Lanthanide cation-templated synthesis of rotaxanes

Article abstract of DOI:10.1039/c3cc45404e

The first lanthanide cation-templated synthesis of an interlocked structure is demonstrated through an interpenetrated assembly between a pyridine N-oxide threading component coordinating to a lanthanide cation complexed within a macrocycle. Stoppering of the pseudo-rotaxane assembly allows for preparation of the [2]rotaxane.

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Lanthanide-cation templated synthesis of rotaxanes
Fabiola Zapata, Octavia A. Blackburn, Matthew J. Langton, Stephen Faulkner and Paul D. Beer*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
5
The first lanthanide cation-templated synthesis of an
interlocked structure is demonstrated through an
interpenetrated assembly between
a
pyridine N-oxide
threading component coordinating to a lanthanide cation
complexed within a macrocycle. Stoppering of the pseudo-
10 rotaxane assembly allows for preparation of the [2]rotaxane.
The development of new innovative strategic templating routes
for the construction of mechanically interlocked molecules with
potential
molecular
switching
and
machine-like
nanotechnological applications is of intense current research
15 interest.1 In addition to their dynamic behaviour, rotaxanes and
catenanes can also be designed to contain topologically unique
three-dimensional cavities for molecular recognition and sensing
applications.2 Although transition metal cation, and to a lesser
extent alkali and alkaline earth metal cation, templates have been
20 imaginatively exploited in the synthesis of rotaxanes and
catenanes,3 to the best of our knowledge, the ultilization of
lanthanides as potential templating reagents for interlocked
molecular framework assembly has not been demonstrated.4 This
is somewhat surprising given the usefulness of luminescent
25 lanthanide complexes in imaging and assay.5 We describe herein
the first lanthanide-cation templated synthesis of a rotaxane.
Adapting our recently reported sodium and barium cation
templated synthesis of a rotaxane using the pyridine N-oxide
motif,6 the synthetic strategy undertaken for the preparation of the
30 target lanthanide-[2]rotaxane is shown in Scheme 1. A kinetically
stable lanthanide complexed DOTA cyclen derivative integrated
into a macrocyclic structural framework, forms initially a pseudo-
rotaxane assembly with an appropriately functionalized pyridine
N-oxide threading component, where the pyridine N-oxide ligand
35 serves to satisfy the lanthanide cation’s coordination sphere.
Subsequent stoppering of the interpenetrated assembly produces
the novel lanthanide containing interlocked structure.
50
Scheme 1. Schematic representation for the preparation of the target
lanthanide-[2]rotaxane.
Two of the nitrogen atoms of cyclen were selectively alkylated
with tert-butyl bromoacetate to give bis-ester cyclen 1, using
established procedures.7 The bridging unit 2 was prepared by
55 condensing two equivalents of chloroacetylchloride with the
corresponding bis-amine derivative8 (see SI). Reaction of the 1,7-
DO2A diester (1) and the bis-amide compound 2 in acetonitrile
under basic conditions afforded macrocycle 3, which was
isolated in 70 % yield after purification by recrystallization from
60 diethyl ether. Cleavage of the tert-butyl ester groups in 3
followed by complexation of the resulting product with either
lutetium or europium lanthanide trifluoromethanesulfonate salts
in methanol, produced the lanthanide complexes 4a and 4b in a
quantitative yield. The condensation reaction between 3,5-bis-
65 chlorocarbonyl pyridine and two equivalents of 3-
bromopropylamine hydrobromide in dry CH2Cl2 in the presence
The synthetic procedure used for preparation of the lanthanide
macrocyclic component 4a and 4b of the target [2]rotaxane
40 system and the bis-azide functionalised pyridine N-oxide thread
component is outlined in Scheme 2.
Chemistry Research Laboratory, Department of Chemistry, University of
Oxford, Mansfield Road, Oxford, OX1 3TA (UK), Fax: (+44) 1865-272-
45 690, E-mail: paul.beer@chem.ox.ac.uk
† Electronic Supplementary Information (ESI) available. Experimental
details for synthetic and spectroscopic proceedures, and additional
characterisation. See DOI: 10.1039/b000000x/
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Scheme 2. Synthesis of a) lanthanide macrocycles complexes and b) bis-
azide pyridine N-oxide thread component.
Figure 1.High resolution electrospray ionization mass spectrum of
[2]rotaxane 8b (top) with theoretical isotope model for [M-TfO+Na]2+
(bottom).
