Structural alteration of hybrid supramolecular capsule induced by guest encapsulation

Article abstract of DOI:10.1021/ja207092c

Figure Presented Heterofunctionalized C_2v symmetrical cavitand 1 with 4-pyridylethynyl and 3-carbamoylphenyl groups in alternating arrangement was designed and synthesized. A 1:1 mixture of the cavitand 1 and a cis-coordinated palladium(II) or platinum(II) complex self-assembled into a hybrid supramolecular capsule via both metal-ligand coordination bonds and hydrogen bonds. Formation of the capsular assembly was confirmed by NMR spectroscopy and mass spectrometry. The hybrid capsule encapsulated the appropriate guest, the molecular sizes of which fit the size of the capsular cavity. Structural alteration of the hybrid capsule was induced by the guest encapsulation. A C_2h structure for the encapsulation complex was assigned by 2D NMR spectra analysis. Thermodynamic and kinetic properties of the guest encapsulation were investigated. The kinetics of in/out guest exchange was strongly influenced by hydrogen bonding in the hybrid capsule.

Full text of DOI:10.1021/ja207092c

ARTICLE
pubs.acs.org/JACS
Structural Alteration of Hybrid Supramolecular Capsule Induced by
Guest Encapsulation
Masamichi Yamanaka,*,† Masashi Kawaharada,† Yuki Nito,† Hikaru Takaya,‡ and Kenji Kobayashi†
†Department of Chemistry, Faculty of Science, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan
‡International Research Center for Elements Science, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan
S Supporting Information
b
ABSTRACT:
Heterofunctionalized C2v symmetrical cavitand 1 with 4-pyridylethynyl and 3-carbamoylphenyl groups in alternating arrangement
was designed and synthesized. A 1:1 mixture of the cavitand 1 and a cis-coordinated palladium(II) or platinum(II) complex self-
assembled into a hybrid supramolecular capsule via both metalꢀligand coordination bonds and hydrogen bonds. Formation of the
capsular assembly was confirmed by NMR spectroscopy and mass spectrometry. The hybrid capsule encapsulated the appropriate
guest, the molecular sizes of which fit the size of the capsular cavity. Structural alteration of the hybrid capsule was induced by the
guest encapsulation. A C2h structure for the encapsulation complex was assigned by 2D NMR spectra analysis. Thermodynamic and
kinetic properties of the guest encapsulation were investigated. The kinetics of in/out guest exchange was strongly influenced by
hydrogen bonding in the hybrid capsule.
’ INTRODUCTION
bearing pyridylethynyl and phenylureido groups and a cis-co-
ordinated platinum(II) complex via both metalꢀligand coordi-
nation bonds and hydrogen bonds.8
Self-assembly is a smart approach to access nanoscale archi-
tecture. Spontaneous assembly of well-designed units enables the
construction of complicated structures, whereas it is often difficult to
build them via the classical covalent approach.1 Capsular struc-
tures with isolated nanoscale cavities are interesting targets for
the creation of discrete assemblies. To date, varieties of molecular
capsules have been reported using noncovalent interactions as
the attractive forces.2 Encapsulated guest molecules inside the
isolated cavity sometimes show unique behavior that is different
from the bulk phase. For example, acceleration of reaction and
stabilization of labile guest molecules can be achieved by encap-
sulation.3 To create a supramolecular capsule, the cavitand4 derived
from calix[4]resorcinarene is one of the most useful platforms.
The cavitand originally possesses the exact size of the cavity, and
it is possible to introduce adequate functional groups at the upper
rim to conduct self-assembly while controlling their orientation.
The creation of many cavitand-based capsular assemblies through
hydrogen bonds,5 metalꢀligand coordination bonds,6 and other
interactions7 has been achieved. We have developed a hybrid
supramolecular capsule assembled by a C2v symmetrical cavitand
The dynamics of a guest molecule encapsulated in the isolated
nanospace of a supramolecular capsule are restricted. The
restriction results in novel isomerisms characteristic of encapsu-
lation complexes.9ꢀ11 Rebek and co-workers reported social iso-
mers and constellational isomers in multimolecular encapsulation.9
These isomers originate from restriction on the tumbling of an
unsymmetrical guest molecule along the long axis and/or change
in their arrangement relative to each other. Unsymmetrical guest
encapsulation in the unsymmetrical heterodimeric capsule and
restriction of guest tumbling along the long axis causes orienta-
tional isomers.10 Furthermore, the symmetry of the capsule is
reduced as a consequence of restricting not only vertical tum-
bling but also horizontal rotation of the guest motion.11 Although
much attention has been paid to controlling the guest dynamics,
the restriction of capsular dynamics in encapsulation complexes
Received: July 28, 2011
Published: September 12, 2011
r
2011 American Chemical Society
16650
dx.doi.org/10.1021/ja207092c J. Am. Chem. Soc. 2011, 133, 16650–16656
|

Journal of the American Chemical Society
ARTICLE
Scheme 1. Hybrid Capsular Formation of Cavitand 1 and Metal Complex and the Guest Encapsulation
has been rarely reported.12 Guest encapsulation leading to
Scheme 2. Synthesis of C2v Symmetrical Cavitand 1
structural alteration of capsular assembly is an interesting subject
because the alteration is induced by weak van der Waals inter-
actions. Here, we report (1) the synthesis of a heterofunctiona-
lized C2v symmetrical cavitand 1 with 4-pyridylethynyl and
3-carbamoylphenyl groups in alternating arrangement at the
upper rim, (2) self-assembly of 1 and a cis-coordinated palladium-
(II) or platinum(II) complex into a hybrid capsule via both
metalꢀligand coordination bonds and hydrogen bonds, and (3)
structural alteration of the hybrid capsule induced by guest
encapsulation (Scheme 1).
