Anion recognition and cation-induced molecular motion in a heteroditopic [2]rotaxane

Article abstract of DOI:10.1002/chem.201002405

A heteroditopic [2]rotaxane consisting of a calix[4]diquinone- isophthalamide macrocycle and 3,5-bis-amide pyridinium axle components with the capability of switching between two positional isomers in response to barium cation recognition is synthesised. The anion binding properties of the rotaxane's interlocked cavity together with Na⁺, K⁺, NH₄⁺ and Ba²⁺ cation recognition capabilities are elucidated by ¹H NMR and UV-visible spectroscopic titration experiments. Upon binding of Ba²⁺, molecular displacement of the axle's positively charged pyridinium group from the rotaxane's macrocyclic cavity occurs, whereas the monovalent cations Na⁺, K⁺ and NH₄⁺ are bound without causing significant co-conformational change. The barium cation induced shuttling motion can be reversed on addition of tetrabutylammonium sulfate. Copyright

Full text of DOI:10.1002/chem.201002405

DOI: 10.1002/chem.201002405
Anion Recognition and Cation-Induced Molecular Motion in a
[2]Rotaxane
ACHTUNGTRENHNUNG eteroditopic
Alexandre V. Leontiev, Charlotte A. Jemmett, and Paul D. Beer*[a]
Dedicated to the memory of Professor Dmitry M. Rudkevich (1963–2007)
Abstract: A heteroditopic [2]rotaxane
Ba2+ cation recognition capabilities are
elucidated by H NMR and UV-visible
spectroscopic titration experiments.
Upon binding of Ba2+, molecular dis-
placement of the axleꢀs positively
charged pyridinium group from the ro-
1
consisting of a calix[4]diquinone–iso-
phthalamide macrocycle and 3,5-bis-
amide pyridinium axle components
with the capability of switching be-
tween two positional isomers in re-
sponse to barium cation recognition is
synthesised. The anion binding proper-
ties of the rotaxaneꢀs interlocked cavity
taxaneꢀs macrocyclic cavity occurs,
whereas the monovalent cations Na+,
+
K+ and NH4 are bound without caus-
ing
significant
co-conformational
change. The barium cation induced
shuttling motion can be reversed on
addition of tetrabutylammonium sul-
fate.
Keywords: anions · molecular mo-
tion · receptors · rotaxanes · tem-
plate synthesis
+
together with Na+, K+, NH4 and
Introduction
chlorides as contact ion-pair species.[9] Combining molecular
design features from both areas, herein we report the syn-
thesis of a novel heteroditopic [2]rotaxane system with the
dual capability of exhibiting anion and cation recognition
properties, together with cation-induced dynamic shuttling
behaviour (Figure 1).
The innovative construction of catenane and rotaxane inter-
locked molecules of increasing complexity and function is
continuing to attract intense research interest in the chemi-
cal community.[1] In particular, whilst the use of external
stimuli to control mechanical-bond molecular motion allows
for their incorporation into nanoscale molecular switches
and machines,[2] three-dimensional interlocked host cavities
have exceptional promise in future chemical sensor design.[3]
Although cation[4] and to a much lesser extent anion[5] bind-
ing interlocked host systems have been reported for recogni-
tion and dynamic applications,[6] the design and synthesis of
heteroditopic interlocked systems has remained largely un-
derdeveloped.[7] We have undertaken a research programme
with the objective of exploiting the topological cavities of
rotaxanes and catenanes in anion host–guest chemistry.[8] In
addition, we have recently reported heteroditopic calix[4]di-
quinone receptors that bind Group I metal and ammonium
Results and Discussion
Design and synthetic strategy: The heteroditopic macrocy-
clic component 1 of the target [2]rotaxane system, shown in
Scheme 1, consists of a calix[4]diquinone ether cation recog-
nition site covalently linked by hydroquinone groups to an
isophthalamide anion binding motif.
Such a macrocycle is designed to facilitate anion-templat-
ed interpenetrated assembly with a 3,5-bis-amide-substituted
pyridinium chloride threading component through coopera-
tive association of the unsaturated chloride anion of the ion
pair to the macrocycle isophthalamide binding site and fa-
vourable p–p stacking interactions between the electron-
rich hydroquinone groups and the positively charged elec-
tron-deficient pyridinium group. With appropriate functional
groups, such as azide, appended to the pyridinium chloride
threading component, a stoppering synthetic strategy using
click chemistry[10] is exploited to prepare the heteroditopic
[2]rotaxane system (Scheme 2).
[a] Dr. A. V. Leontiev, C. A. Jemmett, Prof. P. D. Beer
Department of Chemistry, Chemistry Research Laboratory
University of Oxford, Mansfield Road, Oxford, OX1 3TA (UK)
Fax : (+44)1865-272690
E-mail: paul.beer@chem.ox.ac.uk
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002405.
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FULL PAPER
Scheme 2. Target heteroditopic [2]rotaxane assembly formed by chloride
anion templation and p–p stacking interactions.
the axle being displaced from the rotaxaneꢀs macrocycle
cavity (Figure 1b).
Synthesis of the rotaxane: The heteroditopic macrocyclic
component 1 was synthesised in 42% yield by oxidation of
calixarene macrocycle precursor 2[12] with Tl
ACTHNUGTRNEGNU(CF3COO)3
(Scheme 3a). The synthetic route to the bis-azide-function-
alised pyridinium chloride thread component, 3·Cl, is out-
lined in Scheme 3b. The bis-azide pyridine derivative 4 was
prepared in 69% yield by a condensation reaction between
3,5-bis-chlorocarbonyl pyridine and 3-azidopropylamine hy-
drochloride (2 equiv) in dry CH2Cl2 in the presence of trie-
thylamine. Methylation of 4 was achieved in 50% yield by
using excess trimethyloxonium tetrafluoroborate to give
3·BF4. The chloride salt 3·Cl was isolated by using an anion
exchange resin. The propensity for macrocycle 1 to form an
interpenetrative assembly with the pyridinium diazide 3·Cl
Figure 1. Heteroditopic [2]rotaxane design with the capability to a) selec-
tively bind anions and b) undergo cation-induced molecular shuttling.
