Towards controlling the threading direction of a calix[6]arene wheel by using nonsymmetric axles

Article abstract of DOI:10.1002/chem.200801926

The possibility of obtaining full control on the direction of axle threading in calix[6]arene wheel 1 either from its upper or lower rim was evaluated in solution. To this aim, we prepared nonsymmetric axles characterised by a 4,4′-bipyridinium recognition unit with two alkyl side chains, one of which terminates with a stopper, and the other with either ammonium (2), hydroxy (3) or methyl (4 and 5) head groups. When the axles were mixed with 1 in apolar solvents at room temperature, the formation of oriented pseudorotaxanes derived from the threading of the axles from the upper rim was observed. The stability constants of such complexes are in the order of 10⁷M ^-1 and are almost independent of the type of axle. A detailed thermodynamic and kinetic study revealed that stability constants and activation parameters for complex formation between 1 and axles 2 and 3 are of the same order of magnitude, suggesting a common threading process. However, upon heating a solution of 1 and 2 in benzene at 340 K, the formation of another supramolecular complex was observed, the structure of which is consistent with an oriented pseudorotaxane derived from the threading of axle 2 from the lower rim of the calixarene wheel. By carrying out the threading-stoppering reaction sequence between 1 and 2 in the presence of an excess of diphenylacetyl chloride, the orientational rotaxane isomers R1 and R2, derived from lower- and upper-rim threading, respectively, were collected in about a ratio of 7:3 as the unique chromatographic fraction. Our results suggest that at room temperature the threading process is under kinetic control for all axles. On increasing the temperature only the threading behaviour of axle 2 is substantially modified, most likely because the process becomes thermodynamically controlled owing to the peculiar recognition properties of the ammonium head of this axle.

Full text of DOI:10.1002/chem.200801926

DOI: 10.1002/chem.200801926
Towards Controlling the Threading Direction of a Calix[6]arene Wheel by
Using Nonsymmetric Axles
Arturo Arduini,*[a] Rocco Bussolati,[a] Alberto Credi,*[b] Giovanni Faimani,[a]
Sandrine Garaudꢀe,[b] Andrea Pochini,[a] Andrea Secchi,[a] Monica Semeraro,[b]
Serena Silvi,[b] and Margherita Venturi[b]
Abstract: The possibility of obtaining
full control on the direction of axle
pendent of the type of axle. A detailed
thermodynamic and kinetic study re-
vealed that stability constants and acti-
vation parameters for complex forma-
tion between 1 and axles 2 and 3 are of
the same order of magnitude, suggest-
ing a common threading process. How-
ever, upon heating a solution of 1 and
2 in benzene at 340 K, the formation of
another supramolecular complex was
observed, the structure of which is con-
sistent with an oriented pseudorotax-
ane derived from the threading of axle
2 from the lower rim of the calixarene
wheel. By carrying out the threading–
stoppering reaction sequence between
1 and 2 in the presence of an excess of
diphenylacetyl chloride, the orienta-
tional rotaxane isomers R1 and R2, de-
rived from lower- and upper-rim
threading, respectively, were collected
in about a ratio of 7:3 as the unique
chromatographic fraction. Our results
suggest that at room temperature the
threading process is under kinetic con-
trol for all axles. On increasing the
temperature only the threading behav-
iour of axle 2 is substantially modified,
most likely because the process be-
comes thermodynamically controlled
owing to the peculiar recognition prop-
erties of the ammonium head of this
axle.
threading in calix[6]arene wheel
1
either from its upper or lower rim was
evaluated in solution. To this aim, we
prepared nonsymmetric axles charac-
terised by a 4,4’-bipyridinium recogni-
tion unit with two alkyl side chains,
one of which terminates with a stopper,
and the other with either ammonium
(2), hydroxy (3) or methyl (4 and 5)
head groups. When the axles were
mixed with 1 in apolar solvents at
room temperature, the formation of
oriented pseudorotaxanes derived from
the threading of the axles from the
upper rim was observed. The stability
constants of such complexes are in the
order of 107 mꢀ1 and are almost inde-
Keywords: calixarenes · molecular
devices · rotaxanes · self-assembly ·
supramolecular chemistry
Introduction
chemical properties and the spatial arrangement of the frag-
ments or components that constitute their skeleton.[1–3] The
design and synthesis of these systems can profit from the
principles and methods of supramolecular chemistry,[4] al-
though emergent properties are sometimes difficult to pre-
dict on the basis of the characteristics of the molecular com-
ponents. Hence, the ability of a molecular device to perform
a programmed task has to be experimentally examined
through the acquisition of the thermodynamic and kinetic
parameters associated with its functioning. This aspect is
particularly important when these systems originate from
self-assembly processes, respond to external stimuli and
function as molecular machines.[1,2a,c–p,5] It thus appears that
the development of devices with advanced functionalities,
possibly suitable for practical applications, derives from an
iterative process in which specific functions are conferred to
the assembly through the fine-tuning of the properties
stored on its components.[6]
The operation of molecular devices capable of performing
programmed tasks is directly connected with the physico-
[a] Prof. A. Arduini, Dr. R. Bussolati, Dr. G. Faimani, Prof. A. Pochini,
Dr. A. Secchi
Dipartimento di Chimica Organica e Industriale
Universitꢀ di Parma; via G.P. Usberti 17/a
43100 Parma (Italy)
Fax : (+39)052-190-5472
E-mail: arturo.arduini@unipr.it
[b] Prof. A. Credi, Dr. S. Garaudꢁe, M. Semeraro, Dr. S. Silvi,
Prof. M. Venturi
Dipartimento di Chimica “G. Ciamician”, Universitꢀ di Bologna
Via Selmi 2, 40126 Bologna (Italy)
Fax :ACHTUNGTRENNUNG(+39)051-209-9540
E-mail: alberto.credi@unibo.it
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200801926.
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FULL PAPER
Pseudorotaxanes are supramolecular complexes minimally
composed of a wheel-type host surrounding an axle-type
guest.[7] The assembly/disassembly of the axle and wheel
components of a pseudorotaxane, which resembles the
threading/dethreading of a needle, can be controlled by ex-
ternal stimulation.[1,8] Studies on switchable pseudorotax-
anes[9] are most important for the development of molecular
machines based on rotaxanes, catenanes and related inter-
locked molecules. Specifically, the development of a pseu-
dorotaxane motif capable of performing unidirectional
threading and dethreading processes[10] under control of ex-
ternal stimuli (Figure 1a) would be important for the con-
struction of rotary motors based on catenanes (Figure 1b)
and processive linear motors based on rotaxanes (Fig-
ure 1c).[2h]
Figure 1. Representation of stimuli-controlled unidirectional threading/
dethreading of a [2]pseudorotaxane (a), a rotary motor based on a [2]cat-
enane (b) and a processive linear motor based on a [2]rotaxane (c).
Scheme 1. Structural formulae and schematic representation of wheel 1
and 4,4’-bipyridinium-based axles 2–5 used in this study. Ts=tosyl.
We recently demonstrated[6b,11–13] that the use of the heter-
oditopic nonsymmetric tris(phenylureido)calix[6]arene de-
rivative 1 (Scheme 1) as a three-dimensional macrocyclic
component for obtaining oriented pseudorotaxanes and ro-
taxanes brings about a significant increase in structural com-
plexity because, in principle, it is possible to selectively ad-
dress the threading of suitable axles from its upper or lower
rim. In fact, we showed that in apolar media (e.g., benzene)
1 is able to act as a very efficient[11] wheel that can be
threaded exclusively from the upper rim by axles derived
from dialkyl-4,4’-bipyridinium salts to yield oriented pseu-
ing the counteranions of the axle, can assist the insertion of
the cationic portion of the axle into the cavity from this rim
and 3) three methoxy groups at the lower rim that, in apolar
media, are oriented towards the interior of the cavity in the
NMR timescale, thereby hindering the access of the guest
from this direction.
