Controlling the rate of shuttling motions in [2]rotaxanes by electrostatic interactions: A cation as solvent-tunable brake

Article abstract of DOI:10.1039/b506756a

A series of rotaxanes, with phenolic axle centerpieces and tetralactam macrocycles as the wheels, has been prepared in good yields. The threaded rotaxane structure is confirmed in the gas phase by tandem mass spectrometric experiments through a detailed f

Full text of DOI:10.1039/b506756a

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A R T I C L E
Controlling the rate of shuttling motions in [2]rotaxanes by
electrostatic interactions: a cation as solvent-tunable brake†
a
a
a
a
Pradyut Ghosh,‡ Guido Federwisch, Michael Kogej, Christoph A. Schalley,*
b
b
b
c
Detlev Haase, Wolfgang Saak, Arne L u¨ tzen* and Ruth M. Gschwind*
Kekul e´ -Institut f u¨ r Organische Chemie und Biochemie der Universit a¨ t,
a
Gerhard-Domagk-Str. 1, D-53121, Bonn, Germany. E-mail: c.schalley@uni-bonn.de;
Fax: +49-228-735662; Tel: +49-228-735784
Institut f u¨ r Reine und Angewandte Chemie der Universit a¨ t, Postfach 2503, D-26111,
Oldenburg, Germany. E-mail: arne.luetzen@uni-oldenburg.de; Fax: +49-441-7983329;
Tel: +49-441-7983706
Institut f u¨ r Organische Chemie der Universit a¨ t, Universit a¨ tsstr. 31, D-93053, Regensburg,
Germany. E-mail: ruth.gschwind@chemie.uni-regensburg.de; Fax: +49-941-9434617;
Tel: +49-941-9434625
b
c
Received 13th May 2005, Accepted 17th June 2005
First published as an Advance Article on the web 1st July 2005
A series of rotaxanes, with phenolic axle centerpieces and tetralactam macrocycles as the wheels, has been prepared
in good yields. The threaded rotaxane structure is confirmed in the gas phase by tandem mass spectrometric
experiments through a detailed fragmentation pattern analysis, in solution by NMR spectroscopy, and in the solid
1
1
1
1
state through X-ray crystallography. A close inspection of the H, H NOESY and H, H ROESY NMR data reveals
the wheel to travel along the axle between two degenerate diamide “stations” close to the two stoppers. By
deprotonation of a phenolic OH group in the axle centerpiece with Schwesinger’s P1 base, surprisingly no additional
shuttling station is generated at the axle center, although the wheel could form rather strong hydrogen bonds with the
1
1
phenolate. Instead, the wheel continues to travel between the two diamide stations. Experimental data from H, H
NOESY spectra, together with theoretical calculations, show that strong electrostatic interactions between the
phenolate moiety and the P1 cation displace the wheel from the “phenolate station”. The cation acts as a “brake” for
the shuttling movement. Instead of suppressing the shuttling motion completely, as observed in other rotaxanes, our
rotaxane is the first system in which electrostatic interactions modulate the speed of the mechanical motion between a
fast and a slow motion state as a response to a reversible external stimulus. By tuning these electrostatic interactions
through solvent effects, the rate of movement can be influenced significantly, when for example different amounts of
DMSO are added to dichloromethane. Besides the shuttling motion, circumrotation of the wheel around the axle is
observed and analyzed by variable temperature NMR spectroscopy. Force field and AM1 calculations are in good
agreement with the experimental findings.
Introduction
1@2–1@4 (Scheme 1) which bear a phenolic OH group in the
center of their axles. Since the wheels are of the tetralactam
1,2
Since the mid-eighties, different template effects have been de-
veloped in order to provide facile access to mechanically bound
species, among them coordination to a central metal ion, and
complex formation through p-donor–p-acceptor interactions,
or hydrogen bonding to cations, neutrals, or anions. The
21
type, they are capable of forming hydrogen bonds with the
7,22
12
axle.
Recently, Leigh et al. reported a system in which
3
protonation and deprotonation of such an OH group induced
the motion of a smaller tetralactam wheel between two different
stations along the axle. In the deprotonated state, the wheel is
4
5
6
7
8
synthesis and characterization of molecular machines based
on such interlocked molecules is a rapidly growing field in
9
supramolecular chemistry. Mechanically interlocked species
combine motional freedom of their parts relative to each other
10
with high stability due to the mechanical bond, so that the
1
1
12
control of molecular motion by external stimuli such as pH,
13
14
light, or electrons is an attractive goal. Many other functional
properties have been studied, for example, the electron or
1
5
energy transfer from one stopper to the other, the quenching
16
of luminescence in self-assembled pseudorotaxanes, the pho-
toswitchability of the catenanes’ ring geometry, the electric
conductance through poly(rotaxanes) and the implementation
of logic functions at the molecular level, just to name a few.
