Slow shuttling in an amphiphilic bistable [2]rotaxane incorporating a tetrathiafulvalene unit

Article abstract of DOI:10.1002/1521-3773(20010401)40:7<1216::AID-ANIE1216>3.0.CO;2-W

Separation of the two translational isomers by preparative thin-layer chromatography (see picture) and a kinetic study of their interconversion are possible when a central barrier is inserted between two stations on the rod section in the dumbbell compone

Full text of DOI:10.1002/1521-3773(20010401)40:7<1216::AID-ANIE1216>3.0.CO;2-W

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Slow Shuttling in an Amphiphilic Bistable
[2]Rotaxane Incorporating a Tetrathiafulvalene
Unit**
Jan O. Jeppesen, Julie Perkins, Jan Becher,* and
J. Fraser Stoddart*
The mechanically interlocked components of nondegener-
ate catenanes and rotaxanes[1] can be induced to switch
between different ground-state geometries (co-conforma-
tions) in response to either physical (light activation) or
chemical (redox or pH changes) stimuli.[2] Since the ring and
dumbbell components of these highly ordered molecular
assemblies can be induced to perform relative motions, such
as circumrotation[3] (rotary motion) and shuttling[4] (linear
motion), catenanes and rotaxanes[1] are now prime candidates
for the construction of artificial molecular machines[5, 6] and
the fabrication of molecular electronic devices.[7, 8] In recent
years, a number of different protocols, based on self-assem-
bly,[9] have been developed[3, 4, 10] for the template-directed
synthesis[11] of rotaxanes. Among the desirable features for the
redox-controllable, amphiphilic [2]rotaxanes that have been
employed to fabricate single-molecule-thick electrochemical
junctions in electronic devices are 1) the siting of redox-active
units along the rod section of the dumbbell component and
2) the presence of both hydrophobic and hydrophilic groups
as stoppers at the ends of the dumbbell component.
Figure 1. The concept of a slow molecular shuttle with a knob hindering
the interconversion between the green and red translational isomers of an
amphiphilic bistable [2]rotaxane.
phobic tetraarylmethane stopper at the other end.[18] Further-
more, we demonstrate the separation of the two possible
translational isomers and discuss the kinetic and thermody-
namic processes involved in the slow interconversion of the
two isomers.
The dumbbell-shaped compound 10 was synthesized as
illustrated in Scheme 1. The monotosylate 2 was obtained in
48% yield by reaction of the diol[19] 1 with one equivalent of p-
toluenesulfonyl chloride (TsCl). Alkylation of the hydro-
phobic tetraarylmethane-based stopper[10d, 18] 3 with 2 in
MeCN in the presence of K2CO3 gave (80%) the alcohol 4,
which was subsequently brominated using CBr4 and Ph3P in
CH2Cl2 to afford the bromide 5 in 94% yield. A solution of
the recently described[18, 20] asymmetric monopyrrolo-TTF
building block 6 in THF was treated with one equivalent of
CsOH ´ H2O. This procedure generated the TTF-monothio-
late, which was alkylated with one equivalent of the bromide 5
to afford the TTF derivative 7 in 74% yield. Removal of the
tosyl protecting group was carried out in near quantitative
yield by refluxing 7 in THF/MeOH (1/1) in the presence of an
excess of NaOMe. An 83% yield of compound 10 was
obtained following N-alkylation of the pyrrole unit in 8 with
the hydrophilic stopper[18] 9 in DMF containing NaH. Self-
assembly of the [2]rotaxane 13 ´ 4PF6 was achieved
(Scheme 2) in 23% yield using 10 as the template for the
formation of the encircling CBPQT4‡ unit from its dicationic
precursor[3] 11 ´ 2PF6 and 1,4-bis(bromomethyl)benzene (12).
The molecular shuttle was isolated as an analytically pure
brown solid after column chromatography using a solution of
NH4PF6 in Me2CO as eluent. The fast atom bombardment
mass spectrum (FAB-MS) of this brown solid shows intense
peaks at m/z 2921, 2776, 2631, 1388, 1316, and 1243 which
In the context of such devices, the tetrathiafulvalene (TTF)
unit (which has found widespread use[12] in materials chem-
istry) is an ideal redox-active unit in view of its excellent p-
electron-donating properties. It forms[13] a strong green 1:1
1
complex (Ka ˆ 8000m in MeCN)[4c] with cyclobis(paraquat-
p-phenylene)[14] (CBPQT4‡) for incorporation into a redox-
switchable [2]rotaxane also containing a 1,5-dioxynaphtha-
lene (DNP) ring system which also interacts, but somewhat
more weakly[15] with CBPQT4‡ to afford a red color in the
process. Although a TTF unit and a DNP ring system have
been incorporated[16] into the crown ether ring component of a
redox-switchable [2]catenane, which has already been em-
ployed in the fabrication of a solid-state electronically
reconfigurable switch,[7] no rotaxanes containing these two
recognition sites for a CBPQT4‡ component have been
described in the literature.[17] Here, we report the template-
directed synthesis of an amphiphilic bistable [2]rotaxane
(Figure 1) in which the ring component is CBPQT4‡ and the
dumbbell componentÐcontaining a monopyrrolo-TTF unit
and a DNP ring system within its rod sectionÐis terminated
by a hydrophilic dendritic stopper at one end and a hydro-
[*] Prof. J. F. Stoddart, J. O. Jeppesen, Dr. J. Perkins
Department of Chemistry and Biochemistry
University of California, Los Angeles
405 Hilgard Avenue, Los Angeles, CA 90095-1569 (USA)
Fax : (‡ 1)310-206-1843
‡
‡
‡
correspond to the [M PF6] , [M 2PF6] , [M 3PF6] ,
[M 2PF6]2‡, [M 3PF6]2‡, and [M 4PF6]2‡ ions, respec-
tively.