The use of a more polar solvent, for example, acetonitrile,
has a profound effect on the threading outcome. In fact, sol-
dorotaxanes
(Figure 2).[6b,12]
This behaviour was explained
by analysing the main chemical
and structural features of 1 as a
host, which are 1) a p-donor
macrocyclic cavity that, because
of its width, can include the
positively charged bipyridinium
unit of the axle, but not togeth-
er with its counteranions;
2) three efficient hydrogen-
bond donor ureidic groups at
Figure 2. Representation of the two pseudorotaxane orientational isomers, “up” and “down”, that can form
the upper rim that, by complex- upon threading a rivet-like nonsymmetric axle (A) through a nonsymmetric wheel (W).
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A. Arduini, A. Credi et al.
vent polarity affects both the concentration of active guest
available in solution and the binding ability of the wheel, by
changing the extent of ion pairing of the axle and decreasing
the pivoting role of the three ureidic groups of the host, re-
spectively. Additionally, in acetonitrile the three methoxy
groups of the calixarene reside outside the cavity in the
NMR spectroscopy timescale, thus decreasing the steric
crowding at the lower rim. As a result, bipyridinium-type
axles can enter the wheel from both the upper and the
lower rim, yielding a mixture of pseudorotaxane orientation-
al isomers (Figure 2).[12] The stoppering reactions of such a
mixture yielded a mixture of orientational rotaxane isomers,
the proportion of which reflects the original ratio between
the corresponding pseudorotaxane isomers.[12]
dorotaxane self-assembly; 2) two alkyl side chains, one of
which has 3) a dumb stopper moiety, whereas the other one
terminates with 4) a specific head group. The formulae of
axles 2–5 investigated are shown in Scheme 1. The stoppers
were either a diphenylacetic ester (2, 4 and 5) or a diphenyl-
acetic amide (3) groups, whereas we chose ammonium (2),
hydroxy (3) and methyl (4 and 5) units as the head groups.
Compounds 4 and 5 differ only in the length of the alkyl
chain that connects the bipyridinium unit with the stopper.
Axles 2, 3 and 5 were synthesised in reasonable yield, as
summarised in Scheme 2. Compound 4 was available from
previous investigations.[6b,11]
NMR spectroscopic characterisation
To obtain pseudorotaxanes and rotaxanes characterised
by a univocal and programmable relative orientation of
their components, it is important to gain a deep understand-
ing of the structural, thermodynamic and kinetic factors that
govern the threading processes.[10,11,14] Herein we report a
study on the interplay between thermodynamic and kinetic
control as key elements to determine the threading direction
of different nonsymmetric axles in the nonsymmetric wheel
1. We suggest that the nature of the head groups appended
to the central 4,4’-bipyridinium recognition unit of the axle
could play an active role during the processes that lead to
the formation of oriented pseudorotaxanes.
Threading processes: In separate experiments, compounds 2,
4 and 5 were equilibrated with 1 in C6D6 at room tempera-
ture for 3 h (Scheme 3). The purple solutions obtained after
removal of the undissolved axle were then analysed at
1
298 K with H NMR spectroscopy techniques. As expected,
the structure of pseudorotaxanes [1ꢁ4] and [1ꢁ5] is in full
agreement with a supramolecular complex derived from the
insertion of the axle from the upper rim of the calixarene
(Scheme 3 and Figures S2 and S12 in the Supporting Infor-
mation).[6b] The same direction of threading into the wheel
was also verified for [1ꢁ2] as evidenced, for example, by the
resonances of the protons 1 and a (Figure 3a; see Scheme 3
for numbering). The fact that these protons resonate at d=
4.16 and 5.25 ppm, respectively, is consistent with the orien-
tation of the stopper at the upper rim of the calixarene. The
presence of only one set of signals, in agreement with pseu-
dorotaxanes with the stopper in proximity to the upper rim
of the calixarene, suggests that under these experimental
conditions neither the nature of the axle terminus nor unfav-
ourable interactions between the different stoppers and the
upper rim of the calixarene affect the direction of the
threading process.
Results and Discussion
Design
To evidence possible effects of the structural features of the
axles on the threading direction into wheel 1, we designed a
family of nonsymmetric axles characterised by 1) a 4,4’-bi-
pyridinium central unit which, by exhibiting an efficient rec-
ognition towards the cavity of 1,[15] is able to drive the pseu-
Scheme 2. Reagents and conditions: a) Boc2O (Boc=tert-butyloxycarbonyl), MeOH, NEt3, reflux, 1 h; b) TsCl, DMAP, NEt3, CH2Cl2, 2 d; c) 4,4’-bipyri-
dine, CH3CN, reflux, 3d; d) CH3CN, reflux, 15d; e) trifluoroacetic acid, 1 h; f) Ph2CHCOCl, CH3CN, 12 h; g) TsCl, NEt3, CH2Cl2, 12 h; h) 4,4’-bipyridine,
CH3CN, reflux, 12 h; i) CH3CN, reflux, 15 d; j) Ph2CHCOCl, THF, 48 h; k) 4,4’-bipyridine, CH3CN, reflux, 48 h; l) CH3CN, reflux, 15 d.
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Towards Controlling the Threading Direction of a Calix[6]arene Wheel
FULL PAPER
Scheme 3.
was also observed by maintaining the same samples in tolu-
ene at reflux for 7 days; after that time, together with the
original pseudorotaxane, decomposition byproducts of the
axle were present in solution. On the contrary, in the case of
pseudorotaxane [1ꢁ2]up, a new set of signals that could be
assigned to the other isomer with the stopper at the lower
rim, [1ꢁ2]down, started to appear upon heating (Figure S3 in
the Supporting Information). Unfortunately, the extensive
overlapping and broadening of the signals precluded the un-
ambiguous assignment of all signals.
The experiment was then repeated in C6D6 by heating the
sample containing 1 and 2 at 340 K for 12 h. Upon cooling
to room temperature, two distinct signals for the methine
proton of the diphenylacetyl stopper, consistent with the
presence of two pseudorotaxane isomers, appeared at d=
5.22 (a’) and 5.25 ppm (a) (Figure 3b, see Figure S4 in the
Supporting Information for the full spectra). After peak de-
convolution, the two signals were in a relative ratio of ap-
proximately 7:3. It seems, therefore, that at 340 K the deth-
reading of the original pseudorotaxane [1ꢁ2]up and subse-
quent rethreading to yield the more stable [1ꢁ2]down isomer
takes place (Scheme 3). The fact that [1ꢁ2]up is not obtained
as the exclusive product upon successive cooling to room
temperature suggests that slipping of the ammonium head
through the lower rim is prevented at this temperature, in
keeping with the results of the threading experiment be-
tween 1 and 2.
Figure 3. Expanded region of the 1H NMR spectrum (C6D6, 300 MHz) of
pseudorotaxane [1ꢁ2] at a) 298 K and b) after heating the reaction mix-
ture at reflux for 12 h. a, 1, and a’ and 1’ denote the resonances of axle 2
in [1ꢁ2]up and [1ꢁ2]down, respectively. See Scheme 3 for numbering.
To verify whether the regiochemistry of these processes
derives from kinetic control,[16] they were studied by
1H NMR spectroscopy in [D8]toluene at 370 K. The spectral
region between d=4 and 5 ppm where protons a and 1,
which are diagnostic for the orientation of the stopper with
respect to the calixarene rims, resonate was studied. No iso-
merisation of the originally obtained pseudorotaxanes
[1ꢁ4]up and [1ꢁ5]up was detected after 3 h (Scheme 3). The
presence of only one orientational pseudorotaxane isomer
To gain more insight into these processes we added in-
creasing aliquots of triethylamine to the above 7:3 pseudoro-
taxane mixture to deprotonate the ammonium head of 2,
1
and we analysed the resulting solutions by H NMR spec-
troscopy. We found that the original relative ratio between
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A. Arduini, A. Credi et al.
the two isomers remains constant even in the presence of a
large (6 equiv) excess of base with respect to the ammonium
group, and is unchanged also when this sample was heated
at 340 K for 12 h.