1
was confirmed by qualitative H NMR spectroscopy titration
studies (see Figure S25 in the Supporting Information).
The synthetic route to the target heteroditopic [2]ro-
taxane 5·Cl is outlined in Scheme 4. A solution of macrocy-
cle 1, axle 3·Cl and alkyne-functionalised stopper 6 (2 equiv)
in dichloromethane in the presence of a catalytic amount of
[CuACHTUNGTRNEU(GN CH3CN)4]PF6 was stirred at room temperature for 24 h.
The rotaxane 5·Cl was isolated in 31% yield following pu-
rification by silica gel preparative TLC and characterised by
1H NMR spectroscopy and high-resolution electrospray
mass spectrometry.
Scheme 1. Target calix[4]diquinone-based macrocycle 1.
1
A comparison of the H NMR spectra of the stoppered
axle, macrocycle 1 and rotaxane 5·Cl is shown in Figure 2.
Large downfield shifts are observed in the macrocycle
amide protons 4 and internal isophthalamide proton 1, indi-
cating complexation of the templating chloride anion to the
macrocycle. In addition, upfield shifts of the pyridinium pro-
tons c and b, and amide protons d of the threaded axle com-
ponent are observed due to the combination of p–p stacking
interactions between the electron-deficient pyridinium ring
The rotaxaneꢀs orthogonal interlocked macrocycle iso-
phthalamide–axle pyridinium amide hydrogen-bond-donat-
ing cavity is designed to recognise anionic guest species
(Figure 1a). In contrast, cation binding at the macrocycleꢀs
calix[4]diquinone ether site is predicted to induce a dynamic
conformational change, whereby mutual electrostatic repul-
sion[11] results in the positively charged pyridinium group of
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817

P. D. Beer et al.
Scheme 3. Synthesis of a) calixquinone macrocycle 1 and b) bis-azide thread component 3·Cl.
and the electron-rich hydroqui-
none aromatic groups of the
macrocycle, and polarisation of
the chloride anion towards the
amide hydrogen-bond donors
of the macrocycle. Importantly,
splitting and upfield shifts of
the macrocycle hydroquinone
protons 7 and 8, due to p–p
stacking interactions between
the axle and macrocycle, can
clearly be seen, which is indica-
tive of rotaxane formation.
The [2]rotaxane 5·Cl was fur-
ther characterised by two-di-
mensional
NMR
1H–1H
spectroscopy
ROESY
in
[D6]acetone (Figure 3).[13]
Significant through-space in-
teractions between the pyridini-
um axle and the macrocycle are
observed, most notably be-
tween the hydroquinone pro-
tons 7 and 8 with the pyridini-
um protons b and the amide
protons d of the axle, diagnostic
of the effective p–p stacking in-
teractions between the aromatic
rings. The through-space inter-
actions confirm the conforma-
tional arrangement of the inter-
locked structure to be as postu-
lated. For example, inter-
action iii (b!13) shows the pyr-
idinium methyl group to reside
close to the quinone moiety of
the macrocycle, whilst interac-
Scheme 4. Synthesis of [2]rotaxane 5·Cl. TBTA=tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine.
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Anion Recognition and Cation-Induced Molecular Motion
FULL PAPER
The templating chloride anion was removed from the in-
terlocked cavity through repeated washing of a solution of
5·Cl in chloroform with aqueous NH4PF6 to form 5·PF6 in
65% yield. Evidence of successful anion exchange was ob-
tained from the appearance of characteristic signals in the
19F NMR spectrum and comparison of respective rotaxane
1
salt H NMR spectra (Figure 4).
Figure 2. Partial 1H NMR spectra in CD2Cl2/CD3CN (4:1) at 293 K of
a) stoppered axle fragment, b) [2]rotaxane 5·Cl and c) macrocycle 1.
Figure 4. Partial 1H NMR spectra of a) [2]rotaxane 5·Cl and b) [2]rotax-
ane 5·PF6, in CD2Cl2/CD3CN (4:1) at 293 K.
The observed upfield shifts of the protons involved in the
anion binding site (1, 4, d and c) are indicative of the remov-
al of the chloride anion from the three-dimensional inter-
locked cavity. In addition, the observed downfield shift and
decreased splitting of the hydroquinone protons 7 and 8 re-
flect a slight positional change of the axle within the macro-
cycle cavity. The large upfield shift of the pyridinium methyl
protons a (Dd=0.6 ppm) suggests the axle adopts a co-con-
formation in which it sits lower in the macrocyclic cavity,
causing protons a to experience a shielding effect possibly
arising from the aromatic ring currents of the hydroquinone
groups.
Further evidence of the axle adopting a lower position in
the macrocycle cavity upon anion exchange was obtained by
1H–1H ROESY NMR spectroscopy in [D6]acetone
(Figure 5).[13]
Through-space interactions between the internal isophthal-
amide proton 1 of the macrocycle and the pyridinium
proton c are observed, confirming the increased proximity
of these two moieties upon the removal of chloride. In addi-
tion, the through-space interactions observed between the
pyridinium axle component and the calix[4]diquinone ether
portion of the macrocycle in the ROESY spectrum of 5·Cl
are no longer present, reflecting the increased distance be-
tween them in 5·PF6.
1
Figure 3. Partial H–1H ROESY NMR of rotaxane 5·Cl in [D6]acetone at
293 K. Cross-couplings are shown in the schematic diagram above.
Anion and cation binding studies: Having successfully syn-
thesised the novel [2]rotaxane system 5·PF6 and established,
tion viii (h!5) reveals the triazole unit to be close to the
1
isophthalamide motif of the macrocycle.
by H–1H ROESY NMR spectroscopy, the symmetrical ar-
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P. D. Beer et al.