This study utilizes a recently published synthesis for the
generation of a series of molecular shuttles based on [2]rotaxanes
17
18
19
20
†
Electronic supplementary information (ESI) available: synthetic pro-
tocols, experimental details, theoretical calculations not included in the
main text. See http://dx.doi.org/10.1039/b506756a
Scheme 1 Structures of rotaxanes 1@2–1@6 (2–6 are differently sub-
stituted wheels; symmetrical 5 and 6 have been used in the calculations
below to reduce the computer time necessary).
‡
Present address: Central Salt & Marine Chemicals Research Institute,
G. B. Marg, Bhavnagar, 364002, India.
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 6 9 1 – 2 7 0 0
2 6 9 1

View Article Online
−
located at the phenolate station due to the formation of stronger
hydrogen bonds. In contrast, our rotaxanes have symmetrical
axles with two identical stations close to the two stoppers that
permit degenerate shuttling processes between the two axle
signals at the m/z ratios for the deprotonated axle 1 (m/z =
805) nor the deprotonated wheel 4− (m/z = 960). In marked
contrast, strong signals for axle and wheel are observed under
the same conditions, when a sample was analyzed that contained
a 1 : 1 mixture of 1 and 4 (bottom trace), which can form the
23
ends. Surprisingly, in view of the literature precedent, addition
of acids and bases to these rotaxanes does not switch the
wheel position between the peripheral diamide and the central
phenolate stations, but allows tuning of the shuttling rate of the
wheel between the two diamide stations. The novel features of
the present rotaxanes are that the speed of wheel shuttling can
be switched between “fast” and “slow” by a reversible external
stimulus rather than switching it “off” or “on” and that solvent
effects provide means to tune the shuttling speed in the “slow-
motion” state.
−
corresponding non-threaded hydrogen-bonded complex 1 ·4.
This complex is indeed observed as a minor signal at m/z = 1767.
Variations of the ionization conditions significantly affected the
relative ratio of this complex ion and the ions corresponding
to free axle and wheel, while they had virtually no effect on
the spectrum of the rotaxane. Even more conclusive are the
25
negative ion MS/MS spectra shown in Fig. 2. After careful
isolation of the monoisotopic rotaxane parent ion 1 @4 at
−
m/z 1767, argon is introduced into the FT-ICR cell as the
collision gas and the ions are subjected to collision-induced
dissociation (CID). The rotaxane decomposes by fragmentation
of the axle thereby releasing the wheel (top trace). Only a very
minor signal is seen for the intact deprotonated axle at m/z =
Results and discussion
1
.
Synthesis and characterization of rotaxane structure
8
05, which can be traced back to a significantly more energy-
Rotaxanes 1@2–1@4 have been synthesized utilizing the re-
demanding cleavage of the wheel. Rather, fragments of the axle
are observed at m/z = 518, 505, and 243, which correspond
to the bond cleavages and 1,2-elimination reactions indicated
in Fig. 2. Thus, the fragmentation of covalent bonds within the
axle leads to simultaneous cleavage of the mechanical bond.
20
cently publishedtemplate strategy (for details, see the electronic
supplementary information). The threaded topology of these
rotaxanes can be unambiguously characterized in the gas phase,
in solution, and in the solid state. Thus, three independent pieces
of evidence for the rotaxane structure are available:
−
Again, the axle-wheel complex 1 ·4 formed under identical
(
i) The negative-mode ESI mass spectra of rotaxane 1@4 and
electrospray ionization conditions and treated exactly the same
way as the rotaxane behaves differently. As expected for a non-
covalently hydrogen-bonded species, wheel 4 is lost in the CID
a 1 : 1 mixture of axle 1 and wheel 4 (Fig. 1) provide evidence
24
for a rotaxane structure. Ionization of the rotaxane to yield an
anion can easily be achieved with this soft ionization technique
through deprotonation of the phenol in the axle centerpiece. The
spectrum of the rotaxane (Fig. 1, top trace) does not show any
−
experiment and the negatively charged axle 1 is formed as the
major product at m/z = 805. The consecutive fragmentations
of the axle are similar to the fragments observed for the
Fig. 1 Negative ion ESI mass spectra of ca. 10 lM methanol solutions
of rotaxane 1@4 (top trace) and a 1 : 1 mixture of its components 1 and
−
Fig. 2 MS/MS mass spectra of collisionally activated ions 1 @4
−
4
(bottom trace). The inset on the left shows the region between m/z =
(top) and 1 ·4 (bottom). The inset shows the fragmentation pathways
8
00 and 1000 in order to demonstrate the absence of significant signals
observed for the axle in both spectra between m/z 200 and 550 that lead
to the signals at m/z = 243, 505, and 518. The same fragmentations have
been found in the collision-induced fragmentations of the deprotonated
axle alone.
for the rotaxane axle and wheel. The insets on the right compare the
experimental isotope patterns (top) with those calculated on the basis
of natural abundances (bottom).