E-mail: stoddart@chem.ucla.edu
Prof. J. Becher, J. O. Jeppesen
Department of Chemistry
Odense University (University of Southern Denmark)
Campusvej 55, 5230, Odense M (Denmark)
1
UV/Vis and H NMR spectroscopy indicated the presence
of the two stable translational isomers present in the isolated
product. The UV/Vis spectrum (Figure 2, curvea) recorded in
Me2CO showed a broad charge-transfer (CT) absorption
[**] We thank DARPA and Hewlett ± Packard for generous financial
support and the University of Odense for a Ph.D. scholarship to J.O.J.
1216
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Angew. Chem. Int. Ed. 2001, 40, No. 7

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K2CO3
LiBr (cat.)
MeCN
O
O
X
O
O
O
HO
HO
O
O
Reflux / 20 h
HO
O
O
3
1 X = OH
48%
80%
TsCl
Et3N
4 Y = OH
94%
CBr4 / Ph3P
CH2Cl2 / RT / 40 h
DMAP (cat.)
CH2Cl2 / 20 h
2 X = OTs
5 Y = Br
1.1 equiv CsOH•H2O
MeOH / THF
RT / 1h
O
O
O
2.
1equiv 5
THF
S
CN
S
O
O
S
S
S
S
S
S
S
RT / 24 h
Ts
N
Z
N
7 Z = Ts
S
SMe
SMe
74%
NaOMe
THF / MeOH
Reflux / 20 min
95%
8 Z = H
6
MeO
MeO
O
O
O
O
O
9
O
O
NaH
DMF
O
O
Cl
RT / 45 min
MeO
O
83%
MeO
MeO
O
O
O
O
O
O
O
O
O
O
S
O
O
O
S
S
S
S
N
MeO
O
O
SMe
10
Scheme 1. Synthesis of the dumbbell-shaped compound 10.
Scheme 2. Template-directed synthesis of the [2]rotaxane 13 ´ 4PF6.
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Figure 2. Absorption spectra (Me2CO, 298 K) recorded on a solution of an
equilibrium mixture of the [2]rotaxanes 13 ´ 4PF6 ´ GREEN and 13 ´ 4PF6 ´
RED (curve a) and of the [2]rotaxane 13 ´ 4PF6 ´ RED (curve b) and the
[2]rotaxane 13 ´ 4 PF6 ´ GREEN (curve c) immediately after their isolation.
Allowing the red solution of 13 ´ 4PF6 ´ RED to stand for 24 h at room
temperature regenerates the ªoriginalº spectrum (curve a).
Figure 4. A preparative thin-layer chromatogram (see Experimental
Section) showing the separation of 13 ´ 4PF6 ´ RED from 13 ´ 4PF6 ´
GREEN.
1
band centered on 805 nm (e ˆ 810m 1 cm )Ðwhich is char-
acteristic[13] of co-conformations containing a TTF unit
located ªinsideº CBPQT4‡Ðand a CT absorption band
observed as a shoulder at 540 nm (e ˆ 670m 1 cm )Ðwhich
1
being located ªinsideº CBPQT4‡. Furthermore, no absorption
band is observed in the region 750 ± 850 nm where the CT
interaction resulting from the TTF moiety being located
ªinsideº the tetracationic cyclophane would occur. Leaving
the red solution to stand for 24 h at room temperature gives
back the ªoriginalº spectrum (Figure 2, curve a). The kinetics
of the shuttling of CBPQT4‡ from the DNP recognition site in
13 ´ 4PF6 ´ RED to the TTF recognition site was investigated
by 1H NMR spectroscopy. The 1H NMR spectrum (500 MHz)
of 13 ´ 4PF6 ´ RED was recorded (Figure 5a) at 230 K in
results from the DNP moiety being located ªinsideº the
cyclophane.[19, 21] The 1H NMR spectrum (400 MHz) recorded
at 298 K in (CD3)2CO showed (Figure 3) two singlets at d ˆ
2.64 and 2.47, which can be assigned to the SMe resonances
Figure 3. Partial 1H NMR spectrum of an equilibrium mixture of the
[2]rotaxanes 13 ´ 4PF6 ´ GREEN and 13 ´ 4PF6 ´ RED recorded at 400 MHz
in (CD3)2CO at 298 K.
attached to the TTF unit in 13 ´ 4PF6 ´ GREEN and 13 ´ 4PF6 ´
RED, respectively.[22] The ratio of the two translational
isomers was estimated from the integrals of the two different
SMe resonances to be approximately 1:1.
Thin-layer chromatography (TLC) of 13 ´ 4PF6 showed
green and red spots with similar intensities, thus indicating
the existence of two isolable translational isomersÐone in
which CBPQT4‡ encircles the TTF unit (namely, 13 ´ 4PF6 ´
GREEN) and another in which CBPQT4‡ encircles the DNP
ring system (namely, 13 ´ 4PF6 ´ RED). By employing prepa-
rative thin-layer chromatography (PTLC), it was possible
(Figure 4) to isolate the red translational isomer (13 ´ 4PF6 ´
RED). The UV/Vis spectrum (Figure 2, curveb) of 13 ´ 4PF6 ´
RED reveals a CT absorption band which is observed as a
shoulder at 540 nm. This band results from the DNP moiety
Figure 5. Partial 1H NMR spectra (500 MHz) of the isolated [2]rotaxane
13 ´ 4PF6 ´ RED recorded in (CD3)2CO at a) 230 K/0 h, b) 300 K/1 h,
c) 300 K/3 h, d) 300 K/5 h, e) 300 K/8 h, f) 300 K/21 h. The singlet at d ˆ
2.49 corresponds to the SMe resonance when CBPQT4‡ encircles the 1,5-
dioxynaphthalene ring system and the singlet at d ˆ 2.65 corresponds to the
SMe resonance when CBPQT4‡ encircles the TTF unit.
