Restricted guest tumbling in phosphorylated self-assembled capsules

Article abstract of DOI:10.1021/ja104388t

ABii diphosphonatocavitands self-assemble in chloroform solution to form dimeric molecular capsules. The molecular capsules can incarcerate an N-methylpyridinium or N-methylpicolinium guest. We have demonstrated that the supramolecular assembly acts as a

Full text of DOI:10.1021/ja104388t

Published on Web 10/14/2010
Restricted Guest Tumbling in Phosphorylated Self-Assembled
Capsules
Steven Harthong, Be´atrice Dubessy, Je´roˆme Vachon, Christophe Aronica,
Jean-Christophe Mulatier, and Jean-Pierre Dutasta*
´
Laboratoire de Chimie, Ecole Normale Supe´rieure de Lyon, CNRS, 46 Alle´e d’Italie,
F-69364 Lyon, France
Received May 31, 2010; E-mail: jean-pierre.dutasta@ens-lyon.fr
Abstract: ABii diphosphonatocavitands self-assemble in chloroform solution to form dimeric molecular
capsules. The molecular capsules can incarcerate an N-methylpyridinium or N-methylpicolinium guest.
We have demonstrated that the supramolecular assembly acts as a molecular rotor as a result of the
restricted motion of the guest inside the molecular cavity. In the solid state, X-ray diffraction analysis of the
free host showed that two cavitands interact through strong hydrogen bonds to give the supramolecular
self-assembled capsule. The solid-state structure of the N-methylpicolinium complex is comparable to that
of the free host and indicates that the guest is not a prerequisite for the formation of the capsule. DOSY
NMR studies provided a definitive argument for the formation of the free and complexed supramolecular
capsule in CDCl3 solution. In solution, the tumbling of the N-methylpyridinium and N-methylpicolinium guests
about the equatorial axes of the host can be frozen and differs by the respective energy barriers, with the
larger picolinium substrate having a larger value (∆Gq ) 69.7 kJ mol-1) than the shorter pyridinium guest
(∆Gq ) 44.8 kJ mol-1). This behavior corresponds to the restricted rotation of a rotator in a supramolecular
rotor.
Introduction
could act as a rotator, the mobile part of a molecular rotor or
gyroscope. The trapped guest in the host cavity can play such
The cavitand structure is obtained by the bridging of a
resorcarene molecule with various moieties, including methylene
or higher alkyl groups, aromatic spacers, or silicium and
phosphorus moieties.1,2 Resorcarenes are known to self-assemble
to form dimeric or hexameric molecular capsules with interesting
complexation properties. For example, dicationic species were
encapsulated within solvent (water)-driven resorcarene capsules.3
On the other hand, (hemi)carcerands, made of two covalently
bound cavitands, can encapsulate different guests. It has been
shown that in the latter system, the tumbling of the guest in the
molecular cavity is restricted and often is possible only along
the polar axis of the cavity.4 Thus, different dynamics of
incarcerated guests are observed, depending on the size and
shape of the guest. If the rotation of a molecular entity, either
a molecule or part of it, can be monitored and controlled, it
a role. In these supramolecular systems, the stator and rotator
are not covalently bound. Such features may present advantages
and facilitate their syntheses. In this way, a wider variety of
modular rotating subunits become more accessible without
repeating synthetic efforts. Each part can suitably self-arrange
during the thermodynamic equilibration process. In the design
of new materials from such systems, it also offers the possibility
to limit unfavorable interactions with surfaces in self-assembled
systems, and the supramolecular encaging may prevent undesir-
able mechanical effects or electronic interactions between rotors.
The growing interest in the design of molecular receptors
with nanometer-sized cavities based on self-assembly has
resulted in very sophisticated molecular objects with potential
interest in the design of chemical nanoreactors, containers, or
delivery systems.5 Undoubtedly, many properties of such
systems are still unrevealed and will open new exciting fields
of investigation, including mimicking biological processes and
performing controllable functions at the molecular level. Self-
assembled molecular capsules have been obtained by H-
(1) (a) Cram, D. J.; Cram, J. M. Container Molecules and Their Guests;
Royal Society of Chemistry: Cambridge, U.K., 1994. (b) Timmerman,
P.; Verboom, W.; Reinhoudt, D. N. Tetrahedron 1996, 52, 2663. (c)
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9
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A R T I C L E S
Harthong et al.
bonding,6 coordination to metal atoms,7 and ionic8 or solvo-
phobic interactions9 when a suitable substitution was performed
on the resorcarene structure. However, the driving forces for
encapsulation of guests in these hosts are mainly due to rather
weak CH-π and cation-π interactions or hydrophobic forces.
