Encapsulated guest-host dynamics: Guest rotational barriers and tumbling as a probe of host interior cavity space

Article abstract of DOI:10.1021/ja107656g

The supramolecular host assembly [Ga₄L₆] ^12- (1; L = 1,5-bis[2,3-dihydroxybenzamido]naphthalene) encapsulates cationic guest molecules within its hydrophobic cavity and catalyzes a variety of chemical transformations withi

Full text of DOI:10.1021/ja107656g

Published on Web 10/26/2010
Encapsulated Guest-Host Dynamics: Guest Rotational Barriers
and Tumbling as a Probe of Host Interior Cavity Space
Jeffrey S. Mugridge, Ge´za Szigethy, Robert G. Bergman,* and
Kenneth N. Raymond*
Department of Chemistry, UniVersity of California, Berkeley, and Chemical Science DiVision,
Lawrence Berkeley National Laboratory, Berkeley, California 94720-1460, United States
Received August 24, 2010; E-mail: rbergman@berkeley.edu; raymond@socrates.berkeley.edu
Abstract: The supramolecular host assembly [Ga4L6]12- (1; L ) 1,5-bis[2,3-dihydroxybenzamido]naph-
thalene) encapsulates cationic guest molecules within its hydrophobic cavity and catalyzes a variety of
chemical transformations within its confined interior space. Despite the well-defined structure, the host
ligand framework and interior cavity are very flexible and 1 can accommodate a wide range of guest shapes
and sizes. These observations raise questions about the steric effects of confinement within 1 and how
encapsulation fundamentally changes the motions of guest molecules. Here we examine the motional
dynamics (guest bond rotation and tumbling) of encapsulated guest molecules to probe the steric
consequences of encapsulation within host 1. Encapsulation is found to increase the Ph-CH2 bond rotational
barrier for ortho-substituted benzyl phosphonium guest molecules by 3 to 6 kcal/mol, and the barrier is
found to depend on both guest size and shape. The tumbling dynamics of guests encapsulated in 1 were
also investigated, and here it was found that longer, more prolate-shaped guest molecules tumble more
slowly in the host cavity than larger but more spherical guest molecules. The prolate guests reduce the
host symmetry from T to C1 in solution at low temperatures, and the distortion of the host framework that
is in part responsible for this symmetry reduction is observed directly in the solid state. Analysis of guest
motional dynamics is a powerful method for interrogating host structure and fundamental host-guest
interactions.
formation of unusual or labile guest conformations,8-10 alter
guest reactivity,11-16 and catalyze a variety of chemical
Introduction
transformations.17-21
The active sites of enzymes can dramatically affect the
physical properties and reactivity of bound substrate molecules.
Hydrophobic protein binding pockets present substrates with
an environment that is sterically and electronically different from
that in aqueous solution, and this forms the basis for the
remarkable selectivity and rate accelerations observed in many
biological systems.1,2 Synthetic supramolecular host-guest
systems can function in much the same way. Encapsulated guest
molecules interact with a host cavity through noncovalent
interactions and typically experience a very different steric and
electronic environment inside the host than in bulk solution.
The unique interior environment of supramolecular host mol-
ecules has been shown to stabilize reactive species,3-7 promote
Insight into the remarkable behaviors described above comes
from a detailed understanding of the fundamental host-guest
interactions involved in these supramolecular systems. One
approach to this is the analysis of encapsulated guest confor-
mational and rotational dynamics, which can give information
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10.1021/ja107656g  2010 American Chemical Society

Encapsulated Guest-Host Dynamics
A R T I C L E S
Figure 1. Supramolecular assembly 1 as viewed down the C2 axis of the tetrahedron. (Left) Schematic of 1 with only one ligand shown for clarity; (center)
ball and stick model with one ligand highlighted; (right) space-filling model with the front half of the assembly cut away so that the interior cavity is visible.
about the effects of guest confinement within a host cavity.
Many researchers have investigated how guest encapsulation
or complexation perturbs the motional dynamics of both host
and guest molecules.22-32 In particular, Rebek and co-workers
have extensively examined the physical organic chemistry of
molecules confined within their hydrogen-bonded molecular
capsules (what they have called “inner space”).33-37 Generally,
these studies demonstrate how confinement within a host cavity
restricts the conformational, rotational, and/or translational space
available to guest molecules. Such restriction of guest motional
space can promote an increased local concentration of reactants
or stabilization of reactive guest conformations, leading to a
unique reactivity or catalysis.
can act as a host for suitably sized monocationic40-42 and
neutral43,44 guest molecules. The host structure is very flexible:
guest molecules can enter and exit host 1 by squeezing through
expandable apertures in the ligand framework, and the interior
cavity can distort to accommodate different guest shapes and
sizes.45,46 Host interior cavity volumes ranging from 250 to 450
Å3 have been observed in the solid state.47 The confinement
experienced by guests encapsulated within the host cavity has
been exploited to catalyze pericyclic rearrangements by binding
guests in a reactive conformation,48-50 impose enantioselectivity
on these rearrangements,51 and alter substrate selectivity in C-H
bond activation reactions with an encapsulated iridium com-
plex.52
While the above examples of encapsulated reactivity suggest
that guests are sterically constrained within the host cavity, the
significance and extent of these confinement effects remain
unclear given the dramatic flexibility of the host framework.
Furthermore, it was recently observed in one system that amide
bond rotation is accelerated inside of host 1 compared to its
rate in bulk solution.53 The electronic stabilization of the
hydrophobic transition state for amide bond rotation apparently
overcomes any steric effects which might serve to hinder that
rotation. Herein, we use the motional dynamics of ortho-
substituted benzyl trialkyl phosphonium guest molecules to
quantitatively probe the steric consequences of guest encapsula-
Over the past decade, this effort has investigated the
host-guest dynamics and reactivity of the self-assembled
[Ga4L6]12- supramolecular host (1; Figure 1; L ) 1,5-bis[2,3-
dihydroxybenzamido]naphthalene). The T-symmetric assembly
1 is composed of four Ga(III) metal centers located at the
vertices of a tetrahedron, whose edges are spanned by six
naphthalene-based catecholamide ligands.38,39 The supramo-
lecular complex contains a hydrophobic interior cavity which
(22) Brouwer, E. B.; Enright, G. D.; Ratcliffe, C. I.; Facey, G. A.;
Ripmeester, J. A. J. Phys. Chem. B 1999, 103, 10604–10616.
(23) Chapman, R. G.; Sherman, J. C. J. Org. Chem. 2000, 65, 513–516.
(24) Frischmann, P. D.; Facey, G. A.; Ghi, P. Y.; Gallant, A. J.; Bryce,
D. L.; Lelj, F.; MacLachlan, M. J. J. Am. Chem. Soc. 2010, 132, 3893–
3908.
(40) Parac, T. N.; Caulder, D. L.; Raymond, K. N. J. Am. Chem. Soc. 1998,
120, 8003–8004.
(25) Kitagawa, H.; Kobori, Y.; Yamanaka, M.; Yoza, K.; Kobayashi, K.
Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 10444–10448.
(26) Kulasekharan, R.; Jayaraj, N.; Porel, M.; Choudhury, R.; Sundaresan,
A. K.; Parthasarathy, A.; Ottaviani, M. F.; Jockusch, S.; Turro, N. J.;
Ramamurthy, V. Langmuir 2010, 26, 6943–6953.