’ RESULTS AND DISCUSSION
Synthesis of C2v Cavitand 1. The cavitand 1 with C2v symmetry
was designed to construct a hybrid supramolecular capsule by both
metalꢀligand coordination bonds and hydrogen bonds. The cavi-
tand 1 has two 4-pyridylethynyl groups as ligands for metalꢀligand
coordination and two 3-carbamoylphenyl groups for the hydrogen
bonding in alternating arrangement at the upper rim. The tetra-
bromo cavitand13 2 was converted into cavitand 1 using palladium-
catalyzed cross-coupling reactions twice as key steps (Scheme 2).
C4v tetrabromo cavitand was converted into C2v symmetrical
dibromo-diboronic acid cavitand 3 using a modification of
Sherburn’s procedure.14 The SuzukiꢀMiyaura cross-coupling of
cavitand 3 with 3-bromobenzonitrile resulted in two benzonitriles
being introduced into cavitand 4 in 51% yield. Subsequent Sonoga-
shira-type cross-coupling of cavitand 4 with 4-ethynylpyridine
afforded cavitand 5 in 47% yield.15 Use of typical Sonogashira
coupling conditions in the presence of copper salts was not effective
in affording 5 because of preferential progress of the homocoupling
reaction of 4-ethynylpyridine. Hydrolysis of nitrile groups under
basic conditions afforded C2v symmetrical di(4-pyridylethynyl)-
di(3-carbamoylphenyl) cavitand 1 in 53% yield. Surprisingly, the
alkaline hydrolysis did not produce a carboxylate as a product.
The structure of 1 was confirmed by NMR, mass, and IR spectra.
1
The H NMR spectrum of 1 in CDCl3 showed a symmetrical
species (Figure 1a). The signal of the α-protons of the pyridyl
nitrogen (Hd) was observed at 8.53 ppm. The inner and outer
protons of the methylene bridges (Ha and Hb) and methine protons
(Hc) appeared at 4.44, 5.56, and 4.85 ppm, respectively. Broad
singlet signals appearing at 5.59 and 6.11 ppm were assigned as
amide protons (Hj), because these signals disappeared upon
addition of a small amount of D2O.
Capsular Formation via Self-Assembly of Cavitand 1 and
Metal Complexes. A metalꢀligand coordination bond between
pyridylethynyl groups of the cavitand 1 and cis-coordinated
16651
dx.doi.org/10.1021/ja207092c |J. Am. Chem. Soc. 2011, 133, 16650–16656

Journal of the American Chemical Society
ARTICLE
Figure 2. ESI-FT-ICR MS spectrum of [12Pd2(dppp)2(OTf)4].
amide groups of two molecules of 1 caused a downfield shift of
the amide protons (Hj: Δδ = +0.82, +0.63 ppm). Signals
1
1
1
observed in the H NMR spectrum were assigned by Hꢀ H
COSY and NOESY measurements (Figures S1 and S2). The 1:1
mixture of 1 and Pd(dppp)(OTf)2 at 243 K showed a 1H NMR
spectrum similar to that at 298 K (Figure 1c vs b). The electron
spray ionization (ESI) Fourier transform ion cyclotron reso-
nance mass spectrum (FT-ICR-MS) of the mixture showed a
trivalent molecular ion peak of the capsular assembly {[12Pd2-
(dppp)2OTf]3+} at m/z 1308.5503 (theoretical: 1308.4979)
(Figure 2). These results strongly support the formation of sup-
ramolecular capsule [12Pd2(dppp)2(OTf)4]. The ratio of cavi-
tand 1 to Pd(dppp)(OTf)2 was important for the formation of
the capsular assembly. A 2:1 mixture of cavitand 1 and Pd(dppp)-
(OTf)2 in CDCl3 indicated coexistence of the capsular assembly
and free cavitand 1, and their relatively fast exchange caused signal
1
broadening in the H NMR spectrum (Figure 1d). Capsular
assembly and unidentified assemblies are produced in a 2:3 mixture
of cavitand 1 and Pd(dppp)(OTf)2 in CDCl3 (Figure 1e). Quanti-
tative capsule formation was identified in a 1:1 mixture of cavitand 1
Figure 1. 1H NMR spectra (600 MHz, CDCl3) of (a) 1 alone at 298 K;
(b) [1] = [Pd(dppp)(OTf)2] = 4 mM at 298 K; (c) [1] = [Pd(dppp)-
(OTf)2] = 4 mM at 243 K; (d) [1] = 8 mM and [Pd(dppp)(OTf)2] =
4 mM at 298 K; (e) [1] = 4 mM and [Pd(dppp)(OTf)2] = 6 mM at
298 K; (f) [1] = [Pt(dppp)(OTf)2] = 4 mM at 298 K; (g) [1] =
[Ni(dppp)(OTf)2] = 4 mM at 298 K; (h) [1] = [Pd(dppe)(OTf)2] =
4 mM at 298 K; (i) [1] = [Pd(dppb)(OTf)2] = 4 mM at 298 K;
(j) [1] = [Pd(dpppent)(OTf)2] = 4 mM at 298 K; and (k) [1] =
[Pd(dppf)(OTf)2] = 4 mM at 298 K.
1
and Pt(dppp)(OTf)2, and the H NMR spectrum was similar
to that of [12Pd2(dppp)2(OTf)4] (Figure 1f). On the other
hand, a mixture of 1 and Ni(dppp)(OTf)21did not form a capsule
(Figure 1g). The cavitand signals in the H NMR spectrum of
this mixture coincided with those of cavitand 1 alone.
