ARTICLES

PUBLISHED ONLINE: 26 JANUARY 2014 | DOI: 10.1038/NCHEM.1842

Induced-t catalysis of corannulene

bowl-to-bowl inversion
Michal Jurcek1, Nathan L. Strutt1, Jonathan C. Barnes1, Anna M. Buttereld2, Edward J. Dale1,
Kim K. Baldridge2,3, J. Fraser Stoddart1 and Jay S. Siegel2,3 *
Stereoelectronic complementarity between the active site of an enzyme and the transition state of a reaction is one of the
tenets of enzyme catalysis. This report illustrates the principles of enzyme catalysis (rst proposed by Pauling and Jencks)
through a well-dened model system that has been fully characterized crystallographically, computationally and kinetically.
Catalysis of the bowl-to-bowl inversion processes that pertain to corannulene is achieved by combining ground-state
destabilization and transition-state stabilization within the cavity of an extended tetracationic cyclophane. This synthetic
receptor fulls a role reminiscent of a catalytic antibody by stabilizing the planar transition state for the bowl-to-bowl
inversion of (ethyl)corannulene (which accelerates this process by a factor of ten at room temperature) by an induced-t
mechanism rst formulated by Koshland.
nzymatic catalysis depends strongly on what Pauling1 referred
to as specic complementarity between the active-site structure
of a host and the activated state of a guest. This level of ligand
specicity of an enzyme led Jencks2 to propose the concept of antibody catalysis, in which a specic antibody can be generated in
response to a hapten that resembles the transition state of the reaction in question. Employing this methodology of a transition-state
analogue (TSA), the groups of Lerner3 and Schultz4 developed antibody hydrolases. Since then, many antibodies517 have been programmed to behave like enzymes for standard synthetic organic
reactions (for example, DielsAlder cycloadditions1823) using
strongly binding TSAs. These amazing achievements notwithstanding, there remains a need for a simple kinetically and structurally
well-dened and well-characterized model system to illustrate the
PaulingJencks model. Corannulene2441 (Fig. 1a), a C5v symmetric
bowl-shaped polycyclic aromatic hydrocarbon (bowl depth42
0.87 ) undergoes degenerate bowl-to-bowl inversion along a
well-dened reaction path that passes through a planar D5h
transition state. ExBox 41, a synthetic tetracationic cyclophane43
(Fig. 1b), comprises two p-electron-poor extended bipyridinium
units that selectively bind planar aromatics comparable to the
corannulene transition state (Fig. 1a). Herein, ExBox 41 is shown
to catalyse the bowl-to-bowl inversion process of corannulene;
kinetic, crystallographic and computational studies support this
system as a duciary one that displays catalysis consistent with the
PaulingJencks model.
The energy barrier for bowl-to-bowl inversion of nascent
corannulene has been estimated38 to be 11.5 kcal mol21 from its
ground-state bowl form to its transition-state planar form.
Corannulenes bowl depth (for example, 0.87 from the best
plane of the hub carbon atoms to the best plane of rim carbon
atoms) serves38 as a composite reaction coordinate for the bowlto-bowl inversion process. Substituents in the peri positions of
corannulene cognates demonstrate that the barrier for bowl-tobowl inversion depends38 on the fourth power of this bowl depth;
thus, a 10% modulation in bowl depth results in a 103 change in

rate, which makes the system ideal for studying catalysis induced
by stereoelectronic binding.
Free ExBox 41 is ideally suited43 for binding planar aromatic
guests. Its cavity is 3.5 wide and 11.3 long after taking into
consideration van der Waals radii, and it forms strong one-to-one
arene , ExBox 41 complexes with an array of polycyclic aromatic
hydrocarbons that range in size from two to seven fused rings (coronene
is among the most strongly bonded substrates). In general, greater
surface areas and orbital overlap lead to larger binding constants.
Corannulenes ground-state bowl form, with van der Waals dimensions of 10 4.3 , is too thick to t into ExBox 41 with any appreciable overlap of the p-surface area (Fig. 1). Complexation could occur if
a

4.3

3.4

4.3

0.87

0.0

0.87

b
+
N

+
N
6.9

N
+

3.5

N
+

Figure 1 | Structural formulae and solid-state structures. a,b, The structural

formulae and solid-state structures, obtained by X-ray crystallography, of
corannulene (a) and ExBox 41 (b). The optimized geometry of the planar
transition state of the bowl-to-bowl inversion process of corannulene (a)
was obtained by DFT (B97D/Def2-TZVPP).