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Commun. 1995, 1259–1260.
(41) Parac, T. N.; Scherer, M.; Raymond, K. N. Angew. Chem., Int. Ed.
2000, 39, 1239–1242.
(42) Fiedler, D.; Pagliero, D.; Brumaghim, J. L.; Bergman, R. G.; Raymond,
K. N. Inorg. Chem. 2004, 43, 846–848.
(43) Biros, S. M.; Bergman, R. G.; Raymond, K. N. J. Am. Chem. Soc.
2007, 129, 12094–12095.
(28) Kusukawa, T.; Yoshizawa, M.; Fujita, M. Angew. Chem., Int. Ed. 2001,
40, 1879–1884.
(44) Hastings, C. J.; Pluth, M. D.; Biros, S. M.; Bergman, R. G.; Raymond,
K. N. Tetrahedron 2008, 64, 8362–8367.
(29) Mileo, E.; Yi, S.; Bhattacharya, P.; Kaifer, A. Angew. Chem., Int. Ed.
2009, 48, 5337–5340.
(45) Davis, A. V.; Raymond, K. N. J. Am. Chem. Soc. 2005, 127, 7912–
7919.
(30) Nishimura, N.; Yoza, K.; Kobayashi, K. J. Am. Chem. Soc. 2010, 132,
777–790.
(46) Davis, A. V.; Fiedler, D.; Seeber, G.; Zahl, A.; van Eldik, R.; Raymond,
K. N. J. Am. Chem. Soc. 2006, 128, 1324–1333.
(47) Pluth, M. D.; Johnson, D. W.; Szigethy, G.; Davis, A. V.; Teat, S. J.;
Oliver, A. G.; Bergman, R. G.; Raymond, K. N. Inorg. Chem. 2009,
48, 111–120.
(31) Tominaga, M.; Tashiro, S.; Aoyagi, M.; Fujita, M. Chem. Commun.
2002, 2038–2039.
(32) Vysotsky, M. O.; Pop, A.; Broda, F.; Thondorf, I.; Bo¨hmer, V.
Chem.sEur. J. 2001, 7, 4403–4410.
(48) Fiedler, D.; van Halbeek, H.; Bergman, R. G.; Raymond, K. N. J. Am.
Chem. Soc. 2006, 128, 10240–10252.
(33) Ajami, D.; Rebek, J., Jr. J. Org. Chem. 2009, 74, 6584–6591.
(34) Hooley, R. J.; Shenoy, S. R.; Rebek, J., Jr. Org. Lett. 2008, 10, 5397–
5400.
(49) Fiedler, D.; Leung, D. H.; Bergman, R. G.; Raymond, K. N. Acc.
Chem. Res. 2005, 38, 349–358.
(35) O’Leary, B. M.; Grotzfeld, R. M.; Rebek, J., Jr. J. Am. Chem. Soc.
1997, 119, 11701–11702.
(50) Hastings, C. J.; Fiedler, D.; Bergman, R. G.; Raymond, K. N. J. Am.
Chem. Soc. 2008, 130, 10977–10983.
(36) Purse, B. W.; Butterfield, S. M.; Ballester, P.; Shivanyuk, A.; Rebek,
J., Jr. J. Org. Chem. 2008, 73, 6480–6488.
(51) Brown, C. J.; Bergman, R. G.; Raymond, K. N. J. Am. Chem. Soc.
2009, 131, 17530–17531.
(37) Rebek, J., Jr. Acc. Chem. Res. 2009, 42, 1660–1668.
(38) Caulder, D. L.; Powers, R. E.; Parac, T. N.; Raymond, K. N. Angew.
Chem., Int. Ed. 1998, 37, 1840–1843.
(52) Leung, D. H.; Fiedler, D.; Bergman, R. G.; Raymond, K. N. Angew.
Chem., Int. Ed. 2004, 43, 963–966.
(53) Pluth, M. D.; Bergman, R. G.; Raymond, K. N. J. Org. Chem. 2008,
73, 7132–7136.
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A R T I C L E S
Mugridge et al.
Chart 1. Ortho-Substituted Benzyl Phosphonium Guests54
tion within 1. Encapsulation is found to raise guest bond
rotational barriers by 3-6 kcal/mol and prolate-shaped guest
molecules are found to tumble more slowly inside the host cavity
compared with the tumbling of larger, but more spherically
shaped, guest molecules.
Results and Discussion
Encapsulated Guest Rotational Barriers. A series of ortho-
substituted benzyl trialkyl phosphonium cations (2-6, Chart 1)
were prepared as guest molecules to probe the effects of
confinement within 1 on the motional dynamics of encapsulated
guests. Since host 1 has purely rotational T symmetry (i.e., there
is no mirror symmetry in the host cavity), the aromatic ortho
methyl groups (as well as the aromatic meta substituents) for
encapsulated guests 2-6 are related only by rotation about the
Ph-CH2 bond. Therefore, the ortho (or meta) substituents will
be chemically inequivalent if Ph-CH2 bond rotation is slow
on the NMR time scale. Guests 2-6 are cleanly encapsulated
in 1 in CD3OD solution, and two signals corresponding to the
ortho methyl groups of the encapsulated guest are observed by
1H NMR for each host-guest complex at room temperature
(Figure 2).
Figure 3. 1H NMR spectra at different mixing times (tmix) from the SIR
experiment with [5 ⊂ 1]11- in CD3OD at 296 K. As the inverted 1H NMR
resonance (right) corresponding to one of the ortho aromatic methyl groups
of guest 5 exchanges via Ph-CH2 bond rotation, the intensity of its
uninverted partner (left) initially decreases due to this exchange process.
At longer mixing times, the intensity of both signals increases due to T1
relaxation.
Selective inversion recovery (SIR) NMR experiments55 were
used to measure the rate of Ph-CH2 bond rotation for
encapsulated guests 2-5. One of the chemically inequivalent
1
ortho or meta substituents was selectively spin-labeled (its H
NMR resonance was inverted), and a variable mixing time was
1
waited before colleting a 1D H NMR spectrum. The rate of
exchange between the inverted resonance and its decoalesced
partner (the other ortho or meta guest substituent) can be derived
by monitoring the change in both integrals as a function of the
variable mixing time (Figure 3, Figure 4 left). Since Ph-CH2
bond rotation of the encapsulated guest relates the inequivalent
ortho or meta substituents, this SIR experiment directly measures
the rate of Ph-CH2 bond rotation.
Figure 4. (Top) Observed and calculated integrals from an SIR experiment
with [5 ⊂ 1]11- in CD3OD at 296 K for one of the exchanging Ar-CH3
resonances. (Bottom) Eyring plot used to determine the activation parameters
for Ph-CH2 bond rotation of [5 ⊂ 1]11- in CD3OD.
It should be noted here that another possible mechanism for
exchange between ortho or meta guest substituents is guest
ejection, rapid Ph-CH2 bond rotation in solution, and re-
encapsulation. If guest exchange occurs on a comparable time
scale to Ph-CH2 bond rotation, then the apparent rate of bond
rotation would be affected by guest molecules exiting and
Figure 2. 1H NMR spectrum of [5 ⊂ 1]11- in CD3OD at 296 K (where ⊂
denotes encapsulation), with schematic of encapsulated guest Ph-CH2 bond
rotation. The total host and guest concentrations are [1] ) 7 mM and [5]
) 14 mM. Since Ph-CH2 bond rotation is slow on the NMR time scale,
ortho methyl groups (*) are chemically inequivalent and therefore exhibit
1
different H NMR chemical shifts. Encapsulated guest (b), exterior guest
(2), and host (9) resonances are also labeled.