Next, we paid attention to bidentate phosphine ligands on the
metal center. Dalcanale and co-workers investigated the capsular
assembly of a tetracyano cavitand and various metal complexes.6a,16
Four molecules of Pd(dppp)(OTf)2 and two molecules of the
tetracyano cavitand self-assemble into a capsular structure; however,
Pd(dppe)(OTf)2 [dppe = 1,2-bis(diphenylphosphino)ethane]
and Pd(dppb)(OTf)2 [dppb = 1,4-bis(diphenylphosphino)butane]
did not converge into discrete structures. The PꢀPdꢀP angles of
Pd(dppe)Cl2, Pd(dppp)Cl2, and Pd(dppb)Cl2 based on their
crystal structures were 85.8°, 90.6°, and 94.3°, respectively.17
Consequently, the ClꢀPdꢀCl angles also changed, although the
ratio was small. Values of the ClꢀPdꢀCl angle of Pd(dppe)Cl2,
Pd(dppp)Cl2, and Pd(dppb)Cl2 were 94.2°, 90.8°, and 89.6°,
respectively. These angles are similar to the angles in RCNꢀ
PdꢀNCR. Slight differences between these angles were strik-
ingly reflected in their assemblies because of the rigid structure of
divalent group 10 metal complexes formed discrete aggregates
spontaneously. Consequently, the approaching 3-carbamoylphenyl
groups are easily connected throughhydrogenbonds(Scheme1). A
1:1 mixture of cavitand 1 and Pd(dppp)(OTf)2 [dppp = 1,3-
bis(diphenylphosphino)propane] in CDCl3 showed a highly
1
symmetrical H NMR spectrum, suggesting capsular assembly
(Figure 1b). Pyridylꢀpalladium coordination bond formation
caused a downfield shift of the α-protons of the pyridyl nitrogen
(Hd: δ = 8.85 ppm; Δδ = +0.32 ppm) and an upfield shift of the
β-protons of the pyridyl nitrogen (He: δ = 6.87 ppm; Δδ =
ꢀ0.35 ppm). The signals of the inner and outer protons of the
methylene bridges (Ha and Hb) and methine protons (Hc) were
shifted upfield by 0.09, 0.13, and 0.04 ppm, respectively, relative
to those of cavitand 1 alone. Hydrogen-bond formation between
16652
dx.doi.org/10.1021/ja207092c |J. Am. Chem. Soc. 2011, 133, 16650–16656

Journal of the American Chemical Society
ARTICLE
1
the tetracyano cavitand. In contrast, all mixtures of 1 and palladium
complexes {Pd(dppe)(OTf)2, Pd(dppp)(OTf)2, Pd(dppb)(OTf)2,
Pd(dpppent)(OTf)2, [dpppent = 1,5-bis(diphenylphosphino)-
pentane], and Pd(dppf)(OTf)2 [dppf = 1,10-bis(diphenylphos-
phino)ferrocene]} suggested the formation of capsular assem-
blies. Downfield shifts of the α-protons of the pyridyl nitrogen
and upfield shifts of the β-protons of the pyridyl nitrogen in 1H
NMR spectra were characteristic of pyridylꢀpalladium coordi-
nation bond formation (Figure 1hꢀk). The pyridylethynyl group
on cavitand 1 would be more or less flexible enough to form a
coordination bond with those palladium complexes at different
angles.
infra). The H NMR spectrum of a 4 mM CDCl3 solution of
[12Pd2(dppp)2(OTf)4] in the presence of 10 equiv of 6 at 243 K
showed only encapsulation complex {6@[12Pd2(dppp)2(OTf)4]}
and free 6 (Figure 3b). Most of the protons of the cavitand were
split into two sets of signals. In marked contrast, signals of the
capsule in the absence of 6 did not split into two sets of signals
even at 243 K (Figure 1b vs c). There are two possible explanations
for these splittings. One is that two cavitands forming a capsular
assembly (upper and lower) become nonequivalent, wherein the
encapsulated guest should be desymmetrized. The other is that
the structure of the cavitand itself is altered, but the upper and
lower cavitands are equivalent. In this case, the encapsulated
guest would maintain the symmetry. In fact, 1H NMR signals of
encapsulated 6 maintained their symmetry even at lower tem-
perature. Consequently, structural alteration of the encapsula-
tion complex is caused by desymmetrization of the cavitand itself.
A C2h symmetrical structure for the encapsulation complex,
because of rotational regulation of the aromatic rings of 3-carbam-
oylphenyl groups, was identified by the following experiments
(Scheme 3). Full structural analysis of this encapsulation com-
Guest Encapsulation and Structural Analysis. Cavities
formed by capsular assembly of cavitand 1 and palladium or
platinum complexes must be sizable to encapsulate guest mole-
cules (Chart 1). It was found that trans-4,40-dimethyl stilbene (6)
is an appropriate guest for the hybrid capsule [12Pd2(dppp)2-
1
(OTf)4]. The H NMR spectrum of a 1:10 mixture of [12Pd2-
(dppp)2(OTf)4] and 6 in CDCl3 at 298 K showed new sets of
signals, assignable to {6@[12Pd2(dppp)2(OTf)4]} (Figure 3a).
plex was performed by 1Hꢀ H COSY and NOESY experiments
1
1
The H NMR signals of encapsulated and free guests were
at 243 K. The 1Hꢀ H COSY spectrum enabled the assignment
1
independently observed, indicating that the exchange of guests
in and out of the capsule is slow on the NMR time scale. The
methyl groups of encapsulated 6 showed a large upfield shift (Hk:
δ = ꢀ1.54 ppm; Δδ = ꢀ3.90 ppm) because of the aromatic ring
current effect of the cavity end of the cavitand. Aromatic protons
at the 3,30 and 5,50 positions of encapsulated 6 also showed an
upfield shift (Hl: δ = 6.10 ppm; Δδ = ꢀ1.06 ppm). In contrast to
of the combinations of splitting patterns of the inner and outer
protons of methylene bridges (HaAꢀHbA and HaBꢀHbB) as
shown in Figure S3. Aromatic protons of HfA, HgA, and HhA were
1
1
also identified by correlations in the Hꢀ H COSY spectrum.