Our findings indicate that, in apolar media, axles lacking
the ammonium head enter into the wheel exclusively from
the upper rim. Therefore, axle 3, which terminates with an
OH group, was employed for the synthesis of rotaxane R1
(Scheme 4), which has a diphenylacetamido stopper at the
At this point, one can argue whether the lower-rim
threading observed for 2 is possible, at least in principle,
also for axles 4 and 5. To investigate this issue, we carried
out a new set of threading experiments using the more polar
acetonitrile—a solvent in which the control elements that
operate in benzene are no longer in action.[12] However, we
decided to perform the 1H NMR spectroscopic analysis of
the reaction outcome in C6D6 because this solvent, owing to
its large Aromatic Solvent Induced Shift (ASIS) effect,
allows an unambiguous assignment of the resulting, rather
complex, spectra without affecting the composition of the
isomer mixture.[17] Therefore, acetonitrile was removed and
the reaction products were redissolved in C6D6. Interesting-
ly, an approximately 1:1 mixture of the two orientational
pseudorotaxane isomers was observed for both 4 and 5.
Such a ratio did not change when the solution was heated at
343 K (see Figure S5 in the Supporting Information). It is
worth emphasising that the composition of such a solution
in benzene, prepared by dissolving the 1:1 isomer mixture, is
different from that obtained by mixing the free axle and
wheel components in benzene (see above). The above re-
sults also show that 1) the steric barrier associated with
lower-rim threading of axles 4 and 5 can indeed be over-
come in appropriate conditions, and 2) in acetonitrile the up
and down orientational isomers are endowed with compara-
ble stability. Point 2) is of particular importance because it
shows that the relative stability of the pseudorotaxane iso-
mers is unaffected by the distance of the stopper from the
4,4’-bipyridinium recognition site, thus excluding possible
steric effects, in agreement with molecular models. The for-
mation of a 1:1 mixture of up and down pseudorotaxanes at
room temperature was also observed when these experi-
ments were carried out using 2 as the guest. However, in
this case, upon heating the solution at 340 K for 12 h the
composition of the mixture changed from 1:1 to 7:3 in favor
of the [1ꢁ2]down isomer, that is, to the same isomer ratio ob-
served when 1 and 2 were mixed in C6D6 at 340 K (see
above).
Scheme 4. Reagents
b) Ph2CHCOCl, toluene, 340 K, 7 d.
and
conditions:
a) toluene,
340 K,
2 h;
upper rim and a diphenylacetyl stopper at the lower rim.
According to a previously reported procedure,[12] a slight
excess of axle 3 and wheel 1 were equilibrated at 340 K for
2 h in toluene. An excess of diphenylacetyl chloride was
then added to stopper the pseudorotaxane that had formed,
and the reaction mixture was stirred at 340 K for 7 days
(Scheme 4). After purification by column chromatography,
rotaxane R1 was obtained in 63% yield.[18] The main fea-
1
tures of the H NMR spectrum of R1, recorded in C6D6, are
the broad triplet at d=4.4 ppm and the two singlets at d=
5.19 and 5.22 ppm (Figure 4a; see Figure S6 in the Support-
ing Information for the full spectrum). On the basis of 2D
NMR correlation experiments (Figures S7 and S8 in the
Supporting Information), we assign these signals to the
methylene OCH2 (1’) and the methine protons e’ and a’ of
the axial component, respectively (see Figure 4a and
Scheme 4 for numbering). The upfield shifts of the bipyridi-
nium protons 7’, 8’, 9’ and 10’, that resonate at d=7.02, 6.60,
7.82 and 8.14 ppm, respectively, indicate that this soft cation-
ic portion of the dumbbell is encircled by the soft aromatic
p-donor domain of the wheel. ROESY experiments showed
that the portion of the axle containing the ester moiety is
positioned in proximity to the lower rim, whereas the amide
stopper is at the upper rim of the calixarene. Indeed, in the
expansion of the 2D ROESY spectrum reported in Fig-
ure 4b NOE correlations between the tert-butyl protons (h)
In summary, considering that the only remarkable differ-
ence between axle 2 and axles 4 and 5 is that 2 is equipped
with a cationic ammonium head group, it is reasonable to
think that the peculiar behaviour of axle 2 with respect to
its threading into wheel 1 in apolar solvents is related to
specific interactions between the ammonium unit of 2 and
the various recognition sites incorporated in the structure of
1.
Stoppering of the pseudorotaxanes
The successive step in our investigation was to exploit the
results of the threading experiments described above for the
synthesis of orientational rotaxane isomers[12] following a
threading–stoppering strategy.[7]
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Towards Controlling the Threading Direction of a Calix[6]arene Wheel
FULL PAPER
Figure 4. a) 1H NMR spectrum (expanded region, 300 MHz, C6D6). b) and c) 2D 1H–1H ROESY spectrum (expanded regions, 300 MHz, C6D6, spin
lock=200 ms) of rotaxane R1 showing the most representative correlations derived by the proximity of the axle–wheel protons (double arrows in the
schematic representation and dotted lines in the expansions of the 2D spectrum).
of the wheel with the aromatic protons 9’ and 10’ of the bi-
pyridinium unit are present. In addition, the NOE correla-
tion between protons h of the wheel and protons z’ belong-
ing to the aromatic portion of the amide stopper, clearly
confirms the orientation of the axle within the wheel.
We also performed the threading–stoppering sequence de-
scribed above in the presence of triethylamine, which is ex-
pected to deprotonate the ammonium head of 2. We added
diphenylacetyl chloride to the deep-red homogeneous solu-
tion obtained after mixing a slight excess of 2 to a solution
of 1 in toluene at room temperature in the presence of trie-
thylamine and a catalytic amount of N,N-dimethylaminopyr-
idine (DMAP). At the end of the reaction rotaxane R2, ob-
tained by upper-rim threading (Scheme 5), was isolated in
69% yield as the unique chromatographic fraction.
The peculiar threading behaviour of axle 2 could open the
way for the synthesis of the two orientational isomers R1
and R2 using only axle 2, wheel 1 and diphenylacetyl chlo-
ride as components. It is worth noting that R1 is obtained
from upper-rim threading in the case of axle 3 and from
lower-rim threading in the case of axle 2 (Scheme 4). By
using the same reaction conditions adopted previously, axle
2 and wheel 1 were subjected to the threading–stoppering
reaction sequence with diphenylacetyl chloride. After chro-
matographic purification of the resulting reaction mixture,
the stoppered products were isolated in 35% yield. The
1H NMR spectroscopic analysis showed that the reaction
mixture contains rotaxanes R1 and R2 with a relative ratio
of approximately 7:3, respectively (estimated from the inte-
gral of protons 1 and 1’, see Scheme 4). Although attempts
to separate these two isomers in a quantitative manner
through chromatographic techniques gave unsatisfactory re-
sults, a fraction of almost pure R1 could be isolated.
The signals relative to methine protons e and a in the
stopper are recognisable at d=5.08 and 5.28 ppm, respec-
1
tively, of the H NMR spectrum of R2 in C6D6 (Figure 5a;
see Figure S9 in the Supporting Information for the full
spectrum). As usual, the assignment of the resonances pres-
ent in the spectrum of R2 was carried out through a series
of 2D NMR experiments. Several spatial correlations
(ROESY, Figure S11 in the Supporting Information) were
found between the protons of the phenylureido moieties of
the wheel with protons 4–6 of the hexyl chain stoppered
with the ester function. These data confirm that the axle
chain with the ester moiety is positioned in proximity to the
upper rim of the calix[6]arene wheel. The ROESY experi-
ment also evidenced the presence of correlations between
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A. Arduini, A. Credi et al.
Figure 6. UV-visible absorption spectral changes observed upon titration
of axle 2 (1.6ꢃ10ꢀ5 m) with increasing aliquots of a 1.15ꢃ10ꢀ3 m solution
of wheel 1 in CH2Cl2 at 293 K. The inset shows the corresponding titra-
*
tion data obtained by monitoring the absorbance at 466 nm ( ) and the
fit according to a 1:1 association model (c). The optical path length
was 5.00 cm.