The recent work of Kobayashi and co-workers10 presents a self-
assembled heterodimer capsule made of two cavitands that can
encapsulate a 1,4-diacetoxybenzene derivative. In this example,
the guest molecule can rotate along the north-south axis of
the capsule and behaves as a supramolecular gyroscope. The
energy barrier for the rotation depends on the substitution on
the aromatic guest.
In this work, we considered the formation of molecular
associations involving H-bonds and strong dipolar interactions
between ammonium guests and phosphonate cavitands. Phos-
phonate cavitands represent an original family of molecular hosts
that contain endohedral binding sites, giving them remarkable
binding properties. For instance, the tetra-bridged 4iPO (iiiiPO)
cavitands 1 (Figure 1) are known to bind hard cationic species
efficiently.2,11 Partially phosphorylated cavitands can complex
primary alcohols by means of CH-π interactions and H-bonds
between the alcoholic OH and PO groups, indicating that
increasing the number of PO groups enhances the stability of
the complex.12 We report herein the preparation and behavior
of 2iPO (iiPO) phosphorylated cavitands that bear two phos-
phonate bridging moieties and can self-assemble in solution to
form a molecular capsule. In the presence of a suitable
pyridinium guest, which experiences restricted mobility, the
newly designed capsular complexes act as molecular rotors.
In particular, we investigated the ABii phosphorylated hosts
formed by bridging only two (proximal) sites of the resorcarene
scaffold (Figure 1), which thus still contains free OH functions
that can arrange to form associations mediated by H-bonding.
The cavities of these hosts are preorganized enough to provide
novel self-assembled systems.
Figure 1. Structures of the 4iPO phosphorylated cavitands 1 and the 2iPO
phosphorylated cavitands ABii (3 and 5) and ACii (4 and 6). The labels
AB and AC indicate the proximal and distal positions of the two phosphorus
groups in the 2i derivatives.
reaction of resorcarene 2a or 2b with PhPCl2 followed by
addition of sulfur gave a mixture of the corresponding ABii
derivative 3a or 3b and ACii derivative 4a or 4b. Compounds
3a and 4a were obtained in 24 and 8% yield, respectively. A
similar procedure was used to synthesize cavitands 3b and 4b,
which were obtained with lower yields, probably because of
their lower solubility. However, the phenethyl feet in the new
derivatives 3b and 4b facilitated the formation of single crystals
for X-ray analysis. The subsequent treatment of 3 and 4 with
m-chloroperoxybenzoic acid (MCPBA) led to the derivatives 5
and 6, respectively, in good yields. The NMR spectra of
compounds 3-6 were in accord with a rigid cavity and an
inward orientation of the PdX (X ) S, O) bonds. The ACii
derivatives that were synthesized together with the ABii isomers
behave differently and were not considered in this study.
Binding of Pyridinium Guests. The encapsulation of pyri-
dinium picrate and pyridinium iodide guests, namely, N-
methylpyridinium picrate (PyrPic) and iodide (PyrIod) and
N-methylpicolinium picrate (PicoPic) and iodide (PicoIod), by
cavitand 5a in CD2Cl2 was investigated using 1H and 31P NMR
spectroscopy, which is a useful tool for studying the encapsula-
tion process because of the strong anisotropic shifts due to ring-
current effects from both the host and the pyridinium guest.
Addition of PyrPic to a solution of 5a in CD2Cl2 at 293 K
resulted in the appearance of new signals for the host in the 1H
NMR spectrum that were unambiguously assigned on the basis
of 2D NMR experiments, while the signals of the free host
vanished as the concentration of the guest increased (Figure
2). After addition of 0.5 equiv of guest, only the signals of the
new species were visible. After more than 0.5 equiv of guest
was added, extra peaks from the free guest appeared, indicating
that the host-guest exchange at room temperature is slow on
Results and Discussion
Synthesis. The strategy used to obtain the partially bridged
phosphorus cavitands has been reported elsewhere.13 The
(6) (a) Atwood, J. L. Nature 1997, 389, 469. (b) Heinz, T.; Rudkevich,
D. M.; Rebek, J., Jr. Nature 1998, 394, 764. (c) Shivaniuk, A.; Paulus,
E. F.; Bo¨hmer, V. Angew. Chem., Int. Ed. 1999, 38, 2906. (d)
Kobayashi, K.; Ishii, K.; Sakamoto, S.; Shirasaka, T.; Yamagushi, K.