1
1
The Hꢀ H NOESY spectrum provided much structural in-
formation (Figure S4). NOE correlations between methyl groups
of guest molecule 6 at ꢀ1.65 ppm (Hk‑in) and protons of the
methylene bridges (HaA, HaB, HbA, and HbB) strongly supported
1
the sharp signals of encapsulated guest, H NMR signals of
cavitands of the encapsulation complex (Ha,b(encap.)) were broad-
ened at 298 K. These broadened signals started to split when the
temperature of the sample decreased; however, signals of the
encapsulated guest remained almost unchanged. The fraction of
encapsulation complex increased at lower temperature (vide
Scheme 3. Structure of C2h Symmetrical Guest Encapsulated
Hybrid Capsule
Chart 1. Structure of Guest Molecules
Figure 3. 1H NMR spectra (600 MHz, CDCl3) of [12Pd2(dppp)2(OTf)4] = 4 mM and [6] = 40 mM at (a) 298 K, and (b) 243 K.
16653
dx.doi.org/10.1021/ja207092c |J. Am. Chem. Soc. 2011, 133, 16650–16656

Journal of the American Chemical Society
ARTICLE
Figure 5. 1H NMR spectra (600 MHz, CDCl3) of (a) 11 alone at 298 K;
(b) [11] = [Pd(dppp)(OTf)2] = 8 mM at 298 K. (c) [112Pd2(dppp)2-
(OTf)4] = 4 mM and [6] = 40 mM at 298 K; at (d) [112Pd2(dppp)2-
(OTf)4] = 4 mM and [6] = 40 mM at 243 K.
1
Figure 4. 1Hꢀ H NOESY spectrum of 6@12Pd2(dppp)2(OTf)4 (600
MHz, CDCl3, 243 K, mixing time 0.5 s).
the encapsulation. Similar NOE correlations between encapsu-
lated guest and cavitand were observed between aromatic pro-
tons (Hl‑in) and methylene bridge (HaA, HaB, HbA, and HbB), or
olefinic protons (Hn‑in) and NꢀH protons of the 3-carbamoyl-
phenyl groups (Hj). The aromatic protons of HfA, HfB, HiA, and
HiB appeared at 4.55, 7.23, 7.51, and 5.82 ppm, respectively.
Upfield shifts of HfA and HiB indicated that these protons are
directed toward the inside of the cavity. NOE correlations of
HaAꢀHfA, HbAꢀHfA, HaBꢀHiB, and HbBꢀHiB supported this
assignment. To summarize these assignments, the C2h structure
of the encapsulation complex {6@[12Pd2(dppp)2(OTf)4]}
shown in Scheme 3 was confirmed. Exchange cross-peaks between
of hydrogen bonds for the structural regulation of the hybrid
capsule was performed. C2v cavitand 11 with two pyridylethynyl
groups and two methyl benzoates served as a contrasting com-
pound to 1; it lacked hydrogen-bonding ability. Cavitand 11 was
synthesized by two palladium-catalyzed cross-coupling reactions
of C2v symmetrical dibromo-diboronic acid cavitand 3 (Figure 5a
and Supporting Information). A 1:1 mixture of 11 and Pd-
1
(dppp)(OTf)2 in CDCl3 showed highly symmetrical H NMR
signals, corresponding to capsular assembly [112Pd2(dppp)2-
(OTf)4] (Figure 5b). This means that the capsular structure of
[112Pd2(dppp)2(OTf)4] was constructed only by metalꢀligand
coordination bonds (Scheme 4). The coordination bonding
capsule [112Pd2(dppp)2(OTf)4] could encapsulate 6 in the same
way as the hybrid capsule [12Pd2(dppp)2(OTf)4] (Figure 5c).
HaA and HaB were observed in the Hꢀ H NOESY spectrum,
originating from the interconversion of the C2h capsule (Figure 4).
The rate of the chemical exchange (k value of HaAꢀHaB) was
determined to be 2.44 sꢀ1 at 243 K by EXSY analysis. The
calculated ΔGq of 13.7 kcal/mol corresponds to the activation
barrier for the interconversion resulting from rotation of the
3-carbamoylphenyl groups, as shown in Scheme 3. Structurally
similar guest molecules, such as trans-4,40-dibromo stilbene (7),
1,2-di-p-tolylethane (8), and 1,2-di-p-tolylethyne (9), also en-
capsulated in the hybrid capsule [12Pd2(dppp)2(OTf)4] (Figure
S5). Those encapsulation complexes again showed structural
regulation, and splits of cavitand protons were observed at lower
temperature. A 1:5 mixture of [12Pd2(dppp)2(OTf)4] and 4,40-
1
1
1
For instance, in the H NMR spectrum at 298 K, the methyl
groups of encapsulated 6 showed an upfield shift (δ = ꢀ1.52 ppm;
Δδ = ꢀ3.88 ppm) because of the ring current effect of the
cavitand. Encapsulation complex {6@[112Pd2(dppp)2(OTf)4]}
maintained its symmetry in the 1H NMR spectrum, even at lower
temperature (Figure 5d). The difference between [12Pd2(dppp)2-
(OTf)4] and [112Pd2(dppp)2(OTf)4] clearly indicates the im-
portance of the hydrogen bond for structural alteration of the
hybrid capsule through guest encapsulation.
