Quinone-based, redox-active resorcin[4]arene cavitands

Article abstract of DOI:10.1002/anie.201106031

Catch it if you can! Redox-active resorcin[4]arene cavitands with quinone walls can be reversibly reduced to the hydroquinone form, influencing their host-guest complexation strength. Specifically, a top-covered triptycenequinone cavitand forms kineticall

Full text of DOI:10.1002/anie.201106031

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DOI: 10.1002/anie.201106031
Redox-Active Cavitands
Quinone-Based, Redox-Active Resorcin[4]arene Cavitands**
Igor Pochorovski, Corinne Boudon, Jean-Paul Gisselbrecht, Marc-Olivier Ebert,
W. Bernd Schweizer, and FranÅois Diederich*
Since the preparation of the first quinoxaline-bridged resor-
cin[4]arene cavitand by Cram and co-workers in 1982,[1]
numerous derivatives with various structures and functions
have been prepared and employed as switches,[2] receptors
and sensors,[3] catalysts,[4] and molecular hosts.[5] The most
fascinating feature of top-open resorcin[4]arene cavitands is
their ability to adopt two spatially well-defined conforma-
tions: an expanded “kite” form and a contracted “vase” form.
While various methods have been employed to study the
conformational properties of cavitands,[6] the most convenient
1
one is H NMR spectroscopy. Figure 1 illustrates the vase–
kite1–kite2 equilibrium of a generic cavitand, and how three
situations, vase, kite with slow kite1–kite2 interconversion,
and kite with fast kite1–kite2 interconversion, can be
1
distinguished by H NMR spectroscopy.[7]
The three stimuli that have been identified for switching
the cavitand between its vase and kite forms are changes in
temperature,[1,8] pH,[9] and metal-ion concentration.[6a] Addi-
tionally, cavitands can function as molecular grippers by
binding guest molecules in their vase conformations; these
binding properties have been modulated using changes in
pH,[10] metal-ion complexation,[11] and light.[12] To use redox
Figure 1. Vase–kite1–kite2 equilibrium of a generic cavitand and sum-
1
processes as new stimuli for tuning cavitand properties,
however, is a highly desirable, yet unreached goal.[2] Electro-
chemically induced redox switching, if truly reversible, and
performed on the surface of a metal electrode, could enable
the application of cavitands as molecular grippers.[2,13]
Towards this end, we chose to investigate cavitands contain-
ing the quinone moiety as a new and easily installed redox-
active wall component[8b] and to study how changing their
redox states affects their conformational and binding proper-
ties.
mary of characteristic H NMR features of three situations: vase, kite
with slow kite1–kite2 interconversion, and kite with fast kite1–kite2
interconversion.
n[4]arene cavitands:[6e,7,14] the vase conformation is preferred
more strongly in cavitands with larger walls and in solvents
such as tetrahydrofuran, benzene, and toluene than in
cavitands with smaller walls and in chlorinated solvents
(CD2Cl2, CDCl3, (CDCl2)2). We therefore prepared a series of
quinoid cavitands with different wall sizes (ox-1a–c, Figure 2)
and investigated their conformational preferences in one
member of each solvent class (for the synthesis of all reported
compounds, see the Supporting Information, Section 2).
The 1H NMR spectra (298 K, 500 MHz) of cavitand ox-1b
in CD2Cl2 and [D8]THF are shown in Figure 2. In both
solvents, the cavitand is present in the kite conformation: the
It has been shown that cavitand wall size and solvent
identity can influence the vase–kite equilibrium of resorci-
[*] I. Pochorovski, Dr. M.-O. Ebert, Dr. W. B. Schweizer,
Prof. Dr. F. Diederich
Laboratorium fꢀr Organische Chemie, ETH Zꢀrich
Hçnggerberg, HCI, 8093 Zꢀrich (Switzerland)
E-mail: diederich@org.chem.ethz.ch
*
methine protons ( ) are located at 4.25 ppm in CD2Cl2 and at
Prof. Dr. C. Boudon, Dr. J.-P. Gisselbrecht
4.43 ppm in [D8]THF, respectively. The main difference
between the two solvents, however, is that in CD2Cl2, two
Laboratoire d’Electrochimie et de Chimie Physique du Corps Solide
Institut de Chimie-UMR 7177, C.N.R.S., Universitꢁ de Strasbourg
4, rue Blaise Pascal, 67081 Strasbourg Cedex (France)
~
sharp signals are observed for each of the bowl protons ( and
!
), while in [D8]THF, these signals are close to coalescence.