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(6 Â CH2O, 1 Â CH2O signal missing/overlapping), 105.8 (2 signals), 113.3,
114.7, 114.9, 124.2, 125.2, 125.3, 126.7, 126.8 (2 signals), 130.8, 131.1, 132.3,
139.9, 141.4, 144.3, 144.7, 148.3, 154.3, 154.4, 156.6; FAB-MS: m/z (%): 858
(CD3)2CO and shows, as expected, only one signal for the
SMe protons as a singlet resonating at d ˆ 2.49. The sample
was heated subsequently to 300 K and the shuttling of
CBPQT4‡ from the DNP recognition site in 13 ´ 4PF6 ´ RED
to the TTF recognition site was followed using the SMe
resonances as the probe (Figure 5b ± f). After 21 h at 300 K,
the system had equilibrated and a 1:1 mixture of 13 ´ 4PF6 ´
RED and 13 ´ 4PF6 ´ GREEN was re-established (Figure 5 f).
As a consequence of these spectroscopic variations the color
of the solution changed from red to brown. By employing a
first-order kinetic treatment[23] a rate constant of k ˆ 2 Â
‡
‡
(30) [M‡2] , 856 (27) [M] ; elemental analysis calcd (%) for C53H61BrO5
(857.95): C 74.20, H 7.17; found: C 74.36, H 7.20.
7: A solution of 6[18, 20] (0.27 g, 0.51 mmol) in anhydrous THF (35 mL) was
degassed (Ar, 10 min) before
a solution of CsOH ´ H2O (0.090 g,
0.54 mmol) in anhydrous MeOH (3.5 mL) was added dropwise by syringe
over a period of 1 h at room temperature. The mixture was stirred for
15 min, whereupon a solution of the bromide 5 (0.46 g, 0.54 mmol) in
anhydrous THF (5 mL) was added in one portion and the reaction mixture
was stirred for 24 h at room temperature. The solvent was evaporated and
the resulting yellow residue was dissolved in CH2Cl2 (100 mL), washed with
brine (100 mL) and H2O (2 Â 100 mL), and then dried (MgSO4). Removal
of the solvent gave a yellowish orange semisolid, which was purified by
column chromatography (SiO2, CH2Cl2/hexane 4/1). The broad yellow
band (Rf ˆ 0.3) was collected and concentrated to afford a yellow semisolid,
which was repeatedly dissolved in CH2Cl2 (2 Â 20 mL) and concentrated to
give 7 (0.47 g, 74%) as an analytically pure yellow semisolid. FAB-MS: m/z
1
10 5 s was obtained for the slippage of CBPQT4‡ over the
SMe group, in the direction from 13 ´ 4PF6 ´ RED to 13 ´ 4PF6 ´
GREEN. The corresponding free energy of activation (DG=)
1
for this isomerization is 24 kcalmol .
Although it was not possible to isolate a sufficient amount
‡
(%): 1252 (100) [M] ; elemental analysis calcd (%) for C69H73NO7S7
of 13 ´ 4PF6 ´ GREEN from the PTLC experiment to follow its
(1252.78): C 66.15, H 5.87, N 1.12; found: C 66.34, H 6.02, N 1.05.
1
interconversion into 13 ´ 4PF6 ´ RED by H NMR spectros-
8: Compound 7 (0.42 g, 0.34 mmol) was dissolved in anhydrous THF/
MeOH (1/1, 50 mL) and degassed (Ar, 10 min) before NaOMe (25%
solution in MeOH, 1.1 mL, 0.27 g, 5.0 mmol) was added in one portion. The
yellow solution was refluxed for 20 min and cooled to room temperature,
whereupon the solvent was evaporated. The yellow residue was dissolved in
CH2Cl2 (100 mL), washed with H2O (3 Â 100 mL), and dried (MgSO4).
Removal of the solvent gave a yellow semisolid, which was subjected to
column chromatography (SiO2, CH2Cl2). The yellow band (Rf ˆ 0.5) was
collected and concentrated to give 8 (0.35 g, 95%) as an analytically pure
copy, it proved possible to shift the equilibrium between the
two translational isomers from 1:1 to 9:1 in favor of 13 ´ 4PF6 ´
GREEN by heating a solution of the brown 1:1 mixture in
(CD3)2SO to 425 K. The color of the solution changed from
brown to green upon heating to 425 K. The solution was then
quenched at 273 K (ice bath) and the conversion of 13 ´ 4PF6 ´
GREEN into 13 ´ 4PF6 ´ RED was followed at 300 K using the
signals for the protons on the monopyrrolo-TTF unit and the
DNP ring system as a probe. On this occasion, a first-order
‡
yellow solid. FAB-MS: m/z (%): 1098 (100) [M] ; elemental analysis calcd
(%) for C62H67NO5S6 (1098.60): C 67.78, H 6.15, N 1.27; found: C 67.81, H
6.15, N 1.24.
1
rate constant of 3 Â 10 4 s was obtained for the slippage of
CBPQT4‡ over the SMe group in the direction from 13 ´ 4PF6 ´
GREEN to 13 ´ 4PF6 ´ RED. The associated DG= value is
10: Compounds 8 (0.23, 0.21 mmol) and 9[18] (0.21 g, 0.23 mmol) were
dissolved in anhydrous DMF (10 mL) and degassed (Ar, 10 min) before
NaH (0.021 g of a 60% suspension in mineral oil, 0.53 mmol) was added.