Thermodynamic and Kinetic Properties of Guest Encap-
sulation. A 1:1 mixture of capsule [12Pd2(dppp)2(OTf)4] and
guest 6 showed the encapsulation complex {6@[12Pd2(dppp)2-
1
diiodobiphenyl (10) showed broad signals in the H NMR
spectrum at 298 K (Figure S5). Because the length along the
long axis of 10 is shorter than those of the other guest molecules
(6ꢀ9), the exchange between encapsulated 10 and free 10 would
1
(OTf)4]} and free capsule as separate H NMR signals. The
binding constant (K) at 263 K, determined from the integration
ratios, was estimated to be 214 Mꢀ1 (K = 76 Mꢀ1 at 298 K).
Variable temperature (VT) NMR data and van’t Hoff plot pro-
vided the thermodynamic data of the encapsulation (Figure S7).
Negative values for both ΔH° (ꢀ3.74 kcal/mol) and ΔS°
1
be faster than the NMR time scale. The H NMR spectrum at
243 K showed encapsulation complex [10@12Pd2(dppp)2(OTf)4],
free capsule [12Pd2(dppp)2(OTf)4], and free guest (10) as
independent signals (Figure S5). In addition, the encapsulation
complex [10@12Pd2(dppp)2(OTf)4] at lower temperature was
assigned to the C2h structure similar to other encapsulation com-
plexes as mentioned above. The encapsulation complex {10@-
[12Pd2(dppp)2(OTf)4]} was detected in the FT-ICR-MS as a
tetravalent molecular ion peak at m/z 1045.63 (theoretical
1045.60) (Figure S6).
(ꢀ3.68 cal/mol K) indicated the exothermic enthalpy driven
3
encapsulation nature of the process. The thermodynamic proper-
ties of guest encapsulations are summarized in Table 1. Binding
constants of [12Pd2(dppp)2(OTf)4] with other guest molecules
(7ꢀ10) were smaller than that with 6. A slight alteration in size
and shape of guest molecules influenced the thermodynamic
stabilities of the encapsulation complexes. To our surprise, the
binding constants of [112Pd2(dppp)2(OTf)4] with 6 were similar
to that of [12Pd2(dppp)2(OTf)4] with 6 (K = 192 Mꢀ1 at 263 K;
Non-Hydrogen-Bonding Capsular Assembly. An encapsu-
lation experiment using a supramolecular capsule constructed
from only metalꢀligand coordination bonds to prove the effect
16654
dx.doi.org/10.1021/ja207092c |J. Am. Chem. Soc. 2011, 133, 16650–16656

Journal of the American Chemical Society
ARTICLE
Scheme 4. Self-Assembly of Cavitand 11 and Pd(dppp)(OTf)2 and Guest Encapsulation
Table 1. Thermodynamic Properties of Guest Encapsulation: Equilibrium Constant between Guest Filled and Free Capsules
(K, Mꢀ1) and Corresponding Values of Free Energy (ΔG°, kcal/mol), Enthalpy (ΔH°, kcal/mol), and Entropy (ΔS°, cal/mol K)a
3
capsule
guest
T (K)
Kb
ΔG0
ΔH0
ΔS0
c
d
d
12Pd2(dppp)2(OTf)4
12Pd2(dppp)2(OTf)4
12Pd2(dppp)2(OTf)4
12Pd2(dppp)2(OTf)4
12Pd2(dppp)2(OTf)4
112Pd2(dppp)2(OTf)4
6
263
263
263
263
263
263
214 ( 5
96.5 ( 3
39.5 ( 2
14.0 ( 1
65.5 ( 1
192 ( 1
ꢀ2.80 ( 0.01
ꢀ2.39 ( 0.02
ꢀ1.91 ( 0.02
ꢀ1.39 ( 0.01
ꢀ2.15 ( 0.03
ꢀ2.75 ( 0.01
ꢀ3.74 ( 0.06
ꢀ4.14 ( 0.09
ꢀ6.08 ( 0.04
ꢀ3.23 ( 0.14
ꢀ2.19 ( 0.20
ꢀ4.83 ( 0.16
ꢀ3.68 ( 0.29
ꢀ6.65 ( 0.29
ꢀ15.9 ( 0.10
ꢀ7.07 ( 0.63
ꢀ0.75 ( 0.06
ꢀ7.98 ( 0.68
7
8
9
10
6
a Average of two runs. b K = [guest filled capsule]/[free capsule][guest]. c ΔG° = ꢀRT ln K. d ΔG° = ΔH° ꢀ TΔS°.
K = 56 Mꢀ1 at 298 K). This means that hydrogen bonding of the
hybrid capsule has only a small influence on the thermodynamics
of the guest encapsulation. The exchange rate constants of guest
’ EXPERIMENTAL SECTION
General. Chemicals and solvents required were obtained from
commercial suppliers. 1H, 13C, and 2D NMR spectra were recorded on a
JEOL JNM-ECA600 spectrometer. Mass spectra were measured on a
JMS-T100LC AccTOF (JEOL) or a solariX FT-ICR-MS (Bruker Daltonik
GmbH) spectrometer.