J. Am. Chem. Soc. 2003, 125, 10615.
(7) (a) Jacopozzi, P.; Dalcanale, E. Angew. Chem., Int. Ed. Engl. 1997,
36, 613. (b) Bibal, B.; Tinant, B.; Declercq, J.-P.; Dutasta, J.-P. Chem.
Commun. 2002, 432. (c) Pinalli, R.; Cristini, V.; Sottili, V.; Geremia,
S.; Campagnolo, M.; Caneschi, A.; Dalcanale, E. J. Am. Chem. Soc.
2004, 126, 6516. (d) Park, D. J.; Shin, D. M.; Sakamoto, S.;
Yamagushi, K.; Chung, Y. K.; Lah, M. S.; Hong, J.-L. Chem.sEur.
J. 2005, 11, 235.
(8) Oshovsky, G. V.; Reinhoudt, D. N.; Verboom, W. J. Am. Chem. Soc.
2006, 128, 5270.
(9) Giles, M. D.; Liu, S.; Emanuel, R. L.; Gibb, B. C.; Grayson, S. M.
J. Am. Chem. Soc. 2008, 130, 14430.
(10) (a) Kitagawa, H.; Kobori, Y.; Yamanaka, M.; Yoza, K.; Kobayashi,
K. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 10444. (b) Nishimura,
N.; Kobayashi, K. J. Am. Chem. Soc. 2010, 132, 777.
(11) (a) Nifantyev, E.; Maslennikova, V. I.; Merkulov, R. Acc. Chem. Res.
2005, 38, 108. (b) Irico, A.; Vincenti, M.; Dalcanale, E. Chem.sEur.
J. 2001, 7, 2034.
(12) (a) Paolesse, R.; Di Natale, C.; Nardis, S.; Macagnano, A.; D’amico,
A.; Pinalli, R.; Dalcanale, E. Chem.sEur. J. 2003, 9, 5388. (b) Suman,
M.; Freddi, M.; Massera, C.; Ugozzoli, F.; Dalcanale, E. J. Am. Chem.
Soc. 2003, 125, 12068. (c) Pinalli, R.; Suman, M.; Dalcanale, E. Eur.
J. Org. Chem. 2004, 451.
(13) Vachon, J.; Harthong, S.; Dubessy, B.; Dutasta, J.-P.; Vanthuyne, N.;
Roussel, C.; Naubron, J.-V. Tetrahedron: Asymmetry 2010, 21, 1534.
9
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Phosphorylated Self-Assembled Capsules
A R T I C L E S
Figure 2. 1H NMR spectra (500 MHz, CD2Cl2, 293 K) of (a) free host 5a,
(b) 5a + 0.3 equiv of PyrPic, and (c) 5a + 3.5 equiv of PyrPic. Colors:
red, bound pyridinium; blue, free pyridinium.
Table 1. 1H NMR Chemical Shifts for the Protons of the Free and
Bound N-Methylpyridinium and N-Methylpicolinium Guests in the
Presence of 5a in CD2Cl2 Solution at 293 K
guesta
ArCH3
+NCH3
Hp
Hm
Ho
Figure 3. 1H NMR spectra (500 MHz, CD2Cl2, 293 K) of (a) free host 5a,
(b) 5a + 0.2 equiv of PicoPic, (c) 5a + 0.4 equiv of PicoPic, (d) 5a + 0.5
equiv of PicoPic, and (e) 5a + 1.3 equiv of PicoPic. Colors: red, bound
picolinium; blue, free picolinium.