Scheme 5.
curves (see, e.g., Figure 6, inset) were satisfactorily fitted
with a 1:1 association model; the corresponding apparent
stability constants are gathered in Table 1. On the basis of
the results of the NMR spectroscopy characterisation, these
values are obviously referred to the up orientational iso-
mers.[20]
Table 1. Thermodynamic and kinetic parameters for the self-assembly of
the examined pseudorotaxanes (CH2Cl2, 293 K).
Complex LogK[a]
DGꢂ293
A
k1 ꢃ10ꢀ7[c] DH°[d]
[mꢀ1 sꢀ1 [kJmolꢀ1
DS°[d]
[b]
[kJmolꢀ1
]
E
]
G
]
[JKꢀ1 molꢀ1
]
A
7.0ꢃ0.6 ꢀ39ꢃ3
6.8ꢃ0.2 ꢀ38ꢃ1
6.7ꢃ0.4 ꢀ38ꢃ3
7.2ꢃ0.5 ꢀ40ꢃ3
2.9ꢃ0.2
9.6ꢃ0.6
ꢀ8ꢃ1
15ꢃ2
ꢀ126ꢃ3
ꢀ41ꢃ5
Figure 5. Portion of the 1H NMR spectra (300 MHz, C6D6) showing the
resonances of the methine proton of the two diphenylacetyl stoppers in
rotaxanes a) R2 and b) R1.
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
[a] Apparent stability constant for the pseudorotaxanes. [b] Standard
free-energy change at 293 K associated with the self-assembly process.
[c] Threading rate constant. [d] Activation parameters obtained from
Eyring plots.
proton e at d=5.08 ppm with protons resonating at d=6.5
and 7.7 ppm. The latter resonances were assigned, through
COSY and TOCSY experiments (Figure S10 in the Support-
ing Information), to the protons 17 (NH) of the axle and z
of the stopper, respectively. As a result, the signal at d=
5.08 ppm was identified as that of the methine proton (e) of
the diphenylacetyl unit linked to the hexyl chain through
the amide function.
All the values are quite large and identical within the ex-
perimental error, suggesting that the stability of the com-
plexes derived from upper-rim threading is not affected by
the nature of the head and/or the stopper unit of the axle
component. In particular, the comparison between the sta-
bility constants of [1ꢁ4]up and [1ꢁ5]up (Table 1) shows that
the stopper does not hamper the formation of the complex
even if it is just three methylene units away from the bipyri-
dinium unit.
To gather more information on the self-assembly process-
es, we performed temperature-dependent experiments for
the two prototypical compounds 2 and 3, which have a cat-
ionic (ammonium) and a neutral (hydroxy) head group, re-
spectively. The range of temperatures that could be explored
(from 277 K to 303 K) is limited by the low boiling point of
CH2Cl2;[19] in this range, according to the NMR spectroscopy
UV/Vis spectroscopic investigations
Titration experiments: To determine the stability constants
of the resulting pseudorotaxanes, we titrated compounds 2–
5 with 1 in CH2Cl2 at 293 K.[19,20] In all cases, upon addition
of the wheel to the axle solution we observed the appear-
ance of absorption features in the spectral region comprised
between 320 and 600 nm (Figure 6) which can be attributed
to charge-transfer interactions between the p-electron-ac-
cepting 4,4’-bipyridinium unit of the axles and the p-elec-
tron-rich aromatic cavity of the wheel.[11,13,21] The titration
3236
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Chem. Eur. J. 2009, 15, 3230 – 3242

Towards Controlling the Threading Direction of a Calix[6]arene Wheel
FULL PAPER
data, we are most likely to be dealing with pseudorotaxanes
obtained by upper-rim threading. The stability constants of
the two complexes [1ꢁ2]up and [1ꢁ3]up are almost tempera-
ture independent (Table S1 in the Supporting Information),
indicating that the association between the components is
entropically driven. This finding could suggest that, as previ-
ously noticed,[11,13] solvophobic effects play a role in the self-
assembly process.
Stopped-flow experiments: We studied the kinetics of associ-
ation between wheel 1 and axles 2 and 3 in CH2Cl2 by
means of stopped-flow spectrophotometry. The threading
processes of both axles from the upper rim of the wheel are
characterised by second-order rate constants higher than
107 mꢀ1 sꢀ1 (Figure 7 and Table 1). Temperature-dependent
Figure 8. Temperature dependence (Eyring plot) of the threading rate
&
*
constants of wheel 1 with axles 2 ( ) and 3 ( ) in the temperature range
277–303 K in CH2Cl2.
ent orientational isomers can exist for the pseudorotaxanes
corresponding to each axle–wheel combination.
The central questions that arise in the interpretation of
our results are as follows: 1) Is the different behaviour of
the axles examined mainly related to thermodynamic or ki-
netic effects? 2) Which structural elements built in the mo-
lecular components are responsible for the control of the
threading outcome? The answers to these questions are not
easily found in the case of the present self-assembling sys-
tems. In this section we will try to address the above issues
by combining all of the pieces of information that we have
obtained from our multi-faceted experimental study.
Firstly, in apolar media at room temperature all of the
axles enter the cavity exclusively from the upper rim. Such
behaviour can have two different explanations: 1) the
threading from the lower rim is kinetically disfavoured, or
2) the pseudorotaxane derived from lower-rim threading is
thermodynamically unstable. Hypothesis 2, however, can be
ruled out because, while the up isomer is the sole product
obtained on mixing free wheel and axle, a previously pre-
pared 1:1 mixture of the pseudorotaxane isomers does not
equilibrate to yield the up species at the expense of the
down isomer. Such behaviour clearly indicates that the
threading process is kinetically controlled. Furthermore, it
can be recalled that in CH3CN both orientational isomers
exhibit comparable stabilities, and the examined stoppers
and head groups do not affect the stability of the corre-
sponding up pseudorotaxanes in CH2Cl2. Indeed, molecular
models show that the presence of the stopper on the lower
rim does not cause an appreciable steric hindrance. There-
fore, a difference in the relative stability of the two orienta-
tional isomers large enough that one of them would not be
detected in NMR spectroscopy experiments[23] is not justi-
fied on the basis of these observations.
Figure 7. Stopped-flow kinetic trace recorded at 293 K for the absorbance
change at 261 nm obtained upon mixing 1 and 2 in equimolar amounts in
CH2Cl2. The solid line represents the data fitting according to a second-
order rate equation. The concentration of the compounds after mixing
was 1.0ꢃ10ꢀ5 m and the optical path length was 1.00 cm.
kinetic experiments were also performed in the range 277–
303 K (Table S1 in the Supporting Information). Despite the
limited temperature range, the Eyring plots (Figure 8) show
a poor linearity, an observation which indicates that the self-
assembly of these pseudorotaxanes are mechanistically com-
plex phenomena.[22] Nevertheless, it is interesting to note
that the temperature dependence of the threading rate con-
stant is opposite for the two axles; in particular, negative
and positive values for the activation enthalpy DH° are
found for the threading of axles 2 and 3, respectively
(Table 1). Dethreading rate constants, calculated as the ratio
between the threading rate constants and the stability con-
stants (Table S1 in the Supporting Information), are in the
order of 10 sꢀ1.
Discussion
In this framework, the fact that lower-rim threading is ki-
netically blocked, whereas upper-rim threading is remarka-
bly fast, can be accounted for by considering that 1) the me-
thoxy groups at the lower rim, pointing towards the interior
The axle and wheel components presented in this work are
nonsymmetric; therefore, as depicted in Figure 2, two differ-
Chem. Eur. J. 2009, 15, 3230 – 3242
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3237

A. Arduini, A. Credi et al.
of the cavity in apolar solvents (see Figure 9a), prevent the
slipping of a molecular guest from this side, and 2) the urei-
dic anion receptors at the upper rim assist the rupture of the
ion pair, which is a prerequisite for the insertion of the cat-
ionic axle into the wheel. These kinetic control elements are
practically switched off in CH3CN because in this solvent
the methoxy groups at the lower rim point outward,[6b] and
cation–anion interactions as well as anion coordination by
hydrogen bonding are less important than in CH2Cl2.