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Encapsulated Guest-Host Dynamics
A R T I C L E S
Table 1. Activation Parameters for Ph-CH2 Bond Rotation of Phosphonium Guest Molecules Encapsulated within Host 1 in CD3ODa
a Solvent accessible volumes were calculated in UCSF Chimera.56
entering the host. This is not the case for guests 2-5; guest
exchange was found to be at least 1 order of magnitude slower
than Ph-CH2 bond rotation for each of these guest molecules
(see Supporting Information). Furthermore, for guest 2, whose
guest exchange rate and Ph-CH2 bond rotation rate were closest
in magnitude, it was found that the Ph-CH2 rotation rate was
invariant with the concentration of 2 or the concentration of
the [2 ⊂ 1]11- host-guest complex. Therefore, although
interior-exterior guest exchange does occur in these systems,
it is significantly slower than Ph-CH2 bond rotation and
negligibly affects measurement of the latter.
The rates of encapsulated Ph-CH2 bond rotation for guests
2-5 were measured at different temperatures, and Eyring
analysis was used to determine activation parameters for the
rotational motion (Figure 4, Table 1). The observed Ph-CH2
bond rotational barriers for the encapsulated guests range from
16 to 19 kcal/mol, and the rotational barrier is dominated by
enthalpy. One might have expected larger guest molecules to
be more sterically confined within the host cavity and thus have
the largest Ph-CH2 rotational barriers, but this trend is not
observed. In fact, when comparing the guests 2 versus 4 and 3
versus 5, we find that increasing the steric bulk by adding PEt3
groups instead of PMe3 groups actually lowers the rotational
barrier. This may be a result of the bulkier PEt3 group creating
a larger and more spherical host cavity, such that the energetic
penalty for that expansion is paid upon encapsulation, and the
enlarged interior cavity allows for more facile bond rotation.
On the other hand, comparing guests 2 versus 3 and 4 versus
5, we find that addition of the para methyl group to the aromatic
ring increases the bond rotational barrier. Here, it may be the
case that addition of the para methyl group forces the guests’
ortho methyl groups further from the center of the interior cavity
and closer to the host walls, impeding the rotational process.
These explanations are necessarily somewhat speculative, but
the observed Ph-CH2 bond rotational barriers for encapsulated
guests unambiguously demonstrate that the motional dynamics
of the encapsulated guests are both size and shape dependent.
Rotational Barriers in Bulk Solution. In order to determine
how confinement within the host cavity affects guest motional
dynamics, we wanted to compare the encapsulated bond
rotational barriers reported above with those measured in bulk
solution. Unfortunately, the Ph-CH2 bond rotational barriers
of guests 2-5 cannot be measured in bulk solution because
mirror symmetry relates the ortho and meta aromatic substit-
uents, meaning these substituents will be chemically equivalent
regardless of the bond rotational rate. However, asymmetric
substitution of the aromatic ring at only one meta position breaks
that mirror symmetry, making the now enantiotopic benzyl CH2
protons chemically inequivalent as Ph-CH2 bond rotation
becomes slow on the NMR time scale (Figure 5). Activation
parameters for Ph-CH2 bond rotation of benzyl phosphonium
cations 7 and 8 in CD3OD were measured using SIR experi-
ments on the decoalesced benzyl protons (Table 2).
The Ph-CH2 bond rotational barrier for phosphonium cations
7 and 8 is approximately 13 kcal/mol in CD3OD. Assuming
that the meta and para substituents negligibly affect this
rotational barrier, guests 2-5 must also have rotational barriers
close to 13 kcal/mol in bulk CD3OD solution. Thus, encapsula-
tion within host 1 raises the Ph-CH2 bond rotational barrier
by 3-6 kcal/mol for guests 2-5. This corresponds to between
a 100- and 15 000-fold decrease in the rate of internal bond
rotation upon encapsulation of guests 2-5. To confirm that this
dramatic change in the guest motional dynamics was due to
steric confinement within the host, rather than an electronic
effect imparted by the nonpolar, hydrophobic interior cavity
space, the Ph-CH2 rotational barrier for cation 7 was measured
in a nonpolar solvent. In toluene-d8 (with 10% by volume
CD3OD to aid solubility), the Ph-CH2 rotational barrier for
cation 7 was found to be within error of that measured in
(55) Bain, A. D.; Cramer, J. A. J. Magn. Reson. A 1996, 118, 21–27.
(54) Guest 5 was deuterated at the benzyl position to alleviate peak overlap
1
problems in the encapsulated guest region of the H NMR spectrum.
Peak overlap was not an issue with the other guest molecules studied.
(56) Pettersen, E. F.; Goddard, T. D.; Huang, C. C.; Couch, G. S.;
Greenblatt, D. M.; Meng, E. C.; Ferrin, T. E. J. Comput. Chem. 2004,
25, 1605–1612.
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A R T I C L E S
Mugridge et al.
Figure 5. (Left) Benzyl phosphonium cation 7. Enantiotopic benzyl protons
HA and HB become chemically inequivalent as Ph-CH2 bond rotation
becomes slow on the NMR time scale due to the asymmetric ring
substitution. (Right) Variable temperature 1H NMR spectra showing
decoalescence of HA and HB for cation 7 in CD3OD.
Figure 6. 1H NMR spectra collected at 600 MHz of host-guest complexes
with guests 2-6 in CD3OH at the low temperatures required to observe a
reduction in host symmetry for each complex. For clarity, only the host
amide N-H region (14-12 ppm) and host aromatic C-H region (9-6
ppm) are shown in each spectrum. The spectra are ordered by the
temperature required for host symmetry reduction, such that the host-guest
complexes shown at the top break the symmetry at higher temperatures,
while those at the bottom of the figure require lower temperatures.
CD3OD (see Supporting Information). This suggests that the
rotational barrier is insensitive to changes in the cation’s
electronic environment and that, despite the flexibility of the
host framework and interior cavity, steric confinement within
1 is responsible for the significant increase in guest Ph-CH2
bond rotational barriers observed upon encapsulation.
The guest molecules 3, 5, and 6 require lower temperatures
to break the host symmetry. The symmetry of these host-guest
complexes is ambiguous due to broad and/or overlapping
aromatic C-H and amide N-H host resonances, but it is clear
that the T symmetry of 1 is broken at these temperatures.
Unfortunately, these broad and overlapping host resonances and
the complexity of decoalescence from T to C1 or other
symmetries preclude quantitative measurement of the barrier
to guest tumbling inside of 1. However, based on the temper-
atures required to break the host symmetry, we can make the
qualitative observation that the more prolate guests 2 and 4
tumble more slowly inside of host 1 than the more spherical
guests 3, 5, and 6. Furthermore, comparing guests 2 versus 6,
we see that the larger guest 6, which has additional methyl
groups at the meta positions, actually tumbles more easily within
the host, presumably due to the larger and more spherical cavity
required to encapsulate guest 6.