Anion binding properties of [2]rotaxane 5·PF6: With the
successful removal of the templating chloride anion from
the rotaxane, the anion binding properties of the vacant
three-dimensional interlocked cavity were investigated.
1
Anion H NMR spectroscopy titrations of 5·PF6 with a vari-
ety of tetrabutylammonium (TBA) salts were performed in
a 1:1 CDCl3/CD3OD solvent mixture.
Upon addition of excess amounts of Clꢀ, Brꢀ and AcOꢀ,
significant downfield shifts of the pyridinium proton c (Dd=
0.36, 0.30 and 0.35 ppm) and macrocycle isophthalamide
proton 1 (Dd=0.42, 0.37, and 0.15 ppm) were observed,
which is indicative of the anions binding within the rotaxane
cavity. Furthermore, significant splitting of the macrocycle
hydroquinone protons 7 and 8 and downfield shifts of the
pyridinium N-methyl protons a were also observed, suggest-
ing that, on anion complexation, the axle resumes its origi-
nal co-conformation identified in 5·Cl, with the pyridinium
group being positioned higher in the macrocyclic cavity and,
as a consequence, the N-methyl protons a are removed from
possible shielding effects arising from the aromatic ring cur-
rents of the hydroquinone groups (Figure 6).
Figure 5. Partial 1H–1H ROESY NMR of [2]rotaxane 5·PF6 in
[D6]acetone at 293 K. Cross-couplings are shown in the schematic dia-
gram above.
Figure 6. Partial 1H NMR spectra in CDCl3/CD3OD (1:1), 293 K of
a) 5·PF6, b) 5·PF6 +TBACl (1 equiv) and c) 5·PF6 +TBACl (5 equiv).
ꢀ
rangement of the interlocked positively charged pyridinium
axle within the macrocyclic cavity, we investigated the heter-
oditopic anion and cation binding properties of the rotaxane
system.
The rotaxaneꢀs unique interlocked pyridinium axle and
isophthalamide macrocycle hydrogen-bonding cavity is ex-
pected to have the capability of selectively binding anions of
complementary size and shape within the pseudotetrahedral
anion recognition site (Figure 1a).
In contrast, upon addition of H2PO4 anions, an upfield
shift of pyridinium proton c was observed. From this it can
be inferred that H2PO4 , possibly due to its large size, is
ꢀ
unable to penetrate the interlocked binding cavity and in-
stead associates on the periphery of the rotaxane cavity.
The respective 1:1 stoichiometric association constants Ka
were calculated from the titration data using
WinEQNMR[14] curve fitting software and are shown in
Figure 7 and Table 1.
The rotaxane system is also envisaged to have the capaci-
ty to bind cations at the calix[4]diquinone ether cation rec-
ognition site. It is further speculated that the mutual repul-
sion experienced between the complexed cation and the
positively charged pyridinium group of the axle component
would result in a shuttling motion where the pyridinium
motif is expelled from the macrocyclic cavity (Figure 1b).
As expected, the unique interlocked pyridinium axle and
isophthalamide macrocycle hydrogen-bonding cavity of ro-
taxane 5·PF6 exhibits selectivity for binding chloride, the
templating anion. Bromide is also bound strongly, whereas
weaker binding is observed with the more basic acetate and
dihydrogen phosphate anions. In spite of being bound exter-
1
nally, as evidenced from H NMR spectroscopy titration ex-
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Anion Recognition and Cation-Induced Molecular Motion
FULL PAPER
The cation binding properties of macrocycle 1 and rotax-
ane 5·PF6 were initially probed by UV-visible spectroscopic
analysis of the quinone n!p* absorption band. Quantitative
titrations were performed by using sodium, potassium and
ammonium salts with non-coordinating anions in a solution
of CH2Cl2/CH3CN (4:1); a system chosen for solubility rea-
sons. On addition of the cation guest species, significant
changes were observed in the absorption spectra of both the
macrocycle and the rotaxane (Figure 8).
Figure 7. Change in chemical shift of isophthalamide proton signal 1
upon addition of TBA salts to a 0.7 mm solution of rotaxane 5·PF6 in
CDCl3/CD3OD (1:1) at 293 K.
Table 1. Association constants, Ka, for binding of TBA salts of various
anions to rotaxane 5·PF6 in CDCl3/CD3OD (1:1) at 293 K (errors
<15%).
Figure 8. Observed n!p* absorbance response of a) macrocycle 1 and
b) rotaxane 5·PF6 on addition of NaClO4 (4 equiv) in CH2Cl2/CH3CN
(4:1) at 293 K.
Anion
logKa
Clꢀ
3.70
3.41
2.95
2.70
Brꢀ
ꢀ
H2PO4
By monitoring the absorbance response on the addition of
the cationic guests, 1:1 stoichiometric association constants
were calculated by using the SPECFIT programme.[16]
Table 2 shows that both macrocycle and rotaxane bind all
three cations with, in general, the alkali metal cations being
more strongly bound than ammonium. Importantly, the ro-
AcOꢀ
periments, the rotaxaneꢀs marginal preference for dihydro-
gen phosphate over acetate may reflect the anionꢀs ability to
hydrogen-bond donate to the rotaxane axleꢀs triazole nitro-
gen acceptor atoms. These results suggest that the rotaxane
host cavity is of a superior complementary shape and size
match for halides, in particular, chloride, over the non-spher-
ical oxoanions.
Table 2. Association constants, Ka, for binding of NaClO4, KPF6 and
NH4PF6 to rotaxane 5·PF6 and macrocycle 1 in CH2Cl2/CH3CN (4:1) at
293 K (errors <15%).
Cation
5·PF6 logKa
1 logKa
The rotaxaneꢀs efficacy of anion recognition behaviour is
further highlighted by macrocycle 2 displaying no evidence
of anion binding in this 1:1 CDCl3/CD3OD solvent mix-
ture,[12] whilst pyridinium axle components only weakly bind
halide anions.[8a]
Na+
3.30
3.36
2.70
4.48
4.58
4.48
K+
+
NH4
taxane cation binding association constant values are at
least an order of magnitude lower than those determined
for the macrocycle. The relatively weaker cation binding
properties of the rotaxane can be attributed to unfavourable
electrostatic repulsion and steric effects resulting from the
presence of the positively charged pyridinium axle compo-
nent.