Center for the Chemistry of Integrated Systems, Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, USA,
Organic Chemistry Institute (OCI), University of Zurich, Winterthurerstrasse 190, Zurich, CH-8057, Switzerland, 3 School of Pharmaceutical Science and
Technology, Tianjin University (A210/Building 24), 92 Weijin Road, Nankai District, Tianjin, 300072 PRC, China. * e-mail: dean_spst@tju.edu.cn

222

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NATURE CHEMISTRY

ARTICLES

DOI: 10.1038/NCHEM.1842

e
7.61

7.79

7.28

0.84

0.84

0.85

14.35

14.14

14.48

b
7.05

f
7.24

6.99

0
14.49

14.49

0
14.58

Figure 2 | Ground state versus transition state. a,b, Top and side-on views of the solid-state superstructures, obtained by X-ray crystallography, of
corannulene , ExBox 41 (a) and coronene , ExBox 41 (b) 1:1 complexes. cf, Top and side-on views of the optimized geometries, obtained by DFT
(B97D/Def2-TZVPP), of the ground and transition states of the corannulene , ExBox 41 complex in the gas phase (c,d, respectively) and in the solvent
(Me2CO) model (e,f, respectively).

ExBox 41 and corannulene undergo induced-t conformational

changes (as rst proposed by Koshland4446) and the nal binding
strength would result from an optimization of the energy cost of
induced t against the energy benet of a better p-surface overlap.
The energy stored in the form of strain in the widened ExBox 41 can
be viewed as the potential energy that forces corannulene to adopt a
atter conformation inside ExBox 41, which effectively decreases the
energy barrier for the bowl-to-bowl inversion process. Consequently,
ExBox 41 distorts the bowl-shaped ground state and stabilizes the
planar transition state of corannulene, as it adapts its shape continuously to t the substrate tightly at each intermediate state.

Results and discussion

In the solid-state superstructure (Fig. 2a and Supplementary Fig. 24)
of corannulene , ExBox 41, corannulene is positioned within
ExBox 41 such that the middle ve-membered ring partially overlaps with both para-phenylene rings of ExBox 41. Corannulene is
not centred precisely within ExBox 41, but rather is offset and protrudes on one side. The width of ExBox 41 in the hostguest
complex increases by 0.87 (from 6.92 to 7.79 ) and the bowl
width of corannulene decreases by 0.03 (from 0.87 to 0.84 ),
supporting the induced-t hypothesis.
The same geometrical trends are observed (Fig. 2cf ) when the
optimized (B97D/Def2-TZVPP) geometries for the ground and
transition states of the corannulene , ExBox 41 1:1 complex are
compared4757. The width of ExBox 41 increases by 0.37 and
0.29 in the gas phase and Me2CO, respectively. The bowl depth
of corannulene in the ground state decreases by 0.03 and 0.02
in the gas phase and Me2CO, respectively.

In the present context, coronene can serve as a conceptual TSA

for the bowl-to-bowl inversion of corannulene. The planar conformation of coronene is a consequence of its central six-membered
ring and is to be contrasted, in the case of corannulene, with its
central ve-membered ring, which mandates its bowl-shaped conformation. Indeed, the crystal superstructure43 of coronene ,
ExBox 41 (Fig. 2b) displays an analogous superstructure to that of
the complex between corannulene in its transition state and
ExBox 41. The length and width of ExBox 41 in coronene ,
ExBox 41 have values very close to those obtained for the optimized
geometries of the transition statethat is, approximately 14.5 in
length and 7.1 in width (Fig. 2d,f ).
The binding afnities (Ka) of ExBox 41 with corannulene were
determined (Supplementary Figs 1, 2 and 1823) as roughly
103 M21: Ka 3.12 103+41 M21 (1H NMR spectroscopy,
MeCN-d3), 6.45 103+0.66 103 M21 (isothermal titration
calorimetry (ITC), MeCN), 863+25 M21 (1H NMR spectroscopy,
Me2CO-d6) and 5.02 103+3.1 103 M21 (ITC, Me2CO). The
higher binding afnity in MeCN(-d3) compared with that in
Me2CO(-d6) can be attributed to corannulenes greater solubility
in Me2CO(-d6) than in MeCN(-d3). The binding afnity between
ExBox 41 and corannulene arises from multiple sources, including
charge-transfer interactions, surface-area binding phenomena58,
van der Waals force and solvophobic effects59.
The binding afnity of an aromatic guest towards ExBox 41
increases43 exponentially according to the number of p electrons.
Perylene, like corannulene, has 20 p electrons in the
aromatic system, but perylene is at. The Ka value of perylene
(1H NMR spectroscopy, MeCN-d3) is 88.1 103+67 103 M21