Guest Tumbling Dynamics. The tumbling motion of encap-
sulated guest molecules also provides some information about
the effects of confinement within 1 and how guest size and shape
affect these motional dynamics. When the host-guest com-
plexes [2 ⊂ 1]11- - [6 ⊂ 1]11- are cooled, a reduction in host
symmetry is observed as the tumbling, or reorientation of the
encapsulated guest within the host cavity, becomes slow on the
NMR time scale (Figure 6). The more prolate guests 2 and 4
readily reduce the symmetry of host 1 to C1 at 285 and 273 K,
respectively. The assignment of C1 symmetry for these host-guest
complexes is based on the observation of a very large number
of host aromatic C-H resonances and 11 of the 12 distinct
amide N-H resonances expected for C1 symmetry (significantly
more than the 6 or 4 N-H resonances expected for C2 or C3
host symmetry, respectively) at low temperatures. Additionally,
further cooling of complex [4 ⊂ 1]11- to 253 K reveals all 12
amide NH resonances and 2D 13C-1H NMR experiments further
confirm the assignment of C1 host symmetry (see Supporting
Information for spectra).
To provide further support for this argument, molecular-
mechanics-based conformational searching (MacroModel,57
OPLS 200558) was carried out on models of the host-guest
complexes [2 ⊂ 1]11- and [6 ⊂ 1]11-. The void-space cavities
Table 2. Activation Parameters for Ph-CH2 Bond Rotation of Asymmetric Phosphonium Cations in Bulk CD3OD
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A R T I C L E S
Figure 7. Space-filling models of guests 2 (left) and 6 (right), each
surrounded by the calculated void space inside of 1 for the modeled
host-guest complexes. Guest 6 creates a larger and rounder host cavity
space.
for the lowest energy host-guest conformations were then
calculated using Voidoo.59,60 The calculated host interior cavity
for guest 6 (502 Å3) is larger and more spherical than the cavity
calculated for guest 2 (440 Å3). Figure 7 shows the space-filling
models and calculated void space cavities for guests 2 and 6.
The effect of the additional methyl groups on guest 6 is to
expand the host cavity to a larger volume and more spherical
shape, which facilitates the tumbling of guest 6 within 1, relative
to the more prolate guest 2.
Figure 8. Solid-state structure of [2 ⊂ 1]11- with exterior phosphonium
and potassium cations, interior guest disorder, and solvent omitted for clarity.
The encapsulated guest 2 is shown in green, and the calculated void space
(367 Å3) is shown in blue. The void space is seen to extend well into one
of the host apertures, which is distorted by the para methyl group of
encapsulated 2.
Solid-State Structure of [2 ⊂1]11-. Single crystals suitable
for X-ray diffraction studies were obtained for the host-guest
complex [2 ⊂ 1]11-. The solid-state structure of this complex
provides some insight into the origins of the host symmetry
reduction observed in solution. Encapsulated guest 2 sits within
the host cavity such that its para methyl group points directly
toward, and extends partially into, one of the apertures in the
host framework (Figure 8). The result is that this particular
aperture is significantly dilated, while the three other apertures
in the host framework are contracted (Figure 9). The desym-
metrization of host 1 observed in the solid state is consistent
with the modeling studies presented above and demonstrates
how the 2-fold rotational symmetry of the host is destroyed by
the length of guest 2, which forces a distortion of the host
framework. Rotation of the guest about the host 3-fold axis could
maintain C3 symmetry for the host-guest complex in solution,
but as this process becomes slow at lower temperatures, the
complex is reduced to C1 symmetry.
Unrelated to the above discussion of guest motional dynamics,
the expansion of one of the apertures in the host framework is
significant for host-guest exchange dynamics. We have long
proposed that guest molecules enter and exit the host cavity by
squeezing through the apertures in the host framework. Kinetic
experiments,46 isotope effects,61 the formation of dangling arm
complexes,62 and modeling studies45 all demonstrate that this
is the mechanism for guest exchange, but there has not been
direct structural evidence for host aperture distortion. The
Figure 9. Space-filling representation of the host framework from the solid-
state structure of [2 ⊂ 1]11- as viewed down the dilated aperture (left) and
one of three other contracted apertures (right).
aperture dilation observed in the solid-state structure of [2 ⊂
1]11- is quite large: the area defined by the H-H distances
among the different naphthalene rings that compose the C3-
symmetric apertures is more than twice as large for the dilated
aperture than for the other contracted apertures. Although this
distortion is not nearly large enough to allow the passage of
typical alkyl or benzyl ammonium/phosphonium guest mol-
ecules, it provides direct structural evidence supporting an
aperture-based guest exchange mechanism.
Conclusion
To explore the steric environment experienced by guest
molecules confined within supramolecular host 1, the rotational
and tumbling dynamics for a series of encapsulated benzyltri-
alkyl phosphonium cations were investigated. The motional
dynamics of the encapsulated guest molecules are found to
depend strongly on both guest size and shape. While one might
expect that the motions of larger guest molecules confined within
the cavity of 1 would be more restricted, this was often not
true. In many cases, an increase in guest size was observed to
facilitate both guest rotational and tumbling motions, which we
interpret as the result of a corresponding increase in overall
cavity size or more spherical cavity shape. The bond rotational
(57) MacroModel; Schrodinger: New York, NY, 2010.
(58) Jorgensen, W. L.; Tirado-Rives, J. Proc. Natl. Acad. Sci. U.S.A. 2005,
102, 6665–6670.
(59) Kleywegt, G. J.; Jones, T. A. Acta Crystallogr. 1994, D50, 178–185.
(60) Kleywegt, G. J.; Zou, J. Y.; Kjeldgaard, M.; Jones, T. A. International
Tables for Crystallography; International Union of Crystallography,
Kluwer Academic: Dordrecht, The Netherlands, 2001; Vol. F, Chapter
17.1, pp 353-356, 366-367.
(61) Mugridge, J. S.; Bergman, R.; Raymond, K. Angew. Chem., Int. Ed.
2010, 49, 3635–3637.
(62) Tiedemann, B. E. F.; Raymond, K. N. Angew. Chem., Int. Ed. 2006,
45, 83–86.
9
J. AM. CHEM. SOC. VOL. 132, NO. 45, 2010 16261

A R T I C L E S
Mugridge et al.
Hz, ArC), 122.8 (d, JCP ) 9.5 Hz, ArC), 24.1 (d, JCP ) 50.5 Hz,
CH2), 20.0 (s, c), 19.8 (s, d), 8.2 (d, JCP ) 54.2 Hz, a). 31P{1H}
NMR (202 MHz, D2O): δ 28.2 (s). MS (ESIHR) for C13H22P, calcd
(found) m/z: 209.1454 (209.1455).
barriers for similar phosphonium cations measured in bulk
solution indicate that encapsulation within host 1 raises the
Ph-CH2 bond rotational barrier by 3-6 kcal/mol. This large
change in the rotational dynamics for encapsulated guest
molecules demonstrates that, despite the flexibility of the host
framework and the wide range of accessible cavity volumes,
guest molecules experience a significantly confined steric
environment within the host cavity.
In summary, we have shown that the motional dynamics of
encapsulated guests can provide a sensitive probe of the host
interior space. Furthermore, these dynamics can in principle
provide fundamental information about how the host structure
and flexibility change in different solvents or with different
exterior counterions. These features of guest encapsulation are
important for understanding the changes in guest behavior that
underlie both stabilization of reactive species and host-mediated
catalysis.
