (1.6 eq) + Bu4N·OMs (0.25 eq), CD3CN, 1.0 mM,
70 °C, 12 h; (c) (b) + nBu4N·Cl (1.6 eq), 70 °C, 2 days.
Thermodynamic and Kinetic Considerations for the
Multi-Stimuli Responses. The interconversion between
bowl 1 and capsule 2 was triggered not only by metal–lig-
and stoichiometry but also by various stimuli such as exog-
enous ligands, Brønsted base/acid, solvents, and guest mol-
ecules. We discuss here the interconversion between these
two structures from the thermodynamic and kinetic aspects.
Figure 12. A stoichiometric reaction scheme for the intercon-
version between bowl 1 and capsule 2 by external stimuli. In-
sets show the structures of ligand L excerpted from the DFT-
optimized model of each complex (PBE/DND/COSMO, no ani-
ons are modelled).
Bowl 1 and capsule 2 are constituted in a different com-
position ratio, that is, ZnII:L = 4:3 and 4:4, respectively. Such
compositional difference often allows structural intercon-
version to be induced by the alteration of metal-ligand stoi-
chiometry in the system.7,8a–c For the four external stimuli
tested in this study, on the other hand, conversion of bowl
During the slow conversion from bowl 1 to capsule 2,
some intermediates were detected. For instance, in the case
of the conversion from bowl 1 to capsule 2 by addition of
1
ligand L, the H NMR spectrum initially showed the pres-
ence of a complicated mixture and then showed the gradual
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Journal of the American Chemical Society
Page 8 of 11
This research was supported by JSPS KAKENHI Grant No.
JP16H06509 (Coordination Asymmetry) to M.S. and Grant No.
JP17J06579 (Grant-in-Aid for JSPS Fellows) to K.E..
formation of capsule 2. A complicated mixture of interme-
diates was also observed in the cases of Brønsted base and
some exogenous ligands such as ethylenediamine. On the
other hand, the other exogenous ligands tested, for example,
1,10-phenanthroline (phen) formed a well-defined inter-
mediate, 1·(phen)3 (vide supra), which became involved in
the conversion to capsule 2 only after heating. In contrast,
the reverse conversion from capsule 2 to bowl 1, the inter-
mediate species were not observed probably due to their
high reactivity under the conditions applied.
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REFERENCES
(1) (a) Conn, M. M.; Rebek Jr., J. Self-Assembling Capsules. Chem.
Rev. 1997, 97, 1647–1668. (b) MacGillivray, L. R.; Atwood, J. L.
Structural Classification and General Principles for the Design of
Spherical Molecular Hosts. Angew. Chem., Int. Ed. 1999, 38, 1018–
1033. (c) Hof, F.; Craig, S. L.; Nuckolls, C.; Rebek Jr., J. Molecular En-
capsulation. Angew. Chem., Int. Ed. 2002, 41, 1488–1508. (d) Jor-
dan, J. H.; Gibb, B. C. Molecular Containers Assembled Through the
Hydrophobic Effect. Chem. Soc. Rev. 2015, 44, 547–585. (e) Beuerle,
F.; Gole, B. Covalent Organic Frameworks and Cage Compounds:
Design and Applications of Polymeric and Discrete Organic Scaf-
folds. Angew. Chem., Int. Ed. 2018, 57, 4850–4878.