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(DG 26.74+0.45 kcal mol21)43, approximately 30 times that

obtained for corannulene (3.12 103+41 M21 (1H NMR spectroscopy, MeCN-d3), DG 24.76+0.077 kcal mol21). The energy
loss (1.98+0.46 kcal mol21) that lowers the overall afnity of
corannulene towards ExBox 41 is, again, the result of the strain
generated in the components on complexation.
Variable-temperature 1H NMR experiments were performed on
2:1 (Supplementary Fig. 4), 1:1 (Supplementary Fig. 5) and 1:2 mixtures (Fig. 2 and Supplementary Fig. 6) of ExBox 41 and corannulene-d10 (ref. 60), and on a 1:1 mixture of ExBox 41 and
corannulene (Supplementary Fig. 3) in Me2CO-d6. Depending on
the rate of complexation equilibrium (in/out) and the bowl-tobowl inversion processes on the 1H NMR timescale, one or multiple
sets of signals for ExBox 41 and corannulene were observed. At
162 K in Me2CO-d6 , the complexation equilibrium (in/out) and
the bowl-to-bowl inversion processes are slow relative to the 1H
NMR timescale. In the 1H NMR spectrum (Supplementary Figs 1
and 2) of the 1:1 mixture of ExBox 41 and corannulene, the 32
hydrogens of ExBox 41 give rise to ve signals and the ten hydrogens
of corannulene to one signal. As a result of the face-to-face orientation of corannulene inside ExBox 41, the b and g protons of
ExBox 41, as well as the protons of corannulene, shift upeld,
in contrast to the C6H4 ( para-phenylene) signals of ExBox 41,
which shift downeld. Signals for the a and CH2 protons positioned
in the corners of ExBox 41 are not affected by the shielding effect
of the guest and do not exhibit signicant shifts. In a sample with
a ratio of 2:1 ExBox 41 to corannulene-d10 , two sets of signals,
which arise from bound and unbound ExBox 41, are observed
below the coalescence temperature (Tc) (Supplementary Figs 4
and 9), and two sets of signals for bound and unbound corannulene
are observed below Tc for a sample with a 1:2 ratio of ExBox 41 to
corannulene-d10 (Supplementary Fig. 6). In all mixtures, two sets
of signals are observed additionally for bound ExBox 41 (b and g
protons) below Tc because the signals for the top b and g
protons that face towards the inside of the bowl and for the
bottom b and g protons that face towards the outside of the
bowl each become heterotopic when corannulene does not
undergo bowl-to-bowl inversion, or when the process is slow relative
to the 1H NMR timescale (Fig. 3). One set of signals is observed, in
each case, for the bound and unbound corannulene, which indicates
that its rotation, both inside and outside ExBox 41, is fast on the 1H
NMR timescale, even at low temperatures.
The energy barrier for the bowl-to-bowl inversion process of corannulene inside ExBox 41 was investigated by dynamic 1H NMR
spectroscopy. The difference in chemical shifts for the two sets of
signals of bound ExBox 41 below Tc can be used to determine the
energy barrier and rate for the bowl-to-bowl inversion process
(Fig. 3). The chemical shift of the g protons of ExBox 41 is the
most sensitive to the change of chemical environment, as these
protons are positioned right above and below the centre of the
bound corannulene core. The signals for the g protons were therefore used to determine the energy barrier associated with bowl-tobowl inversion in Me2CO-d6. The sharp singlet for the g protons
at 6.86 ppm broadens (Fig. 3b) and shifts upeld slightly as the
temperature is decreased. When the temperature reaches 190+5 K,
the signal for the g protons becomes broadened into the baseline
and then, at 165 K, appears again as two signals at 7.45 and
5.08 ppm, which correspond to the bottom g2 protons that face
towards the outside and the top g1 protons that face towards the
inside of the corannulene bowl, respectively.
Dynamic 1H NMR line-shape simulations were conducted to
determine the values of the rate constants (k) at various temperatures and to estimate the value (190+5 K) of Tc. The Eyring
equation, DG c 2RT ln(kch/kBTc), was then used to calculate
DG c values at Tc and the Eyring plot (Supplementary Fig. 16) was
used to determine DH and DS values, which were used to calculate
224

