Suit[3]ane

Article abstract of DOI:10.1021/jacs.0c09896

Suitanes are a class of mechanically interlocked molecules (MIMs) that consist of two components: a body with limbs protruding outward and a suit that fits appropriately around it, so that there is no easy way for the suit to be removed from the body. Her

Full text of DOI:10.1021/jacs.0c09896

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Suit[3]ane
Xiao-Yang Chen, Dengke Shen, Kang Cai, Yang Jiao, Huang Wu, Bo Song, Long Zhang, Yu Tan,
Yu Wang, Yuanning Feng, Charlotte L. Stern, and J. Fraser Stoddart*
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ABSTRACT: Suitanes are a class of mechanically interlocked molecules (MIMs) that consist of
two components: a body with limbs protruding outward and a suit that fits appropriately around it,
so that there is no easy way for the suit to be removed from the body. Herein, we report the
synthesis and characterization of a suit[3]ane, which contains a benzotrithiophene derivative
(THBTT) with three protruding hexyl chains as the body and a 3-fold symmetric, extended
pyridinium-based cage, namely, HexaCage6+, as the suit. Central to its realization is effective
templation, provided by THBTT during cage formation, an observation that has been supported
by the strong binding constant between benzotrithiophene (BTT) and the empty cage. The solid-
state structure of the suit[3]ane reveals that the body is confined within the suit’s cavity with its
alkyl chains protruding outward through the orifices in the cage. Notably, such a seemingly
unstable molecule, having three flexible alkyl chains as its only protruding limbs, does not
dissociate after prolonged heating in CD3CN at 100 °C under pressure for 7 days. No evidence for guest exchange with the host was
observed at this temperature in a 2:1 mixture of THBTT and HexaCage6+ in CD3CN. The results indicate that flexible protruding
limbs are sufficient for a suit[3]ane to remain mechanically stable even at high temperatures in solution.
INTRODUCTION
■
Even though the world of mechanically interlocked molecules
(MIMs) has been expanding rapidly during the past 30 years, it
still warrants searching for new and rare molecular
architectures that illustrate the concept of mechanical
bonding.1 It has long been speculated that there exist other
classes of MIMs beyond the archetypal catenanes,2 rotaxanes,3
knots,4 links,5 daisy chains,6 and Borromean rings.7 The
chances are that these additional MIMs do not possess the
closed-loop interlocked rings found in catenanes (Figure 1a) or
the bulky stoppers associated with the dumbbell components,
which trap rings found in rotaxanes (Figure 1b), yet cannot be
taken apart without breaking covalent bonds. We have
suggested8 the name suitane (Figure 1c), to describe MIMs
that are closely analogous to the suits that adorn our bodies.
Typically, a molecule with two or more limbs is described as
the body, which is encompassed by a close-fitting, all-in-one
molecule, known as the suit. By having two or more orifices
through which the limbs can protrude outward, the suit fits
appropriately around the body, so it is practically impossible
for the suit and the body to be separated.
Suitanes are rare in the world of MIMs.8 The fact that
Figure 1. Graphical representations of (a) [2]catenane, (b)
[2]rotaxane, and (c) suit[3]ane.
suitanes are sustained by limbs that extend through the orifices
of their suit from the “torso” associated with their body renders
them quite distinct from rotaxanes. Whereas the dumbbell
components in rotaxanes are usually comprised of rigid and
bulky stoppers, the limbs in suitanes can, in principle, be
flexible and devoid of stoppers. To the best of our knowledge,
this potential is still untapped in the current literature, as most
of the suitane architectures reported to date, both by us8a−c
Received: September 15, 2020
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Scheme 1. Synthesis of HexaCage·6PF6
−
Figure 2. Solid-state structure of HexaCage6+. PF6 anions and solvent molecules are omitted for the sake of clarity. (a) Perspective view of a
space-filling representation superimposed on a tubular one. (b) Side-on view showing the closest plane-to-plane distance between the two
platforms. (c) Plan view showing the dimensions of the cage’s internal cavity and the holes of the platforms.
and by others,8d,e have relied on the use of rigid or bulky limbs.
Such a gap in suitane research, coupled with the general lack of
experimental evidence on their mechanical stability in solution,
prompted us to investigate a new suitane that can potentially
be sustained by flexible protruding limbs.
to-face by three bridging p-xylylene linkers, leaving a large
cavity in between the two platforms to accommodate π-
electron-rich, polycyclic aromatic guests. The fact that the
linkers are spatially separated in a 3-fold symmetric fashion
means that the limbs attached to polycyclic aromatic guests can
protrude outward through the orifices in the cage.