2
6 9 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 6 9 1 – 2 7 0 0

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rotaxane. These experiments confirm the threaded nature of the
rotaxane and permit us to distinguish the mechanically bound
species from a hydrogen-bonded complex of axle and wheel.
The qualitative fragmentation pattern is also in agreement with
energetic considerations. While more than two-thirds of the
hydrogen-bonded complex of 1− and 4 has decomposed, the
sum of all fragments of the rotaxane amounts to only ca. 15%
of all signals in the spectrum. This reflects the weaker bond
strength of the hydrogen-bonded complex versus the strength of
the mechanical bond of the rotaxane that requires cleavage of a
covalent bond for fragmentation. The other rotaxanes behave
similarly so that we refrain from a discussion of their mass
spectra here.
(
ii) The second piece of evidence comes from crystal structure
analysis.§ Suitable single crystals of rotaxane 1@2 were obtained
by slowly evaporating dichloromethane from a saturated solu-
tion of the rotaxane in a 1 : 1 mixture of dichloromethane and
methanol. The Ortep plot (Fig. 3) unambiguously shows the axle
to be threaded with one stopper bound on each side of the wheel.
The axle center piece bears an in/out conformation (for more
details, see below) of the two amide groups next to the phenolate
stabilized through an N–H · · · O–H · · · O=C hydrogen bonding
pattern (dotted lines in Fig. 3). As confirmed by the NMR data
below, the wheel is held on one of the ethylene diamine spacers
by a total of four hydrogen bonds. Each isophthalic acid subunit
of the wheel is connected to one carbonyl group of the axle by
two hydrogen bonds in a forked manner. A–B bond lengths are
1
Fig. 4 H NMR spectra recorded at 333 K in DMF-d
7
of (a) macrocycle
4
, (b) rotaxane 1@4, (c) axle 1, and (d) a 1 : 1 mixture of axle 1 and wheel
4. For the ease of comparison, the rotaxane spectrum is shown between
the spectra of its components. Dotted lines indicate signals which are
shifted in the rotaxane spectrum relative to their positions in the spectra
of the free components.
˚
between 2.96 and 3.33 A and N–H · · · O angles are between 145
◦
and 165 , values typical for such hydrogen bonds.
changes in hydrogen bonding. Instead, a significant shift (Dd =
0
.8 ppm) and sharpening of the phenol OH signal and smaller
shifts of the amide hydrogen atoms of the wheel (Dd = 0.3 and
0
.6 ppm) are observed for the rotaxane relative to their position
in the spectra of the free components. Besides these, upfield
shifts of carbon-centered hydrogen atoms incorporated in the
axle are often found due to the anisotropy of the aromatic rings
incorporated in the wheel. Rather large values of up to 1.7 ppm
10
have been recorded. These anisotropy effects are particularly
large for those parts of the axle located exactly in the center of the
wheel cavity. In the spectrum of 1@4, the largest upfield shifts are
observed for the ethylene diamine spacers in the axle (Dd = 0.7
ppm) indicating that one of the ethylene diamine units is located
inside the wheel cavity as observed in the crystal structure.§ The
methylene signals inside the cavity are averaged with those at the
other half of the axle due to a motion of the wheel along the axle
7
which is fast on the NMR timescale at 333 K in DMF-d . One
can estimate the upfield shift for the inside methylene signals to
be about twice as large as measured (ca. Dd = 1.4 ppm), when this
motion becomes slow on the NMR time scale. That agrees well
10
with the shift differences observed for other rotaxanes earlier
and is confirmed by low temperature data discussed below. Also,
the wheel’s isophthalic acid hydrogen atoms pointing into the
cavity experience a small shift, indicating that they are affected
by the presence of the axle.
Rotaxane 1@4 bears a pyridine, which renders the wheel
2
unsymmetrical. At 233 K in dichloromethane-d , the rotation
Fig. 3 Ortep plot of the X-ray single crystal structure of rotaxane 1@2.
Blue parts represent the axle, black parts the wheel. The dotted lines
indicate hydrogen bonds.
of the wheel is slow on the NMR timescale, as indicated by
the double set of signals (Fig. 5) which correspond to two co-
existing conformations. In one of these, the pyridine part is
hydrogen bonded to the carbonyl oxygen adjacent to the stopper.
In the other one, it is bound to the carbonyl group at the central
phenolate. The two signals for the OH group are found in roughly
a 1 : 3 ratio around 15.4 ppm. Also, the two amide protons of
the wheel adjacent to the pyridine appear as two signals in the
same intensity ratio around 10.3 ppm. Consequently, the two
orientations of the wheel differ only slightly in energy by ca.