H H H1 H
1 H
CH2 1

T > 190 K
H1 = H2 C6H4

CH2

C6H4

DOI: 10.1038/NCHEM.1842

H H H2 H
2
2 H
CH2

CH2

C6H4

CH2
H

4PF6

H H

CH2

C6H4

T < 190 K
H1 H2

C6H4 H C20HD9 H

CH2
H

4PF6

H H
1

CH2

CH2
T (K)
300
290
280
270
260
250
240
230
220
210
200
190
180

H2

170

H1 H
2

H 1
165

10

7
(ppm)

CH2
T (K)

H1 = H2

H1 = H2 CH2

T (K)

C20HD9
200

300

k = 5,400 s1

k = 1,580,000 s1
Sim

Sim

H1 = H2
190

280

k = 3,190 s1

k = 642,000 s1
Sim

H2

Sim

H1
180

k = 1,200 s1

260
k = 251,160 s1

Sim
H2

Sim

H1
165
k = 470 s1
7

6
(ppm)

230
k = 46,500 s1

Sim
5

Sim

(ppm)

Figure 3 | NMR spectroscopy with corannulene-d 10. a, Bowl-to-bowl

inversion process of corannulene inside ExBox 41. The signals for the top g1
protons that face towards the inside of the bowl and the bottom g2 protons
that face towards the outside of the bowl each become heterotopic below
Tc (,190 K). b, Stacked spectra for the variable-temperature 1H NMR
spectroscopic measurements of a 1:2 mixture of ExBox 4PF6 and corannulene-d10
(C20D10) in Me2CO-d6. Tc of the 1H NMR resonances for g protons of
ExBox 4PF6 was determined as 190+5 K. c, Measurements of the rate
constants (k) for the in/out equilibrium process of corannulene and ExBox 41
were conducted by dynamic 1H NMR line-shape simulations (Sim) using the
program iNMR (version 3.2.1). The obtained values of the kinetic parameters
were: DGc 7.91+0.22 kcal mol21, DH 5.62+0.19 kcal mol21,
DS 211.9+0.91 cal mol21 K21, DG 190K 7.88+0.26 kcal mol21.
ExBox 4PF6 spectra, green; corannulene spectra, black.
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NATURE CHEMISTRY
a

H1

H1

H2

ARTICLES

DOI: 10.1038/NCHEM.1842

H2

H1

H1

H2

H2
*

c
HCor-Ar

HCor-Ar

H1 = H2

T (K)

HCor-Ar

300

300

290

290

220

220

210

210

200

200

195

190

190

180

H1

180

H2

3.0

H1

H2

k = 90 s1

170
k = 26 s1

Sim
3.4

3.3

3.2

H2

H1
220

3.1

(ppm)

170

Sim

Sim

230

230

195

k = 530 s1

240

k = 335 s1

240

235

3.1

Sim

Sim

250

240

3.2

k = 2,650 s1

260

245

(ppm)

210

260

270

250

3.3

Sim

k = 2,000 s1

280

260

3.4

k = 6,000 s1

Sim

T (K)

270

H2

220

280
k = 14,580 s1

H1 = H2

T (K)

T (K)

HCor-Ar

280

H1

H1 = H2

H1 = H2

3.0

2.9

2.7

2.5

Sim
2.3

(ppm)

170
3.1

2.9

2.7

2.5

2.3

(ppm)