Not all mechanically interlocked architectures with flexible
protruding limbs qualify to be called suitanes.9 The limbs must
be long enough to thread completely through the orifices of
the suit, so that the energy barrier for the dissociation of the
body from the suit cannot be overcome in solution-based
experiments. Herein, we report the successful realization of this
concept by synthesizing and characterizing a suit[3]ane, which
contains a benzotrithiophene derivative (THBTT) with three
protruding hexyl chains as the body and a 3-fold symmetric,
extended pyridinium-based cage as the suit. We chose the
three-limb-containing suit[3]ane for investigating the mechan-
ical stability of suitanes because, unlike suit[2]anes,8b they do
not require a sterically bulky torso to prevent the suit from
slipping off, while containing the least possible number of
limbs to render them distinct from a labile pseudorotaxane.10
Guided by templation,11 as well as our knowledge of
pyridinium-based cyclophanes,12 we chose THBTT, not only
as an effective template for the synthesis of the suit, but also to
act as the body that would simultaneously be encapsulated
inside the suit, forming the suit[3]ane. Importantly, the new
MIM constitutes an example of a suitane that is held in place
by flexible alkyl chains.
The synthesis of HexaCage·6PF6 is described in Scheme 1.
Subjecting 1synthesized in two steps from commercially
available starting materials (see Scheme S1)to a 6-fold
Suzuki−Miyaura coupling reaction with 1 equiv of 3,5-
dibromopyridine in the presence of 10 mol% Pd(PPh3)4 as
the catalyst and 5 equiv of Cs2CO3 as the base in a highly
dilute solution of N,N-dimethylformamide (DMF) at 110 °C
for 12 h afforded 2 in 11% yield.13 The product was then
treated with a large excess of p-xylylene dibromide (30 equiv)
in DMF at 90 °C for 36 h, followed by counterion exchange
(NH4PF6/H2O) to give 3·3PF6 in 82% yield. Without
purification, 3·3PF6 was subjected to an intramolecular SN2
reaction with 2 in the presence of 30 mol% tetrabutylammo-
nium iodide (TBAI) as the catalyst in a highly dilute solution
of MeCN under reflux for 7 d to furnish the crude product,
which was precipitated as its chloride salt following the
addition of tetrabutylammonium chloride to the reaction
mixture. After reverse-phase column chromatography, Hexa-
Cage·6PF6 was precipitated from the eluent in aqueous
NH4PF6 in 15% yield. It is worth pointing out that the
trimethylsilyl (TMS) groups in 2 are essential to complete the
synthesis of HexaCage6+. In the absence of the TMS groups,
the bromide salt of 33+ is completely insoluble in all common
organic solvents.
RESULTS AND DISCUSSION
■
Synthesis and Structure of HexaCage·6PF6. In
searching for an appropriate suit to make suit[3]ane, we
chose an extended pyridinium-based cyclophane, namely,
HexaCage6+. It features two donut-shaped, π-electron-
deficient-pyridinium-containing platforms that are held face-
Single crystals, suitable for X-ray crystallography, were
obtained by vapor diffusion of i-Pr2O into a solution of
HexaCage·6PF6 in MeCN at room temperature. The solid-
state structure (Figure 2a) of HexaCage6+ confirms that the six
B
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Scheme 2. Synthesis of Suit[3]ane·6PF6
which include (1) its 3-fold symmetrically disposed alkyl
chains that match perfectly the 3-fold symmetry of the orifices
in HexaCage6+, (2) its planar, π-electron-rich core that will
provide strong donor−acceptor interactions with the pyridi-
nium-containing platforms during Suit[3]ane6+ formation by
templation, and (3) its ease of synthesis from commercially
available starting materials.14 See Schemes S5 and S6.