[**] This work was supported by a grant from the Swiss National Science
Foundation (SNF). I.P. acknowledges the receipt of a fellowship
from the Fonds der Chemischen Industrie. We thank Prof. Dr.
Bernhard Jaun for helpful discussions and Dr. Melanie Chiu for
reviewing the manuscript.
This indicates that the kite1–kite2 interconversion is faster in
[D8]THF than in CD2Cl2. Thus, [D8]THF not only stabilizes
the vase conformation more strongly but also the vaselike
transition state[7] for the kite1–kite2 interconversion. The
preference of cavitand ox-1b for the kite conformation was
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201106031.
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Figure 2. Left: Cavitands ox-1a–c and redox interconversion between the quinone and hydroquinone states of cavitand 1b. a) Na2S2O4, CDCl3/H2O
(degassed), 608C, 3 h, quantitative. b) Air, quantitative. Sections of the 1H NMR spectra (298 K, 500 MHz) of cavitands ox-1b and red-1b in
CD2Cl2 (middle) and [D8]THF (right).
further supported by its X-ray crystal structure (crystals from
acetone), which shows the cavitand in the kite form (Figure 3,
upper left; for details on X-ray analyses, see Section 4 in the
Supporting Information).
which correlates with an increased 1H NMR chemical shift of
the methine protons. However, the influence of wall size on
DG°
is small compared to the influence of the solvent:
298K
DG°298K in [D8]THF is, on average, about 0.8 kcalmolꢀ1 lower
The activation parameters for the kite1–kite2 intercon-
version of ox-1a–c in CD2Cl2 and [D8]THF are presented in
Table 1.[15] These data show that in general, increasing wall
than in CD2Cl2 for each cavitand.
For chemical redox-switching studies on the tetraquinone-
cavitand class, we selected the medium-sized cavitand ox-1b,
which was chemically reduced to the corresponding hydro-
quinone form, red-1b, with Na2S2O4 (Figure 2). Cavitand red-
1b cleanly reverts to ox-1b upon exposure to air. This redox
reversibility was confirmed by cyclic voltammetry (CV) and
size (e.g. ox-1a to ox-1c) leads to a slight decrease in DG°
,
298K
rotating-disk voltammetry (RDV).[16] The H NMR spectra
1
(298 K, 500 MHz) of cavitand red-1b in CD2Cl2 and [D8]THF
shown in Figure 2 indicate the presence of the kite form in
both solvents.[17] However, the methine proton signals in red-
1b are shifted downfield compared to the methine protons of
~
!
ox-1b, and the aromatic protons ( and ) exhibit only one
signal each. Thus, in both solvents, the vaselike transition state
for the kite1–kite2 interconversion is stabilized upon reduc-
tion of the cavitand from the quinone to the hydroquinone
state. However, this stabilization is not sufficient to fully
switch the cavitand into the vase form, the prevalence of
which is a prerequisite for binding.
=
=
We presumed that in ox-1a–c, C O···C O repulsions
between neighboring walls prohibit access to the vase
conformation. In order to reduce these repulsive interactions,
we prepared the diquinone-cavitand series ox-2a–c
(Figure 4). A minor influence of wall size on cavitand
conformation was also observed for this series. Figure 4
Figure 3. Crystal structures of cavitands ox-1b (top left, from acetone),
ox-2b (top right, from DMF), ox-3 (bottom left, from [D12]mesitylene),
and ox-3 (bottom right, from DMF) at 100 K. Solvent molecules,
n-hexyl chains, and hydrogen atoms are omitted for clarity. Thermal
ellipsoids are shown at the 50% probability level.
1
shows H NMR spectra (298 K, 300 MHz) of cavitand ox-2b
in CD2Cl2 and [D8]THF. In CD2Cl2, ox-2b is present in the
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Table 1: Kinetic parameters (DH°, DS°, and DG°298K) for the kite1–kite2 interconversion, thermodynamic quantities (DH, DS, and DG298K) for the
[a]
*
vase!kite equilibrium, and chemical shifts d298K ( ) of the methine protons of cavitands ox-1a–c, red-1b, ox-2b, and red-2b, in various solvents.
Cavitand Solvent
Process
DH°
DS°
DG°
DH
DS
DG298K
d298K ( )[ppm]
*
298K
[kcalmolꢀ1
[kcalmolꢀ1
]
[calmolꢀ1 Kꢀ1
]
]
[kcalmolꢀ1
]
[calmolꢀ1 Kꢀ1
]
[kcalmolꢀ1
]
ox-1a
ox-1b
ox-1c
ox-1a
ox-1b
ox-1c
red-1b
red-1b
ox-2b
ox-2b
red-2b
red-2b
(CDCl2)2 kite1!kite2 15.8ꢁ0.3
(CDCl2)2 kite1!kite2 17.2ꢁ0.3
(CDCl2)2 kite1!kite2 16.6ꢁ0.4
ꢀ2.5ꢁ1.1
4.2ꢁ1.2
2.0ꢁ1.3
ꢀ6.4ꢁ1.5
ꢀ2.9ꢁ0.8
n.d.