Upon heating to 340 K, the up pseudorotaxanes obtained
with axles 3, 4 and 5 in benzene at room temperature did
not isomerise. On the other hand, when a 1:1 mixture of ori-
entational isomers (obtained in acetonitrile) was redissolved
in benzene and heated, no change in the isomeric ratio was
detected either. These observations clearly show that the
threading process for axles 3–5 is under kinetic control,
even at 340 K.
The behaviour of the ammonium-terminated axle 2 at
340 K in apolar solvents is the most interesting: it is the
only guest that, at this temperature, is capable of threading
the wheel from the lower rim. The fact that the same ratio
of orientational isomers is obtained irrespective of the start-
ing state (free components or 1:1 mixture of up and down
pseudorotaxanes) suggests that, in this case, the self-assem-
bly process is thermodynamically controlled, with the down
isomer being slightly more favoured than the up one.
The peculiar behaviour of axle 2 must be related to the
presence of the ammonium head group, which is a positively
charged unit with hydrogen-bond donor capabilities. The
fact that [1ꢁ2]down (Figure 9c) is more stable than the up
isomer (Figure 9e) can be explained by considering that the
ureidic units at the upper rim, which can act as both donors
and acceptors of hydrogen bonds, are capable of binding the
ammonium head group as well as coordinating its counter-
anion. The ability of 2 to slip through the lower rim at high
temperature may be again related to the hydrogen-bonding
properties of the ammonium unit. We hypothesise that the
transition state corresponding to lower-rim threading/deth-
reading is stabilised by coordination of the ammonium
group by the crown of oxygen atoms at the lower rim (Fig-
ure 9b), thereby forcing the methoxy units to point outward
and rendering the cavity accessible from this side. We can
also speculate that the negative value of the activation en-
thalpy corresponding to upper-rim threading/dethreading of
2 at around room temperature (Figure 8 and Table 1) may
reflect the binding ability of the ammonium head group to-
wards the ureidic units located at the upper rim (Figure 9d).
In summary, our results indicate that the ammonium head
group of axle 2 represents, as a matter of fact, a second rec-
ognition site (besides the 4,4’-bipyridinium unit) affecting
the pseudorotaxane self-assembly process from both kinetic
and thermodynamic viewpoints. Such a construction is fur-
ther supported by the fact that, on switching off the recogni-
tion properties of the ammonium head group by deprotona-
tion, compound 2 seems to behave similarly to axles 3–5,
which have a dumb head group.
Figure 9. Simplified potential-energy diagram for the threading/dethreading processes of axle 2 into wheel 1, and schematic representation of the possible
structures of the species involved. See the text for more details.
3238
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Chem. Eur. J. 2009, 15, 3230 – 3242

Towards Controlling the Threading Direction of a Calix[6]arene Wheel
FULL PAPER
tion of 7 (5.6 g, 25.8 mmol), triethylamine (3.9 g, 38.4 mmol) and DMAP
(0.12 g, 1 mmol) in CH2Cl2 (100 mL). After stirring for 48 h at room tem-
perature, the reaction was quenched with water (100 mL). The organic
phase was separated, dried over anhydrous Na2SO4 and filtered. The or-
ganic solvent was removed under reduced pressure and the oily residue
was purified by column chromatography (n-hexane/ethyl acetate 9:1) to
afford 8 as a white solid (7.7 g, 81%). M.p. 61.6–62.68C; 1H NMR
(300 MHz, CDCl3): d=1.2–1.3 (m, 4H), 1.3–1.4 (m, 11H), 1.5–1.4 (m,
Conclusion
We have designed, synthesised and investigated a family of
pseudorotaxanes made of a tris(phenylureido)calix[6]arene
wheel and rivet-like axles containing a 4,4’-bipyridinium
unit. As the axle and wheel components are nonsymmetric,
two different orientational isomers, up and down, can exist
2H), 2.32 (s, 3H), 2.9–3.0 (m, 2H); 3.95 (t, 3J
(brs, 1H), 7.31 (d, 3J(H,H)=8 Hz, 2H), 7.77 ppm (d, 3J
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
for each of the pseudorotaxanes examined (Figure 2).
At room temperature in apolar solvents we found that all
axles thread the wheel from the upper rim for kinetic rea-
sons. At higher temperature (340 K), the self-assembly pro-
cesses of axles with uncharged head groups (3–5) are still ki-
netically controlled, and yield the up pseudorotaxane isomer
as the sole threading product. Conversely, the axle with an
ammonium head group (2) is capable of entering the cavity
from the lower rim at 340 K; in this case the self-assembly is
under thermodynamic control and the down isomer is the
favoured threading product. We have exploited these fea-
tures to implement the straightforward synthesis of orienta-
tional rotaxane isomers.
G
2H); 13C NMR (75 MHz, CDCl3): d=21.5, 24.9, 26.0, 28.3, 28.6, 29.7,
40.3, 70.4, 127.7, 129.7, 133.0, 144.6, 155.9 ppm; ESI-MS(+): m/z (%):
394.0 (100); elemental analysis calcd (%) for C18H29NO5S: C 58.20, H
7.87, N 3.77, S 8.63; found: C 58.53, H 7.61, N 3.45, S 8.24.
1-[6-(tert-Butoxycarbonylamino)hexyl]-4,4’-bipyridin-1-ium tosylate (9):
Tosylate 8 (0.3 g, 0.8 mmol) was added to a solution of 4,4’-bipiridyne
(0.2 g, 1.3 mmol) in acetonitrile (50 mL),. After stirring under reflux for
72 h, the solvent was removed under reduced pressure to afford a crude
oily residue that was triturated twice with ethyl acetate (2ꢃ25 mL) to
afford 9 as a white solid (0.37 g, 84%). M.p. 157–1598C; 1H NMR
(300 MHz, CD3CN): d=1.3–1.5 (m, 15H), 1.9–2.0 (m, 2H), 2.29 (s, 3H),
2.97 (q, 3J
1H), 7.12 (d, 3J
(d, 3J(H,H)=7.2 Hz, 2H), 8.30 (d, 3J
(H,H)=7.2 Hz, 2H), 8.88 ppm (d, 3J
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
R
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
U
Our observations suggest that specific interactions be-
tween the ammonium head group of the axle and the two
rims of the wheel can act as thermodynamic and kinetic con-
trol elements for the self-assembly process. These results
represent a remarkable step forward for the construction of
instructed chemical systems[2a,24] in which not only the equi-
librium states but also the dynamic behaviour could be care-
fully controlled. Progress in such a direction will be signifi-
cant for the development of advanced template-directed
synthetic protocols.[25] Moreover, studies of this kind are an
important premise for the design and construction of multi-
component molecular species in which ratcheting effects[2h,26]
allow a full directional control of the intercomponent molec-
ular motions.
(75 MHz, CD3OD): d=19.1, 24.6, 25.0, 26.6, 28.5, 30.2, 38.8, 60.5, 121.4,
121.9, 124.8, 125.0, 127.7, 133.7, 139.5, 141.5, 144.3, 149.6, 152.9 ppm;
ESI-MS(+): m/z (%): 300 (100), 356 (70); elemental analysis calcd (%)
for C28H37N3O5S: C 63.73, H 7.07, N 7.96, S 6.08; found: C 64.14, H 7.11,
N 7.85, S 5.99.