5
20
Scheme 3. Synthesis of lanthanide [2] rotaxanes 8a and 8b.
TBTA = (Tris-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine)
of triethylamine gave the bis–bromo amide pyridine derivative 5
in 50 % yield. Azide nucleophilic substitution followed by
oxidation using oxone afforded the bis-azide pyridine N-oxide
compound 6 in 80 % yield.
The synthesis of the target lanthanide [2]rotaxanes was
achieved by a copper (I) catalysed cycloaddition azide-alkyne
(CuAAC) click stoppering reaction as shown in Scheme 3. A
solution of the appropriate lanthanide macrocyclic complex (4a
and 4b), bis-azide pyridine N-oxide axle precursor 6 and two
15 equivalents of alkyne-functionalised terphenyl stopper 7 in
dichloromethane in the presence of a catalytic amount of
Cu(CH3CN)4PF6 was stirred at room temperature for 48 hours.
After purification using size exclusion chromatography, the
rotaxanes 8a and 8b were isolated in 20 % yield, and were
characterized by high-resolution electrospray mass spectroscopy
(Figure 1) and 1H NMR.9
A comparison of the H NMR spectra of the [2]rotaxane 8a,
1
25 macrocycle 4a and stoppered axle is shown in Figure 2. The
upfield shifts of the macrocycle hydroquinone protons observed
with 8a are diagnostic of aromatic donor – acceptor stacking
interactions between the electron rich hydroquinone groups of the
macrocycle and the electron deficient pyridine N-oxide axle
30 motif. Two-dimensional 1H-1H-ROESY spectroscopy was also
used to confirm the interlocked nature of rotaxane 8a with
through-space correlations between protons in the respective axle
and macrocycle components being identified. (see Figure SI6 in
the Supporting Information).10An equimolar solution of cyclen
10
2
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45 European Union’s Framework Program (FP7/2007-2013) ERC
Advanced Grant Agreement no 267426. M. J. L. thanks the
EPSRC for a DTA studentship.
Notes and references
1
a) E. R. Kay and D. A. Leigh, Pure Appl. Chem., 2008, 80, 17; b) J.
A. Faiz, V. Heitz and J.-P. Sauvage, Chem. Soc. Rev., 2009, 38, 422;
c) L. Fang, M. A. Olson, D. Benı´tez, E. Tkatchouk, W. A. Goddard
III and J. F. Stoddart, Chem. Soc. Rev., 2010, 39, 17; d) 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; e) S. J.
Loeb, Chem. Soc. Rev., 2007, 36, 226-235
50
55
60
65
70
75
80
2
3
a) G. T. Spence and P. D. Beer, Acc. Chem. Res., 2013, 46, 2, 571–
586; b) M. J. Chmielewski, J. J. Davis, P. D. Beer, Org. Biomol.
Chem., 2009, 7, 415-424.
a) J. P. Sauvage, Acc. Chem. Res., 1990, 23, 319; b) J. C. Chambron,
J. P. Collin, V. Heitz, D. Jouvenot, J. M. Kern, P. Mobian, D.
Pomeranc and J. P. Sauvage, Eur. J. Org. Chem., 2004, 1627; c) J. F.
Stoddart, in Templates in Chemistry II, Springer, Berlin/ Heidelberg,
2005, pp. 227–240; d) J. E. Beves, B. A. Blight, C. J. Campbell, D.
A. Leigh and R. T. McBurney, Angew Chem Int Ed, 2011, 50, 9260-
9327; e) J. D. Crowley, S. M. Goldup, A-L. Lee, D. A. Leigh and R.
T. McBurney Chem. Soc. Rev., 2009, 38, 1530-1541.
We have recently reported lanthanide appended rotaxanes, prepared
by post-rotaxane formation. See C. Allain, P. D. Beer, S. Faulkner,
M. W. Jones, A. M. Kenwright, N. L. Kilah, R. C. Knighton, T. J.
Sorensen and M. Tropiano, Chem. Sci. 2013, 4, 489-493. Hoffart
and Loeb have used pyridine N-oxide at the terminus of rotaxanes for
the construction of MOFs. See D. J. Hoffart and S. J. Loeb, Angew.
Chem. Int. Ed., 2005, 44, 901 –904.
a) S. Faulkner, L. S. Natrajan, W. S. Perry and D. Sykes, Dalton
Trans., 2009, 0, 3890-3899; b) C. Allain and S. Faulkner, Future
Med. Chem., 2010, 2, 339-350.