The reaction mixture was stirred for 45 min at room temperature, which
resulted in the initial yellow solution becoming more orange. H2O (40 mL)
was added, followed by the addition of brine (40 mL). The yellow
precipitate was filtered and dried. The crude product was purified by
column chromatography (SiO2, CH2Cl2/EtOAc 2/1). The yellow band
(Rf ˆ 0.4) was collected and the solvent evaporated to afford a yellow oil,
which was repeatedly dissolved in CH2Cl2 (3 Â 20 mL) and concentrated to
yield 10 (0.34 g, 83%) as an analytically pure yellow semisolid. 1H NMR
(CD3COCD3, 400 MHz, 298 K): d ˆ 1.17 (t, J ˆ 7.6 Hz, 3H), 1.26 (s, 18H),
2.38 (s, 3H), 2.57 (q, J ˆ 7.6 Hz, 2H), 3.05 (t, J ˆ 6.4 Hz, 2H), 3.26 (s, 9H),
3.45 ± 3.48 (m, 6H), 3.60 ± 3.63 (m, 6H), 3.74 ± 3.79 (m, 6H), 3.81 (t, J ˆ
6.4 Hz, 2H), 3.90 ± 4.00 (m, 6H), 4.05 ± 4.13 (m, 8H), 4.24 ± 4.27 (m, 4H),
4.88 (s, 2H), 4.96 (s, 2H), 5.00 (s, 6H), 6.72 and 6.75 (AB, J ˆ 2.1 Hz, 2H),
6.79 (d, J ˆ 8.8 Hz, 2H), 6.80 (d, J ˆ 9.1 Hz, 2H), 6.83 (s, 2H), 6.88 ± 6.93
(m, 8H) 7.03 ± 7.12 (m, 10H), 7.15 (d, J ˆ 8.7 Hz, 2H), 7.22 ± 7.33 (m, 8H),
7.36 (d, J ˆ 8.8 Hz, 4H), 7.80 (d, J ˆ 8.5 Hz, 1H), 7.82 (d, J ˆ 8.5 Hz, 1H);
1
22 kcalmol .
In summary, we have devised and completed the synthesis
of an amphiphilic bistable [2]rotaxane comprising two differ-
ent recognition sites, a TTF unit and a DNP ring system, for
CBPQT4‡. The steric hindrance exhibited by the SMe group
situated between the two recognition sites has made it
possible to isolate the translational isomer 13 ´ 4PF6 ´ RED
and to study the kinetics of the shuttling of the tetracationic
cyclophane between the two recognition sites. The process,
which is accompanied by a clearly detectable color change,
1
can also be followed by H NMR and UV/Vis spectroscopy.
This new amphiphilic rotaxane is currently being assessed for
its ability to self-organize into monolayers as a prelude to its
introduction into devices.
‡
FAB-MS: m/z (%): 1966 (100) [M] ; elemental analysis calcd (%) for
C112H127NO18S6 (1967.60): C 68.37, H 6.51, N 0.71; found: C 68.17, H 6.49, N
0.66.
Experimental Section
[3]
13 ´ 4PF6:
A solution of 10 (0.28 g, 0.14 mmol), 11 ´ 2PF6 (0.30 g,
5: Ph3P (0.70 g, 2.67 mmol) was added portionwise to a solution of 4 (1.75 g,
2.20 mmol) and CBr4 (0.88 g, 2.65 mmol) in anhydrous CH2Cl2 (15 mL) at
room temperature. The reaction mixture was stirred for 16 h, whereupon
additional CBr4 (0.88 g, 2.65 mmol), followed by Ph3P (0.70 g, 2.67 mmol)
was added and the reaction mixture was stirred for another 24 h. After
concentration, the residue was purified by column chromatography (SiO2,
CH2Cl2/hexane 2/1). The colorless band (Rf ˆ 0.3) was collected and the
solvent evaporated to afford a colorless oil, which was repeatedly dissolved
in CH2Cl2 (3 Â 50 mL) and concentrated to provide 5 (1.77 g, 94%) as an
analytically pure white semisolid. 1H NMR (CDCl3, 200 MHz, 298 K): d ˆ
1.26 (t, J ˆ 7.6 Hz, 3H), 1.33 (s, 18H), 2.65 (q, J ˆ 7.6 Hz, 2H), 3.54 (t, J ˆ
6.2 Hz, 2H), 3.94 ± 4.10 (m, 8H), 4.14 ± 4.19 (m, 2H), 4.28 ± 4.36 (m, 4H),
6.80 ± 6.89 (m, 4H), 7.06 ± 7.15 (m, 10H), 7.24 ± 7.42 (m, 6H), 7.90 (d, J ˆ
8.4 Hz, 1H), 7.91 (d, J ˆ 8.4 Hz, 1H); 13C NMR (CDCl3, 50 MHz, 298 K):
d ˆ 15.4, 28.3, 30.5, 31.5, 34.4, 63.2 (CAr4), 67.4, 68.0, 69.8, 70.0, 70.2, 71.6
0.42 mmol), and 12 (0.11 g, 0.42 mmol) in anhydrous DMF (10 mL) was
stirred for 10 d at room temperature (after approximately 1 d the color
changed to dark green and a white precipitate was formed). The green
suspension was subjected directly to column chromatography (SiO2) and
recovered 10 was eluted with Me2CO, whereupon the eluent was changed
to Me2CO/NH4PF6 (1.0 g NH4PF6 in 100 mL MeCO) and the brown band
containing 13 ´ 4PF6 was collected. Most of the solvent was removed under
vacuum (T< 308C) followed by the addition of H2O (50 mL). The resulting
precipitate was collected by filtration, washed with Et2O (20 mL), and
dried to afford the [2]rotaxane 13 ´ 4PF6 (0.10 g, 23%) as an analytically
pure brown solid. M.p. 1508C (decomposed without melting); FAB-MS:
‡
‡
‡
m/z (%): 2921 (4) [M PF6] , 2776 (9) [M 2PF6] , 2631 (6) [M 3PF6] ,
1966 (3), 1388 (10) [M 2PF6]2‡, 1315.5 (13) [M 3PF6]2‡, 1243 (6) [M
4PF6]2‡; elemental analysis calcd (%) for C148H159F24N5O18P4S6 ´ 2H2O
Angew. Chem. Int. Ed. 2001, 40, No. 7
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(3068.12): C 57.26, H 5.29, N 2.26; found: C 56.86, H 5.19, N 2.11.