(2) (a) Kumar, A.; Sun, S.-S.; Lees, A. J. Directed Assembly Metal-
locyclic Supramolecular Systems for Molecular Recognition and
Chemical Sensing. Coord. Chem. Rev. 2008, 252, 922–939. (b)
Chakrabarty, R.; Mukherjee, P. S.; Stang, P. J. Supramolecular Coor-
dination: Self-Assembly of Finite Two- and Three-Dimensional En-
sembles. Chem. Rev. 2011, 111, 6810–6918. (c) Cook, T. R.; Stang,
P. J. Recent Developments in the Preparation and Chemistry of
Metallacycles and Metallacages via Coordination. Chem. Rev. 2015,
115, 7001–7045. (d) Nakamura, T.; Ube, H.; Shionoya, M. Elaborate
Metallosupramolecular Architectures Through Desymmetrization
Self-Assembly of Symmetric Building Blocks. Chem. Lett. 2013, 42,
328–334. (e) Castilla, A. M.; Ramsay, W. J.; Nitschke, J. R. Stereo-
chemical Communication within Tetrahedral Capsules. Chem. Lett.
2014, 43, 256–263. (f) Chen, L. J.; Yang, H. B.; Shionoya, M. Chiral
Metallosupramolecular Architectures. Chem. Soc. Rev. 2017, 46,
2555–2576.
(3) (a) Fujita, D.; Ueda, Y.; Sato, S.; Mizuno, N.; Kumasaka, T.; Fu-
jita, M. Self-Assembly of Tetravalent Goldberg Polyhedra from 144
Small Components. Nature 2016, 540, 563–566. (b) Ronson, T. K.;
Meng, W.; Nitschke, J. R. Design Principles for the Optimization of
Guest Binding in Aromatic-Paneled FeII4L6 Cages. J. Am. Chem. Soc.
2017, 139, 9698–9707. (c) Tidmarsh, I. S.; Faust, T. B.; Adams, H.;
Harding, L. P.; Russo, L.; Clegg, W.; Ward, M. D. Octanuclear Cubic
Coordination Cages. J. Am. Chem. Soc. 2008, 130, 15167–15175. (d)
Kusaba, S.; Yamashina, M.; Akita, M.; Kikuchi, T.; Yoshizawa, M. Hy-
drophilic Oligo(lactic acid)s Captured by a Hydrophobic Polyaro-
matic Cavity in Water. Angew. Chem., Int. Ed. 2018, 57, 3706–3710.
(e) Bloch, W. M.; Holstein, J. J.; Dittrich, B.; Hiller, W.; Clever, G. H.
Hierarchical Assembly of an Interlocked M8L16 Container. Angew.
Chem., Int. Ed. 2018, 57, 5534–5538. (f) Zhang, M.; Saha, M. L.;
Wang, M.; Zhou, Z.; Song, B.; Lu, C.; Yan, X.; Li, X.; Huang, F.; Yin, S.;
Stang, P. J. Multicomponent Platinum(II) Cages with Tunable Emis-
sion and Amino Acid Sensing. J. Am. Chem. Soc. 2017, 139, 5067–
5074. (g) Zhang, C.; Sikligar, K.; Patil, R. S.; Barnes, C. L.; Baker, G.
A.; Atwood, J. L. A M18L6 Metal-Organic Nanocapsule with Open
Windows Using Mixed Macrocycles. Chem. Commun. 2018, 54,
635–637.
(4) (a) Ahmad, N.; Younus, H. A.; Chughtai, A. H.; Verpoort F.
Metal-Organic Molecular Cages: Applications of Biochemical Impli-
cations. Chem. Soc. Rev. 2015, 44, 9–25. (b) Casini, A.; Woods, B.;
Wenzel, M. The Promise of Self-Assembled 3D Supramolecular Co-
ordination Complexes for Biomedical Applications. Inorg. Chem.
2017, 56, 14715–14729. (c) Zhao, L.; Jing, X.; Li, X.; Guo, X.; Zeng,
L.; He, C.; Duan C. Catalytic Properties of Chemical Transformation
Within the Confined Pockets of Werner-Type Capsules. Coord.
Chem. Rev. 2017, 378, 151–187
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■
CONCLUSIONS
In this study, we have demonstrated that self-assembled
ZnII complexes with a ZnII-porphyrin-based ligand L afford
an interconversion system of a bowl-shaped [ZnII L3X6] (1)
4
and a capsule-shaped [ZnII L4] (2). These complexes were
4
interconverted not only by changing the metal-ligand stoi-
chiometry but also by applying various stimuli: exogenous
ligands, Brønsted base/acid, solvents, and guest molecules.