Monovalent cation binding properties of [2]rotaxane 5·PF6:
Having established the rotaxane binds anions, we turned our
attention towards its ability to complex cations. Calix[4]di-
quinone polyether based receptors have previously been re-
ported to successfully bind Group I and II metal and ammo-
nium cations at the oxygen-rich lower rim of the quinone
moiety.[15] Therefore, the incorporation of such a calix[4]di-
quinone ether group into the macrocyclic component of the
rotaxane may result in its ability to bind cations. It was en-
visaged that the mutual repulsion arising between the bound
cationic guest and the positively charged pyridinium nitro-
gen of the axle component could lead to a structural dis-
placement of the rotaxane system with the pyridinium ring
being expelled from the macrocyclic cavity.
To gain more insight into the cation binding properties of
1
rotaxane 5·PF6, H NMR spectroscopy titrations were under-
taken with the same sodium, potassium and ammonium
salts. Addition of excess amounts of the cations resulted in
upfield shifts of the pyridinium N-methyl protons a (Dd=
0.21, 0.17 and 0.13 ppm) and the calix[4]diquinone methyl-
ene protons 13 (Dd=0.13, 0.14 and 0.14 ppm) (Figure 9 and
Figure S26 in the Supporting Information). These results
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P. D. Beer et al.
Comparison of the ROESY
spectra before and after the ad-
dition of five equivalents of
sodium cations show similar
through-space interactions exist
between the pyridinium axle
and the macrocycle. Important-
ly, after addition of sodium cat-
ions, through-space interactions
between the hydroquinone pro-
tons 7 and 8 and the N-methyl
pyridinium protons a and aro-
matic pyridinium protons b and
c are still observed, confirming
that the axle remains symmetri-
cally positioned within the mac-
rocyclic cavity, stabilised by p–
p stacking interactions between
the macrocycleꢀs hydroquinone
aromatic rings. It is noteworthy
that the axleꢀs positively
charged pyridinium group ap-
Figure 9. Change in chemical shift of proton 13 upon addition of monovalent cation salts to a 2 mm solution of
rotaxane 5·PF6 in CD2Cl2/CD3CN (4:1) at 293 K and NH4PF6 to rotaxane 5·PF6 in CD2Cl2/CD3CN (4:1), 293 K
(errors <10%).
suggest that binding of the cations within the rotaxane
cavity at the calix[4]diquinone ether cation recognition site
induces the pyridinium axle to reside lower in the macrocy-
clic cavity, causing N-methyl protons a to experience a
shielding effect possibly arising from the aromatic ring cur-
rents of the hydroquinone groups.
pears not to have been expelled from the rotaxane cavity
upon sodium cation binding.
Barium cation induced molecular motion: In the hope that
increasing the positive charge of the cation guest might
induce rotaxane molecular motion, the binding of the
barium dication by rotaxane 5·PF6 and macrocycle 1 was in-
vestigated.
Association constants were calculated from the titration
data (Figure 9 and Table 3) using WinEQNMR, by monitor-
ing one set of the calix[4]diquinone methylene protons 13.
The values obtained are in general agreement with the asso-
ciation constants derived from the UV-visible spectroscopic
titrations (Table 2) and show Na+ and K+ to be bound
The binding of Ba2+ to macrocycle 1 and rotaxane 5·PF6
was initially probed by UV-visible spectroscopic analysis of
the quinone n!p* absorption band. Quantitative titrations
were carried out with BaACHTNUGTRNEUGN(ClO4)2 and the respective 1:1 asso-
+
more strongly than the NH4 cation.
ciation constants were calculated by using the SPECFIT
programme (Table 4).
Table 3. Association constants, Ka, for binding of NaClO4, KPF6 and
NH4PF6 to rotaxane 5·PF6 in CD2Cl2/CD3CN (4:1), 293 K (errors
<10%).
Table 4. Association constants, Ka, for binding of BaACTHNUGTRNEUG(N ClO4)2 to rotaxane
5·PF6 and macrocycle 1 in various CH2Cl2/CH3CN mixtures at 293 K
(errors <15%).
Cation
logKa
Na+
3.64
3.58
2.90
CH2Cl2/CH3CN
5·PF6 logKa
1 logKa
K+
4:1
1:1
>6
4.26
>6
5.10
+
NH4
Both macrocycle and rotaxane form very stable com-
plexes with divalent Ba2+ ions in the original solvent
system, CH2Cl2/CH3CN (4:1), in fact too strong to be relia-
bly quantified by the SPECFIT computer programme.
Therefore, analogous titrations were carried out in the more
competitive 1:1 CH2Cl2/CH3CN solvent system. Even in this
solvent mixture, the association constants for the binding of
Ba2+ to each receptor are much larger than those deter-
mined for the binding of the monovalent cations in CH2Cl2/
CH3CN (4:1) (Table 2). In agreement with the association
constants derived from the UV-visible titrations with mono-
valent cations, macrocycle 1 is found to bind Ba2+ more ef-
Aside from the perturbation of the protons directly in-
volved in the cation recognition site (a and 13), 1H NMR
spectroscopic analysis provided no indication of any major
co-conformational change occurring within the interlocked
rotaxane structure on complexation of the cationic guest
species. The spectrum of 5·PF6 remained largely unchanged
on addition of the monovalent salts.
Further investigations into the three-dimensional struc-
ture of rotaxane 5·PF6 on addition of Na+ cations were car-
1
ried out by using H–1H ROESY NMR spectroscopy experi-
ments (Figure S23 in the Supporting Information).
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Anion Recognition and Cation-Induced Molecular Motion
FULL PAPER
fectively than rotaxane 5·PF6 because of unfavourable elec-
trostatic and steric effects.