Figure 3. Equilibrium between HexaCage·6PF6 and BTT and their
1:1 complex. (a) Binding constant of BTT⊂HexaCage·6PF6 in
CD3CN at room temperature, determined by NMR titration. (b)
1
In order to find out whether or not the three alkyl chains of
THBTT are essential for its torso to be trapped inside
HexaCage6+, we measured the binding constant between
HexaCage·6PF6 and benzotrithiophene (BTT) in CD3CN at
room temperature. Without the three alkyl chains present in
THBTT, BTT is expected to be small enough to go in and out
of the cavity of HexaCage6+ relatively freely in solution. An 1H
NMR titration experiment (Figure S23) revealed (Figure 3a)
that HexaCage·6PF6 binds BTT with a Ka value of 9.20 × 104
M−1 in CD3CN at room temperature. Such a large binding
constant is indicative of a strong templation effect by THBTT
during Suit[3]ane6+ formation. The association between the
host and the guest is also dynamic,15 as revealed (Figure 3b)
by the VT 1H NMR spectroscopy of a 2:1 mixture of
HexaCage·6CF3COO and BTT in CD3OD. These observa-
Stacked VT H NMR spectra (600 MHz) for a 1:2 molar ratio of
BTT to HexaCage·6CF3COO over a range of temperatures (−70 up
to 60 °C) in CD3OD with a coalescence temperature (Tc) of
approximately −50 °C.
pyridinium units are embedded in the two opposing, parallel
hexameric platforms, which are flanked by three bridging p-
xylylene linkers. The distance between the two hexameric
platforms is 7.0 Å, allowing for near-perfect cofacial [π···π]
stacking interactions (Figure 2b) between HexaCage6+, acting
as a suit, and an aromatic torso. The openings between the
bridging p-xylylene linkers, which measure 10.4 Å in width
(Figure 2b), are more than large enough to accommodate
three limbs attached to the aromatic torso in a 3-fold
symmetric manner. The hexameric platforms, which have a
diameter of approximately 11 Å (Figure 2c), also provide a
sufficiently large binding surface to interact with an aromatic
torso in the cavity sustained by [π···π] stacking interactions.
Host−Guest Binding Constant and Structure of BTT⊂
HexaCage·6PF6. The solid-state structure of HexaCage6+
indicates that it should be capable of binding planar, π-
electron-rich aromatic guests with high affinities. This
realization led us to consider THBTT as an effective template
for the synthesis of Suit[3]ane6+ based on HexaCage6+ as the
suit. The use of THBTT as a template has several advantages,
1
tions confirm the dynamic equilibrium on the H NMR time
scale between the associated and dissociated forms of the
BTT⊂HexaCage6+ in solution, indicating that the protruding
limbs are indeed required to lock the torso of THBTT inside
HexaCage6+ permanently.
Single crystals, suitable for X-ray crystallography, were
obtained by vapor diffusion of i-Pr2O into a solution of the
2:1 molar complex of BTT⊂HexaCage·6PF6 in MeCN at
room temperature. BTT is sandwiched (Figure 4b) between
the two hexameric platforms with a plane-to-plane, pairing
C
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Figure 4. Solid-state superstructure of BTT⊂HexaCage6+ with a superimposed space-filling representation of the guest molecule on a tubular
representation of the host. PF6− anions, solvent, disordered TMS groups, and BTT molecules are all omitted for the sake of clarity. (a) Perspective
view. (b) Side-on view showing the closest plane-to-plane distance between and the platforms. (c) Plan view showing the closest distance between
and the p-xylylene linkers.
Figure 5. 1H NMR spectra (500 MHz, CD3CN, 298 K) of THBTT, HexaCage·6PF6 and Suit[3]ane·6PF6, highlighting the chemical shift changes
for the signals associated with protons in each compound.
distance of 3.5 Å. Not surprisingly, the thiophene units of BTT
(Figure 4a) pair with the more π-electron-deficient pyridinium
units in the hexameric platforms of HexaCage6+. The distance
(Figure 4c) between the hydrogen atom on the 2′ carbon of
the thiophene unit and the phenyl ring is approximately 2.7 Å.
The C−H bond, however, is not pointing toward the center of
the phenyl ring, indicating a lack of strong [C−H···π]
interactions between the host and the guest. Based on the
solid-state superstructure, the surface area overlap percentage
(Figure S34) of BTT with respect to the hexameric platform
was estimated to be 96%. This observation supports the
effective donor−acceptor interactions between BTT and the
hexameric platforms, and suggests that THBTT should serve
as an effective template during Suit[3]ane6+ formation.