1-[6-(tert-Butoxycarbonylamino)hexyl]-1’-[6-(2,2-diphenylacetoxy)hexyl]-
4,4’-bipyridine-1,1’-diium ditosylate (11): A catalytic amount of KI was
added to a solution of compounds 9 (0.38 g, 0.6 mmol) and 10 (0.75 g,
1.6 mmol) in acetonitrile (20 mL). The resulting mixture was heated at
reflux for 15 days and then cooled to room temperature. Axle 7 was re-
covered from the mixture by suction filtration as a yellow solid that was
triturated twice (2ꢃ20 mL) with ethyl acetate to afford 11 as a white
solid (0.58 g, 90%). M.p. 116–1188C; 1H NMR (300 MHz, CD3OD): d=
1.3–1.5 (m, 19H), 1.5–1.7 (m, 2H), 1.9–2.0 (m, 4H), 2.34 (s, 6H), 3.01 (t,
3J
5.06 (s, 1H), 7.2–7.4 (m, 14H), 7.69 (d, J
(H,H)=6.6 Hz, 4H), 9.16 (d, 3J(H,H)=6.6 Hz, 2H), 9.20 ppm (d, 3J-
(H,H)=6.6 Hz, 2H); 13C NMR (75 MHz, CD3OD): d=21.6, 26.5, 26.8,
(H,H)=6.3 Hz, 2H), 4.13 (t, 3J
ACHUTNGTRENNUG AHCTUNGTRENN(UNG H,H)=6.6 Hz, 2H), 4.6–4.7 (m, 4H),
3
3
AHCTUNGTERG(NNUN H,H)=8.1 Hz, 4H), 8.59 (d, J-
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
27.0, 27.4, 29.1, 29.5, 30.9, 32.6, 32.7, 41.3, 58.5, 63.4, 63.5, 66.1, 127.2,
128.6, 129.9, 130.0, 130.1, 140.6, 142.0, 143.8, 147.3, 151.5 ppm; ESI-
MS(+): m/z (%): 300 (80), 452 (100), 651 (25); elemental analysis calcd
(%) for C55H67N3O10S2: C 66.44, H 6.79, N 4.23, S 6.45; found: C 66.73, H
6.81, N 4.02, S 6.23.
Experimental Section
Synthesis of the compounds: Toluene and dichloromethane were dried
using standard procedure, all other reagents were of reagent grade quali-
ty as obtained from commercial suppliers and were used without further
purification. 1H and 13C spectra were recorded at 300 and 75 MHz respec-
tively. Chemical shifts are expressed in ppm (d) using the residual solvent
signals as an internal reference. Mass spectra were determined in the ESI
mode. Compounds 1,[6b] 10,[12] 14,[27] 16[27] and 19[28] were synthesised ac-
cording to literature procedures.
Axle (2):
A solution of 11 (0.3 g, 0.3 mmol) in trifluoroacetic acid
(10 mL) was stirred at room temperature for 1 h. The solvent was com-
pletely removed under reduced pressure to give 2 as yellowish oil (0.25 g,
95%). 1H NMR (300 MHz, CD3OD): d=1.4 (brs, 4H), 1.5 (brs, 4H),
1.6–1.7 (m, 4H), 1.9–2.2 (m, 4H), 2.30 (s, 6H), 2.92 (t, 3J
ACHTUNGTRENNUNG
2H), 4.13 (t, 3J
(H,H)=6.5 Hz, 2H), 4.65 (t, 3J
ACHUTGTNRENNUG CAHTUNGTRENNUNG
(t, 3J
AHCTUNGTRENNUNG
N-Boc-6-aminohexan-1-ol (7): Di-tert-butyl dicarbonate (11.5 g,
52.7 mmol) was added to a solution of 6 (3 g, 26 mmol) in a 9:1 (v/v) mix-
ture of methanol/triethylamine (250 mL). After stirring under reflux for
1 h, the solvent was removed under reduced pressure. The residue was re-
dissolved in CH2Cl2 (100 mL) and water (100 mL). The separated organic
phase was dried over anhydrous Na2SO4 and evaporated under reduced
A
R
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
CD3OD): d=21.6, 26.5, 26.8, 27.0, 28.4, 29.5, 32.4, 32.6, 40.7, 58.5, 63.3,
63.4, 66.1, 127.2, 128.6, 129.9, 130.0, 130.1, 140.6, 142.1, 143.9, 147.4,
151.5, 151.6, 174.5 ppm; ESI-MS(+): m/z (%): 452 (95), 551 (100); ele-
mental analysis calcd (%) for C52H60F3N3O10S2: C 61.95, H 6.00, N 4.17, S
6.36; found: C 62.07, H 6.13, N 4.12, S 6.29.
pressure to afford
7
as an oily compound (5.5 g, 95%). 1H NMR
3
(300 MHz, CDCl3): d=1.0–1.5 (m, 17H), 2.9 (brs, 2H), 3.39 (t, J
(H,H)=
6.6 Hz, 2H), 3.50 (s, 1H), 5.0 ppm (brs, 1H); 13C NMR (75 MHz,
CDCl3): d=25.2, 26.3, 28.3, 29.9, 40.4, 62.3, 79.1, 156.1 ppm; ESI-MS(+):
m/z (%): 240.1 (100); elemental analysis calcd (%) for C11H23NO3: C
60.80, H 10.67, N 6.45; found: C 60.55, H 10.71, N 6.38.
N-(6-Hydroxyhexyl)-2,2-diphenylacetamide (12): Diphenylacetyl chloride
(0.39 g, 1.71 mmol) was added to a solution of 6-aminohexan-1-ol 6
(0.2 g, 1.71 mmol) and triethylamine (0.21 g, 2.0 mmol) in acetonitrile
(20 mL). The resulting solution was stirred at room temperature for 12 h.
The solvent was then removed under reduced pressure and the resulting
solid residue taken up with ethyl acetate (20 mL) and with a 10% (w/v)
6-(tert-Butoxycarbonylamino)hexyl tosylate (8): A solution of tosyl chlo-
ride (6.3 g, 33.3 mmol) in CH2Cl2 (50 mL) was added dropwise to a solu-
Chem. Eur. J. 2009, 15, 3230 – 3242
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3239

A. Arduini, A. Credi et al.
aqueous solution of HCl (20 mL). The organic layer was separated,
washed with water, dried over anhydrous Na2SO4 and filtered. After
evaporation of the solvent under reduced pressure, the solid residue was
purified by column chromatography (hexane/ethyl acetate 3:7) to afford
12 as colourless oil (0.48 g, 90%). 1H NMR (300 MHz, CDCl3): d=1.2–
60.8, 66.9, 127.4, 127.6, 128.2, 128.4, 132.8, 138.8, 143.6, 172.2 ppm; ESI-
MS(+): m/z (%): 423 (100); elemental analysis calcd (%) for C24H24O5S:
C 67.90, H 5.70, S 7.55; found: C 67.92, H 5.80, S 7.48.
1-[3-(2,2-Diphenylacetoxy)propyl]-4,4’-bipyridin-1-ium tosylate (18):
A
solution of 16 (0.64 g 1.5 mmol) and 4,4’-bipiridyne (0.47 g, 3 mmol) in
acetonitrile (50 mL) was heated at reflux for 48 h. After this period, the
solvent was evaporated to dryness under reduced pressure. Purification
of the crude solid residue by precipitation from a mixture hexane/CH2Cl2
afforded 18 as a yellow solid (0.5 g, 57%). M.p. 53–558C; 1H NMR
1.4 (m, 4H), 1.4–1.6 (m, 4H), 2.4 (br s, 1H), 3.27 (q, 3J
2H), 3.58 (t, 3J
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
7.4 ppm (m, 10H); 13C NMR (75 MHz, CDCl3): d=25.1, 29.3, 32.3, 39.6,
56.9, 59.1, 62.5, 127.2, 128.6, 128.8, 139.4, 171.8 ppm; ESI-MS(+): m/z
(%): 335 (100); elemental analysis calcd (%) for C20H25NO2: C 77.14, H
8.09, N 4.50; found: C 77.25, H 8.01, N 4.55.