(
iii) Evidence for the rotaxane structure in solution is also
1
available from NMR experiments. Fig. 4 compares the H-NMR
spectra of free wheel 4 (trace a), the rotaxane 1@4 (trace b),
the axle 1 (trace c) and a 1 : 1 mixture of axle 1 and wheel 4
trace d) in DMF-d
only reveals shifts of the amide protons that are likely due to
(
7
at 333 K. The mixture of both components
§
CCDC reference number 230812. See http://dx.doi.org/10.1039/
b506756a for crystallographic data in CIF or other electronic format.
−
1
2 kJ mol .
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 6 9 1 – 2 7 0 0
2 6 9 3

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intermolecular hydrogen bonds to the wheel. A second internal
hydrogen bond is formed between the OH group of the phenol
and the out CO group. This structural feature is confirmed in
solution by NOE contacts of the NH protons of the inner amide
moieties (Fig. 6).
1
2 2
Fig. 5 H NMR spectrum of 1@4 in CD Cl at 233 K. Note that two
signals for the OH and NH protons indicate formation of two different
conformers which slowly interconvert on the NMR time scale.
−
The structures of rotaxanes 1@2 and 1 @2 were investigated
in detail in solution. Two main questions arise: (a) Is the
structure of 1@2 in solution identical to the crystal structure as
suggested by the chemical shifts discussed above? (b) Does the
−
deprotonation to 1 @2 introduce a different shuttling station
and therefore a different structure of the whole rotaxane? To
answer these questions and to gain further insight into the
−
1
1
structures of 1@2 and 1 @2 in solution, H, H NOESY and
1
1
H, H ROESY spectra of both rotaxanes were recorded in
dichloromethane-d at 233 K (for the nomenclature used to
2
denote the individual protons in the Figures, see Scheme 2).
For the interpretation of the obtained dipolar interactions, the
remaining dynamic behaviour of both rotaxanes has to be taken
into account (see below). Thus, even at this low temperature,
both rotaxanes show a shuttling of the symmetrical wheel along
the axle as well as a rotation of the wheel fast relative to the
shuttling motion, but slow on the NMR time scale. The dynamic
behavior of the rotaxanes together with the fact that the nuclear
Overhauser effect strongly overestimates small distances in short
time contacts, allow only a qualitative analysis of the NOESY
and ROESY spectra.
Fig. 6 Selected NOE contacts revealing the reorientation of the two
amide groups adjacent to the central axle phenol(ate) in the protonated
and deprotonated forms of 1@2 (s: strong, m: medium, w: weak
contacts).
Furthermore, close interproton contacts between the phenyl
stopper of the covered half of the axle and the protons of
the wheel are expected from the crystal structure of 1@2. As
example of the NOE pattern of these contacts, typical cross
peaks of the ortho-protons of this stopper are shown in Fig. 7a1
and 7a2. Similar close contacts to the wheel are found for the
amide proton next to this stopper (see Fig. 7a3). In all of
these spectra, the intensities of the cross peaks between axle
and wheel are nearly equally distributed over the exchanging
protons in the wheel, e.g. the amide protons of the wheel (see
Fig. 7a2), indicating the fast rotation of the wheel. In contrast,
Scheme 2 Nomenclature used for the identification of individual
protons. A and W denote the two rotaxane components, superscripts
identify the particular proton (letters for axle protons, numbers for wheel
protons), and subscripts label the two halves of axle and wheel resulting
from desymmetrization of the spectra under slow exchange conditions
at lower temperatures.
The crystal structure of 1@2§ is ideal for comparison with
the NOE data. A close inspection of the crystal structure shows
some main structural characteristics: (a) The wheel is directly
positionedover theethylene spacer of the covered halfofthe axle.
Various NOE cross signals between these methylene protons and
the amide protons as well as the aromatic protons of the wheel
directed towards the axle confirm this structural feature. (b)
A second characteristic of 1@2 is the in/out-conformation of
the inner amide NH protons also found in the calculations (see
below), with the wheel being positioned on the in part of the axle
1
1
−
Fig. 7 Sections of H, H NOESY spectra of 1@2 (a) and 1 @2 (b)
at 233 K in mixtures of CD Cl and DMSO-d . Selected cross signals
between the phenyl stopper of the half of the axle covered by the wheel
1 and 2) as well as the amide proton next to this stopper and protons
of the wheel (3) show the similarity of the wheel position in 1@2 and
@2 in solution and the crystal structure of 1@2. For the nomenclature
applied to distinguish individual protons, see Scheme 2.
2
2
6
(
(
see Fig. 3). There, the in NH proton forms an internal hydrogen
1
−
bond to the central phenol oxygen and the in CO is able to form
2
6 9 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 6 9 1 – 2 7 0 0

View Article Online
the other half of the axle, uncovered by the wheel, as well as the
other stopper do not show any dipolar interactions to the wheel
(
NOESY spectra not shown). In addition to the few discussed
characteristics, the whole qualitative NOE pattern of 1@2 is
in accordance with its crystal structure. Therefore, a structural
similarity between the structure of 1@2 in the solid state and in
solution is proposed.