Further evidence of barium cation induced molecular dis-
placement of the pyridinium axle was provided by the
1H–1H ROESY NMR spectrum of rotaxane of 5·PF6 after
To investigate the binding of Ba2+ within the rotaxane
cavity further, and its potential to induce molecular motion,
1H NMR spectroscopy titrations were performed in CD2Cl2/
CD3CN (4:1). In contrast to the results obtained on addition
of monovalent cations, the addition of divalent Ba2+ cations
to a solution of rotaxane 5·PF6, resulted in significant
addition of Ba
(Figure 11).
ACHTUNGNERTN(NUG ClO4)2 (3 equiv) in CD2Cl2/CD3CN (4:1)
Comparison of the ROESY spectra obtained before and
after the addition of barium cations show contrasting
through-space interactions exist between the pyridinium
axle and the macrocycle. Importantly, on complexation of
Ba2+ cations, cross-coupling interactions can be seen be-
tween one triazole proton h and the macrocycle internal iso-
phthalamide proton 1, and amide protons 4. These interac-
tions confirm the cation-induced expulsion of the pyridinium
motif and reveal a triazole unit to reside within the macro-
cyclic cavity instead. The position of the penetrated triazole
1
changes to the H NMR spectra of the rotaxane (Figure S27
in the Supporting Information).
1H NMR spectroscopic analysis of an equimolar solution
of BaACHTUNGTRENNUNG(ClO4)2 and rotaxane 5·PF6 revealed large upfield
shifts of the axle methylene protons e and f, and downfield
shifts of the macrocycle hydroquinone protons 7 and 8.
These observed changes reveal the association of the barium
cation at the calix[4]diquinone recognition site has a far
greater effect on the co-conformation of the interlocked
system.
On addition of excess barium cations, significant splitting
of notably the aliphatic axle protons e, f, g and i, and the tri-
azole protons h was observed. These signals, representing
ꢀ
ꢀ
ꢀ
ꢀ
pairs of CH2 , and CH groups of the axle related by
symmetry in the structure of 5·PF6, generate two distinct sig-
nals on complexation of Ba2+, indicative of the desymmetri-
sation of the rotaxane structure. The chemical inequivalence
of the two axle arms reveals a positional change of the
threaded component within the macrocyclic cavity, suggest-
ing the higher charge density of the doubly charged Ba2+
cation, with respect to the monovalent cations, bound within
the host cavity, is sufficient to displace the positively
charged pyridinium ring from its symmetrical, ꢂstackedꢀ ar-
rangement between the hydroquinone groups of the macro-
cycle.
1
The H NMR spectrum of the 3:1 mixture of Ba
N
and rotaxane 5·PF6 was fully assigned by using gCOSY,
HSQC and HMBC NMR spectroscopic investigations
(Figure 10).
Figure 11. 1H–1H ROESY NMR of rotaxane 5·PF6 with of Ba
ACHTUNGTRENNUNG(ClO4)2
(3 equiv) in CD2Cl2/CD3CN (4:1) at 293 K. Cross-couplings are shown in
the schematic diagram above.
1
Figure 10. Partial H NMR spectra of rotaxane 5·PF6 after addition of Ba-
ACHTUNGTRENNUNG(ClO4)2 (3 equiv) in CD2Cl2/CD3CN (4:1) at 293 K.
Chem. Eur. J. 2011, 17, 816 – 825
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P. D. Beer et al.
group allows it, in principle, to coordinate to the bound
Ba2+ cation through the basic nitrogen atom present in the
motif providing an extra stabilising interaction.[6b,17]
Experimental Section
General: All solvents and reagents were purchased from commercial sup-
pliers and used as received unless otherwise stated. Dry solvents were ob-
tained by purging with nitrogen and then passing through an MBraun
MPSP-800 column. H2O was deionised and microfiltered by using a
Milli-Q Millipore machine. Et3N was distilled and stored over KOH.
TBA salts were stored in a vacuum desiccator containing phosphorus
pentoxide prior to use. 1H, 13C, 19F and 31P NMR spectra were recorded
on a Varian Mercury-VX 300, a Varian Unity Plus 500 or a Bruker
AVII500 spectrometer with cryoprobe at 293 K. Chemical shifts are
quoted in parts per million relative to the residual solvent signal. Mass
spectra were obtained by using a Micromass GCT (EI) instrument, a Mi-
cromass LCT (ESMS) instrument or a Maldi Micro MX instrument.
Electronic absorption spectra were recorded on a PG T60 U spectropho-
tometer. Microwave reactions were carried out by using a Biotage Initia-
tor 2.0 microwave. Melting points were recorded on a Gallenkamp capil-
lary melting point apparatus and are uncorrected.
Reversing the cation-induced molecular motion: With the
ambitious target of cation-induced molecular motion real-
ised, investigations turned towards the potential switchable
1
nature of the interlocked molecular shuttle. H NMR spec-
troscopy titrations of a 3:1 mixture of BaACHTNURTGNEUNG(ClO4)2 and rotax-
ane 5·PF6 in CD2Cl2/CD3CN (4:1) were performed by using
(TBA)2SO4, with the aim of extracting Ba2+ from the inter-
locked host cavity through precipitation of BaSO4 (Fig-
ure S28 in the Supporting Information). Upon addition of
2ꢀ
SO4 (3 equiv), the splitting of the aliphatic proton groups i
and e, caused by the desymmetrisation of the rotaxane struc-
1
ture, was no longer observed and the H NMR spectrum ob-
[2]Rotaxane 5·Cl: A mixture of 3·Cl (0.013 g, 0.034 mmol), 6 (0.033 g,
0.068 mmol), 1 (0.030 g, 0.029 mmol) and TBTA (0.003 g, 0.005 mmol) in
CH2Cl2 (2 mL) was degassed via a freeze–pump–thaw method. Under a
tained resembles that of the ꢂfreeꢀ rotaxane 5·PF6. This indi-
cates that the Ba2+ cations have been removed from the cal-
ix[4]diquinone ether cation recognition site, allowing the
positively charged axle to subsequently resume its original,
symmetrical position within the macrocyclic cavity. These re-
sults suggest that the rotaxane structure can be switched re-
versibly between two positional isomers by the addition and
subsequent removal of barium cations.