Pyrfree
Pyrbound
∆δfree-bound
Picofree
Picobound
∆δfree-bound
-
-
-
2.70
-0.60
3.30
4.58
0.98
3.60
4.40
0.95
3.45
8.46
4.74
3.72
-
-
-
8.06
5.58
2.48
7.80
5.86
1.94
9.10
6.17
2.93
8.80
6.04
2.76
assembly under slow-exchange conditions on the NMR time
scale at room temperature. The upfield chemical shifts of all of
the protons of the encapsulated guests suggest the formation in
solution of a molecular capsule made of two cavitands that
totally entrap the guests. From the NMR titration experiments,
it was not possible to extract accurate association constant
a Picrate salt.
the 1H NMR time scale. The 1:2 stoichiometry of the complex
was determined from the integration of the host and guest
signals. Each proton of the guest underwent a strong upfield
shift (Table 1). This can be explained by the formation of a 1:2
PyrPic@(5a)2 guest-host complex in which the encapsulated
pyridinium is trapped between two cavitands. The two bound
values. Such values could only be estimated to be >105 M-1
,
emphasizing the high stability of the complexes.14
X-ray Analysis of Host and Host-Guest Supramolecular
Assemblies. The presence of the dimeric capsule was further
supported by the X-ray diffraction molecular structures of the
parent derivatives 5b (Figure 4) and PicoIod@(5b)2 (Figure 5).
A set of NMR experiments in solution analogous to those
performed with 5a showed similar behavior for 5b with the
N-methylpicolinium salt (Figure S11 in the Supporting Informa-
tion). In the solid, the free host 5b and its picolinium complex
have very comparable structures. Both exist as a molecular
capsule made of two cavitands 5b facing each other at their
wide rims and assembled by means of four strong H-bonds
between the PO groups of one cavitand and the OH groups of
the other. In the free capsule, the average PO · · ·OH distances
is 2.64 Å, and the main axes of the two cavitands are 3.55 Å
apart,15 leading to a shift of one cavitand relative to the other
(Figure 4). Two methanol molecules from the crystallization
solution (CH2Cl2/MeOH) are present in the cavity but do not
participate in the formation of the capsule.
cavitands gave only one set of signals in the H and 31P NMR
spectra, indicating that they are chemically equivalent. The
behavior was similar with the iodide salt PyrIod (data not
shown).
1
The same experiment was run with PicoPic as the guest. The
addition of PicoPic to a solution of 5a in CD2Cl2 led to the
formation of the 1:2 PicoPic@(5a)2 complex, which exhibited
the typical upfield-shifted signals for the encapsulated guest
(Figure 3 and Table 1). As for the pyridinium salt, the exchange
between free and encapsulated guest at room temperature is slow
on the 1H NMR time scale. Addition of more than 0.5 equiv of
guest showed the signals of the free guest. Moreover, in the
complex, each of the host signals in the 1H and 31P NMR spectra
were split into two resonances, indicating that the two cavitands
in PicoPic@(5a)2 are not chemically equivalent. N-Methylpi-
colinium picrate and iodide guests behaved similarly (see
Figures S12-S14 in the Supporting Information).
(14) Under slow exchange conditions on the NMR time scale, the addition
of aliquots of a millimolar solution of guest to a millimolar solution
of host revealed only the host-guest complex and the free host. The
free guest was undetectable in the NMR spectra because of an
expectedly large association constant Kassoc. Thus, the concentration
of the undetectable species could be estimated only to e2-5% of the
starting concentration. In this case, only a lower value of Kassoc could
be estimated.
These results show that pyridinium and picolinium cations
combine with 5a to form a 1:2 guest@(5a)2 supramolecular
(15) The main axis chosen for the cavitand corresponds to the C4 pseudoaxis
of the resorcarene structure.
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A R T I C L E S
Harthong et al.
Scheme 1. Synthesis of the CH2-Bridged ABii Cavitands 7a and 7b
Table 2. Diffusion Coefficients for 1, 5, Guest + 5, and 7 and the
Corresponding Hydrodynamic Volume Ratios As Determined by
DOSY NMR Spectroscopy in CDCl3 (T ) 298 K)
Figure 4. Stereoview of the X-ray structure of the capsular dimeric
assembly [5b·CH3OH]2.
compound x
D(x) (m2 s-1
)
VH(x)/VH(1)
VH(x)/VH(7)
5a
3.29 × 10-10
3.14 × 10-10
4.27 × 10-10
4.67 × 10-10
3.91 × 10-10
3.96 × 10-10
4.87 × 10-10
4.95 × 10-10
2.2
2.5
1
0.8
1.9
1.9
1
2.9
3.3
1.3
1
2.0
1.9
1.1
1
Pico + 5a
1a
7a
5b
Pico + 5b
1b
7b
0.9
π-electron-deficient picolinium ring is sandwiched between the
1,3-dihydroxy aromatic rings of the two cavitands with a
separation of 3.56 Å. It is noteworthy that the picolinium guest
encapsulation does not dramatically change the structure of the
capsule, which is almost superimposable with that observed in
the free host.