16.6ꢁ0.5
16.0ꢁ0.5
16.0ꢁ0.5
15.7ꢁ0.6
15.3ꢁ0.3
n.d.
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
4.15
4.25
4.30
4.35
4.43
4.51
4.39
4.87
4.36, 3.74
5.59 br
4.48, 3.53
5.79, 5.62
[D8]THF
[D8]THF
[D8]THF
kite1!kite2 13.7ꢁ0.4
kite1!kite2 14.4ꢁ0.2
kite1!kite2
n.d.
n.b.
(CDCl2)2 kite1!kite2
n.d.
n.d.
[D8]THF
CD2Cl2
kite1!kite2
7.7ꢁ0.4[b] ꢀ8.4ꢁ1.6[b]
10.2ꢁ0.6[b]
kite1!kite2 15.6ꢁ0.2
9.5ꢁ0.6
12.8ꢁ0.3
–
–
–
[D8]THF
CD2Cl2
[D8]THF
vase!kite
kite1!kite2
vase!kite
–
n.d.
–
–
–
ꢀ3.0ꢁ0.1
ꢀ16.1ꢁ0.5
1.8ꢁ0.2
n.d.
–
n.d.
–
–
–
–
ꢀ0.7ꢁ0.1
ꢀ6.8ꢁ0.6
1.3ꢁ0.2
[a] DH°, DS°, and DG°
determined using inversion-transfer NMR experiments at various temperatures and subsequent Eyring analysis, unless
298K
otherwise stated. DH, DS, and DG298K determined by integration of distinct 1H NMR signals corresponding to the vase and kite conformations at low
temperatures and subsequent van’t Hoff analysis. Errors are given at the 95% confidence level. n.d.=not determined because of poor solubility.
[b] Determined using iterative line-shape fitting of variable-temperature 1H NMR spectra and subsequent Eyring analysis.
Figure 4. Left: Cavitands ox-2a–c and redox interconversion between the quinone and hydroquinone states of cavitand 2b. a) Na2S2O4, CDCl3/H2O
(degassed), 608C, 3 h, quantitative. b) Air, quantitative. Sections of the 1H NMR spectra (298 K, 300 MHz) of cavitands ox-2b and red-2b in
CD2Cl2 (middle) and [D8]THF (right).
kite conformation,[18] though the activation barrier for the
kite1–kite2 interconversion is significantly lower (12.8 kcal
molꢀ1) than that of ox-1b (16.0 kcalmolꢀ1). In contrast,
[D8]THF provides the requisite stabilization for ox-2b to
access the vase conformation: the methine protons appear at
5.59 ppm as a broad signal. X-ray crystallographic studies
further support the higher intrinsic preference of cavitand ox-
2b for the vase conformation; it crystallized in the vase form
from DMF (Figure 3, upper right).[19] 1H NMR spectra
(298 K, 300 MHz) of red-2b, the reduced form of ox-2b, in
CD2Cl2 and [D8]THF are shown in Figure 4. The conforma-
tional preferences do not significantly change: as with ox-2b,
red-2b is present in the kite form in CD2Cl2 and in the vase
form in [D8]THF.
Having investigated the conformational and electrochem-
ical properties of the new cavitands, we turned our attention
to binding studies. These were performed in [D12]mesitylene,
which is too big to be able to compete with guests for the
binding site. Similar to other open-top cavitands, however,
binding of various aromatic and alicyclic molecules was weak
(Ka < 2), with fast guest exchange on the NMR timescale.[20]
We attributed this to the open-top structure of the cavi-
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fact that cavitands of this type have no inherent preference for
one conformation over the other, such that mainly solvent
influence determines the observed conformation.
In summary, we have prepared and studied novel, redox-
active, quinone-based resorcin[4]arene cavitands. Cavitands
with four quinone units exist only in the kite conformation,
while cavitands containing two quinone and two quinoxaline
units can access both the kite and the vase forms. Their actual,
observed conformation is strongly solvent dependent. For the
first time, X-ray structures of both the vase and kite forms of a
resorcin[4]arene-based cavitand (ox-3) were obtained. The
top-covered cavitands ox/red-3 form kinetically stable host–
guest complexes on the NMR timescale with various cyclo-
alkanes. Guest release can be induced by protonation of the
quinoxaline nitrogens. Notably, the binding strength can also
be modulated by changing the redox state of the cavitand.