Synthesis and Characterization of Suit[3]ane·6PF6. In
order for THBTT to act as a good template during the
synthesis of Suit[3]ane6+, the reaction between 2 and 3·3PF6
needs to be carried out at room temperature in the presence of
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Figure 6. Solid-state structure of Suit[3]ane6+ with a superimposed space-filling representation of the body in a tubular representation of the host.
PF6− anions, solvent, and disordered TMS groups are all omitted for the sake of clarity. (a) Perspective view. (b) Side-on view showing the closest
plane-to-plane distance between THBTT and the platforms. (c) Plan view showing the closest distances between the alkyl chains of THBTT and
the p-xylylene linkers.
a large excess of THBTT. This one-step protocol for the
synthesis of Suit[3]ane·6PF6 is outlined in Scheme 2.
Treatment of 3·3PF6 with 1 equiv of 2 afforded Suit[3]ane·
6PF6 in 13% yield as well as HexaCage·6PF6 in 9% yield after a
7 day, room-temperature reaction employing 10 equiv of
THBTT as the template, 30 mol% TBAI as the catalyst, and
DMF (3 mM) as the solvent.16 Purification of Suit[3]ane·6PF6
followed the same procedure as that used in the synthesis of
HexaCage·6PF6. Notably, most of the remaining THBTT can
be recovered by simply extracting the crude reaction mixture
with hexanes. See Scheme S7 for more details.
encapsulated (Figure 6a) inside the cavity of HexaCage6+, with
its three hexyl chains protruding through the openings between
the p-xylylene linkers. The torso of THBTT shares a plane-to-
plane distance of 3.5 Å (Figure 6b) with the two hexameric
platforms, similar to that in the BTT⊂HexaCage6+ complex.
Remarkably, the thiophene components of THBTT are not
To gain insights into the structure of Suit[3]ane·6PF6 in
1
solution, we compared its H NMR spectrum recorded in
CD3CN with the spectra of HexaCage·6PF6 and THBTT. The
resonance (Figure 5) for H-1 on the core of THBTT,
originally observed at 7.28 ppm, experiences a significant
upfield shift (all the way up to 5.11 ppm) when encapsulated
inside HexaCage6+. This dramatic upfield shift indicates a
strong shielding environment in the cavity of HexaCage6+
provided by the two hexameric platforms. Notably, such a
shielding effect is reciprocated with respect to THBTT and the
platforms themselves, as evidenced by the dramatic upfield
shifts of the resonance for the platforms’ central protons H-b
and H-d in Suit[3]ane6+. In particular, protons H-d, which are
slightly tilted toward the cavity of HexaCage6+ (Figure 2),
experience a much stronger shielding effect by THBTT (from
8.12 to 6.25 ppm) compared to that for protons H-b (from
9.27 to 8.30 ppm). Although changes in the chemical shifts of
the platforms’ peripheral protons H-a and H-c seem to be
minor, they provide more information as to how THBTT is
aligned with respect to the platforms of HexaCage6+. Whereas
the resonance for protons H-c from the TMS-benzenoid units
are shifted slightly upfield, the resonance for protons H-a from
the pyridinium units experience a slight downfield shift. A
possible explanation for this unusual shifting pattern is that,
unlike BTT, which pairs with the more π-electron-deficient
pyridinium units in HexaCage6+, THBTT aligns its thiophene
units more closely with the TMS-benzenoid units of
HexaCage6+, so that its three alkyl chains can extend outward
through the orifices in the cage. The resonances for the
platforms’ peripheral protons H-a and H-c, as well as for the
methylene protons H-f on the bridging linkers in Suit[3]ane·
6PF6 also appear as doublets and quadruplets, respectively, on
account of the lower symmetry of THBTT compared with that
of HexaCage6+.
1
Figure 7. (a) Stacked H NMR spectra (500 MHz, CD3CN, 298 K)
of Suit[3]ane·6PF6 (1 mM) over the course of 7 days of heating at
100 °C under pressure. (b) Stacked H NMR spectra (500 MHz,
CD3CN, 298 K) of the 2:1 molar mixture of THBTT and HexaCage·
6PF6 (1 mM) over the course of 7 days of heating at 100 °C under
pressure.