K11[2 ⊂ 1]. The title host-guest complex was prepared in situ
by mixing 2[Cl] (2.70 mg, 0.011 mmol) and host K11[1] (20.0 mg,
0.006 mmol) in 800 µL of CD3OD (5% DMSO-d6) in an NMR
1
tube. For H NMR (500 MHz, CD3OD/5% DMSO-d6), due to a
very broad aromatic host region at room temperature, only
encapsulated guest peaks are tabulated; see Figure S37 for full 1H
NMR spectrum: δ 4.80 (s, 1H, encaps ArH), 3.78 (s, 1H, encaps
ArH), 0.68 (s, 3H, encaps ArCH3), 0.64 (s, 3H, encaps ArCH3),
0.54 (s, 3H, encaps ArCH3), 0.18 (m, 2H, encaps CH2), -0.75 (d,
JPH ) 13.4 Hz, 9H, encaps P(CH3)3). 31P{1H} NMR (243 MHz,
CD3OD/5% DMSO-d6): δ 26.2 (s, encaps 2). HRMS (ESI-QTOF):
calcd (found) m/z: [1 + 2 + 8K+]3- 1119.6914 (1119.6898), [1 +
2 + H+ + 7K+]3- 1107.0394 (1107.0388), [1 + 2 2H+ + 6K+]3-
1094.3876 (1094.3870), [1 + 2 + 7K+]4- 830.0278 (830.0230),
[1 + 2 + H+ + 6K+]4- 820.5389 (820.5378), [1 + 2 + 2H+
+
5K+]4- 810.7999 (810.7924), [1 + 2 +H+ + 5K+]5- 648.4385
(648.4313), [1 + 2 +2H+ + 4K+]5- 641.0474 (641.0477).
Experimental Section
2,6-Dimethylbenzyl Trimethylphosphonium Chloride (3[Cl]).
The title compound was prepared analogously to compound 2 from
2,6-dimethylbenzyl chloride (400 mg, 2.6 mmol) and trimethyl
phosphine (0.53 mL, 5.2 mmol). The product was isolated as a
white solid with yield: 104 mg (17%). 1H NMR (500 MHz, D2O):
δ 7.18 (br, m, 3H, ArH), 3.79 (d, JPH ) 16 Hz, 2H, benzyl CH2),
2.32 (s, 6H, ArCH3), 1.85 (d, JPH ) 14.1 Hz, 9H, PMe3). 13C{1H}
NMR (125 MHz, D2O): δ 137.7 (d, JPC ) 5.8 Hz, ArC), 128.9 (d,
General. Unless otherwise noted, manipulations were carried
out using standard Schlenk and high-vacuum techniques and all
chemicals were obtained from commercial suppliers and used
without further purification. All glassware was oven-dried at 150
°C. All solvents were sparged with nitrogen prior to use. Diethyl
ether was dried by passing the solvent through columns of activated
alumina under nitrogen pressure.63 Supramolecular host assembly
K11[1] was prepared as previously described38 and stored under
nitrogen. All host-guest complexes were prepared in situ by mixing
1 equiv of host K11[1] with 2 equiv of guest in CD3OD (∼5%
DMSO-d6 was added to aid solubility) under a nitrogen atmosphere;
the host-guest complexes were all formed quantitatively. 2 equiv
of guest were used so that SIR experiments to measure the guest
exchange kinetics (which require an exterior guest population) could
be carried out on the same solution used to measure bond rotation.
A host concentration of 7 mM was used for all rotational barrier
and guest tumbling measurements. All SIR NMR experiments were
carried out on a Bruker AV-500 NMR spectrometer, and all variable
JPC ) 3.6 Hz, ArC), 128.1 (d, JPC ) 4.1 Hz, ArC), 126.0 (d, JPC
)
8.6 Hz, ArC), 24.3 (d, JPC ) 50.4 Hz, benzyl CH2), 20.1 (s, ArCH3),
8.2 (d, JPC ) 54 Hz, PMe3). 31P{1H} NMR (202 MHz, D2O): δ
27.1 (s). MS (ESIHR) for C12H20P, calcd (found) m/z: 195.1297
(195.1296).
K11[3 ⊂ 1]. The title host-guest complex was prepared in situ
by mixing 3[Cl] (2.56 mg, 0.011 mmol) and host K11[1] (20.0 mg,
0.006 mmol) in 800 µL of CD3OD (5% DMSO-d6) in an NMR
tube. 1H NMR (500 MHz, CD3OD/5% DMSO-d6): δ 13.49 (s, host
NH), 8.05 (br, 12H, host ArH), 7.66 (d, JHH ) 8.70 Hz, 12H, host
ArH), 7.34 (d, JHH ) 8.1 Hz, 12H, host ArH), 6.97 (t, JHH ) 8.1
Hz, 12H, host ArH), 6.74 (d, JHH ) 7.6 Hz, 12H, host ArH), 6.60
(t, JHH ) 8.1 Hz, 12H, host ArH), 4.88 (t of d, 2JHH ) 7.5 Hz, 3JHH
) 2.6 Hz, 1H, encaps ArH), 4.54 (br, 1H, encaps ArH), 4.19 (br,
1
temperature H NMR spectra used in the guest tumbling analysis
were collected on a Bruker AV-600 NMR spectrometer. Chemical
shifts are reported in parts per million (δ) relative to residual protic
solvent resonances. For 31P{1H} NMR spectra, chemical shifts are
reported relative to a triethyl phosphate internal standard. Multi-
plicities of NMR resonances are reported as s ) singlet, d )
doublet, t ) triplet, m ) multiplet, and br ) broad. For the NMR
chemical shift data of host-guest complexes, host denotes signals
corresponding to assembly 1 and encaps denotes signals corre-
sponding to the encapsulated guest; only encapsulated guest signals
are tabulated. All mass spectra were recorded at the UC Berkeley
Mass Spectrometry facility. Mass spectra of all host-guest as-
semblies were acquired on a Waters QTOF API mass spectrometer
from methanol, and all other mass spectra were acquired on a
Thermo Scientific LTQ-Orbitrap XL mass spectrometer.
1H, encaps ArH), 0.17 (s, 6H, encaps ArCH3), -0.02 (m, JPH
)
14.6 Hz, 2H encaps benzyl CH2), -1.12 (d, J ) 13.5 Hz, 9H,
encaps PMe3). 31P{1H} NMR (243 MHz, CD3OD/5% DMSO-d6):
δ 25.8 (s, encaps 3). (ESI-QTOF): calcd (found) m/z: [1 + 3 +
8K+]3- 1115.0195 (1115.0140), [1 + 3 + H+ + 7K+]3- 1102.3676
(1102.3652), [1 + 3 + 2H+ + 6K+]3- 1089.7157 (1089.7036), [1
+ 3 + 7K+]4- 826.5239 (826.5271), [1 + 3 + H+ + 6K+]4-
817.0349 (817.0303), [1 + 3 + 2H+ + 5K+]4- 807.5460 (807.5465),
[1 + 3 + H+ + 5K+]5- 645.8353 (645.8375), [1 + 3 + 2H+
+
4K+]5- 638.0442 (638.0410).
2,4,6-Trimethylbenzyl Triethylphosphonium Chloride (4[Cl]).