L. M. Hancock and P. D. Beer, Chem. Comm., 2011, 47, 6012-6014
a) L. M. De León-Rodríguez, Z. Kovacs, A. C. Esqueda- Oliva, A. D.
Miranda-Olvera, Tetrahedron Letters, 2006, 47, 6937-6940; b) T.
Hirayama, M. Taki, A. Kodan, H. Kato, Y. Yamamoto, Chem.
Commun., 2009, 3196-3198.
Figure 2. Partial 1H NMR spectra in CDCl3/CD3OD 1:1 at 293 K of (a)
macrocycle 4a, (b) [2] rotaxane 8a, and (c) axle. For atom labels see
scheme 3.
macrocycle 3 and pyridine N-oxide derivative 6 in CD2Cl2
revealed no upfield perturbations of the macrocycle’s
hydroquinone protons which suggests the contribution of
aromatic donor – acceptor interactions to the overall mechanical
bond formation process is minimal and highlights the crucial
templating role of the lanthanide cation11.
The luminescence from the europium centre was also used to
probe the structure of macrocycle 4b and rotaxane 8b in 1:1
CH2Cl2:CH3OH and in 1:1 CD2Cl2:CD3OD. In the former solvent
mixture, the observed luminescence lifetime of 8b was found to
be 0.94 ms, while in deuterated media the luminescence lifetime
15 increased to 1.18 ms. Understanding solvation of even simple
systems in binary solvent mixtures is not straightforward, but
given the residual charge on the lanthanide centre, it is reasonable
to assume that any inner sphere solvent at the europium ion will
be comprised of methanol rather than DCM molecules. As such it
20 is possible to estimate q, the number of inner sphere solvent
molecules bound to the lanthanide, from the equation q =
2.4(CH3OH-1 - CD3OD-1 – 0.125 – 0.0375x), where x is the number
of exchangeable amide N-H oscillators close to the metal
centre.12 In this case, the calculated value of q is 0 if we assume
25 that all four amide N-H oscillators contribute (including the two
on the axle), which certainly equates to exclusion of methanol
from the inner coordination sphere in 8b, and suggests that the
pyridine N-oxide oxygen atom acts as an axial donor to the
lanthanide. The luminescence lifetime of 4b in 1:1
30 CH2Cl2:CH3OH is shorter and a biexponential fit gives 0.20 and
0.63 ms, indicating solvation at the europium centre in contrast to
8b.
5
4
5
10
6
7
8
9
L. M. Hancock and P. D. Beer, Chem. Eur. J., 2009, 15, 42-44
The by-products from the reaction were non-interlocked macrocycle
and axle.
85 10 Addition of
1 equivalent of axle to macrocycle 4a, in 1:1
CD2Cl2/CD3OD, revealed no perturbation of the hydroquinone
protons in the 1H NMR spectrum. This further confirms that the
upfield shifted hydroquinones observed in rotaxane 8a are due to the
interlocked nature of the axle and macrocycle components, and
demonstrates that the stopper components prevent the macrocycle
threading/dethreading. This rules out the possibility of the axle
perching on the outside of the macrocycle, and confirms that the
rotaxane is mechanically interlocked (See SI).
90
95
11 The copper (I) catalysed (CuAAC) stoppering rotaxane synthesis
reaction cannot be undertaken in the absence of the lanthanide cation
template because of the propensity of the DOTA ligand to complex
copper.
12 a) A. Beeby, I. M. Clarkson, R. S. Dickens, S. Faulkner, D. Parker, L.
Royle, A. S. de Sousa, J. A. G. Williams, M. Woods, J. Chem. Soc.,
Perkin Trans. 2, 1999, 493; b) S. Faulkner, S. J. A. Pope, B. P.
Burton-Pye, Appl. Spec. Rev., 2005, 40, 1-31.
100
In summary, the first lanthanide-cation templated synthesis of an
35 interlocked structure has been demonstrated. A pyridine N-oxide
ligand threading component coordinates to
a lutetium or
europium lanthanide complexed DOTA cyclen motif which is
itself incorporated into a macrocycle. The novel lanthanide
[2]rotaxanes are prepared through stoppering of the
40 pseudorotaxane assemblies.
F.Z. acknowledges the Ministry of Education of Spain for a
Postdoctoral contract (Programa Nacional de Movilidad de
Recursos Humanos del Plan Nacional I+D+I 2008-2011). O. A.
B. thanks the European Research Council for funding under the
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