nitrogen atmosphere, [CuACTHNUTRGNEUNG(CH3CN)4]PF6 (0.002 g, 0.005 mmol) was added
and the mixture was stirred at room temperature overnight. The solvent
was then removed in vacuo and the crude reaction mixture was purified
by silica gel preparative TLC (EtOAc/MeOH 95:5) to give 5·Cl as a
yellow solid (0.022 g, 0.009 mmol, 31%). 1H NMR (500 MHz,
[D6]acetone): d=9.73 (s, 1H), 9.42 (s, 1H), 9.21 (s, 2H), 8.90 (s, 2H),
8.70 (s, 2H), 8.20 (d, J=7.9 Hz, 2H), 8.16 (s, 2H), 7.60 (t, J=7.9 Hz,
1H), 7.32–6.94 (m, 42H), 6.49 (d, J=8.8 Hz, 4H), 6.29 (d, J=8.8 Hz,
4H), 5.51 (s, 3H), 5.18 (s, 4H), 4.51 (d, J=12.9 Hz, 4H), 4.40 (t, J=
7.3 Hz, 4H), 4.34 (s, 4H), 4.11 (s, 4H), 4.01 (s, 4H), 3.79 (s, 4H), 3.39 (s,
4H), 3.32 (d, J=12.9 Hz, 4H), 2.20–2.18 (m, 4H), 1.30 (s, 36H),
1.11 ppm (s, 18H); 13C NMR (125 MHz, [D6]acetone): d=189.3, 186.5,
166.5, 161.0, 157.6, 154.3, 154.1, 153.1, 150.2, 149.2, 148.3, 146.9, 146.7,
145.1, 144.4, 140.4, 136.8, 134.9, 133.6, 133.1, 132.9, 132.4, 131.8, 131.5,
130.8, 129.9, 128.3, 126.7, 125.2, 124.6, 115.1, 114.4, 74.6, 68.5, 66.1, 64.3,
62.4, 52.0, 48.5, 42.1, 37.9, 34.9, 34.7, 31.7, 31.1 ppm; ESI-HRMS: m/z
calcd for C150H160N11O16: 2371.2039 [MꢀCl]+; found: 2371.1930.
Conclusion
A rare example of a heteroditopic [2]rotaxane system has
been prepared through a chloride anion templated click
stoppering synthetic methodology. By virtue of the inter-
locked structure consisting of a calix[4]diquinone–isophthal-
[2]Rotaxane 5·PF6: A solution of 5·Cl (0.02 g, 0.008 mmol) in chloroform
(2 mL) was repeatedly washed with a 0.1m aqueous solution of NH4PF6
(10ꢃ1 mL) and water (10ꢃ1 mL). The solvent was then removed in
vacuo to give the product as a yellow solid (0.013 g, 0.005 mmol, 65%).
1H NMR (500 MHz, [D6]acetone): d=9.19 (s, 1H), 9.06 (s, 2H), 8.74 (s,
1H), 8.58 (s, 2H), 8.11–8.08 (m, 6H), 7.58 (t, J=7.7 Hz, 1H), 7.33–6.97
(m, 42H), 6.58 (s, 8H), 5.18 (s, 4H), 4.95 (s, 3H), 4.51 (d, J=6.6 Hz,
4H), 4.25–4.21 (m, 8H), 4.07–4.03 (m, 8H), 3.79–3.78 (m, 4H), 3.55–3.51
(m, 4H), 3.42 (d, J=12.9 Hz, 4H), 2.29–2.26 (m, 4H), 1.31 (s, 36H),
1.16 ppm (s, 18H); 13C NMR (125 MHz, [D6]acetone): d=190.1, 186.8,
167.8, 161.2, 157.5, 154.7, 153.9, 153.4, 149.7, 149.3, 148.3, 147.1, 145.9,
145.1, 144.6, 141.0, 140.5, 138.5, 135.9, 134.7, 133.4, 132.9, 131.5, 131.4,
130.4, 129.8, 129.7, 129.1, 128.3, 127.6, 126.7, 126.1, 125.2, 125.0, 116.1,
115.3, 114.4, 73.9, 68.7, 67.7, 64.4, 62.3, 51.3, 48.5, 40.6, 38.7, 34.9, 34.7,
31.8, 31.7 ppm; 19F NMR (282 MHz, [D6]acetone): d=ꢀ72.6 ppm (d, J=
708 Hz); ESI-HRMS: m/z calcd for C150H160N11O16: 2371.2039 [MꢀPF6]+;
found: 2371.2007.
ACHTUNGTRENNUNGamide macrocycle and 3,5-bis-amide pyridinium axle compo-
nents, the rotaxane exhibits anion and cation recognition
properties, and is capable of utilising cation–cation electro-
static repulsion to stimulate shuttling behaviour. 1H NMR
spectroscopy anion titration studies reveal the interlocked
orthogonal three-dimensional pyridinium axle–isophthal-
amide macrocycle hydrogen-bonding cavity binds chloride
and bromide more strongly than basic oxoanions, acetate
and dihydrogen phosphate. The rotaxane also very strongly
binds the barium dication and monocations, sodium, potassi-
um and ammonium, at the oxygen-rich calix[4]diquinone
ether recognition site, as evidenced by UV-visible spectro-
scopic and 1H NMR titration investigations. Whereas the
monocations are bound without causing significant co-con-
formational structural change of the rotaxane, barium cation
complexation effects a molecular displacement of the axleꢀs
positively charged pyridinium group from the rotaxaneꢀs
macrocyclic cavity by mutual electrostatic repulsion. The
barium cation induced rotaxane shuttling motion is reversed
on addition of tetrabutylammonium sulfate.