Preparative thin-layer chromatography (PTLC) was performed at room
temperature on UNIPLATE silica gel PTLC plates with Me2CO/NH4PF6
(1.0 g NH4PF6 in 100 mL Me2CO) as eluent. Immediately after elution, the
red band containing 13 ´ 4PF6 ´ RED was extracted into Me2CO. The
solvent was removed under vacuum (T< 108C) and the red residue
dissolved in (CD3)2CO to give a red solution, which was cooled to 788C in
a Me2CO/dry ice bath. Although 13 ´ 4PF6 ´ GREEN seems to be less polar
than 13 ´ 4PF6 ´ RED, it was only possible to extract an extremely small
amount of 13 ´ 4PF6 ´ GREEN from the silica on the PTLC plate. The UV/
Vis spectrum recorded in (CD3)2CO at 298 K of this fraction shows, as
expected, only a broad charge-transfer (CT) absorption band centered on
801 nm.
Stoddart, P. J. Kuekes, R. S. Williams, J. R. Heath, Science 1999, 285,
391 ± 394; b) E. W. Wong, C. P. Collier, M. Belohradsky, F. M. Raymo,
J. F. Stoddart, J. R. Heath, J. Am. Chem. Soc. 2000, 122, 5831 ± 5840.
[9] a) J. S. Lindsey, New J. Chem. 1991, 15, 153 ± 180; b) G. M. Whitesides,
J. P. Mathias, C. T. Seto, Science 1991, 254, 1312 ± 1319; c) D. Philp, J. F.
Stoddart, Synlett 1991, 445 ± 458; d) D. Philp, J. F. Stoddart, Angew.
Chem. 1996, 108, 1242 ± 1286; Angew. Chem. Int. Ed. Engl. 1996, 35,
1155 ± 1196; e) M. C. T. Fyfe, J. F. Stoddart, Acc. Chem. Res. 1997, 30,
393 ± 401; f) J. Rebek, Jr., Acc. Chem. Res. 1999, 32, 278 ± 286.
[10] a) A. G. Kolchinski, D. H. Busch, N. W. Alcock, J. Chem. Soc. Chem.
Commun. 1995, 1289 ± 1291; b) P. R. Ashton, P. T. Glink, J. F. Stod-
dart, P. A. Tasker, A. J. P. White, D. J. Williams, Chem. Eur. J. 1996, 2,
Â
729 ± 736; c) N. Solladie, J.-C. Chambron, C. O. Dietrich-Buchecker,
J.-P. Sauvage, Angew. Chem. 1996, 108, 957 ± 960; Angew. Chem. Int.
Ed. Engl. 1996, 35, 906 ± 909; d) P. R. Ashton, R. Ballardini, V.
Balzani, M. Belohradsky, M. T. Gandolfi, D. Philp, L. Prodi, F. M.
Raymo, M. V. Reddington, N. Spencer, J. F. Stoddart, M. Venturi, D. J.
Williams, J. Am. Chem. Soc. 1996, 118, 4931 ± 4951; e) A. S. Lane,
D. A. Leigh, A. Murphy, J. Am. Chem. Soc. 1997, 119, 11092 ± 11093;
f) A. P. Lyon, D. H. Macartney, Inorg. Chem. 1997, 36, 729 ± 736; g) S.
Anderson, R. T. Aplin, T. D. W. Claridge, T. Goodson III, A. C.
Maciel, G. Rumbles, J. F. Ryan, H. L. Anderson, J. Chem. Soc. Perkin
Trans. 1 1998, 2383 ± 2398.
Received: November 17, 2000 [Z16129]
[1] a) G. Schill, Catenanes, Rotaxanes and Knots, Academic Press, New
York, 1971; b) D. M. Walba, Tetrahedron 1985, 41, 3161 ± 3212;
c) C. O. Dietrich-Buchecker, J.-P. Sauvage, Chem. Rev. 1987, 87,
795 ± 810; d) H. W. Gibson, H. Marand, Adv. Mater. 1993, 5, 11 ± 21;
e) D. B. Amabilino, J. F. Stoddart, Chem. Rev. 1995, 95, 2725 ± 2828;
f) R. Jäger, F. Vögtle, Angew. Chem. 1997, 109, 966 ± 980; Angew.
Chem. Int. Ed. Engl. 1997, 36, 930 ± 944; g) G. A. Breault, C. A.
Hunter, P. C. Mayers, Tetrahedron 1999, 55, 5265 ± 5293; h) Molecular
Catenanes, Rotaxanes and Knots (Eds.: J.-P. Sauvage, C. O. Dietrich-
Buchecker), Wiley-VCH, Weinheim, 1999.
[11] a) D. H. Busch, N. A. Stephenson, Coord. Chem. Rev. 1990, 100, 119 ±
154; b) S. Anderson, H. L. Anderson, J. K. M. Sanders, Acc. Chem.