Figure 4 | NMR spectroscopy with ethylcorannulene. a,b, Bowl-to-bowl inversion process (top) and stacked spectra (bottom) for the variable-temperature
1
H NMR spectroscopic measurements of ethylcorannulene (a) and a 2:1 mixture of ExBox 4PF6 and ethylcorannulene (b) in Me2CO-d6. Tc values of the 1H
resonances for CH2 protons of ethylcorannulene were determined as 240+5 K for nascent ethylcorannulene (a) and 195+5 K for bound ethylcorannulene
(b). c,d, Measurements of the rate constants (k) for the bowl-to-bowl inversion processes of nascent ethylcorannulene (c) and ethylcorannulene inside
ExBox 41 (d) were conducted by dynamic 1H NMR line-shape simulations (Sim) using the program iNMR (version 3.2.1). The obtained values of the kinetic
parameters were: DG c 11.2+0.12 kcal mol21, DH 9.95+0.49 kcal mol21, DS 24.35+2.0 cal mol21 K21, DG 190K 10.8+0.62 kcal mol21 (c), and
DG c 8.82+0.12 kcal mol21, DH 7.16+0.27 kcal mol21, DS 28.14+1.2 cal mol21 K21, DG 190K 8.71+0.36 kcal mol21 (d). ExBox 4PF6 spectra,
green; corannulene spectra, black, HDO (2.81 ppm at 300 K), H2O (2.77 ppm at 300 K) and CHD2COCD3 (2.05 ppm) spectra, pink; ,ExBox 41,
green asterisks; Ar, aryl.

DG T values by using the equation DG T DH 2 TDS . The DG T

values at 190 K (DG 190K) were used to compare energy barriers of
different processes.
The energy barrier (DG 190K) (corresponding to either the in/out
equilibrium or the bowl-to-bowl inversion process) was found to be
7.88+0.26 kcal mol21 (DG c 7.91+0.22 kcal mol21) for the 1:2
mixture of ExBox 41 and corannulene-d10 (Fig. 3 and Supplementary
Fig. 7). For a comparison, the value of the energy barrier (DGc) for
the 2:1 (Supplementary Fig. 4) and 1:1 (Supplementary Fig. 5)
mixtures of ExBox 41 and corannulene-d10 was found to be
7.91+0.22 kcal mol21 on average. The 7.88+0.26 kcal mol21
value is smaller, by 3.6 kcal mol21, than that (11.5 kcal mol21) of
the estimated38 energy barrier for free corannulene. The bowl-tobowl inversion process of unbound parent corannulene cannot
be observed in this system because of symmetry degeneracy38.
The energy barrier for the bowl-to-bowl inversion of corannulene
inside ExBox 41 was also calculated using density functional theory
(DFT) (B97D/Def2-TZVPP)4757. The calculated values for the
energy barrier associated with this process are 8.77 kcal mol21 in
the gas phase and 8.47 kcal mol21 using a continuum solvent model
(Me2CO), both of which are in reasonable agreement with the value
obtained experimentally in Me2CO-d6 (7.88+0.26 kcal mol21).
The bowl-to-bowl inversion process of ethylcorannulene
inside ExBox 41 was studied by dynamic 1H NMR spectroscopy to

evaluate more accurately whether the 7.88+0.26 kcal mol21 value

for the energy barrier corresponds to the bowl-to-bowl inversion
or rather to the in/out equilibrium process. Ethylcorannulene
shows a very similar binding afnity to ExBox 41 in both
MeCN-d3 (Ka 2.86 103+0.72 103 M21) and Me2CO-d6
(Ka 530+31 M21) compared to those obtained for corannulene
(Supplementary Figs 10 and 11). Moreover, the sterically nondemanding ethyl substituent should not alter36 the bowl depth of
the corannulene core signicantly and, thus, the energy barrier for
the bowl-to-bowl inversion process should be very close to that
observed for corannulene. The 1H NMR signals for the CH2
protons of ethylcorannulene (which become heterotopic when the
bowl-to-bowl inversion is slow relative to the 1H NMR timescale)
were used to determine the energy-barrier values (DG 190K) in
Me2CO-d6. These values were found to be 10.8+0.62 kcal mol21
for nascent ethylcorannulene (Fig. 4a,c and Supplementary Figs
12 and 13) and 8.71+0.36 kcal mol21 for the 2:1 mixture of
ExBox 41 and ethylcorannulene (Fig. 4b,d and Supplementary
Figs 14 and 15). This decrease of 2.09+0.72 kcal mol21 in the
energy barrier demonstrates the ability of ExBox 41 to catalyse the
bowl-to-bowl inversion of ethylcorannulene, and accelerate this
process by a factor of ten at room temperature based on the rate
constants obtained from 1H NMR line-shape simulations
(see Supplementary Figs 13 and 15).