Dibromo-bis(3-cyanophenyl) Cavitand (4). A mixture of cavitand 3
(3.50 g, 2.98 mmol), 3-bromobenzonitrile (2.17 g, 11.9 mmol), PdCl2-
(PPh3)2 (544 mg, 0.77 mmol), AsPh3 (913 mg, 2.98 mmol), and Cs2CO3
(7.77 g, 23.8 mmol) in 1,4-dioxane (90 mL) and H2O (9.0 mL) was
refluxed for 3 days under an argon atmosphere. The reaction mixture
was concentrated under reduced pressure, and then H2O and EtOAc
were added. The separated organic layer was washed with H2O and brine
successively and dried over Na2SO4. After removal of solvent, the
crude mixture was purified by column chromatography (SiO2 EtOAc/
hexane = 1/20). The desired product 4 was obtained as a pale yellow
solid (1.96 g, 51% yield).
1
molecule were calculated from 1Hꢀ H NOESY spectra. Values
of the rate constant (kꢀ1) and activation energy (ΔG q) for the
ꢀ1
release of encapsulated 6 from [12Pd2(dppp)2(OTf)4] or [112Pd2-
(dppp)2(OTf)4] at 298 K were determined by EXSY analyses
(Figures S8 and S9). The release rate constant (kꢀ1) of guest 6
from the hybrid capsule [12Pd2(dppp)2(OTf)4] was 0.034 sꢀ1
.
On the other hand, the release rate constant (kꢀ1) of guest 6
from the capsule that lacked hydrogen-bonding ability [112Pd2-
(dppp)2(OTf)4] was 5 times faster (0.173 sꢀ1). Approximately 1
kcal/mol difference existed in their activation energies (19.4
kcal/mol for [12Pd2(dppp)2(OTf)4], 18.5 kcal/mol for [112Pd2-
(dppp)2(OTf)4]). Hydrogen bonding of the hybrid capsule
strongly influenced the kinetics of in/out guest exchange.
Mp 129 °C; 1H NMR (CDCl3) δ 0.90 (t, J = 6.9 Hz, 12H), 1.28ꢀ1.46
(m, 40H), 2.25ꢀ2.29 (m, 8H), 4.28 (d, J = 7.6 Hz, 4H), 4.84 (t, J = 8.2
Hz, 4H), 5.58 (d, J = 7.6 Hz, 4H), 7.16 (s, 2H), 7.23 (s, 2H), 7.28 (d, J =
7.6 Hz, 2H), 7.40 (s, 2H), 7.53 (d, J = 7.9 Hz, 2H), 7.65 (d, J = 7.9 Hz,
2H); 13C NMR (CDCl3) δ 14.25, 22.80, 27.96, 29.50, 29.84, 30.24,
31.99, 37.50, 99.50, 112.77, 113.33, 118.59, 119.12, 121.16, 127.90,
129.21, 131.27, 133.64, 134.14, 135.47, 138.88, 139.39, 152.31, 152.46;
HRMS (ESI, M + Na+) calcd for C74H84Br2N2NaO8: 1309.4492; found
1309.4518.
Bis(4-pyridylethynyl)-bis(3-cyanophenyl) Cavitand (5). A mixture of
cavitand 4 (1.24 g, 0.96 mmol), 4-pyridylacetylene (595 mg, 5.77 mmol),
PdCl2(PPh3)2 (202 mg, 0.29 mmol), and AsPh3 (295 mg, 0.96 mmol)
in 1,4-dioxane (32 mL) was refluxed for 3 days under an argon atmos-
phere. After the same treatment described above, the crude mixture was
’ CONCLUSIONS
We have demonstrated that 4-pyridylethynyl and 3-carbam-
oylphenyl bound C2v symmetrical cavitand and divalent palla-
dium complexes self-assemble into a hybrid supramolecular
capsule via both metalꢀligand coordination bonds and hydrogen
bonds. Encapsulations of appropriate guest molecules were identi-
fied. Structural alteration of the hybrid capsule was observed
through guest encapsulation. The C2h structure of the encapsulation
complex was confirmed by NMR analysis. The hydrogen bonding of
the hybrid capsule has only a small influence on the thermodynamic
properties of guest encapsulation. In marked contrast, the kinetic
properties of guest encapsulations change, depending on the
presence or absence of hydrogen-bonding moieties in the capsule.
16655
dx.doi.org/10.1021/ja207092c |J. Am. Chem. Soc. 2011, 133, 16650–16656

Journal of the American Chemical Society
ARTICLE
purified by column chromatography (SiO2 EtOAc/hexane = 1/2).
The desired product 5 was obtained as a pale yellow solid (602 mg,
47% yield).
Fujita, M. Angew. Chem., Int. Ed. 2009, 48, 3418–3438. (d) Pluth, M. D.;
Bergman, R. G.; Raymond, K. N. Acc. Chem. Res. 2009, 42, 1650–1659.
(e) Breiner, B.; Clegg, J. K.; Nitschke, J. R. Chem. Sci. 2011, 2, 51–56.
(4) Cram, D. J. Science 1983, 219, 1177–1183.
1
Mp 258ꢀ259 °C; H NMR (CDCl3) δ 0.91 (t, J = 6.9 Hz, 12H),
(5) (a) Chapman, R. G.; Sherman, J. C. J. Am. Chem. Soc. 1995,
117, 9081–9082. (b) Heinz, T.; Rudkevich, D. M.; Rebek, J., Jr. Nature
1998, 394, 467–466. (c) L€utzen, A.; Renslo, A. R.; Schalley, C. A.;
O’Leary, B. M.; Rebek, J., Jr. J. Am. Chem. Soc. 1999, 121, 7455–7456.