Now, the question needs to be addressed whether the depro-
−
tonation to 1 @2 introduces a new, better shuttling station and
affects the whole structure. For deprotonation, Schwesinger’s P1
26
base was used, because the large, lipophilic cation improves the
solubility of the resulting salt even to beyond that of the neutral
rotaxane. As expected, the deprotonation leads to a change of
the intramolecular hydrogen bonding pattern of the axle from an
in/out to an in/in conformation of the inner amide NH protons
1
1
−
Fig. 8 Section of a H, H NOESY spectrum of 1 @2 at 233 K in
CD Cl and 10% DMSO-d showing dipolar interactions between the
2
2
6
NH proton of the P1 cation (NHP1) and protons on the uncovered half
of the axle as well as the wheel.
(
see Fig. 6). This is indicated by a significant low field shift of
these NH protons by more than 3 ppm combined with a modified
NOE pattern. Now both inner NH protons build hydrogen
bonds to the phenolate oxygen. However, slightly different NOE
contacts between the two NH protons and the aromatic protons
of the phenolate moiety in meta position indicate a small twist of
the free half of the axle caused by the presence of the P1 base (see
below). Beside that and chemical shift deviations of the other
NH protons, influenced by the change in pH, the chemical shifts
2
. Calculations
For the further discussion of the dynamic features, it is advan-
tageous to study the rotaxanes in greater detail by theory, which
may complement the experimental results by adding more subtle
structural features to the picture. Therefore, AM1 calculations
were performed (for details, see the supplementary informa-
tion) with the MOPAC algorithm implemented in the Cache 5.0
27
2
8
−
29
of 1 @2 and 1@2 are surprisingly similar (see the supplementary
program package. The structures chosen for these calculations
information, Table S1), especially the chemical shifts of the
ethylene spacers covered by the wheel, which, although they
should be most affected by a different position of the wheel,
are nearly identical (Table 1). A further proof for an almost
were generated with 3000 step Monte Carlo conformational
searches of favorable conformations with the Amber* force field
30
implemented in MacroModel 8.0. Generally, the force-field
calculations and the AM1 results are in good agreement with
each other so that we can concentrate on the AM1 calculations.
Rotaxanes 1@5 and 1@6 and their deprotonated analogues
−
unaltered position of the wheel in 1 @2 and 1@2 is given by the
comparison of the intermolecular NOE pattern between axle
and wheel. No significant differences between their NOE derived
interproton contacts are observed. This is exemplarily shown in
Fig. 7 for the characteristic NOE cross signals discussed above.
−
−
1 @5 and 1 @6 were optimized in different conformations with
a maximum number of hydrogen bonds (see Fig. 9 and the
supplementary information). Three low-energy conformations
were identified for 1@5 (type I to III in Fig. 9, top row). In the
most favorable structure, the wheel is bound to the two carbonyl
groups attached to one of the two ethylene diamine spacers.
The wheel is located on one of the arms close to a stopper, and
remote from the axle centerpiece. The second best conformer,
−
Therefore, we conclude that in 1 @2 an in/in conformation is
formed within the axle center piece, but compared to 1@2 the
position of the wheel is identical.
−
Thus, the wheel in 1 @2 does not use the phenolate moiety
to build hydrogen bridges and no new shuttling station is
12
−1
introduced here as expected from previous work. An expla-
nation supported by experiment involves strong electrostatic
interactions between the negative charge at the phenolate moiety
and the positive charge of the P1 cation. From the NOESY
which is higher in energy by ca. 14 kJ mol bears the wheel
hydrogen bonded to the two carbonyl groups of the isophthalic
dicarboxamide centerpiece of the axle. The third structure is
−
1
about 20 kJ mol higher in energy than the first one. Here,
hydrogen bonding again connects the amide NH hydrogens of
the wheel with the two carbonyl groups of one of the axle side
chains. The difference between the structures I and III can best
be explained using Fig. 6 (top). In the type I structure the wheel
is located on the axle branch with the amide group in its in
conformation. This is the structure found in the crystal. In the
type III structure, the wheel is however shifted towards the other
branch of the axle which is connected to the central phenolate
by the out amide group. Consequently, the calculations confirm
in excellent agreement with the crystal structure§ and the NMR
data that the wheel of the neutral rotaxane 1@5 is likely drawn
towards one of the stoppers and is shifted away from the axle
centerpiece.