Figure 5. Stereoview of the X-ray structure of the supramolecular complex
PicoIod@(5b)2.
A question arises concerning the structure of the complexes
and the driving forces for the encapsulation. It is known that
the CH3N+ group is strongly bound to the cavity of phospho-
rylated cavitands by efficient PO· · ·N+ interactions and van der
Waals interactions between the CH3N+ methyl group and the
aromatic cavity.11,16 Examination of the X-ray structure of
PicoIod@(5b)2 showed that the N+ atom of the guest is tightly
bound to two PO oxygen atoms (average PO · · ·N distance )
3.85 Å). The two cavitands are assembled by means of four
strong H-bonds with an average PO · · ·OH distance of 2.63 Å
between the PO group of one cavity and the OH of the other.
In comparison, the free capsule discussed above has a distance
of 2.64 Å. Interestingly, the iodide anion is located in the
pseudocavity formed by the phenethyl groups at the narrow rim
of the cavitand, as previously observed with phosphonatocav-
itand complexes (Figure S18 in the Supporting Information).17
As in the free capsule (5b)2, the two cavitands roughly face
each other at their wide rims but have their respective main
axes shifted by 3.44 Å. This results from an inclination of the
guest relative to the main axes of the cavitands (46° with respect
to the picolinium CH3-CH3 axis). Consequently, the CH3 heads
point toward the aromatic rings bearing the two phosphonate
groups in their respective cavities (Figure 5). Moreover, the
Is the Capsular Structure Maintained in Solution? DOSY
and ROESY NMR Experiments. In order to determine whether
the free capsule exists in solution, we performed diffusion-
ordered NMR spectroscopy (DOSY) experiments.18 It was
convenient to compare the self-diffusion constants D of 5a and
its complex with those of cavitands 1a and 7a as external
references. We chose these two reference molecules because
of their very similar structures and the absence of phenol OH
groups at the wide rim, which excludes dimeric or higher self-
association. Compound 7a was previously synthesized by
Dalcanale and co-workers12b through the introduction of the two
phosphonate moieties on the doubly methylene-bridged resor-
carene precursor. In the present case, the addition of an excess
of CH2ClI to cavitand 5a afforded 7a in 33% yield (Scheme
1). Cavitand 1a has been described previously.19
The results reported in Table 2 indicate two different
behaviors for 5a alone and 5a in presence of the picolinium
guest on one hand and for 1a and 7a on the other hand. The
diffusion coefficients of 5a and 5a in the presence of picolinium
salt are almost identical (i.e., the ratio of the diffusion coefficient
for host 5a to that for its picolinium complex is Dhost/Dcplx
≈
1.0), but they are smaller than those of 1a and 7a in the same
solvent. The ratio of the diffusion coefficients, which are related
tothehydrodynamicradiirH ofthespeciesbytheStokes-Einstein
equation (D ) kBT/6πηrH), was used to obtain an estimate of
(16) (a) Delangle, P.; Mulatier, J.-C.; Tinant, B.; Declercq, J.-P.; Dutasta,
J.-P. Eur. J. Org. Chem. 2001, 3695. (b) Bibal, B.; Tinant, B.;
Declercq, J.-P.; Dutasta, J.-P. Supramol. Chem. 2003, 15, 25. (c)
Yebeutchou, R. M.; Tancini, F.; Demitri, N.; Geremia, S.; Mendichi,
R.; Dalcanale, E. Angew. Chem., Int. Ed. 2008, 47, 4504. (d) Biavardi,
E.; Battistini, G.; Montalti, M.; Yebeutchou, R. M.; Prodi, L.;
Dalcanale, E. Chem. Commun. 2008, 1638.