Res. 1993, 26, 469 ± 475; c) R. Hoss, F. Vögtle, Angew. Chem. 1994, 106,
389 ± 398; Angew. Chem. Int. Ed. Engl. 1994, 33, 375 ± 384; d) F. M.
Raymo, J. F. Stoddart, Pure Appl. Chem. 1996, 68, 313 ± 322; e) T. J.
Hubin, A. G. Kolchinski, A. L. Vance, D. L. Busch, Adv. Supramol.
Chem. 1999, 5, 237 ± 357; f) T. J. Hubin, D. L. Busch, Coord. Chem.
Rev. 2000, 200 ± 202, 5 ± 52.
[12] For reviews on TTF chemistry, see a) M. Adam, K. Müllen, Adv.
Mater. 1994, 6, 439 ± 459; b) T. Jùrgensen, T. K. Hansen, J. Becher,
Chem. Soc. Rev. 1994, 23, 41 ± 51; c) M. R. Bryce, J. Mater. Chem. 1995,
5, 1481 ± 1496; d) J. Garin, Adv. Heterocycl. Chem. 1995, 62, 249 ± 304;
e) G. Schukat, E. Fanghänel, Sulfur Rep. 1996, 18, 1 ± 294; f) M. R.
Bryce, J. Mater. Chem. 2000, 10, 589 ± 598; g) M. B. Nielsen, C.
Lomholt, J. Becher, Chem. Soc. Rev. 2000, 29, 153 ± 164.
[2] J. F. Stoddart, Chem. Aust. 1992, 59, 546 ± 547 and 581.
[3] P.-L. Anelli, P. R. Ashton, R. Ballardini, V. Balzani, M. T. Gandolfi,
T. T. Goodnow, A. E. Kaifer, D. Philp, M. Pietraszkiewicz, L. Prodi,
M. V. Reddington, A. M. Z. Slawin, N. Spencer, C. Vicent, D. J.
Williams, J. Am. Chem. Soc. 1992, 114, 193 ± 218.
[4] a) P.-L. Anelli, N. Spencer, J. F. Stoddart, J. Am. Chem. Soc. 1991, 113,
Â
5131 ± 5133; b) R. A. Bissell, E. Cordova, A. E. Kaifer, J. F. Stoddart,
Nature 1994, 369, 133 ± 137; c) P.-L. Anelli, M. Asakawa, P. R. Ashton,
Â
R. A. Bissell, G. Clavier, R. Gorski, A. E. Kaifer, S. J. Langford, G.
Mattersteig, S. Menzer, D. Philp, A. M. Z. Slawin, N. Spencer, J. F.
Stoddart, M. S. Tolley, D. J. Williams, Chem. Eur. J. 1997, 3, 1113 ±
1135; d) D. A. Leigh, A. Troisi, F. Zerbetto, Angew. Chem. 2000, 112,
358 ± 361; Angew. Chem. Int. Ed. 2000, 39, 350 ± 353; e) P. R. Ashton,
R. Ballardini, V. Balzani, A. Credi, R. Dress, E. Ishow, C. J.
Kleverlaan, O. Kocian, J. A. Preece, N. Spencer, J. F. Stoddart, M.
Venturi, S. Wenger, Chem. Eur. J. 2000, 6, 3558 ± 3574.
[13] a) D. Philp, A. M. Z. Slawin, N. Spencer, J. F. Stoddart, D. J. Williams,
J. Chem Soc. Chem. Commun. 1991, 1584 ± 1586; b) W. Devonport,
M. A. Blower, M. R. Bryce, L. M. Goldenberg, J. Org. Chem. 1997, 62,
885 ± 887.
Â
[14] M. Asakawa, W. Dehaen, G. Lꢁabbe, S. Menzer, J. Nouwen, F. M.
Raymo, J. F. Stoddart, D. J. Williams, J. Org. Chem. 1996, 61, 9591 ±
[5] a) J. A. Preece, J. F. Stoddart, Nanobiology 1994, 3, 149 ± 166; b) M.
Â
Â
9595.
Gomez-Lopez, J. A. Preece, J. F. Stoddart, Nanotechnology 1996, 7,
183 ± 192; c) M. D. Ward, Chem. Ind. 1997, 640 ± 645; d) V. Balzani, M.
1
[15] A Ka value of 768m in MeCN has been reported for the complex-
ation between 1,5-dihydroxynaphthalene and CBPQT4‡. See: R.
Castro, K. R. Nixon, J. D. Evenseck, A. E. Kaifer, J. Org. Chem. 1996,
61, 7298 ± 7303.
Â
Â
Gomez-Lopez, J. F. Stoddart, Acc. Chem. Res. 1998, 31, 405 ± 414;
e) J.-P. Sauvage, Acc. Chem. Res. 1998, 31, 611 ± 619; f) A. Niemz,
V. M. Rotello, Acc. Chem. Res. 1999, 32, 42 ± 52; g) A. E. Kaifer, Acc.
Chem. Res. 1999, 32, 62 ± 71; h) L. Fabbrizzi, M. Licchelli, P.
Pallavicini, Acc. Chem. Res. 1999, 32, 846 ± 853; i) D. A. Leigh, A.
Murphy, Chem. Ind. 1999, 178 ± 183; j) M. D. Ward, Chem. Ind. 2000,
22 ± 26; k) V. Balzani, A. Credi, F. M. Raymo, J. F. Stoddart, Angew.
Chem. 2000, 112, 3486 ± 3531; Angew. Chem. Int. Ed. 2000, 39, 3348 ±
3391.