Acknowledgements
We thank the EPSRC for a postdoctoral fellowship (EP/E033962/1)
(A.V.L.).
[1] For reviews, see a) K. Konstas, S. J. Langford, M. J. Latter, Int. J.
Mol. Sci. 2010, 11, 2453–2472; b) V. Balzani, A. Credi, M. Venturi,
Chem. Soc. Rev. 2009, 38, 1542–1550; c) E. R. Kay, D. A. Leigh,
Pure Appl. Chem. 2008, 80, 17–29; d) A. Rescifina, C. Zagni, D.
824
www.chemeurj.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 816 – 825

Anion Recognition and Cation-Induced Molecular Motion
FULL PAPER
Iannazzo, P. Merino, Curr. Org. Chem. 2009, 13, 448–481; e) B. H.
Northrop, A. B. Braunschweig, P. M. Mendes, W. R. Dichtel, J. F.
Stoddart in Handbook of Nanoscience Engineering and Technology,
2nd ed. (Eds.: W. A. Goddard III, D. W. Brenner, S. E. Lyshevski,
G. J. Iafrate), CRC Press, Boca Raton, 2007, Ch. 11, pp. 1–48;
f) E. R. Kay, D. A. Leigh, F. Zerbetto, Angew. Chem. 2007, 119, 72–
196; Angew. Chem. Int. Ed. 2007, 46, 72–191.
116, 1242–1244; Angew. Chem. Int. Ed. 2004, 43, 1222–1224;
k) B. W. Laursen, S. Nygaard, J. O. Jeppesen, J. F. Stoddart, Org.
Lett. 2004, 6, 4167–4170.
[7] a) X. Wang, J. Zhu, D. B. Smithrud, J. Org. Chem. 2010, 75, 3358–
3370; b) M. J. Barrell, D. A. Leigh, P. J. Lusby, A. M. Z. Slawin,
Angew. Chem. 2008, 120, 8156–8159; Angew. Chem. Int. Ed. 2008,
47, 8036–8039; c) M. J. Deetz, R. Shukla, B. D. Smith, Tetrahedron
2002, 58, 799–805.
[8] a) A. J. McConnell, C. J. Serpell, A. L. Thompson, D. R. Allan, P. D.
Beer, Chem. Eur. J. 2010, 16, 1256–1264; b) L. M. Hancock, P. D.
Beer, Chem. Eur. J. 2009, 15, 42–44; c) M. D. Lankshear, P. D. Beer,
Coord. Chem. Rev. 2006, 250, 3142–3160; d) M. R. Sambrook, P. D.
Beer, J. A. Wisner, R. L. Paul, A. R. Cowley, F. Szemes, M. G. B.
Drew, J. Am. Chem. Soc. 2005, 127, 2292–2302.
[9] a) M. D. Lankshear, I. M. Dudley, K.-M. Chan, A. R. Cowley, S. M.
Santos, V. Felix, P. D. Beer, Chem. Eur. J. 2008, 14, 2248–2263;
b) M. D. Lankshear, I. M. Dudley, K.-M. Chan, P. D. Beer, New J.
Chem. 2007, 31, 684–690; c) M. D. Lankshear, A. R. Cowley, P. D.
Beer, Chem. Commun. 2006, 612–614.
[10] a) K. D. Hꢅnni, D. A. Leigh, Chem. Soc. Rev. 2010, 39, 1240–1251;
b) M. Bria, J. Bigot, G. Cooke, J. Lyskawa, G. Rabani, V. M. Rotello,
P. Woisel, Tetrahedron 2009, 65, 400–407.
[2] a) Q. Li, W. Zhang, O. S. Miljani, C. B. Knobler, J. F. Stoddart, O. M.
Yaghi, Chem. Commun. 2010, 46, 380–382; b) A. Coskun, P. J.
Wesson, R. Klajn, A. Trabolsi, L. Fang, M. A. Olson, S. K. Dey,
B. A. Grzybowski, J. F. Stoddart, J. Am. Chem. Soc. 2010, 132, 4310–
4320; c) D. Li, W. F. Paxton, R. H. Baughman, T. J. Huang, J. F.
Stoddart, P. S. Weiss, MRS Bull. 2009, 34, 671–681; d) S. Silvi, M.
Venturi, A. Credi, J. Mater. Chem. 2009, 19, 2279–2294; e) E. Coro-
nado, P. Gavina, S. Tatay, Chem. Soc. Rev. 2009, 38, 1674–1689.
[3] a) J. J. Davis, G. A. Orlowski, H. Rahman, P. D. Beer, Chem.
Commun. 2010, 46, 54–63; b) M. J. Chmielewski, J. J. Davis, P. D.
Beer, Org. Biomol. Chem. 2009, 7, 415–424.
[4] a) J.-P. Sauvage, J.-P. Collin, S. Durot, J. Frey, V. Heitz, A. Sour, C.
Tock, C. R. Chim. 2010, 13, 315–328; b) S.-Y. Hsueh, C.-C. Lai, S.-
H. Chiu, Chem. Eur. J. 2010, 16, 2997–3000; c) M. Chen, S. Han, L.
Jiang, S. Zhou, F. Jiang, Z. Xu, J. Liang, S. Zhang, Chem. Commun.
2010, 46, 3932–3934; d) J.-C. Chambron, M. Meyer, Chem. Soc. Rev.
2009, 38, 1663–1673; e) D. A. Leigh, P. J. Lusby, A. M. Z. Slawin,
D. B. Walker, Angew. Chem. 2005, 117, 4633–4640; Angew. Chem.
Int. Ed. 2005, 44, 4557–4564; f) G. Kaiser, T. Jarrosson, S. Otto, Y.-
F. Ng, A. D. Bond, J. K. M. Sanders, Angew. Chem. 2004, 116, 1993–
1996; Angew. Chem. Int. Ed. 2004, 43, 1959–1962; g) T. Iijima, S. A.