The [ZnIIX6] species, which come from the difference in
metal-ligand ratios between the two complexes, played piv-
otal roles in the unique multi-stimuli responsiveness of this
interconversion system. This finding would provide a de-
sign principle of multi-stimuli responsive systems, which
may lead to versatile or multifunctional responsive materi-
als. Moreover, sequestration of guest anions was induced in
association with conversion from open-shaped bowl 1 to
closed-shaped capsule 2, suggesting high potential of this
system as a molecular transporter.
■
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.???????. Crystal-
lographic files are also deposited with the Cambridge Crystal-
lographic Data Center as CCDC 1936146 and 1936147.
Experimental procedures, characterization of compounds,
NMR spectra, ESI-MS spectra, UV-vis absorption spectra, crys-
tallographic data, details of the structural refinement, and
structure comparison (PDF)
Single-crystal X-ray diffraction data for 1’ (CIF)
Single-crystal X-ray diffraction data for 2 (CIF)
■
AUTHOR INFORMATION
Corresponding Author
*shionoya@chem.s.u-tokyo.ac.jp
ORCID
Kenichi Endo: 0000-0002-4128-6514
Hitoshi Ube: 0000-0003-2501-7610
Mitsuhiko Shionoya: 0000-0002-9572-4620
Notes
(5) (a) Ueda, Y.; Ito, H.; Fujita, D.; Fujita, M. Permeable Self-As-
sembled Molecular Containers for Catalyst Isolation Enabling Two-
Step Cascade Reactions. J. Am. Chem. Soc. 2017, 139, 6090–6093.
(b) Haynes, C. J. E.; Zhu, J.; Chimerel, C.; Hernández-Ainsa, S.; Rid-
dell, I. A.; Ronson, T. K.; Keyser, U. F.; Nitschke, J. R. Blockable
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS
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Zn10L15 Ion Channels Through Subcomponent Self-Assembly. An-
Xie, T. Z.; Endres, K. J.; Guo, Z.; Ludlow III, J. M.; Moorefield, C. N.;
Saunders, M. J.; Wesdemiotis, C.; Newkome, G. R. Controlled Inter-
conversion of Superposed-Bistriangle, Octahedron, and Cubocta-
hedron Cages Constructed Using a Single, Terpyridinyl-Based Pol-
yligand and Zn2+. J. Am. Chem. Soc. 2016, 138, 12344–12347.
(12) (a) Sun, S. S.; Anspach, J. A.; Lees, A. J. Self-Assembly of Tran-
sition-Metal-Based Macrocycles Linked by Photoisomerizable Lig-
ands: Examples of Photoinduced Conversion of Tetranuclear-Dinu-
clear Squares. Inorg. Chem. 2002, 41, 1862–1869. (b) Li, M.; Chen,
L.-J.; Cai, Y.; Luo, Q.; Li, W.; Yang, H.-B.; Tian, H.; Zhu, W.-H. Light-
Driven Chiral Switching of Supramolecular Metallacycles with Pho-
toreversibility. Chem 2019, 5, 634–648. (c) Li, M.; Chen, L. J.; Zhang,
Z.; Luo, Q.; Yang, H. B.; Tian, H.; Zhu, W. H. Conformer-Dependent
Self-Assembled Metallacycles with Photo-Reversible Response.
Chem. Sci. 2019, 10, 4896–4904. (d) Zheng, W.; Wang, W.; Jiang, S.
T.; Yang, G.; Li, Z.; Wang, X. Q.; Yin, G. Q.; Zhang, Y.; Tan, H.; Li, X.;
Ding, H.; Chen, G.; Yang, H. B. Supramolecular Transformation of
Metallacycle-Linked Star Polymers Driven by Simple Phosphine
Ligand-Exchange Reaction. J. Am. Chem. Soc. 2019, 141, 583–591.