−
spectra of 1 @2, dipolar interactions between the base and the
free half of the axle are detected. The strongest intermolecular
NOEs for the NH proton of the base are observed to the meta
position of the phenolate moiety (Fig. 8) and to the protons of
the ethylene groups on the uncovered half of the axle. This as
well as other NOE cross peaks not discussed in detail indicate
that the cation approaches the phenolate moiety from the
uncovered side of the axle and pushes the wheel away from the
phenolate moiety. Thus, the sum of the electrostatic interactions
between the charged moieties and the hydrogen bonds at the
diamide station seems to be stronger than the otherwise more
favorable hydrogen bridges between the wheel amide groups
and the phenolate oxygen. This structural explanation is further
confirmed by the theoretical calculations as well as the dynamic
behavior discussed below.
Three low-energy conformations have also been found for the
−
−1
deprotonated rotaxane 1 @5 which are within 5 kJ mol in
energy. In the lowest energy structure, the wheel is located at the
center of the axle (type I in Fig. 9, middle row). Two hydrogen
bonds are formed between the wheel and the phenolate, two
additional hydrogen bonds between the second half of the wheel
and one of the carbonyl groups adjacent to the central phenolate.
The type II structure corresponds to the wheel binding to the
phenolate and the more distant carbonyl group by a total of
four hydrogen bonds. Finally, the wheel is located on one of
the arms of the axle the in the third structure (type III). This
third structure is analogous to the most favorable geometry of
the protonated form. The NOE experiments discussed above
strongly disagree with the calculations for the anionic rotaxane
−
Table 1 Chemical shifts of the ethylene protons of 1 @2 and 1@2 in a
2 2 6
mixture of CD Cl and DMSO-d at 233 K
a
−
1
1
Proton
1 @2 H/ppm
1@2 H/ppm
h
A
c
2.13
2.07
3.33
3.40
2.12
2.10
3.59
3.44
i
A
c
h
A
f
i
A
f
a
For the nomenclature, see Scheme 2.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 6 9 1 – 2 7 0 0
2 6 9 5

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−
Fig. 9 Top: three low-energy conformations of 1@5. Center: three energetically favorable conformations of the corresponding anion 1 @5. Bottom:
−
+
two conformations of the complex of deprotonated rotaxane and P1 cation 1 @5·P1 revealing the importance of a close contact between cation and
anion.
alone, i.e. without counterion and solvents. Instead, the presence
of the counterion in close proximity of the axle is supported by
the observation of NOE contacts between the P1 cation and
the axle. Consequently, several conformations of the rotaxane
were re-optimized with the counterion as close to the axle center
piece as possible. These calculations provide a result which is
in excellent agreement with the NOE contacts derived from the
NMR experiments discussed above. A rotaxane conformation
remote positions so that the energies will further be biased in
favor of the structure found in the NMR experiments. The wheel
will reside close to the stoppers and not switch to the phenolate,
if this assumption holds true.
Finally, the pyridine wheel 6 behaves quite similarly so that
we shall refrain from an in-depth discussion of the rotaxanes
−
1@6 and 1 @6 here. It should, however, be mentioned that the
−
1
energy differences are small (ca. 6 kJ mol ) between structures
with the pyridine close to the central phenol and those where
the pyridine is bound to the carbonyl group adjacent to the
stoppers. These calculations provide a rationalization for the
(
type III) with the wheel shifted to one side of the axle and
the cation in direct contact with the phenolate maximizes the
electrostatic interactions and thus is energetically most favorable
1
(
Fig. 9, bottom row). Any conformation bearing the wheel
finding of two different structures in a 1 : 3 ratio in the H
hydrogen bonded to the central phenolate makes this close
contact between the two charges impossible and renders these
conformations energetically less favorable. One example which
is less favorable by ca. 30 kJ mol−1 is shown in Fig. 9 (type I).
Consequently, the calculations predict that the wheel position
should remain the same independent of the protonation state.
They also reveal that it is mandatory to take into account the
counterion effects.
NMR spectra of 1@4. It turns out that all structures (with
one exception) maximizing the distance between the phenol and
the pyridine nitrogen are slightly more favorable and we thus
tentatively assign this arrangement to the set of more intense
signals in the NMR spectrum shown in Fig. 5.
3
. Dynamic properties: shuttling and rotary motions
Since the calculations have been performed for isolated species
without the surrounding solvent, electrostatic interactions be-
tween the P1 cation and the phenolate are likely overestimated
as compared to the situation in solution, where they are reduced
by the dielectricity constant of the solvent. As a consequence,
the energy difference between the two conformations shown
for 1 @5·P1 will be lower in the real system. If solvation
of the cation is strong enough to generate free ions rather
than ion pairs, the wheel might still not move to the central
phenolate. The energy differences between type I–III structures
of the deprotonated rotaxane are rather small. Although the
calculations predict a slight preference for the wheel to shift
towards the phenolate, solvent effects need to be taken into
account. Close to the anion, one can expect to find stronger
interactions of solvent molecules and rotaxane than in more
An analysis of the dynamic properties must take into account
several different motions. The first one is shuttling of the wheel
along the axle. In principle, axle 1 offers three diamide stations to
wheel 2 in the protonated form of the rotaxane. Two are located
close to the stoppers separated by the two ethylene diamine
moieties. The third one is the hydroxy isophthaloylamide in
the axle center. Since NMR experiments, the crystal structure,
and calculations agree with each other that the wheel is more
favorably bound to one of the peripheral stations, one expects to
observe a degenerate shuttling motion between the two ends of
the axle. The second motion is the rotation of the wheel around
the axle which likely superimposes the shuttling motion. Both
motions can be expected to be affected by the protonation state
of the axle center piece. Thus, both states need to be examined
with respect to their dynamic features.
