Sodium and barium cation-templated synthesis and cation-induced molecular pirouetting of a pyridine N-oxide containing [2]rotaxane

Article abstract of DOI:10.1039/c1cc11224d

Sodium and barium metal cation templation has been used to construct a novel pyridine N-oxide containing [2]rotaxane. Upon addition and removal of metal cations, the macrocyclic component is observed to undergo a pirouetting motion around the pyridine N-oxide axle.

Full text of DOI:10.1039/c1cc11224d

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COMMUNICATION
Sodium and barium cation-templated synthesis and cation-induced
molecular pirouetting of a pyridine N-oxide containing [2]rotaxanewz
Laura M. Hancock and Paul D. Beer*
Received 1st March 2011, Accepted 22nd March 2011
DOI: 10.1039/c1cc11224d
Sodium and barium metal cation templation has been used to
construct a novel pyridine N-oxide containing [2]rotaxane.
Upon addition and removal of metal cations, the macrocyclic
component is observed to undergo a pirouetting motion around
the pyridine N-oxide axle.
Motivated by the potential dynamic function of mechanically
interlocked molecules for molecular switching and machine-like
nanotechnological applications,1 the development of new
Scheme 1 Schematic representation of cation-induced molecular
innovative strategic routes for their construction is of intense
current research interest.2 Although transition metal cation
templates have been impressively utilised in the synthesis of
rotaxanes and catenanes,3 the exploitation of alkali and alkaline
earth metal cations as potential templating reagents for inter-
locked molecular assembly remains largely underdeveloped.4
We have recently reported a heteroditopic calix[4]diquinone
macrocycle 1 which is capable of strongly binding group 1 and
2 metal cations at the calix[4]diquinone recognition site
and anions at the isophthalamide motif.5 By integrating an
appropriate ligating motif designed to complex hard metal
cations into an axle component, we describe herein the sodium
and barium cation-templated synthesis of a novel pyridine
N-oxide containing [2]rotaxane which exhibits cation-induced
dynamic molecular pirouetting behaviour. The pyridine
N-oxide axle component serves to satisfy the coordination
sphere of a metal cation complexed by the rotaxane’s
calix[4]diquinone macrocycle, and upon removal of the metal
cation, the macrocycle undergoes molecular rotation about the
axle, driven by favourable hydrogen bonding interactions
between the pyridine N-oxide’s oxygen dipole and the
isophthalamide group of the macrocycle (Scheme 1).
pirouetting.
barium as both are known to form strong complexes with
macrocycle 1.5 A Huisgen 1,3-dipolar cycloaddition stoppering
reaction was used to prepare the rotaxane. DIPEA and
Cu(MeCN)4PF6 were added to an equimolar CH2Cl2 solution
of macrocycle 1, pyridine N-oxide axle precursor 2, alkyne
stopper
3 and metal cation perchlorate salt. Following
preparative TLC purification, rotaxane 4 was isolated in 50%
and 28% yields using sodium and barium cations respectively.
An analogous synthetic procedure in the absence of metal
cation afforded the rotaxane in only 10% yield which highlights
the effective templating roles both sodium and barium cations
play in rotaxane formation.
The new [2]rotaxane was characterised by 1H NMR, 13C NMR
1
and ESMS. The H NMR spectra of rotaxane samples isolated
from reactions in the presence and absence of cations were shown
to be identical which indicates that the cationic template had been
removed during chromatographic purification. The 1H NMR
spectrum of rotaxane 4, along with the spectra of component
macrocycle 1 and axle for comparison is shown in Fig. 1.
The 1D 1H NMR spectrum of the rotaxane provides evidence
for p–p stacking between the macrocycle’s electron rich
hydroquinone and axle electron deficient pyridine N-oxide
aromatic surfaces, as signified by upfield shifts of hydroquinone
protons g and h, and pyridine protons b and g compared to
their component parts. Importantly, signals corresponding to
macrocycle amide d and cavity c protons are observed to have
shifted significantly downfield in the rotaxane which implies
that the pyridine N-oxide oxygen dipole is bound in the
isophthalamide cleft of the macrocycle.6
The metal cation-templated synthesis of target rotaxane 4
was carried out according to Scheme 2. The cations chosen to
template interlocked structure formation were sodium and
Chemistry Research Laboratory, Department of Chemistry, University
of Oxford, Mansfield Road, Oxford, OX1 3TA, UK.
E-mail: paul.beer@chem.ox.ac.uk; Fax: +44 (0)1865 272960;
Tel: +44 (0)1865 285182
w This article is part of a ChemComm ‘Supramolecular Chemistry’
web-based themed issue marking the International Year of Chemistry
2011.
The position of the macrocycle in relation to the pyridine
N-oxide axle component was verified by 2D ROESY NMR
(Fig. 2). Expected correlations 1 (b1 - g,h), 2 (g - g,h) and
3 (e2 - g,h) were observed between macrocycle hydroquinone
z Electronic supplementary information (ESI) available: Synthesis, 1H
and 13C NMR spectra of compounds 2 and 4. 1H NMR spectra of
4 + 1 eq. Ba(ClO4)2 + 1 eq. (TBA)2SO4. See DOI: 10.1039/c1cc11224d
c
6012 Chem. Commun., 2011, 47, 6012–6014
This journal is The Royal Society of Chemistry 2011