(13) (a) Burke, M. J.; Nichol, G. S.; Lusby, P. J. Orthogonal Selection
and Fixing of Coordination Self-Assembly Pathways for Robust
Metallo-Organic Ensemble Construction. J. Am. Chem. Soc. 2016,
138, 9308–9315. (b) Wang, S.; Sawada, T.; Fujita, M. Capsule-Bowl
Conversion Triggered by a Guest Reaction. Chem. Commun. 2016,
52, 11653–11656. (c) Yadav, A.; Gupta, A. K.; Steiner, A.; Boomis-
hankar R. Mapping the Assembly of Metal-Organic Cages into Com-
plex Coordination Networks. Chem. Eur. J. 2017, 23, 18296–18302.
(d) Liu, J. J.; Lin, Y. J.; Li, Z. H.; Jin, G. X. Self-Assembled Half-Sand-
wich Polyhedral Cages via Flexible Schiff-Base Ligands: An Unusual
Macrocycle-To-Cage Conversion. Dalton Trans. 2016, 45, 13675–
13679. (e) Liu, D.; Jiang, Z.; Wang, M.; Yang, X.; Liu, H.; Chen, M.;
Moorefield, C. N.; Newkome, G. R.; Li, X.; Wang, P. 3D Helical and 2D
Rhomboidal Supramolecules: Stepwise Self-Assembly and Dy-
namic Transformation of Terpyridine-Based Metallo-Architec-
tures. Chem. Commun. 2016, 52, 9773–9776.
(14) (a) Hiraoka, S.; Harano, K.; Shiro, M.; Shionoya, M. Quantita-
tive Dynamic Interconversion Between Ag(I)-Mediated Capsule
and Cage Complexes Accompanying Guest Encapsulation/Release.
Angew. Chem., Int. Ed. 2005, 44, 2727–2731. (b) Kuwabara, J.; Stern,
C. L.; Mirkin, C. A. A Coordination Chemistry Approach to a Multief-
fector Enzyme Mimic. J. Am. Chem. Soc. 2007, 129, 10074–10075.
(c) Zheng, Y. R.; Lan, W. J.; Wang, M.; Cook, T. R.; Stang, P. J. Designed
Post-Self-Assembly Structural and Functional Modifications of a
Truncated Tetrahedron. J. Am. Chem. Soc. 2011, 133, 17045–17055.
(d) Han, M.; Michel, R.; He, B.; Yu-Chen, S.; Stalke, D.; John, M.;
Clever, G. H. Light-Triggered Guest Uptake and Release by a Photo-
chromic Coordination Cage. Angew. Chem., Int. Ed. 2013, 52, 1319–
1323. (e) Kishi, N.; Akita, M.; Yoshizawa, M. Selective Host-Guest
Interactions of a Transformable Coordination Capsule/Tube with
Fullerenes. Angew. Chem., Int. Ed. 2014, 53, 3604–3607. (f) Preston,
D.; Fox-Charles, A.; Lo, W. K.; Crowley, J. D. Chloride Triggered Re-
versible Switching from a Metallosupramolecular [Pd2L4]4+ Cage to
a [Pd2L2Cl4] Metallo-Macrocycle with Release of Endo- and Exo-He-
drally Bound Guests. Chem. Commun. 2015, 51, 9042–9045. (g)
Zhang, D.; Ronson, T. K.; Güryel, S.; Thoburn, J. D.; Wales, D. J.;
Nitschke, J. R. Temperature Controls Guest Uptake and Release
from Zn4L4 Tetrahedra. J. Am. Chem. Soc. 2019, 141, 14534−14538.