(18) (a) Brand, T.; Cabrita, E. J.; Berger, S. Prog. NMR Spectrosc. 2005,
46, 159–196. (b) Cohen, Y.; Avram, L.; Frish, L. Angew. Chem., Int.
Ed. 2005, 44, 520.
(17) (a) De Zorzi, R.; Dubessy, B.; Mulatier, J.-C.; Geremia, S.; Randaccio,
L.; Dutasta, J.-P. J. Org. Chem. 2007, 72, 4528. (b) Dubessy, B.;
Harthong, S.; Aronica, C.; Bouchu, D.; Busi, M.; Dalcanale, E.;
Dutasta, J.-P. J. Org. Chem. 2009, 74, 3923.
(19) Melegari, M.; Suman, M.; Pirondini, L.; Moiani, D.; Massera, C.;
Ugozzoli, F.; Kalenius, E.; Vainiotalo, P.; Mulatier, J.-C.; Dutasta,
J.-P.; Dalcanale, E. Chem.sEur. J. 2008, 14, 5772.
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Phosphorylated Self-Assembled Capsules
A R T I C L E S
Figure 6. Main ROESY correlations observed between the bound guest
and the capsular host.
the hydrodynamic volume ratio (Table 2).20 We see that VH(5a)
≈ VH(Pico + 5a) ≈ 2.3VH(1a) ≈ 3.0VH(7a), supporting the
formation of the (5a)2 capsule both for the free host and the
Figure 7. 1H NMR spectra (500 MHz, CD2Cl2) of 5a + 3.5 equiv of PyrPic
at (a) 203 and (b) 293 K (red, bound guest; blue, free guest).
1
complex. This was not foreseeable from the H NMR spectra
of 5a. Furthermore, we showed by 1H NMR spectroscopy that
in a 2:1 mixture of 5a and picolinium salt, only the Pico@(5a)2
complex was observed. The DOSY data argue that free 5a in
solution exists as a dimeric assembly and that the guest is not
a prerequisite for formation of the capsular structure. We
similarly examined the behavior of 5b alone and 5b in the
presence of the picolinium guest and compared their self-
diffusion coefficients with those of 1b and 7b. Compounds 1b
and 7b were synthesized following the procedures used for 1a
and 7a. The results reported in Table 2 led to the same
conclusion as drawn for the C11H23-substituted compounds, with
VH(5b) ≈ VH(Pico + 5b) ≈ 1.9VH(1b) ≈ 2.0VH(7b). The
structure of the free host in CDCl3 solution corresponds to the
(5b)2 self-assembled molecular capsule and is thus closely
related to the one observed in the solid state by X-ray diffraction.
It is noteworthy that the long-chain substituents in 5a, a prolate
ellipsoid assembly, probably lead to an overestimated molecular
volume. The overestimation is minimized with the shorter
phenethyl groups in 5b, which results in a more spherical
assembly.20 This can explain why VH(5a) is slightly greater than
2VH(1a) and 2VH(7a) whereas the value of VH(5b) is almost
equal to 2VH(1b) and 2VH(7b).
It is interesting to compare the results of rotating-frame
Overhauser effect spectroscopy (ROESY) experiments run in
CD2Cl2 solution for the PicoIod@(5a)2 complex with the solid-
state structure of the parent PicoIod@(5b)2. This allows for the
determination of the spatial proximity of the protons involved
in the host-guest association in solution. The main cross-peaks
were measured between the CH3 groups of the N-methylpi-
colinium guest and the H1c proton at the wide rim of the opposite
cavity (C-C distance in the crystal is 3.91 Å) and the H1a and
H2 protons of its own cavity (C-C distances in the crystal are
3.62 and 3.23-3.84 Å, respectively). No other significant
correlations between host and guest were measured in the
ROESY spectra (Figure 6 and Figure S9 in the Supporting
Information). The agreement between the data from the solution
and those from the solid state suggests that on the NMR time
scale, the preferred average orientation of the guest inside the
capsule in solution is similar to that observed in the crystal.
Guest Tumbling Dynamics: NMR Characterization of the
Guest@(5a)2 Supramolecular Rotor. The dimeric capsules (5a)2
and (5b)2 exist preferentially in solution, as evidenced by the
Figure 8. VT 1H NMR spectra (200 MHz, C2D2Cl4) of 5a + 0.5 equiv of
PicoPic.