1
Single crystals, suitable for X-ray crystallography, were
obtained by vapor diffusion of i-Pr2O into a solution of
Suit[3]ane·6PF6 in MeCN at room temperature. THBTT is
E
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completely centered (Figure 6c) with respect to the hexameric
platforms. Neither are the three hexyl chains arranged (Figure
6c) in a perfect 3-fold symmetrical manner. One possible
explanation is that the three thiophene cores of THBTT have a
strong tendency to pair with the three electron-deficient
pyridinium units on the platforms. Because of the restricted
movement of THBTT inside Suit[3]ane6+ as a result of
mechanical bonding, THBTT only accommodates (Figure 6c)
one such pairing interaction by sliding toward the opening of
the cage, leaving the other two thiophene units paired with the
less electron-deficient TMS-benzenoid units. Normally, this
spatial arrangement would be an electronically unfavorable
coconformation if it were a labile host−guest complex. In this
case, however, the steric interactions prevent the body from
casting off the suit, as demonstrated (Figure 6c) by the very
close distances between two of the hexyl chains of THBTT
and the p-xylylene linkers of the cage. The distances of the
closest hydrogen atoms on the hexyl chains from hydrogen
atoms on the p-xylylene linkers are 2.4 and 2.6 Å.
AUTHOR INFORMATION
Corresponding Author
■
J. Fraser Stoddart − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States; School of
Chemistry, University of New South Wales, Sydney, New
South Wales 2052, Australia; orcid.org/0000-0003-
3161-3697; Email: stoddart@northwestern.edu
Authors
Xiao-Yang Chen − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States;
orcid.org/0000-0003-3449-4136
Dengke Shen − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States; Institutes
of Physical Science and Information Technology, Anhui
University, Hefei 230601, China; orcid.org/0000-0002-
3251-2372
Kang Cai − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States;
orcid.org/0000-0002-8883-0142
Yang Jiao − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States
Huang Wu − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States;
orcid.org/0000-0002-7429-0982
Suit[3]ane·6PF6 was found (Figure 7a) to be stable in
CD3CN at 100 °C under pressure over a period of 7 days. No
1
decomplexation was detected by H NMR spectroscopy. To
confirm that this thermal stability of Suit[3]ane·6PF6
originates from mechanical bonding, rather than the strong
donor−acceptor interactions between THBTT and the cage,
we carried out an experiment where we subjected a 2:1 molar
mixture of THBTT and HexaCage·6PF6 in CD3CN at 100 °C
Bo Song − Department of Chemistry, Northwestern University,
Evanston, Illinois 60208, United States; orcid.org/0000-
0002-4337-848X
Long Zhang − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States;
orcid.org/0000-0002-4631-158X
1
under pressure for 7 days. An H NMR spectrum (Figure 7b)
confirmed that no THBTT enters inside HexaCage6+ during
this time, indicating that the body is unable to get into the suit
even at high temperatures. These results lend support to the
mechanical stability of Suit[3]ane6+ endowed by its three
flexible alkyl chains.
Yu Tan − Department of Chemistry, Northwestern University,
Evanston, Illinois 60208, United States
Yu Wang − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States;
orcid.org/0000-0002-0085-3308
Yuanning Feng − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States;
orcid.org/0000-0002-8832-0767
CONCLUSION
■
We have introduced a new template-directed strategy for the
synthesis of a suit[3]ane. As a result of a series of NMR
spectroscopic experiments carried out on a dynamic 1:1
complex between a suit and a torso, we have demonstrated that
the three protruding limbs need to be added to the torso in
order to make a suit[3]ane that is mechanically stable. In
relation to the previously reported suitanes,8 the body of
suit[3]ane is held in place mechanically by flexible protruding
limbs, a property that exemplifies the importance of steric
factors in addition to electronic interactions in stabilizing
suitanes.
Charlotte L. Stern − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States
Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.0c09896
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
ASSOCIATED CONTENT
■
■
Financial support from Northwestern University is gratefully
acknowledged. This work made use of the IMSERC at
Northwestern University, which received support from the
NIH (1S10OD012016-01/1S10RR019071-01A1), Soft and
Hybrid Nanotechnology Experimental (SHyNE) Resource
(NSF ECCS-1542205), the State of Illinois, and the Interna-
tional Institute for Nanotechnology (IIN).
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The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.0c09896.
Detailed experimental procedures and characterization
data (NMR spectroscopy, UV−vis spectroscopy, cyclic
voltammetry, X-ray crystallography) (PDF)
Crystallographic information file for HexaCage·6PF6
REFERENCES
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Crystallographic information file for BTT⊂HexaCage·
6PF6 (CIF)
Crystallographic information file for Suit[3]ane·6PF6
(CIF)
F
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