(15) Lifschitz, A. M.; Rosen, M. S.; McGuirk, C. M.; Mirkin, C. A. Al-
losteric Supramolecular Coordination Constructs. J. Am. Chem. Soc.
2015, 137, 7252–7261.
gew. Chem., Int. Ed. 2017, 56, 15388–15392. (c) Hong, C. M.;
Morimoto, M.; Kapustin, E. A.; Alzakhem, N.; Bergman, R. G.; Ray-
mond, K. N.; Toste, F. D. Deconvoluting the Role of Charge in a Su-
pramolecular Catalyst. J. Am. Chem. Soc. 2018, 140, 6591–6595. (d)
Cullen, W.; Metherell, A. J.; Wragg, A. B.; Taylor, C. G. P., Williams, N.
H.; Ward, M. D. Catalysis in a Cationic Coordination Cage Using a
Cavity-Bound Guest and Surface-Bound Anions: Inhibition, Activa-
tion, and Autocatalysis. J. Am. Chem. Soc. 2018, 140, 2821–2828. (e)
Zhao, L.; Wei, J.; Zhang, J.; He, C.; Duan, C. Encapsulation of a
Quinhydrone Cofactor in the Inner Pocket of Cobalt Triangular
Prisms: Combined Light-Driven Reduction of Protons and Hydro-
genation of Nitrobenzene. Angew. Chem., Int. Ed. 2017, 56, 15284–
15288. (f) Martí-Centelles, V.; Lawrence, A. L.; Lusby, P. J. High Ac-
tivity and Efficient Turnover by a Simple, Self-Assembled "Artificial
Diels-Alderase". J. Am. Chem. Soc. 2018, 140, 2862–2868. (g) Bhat,
I. A.; Devaraj, A.; Howlader, P.; Chi, K. W.; Mukherjee, P. S. Prepara-
tion of a Chiral Pt12 Tetrahedral Cage and Its Use in Catalytic Mi-
chael Addition Reaction. Chem. Commun. 2018, 54, 4814–4817. (h)
Preston, D.; Gordon, K. C.; Sutton, J. J.; Crowley J. D. A Nona-Nuclear
Heterometallic Pd3Pt6 "Donut" Shaped Cage: Molecular Recogni-
tion and Photocatalysis. Angew. Chem., Int. Ed. 2018, 57, 8659–
8663.
(6) (a) McConnell, A. J.; Wood, C. S.; Neelakandan, P. P.; Nitschke,
J. R. Stimuli-Responsive Metal-Ligand Assemblies. Chem. Rev. 2015,
115, 7729–7793. (b) Wang, W.; Wang, Y. X.; Yang, H. B. Supramo-
lecular Transformations Within Discrete Coordination-Driven Su-
pramolecular Architectures. Chem. Soc. Rev. 2016, 45, 2656–2693.
(7) (a) Hiraoka, S.; Yi, T.; Shiro, M.; Shionoya, M. Triangular and
Tetrahedral Array of Silver(I) Ions by a Novel Disk-Shaped Triden-
tate Ligand: Dynamic Control of Coordination Equilibrium of the
Silver(I) Complexes. J. Am. Chem. Soc. 2002, 124, 14510–14511. (b)
Harano, K.; Hiraoka, S.; Shionoya, M. 3 nm-Scale Molecular Switch-
ing Between Fluorescent Coordination Capsule and Nonfluores-
cent Cage. J. Am. Chem. Soc. 2007, 129, 5300–5301. (c) Hiraoka, S.;
Sakata, Y.; Shionoya, M. Ti(IV)-Centered Dynamic Interconversion
Between Pd(II), Ti(IV)-Containing Ring and Cage Molecules. J. Am.
Chem. Soc. 2008, 130, 10058–10059.
(8) (a) Sakata, Y.; Hiraoka, S.; Shionoya, M. Site-Selective Ligand
Exchange on a Heteroleptic Ti(IV) Complex Towards Stepwise
Multicomponent Self-Assembly. Chem. Eur. J. 2010, 16, 3318–3325.