The title compound was prepared analogously to compound 2[Cl]
starting with R2-chloroisodurene (300 mg, 1.8 mmol) and trieth-
ylphosphine (0.8 mL, 5.3 mmol), which gave 125 mg (30%) of a
2,4,6-Trimethylbenzyl Trimethylphosphonium Chloride (2[Cl]).
To a degassed solution of R2-chloroisodurene (1.0 g, 5.9 mmol) in
20 mL of ether was added trimethylphosphine (1.5 mL, 15 mmol)
via syringe, and the solution was stirred for 24 h. The resulting
white precipitate was collected by filtration, dissolved in a minimal
amount of methylene chloride, and precipitated with excess diethyl
ether, and residual solvent was removed overnight under vacuum
1
white solid after workup. H NMR (500 MHz, D2O): δ 6.87 (s,
2H, ArH), 3.52 (d, JPH ) 14.5 Hz, 2H, CH2), 2.16 (s, 6H, ortho-
ArCH3), 2.09 (s, 3H, para-ArCH3), 2.08 (m, 6H, PCH2CH3), 0.99
(d of t, JPH ) 18.0 Hz, JHH ) 7.6 Hz, 9H, PCH2CH3). 13C{1H}
NMR (100 MHz, D2O): δ 138.3 (d, JPC ) 3.8 Hz, ArC), 137.5 (d,
1
to give 1.19 g (83%) of a fluffy white solid. H NMR (400 MHz,
D2O): δ 6.90 (s, 2H, ArH), 3.62 (d, JPH ) 15.4 Hz, 2H, CH2), 2.16
JPC ) 4.7 Hz, ArC), 129.5 (d, JPC ) 3.1 Hz, ArC), 122.9 (d, JPC
)
(s, 6H, o-ArCH3), 2.13 (s, 3H, p-ArCH3), 1.73 (d, JPH ) 14.2 Hz,
8.5 Hz, ArC), 20.1 (s, ArCH3), 19.8 (d, JPC ) 46.2 Hz, CH2), 19.7
(s, ArCH3), 12.4 (d, JPC ) 47.8 Hz, PCH2CH3), 4.6 (s, PCH2CH3).
31P{1H} NMR (202 MHz, D2O): δ 38.0 (s). MS (ESIHR) for
C16H28P, calcd (found) m/z: 251.1923 (251.1924).
9H, P(CH3)3). 13C{1H} NMR (100 MHz, D2O): δ 138.3 (d, JCP
)
4.4 Hz, ArC), 137.7 (d, JCP ) 5.9 Hz, ArC), 129.6 (d, JCP ) 3.7
K11[4 ⊂ 1]. The title host-guest complex was prepared in situ
(63) Alaimo, P. J.; Peters, D. W.; Arnold, J.; Bergman, R. G. J. Chem.
Educ. 2001, 78, 64.
by mixing 4[Cl] (3.19 mg, 0.011 mmol) and host K11[1] (20.0 mg,
9
16262 J. AM. CHEM. SOC. VOL. 132, NO. 45, 2010

Encapsulated Guest-Host Dynamics
A R T I C L E S
0.006 mmol) in 800 µL of CD3OD (5% DMSO-d6) in an NMR
(br m, 9H, PCH2CH3). 2H NMR (92 MHz, D2O): δ 3.65 (br, CD2).
13C{1H} NMR (151 MHz, D2O): δ 137.6 (d, J ) 4.2 Hz, ArC),
129.0 (d, J ) 2.8 Hz, ArC), 128.2 (d, J ) 3.3 Hz, ArC), 126.2 (d,
J ) 8.3 Hz, ArC), 20.3 (s, ArCH3), 12.6 (d, J ) 48 Hz, PCH2CH3),
4.8 (d, J ) 5.6 Hz, PCH2CH3). 31P{1H} NMR (243 MHz, D2O): δ
37.9 (s). (ESIHR) for C15H24D2P, calcd (found) m/z: 239.1890
(239.1892).
1
tube. For H NMR (500 MHz, CD3OD/5% DMSO-d6), due to a
very broad aromatic host region at room temperature, only
encapsulated guest peaks are tabulated; see Figure S38 for full 1H
NMR spectrum: δ 4.98 (s, 1H, encaps ArH), 4.22 (s, 1H, encaps
ArH), 1.42 (s, 3H, encaps ArCH3), 1.08 (s, 3H, encaps ArCH3),
0.63 (s, 3H, encaps ArCH3), 0.44 (m, 2H, encaps CH2), -0.90 (m,
9H, encaps PCH2CH3), -1.10 (m, 6H, encaps PCH2CH3). 31P{1H}
NMR (243 MHz, CD3OD/5% DMSO-d6): δ 36.1 (s, encaps 4).
HRMS (ESI-QTOF): calcd (found) m/z: [1 + 4 + 8K+]3-
1133.7070 (1133.6980), [1 + 4 +H+ + 7K+]3- 1121.0552
(1121.0425), [1 + 4 + 2H+ + 6K+]3- 1108.4032 (1108.3844), [1
+ 4 + 6K+ + H+]4- 830.8006 (830.7920), [1 + 4 + 5K+ + 2H+]4-
821.5617 (821.5452), [1 + 4 + 2H+ + 4K+]5- 649.4568 (649.4437).
2,6-Dimethylbenzyl-d2 Alcohol. A 250 mL Schlenk flask was
charged with a stir bar, and lithium aluminum deuteride (2.54 g,
60.6 mmol), purged with nitrogen, and diethyl ether (60 mL) were
added Via cannula to form a gray slurry. An addition funnel was
added to the Schlenk flask and charged with 2,6-dimethylbenzoic
acid (1.3 g, 8.7 mmol) dissolved in diethyl ether (30 mL). The
acid solution was slowly added dropwise over 45 min to the LAD
solution with vigorous stirring. Once the addition was complete,
the addition funnel was replaced with a reflux condenser and the
heterogeneous reaction mixture was heated at reflux for 5 days.