1H NMR and DOSY experiments, and their structures are closely
related to that in the solid state described above. Thus, the
formation of the capsule is not a consequence of the encapsula-
tion of the charged guest but rather the stabilizing effect of the
self-assembly of two cavitands through strong H-bonding. Here
we underline an important point that concerns the dynamics of
the encapsulated guest and the behavior of the two complexes,
which differ as a function of the temperature. At 293 K in
CD2Cl2 solution, the two cavitands in PyrPic@(5a)2 were
indistinguishable by NMR analysis (one set of signals for both
cavitands; Figure 2), whereas they were distinguishable in
PicoPic@(5a)2 (two sets of signals; Figure 3). When the
PyrPic@(5a)2 sample was cooled to 203 K, each of the host
signals split into two resonances, and the two cavitands were
thus differentiated, leading to a situation similar to that observed
with PicoPic@(5a)2 at room temperature (Figure 7). On the other
hand, when a solution of PicoPic@(5a)2 in C2D2Cl4 was heated
to 360 K, we observed a change in the 1H NMR spectra leading
to the average of the signals of the two cavitands, a situation
analogous to that observed with PyrPic@(5a)2 at room tem-
perature (Figure 8).
This behavior was also observed using variable-temperature
(VT) 31P NMR spectroscopy. At room temperature, only one
resonance for the phosphorus nuclei in PyrPic@(5a)2 was
detected. When the temperature was lowered to 220 K, two 1:1
signals corresponding to each cavitand were detected (Figure
9a). Similarly, the 1:1 signals observed at room temperature
(20) Macchioni, A.; Ciancaleoni, G.; Zuccaccia, C.; Zuccaccia, D. Chem.
Soc. ReV. 2008, 37, 479.
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A R T I C L E S
Harthong et al.
Table 3. Kinetic Parameters for the Guest Tumbling in
PyrIod@(5a)2 and PicoIod@(5a)2 Complexes
a
)
complex
∆Gq (kJ mol-1
∆Hq (kJ mol-1
)
∆Sq (J K-1 mol-1
)
PyrIod@(5a)2
PicoIod@(5a)2
44.8
69.7
46.8
72.6
6.8
9.7
a T ) 300 K.
positions and the two protons in the meta positions without
exchanging the CH3N+ and Pyr-Hp (or Pico-CCH3) positions,
and (ii) rotation about the transverse direction (i.e., about any
axis in the XY plane), which exchanges the CH3N+ and Pyr-Hp
(or Pico-CCH3) positions. If the tumbling occurs only via the Z
axis, the two cavitands constituting the capsule should look
different in the NMR spectra, as observed with the picolinium
guest at room temperature and below and with the pyridinium
guest at low temperature. Tumbling in the XY plane would
average the NMR spectra of the two cavitands and make their
signals indistinguishable, as observed with the pyridinium guest
at room temperature and above and with the picolinium guest
at high temperature.
The energy barriers for guest tumbling in PyrIod@(5a)2 and
PicoIod@(5a)2 were estimated from the VT 31P NMR experi-
ments. Bandwidth analysis afforded ∆Gq, ∆Hq, and ∆Sq values
(Table 3). 1H VT NMR experiments gave similar results,
although these had lower confidence because of the difficulties
resulting from the simulation of the experimental spectra, which
were less well resolved, and because of overlapping signals (data
not shown). It is interesting to compare these data with those
reported previously for the rotational movement of guests in
the cavity of carceplexes. For instance, the movement of
dimethylacetamide, dimethylformamide, or N-methylpyrrolidi-
Figure 9. Experimental and calculated 31P NMR spectra at different
temperatures for (a) 5a + 1 equiv of PyrPic in CD2Cl2 and (b) 5a + 1
equiv of PicoPic in C2D2Cl4.
none guests in carceplexes can be highly constrained, with
21
energy barriers ranging from 40 to 65 kJ mol-1
.