Vignon, H.-R. Tseng, T. Jarrosson, J. K. M. Sanders, F. Marchioni,
M. Venturi, E. Apostoli, V. Balzani, J. F. Stoddart, Chem. Eur. J.
2004, 10, 6375–6392.
[11] a) S. Nygaard, Y. Liu, P. C. Stein, A. H. Flood, J. O. Jeppesen, Adv.
Funct. Mater. 2007, 17, 751–762; b) M. J. Gunter, Eur. J. Org. Chem.
2004, 1655–1673; c) M. Asakawa, P. R. Ashton, V. Balzani, S. E.
Boyd, A. Credi, G. Mattersteig, S. Menzer, M. Montalti, F. M.
Raymo, C. Ruffilli, J. F. Stoddart, M. Venturi, D. J. Williams, Eur. J.
Org. Chem. 1999, 985–994; d) M. J. Gunter, M. R. Johnston,
Chem. Soc. Chem. Commun. 1994, 829–830.
J
[12] M. D. Lankshear, N. H. Evans, S. R. Bayly, P. D. Beer, Chem. Eur. J.
2007, 13, 3861–3870.
[5] a) A. Brown, K. M. Mullen, J. Ryu, M. J. Chmielewski, S. M. Santos,
V. Felix, A. L. Thompson, J. E. Warren, S. I. Pascu, P. D. Beer, J.
Am. Chem. Soc. 2009, 131, 4937–4952; b) M. D. Lankshear, P. D.
Beer, Acc. Chem. Res. 2007, 40, 657–668; c) M. J. Gunter, S. M. Far-
quhar, K. M. Mullen, New J. Chem. 2004, 28, 1443–1449; d) G. M.
Hꢄbner, C. Reuter, C. Seel, F. Vogtle, Synthesis 2000, 103–108;
e) A. Andrievsky, F. Ahuis, J. L. Sessler, F. Vçgtle, D. Gudat, M.
Moini, J. Am. Chem. Soc. 1998, 120, 9712–9713.
[6] For selected examples of cation-switchable catenanes and rotaxanes,
see a) G. J. E. Davidson, S. Sharma, S. J. Loeb, Angew. Chem. Int.
Ed. 2010, 49, 4938–4942; b) J. D. Crowley, S. M. Goldup, A.-L. Lee,
D. A. Leigh, R. T. McBurney, Chem. Soc. Rev. 2009, 38, 1530–1541;
c) D. S. Marlin, D. G. Cabrera, D. A. Leigh, A. M. Z. Slawin, Angew.
Chem. 2006, 118, 83–89; Angew. Chem. Int. Ed. 2006, 45, 77–83;
d) D. A. Leigh, P. J. Lusby, A. M. Z. Slawin, D. B. Walker, Chem.
Commun. 2005, 4919–4921; for selected examples of anion-switcha-
ble catenanes and rotaxanes, see e) J. J. Gassensmith, S. Matthys, J.-
J. Lee, A. Wojcik, P. V. Kamat, B. D. Smith, Chem. Eur. J. 2010, 16,
2916–2921; f) T.-C. Lin, C.-C. Lai, S.-H. Chiu, Org. Lett. 2009, 11,
613–616; g) K.-Y. Ng, V. Felix, S. M. Santos, N. H. Rees, P. D. Beer,
Chem. Commun. 2008, 1281–1283; h) Y.-L. Huang, W.-C. Hung, C.-
C. Lai, Y.-H. Liu, S.-M. Peng, S.-H. Chiu, Angew. Chem. 2007, 119,
6749–6753; Angew. Chem. Int. Ed. 2007, 46, 6629–6633; i) C.-F. Lin,
C.-C. Lai, Y.-H. Liu, S.-M. Peng, S.-H. Chiu, Chem. Eur. J. 2007, 13,
4350–4355; j) C. M. Keaveney, D. A. Leigh, Angew. Chem. 2004,
[13] The 2D ROESY NMR spectra (Figures 3 and 5) recorded in
[D6]acetone were found to be of superior quality than analogous
spectra recorded in CD2Cl2/CD3CN (4:1). Also precipitation prob-
lems were encountered when undertaking cation and anion binding
studies in [D6]acetone.
[14] M. J. Hynes, J. Chem. Soc. Dalton Trans. 1993, 311–312.
[15] a) P. R. A. Webber, P. D. Beer, G. Z. Chen, V. Felix, M. G. B. Drew,
J. Am. Chem. Soc. 2003, 125, 5774–5785; b) P. R. A. Webber, A.
Cowley, P. D. Beer, Dalton Trans. 2003, 3922–3926; c) T. D. Chung,
J. Park, J. Kim, H. Lim, M. J. Choi, J. R. Kim, S. K. Chang, H. Kim,
Anal. Chem. 2001, 73, 3975–3980; d) A. Casnati, R. Ungaro in Cal-
ixarenes in Action (Eds: L. Mandolini, R. Ungaro), Imperial College
Press, London, 2000, pp. 62–84; e) M. Gꢆmez-Kaifer, P. A. Reddy,
C. D. Gutsche, L. Echegoyen, J. Am. Chem. Soc. 1997, 119, 5222–
5229; f) T. D. Chung, S. K. Kang, J. Kim, H.-s. Kim, H. Kim, J. Elec-
troanal. Chem. 1997, 438, 71–78; g) T. D. Chung, D. Choi, S. K.
Kang, S. K. Lee, S.-K. Chang, H. Kim, J. Electroanal. Chem. 1995,
396, 431–439.
[16] SPECFIT n. 2.02, Spectrum Software Associates, Chapel Hill, NC
(USA), 1993.
[17] H. Zheng, W. Zhou, J. Lv, X. Yin, Y. Li, H. Liu, Y. Li, Chem. Eur. J.
2009, 15, 13253–13262.
Received: August 19, 2010
Published online: November 24, 2010
Chem. Eur. J. 2011, 17, 816 – 825
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