(300 MHz, CDCl3): d=2.26 (s, 3H), 2.3–2.4 (m, 2H), 4.14 (t, 3J
5.4 Hz, 2H), 4.79 (t, 3J(H,H)=6.6 Hz, 2H), 4.97 (s, 1H), 7.07 (d, 3J-
(H,H)=8.0 Hz, 2H), 7.2–7.3 (m, 10H), 7.53 (d, 3J
(H,H)=6.5 Hz, 2H),
ACHTUNGTRENNUNG(H,H)=
AHCTUNGTRENNUNG
6-(2,2-Diphenylacetamido)hexyl tosylate (13): Tosyl chloride (0.23 g,
1.22 mmol) and a catalytic amount of DMAP were added to a solution of
compound 12 (0.25 g, 0.81 mmol) and triethylamine (0.17 g, 1.62 mmol)
in CH2Cl2 (20 mL). After stirring for 12 h at room temperature, the reac-
tion was quenched with water (20 mL). The organic phase was separated,
dried over anhydrous Na2SO4 and filtered. The organic solvent was re-
moved under reduced pressure and the oily residue was purified by
column chromatography (hexane/ethyl acetate 7:3, then 6:4) to afford 13
A
ACHTUNGTRENNUNG
3
3
3
7.72 (d, J
N
ACHTUNGTNER(NUNG H,H)=6.5 Hz, 2H), 8.76 (d, J-
A
ACHTUNGTRENNUNG
CDCl3): d=19.0, 27.9, 54.3, 56.5, 59.1, 119.2, 123.7, 123.6, 125.2, 126.4,
126.5, 136.1, 137.3, 138.8, 141.4, 143.7, 148.9, 151.1, 169.9 ppm; ESI-
MS(+): m/z (%): 409 (100); elemental analysis calcd (%) for
C34H32N2O5S: C 70.32, H 5.55, N, 4.82, S 5.52; found: C 70.14, H 5.50, N
4.77, S 5.61.
1
as a colourless oil (0.17 g, 44%). H NMR (300 MHz, CDCl3): d=1.1–1.4
Axle 5:
A solution of 18 (0.5 g, 0.9 mmol) and tosylate 19 (0.4 g,
(m, 4H), 1.4–1.5 (m, 2H), 1.5–1.7 (m, 2H), 2.43 (s, 3H), 3.2 (brs, 2H),
2.3 mmol) in acetonitrile (50 mL) was poured in a sealed glass reactor
where the reaction mixture was heated at 1008C (CAUTION!) for 48 h.
After cooling to room temperature, the reaction mixture was transferred
from the reactor and the solvent was evaporated to dryness under re-
duced pressure. Purification of the crude solid residue by precipitation
from a mixture CH3CN/ethyl acetate afforded 5 as a white solid (0.45 g,
62%). M.p. 117–1208C; 1H NMR (300 MHz, CD3CN): d=0.89 (t, 3J-
3.98 (t, 3J
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
d=24.9, 26.0, 28.6, 29.2, 39.5, 59.0, 70.4, 127.1, 127.8, 128.6, 128.8, 129.8,
133.0, 139.5, 144.7, 171.8 ppm; ESI-MS(+): m/z (%): 316 (100), 489 (97);
elemental analysis calcd (%) for C27H31NO4S: C 69.65, H 6.71, N 3.01, S
6.89; found: C 69.82, H 6.75, N 2.99, S 6.75.
1-(6-Hydroxyhexyl)-4,4’-bipyridin-1-ium tosylate (15): 6-hydroxyhexyl to-
sylate (14) (1.29 g, 4.73 mmol) and 4,4’-bipiridyne (1.1 g, 7.1 mmol) were
dissolved in acetonitrile (100 mL) and heated at reflux overnight. The
solvent was then removed under reduced pressure to afford a crude solid
residue that was triturated with ethyl acetate (2ꢃ25 mL) to give 15 as a
white solid (0.60 g, 30%). M.p. 202–2058C; 1H NMR (300 Hz, CD3CN):
ACHTUNGERTN(NUNG H,H)=4.5 Hz, 3H), 1.3–1.4 (m, 4H), 1.9–2.0 (m, 2H), 2.24 (s, 6H), 2.3–
3
2.4 (m, 2H), 4.24 (t, J
7.12 (d, 3J(H,H)=8.1 Hz, 4H), 7.2–7.3 (m, 10H), 7.58 (d, 3J
6.9 Hz, 2H), 8.33 (d, 3J(H,H)=8.2 Hz, 4H), 8.46 (d, 3J
(H,H)=6.9 Hz,
2H), 8.85 (d, 3J(H,H)=6.9 Hz, 2H), 8.97 ppm (d, 3J
(H,H)=6.9 Hz, 2H);
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
13C NMR (75 MHz, CD3CN): d=16.2, 23.4, 24.9, 30.8, 32.7, 33.8, 59.1,
62.3, 64.8, 65.0, 120.5, 128.9, 130.0, 130.1, 130.3, 131.6, 133.1, 142.2, 147.6,
152.1, 175.1 ppm; ESI-MS(+): m/z (%): 651 (100); elemental analysis
calcd (%) for C46H50N2O8S2: C 67.13, H 6.12, N 3.40, S 7.79; found: C
67.24, H 6.00, N 3.33, S 7.82.
d=1.2–1.5 (m, 6H), 1.9–2.0 (m, 2H), 2.26 (s, 3H), 3.42 (t, 3J
6.1 Hz, 2H), 4.57 (t, 3J(H,H)=7.6 Hz, 2H), 7.10 (d, 3J
(H,H)=7.9 Hz,
2H), 7.59 (d, 3J(H,H)=7.9 Hz, 2H), 7.78 (d, 3J
(H,H)=6.1 Hz, 2H), 8.29
(d, 3J(H,H)=6.1 Hz, 2H), 8.79 (d, 3J(H,H)=6 Hz, 2H), 8.93 ppm (d, 3J-
(H,H)=6 Hz, 2H); 13C NMR (75 MHz, CD3CN): d=20.9, 25.5, 25.9,
ACHTUNGTRNE(NUNG H,H)=
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
Rotaxane R1: Axle 3 (0.04 g, 0.04 mmol) was suspended in a solution of
1 (0.11 g, 0.08 mmol) in dry toluene (10 mL). The resulting heterogene-
ous mixture was stirred and heated at 708C until the solution turned to a
deep-red colour (ꢄ2 h). Diphenylacetyl chloride (0.01 g, 0.06 mmol) was
then added and the reaction mixture was heated at 708C for a further
7 days. The solvent was completely removed under reduced pressure and
the reddish solid residue containing a mixture of the two rotaxanes was
purified by column chromatography (CH2Cl2/methanol 20:1; Rf =0.3) to
31.5, 32.7, 61.8, 122.6, 126.3, 126.5, 127.7, 129.1, 139.5, 141.8, 145.9, 151.5,
153.8 ppm; ESI-MS(+): m/z (%): 257 (100); elemental analysis calcd (%)
for C23H28N2O4S: C 64.46, H 6.59, N 6.54, S 7.48; found: C 64.52, H 6.44,
N 6.61, S 7.32.
Axle (3): A catalytic amount of KI was added to a solution of 13 (0.15 g,
0.32 mmol) and 15 (0.28 g, 0.64 mmol) in acetonitrile (20 mL). The reac-
tion mixture was heated under reflux for 15 days. The resulting heteroge-
neous solution was cooled to room temperature to afford a yellow solid
precipitate of 3 (0.12 g, 40%), which was collected by filtration. M.p.
133–1358C; 1H NMR (300 MHz, CD3OD): d=1.2–1.6 (m, 12H), 1.9–2.1
afford R1 as
a
red solid (0.06 g, 63%). M.p. 301–3038C; 1H NMR
(300 MHz, C6D6,): d=0.9 (brs, 2H), 1.0 (brs, 2H), 1.1–1.3 (m, 11H), 1.4–
1.6 (m, 4H), 1.7 (brs, 2H), 1.77 (s, 27H), 1.8–2.0 (m, 4H), 2.09 (s, 6H),
2.2 (brs, 2H), 3.4–3.6 (m, 14H), 3.7 (brs, 6H), 3.9 (brs, 6H), 4.0 (brs,
(m, 4H), 2.34 (s, 6H), 3.2 (brs, 2H), 3.55 (t, 3J
4.7 (m, 4H), 4.94 (s, 1H), 7.2–7.3 (m, 14H), 7.66 (d, 3J
4H), 8.6 (brs, 4H), 9.17 (d, 3J(H,H)=6.6 Hz, 2H), 9.21 ppm (d, 3J-
(H,H)=6.6 Hz, 2H); 13C NMR (75 MHz, CD3OD): d=21.6, 26.7, 26.8,
ACHTUNGTRENNUNG
T
11H), 4.4 (brs, 2H), 4.62 (d, 2J
1H), 6.6 (brd, 2H), 6.79 (t, 3J
7.2 (m, 15H), 7.2–7.4 (m, 7H), 7.53 (d, 3J
3H), 7.75 (d, 3J
(H,H)=7.6 Hz, 8H), 7.8 (brd, 2H), 8.0 (brd, 6H), 8.1
ACHTUNGTRENNUNG
N
ACHTUNGTRENNUNG
U
ACHTUNGTRENNUNG
27.3, 30.2, 30.7, 32.6, 32.8, 33.5, 40.3, 59.4, 62.9, 63.4, 63.5, 127.2, 128.3,
128.6, 129.3, 129.7, 130.2, 131.4, 141.6, 142.0, 144.0, 47.3, 151.5,
174.9 ppm; ESI-MS(+): m/z (%): 450 (35), 551 (100); elemental analysis
calcd (%) for C50H59N3O8S2: C 67.16, H 6.65, N 4.70, S 7.17; found: C
67.20, H 6.58, N 6.62, S 7.09.