Now that we have demonstrated the proof of principle for the
redox switching of cavitand properties, developing cavitands
in which the redox-switching is even more pronounced would
bring us closer to utilizing cavitands in advanced-materials
applications.
Figure 5. Redox interconversion between the quinone and hydroqui-
none states of cavitand 3. a) H2, Pd/C, THF (degassed), 258C, 30 min,
quantitative. b) Air, quantitative.
tands[6e,10] and to their structural flexibility.[21] To address the
first issue, we prepared the triptycene-derived diquinone
cavitand ox-3 and its reduced form, red-3 (Figure 5).
1H NMR studies showed that the conformational proper-
ties of cavitands ox-3 and red-3 are very similar to those of
cavitands ox-2a–c and red-2a–c. However, ox-3 and red-3
form kinetically stable host–guest complexes on the NMR
timescale with various cycloalkanes, with the highest binding
constants measured for cyclohexane (Table 2). In pure
Received: August 26, 2011
Published online: November 14, 2011
Table 2: Association constants Ka between cavitands ox-3 and red-3, and
various cycloalkanes ([D12]mesitylene, 298 K).[a,b]
Keywords: cavitands · host–guest systems · quinones ·
Guest
Ka(ox-3ꢂguest) [mꢀ1
]
Ka(red-3ꢂguest) [mꢀ1
]
.
redox switching · supramolecular chemistry
cyclopentane
cyclohexane
cycloheptane
3.2
19.2
6.3
<0.1
3.1
1.6
[a] Determined by integration of the 1H NMR resonances of the relevant
species, relative to 1,3,5-trimethoxybenzene as an internal standard.
[b] Error in Ka is estimated to be roughly 20%.
[1] J. R. Moran, S. Karbach, D. J. Cram, J. Am. Chem. Soc. 1982, 104,
5826 – 5828.
[2] V. A. Azov, A. Beeby, M. Cacciarini, A. G. Cheetham, F.
Diederich, M. Frei, J. K. Gimzewski, V. Gramlich, B. Hecht, B.
Jaun, T. Latychevskaia, A. Lieb, Y. Lill, F. Marotti, A. Schlegel,
R. R. Schlittler, P. J. Skinner, P. Seiler, Y. Yamakoshi, Adv.
Funct. Mater. 2006, 16, 147 – 156.
[3] a) M. Melegari, M. Suman, L. Pirondini, D. Moiani, C. Massera,
F. Ugozzoli, E. Kalenius, P. Vainiotalo, J. C. Mulatier, J. P.
Dutasta, E. Dalcanale, Chem. Eur. J. 2008, 14, 5772 – 5779; b) L.
Pirondini, E. Dalcanale, Chem. Soc. Rev. 2007, 36, 695 – 706.
[4] a) B. W. Purse, J. Rebek, Proc. Natl. Acad. Sci. USA 2005, 102,
10777 – 10782; b) R. J. Hooley, J. Rebek, Chem. Biol. 2009, 16,
255 – 264.
[5] a) J. Rebek, Acc. Chem. Res. 2009, 42, 1660 – 1668; b) F. Hof,
S. L. Craig, C. Nuckolls, J. Rebek, Angew. Chem. 2002, 114,
1556 – 1578; Angew. Chem. Int. Ed. 2002, 41, 1488 – 1508.
[6] a) M. Frei, F. Marotti, F. Diederich, Chem. Commun. 2004,
1362 – 1363; b) P. Pagliusi, F. Lagugne-Labarthet, D. K. Shenoy,
E. Dalcanale, Y. R. Shen, J. Am. Chem. Soc. 2006, 128, 12610 –
12611; c) V. A. Azov, A. Schlegel, F. Diederich, Angew. Chem.
2005, 117, 4711 – 4715; Angew. Chem. Int. Ed. 2005, 44, 4635 –
4638; d) I. Pochorovski, B. Breiten, W. B. Schweizer, F. Die-
derich, Chem. Eur. J. 2010, 16, 12590 – 12602; e) L. D. Shirtcliff,
H. Xu, F. Diederich, Eur. J. Org. Chem. 2010, 846 – 855.
[7] V. A. Azov, B. Jaun, F. Diederich, Helv. Chim. Acta 2004, 87,
449 – 462.