(b) Li, J. R.; Zhou, H. C. Bridging-Ligand-Substitution Strategy for
the Preparation of Metal-Organic Polyhedra. Nat. Chem. 2010, 2,
893–898. (c) Prusty, S.; Yazaki, K.; Yoshizawa, M.; Chand, D. K. A
Truncated Molecular Star. Chem. Eur. J. 2017, 23, 12456–12461.
(d) Bloch, W. M.; Holstein, J. J.; Hiller, W.; Clever, G. H. Morphologi-
cal Control of Heteroleptic cis- and trans-Pd2L2L'2 Cages. Angew.
Chem., Int. Ed. 2017, 56, 8285–8289. (e) d'Aquino, A. I.; Cheng, H.
F.; Barroso-Flores, J.; Kean, Z. S.; Mendez-Arroyo, J.; McGuirk, C. M.;
Mirkin, C. A. An Allosterically Regulated, Four-State Macrocycle. In-
org. Chem. 2018, 57, 3568–3578. (f) Preston, D.; Barnsley, J. E.; Gor-
don, K. C.; Crowley, J. D. Controlled Formation of Heteroleptic
[Pd2(La)2(Lb)2]4+ Cages. J. Am. Chem. Soc. 2016, 138, 10578–10585.
(9) (a) Fujita, M.; Ibukuro, F.; Hagihara, H.; Ogura K. Quantitative
Self-Assembly of a [2]Catenane from Two Preformed Molecular
Rings. Nature 1994, 367, 720–723 (b) Liu, C. L.; Zhou, L. P.; Tripa-
thy, D.; Sun, Q. F. Self-Assembly of Stable Luminescent Lanthanide
Supramolecular M4L6 Cages with Sensing Properties Toward Ni-
troaromatics. Chem. Commun. 2017, 53, 2459–2462.
1
2
3
4
5
6
7
8
9
10
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12
13
14
15
16
17
18
19
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21
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40
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42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(10) (a) Scherer, M.; Caulder, D. L.; Johnson, D. W.; Raymond, K.
N. Triple Helicate-Tetrahedral Cluster Interconversion Controlled
by Host-Guest Interactions. Angew. Chem., Int. Ed. 1999, 38, 1587–
1592. (b) Hong, C. M.; Kaphan, D. M.; Bergman, R. G.; Raymond, K.
N.; Toste, F. D. Conformational Selection as the Mechanism of Guest
Binding in a Flexible Supramolecular Host. J. Am. Chem. Soc. 2017,
139, 8013–8021.
(11) (a) Fujita, M.; Sasaki, O.; Mitsuhashi, T.; Fujita, T.; Yazaki, J.;
Yamaguchi, K.; Ogura, K. On the Structure of Transition-Metal-
Linked Molecular Squares. Chem. Commun. 1996, 1535–1536. (b)
(16) (a) Monod, J.; Changeux J.-P., Jacob, F. Allosteric Proteins and
Cellular Control Systems. J. Mol. Biol. 1963, 6, 306–329. (b) Perutz,
M. F.; Stereochemistry of Cooperative Effects in Haemoglobin:
Haem–Haem Interaction and the Problem of Allostery. Nature
1970, 228, 726–734. (c) Saibil, H. R.; Fenton, W. A.; Clare, D. K.; Hor-
wich, A. L. Structure and Allostery of the Chaperonin GroEL. J. Mol.
Biol. 2013, 425, 1476–1487.
(17) (a) Monod, J.; Wyman, J.; Changeux J.-P. On the Nature of Al-
losteric Transitions: a Plausible Model. J. Mol. Biol. 1965, 12, 88–
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Journal of the American Chemical Society
Page 10 of 11
118. (b) Yuan, Y.; Tam, M. F.; Simplaceanu, V.; Ho C. New Look at
Zinc(II) Center Formation Under Well-Balanced Aqueous Condi-
Hemoglobin Allostery. Chem. Rev. 2015, 115, 1702–1724.