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Gcatalysis
2.5 kcal mol1

E (kcal mol1)

14.9

Gbound

Gunbound

8.5

Gunbound

4.0
Gbound

Gbinding
0

DOI: 10.1038/NCHEM.1842

bowl depth was found to be 0.84 (X-ray diffraction, Fig. 2a) and
0.85 (DFT, Fig. 2e). The portion of the energy-barrier decrease
related to the ground-state destabilization of corannulene inside
ExBox 41 has been calculated by DFT (B97D/Def2-TZVPP)4757 to
be 0.5 kcal mol21. Considering that the energy-barrier decrease
(DDG catalysis) for the bowl-to-bowl inversion of corannulene inside
ExBox 41 was calculated to be 2.5 kcal mol21 and for ethylcorannulene inside ExBox 41 it was found to be 2.09+0.72 kcal mol21,
DDG catalysis is not merely the result of corannulene ground-state
destabilization (0.5 kcal mol21), but mainly of stabilization
(2.0 kcal mol21) of the planar transition-state structure in the
bowl-to-bowl inversion process of corannulene (Fig. 5b).

Conclusion
Bowl

Flat

Bowl

b
GTS stabilization
10.9 kcal mol1

2.0 kcal mol1

Gunbound

Gbound

Bound

Bound

Unbound
Bowl

GGS destabilization

Unbound
Flat

0.5 kcal mol1

Bowl

Figure 5 | Energy prole. a, Comparison of the relative-energy (E) proles

for the bowl-to-bowl inversion of corannulene (black) and corannulene ,
ExBox 41 (green) in Me2CO calculated by DFT (B97D/Def2-TZVPP). The
value of the energy-barrier decrease (DDG catalysis) was determined as
2.5 kcal mol21. b, Absolute contributions of ground-state (GS) destabilization
(0.5 kcal mol21) and transition-state (TS) stabilization (2.0 kcal mol21) to the
overall energy-barrier decrease (DDG catalysis) of the bowl-to-bowl inversion
process of corannulene inside ExBox 41 calculated by DFT (B97D/Def2-TZVPP).

The energy barrier in free corannulene determined by DFT

(B97D/Def2-TZVPP)4757 was found to be 10.92 kcal mol21 in
Me2CO, and an energy barrier of 8.47 kcal mol21 was calculated
for corannulene , ExBox 41 in Me2CO. The calculated energybarrier decrease (2.45 kcal mol21) for corannulene in Me2CO
(Fig. 5a) is in excellent agreement with that (2.09+0.72 kcal mol21)
measured for ethylcorannulene in Me2CO-d6. Moreover, the
2.09+0.72 kcal mol21 energy-barrier decrease is in a very close agreement with the value of the energy loss (2.03+0.47 kcal mol21;
binding energy (DG) of perylene43 versus ethylcorannulene
(Supplementary Fig. 11) inside ExBox 41 in MeCN-d3) that occurs
on complexation as a result of induced-t conformational
changes, demonstrating that this stored potential energy
effectively decreases the energy barrier of the bowl-to-bowl inversion process. The 7.88+0.26 kcal mol21 value obtained for
corannulene , ExBox 41 in Me2CO-d6 must, therefore, correspond
to the energy barrier of the out process, a conclusion that was
supported by dynamic 2H NMR measurements and line-shape
analysis for corannulene-d10 , ExBox 41 in Me2CO (Supplementary
Fig. 17, DG 190K (out) 8.16+0.21 kcal mol21). The value of
the energy barrier for the bowl-to-bowl inversion process of
corannulene , ExBox 41 (energy loss of 1.98+0.46 kcal mol21)
is expected to be very close to that obtained for ethylcorannulene
(8.71+0.36 kcal mol21).
It has been shown38 that decreasing the bowl depth of corannulene
by modifying its periphery (and so, effectively, destabilizing its
ground state) lowers the energy barrier for the bowl-to-bowl inversion process. In the corannulene , ExBox 41 complex, corannulenes
226