−
+
2
6 9 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 6 9 1 – 2 7 0 0

View Article Online
−
A first approach to these properties are temperature depen-
Table 2 Rate constants k of the shuttling motion of 1 @2 at 233 K. The
1 1
−
values were derived from H, H EXSY spectra using different solvent
mixtures
dent NMR experiments. At 233 K, 1@2 and 1 @2 in CD
2
Cl
2
7
as well as DMF-d exhibit two sets of signals for both the
axle and the wheel. This indicates that both motions, shuttling
and wheel rotation, are slow processes compared to the NMR
timescale. Consequently, we have extended this NMR study to
the temperature range between 223 and 293 K in both solvents.
Not unexpectedly, the spectral changes are complex and thus we
discuss here the most clear-cut case only.
2
−1a
Solvent mixtures
k × 10− /s
CD
CD
CD
CD
2
2
2
2
Cl
Cl
Cl
Cl
2
2
2
2
5.1
7.0
10.4
10.5
10.9
9.1
+ 10% DMSO-d
+ 20% DMSO-d
+ 40% DMSO-d
6
6
6
1
DMF-d7
The temperature dependent H NMR spectra for deproto-
−
DMF-d
DMF-d
DMF-d
7
7
7
+ 20% DMSO-d
+ 40% DMSO-d
+ 60% DMSO-d
6
6
6
nated rotaxane 1 @2 in dichloromethane are depicted in Fig. 10.
8.8
9.8
If one follows the two wheel NH signals from the bottom
spectrum to the top (dashed lines), it becomes clear that they
a
Error range ± 0.5 × 10−2/s−1
.
coalesce at a temperature of T
c
= 278 ± 2 K and form one broad
signal above that temperature. This coalescence is related to the
circumrotation of the wheel around the axle which leads to fast
exchange of the two sides of the wheel at higher temperatures.
‡
−1
From the measurements, a barrier of ca. DG = 54 ± 2 kJ mol
the tetralactam wheel passes over a 3,5-di-t-butyl phenyl stopper
with a half life of ca. 60 h at 333 K. In our rotaxanes, the axle
center piece does not have the large t-butyl groups, and thus
the barrier is lower and the shuttling reaction faster than the
deslipping reaction examined before.
can be calculated for this motion. This can be further verified
by another pair of signals that also exhibits coalescence due to
the same dynamic process: The two CH protons of the wheel’s
isophthalic acid units adjacent to the two amide groups (dotted
lines) fall together in one signal at T
this signal has already sharpened significantly. Again, the barrier
c
= 269 ± 2 K. At 293 K
To determine the dynamic behavior of movements being
slow on the NMR time scale, also two dimensional EXSY
spectra can be used. In addition to the better signal dispersion
‡
−1
31
can be determined and amounts to ca. DG = 54 ± 2 kJ mol .
This barrier has been confirmed by EXSY experiments (57 ±
of the exchange signals in the two dimensional spectra, also
slow exchange rates can be determined from the integrals of
the respective diagonal signals, exchange cross signals and the
mixing time. This makes it possible to determine the shuttling
rate of the wheel along the axle by EXSY NMR experiments.
For the determination of the exchange rates, the proton signals
−
1
2
kJ mol ).
h
c,f
i
(
A
and A ) of the ethylene spacers were chosen, since
c,f
the wheel shuttling motion causes the largest chemical shift
difference for these protons from the free to the occupied
shuttling position (see above). To elucidate the influence of
−
the solvent on the shuttling movement, EXSY spectra of 1 @2
were recorded in dichloromethane-d
dichloromethane-d with increasing amounts of DMSO-d
in mixtures of DMF-d with increasing amounts of DMSO-d
2
, in DMF-d
7
, in mixtures of
2
6
, and
7
6
.
.
The respective rate constants are given in Table 2.
−
The slowest shuttling rate of 1 @2 is observed in pure CD
2
Cl
2
The addition of 10% DMSO-d
the shuttling rate by 40%, the addition of 20% DMSO-d
to a doubling of the shuttling rate (experimental error: ± 10%).
Since further addition of DMSO-d does not lead to a further
increase of the rate constant, a plateau for the shuttling rate
appears to be reached. In pure DMF-d , the rate constant for
the shuttling starts already at the plateau value of ca. 0.1 s .