(d) Kobayashi, K.; Shirasaka, T.; Yamaguchi, K.; Sakamoto, S.; Horn, E.;
Furukawa, N. Chem. Commun 2000, 41–42. (e) Ebbing, M. H. K.; Villa,
M.-J.; Valpuesta, J.-M.; de Mendoza, J. Proc. Natl. Acad. Sci. U.S.A. 2002,
99, 4962–4966. (f) Kobayashi, K.; Ishii, K.; Sakamoto, S.; Shirasaka, T.;
Yamaguchi, K. J. Am. Chem. Soc. 2003, 125, 10615–10624. (g) Yamanaka,
M.; Ishii, K.; Yamada, Y.; Kobayashi, K. J. Org. Chem. 2006, 71, 8800–
8806. (h) Kobayashi, K.; Kitagawa, R.; Yamada, Y.; Yamanaka, M.;
Suematsu, T.; Sei, Y.; Yamaguchi, K. J. Org. Chem. 2007, 72, 3342–
3346. (i) Ajami, D.; Rebek, J., Jr. Angew. Chem., Int. Ed. 2007, 46, 9283–
9286. (j) Park, Y. S.; Paek, K. Org. Lett. 2008, 10, 4867–4870. (k) Harthong,
S.; Dubessy, B.; Vachon, J.; Aronica, C.; Mulatier, J.-C.; Dutasta, J.-P.
J. Am. Chem. Soc. 2010, 132, 15637–15643.
(6) (a) Jacopozzi, P.; Dalcanale, E. Angew. Chem., Int. Ed. Engl. 1997,
36, 613–615. (b) Fox, O. D.; Dalley, N. K.; Harrison, R. G. J. Am. Chem.
Soc. 1998, 120, 7111–7112. (c) Fox, O. D.; Drew, M. G. B.; Beer, P. D.
Angew. Chem., Int. Ed. 2000, 39, 135–140. (d) Pinalli, R.; Cristini, V.;
Sottili, V.; Geremia, S.; Campagnolo, M.; Caneschi, A.; Dalcanale, E.
J. Am. Chem. Soc. 2004, 126, 6516–6517. (e) Kobayashi, K.; Yamada, Y.;
Yamanaka, M.; Sei, Y.; Yamaguchi, K. J. Am. Chem. Soc. 2004, 126,
13896–13897. (f) Park, S. J.; Shin, D. M.; Sakamoto, S.; Yamaguchi, K.;
Chung, Y. K.; Lah, M. S.; Hong, J.-I. Chem.-Eur. J. 2005, 11, 235–241.
(g) Haino, T.; Kobayashi, M.; Chikaraishi, M.; Fukazawa, Y. Chem.
Commun. 2005, 2321–2323. (h) Ugono, O.; Moran, J. P.; Holman, K. T.
Chem. Commun. 2008, 1404–1406. (i) Schr€oder, T.; Brodbeck, R.;
Letzel, M. C.; Mix, A.; Schnatwinkel, B.; Tonigold, M.; Volkmer, D.;
Mattay, J. Tetrahedron Lett. 2008, 49, 5939–5942.
1.32ꢀ1.47 (m, 40H), 2.24ꢀ2.35 (m, 8H), 4.39 (d, J = 6.9 Hz, 4H), 4.85
(t, J = 7.9 Hz, 4H), 5.61 (d, J = 6.9 Hz, 4H), 7.23 (d, J = 6.2 Hz, 4H), 7.25
(s, 2H), 7.26 (s, 2H), 7.29 (d, J = 7.6 Hz, 2H), 7.40 (s, 2H), 7.54 (t, J =
7.6 Hz, 2H), 7.66 (d, J = 7.6 Hz, 2H), 8.56 (d, J = 6.2 Hz, 4H); 13C NMR
(CDCl3) δ 14.25, 22.80, 27.96, 29.50, 29.83, 30.05, 31.73, 31.99, 36.92,
85.62, 94.86, 99.44, 112.22, 112.77, 118.61, 121.00, 121.37, 125.58,
127.94, 129.30, 130.90, 131.28, 133.55, 135.55, 138.58, 138.97, 150.00,
152.49, 155.77; HRMS (ESI, M + Na+) calcd for C88H92N4NaO8:
1355.6813; found 1355.6832.
Bis(4-pyridylethynyl)-bis(3-carbamoylphenyl) Cavitand (1). A mix-
ture of cavitand 5 (630 mg, 0.47 mmol) and KOH (2.65 g, 47.2 mmol) in
1,4-dioxane (13 mL), H2O (6.0 mL), and EtOH (4.0 mL) was refluxed
for 2 days under an argon atmosphere. After the same treatment
described above, the crude mixture was recrystallized from EtOH. The
desired product 1 was obtained as a pale yellow solid (340 mg, 53%
yield).
1
Mp 151ꢀ152 °C; H NMR (CDCl3) δ 0.91 (t, J = 7.2 Hz, 12H),
1.29ꢀ1.49 (m, 40H), 2.25ꢀ2.35 (m, 8H), 4.44 (d, J = 6.9 Hz, 4H), 4.85
(t, J = 7.9 Hz, 4H), 5.67 (d, J = 6.9 Hz, 4H), 5.59 (brs, 2H), 6.11 (brs,
2H), 7.22 (d, J = 5.5 Hz, 4H), 7.25 (s, 2H), 7.26 (s, 2H), 7.35 (d, J =
7.6 Hz, 2H), 7.51 (t, J = 7.6 Hz, 2H), 7.53 (s, 2H), 7.75 (d, J = 7.6 Hz,
2H), 8.53 (d, J = 5.5 Hz, 4H); 13C NMR (CDCl3) δ 14.27, 22.82, 28.02,
29.53, 29.87, 30.11, 32.01, 36.92, 85.98, 94.64, 99.49, 112.19, 120.32,
121.41, 125.62, 126.11, 128.72, 129.02, 129.33, 131.12, 133.11, 135.03,
138.54, 138.66, 149.92, 152.62, 155.79, 159.73, 168.64; HRMS (ESI,
M + Na+) calcd for C88H96N4NaO10: 1391.7024; found 1391.7010.