In summary, we have identied a catalytic biomimetic system in

which the energy-barrier decrease of the bowl-to-bowl inversion
of corannulene and ethylcorannulene is achieved by combining
the effects of the ground-state destabilization and transition-state
stabilization within the cavity of a synthetic receptor, which comprises two extended bipyridinium units joined end-to-end by two
para-xylylene linkers. This tetracationic cyclophane adopts a role
similar to that of a catalytic antibody, wherein the planar transition
state of the guest is stabilized through the stereoelectronic reorganization of the host in the hostguest complex from a strained to an
energetically favourable conformation. These experimental observations, in conjunction with DFT calculations, provide an alternative induced-t mechanism (transition-state stabilization versus
ground-state destabilization) for lowering the energy barrier of the
bowl-to-bowl inversion process of corannulene. In this simple textbook example, catalysis of the inversion process in corannulene
induced by stereoelectronic binding of corannulene inside a synthetic receptor can be followed along one reaction coordinate,
where the reactant and the product are identical.

Methods
Computational data. Four pdb les (Supplementary pdbs 14) of the optimized
geometries (B97D/Def2-TZVPP) of the ground and transition states of corannulene
, ExBox 41 complex in the gas phase and in Me2CO are available in the
Supplementary Information.
X-ray crystallography. The crystallographic data for corannulene ,
ExBox 4PF6(MeCN)7 are available free of charge from the Cambridge
Crystallographic Data Centre (CCDC) via www.ccdc.cam.ac.uk/data_request/cif.
CCDC Number: 950390.
Method. Corannulene (0.7 mg, 3 mmol) was added to a solution of ExBox 4PF6
(3.0 mg, 2.4 mmol) in MeCN (0.8 ml) and, after it had dissolved, the mixture was
passed through a 0.45 mm lter equally into three 1 ml tubes. The tubes were
placed together in one 20 ml vial that contained i-Pr2O (3 ml) and the vial was
capped. Slow vapour diffusion of i-Pr2O into the 1.25:1 solution of corannulene and
ExBox 4PF6 in MeCN over a period of three days yielded yellow single crystals
(0.27 0.22 0.07 mm) of corannulene , ExBox 4PF6(MeCN)7 (space group
P, Supplementary Section S6b). The solid-state superstructure of corannulene ,
ExBox 4PF6(MeCN)7 is shown in Supplementary Fig. 24.
Crystal parameters. [C20H10 , C48H40N4 (PF6)4] (CH3CN)7: yellow block
(0.27 0.22 0.07 mm), triclinic, P, a 17.8249(5), b 20.7626(6),
c 24.4682(7) , a 84.8192(14), b 86.0993(15), g 66.3786(14)8,
V 8,257.8(4) 3, Z 4, T 100.05 K, rcalc 1.440 g cm23, m 1.782 mm21.
Of a total of 75,420 reections that were collected, 27,233 were unique. Final
R1(F 2 . 2sF 2) 0.0808 and wR2 0.2272. Data were collected at 100 K on a Bruker
Kappa APEX CCD diffractometer equipped with a CuKa microsource with Quazar
optics. SADABS-2008/1 (Bruker, 2008) was used for the absorption correction.
wR2(int) was 0.0478 before and 0.0387 after correction. The ratio of minimum to
maximum transmission was 0.8801. The half correction factor was 0.0015. Group
anisotropic displacement parameters were rened for the disordered MeCN
molecules. Distance restraints were rened for the disordered nitrogen atom N(14)
in the MeCN molecule. Rigid bond restraints (estimated standard deviation (e.s.d.)
0.01) were imposed on the displacement parameters as well as restraints on similar
amplitudes (e.s.d. 0.05) separated by less than 1.7 on the disordered PF62 ions and
the disordered atoms of the para-phenylene ring in ExBox 4PF6. Renement of F 2
was performed against all reections. The weighted R-factor wR and goodness of t S
are based on F 2, and conventional R-factors R are based on F, with F set to zero for
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DOI: 10.1038/NCHEM.1842