Fig. 1 Partial 1H NMR (300 MHz) spectra in CDCl3 at 293 K of (a)
component axle, (b) rotaxane 4 and (c) macrocycle 1.
1
Fig. 2 Partial H–1H ROESY spectrum (500 MHz) of [2]rotaxane 4
in CDCl3 at 293 K. Cross couplings are shown in the schematic
diagram below.
templating effect operates via a pseudorotaxane assembly
where the pyridine N-oxide motif of the axle precursor
coordinates to the macrocycle calix[4]diquinone bound metal
cation. With this in mind it was of interest to investigate whether
metal cation addition to rotaxane 4 would induce a 1801 rotation
of the macrocycle whereby the axle pyridine N-oxide is displaced
from hydrogen bonding to the isophthalamide cleft by complexing
to the metal cation bound by the macrocycle calix[4]diquinone
unit (Scheme 1).
Scheme 2 Synthesis of rotaxane 4.
protons and protons in the vicinity of the pyridine N-oxide
motif. Importantly, interaction 4 (b2 - d) indicates that the axle
pyridine N-oxide oxygen is pointing into the isophthalamide
cleft confirming observations from the 1D 1H NMR spectrum.
The significant improvement of rotaxane yield, of up to five
times with sodium cations, suggests that this metal cation
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 6012–6014 6013