[D12]mesitylene, ox-3 and red-3 are present in the kite
conformation (the methine protons appear at 3.9 and
4.1 ppm (ox-3) and at 3.9 and 4.5 ppm (red-3); see Section 6
in the Supporting Information). Upon addition of excess
cyclohexane, guest-induced switching to the vase conforma-
tion occurs in both ox-3 and red-3 (the methine protons shift
to 5.8 and 5.9 ppm (ox-3 complex) and to 5.9 and 6.0 ppm
(red-3 complex)), and encapsulated cyclohexane is observed
(ꢀ2.9 ppm (ox-3 complex) and ꢀ3.2 (red-3 complex)).
Importantly, the Ka values of complexes of cavitand ox-3
are higher than those of red-3 (Table 2). This is possibly
because DG298K for the kite!vase switching of ox-3 is smaller
than that of red-3, in analogy to the difference in the kite!
vase switching processes of the ox-2b/red-2b pair (Table 1).
Complete guest release was showcased for ox-3: protonation
of the quinoxaline nitrogens using trifluoroacetic acid (TFA)
switched the cavitand back to the kite conformation, thereby
releasing cyclohexane.
X-ray crystal structures showing cavitand ox-3 in both
conformations, vase and kite, were obtained (Figure 3): ox-3
crystallized in the vase form from DMF and in the kite form
from [D12]mesitylene, which also reflects the solution-state
conformational preferences of ox-3 in these solvents. ox-3 is
the first resorcin[4]arene-based cavitand that has been
crystallized in both the vase and kite forms, highlighting the
[8] a) J. R. Moran, J. L. Ericson, E. Dalcanale, J. A. Bryant, C. B.
Knobler, D. J. Cram, J. Am. Chem. Soc. 1991, 113, 5707 – 5714;
b) D. J. Cram, L. M. Tunstad, C. B. Knobler, J. Org. Chem. 1992,
57, 528.
[9] P. J. Skinner, A. G. Cheetham, A. Beeby, V. Gramlich, F.
Diederich, Helv. Chim. Acta 2001, 84, 2146 – 2153.
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ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
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[10] a) T. Gottschalk, B. Jaun, F. Diederich, Angew. Chem. 2007, 119,
264 – 268; Angew. Chem. Int. Ed. 2007, 46, 260 – 264; b) T.
Gottschalk, P. D. Jarowski, F. Diederich, Tetrahedron 2008, 64,
8307 – 8317.
[11] F. Durola, J. Rebek, Angew. Chem. 2010, 122, 3257 – 3259;
Angew. Chem. Int. Ed. 2010, 49, 3189 – 3191.
[12] O. B. Berryman, A. C. Sather, J. Rebek, Chem. Commun. 2011,
47, 656 – 658.
[13] M. Frei, F. Diederich, R. Tremont, T. Rodriguez, L. Echegoyen,
Helv. Chim. Acta 2006, 89, 2040 – 2057.
[14] P. Roncucci, L. Pirondini, G. Paderni, C. Massera, E. Dalcanale,
V. A. Azov, F. Diederich, Chem. Eur. J. 2006, 12, 4775 – 4784.
[15] A detailed description about how activation parameters have
been determined is given in the the Supporting Information
(Section 5).
[16] Detailed information on the CV and RDV data of all new
compounds and substituted quinone and quinoxaline reference
compounds are in the Supporting Information (Section 7).
[17] A variable-temperature (VT) NMR scan in [D8]THF showed
that upon cooling, the methine protons of red-1b decoalesce and
reappear as two broad signals at 5.9 ppm and 4.7 ppm below
210 K (see Section 5.6 in the Supporting Information). Such VT
behavior has not been observed for resorcin[4]arene cavitands.
Two different dynamic processes could account for the observed
low-temperature spectrum: 1) a slow vase–kite interconversion;
2) a slow interconversion between structures in which two walls
are in the kite position and two in the vase. VT NMR analysis of
red-1b in CD2Cl2 was hampered by gelation at low temperatures.
[18] Two sets of methine protons located at 3.74 ppm and 4.36 ppm
are observed. In analogy to tetraquinone- and tetraquinoxaline-
cavitands, the signal at 3.74 ppm can be assigned to the methine
protons below the quinoxaline unit, while the signal at 4.36 ppm
corresponds to methine protons below the quinone wall.
[19] An X-ray structure (crystals obtained from toluene) also
showing cavitand ox-2b in the vase conformation is in the
Supporting Information (Section 4.4).
[20] For more details on these binding experiments see the Support-
ing Information (Section 8).
[21] D. M. Rudkevich, G. Hilmersson, J. Rebek, J. Am. Chem. Soc.
1998, 120, 12216 – 12225.
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