ACHTUNGTRENNUNG
(brs, 2Hs), 8.3 ppm (brd, 4H); 13C NMR (75 MHz, C6D6): d=15.6, 21.2,
25.3, 25.9, 28.0, 28.7, 29.6, 30.1, 30.2, 30.8, 31.8, 31.9, 34.9, 39.4, 40.1, 57.7,
59.4, 60.7, 61.4, 65.1, 66.7, 70.3, 72.4, 117.1, 118.5, 121.6, 121.8, 125.0,
126.1, 126.9, 127.4, 132.5, 134.2, 137.9, 139.6, 139.9, 140.7, 171.3, 141.5,
143.3, 143.5, 144.7, 146.5, 148.5, 153.2, 153.9, 172.2 ppm; ESI-MS(+): m/z
(%): 1105 (100) [R1–2Tsꢀ]2+, 2210 [R1ꢀH]+; elemental analysis calcd
(%) for C154H177N9O21S2: C 72.42, H 6.98, N 4.94, S 2.51; found: C 72.85,
H 6.77, N 4.72, S 2.39.
3-(Tosyloxy)propyl 2,2-diphenylacetate (17): A solution of tosylate 16
(2.5 g, 10 mmol) and diphenylacetylchloride (2.3 g, 10 mmol) in THF
(100 mL) was stirred at room temperature for 48 h. The reaction mixture
was then diluted with water (50 mL) and ethyl acetate (50 mL). The or-
ganic layer was separated, dried over anhydrous Na2SO4 and filtered.
After evaporation of the solvent under reduced pressure, the oily residue
was purified by column chromatography (hexane/ethyl acetate 75:25) to
afford 17 as a yellowish oil (2.67 g, 63%). 1H NMR (300 MHz, CDCl3):
Rotaxane R2: Axle 2 (0.04 g, 0.04 mmol) was suspended in a solution of
1 (0.06 g, 0.04 mmol) in dry toluene (10 mL), and the resulting colorless
solution was stirred at room temperature. After 2 h, when the solution
was homogeneous, diphenylacetyl chloride (0.01 g, 0.05 mmol), triethy-
lammine (0.01 g, 0.08 mmol) and a catalytic amount of DMAP were
added. After 5 h the solvent was completely removed under reduced
pressure and the reddish solid residue was purified by column chroma-
d=2.35 (s, 3H), 2.45 (m, 2H), 3.66 (t, 3J
(H,H)=6.3 Hz, 2H), 5.05 (s, 1H), 7.3–7.4 (m, 12H), 7.81 ppm (d, J-
ACHTUNGTRENNUNG
(H,H)=8.8 Hz, 2H); 13C NMR (75 MHz, CDCl3): d=21.6, 28.4, 56.9,
ACHTUNGTNER(NUNG H,H)=6.1 Hz, 2H), 4.10 (t, J-
ACHTUNGTRENNUNG
3240
www.chemeurj.org
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 3230 – 3242

Towards Controlling the Threading Direction of a Calix[6]arene Wheel
FULL PAPER
tography (CH2Cl2/methanol 20:1) to afford R2 as a red solid (0.07 g,
Table S1 in the Supporting Information together with those of the corre-
sponding first-order dethreading rate constants.
69%). M.p. 251–2538C; 1H NMR (300 MHz, C6D6): d=0.5–0.7 (m, 4H),
3
0.8–1.0 (m, 2H), 1.18 (t, J
N
2H), 1.6 (brs, 6H), 1.78 (s, 27H), 2.1 (brs, 2H), 3.3–3.4 (m, 2H), 3.4–3.6
(m, 10H), 3.7 (brs, 6H), 3.8 (brs, 2H), 3.9 (brs, 6H), 3.93 (s, 9H), 4.11 (t,
3J(H,H)=6 Hz, 2H), 4.56 (d, 2J
ACHTUNGTRENNUNG ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
Acknowledgements
A
ACHTUNGTRENNUNG
This research was partly supported by the EU (STREP “Biomach”
NMP4-CT-2003-505487), the Italian Ministry of University and Research
(FIRB “Manipolazione Molecolare per Macchine Nanometriche” and
PRIN “Sistemi Supramolecolari per la costruzione di macchine moleco-
lari, conversione dellꢄenergia, sensing e catalisi”) and the Universities of
Bologna and Parma. We thank the Centro Interdipartimentale di Misure
“G. Casnati” of the University of Parma for NMR spectroscopy measure-
ments.
9.42 (s, 3H), 9.62 ppm (s, 3H); 13C NMR (75 MHz, C6D6): d=15.2, 24.9,
25.4, 27.0, 27.1, 27.5, 28.4, 29.1, 29.5, 29.9, 30.3, 31.6, 34.6, 39.7, 57.4, 58.6,
60.3, 61.2, 64.6, 66.3, 69.9, 72.5, 116.4, 117.4, 121.1, 124.2, 124.9, 126.9,
128.5, 128.6, 128.7, 128.9, 129.2, 132.2, 134.0, 136.7, 139.2, 140.7, 143.0,
143.7, 145.3, 147.6, 148.1, 148.2, 152.8, 153.5, 171.0, 172.2 ppm; ESI-
MS(+): m/z (%): 1105 (100) [R2ꢀ2Tsꢀ]2+, 2247 (5) [R2ꢀ2Tsꢀ+Clꢀ]+; el-
emental analysis calcd (%) for C154H177N9O21S2: C 72.42, H 6.98, N 4.94,
S 2.51; found: C 72.75, H 6.88, N 4.98, S 2.45.
Absorption spectra and titration experiments: Measurements were car-
ried out on air-equilibrated solutions in CH2Cl2 (Merck Uvasol) in the
concentration range from 1.0ꢃ10ꢀ5 to 2.5ꢃ10ꢀ4 m. UV/Vis absorption
spectra were recorded by using either 1 cm or 5 cm path length cells with
a Perkin–Elmer Lambda 40 spectrophotometer for the spectra performed
at ambient temperature, or a Varian Cary 50 Bio instrument for the ex-
periments in which the temperature of the cell block was thermostated
by using a circulating constant temperature bath maintained at the re-
quired temperature. Titrations were performed by adding, with a micro-
syringe, small aliquots (typically 20 mL) of a concentrated (2ꢃ10ꢀ4–2ꢃ
10ꢀ3 m) solution of wheel 1 to a solution (2.50 mL) of the axle species ex-
amined. The UV/Vis absorption changes were monitored throughout the
titration. The apparent stability constants of the pseudorotaxanes were
calculated by fitting the absorption titration spectra by means of the
SPECFIT software[29] using a 1:1 association model. Because of the large
values of the stability constants, titrations were performed in dilute con-
ditions (the typical concentration of the titrated species was 1.0ꢃ10ꢀ5 m)
to ensure that the curvature at the intersection of the two linear regions
of the plot could be clearly seen. Moreover, the results of the fittings
were tested by simulating the titration plots with stability constants
higher and lower than those determined by the software.
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Received: September 18, 2008
Published online: February 10, 2009
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