[16] V. Balzani, A. Credi, G. Mattersteig, O. A. Matthews, F. M. Raymo,
J. F. Stoddart, M. Venturi, A. J. P. White, D. J. Williams, J. Org. Chem.
2000, 65, 1924 ± 1936.
[17] For examples of catenanes, rotaxanes, and pseudorotaxanes contain-
ing TTF, see a) P. R. Ashton, R. A. Bissell, N. Spencer, J. F. Stoddart,
M. S. Tolley, Synlett 1992, 923 ± 926; b) T. Jùrgensen, J. Becher, J.-C.
Chambron, J.-P. Sauvage, Tetrahedron Lett. 1994, 35, 4339 ± 4342;
c) Z.-T. Li, P. C. Stein, N. Svenstrup, K. H. Lund, J. Becher, Angew.
Chem. 1995, 107, 2719 ± 2723; Angew. Chem. Int. Ed. Engl. 1995, 34,
2524 ± 2528; d) Z.-T. Li, J. Becher, Chem. Commun. 1996, 639 ± 640;
e) Z.-T. Li, P. C. Stein, J. Becher, D. Jensen, P. Mùrk, N. Svenstrup,
Chem. Eur. J. 1996, 2, 624 ± 633; f) M. Asakawa, P. R. Ashton, V.
Balzani, A. Credi, G. Mattersteig, O. A. Matthews, N. Montalti, N.
Spencer, J. F. Stoddart, M. Venturi, Chem. Eur. J. 1997, 3, 1992 ± 1996;
g) Z.-T. Li, J. Becher, Synlett 1997, 557 ± 560; h) M. B. Nielsen, Z.-T. Li,
J. Becher, J. Mater. Chem. 1997, 7, 1175 ± 1187; i) M. Asakawa, P. R.
Ashton, V. Balzani, A. Credi, G. Hamers, G. Mattersteig, N. Montalti,
A. N. Shipway, N. Spencer, J. F. Stoddart, M. S. Tolley, M. Venturi,
A. J. P. White, D. J. Williams, Angew. Chem. 1998, 110, 357 ± 361;
Angew. Chem. Int. Ed. 1998, 37, 333 ± 337; j) M. B. Nielsen, N. Thorup,
J. Becher, J. Chem. Soc. Perkin Trans. 1 1998, 1305 ± 1308; k) A. Credi,
M. Montalti, V. Balzani, S. J. Langford, F. M. Raymo, J. F. Stoddart,
New J. Chem. 1998, 22, 1061 ± 1065; l) M. Asakawa, P. R. Ashton, V.
[6] For examples of compounds reminiscent of rotary motors, see a) J. K.
Gimzewski, C. Joachim, R. R. Schlittler, V. Langlais, H. Tang, I.
Johannsen, Science 1998, 281, 531 ± 533; b) T. R. Kelly, H. De Silva,
R. A. Silva, Nature 1999, 401, 150 ± 152; c) T. R. Kelly, R. A. Silva, H.
De Silva, S. Jasmin, Y. Zhao, J. Am. Chem. Soc. 2000, 122, 6935 ± 6949;
d) N. Koumura, R. W. J. Zijlstra, R. A. van Delden, N. Harada, B. L.
Feringa, Nature 1999, 401, 152 ± 155; e) B. L. Feringa, R. A. van Del-
den, N. Koumura, E. M. Geertsema, Chem. Rev. 2000, 100, 1789 ±
1816.
[7] For investigations relating to a [2]catenane-based solid-state electroni-
cally reconfigurable switch, see a) M. Asakawa, M. Higuchi, G.
Mattersteig, T. Nakamura, A. R. Pease, F. M. Raymo, T. Shimizu, J. F.
Stoddart, Adv. Mater. 2000, 12, 1099 ± 1102; b) C. P. Collier, G.
Mattersteig, E. W. Wong, Y. Lou, K. Beverly, J. Sampaio, F. M.
Raymo, J. F. Stoddart, J. R. Heath, Science 2000, 289, 1172 ± 1175.
[8] For electronically configurable molecular-based logic gates, see
a) C. P. Collier, E. W. Wong, M. Belohradsky, F. M. Raymo, J. F.
1220
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Angew. Chem. Int. Ed. 2001, 40, No. 7

COMMUNICATIONS
Balzani, S. E. Boyd, A. Credi, G. Mattersteig, S. Menzer, M. Montalti,
F. M. Raymo, C. Ruffilli, J. F. Stoddart, M. Venturi, D. J. Williams, Eur.
J. Org. Chem. 1999, 985 ± 994; m) J. Lau, M. B. Nielsen, T. Thorup,
M. P. Cava, J. Becher, Eur. J. Org. Chem. 1999, 3335 ± 3341; n) D.
Jensen, M. B. Nielsen, J. Lau, K. B. Jensen, R. Zubarev, E. Levillain, J.
Becher, J. Mater. Chem. 2000, 10, 2249 ± 2258.
[18] Recently, we reported the first [2]rotaxane with one p-electron-rich
asymmetric monopyrrolo-TTF unit situated in the rod section of an
amphiphilic dumbbell component. See: J. O. Jeppesen, J. Perkins, J.
Becher, J. F. Stoddart, Org. Lett. 2000, 2, 3547 ± 3550.
one of the simplest amines with a stereogenic nitrogen atom
and its behavior has been closely examined in solution.[3, 4]
The nitrogen atom inverts rapidly at room temperature, a
motion that can be frozen out at low temperatures. The
activation barrier for inversion/rotationÐthe process that
converts the molecule into its mirror imageÐis approximately
[19] P. R. Ashton, R. Ballardini, V. Balzani, S. E. Boyd, A. Credi, M. T.