The resulting suspension was cooled to 0 °C, and a saturated
aqueous solution of sodium sulfate was slowly added dropwise until
any unreacted LAD had been quenched. Significant heat was
evolved as the LAD was quenched, and care was taken to add the
aqueous solution slowly enough that the reaction mixture stayed
cool during quenching. The precipitated inorganic solids were
removed by vacuum filtration over a bed of Celite and washed with
diethyl ether (3 × 50 mL) and water (50 mL). The layers of the
filtrate were separated, the aqueous layer was washed with diethyl
ether (2 × 30 mL), and the organics were combined and dried over
sodium sulfate. The sodium sulfate was removed by vacuum
filtration, and the diethyl ether was removed under reduced pressure
K11[5 ⊂ 1]. The title host-guest complex was prepared in situ
by mixing 5[Br] (3.05 mg, 0.011 mmol) and host 1 (20.0 mg, 0.006
mmol) in 800 µL of CD3OD (5% DMSO-d6) in an NMR tube. 1H
NMR (500 MHz, CD3OD/5% DMSO-d6): δ 8.26 (br, 12H, host
ArH), 7.75 (br, 12H, host ArH), 7.31 (d, JHH ) 8.3 Hz, 12H, host
ArH), 6.63 (d, JHH ) 7.3 Hz, 12H, host ArH), 6.39 (t, JHH ) 7.8
3
4
Hz, 12H, host ArH), 5.30 (t of d, JHH ) 7.7 Hz, JHH ) 2.3 Hz,
1H encaps ArH), 5.04 (d, JHH ) 7.6 Hz, 1H, encaps ArH), 0.98 (s,
3H, encaps ArCH3), 0.38 (s, 3H, encaps ArCH3), -0.79 (d of t,
JPH ) 18.3 Hz, JHH ) 7.6 Hz, 9H, encaps PCH2CH3), -1.18 (m,
6H, PCH2CH3). 31P{1H} NMR (243 MHz, CD3OD/5% DMSO-
d6): δ 35.8 (s, encaps 5). HRMS (ESI-QTOF): calcd (found) m/z:
[1 + 5 + 8K+]3- 1129.7061 (1129.7013), [1 + 5 + H+ + 7K+]3-
1117.0541 (1117.0553), [1 + 5 + 2H+ + 6K+]3- 1104.4022
(1104.3950), [1 + 5 + 7K+]4- 837.5388 (837.5270), [1 + 5 + H+
+ 6K+]4- 828.0498 (828.0517), [1 + 5 + 2H+ + 5K+]4- 818.5609
(818.5566), [1 + 5 + H+ + 5K+]5- 654.4473 (654.4441), [1 + 5
+ 2H+ + 4K+]5- 646.8561 (646.8483).
2,3,4,5,6-Pentamethylbenzyl Trimethylphosphonium Bromide
(6[Br]). The title compound was prepared analogously to compound
2[Cl] starting from 2,3,4,5,6-pentamethyl benzyl bromide (325 mg,
1.30 mmol) and trimethyl phosphine (0.42 mL, 4.00 mmol). The
product was isolated as a white solid with a yield of 330 mg (77%).
1H NMR (500 MHz, D2O): δ 3.90 (d, JPH ) 15.5 Hz, 2H, benzyl
CH2), 2.22 (m, 15H, ArCH3), 1.79 (d, JPH ) 14.1 Hz, 9H, PMe3).
13C{1H} NMR (125 MHz, D2O): δ 135.5 (d, J ) 4.4 Hz, ArC),
134.4 (d, J ) 3.6 Hz, ArC), 133.1 (d, J ) 5.4 Hz, ArC), 122.8 (d,
J ) 9.0 Hz, ArC), 24.8 (d, JCP ) 50.5 Hz, CH2), 17.7 (d, J ) 1.6
Hz, ArCH3), 16.1 (s, ArCH3), 16.0 (d, J ) 1.2 Hz, ArCH3), 7.8 (d,
JCP ) 54.1 Hz, PMe3). 31P{1H} NMR (162 MHz, D2O): δ 28.3 (s).
(ESIHR) for C15H26P, calcd (found) m/z: 237.1767 (237.1767).
K11[6 ⊂ 1]. The title host-guest complex was prepared in situ
by mixing guest 6 (3.52 mg, 0.011 mmol) and host 1 (20.0 mg,
0.006 mmol) in 800 µL of CD3OD (5% DMSO-d6) in an NMR
tube. 1H NMR (500 MHz, CD3OD/5% DMSO-d6): δ 8.02 (br, 12H,
host ArH), 7.66 (br, 12H, host ArH), 7.19 (d, JHH ) 8.5 Hz, 12H,
host ArH), 6.95 (br, 12H, host ArH), 6.57 (d, JHH ) 7.7 Hz, host
12H, ArH), 6.28 (t, JHH ) 8.1 Hz, 12H, host ArH), 0.96 (s, 3H,
encaps ArCH3), 0.16 (s, 3H, encaps CH3), -0.09 (s, 3H, encaps
CH3), -0.13 (s, 3H, encaps CH3), -0.22 (s, 3H, encaps CH3),
-0.47 (d, JPH ) 13.0 Hz, 9H, encaps PMe3). HRMS (ESI-QTOF):
calcd (found) m/z: [112- + 6+ + 8K+]3- 1129.0352 (1129.0127),
[112- + 6+ + H+ + 7K+]3- 1116.3833 (1116.3582), [112- + 6+ +
2H+ + 6K+]3- 1103.1313 (1103.7015), [112- + 6+ + 7K+]4-
837.0356 (837.0129), [112- + 6+ + H+ + 6K+]4- 827.2967
(827.2755), [112- + 6+ + 2H+ + 5K+]4- 817.8077 (817.7846),
1
to yield an off-white solid (857 mg, 71%). H NMR (600 MHz,
CDCl3): δ 7.14 (t, JHH ) 7.4 Hz, 1H, ArH), 7.06 (d, JHH ) 7.5 Hz,
2
2H, ArH), 3.47 (s, 1H, OH), 2.43 (s, 6H, ArCH3). H{1H} NMR
(92 MHz, CDCl3): δ 4.59 (s, CD2). 13C{1H} NMR (151 MHz,
CDCl3): δ 137.4, 136.4, 128.2, 127.8 (s, ArC), 57.9 (quintet, JCD
) 21.6 Hz, CD2), 19.2 (s, ArCH3).
2,6-Dimethylbenzyl-d2 Bromide. A 250 mL round-bottom flask
was charged with a stir bar and 2,6-dimethylbenzyl-d2 alcohol (850
mg, 6.15 mmol) dissolved in diethyl ether (100 mL). The solution
was sparged with nitrogen and cooled to -50 °C with a dry ice/
isopropyl alcohol cold bath. Phosphorus tribromide (0.71 mL, 7.40
mmol) was added dropwise to the reaction solution over 15 min
by syringe. The solution was allowed to slowly warm to room
temperature and stirred overnight (16 h) under nitrogen, during
which time the solution changed from colorless to faint orange.
The reaction was quenched by pouring the solution over ice (50
mL). The layers were separated, and the aqueous layer was washed
with diethyl ether (2 × 50 mL). The organic layers were combined,
washed with a saturated aqueous solution of sodium bicarbonate
(75 mL), and dried with magnesium sulfate. The magnesium sulfate
was removed by vacuum filtration, and the diethyl ether was
removed under reduced pressure to yield a white solid (600 mg,
[112- + 6+ + 6K+]5- 661.8359 (661.8124), [112- + 6+ + H+
+
5K+]5- 654.2448 (654.2300).
2,4,6-Trimethyl-3-chloromethylbenzyl Trimethylphosphonium
Chloride (7[Cl]). 2,4-Bis(chloromethyl)-1,3,5-trimethylbenzene (500
mg, 2.3 mmol) was dissolved in 130 mL of diethyl ether in a 250
mL Schlenk flask with a stir bar. The solution was sparged with
nitrogen for 15 min, and trimethyl phosphine (0.24 mL, 2.3 mmol)
was added via syringe. The solution was stirred under a nitrogen
atmosphere for 2 days after which time the resulting white solid
was collected by vacuum filtration and washed with diethyl ether
(2× 50 mL) and the residual solvent was removed overnight under
1
49%). H NMR (500 MHz, CDCl3): δ 7.09 (t, JHH ) 7.5 Hz, 1H,
ArH), 7.02 (d, JHH ) 7.5 Hz, 2H, ArH), 2.40 (s, 6H, ArCH3).
2H{1H} NMR (77 MHz, CDCl3): δ 4.56 (s, CD2). 13C{1H} NMR
(151 MHz, CDCl3): δ 137.7, 134.1, 129.5, 128.8 (s, ArC), 19.6 (s,
ArCH3).