negative F 2. The threshold expression of F 2 . 2sF 2 is used only to calculate

R-factors(greater than), and so on, and is not relevant to the choice of reections for
renement. R-factors based on F 2 are statistically about twice as large as those
based on F, and R-factors based on all data will be even larger.
1
H NMR spectroscopy. The 1H NMR (298 K, 500 or 600 MHz) titrations were
performed by adding small volumes of a solution of (ethyl)corannulene in
Me2CO-d6 or MeCN-d3 to a solution of ExBox 4PF6 in Me2CO-d6 or MeCN-d3 ,
respectively. The upeld shifts of the 1H NMR resonances for g protons were
observed and used to determine the association constants (Ka). The Ka values were
calculated using Dynat61, a program that employs nonlinear least-squares
regression on hostguest binding data. Measurements of the rate constants (k) for
the bowl-to-bowl inversion process of (ethyl)corannulene were conducted62
by dynamic 1H NMR line-shape simulations using the program iNMR
(version 3.2.1). The Eyring equation, DG c 2RT ln(kch/kBTc), was used to
calculate63 the DG c values at Tc. The DH and DS values were obtained
through an Eyring plot (1/T against ln(k/T ), Supplementary Fig. 16) generated
using rate constants (k) determined by dynamic 1H NMR line-shape
simulations (Supplementary Figs 7, 13 and 15). The DG 190K values were
obtained using equation DG T DH 2 TDS .

ITC. The ITC measurements were performed in dry, degassed Me2CO and MeCN at
298 K. A solution of ExBox 4PF6 was used as the host solution in a 1.8 ml cell.
Solutions of corannulene were added by injecting 10 ml of titrant successively
over 20 seconds (25) with intervals of 300 seconds between each injection.
Experiments were repeated three times. Thermodynamic information was
calculated using a one-site binding model to utilize data, from which the heat of
dilution of the guest was subtracted, with the average of three runs reported
(Supplementary Figs 1823).

Received 15 August 2013; accepted 9 December 2013;

published online 26 January 2014

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Acknowledgements
The authors thank M. Stuparu for synthesizing bromocorannulene and C. L. Stern for
performing the X-ray crystallographic analysis. This research is part of the Joint Center of
Excellence in Integrated Nano-Systems (JCIN) at King Abdul-Aziz City for Science and
Technology (KACST) and Northwestern University (NU) (Project 34-947). The authors
would like to thank both KACST and NU for their continued support of this research. We
also acknowledge support from the World Class University Program (R-31-2008-00010055-0) in Korea. M.J. gratefully acknowledges The Netherlands Organisation for
Scientic Research and the Marie Curie Cofund Action (Rubicon Fellowship). N.L.S. and
E.J.D. are supported by a Graduate Research Fellowship from the National Science
Foundation. J.C.B. is supported by a National Defense Science and Engineering Graduate
Fellowship from the Department of Defense and gratefully acknowledges receipt of a Ryan
Fellowship from the NU International Institute for Nanotechnology. K.K.B. and J.S.S.
gratefully acknowledge the Swiss National Science Foundation, the Qian Ren Scholar
Program of China and the Synergetic Innovation Center of Chemical Science and
Engineering (Tianjin).

Author contributions
M.J., N.L.S., J.C.B., J.F.S. and J.S.S. conceived the project and prepared the manuscript. M.J.,
J.C.B., A.M.B. and E.J.D. synthesized the different molecules studied in this work. M.J. and
N.L.S. carried out NMR studies. K.K.B. performed DFT calculations. M.J., N.L.S., J.C.B.,
K.K.B., J.F.S. and J.S.S. investigated the bowl-to-bowl inversion process.

Additional information
Supplementary information and chemical compound information are available in the
online version of the paper. Reprints and permissions information is available online at
www.nature.com/reprints. Correspondence and requests for materials should be
addressed to J.S.S.

Competing nancial interests

The authors declare no competing nancial interests.

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