’ ASSOCIATED CONTENT
(7) (a) Gibb, C. L. D.; Gibb, B. C. J. Am. Chem. Soc. 2004, 126,
11408–11409. (b) Oshovsky, G. V.; Reinhoudt, D. N.; Verboom, W.
J. Am. Chem. Soc. 2006, 128, 5270–5278. (c) Giles, M. D.; Liu, S.;
Emanuel, R. L.; Gibb, B. C.; Grayson, S. M. J. Am. Chem. Soc. 2008, 130,
14430–14431. (d) Lledꢀo, A.; Restorp, P.; Rebek, J., Jr. J. Am. Chem. Soc.
2009, 131, 2440–2441.
S
Supporting Information. Synthetic procedures and spec-
b
tral data. This material is available free of charge via the Internet
at http://pubs.acs.org.
’ AUTHOR INFORMATION
(8) Yamanaka, M.; Toyoda, N.; Kobayashi, K. J. Am. Chem. Soc.
2009, 131, 9880–9881.
Corresponding Author
smyaman@ipc.shizuoka.ac.jp
(9) (a) Shivanyuk, A.; Rebek, J., Jr. J. Am. Chem. Soc. 2002, 124,
12074–12075. (b) Shivanyuk, A.; Rebek, J., Jr. Angew. Chem., Int. Ed.
2003, 42, 684–686. (c) Yamanaka, M.; Shivanyuk, A.; Rebek, J., Jr. Proc.
Natl. Acad. Sci. U.S.A. 2004, 101, 2669–2672. (d) Yamanaka, M.; Rebek,
J., Jr. Chem. Commun. 2004, 1690–1691.
’ ACKNOWLEDGMENT
This work was supported in part by Grants-in-Aid from the
Ministry of Education, Science, Sports, Culture, and Technology
of Japan (no. 22750125). The research was partially carried out
using an instrument at the Center for Instrumental Analysis of
Shizuoka University. The FT-ICR-MS analysis was supported by
the Collaborative Research Program of Institute for Chemical
Research, Kyoto University.
(10) Kobayashi, K.; Ishii, K.; Yamanaka, M. Chem.-Eur. J. 2005,
11, 4725–4734.
(11) Kitagawa, H.; Kobori, Y.; Yamanaka, M.; Yoza, K.; Kobayashi,
K. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 10444–10448.
(12) Capsular structure was distorted and the symmetry was reduced
by interior modification with bis-surfonate anion: Hiraoka, S.; Kiyokawa,
M.; Hashida, S.; Shionoya, M. Angew. Chem., Int. Ed. 2010, 49, 138–143.
(13) Moran, J. R.; Karbach, S. K.; Cram, D. J. J. Am. Chem. Soc. 1982,
104, 5826–5828.
’ REFERENCES
(14) Barrett, E. S. B.; Irwin, J. L.; Turner, P.; Sherburn, M. S. J. Org.
Chem. 2001, 66, 8227–8229.
(1) (a) Philp, D.; Stoddart, J. F. Angew. Chem., Int. Ed. Engl. 1996,
35, 1154–1196. (b) Prins, L. J.; Reinhoudt, D. N.; Timmerman, P.
Angew. Chem., Int. Ed. 2001, 40, 2382–2426.
(2) (a) Hof, F.; Craig, S. L.; Nuckolls, C.; Rebek, J., Jr. Angew. Chem.,
Int. Ed. 2002, 41, 1488–1508. (b) Seidel, S. R.; Stang, P. J. Acc. Chem. Res.
2002, 35, 972–983. (c) Fujita, M.; Tominaga, M.; Hori, A.; Therrien, B.
Acc. Chem. Res. 2005, 38, 369–378. (d) Dalgarno, S. J.; Power, N. P.;
Atwood, J. L. Coord. Chem. Rev. 2008, 252, 825–841.
(15) Tougerti, A.; Negri, S.; Jutand, A. Chem.-Eur. J. 2007, 13, 666–676.
(16) Fochi, F.; Jacopozzi, P.; Wegelius, E.; Rissanen, K.; Cozzini, P.;
Marastoni, E.; Fisicaro, E.; Manini, P.; Fokkens, R.; Dalcanale, E. J. Am.
Chem. Soc. 2001, 123, 7539–7552.
(17) (a) Steffen, W. L.; Palenik, G. J. Inorg. Chem. 1976, 15,
2432–2439. (b) Makhaev, V. D.; Dzhabieva, Z. M.; Konovalikhin,
S. V.; D’yachenko, O. A.; Belov, G. P. Russ. J. Coord. Chem. 1996, 22,
598–602.
(3) (a) Rebek, J., Jr. Angew. Chem., Int. Ed. 2005, 44, 2068–2078.
(b) Fiedler, D.; Leung, D. H.; Bergman, R. G.; Raymond, K. N. Acc.
Chem. Res. 2005, 38, 349–358. (c) Yoshizawa, M.; Klosterman, J. K.;
16656
dx.doi.org/10.1021/ja207092c |J. Am. Chem. Soc. 2011, 133, 16650–16656