Â
Â
Gandolfi, M. Gomez-Lopez, S. Iqbal, D. Philp, J. A. Preece, L. Prodi,
H. G. Ricketts, J. F. Stoddart, M. S. Tolley, M. Venturi, A. J. P. White,
D. J. Williams, Chem. Eur. J. 1997, 3, 152 ± 170.
1
7.5 kcalmol at 160 K in CBrF3. Extrapolated to room
[20] J. O. Jeppesen, K. Takimiya, F. Jensen, T. Brimert, K. Nielsen, N.
1
temperature, the rate of racemization is about 107 s .
Thorup, J. Becher, J. Org. Chem. 2000, 65, 5794 ± 5805.
Â
Â
[21] a) R. Wolf, M. Asakawa, P. R. Ashton, M. Gomez-Lopez, C. Hamers,
S. Menzer, I. W. Parsons, N. Spencer, J. F. Stoddart, M. S. Tolley, D. J.
Williams, Angew. Chem. 1998, 110, 1018 ± 1022; Angew. Chem. Int. Ed.
The same amine shows starkly different behavior within the
racemic receptacle molecule 2 (Figure 1).[2] The inversion/
rotation of 1 within 2 is slow on the NMR timescale at room
temperature, and even at 323 K. A portion of the NMR
spectrum of 1 in 2 is shown and highlights the consequences of
amine complexation: large upfield shifts, emergence of
coupling details, an overall expansion of the spectrum, and
the doubling of its resonances. The last feature reflects the
modest (about 2:1) diastereoselectivity of the racemic recep-
tacle for the amine enantiomers.
Â
1998, 37, 975 ± 979; b) V. Balzani, P. Ceroni, A. Credi, M. Gomez-
Lopez, C. Hamers, J. F. Stoddart, R. Wolf, New J. Chem. 2001, 25, 25 ±
Â
31.
[22] A SMe group attached to a TTF unit reveals significant changes in its
chemical shift when the TTF unit is located ªinsideº CBPQT4‡
.
Typically, it resonates at d ˆ 2.64 whereas an ªuncomplexedº SMe
group has a d value of about 2.40. See ref. [18].
[23] The rate constant k was obtained from the slope of a plot of logI(SMe,
13 ´ 4PF6 ´ RED) against t, where I(SMe, 13 ´ 4PF6 ´ RED) denotes the
integral of the SMe resonance for the red translational isomer,
13 ´ 4PF6 ´ RED, and t is the time.
The guest exchange rates into and out of 2 are slow on the
NMR timescale and separate signals are seen for free and
bound guest.[5] Steric barriersÐmechanical bondsÐisolate
the amine from the bulk solution and costly conformational
changes (including the rupture of hydrogen bonds) are
necessary to allow the passage of molecules into and out of
the cavity. The rate of this process for 1, as measured by an
Isolation of an Acid/Base Complex in Solution
Puts the Brakes on Nitrogen Inversion**
1
exchange spectroscopy (EXSY) experiment, is 2 s at room
temperature and corresponds to
a barrier of about
1
Paul L. Wash, Adam R. Renslo, and Julius Rebek, Jr.*
17 kcalmol . However, EXSY experiments on the bound
guest failed to show exchange between diastereomeric com-
plexes, even at 323 K. Accordingly, the lowest energy path for
interconversion of diastereomers of the complex involves
dissociation to the free components in solution and then their
recombination.
Acid/base interactions pervade chemistry and dominate
molecular recognition in biology. The isolation of individual
acid/base complexes can be achieved in the gas phase at low
pressures[1] and in the solid or glassy states within inert
matrices. In solution, rapid diffusion permits the frequent
exchange of acid/base partners and the characterization of
individual complexes requires the fastest of spectroscopic
techniques. We have recently introduced a synthetic host that
features an inwardly directed carboxy group on its concave
surface,[2] and we apply it here to the study of isolated acid/
base interactions. The results augur well for the observation
and characterization of short-lived intermediates in these
receptacles.
What causes the large energetic barrier to the process of
Equation (2): the interconversion of the diastereomeric com-
plexes of 1 within 2? The attractive forces between the acid
and base must contribute but they cannot be a large factor.
The model (racemic) acid 3 was used as a model for estimating
the effects of acid/base attraction. The carboxy groups of both
2 and 3 are derived from Kempꢁs triacid[6, 7] and
are attached to the aromatic residues through
an N-acylbenzimidazole function; they are
inherently chiral. Complexes of 3 with 1
exchange/interconvert rapidly on the NMR
The effects are demonstrated with the amine base N-ethyl-
N-methyl-N-isopropylamine [1, Eq. (1)]. This base features
timescale in CH2Cl2 at ambient temperature,
and low temperatures are required to distin-
guish the diastereomers. Dynamic NMR ex-
[*] Prof. Dr. J. Rebek, Jr., Dr. P. L. Wash, Dr. A. R. Renslo
The Skaggs Institute for Chemical Biology and
Department of Chemistry
periments show an activation barrier of 10.5 Æ
The Scripps Research Institute
1
10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
Fax: (‡1)858-784-2876
0.5 kcalmol for the exchange process at the
coalescence temperature (Tc ˆ 230 K). There is nothing
unusual about this acid/base pair: the complex of 1 with 2,2-
dimethylpropionic (pivalic) acid also shows a barrier of
10.3 kcalmol 1 at Tc ˆ 230 K for the inversion/rotation of the
amine.
E-mail: jrebek@scripps.edu
[**] We are grateful for financial support from the Skaggs Research
Foundation and the National Institutes of Health. We are pleased to
acknowledge advice from Professors Stephen Craig and Dmitry
Rudkevich.
Angew. Chem. Int. Ed. 2001, 40, No. 7
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1433-7851/01/4007-1221 $ 17.50+.50/0
1221