6
leads to a significant increase of
6
, even
6
7
−
1
6
Increasing amounts of DMSO-d do not significantly affect the
rate constants.
Now the question arises, whether these solvent effects can
be explained by structural aspects. The NOE studies together
with the theoretical calculations discussed above showed that
the electrostatic interaction between the phenolate moiety and
the P1 cation contributes to the displacement of the wheel from
1
Fig. 10 Temperature-dependent H NMR spectra (aromatic and NH
−
regions) of 1 @2 in CD
2
Cl
2
. Coalescence is observed at T
c
= 278 ± 2 K
7a,b
5a,b
for W (dashed lines) and at T
c
= 269 ± 2 K for W (dotted lines).
c,f
j
Note that the axle’s NH signals (A ) remain unaffected even at higher
temperatures.
the “phenolate station”. From the most favorable structure of
−
1
@2·P1 in Fig. 9, it becomes clear that the cation–phenolate
Since the two signals of the axle’s two amide protons at
around 12 ppm do not coalesce even at 293 K, the shuttling
motion must have a higher activation barrier and is therefore
considerably slower than rotation of the wheel. Consequently,
it suffers from a significant steric barrier beyond mere cleavage
of hydrogen bonds. While the circumrotation around the thin,
thread-like ethylene diamine spacer groups can easily proceed
through dissociation of all four hydrogen bonds in the absence of
significant steric barriers, the phenol axle center piece appears to
be a steric obstacle on the way of the wheel when traveling along
the axle. This aspect can be related to our previous deslippage
experiments, in which the aspect of steric size of stopper groups
interactions will hinder the shuttling movement: the stronger the
electrostatic interactions between the counterions the stronger
the effect of the “cation brake”. Thus, in apolar solvents, the
brake should work best. The more DMSO is added (which
solvates the cation and lowers the electrostatic interactions) the
faster the shuttling becomes. At a distinct amount of solvation,
the shuttling speed reaches a plateau value, it is not further
influenced by the cation brake.
This structural explanation can be directly confirmed by the
experimentally derived rate constants and the corresponding
−
NOE data. In pure CD
2
Cl
2
, the rate constant of 1 @2 is at
the lowest value and simultaneously NOE contacts of medium
intensity are detected between the NH proton of the P1 cation
10
was closely examined. In these experiments, it turned out that
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 6 9 1 – 2 7 0 0
2 6 9 7

View Article Online
and protons of the axle as well as the wheel of the rotaxane.
By addition of 10% DMSO-d the rate constant increases. This
is accompanied by reduced, but still detectable NOE contacts
Fig. 8 and 11). Starting from 20% DMSO-d , the NOE contacts
to the base are below the detection limit (Fig. 11) and the
rate constants reach their plateau value. In DMF-d , already
shuttling motion, because the cation is bound by non-covalent
forces and can reversibly dissociate, let the wheel pass over
the phenolate, and reassociate subsequently. Consequently, the
shuttling speed can be modulated for the first time by addition
of acids and bases between a fast- and a slow-motion mode
rather than switching it on and off. Depending on the solvent,
the electrostatic interactions of cation and axle—and with them,
the barrier for shuttling and its rate—can be fine tuned.
Modulating the speed through electrostatic interactions and
tuning that modulation by the choice of solvent provide an
interesting combination of complementary ways to adjust the
dynamic features at will with high precision in the rotaxanes
presented here. Although the effects found for the present system
are still not very large, our system provides a proof-of-principle
for the hypothesis that external stimuli can control the rate of
molecular motions. In future, the effects may become larger
through a fine-tuning of the axle structure modifying the steric
barrier imposed by the central phenolate.
6
(
6
7
the pure solvent solvates the base strongly enough to prevent
NOE contacts as well as to induce rate constants on the plateau
value. Although the solvation of the cation affects the shuttling
movement, the structure and the preferred position of the wheel
are not influenced by the use of different solvents. This is
−
indicated by very similar chemical shifts of the protons of 1 @2
in all these solvents. Interestingly, also protonated 1@2 shows
−
1
a very similar plateau value of about 0.10 s in mixtures of
32
CD
2
Cl
2
6
and DMSO-d . In conclusion, the shuttling rate can be
switched between a protonated fast-motion and a deprotonated
slow-motion state in dichloromethane.
Acknowledgements
We are grateful to the Deutsche Forschungsgemeinschaft (DFG)
and the Fonds der Chemischen Industrie (FCI) for financial
support. PG acknowledges a postdoctoral fellowship from the
Alexander-von-Humboldt foundation. CAS thanks the DFG
for a Heisenberg fellowship and the FCI for a Dozenten-
stipendium.
References and notes
1
1
−
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6
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12
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6 9 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 6 9 1 – 2 7 0 0

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