(18) (a) Riddell, I. A.; Ronson, T. K.; Clegg, J. K.; Wood, C. S.; Bil-
beisi, R. A.; Nitschke, J. R. Cation- and Anion-Exchanges Induce Mul-
tiple Distinct Rearrangements within Metallosupramolecular Ar-
chitectures. J. Am. Chem. Soc. 2014, 136, 9491–9498. (b) Rizzuto, F.
J.; Pröhm, P.; Plajer, A. J.; Greenfield, J. L.; Nitschke, J. R. Hydrogen-
Bond-Assisted Symmetry Breaking in a Network of Chiral Metal−
Organic Assemblies. J. Am. Chem. Soc. 2019, 141, 1707–1715. (c)
Roberts, D. A.; Pilgrim, B. S.; Sirvinskaite, G.; Ronson, T. K.; Nitschke,
J. R. Covalent Post-assembly Modification Triggers Multiple Struc-
tural Transformations of a Tetrazine-Edged Fe4L6 Tetrahedron. J.
Am. Chem. Soc. 2018, 140, 9616–9623.
(19) (a) Lee, H.; Elumalai, P.; Singh, N.; Kim, H.; Lee, S. U.; Chi, K.
W. Selective Synthesis of Ruthenium(II) Metalla[2]Catenane via
Solvent and Guest-Dependent Self-Assembly. J. Am. Chem. Soc.
2015, 137, 4674–4677. (b) Cullen, W.; Hunter, C. A.; Ward, M. D. An
Interconverting Family of Coordination Cages and a meso-Helicate;
Effects of Temperature, Concentration, and Solvent on the Product
Distribution of a Self-Assembly Process. Inorg. Chem. 2015, 54,
2626–2637.
tions. Angew. Chem., Int. Ed. 2013, 52, 720–723. (b) Nakamura, T.;
Ube, H.; Shionoya, M. Silver-Mediated Formation of a Cofacial Por-
phyrin Dimer with the Ability to Intercalate Aromatic Molecules.
Angew. Chem., Int. Ed. 2013, 52, 12096–12100. (c) Nakamura, T.;
Ube, H.; Miyake, R.; Shionoya, M. A C60-Templated Tetrameric Por-
phyrin Barrel Complex via Zinc-Mediated Self-Assembly Utilizing
Labile Capping Ligands. J. Am. Chem. Soc. 2013, 135, 18790–18793.
(d) Ube, H.; Endo, K.; Sato, H.; Shionoya, M. Synthesis of Hetero-
multinuclear Metal Complexes by Site-Selective Redox Switching
and Transmetalation on a Homo-multinuclear Complex J. Am. Chem.
Soc. 2019, 141, 10384–10389.
(21) (a) Durot, S.; Taesch, J.; Heitz, V. Multiporphyrinic Cages: Ar-
chitectures and Functions. Chem. Rev. 2014, 114, 8542–8578. (b)
Wood, D. M.; Meng, W.; Ronson, T. K.; Stefankiewicz, A. R.; Sanders,
J. K.; Nitschke, J. R. Guest-Induced Transformation of a Porphyrin-
Edged FeII4L6 Capsule into a CuIFeII2L4 Fullerene Receptor. Angew.
Chem., Int. Ed. 2015, 54, 3988–3992. (c) Rizzuto, F. J.; Nitschke, J. R.
Stereochemical Plasticity Modulates Cooperative Binding in a
CoII12L6 Cuboctahedron. Nat. Chem. 2017, 9, 903–908.
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50
51
52
53
54
55
56
57
58
59
60
(20) (a) Nakamura, T.; Ube, H.; Shiro, M.; Shionoya, M. A Self-As-
sembled Multiporphyrin Cage Complex Through Three Different
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