A limiting
case was shown in the recent work of Kobayashi and co-
workers10 on a self-assembled capsule involving boronic ester
bonds within which the encapsulated aromatic guest rotated only
along the long axis of the cage. In our case, the energy barriers
are in the range 45-70 kJ mol-1, which is an unexpected result
considering the noncovalent character of the cage. Moreover,
these results demonstrate the restricted tumbling of the guest
that acts as a molecular rotator inside the capsule.22
Figure 10. (a) Side and (b) top views of the X-ray structure of
PicoIod@(5b)2 that emphasize the formation of the supramolecular rotor.
for the complex PicoPic@(5a)2 vanished at 353 K and above
to give one averaged 31P NMR signal (Figure 9b). VT
experiments performed with the free host 5a, which forms a
(5a)2 capsule in solution, did not detect changes in the 1H NMR
spectra. This means that the temperature dependence observed
with the complexes is inherent to the host-guest association
and also demonstrates the high stability of the dimeric capsule.
These experiments reveal that the two cavitands in
PyrPic@(5a)2 at low temperature and in PicoPic@(5a)2 at room
temperature experience different chemical environments. The
“north” and “south” hemispheres of the capsule can be dif-
ferentiated only if tumbling is restrained inside the cavity on
the NMR time scale. This can be explained by considering the
slowing of the tumbling of the guest in the restrictive environ-
ment of the inner cavity of the capsule. The interaction of the
CH3N+ group of the guest with one cavitand and of the group
in the para position on the guest aromatic ring with the other
cavitand results in the upfield shielding of the respective protons
of the encapsulated guest. The tumbling of the guest can be
roughly decomposed into two main rotations (Figure 10): (i)
rotation about the N-Cpara direction of the guest (i.e., about
the Z axis), which exchanges the two protons in the ortho
Conclusion
In summary, we have described the self-assembly of ABii
diphosphonatocavitands that form dimeric capsular structures
by means of strong H-bonds between OH phenol groups and
PO H-bond acceptors. The capsules are stable in CDCl3 and
CD2Cl2 solutions and can encapsulate an N-methylpyridinium
or N-methylpicolinium guest. We have demonstrated that guest
encapsulation is not a prerequisite for the formation of the
capsule. The supramolecular capsules are stable over a wide
range of temperature, and the encapsulated guest experiences a
restricted tumbling movement inside the capsular cavity. Free
rotation of the guest was observed only about the long axis of
the host, while rotation about the short equatorial axes of the
host can be frozen for both guests. The longer N-methylpi-
colinium substrate was more tightly encapsulated inside the
capsular cavity than was the N-methylpyridinium guest and had
(21) (a) Sherman, J. C.; Knobler, C. B.; Cram, D. J. J. Am. Chem. Soc.
1991, 113, 2194. (b) Peak, K.; Ihm, H.; Lee, H. C.; No, K. T. J. Org.
Chem. 2001, 66, 5736.
(22) Jose, D.; Datta, A. J. Phys. Chem. Lett. 2010, 1, 1363.
9
15642 J. AM. CHEM. SOC. VOL. 132, NO. 44, 2010

Phosphorylated Self-Assembled Capsules
A R T I C L E S
Acknowledgment. We thank Florence Vial and Laurent Goujon
for experimental contributions in the early stages of this work. The
Centre de Diffractome´trie Henri Longchambon (CDHL, Institute
of Chemistry, Lyon) is acknowledged for X-ray facilities access.
a higher energy barrier for the tumbling process (69.7 vs 44.8
kJ mol-1, respectively). Thus, the tumbling of N-methylpi-
colinium is slow on the NMR time scale at room temperature,
as the signals corresponding to the two cavitands can be
differentiated in their 1H and 31P NMR spectra. These supramo-
lecular architectures possess endohedral functionalities, a feature
representing a new step in the area of nanoscale engineering
that associates the simplicity of self-assembly with the incor-
poration of functionalities, which could lead to artificial enzyme
mimetics, molecular magnets, sensors, or delivery systems. The
present system can provide insights into the design of new
molecular rotors. Current work to further exploit these results
in order to conceive novel functional materials is underway.
Supporting Information Available: Synthetic details; 1H and
13C NMR spectra of 7a and 3b-7b; VT NMR spectra; ROESY
and DOSY experimental details; and X-ray crystallographic data
(CIF) and additional molecular structure views for (5b)2 (CCDC
775618) and PicoIod@(5b)2 (CCDC 775619). This material is
available free of charge via the Internet at http://pubs.acs.org.
JA104388T
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