2,6-Dimethylbenzyl-d2 Triethylphosphonium Bromide (5[Br]).
The title compound was prepared analogously to 2[Cl] starting from
2,6-dimethylbenzyl-d2 bromide (550 mg, 2.73 mmol) and trieth-
ylphosphine (0.81 mL, 5.47 mmol). After workup, 754 mg of white
solid (87%) were obtained. 1H NMR (600 MHz, D2O): δ 7.17 (br,
3H, ArH), 2.33 (s, 6H, ArCH3), 2.23 (br m, 6H, PCH2CH3), 1.13
1
vacuum. Yield ) 70 mg (10%). H NMR (400 MHz, CD3OD): δ
7.05 (s, 1H, ArH), 4.75 (s, 2H, CH2Cl), 3.90 (d, JPH ) 12.8 Hz,
2H, CH2P), 2.44 (s, 3H, ArCH3), 2.38 (s, 3H, ArCH3), 2.34 (s, 3H,
ArCH3), 1.86 (d, JPH ) 11.6 Hz, 9H, PMe3). 13C{1H} NMR (125
MHz, CH3OD): δ 137.9 (d, J ) 5.4 Hz, ArC), 137.5 (d, J ) 4.3
9
J. AM. CHEM. SOC. VOL. 132, NO. 45, 2010 16263

A R T I C L E S
Mugridge et al.
Table 3. Crystallographic Data and Structural Refinement
Hz, ArC), 136.9 (d, J ) 5.4 Hz, ArC), 133.8 (d, J ) 3.7 Hz, ArC),
131.1 (d, J ) 3.7 Hz, ArC), 124.1 (d, J ) 9.3 Hz, ArC), 40.9 (s,
CH2Cl), 24.3 (d, JCP ) 49.8 Hz, CH2P), 20.1 (d, JCP ) 1.7 Hz,
ArCH3), 17.8 (d, JCP ) 1.3 Hz, ArCH3), 15.7 (d, JCP ) 1.7 Hz,
ArCH3), 7.4 (d, JCP ) 54.2 Hz, PMe3). 31P{1H} NMR (162 MHz,
CH3OD): δ 28.3 (s). (ESIHR) for C14H23ClP, calcd (found) m/z:
257.1220 (257.1223).
2,4,6-Trimethyl-3-chloromethylbenzyl Triethylphosphonium Chlo-
ride (8[Cl]). The title compound was prepared from 2,4-bis(chlo-
romethyl)-1,3,5-trimethylbenzene (500 mg, 2.3 mmol) and triethyl
phosphine (0.31 mL, 2.1 mmol) analogously to compound 7[Cl].
Information for the Solid-State Structure of Host-Guest Complex
K724[2 ⊂ 1]
Formula
Molecular weight
Crystal appearance, color
C214.5H216.5Ga4K3N13O44.25P5
4235.54
Plate, yellow
Crystal dimensions (max, med, min/mm) 0.12 × 0.8 × 0.1
Crystal system
Space group
Triclinic
P1
j
a (Å)
20.380(4)
b (Å)
20.556(4)
c (Å)
35.192(7)
1
Yield ) 36 mg (5%). H NMR (600 MHz, CH3OD): δ 7.06 (s,
R (deg)
90.28(3)
92.80(3)
109.91(3)
13841(5), 2
1.611
99023/33712
1.097
R1 ) 0.1038, wR2 ) 0.3028
1H, ArH), 4.76 (s, 2H, CH2Cl), 3.86 (d, JPH ) 14.6 Hz, CH2P),
2.46 (br, 3H, ArCH3), 2.39 (br, 6H, 2× ArCH3), 2.29 (m, 6H,
PCH2CH3), 1.16 (d of t, 9H, JPH ) 18.1 Hz, JHH ) 7.6 Hz,
PCH2CH3). 13C{1H} NMR (151 MHz, CH3OD): δ 138.1 (m, 2×
ArC), 137.2 (d, J ) 7.6 Hz, ArC), 134.3 (d, J ) 3.2 Hz, ArC),
131.5 (d, J ) 3.2 Hz, ArC), 124.7 (d, J ) 8.9 Hz, ArC), 41.2 (s,
CH2Cl), 21.0 (d, JCP ) 0.8 Hz, ArCH3), 18.3 (d, JCP ) 0.8 Hz,
ArCH3), 16.2 (d, JCP ) 1.2 Hz, ArCH3), 12.8 (d, JCP ) 47.8 Hz,
PCH2CH3), 4.7 (d, JCP ) 5.6 Hz, PCH2CH3). 31P{1H} NMR (243
MHz, CH3OD): δ 38.5 (s). (ESIHR) for C17H29ClP, calcd (found)
m/z: 299.1690 (299.1692).
ꢀ (deg)
γ (deg)
Volume (Å3), Z
Absorption coefficient, µ (mm-1
Reflections collected/unique
Goodness-of-fit on F2
Final R indices [I > 2σ(I)]
)
Acknowledgment. The authors would like to thank Dr. Jamin
Krinsky and Dr. Kathleen Durkin for assistance with computational
and modeling studies and acknowledge NSF Grants CHE-0233882
and CHE-0840505, which fund the UC Berkeley Molecular
Graphics and Computational Facility. We also thank Dr. Michael
Pluth, Dr. Carmelo Sgarlata, Courtney Hastings, and Casey Brown
for helpful discussions. This work has been supported by the
Director, Office of Science, Office of Basic Energy Sciences, and
the Division of Chemical Sciences, Geosciences, and Biosciences
of the U.S. Department of Energy at LBNL under Contract No.
DE-AC02-05CH11231 and an NSF predoctoral fellowship to J.S.M.
Solid-State Structure of K724[2 ⊂ 1]. X-ray quality single
crystals of the host-guest complex [2 ⊂ 1]11- were grown by
diffusing acetone into a DMF/MeOH solution of host 1 and guest
2 at 5 °C. Diffraction data were collected on a Bruker MicroStar-H
X8 APEXII diffractometer with a Bruker APEXII-CCD area
detector using Cu KR radiation. Data were integrated using
SAINT,64 and an absorption correction was applied using SAD-
ABS65 (within the Apex2 software suite). The structure was solved
using direct methods (SIR92) and refined using Fourier techniques
in SHELX-97.66 Table 3 lists some of the crystallographic data
and structural refinement information. Further refinement details
and a discussion of the disorder modeling can be found in the
Supporting Information.
Supporting Information Available: SIR fits and measured rate
constants for guest bond rotation and exchange, Eyring plots
used to determine activation parameters for bond rotation,
additional NMR spectra of host-guest complexes, and refine-
ment details for the solid-state host-guest structure. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(64) SAINT: SAX Area-Detector Integration Program; Siemens Industrial
Automation, Inc.: Madison, WI, 1999.
(65) Sheldrick, G. M. SADABS: Siemens Area Detector Absorption
Correction Program; University of Gottingen: Germany, 2005.
(66) Sheldrick, G. M. SHELX97: Programs for Crystal Structure Analysis;
Institut fur Anorganische Chemie der Universitat: Gottingen, Germany,
1998.
JA107656G
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16264 J. AM. CHEM. SOC. VOL. 132, NO. 45, 2010