Notes and references
1 V. Balzani, M. Venturi and A. Credi, Molecular Devices and
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2 For some recent reviews of various strategies to mechanically
interlocked structure formation, see: M. D. Lankshear and
P. D. Beer, Acc. Chem. Res., 2007, 40, 657; M. S. Vickers and
P. D. Beer, Chem. Soc. Rev., 2007, 36, 211; W. R. Dichtel, O.
S. Miljanic, W. Zhang, J. M. Spruell, K. Patel, I. Aprahamian,
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J. R. Heath and J. F. Stoddart, Acc. Chem. Res., 2008, 41, 1750;
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3 J. P. Sauvage, Acc. Chem. Res., 1990, 23, 319; J. C. Chambron,
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D. Pomeranc and J. P. Sauvage, Eur. J. Org. Chem., 2004, 1627;
Fig. 3 Partial 1H NMR (500 MHz) spectra in 5 : 1 CDCl3/CD3CN at
293 K of (a) rotaxane 4 + 1 eq. Ba(ClO4)2, (b) rotaxane 4 and
(c) rotaxane 4 + 1 eq. NaClO4.
Proton NMR spectra of the rotaxane in CDCl3 were
recorded in the presence of one equivalent of Ba(ClO4)2 and
NaClO4 (Fig. 3).
C. A. Schalley, F. Vogtle, K. H. Dotz, F. Arico, J. D. Badjic,
´
¨
¨
Chemical shift perturbations of a number of protons in the
rotaxane are observed upon addition of both cations. Notably
macrocycle amide proton d is observed to move significantly
upfield indicating that the axle pyridine N-oxide motif is no longer
bound in the macrocycle’s isophthalamide cleft. In addition,
increased splitting of the macrocycle hydroquinone protons g
and h is observed indicating an alternative position of the axle
pyridine N-oxide unit between the hydroquinone surfaces.7 The
majority of protons in the vicinity of the pyridine N-oxide motif
were also observed to shift upfield implying that they now reside
in a different environment. All metal cation induced chemical shift
perturbations noted above are indicative of the macrocycle
undergoing a 1801 rotation to enable the axle pyridine N-oxide
to coordinate to the calix[4]diquinone bound metal cation.8
It was possible to reverse the barium cation-induced
pirouetting motion by addition of one equivalent of (TBA)2-
SO4, whereby BaSO4 precipitated. Following removal of
barium cations, the perturbed proton signals all reverted back
to their original chemical shift positions (see ESIz). In parti-
cular, a downfield shift of amide proton d implies that the axle
pyridine N-oxide oxygen is again hydrogen bonded to the
macrocycle isophthalamide unit.
S. J. Cantrill, A. H. Flood, K. C. F. Leung, Y. Liu and
J. F. Stoddart, in Templates in Chemistry II, Springer, Berlin/
Heidelberg, 2005, pp. 227–240; J. D. Crowley, S. M. Goldup,
A.-L. Lee, D. A. Leigh and R. T. McBurney, Chem. Soc. Rev.,
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4 S. L. Castro, O. Just and W. S. Rees Jr., Angew. Chem., Int. Ed.,
2000, 39, 933–935; G. Kaiser, T. Jarrosson, S. Otto, Y.-F. Ng,
A. D. Bond and J. K. M. Sanders, Angew. Chem., Int. Ed., 2004,
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5 A. V. Leontiev, C. A. Jemmett and P. D. Beer, Chem.–Eur. J.,
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6 Hydrogen bonding interactions of pyridine N-oxide with
isophthalamide protons is a known phenomenon: M. Chen,
S. Han, L. Jiang, S. Zhou, F. Jiang, Z. Xu, J. Liang and
S. Zhang, Chem. Commun., 2010, 46, 3932.
7 The difference in chemical shift perturbations of rotaxane
hydroquinone protons g, h upon addition of barium and sodium
is attributed to the difference in ionic radii of the two cations
causing the pyridine N-oxide axle to adopt a slightly different
position between the hydroquinone units.
8 2D ROESY NMR of rotaxane 4 upon addition of sodium and
barium cations revealed expected interactions between pyridine
N-oxide and hydroquinone protons (b - g,h). However, it was
difficult to elucidate any other through space cross coupling
interactions due to the overlap of a number of peaks in the 1D
1H NMR spectrum.
9 Hoffart and Loeb have used pyridine N-oxide at the termini of
rotaxanes for the construction of MOFs: D. J. Hoffart and
S. J. Loeb, Angew. Chem., Int. Ed., 2005, 44, 901; D. J. Hoffart
and S. J. Loeb, Supramol. Chem., 2007, 19, 89.
10 Leigh et al. have used nitrone in rotaxane templation:
D. M. D’Souza, D. A. Leigh, L. Mottier, K. M. Mullen,
F. Paolucci, S. J. Teat and S. Zhang, J. Am. Chem. Soc., 2010,
132, 9465.
In conclusion, we have exploited the strong interaction of
alkali metal cations with both macrocycle calix[4]diquinone and
pyridine N-oxide to template the formation of a [2]rotaxane. To
the best of our knowledge, this is the first example of using the
pyridine N-oxide motif in the templated construction of an
interlocked structure,9,10 and represents one of the very few alkali
metal cation-templated rotaxanes reported to date. We have also
shown that the rotaxane undergoes a rare pirouetting molecular
motion11 upon addition and removal of sodium and barium
cations.4 The design and synthesis of switchable interlocked
systems for nanotechnological applications continues in our
laboratories.
11 I. Murgu, J. M. Baumes, J. Eberhard, J. J. Gassensmith,
E. Arunkumar and B. D. Smith, J. Org. Chem., 2011, 76,
688; H. Zheng, W. Zhou, J. Lv, X. Yin, Y. Li, H. Liu and
Y. Li, Chem.–Eur. J., 2009, 15, 13253; J.-M. Kern, L. Raehm,
J.-P. Sauvage, B. Divisia-Blohorn and P.-L. Vidal, Inorg.
Chem., 2000, 39, 1555; L. Raehm, J.-M. Kern and J.-P. Sauvage,
Chem.–Eur. J., 1999, 5, 3310; M. Linke, J. C. Chambron,
V. Heitz and J. P. Sauvage, J. Am. Chem. Soc., 1997, 119,
11329.
We thank EPSRC for
a studentship (L.M.H.), and
Dr Alexandre Leontiev for supplying macrocycle 1 and for
useful discussions.
c
6014 Chem. Commun., 2011, 47, 6012–6014
This journal is The Royal Society of Chemistry 2011