Polyatomic anion assistance in the assembly of [2]pseudorotaxanes

Article abstract of DOI:10.1021/ja301900s

We describe the use of polyatomic anions for the quantitative assembly of ion-paired complexes displaying pseudorotaxane topology. Our approach exploits the unique ion-pair recognition properties exhibited by noncovalent neutral receptors assembled through hydrogen-bonding interactions between a bis-calix[4]pyrrole macrocycle and linear bis-amidepyridyl-N-oxides. The complexation of bidentate polyatomic anions that are complementary in size and shape to the receptor's cavity, in which six NH hydrogen-bond donors converge, induces the exclusive formation of four particle-threaded assemblies.

Full text of DOI:10.1021/ja301900s

Communication
pubs.acs.org/JACS
Polyatomic Anion Assistance in the Assembly of [2]Pseudorotaxanes
Virginia Valderrey,‡ Eduardo C. Escudero-Adan,‡ and Pablo Ballester*,‡,§
́
‡Institute of Chemical Research of Catalonia (ICIQ), Avgda. Països Catalans 16, 43007 Tarragona, Spain
§Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys, 23, 08018 Barcelona, Spain
S
* Supporting Information
counterion is bound opposite to the anion in the shallow
aromatic cavity defined by the calix[4]pyrrole.
Hay coupling of calix[4]pyrrole 3 templated by one
equivalent of 4,4′-bispyridine-1,1′-dioxide afforded macrocycle
1 in 60% yield (Scheme 1). The heteroditopic linear
ABSTRACT: We describe the use of polyatomic anions
for the quantitative assembly of ion-paired complexes
displaying pseudorotaxane topology. Our approach ex-
ploits the unique ion-pair recognition properties exhibited
by noncovalent neutral receptors assembled through
hydrogen-bonding interactions between a bis-calix[4]-
pyrrole macrocycle and linear bis-amidepyridyl-N-oxides.
The complexation of bidentate polyatomic anions that are
complementary in size and shape to the receptor’s cavity,
in which six NH hydrogen-bond donors converge, induces
the exclusive formation of four particle-threaded assem-
blies.
Scheme 1. Synthetic Scheme for the Preparation of
Macrocycle 1 and Structures of Bis-amidepyridyl-N-oxides 2
and the Tetrabutylammoniun Ion-Pairs of Polyatomic
Anions 4
atenanes and rotaxanes are mechanically locked structures
C
with potential application in molecular machinery.1,2
Supramolecular assistance facilitates the preparation of these
interpenetrated topologies.3 A key intermediate for their
construction is the noncovalent pseudorotaxane, where a linear
molecule is threaded through the annulus of a macrocycle.4
Thus, the development of new supramolecular strategies and
interweaving motifs for the construction of pseudorotaxanes is
a topic of current interest.5,6 Specifically, examples of template
assistance for the formation of rotaxanes, catenanes, and
pseudorotaxanes using cations,7−10 anions,11−13 hydrogen
bonds,14−16 hydrophobic interactions,17,18 and π−π interac-
tions19,11,12 have all been reported. A general and versatile
templating strategy for the construction of threaded assemblies
that combines halide recognition by the macrocyclic
component with strong ion-pairing of the linear component
has been developed.20 Here, we report the use of polyatomic
anions for the quantitative construction of pseudorotaxane-like
assemblies, which does not involve ion-pairing with the linear
component. Rather, the approach described herein exploits the
exceptional ion-pair recognition properties21 of a self-assembled
ditopic interwoven receptor.
components, 3,5-pyridinecarboxamide-N-oxides 2, were pre-
pared following described procedures for similar com-
pounds.24,8
The addition of 0.5 equiv of N-oxide 2a to a millimolar
CDCl3 solution of 1 produced broadening of the pyrrole NH
proton signal, preventing direct observation but suggesting
hydrogen-bonding interactions (N−H···O) between the
pyrrole NHs and the N-oxide oxygen. Likewise, the H1, H2,
and H3 proton signals for N-oxide 2a are not detected due to
broadening (Figure 1b). The doublet corresponding to the H5
protons of the meso-phenyl residues in 1 also broadened
beyond detection. Lowering the temperature to 233 K enabled
the observation of two well-resolved downfield doublets
corresponding to the meso-phenyl aromatic protons of free 1
(H4, H5) and two broad signals that were assigned to the same
protons in the bound macrocycle (Figure S16, Supporting
Information [SI]). The integral ratio of free and bound signals
is 1:1. Taken together, these observations suggested the
The hydrogen-bonding complementarity that exists between
homoditopic calix[4]pyrrole macrocyle 1 and ditopic linear m-
bis-amide-pyridyl-N-oxides 2 induces the assembly of neutral
interwoven receptors 1·2.22 The 1·2 complex has a
pseudorotaxane topology,23 and its components feature a
binding site of six convergent hydrogen-bond NH donors: two
from bound bis-amide and four from the opposing calix[4]-
pyrrole cap of 1. At millimolar concentrations, the complex-
ation of bidentate polyatomic anions, complementary in size
and shape to the cavity creates an ion-paired complex 4⊃1·2
displaying pseudorotaxane topology. The tetrabutylammonium
Received: February 26, 2012
Published: March 19, 2012
© 2012 American Chemical Society
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Scheme 2. Two-Step Quantitative Self-Assembly of 4a⊃1·2a
bonds its N-oxide group to one of the calix[4]pyrrole caps of
macrocycle 1 as described for the 1·2a complex. Furthermore,
the polyatomic anion guest hydrogen bonds simultaneously to
the amide NHs of 2a at one end and to the opposing
calix[4]pyrrole unit of 1.27 The cyanate anion is included in the
three-dimensional (3D) cavity defined by the macrocycle and
the linear component of the pseudorotaxane, in which up to six
hydrogen-bond donors converge, whereas the tetrabutylammo-
nium counterion is located in the shallow external cavity
defined by the pyrrole rings opposite to the included anion.
Thus, pseudorotaxane-like complex 4a⊃1·2a displays a
separated ion-pair arrangement. In short, ion-pair 4a acts as a
template capable of driving the equilibria toward the
quantitative assembly of a four-particle aggregate with
pseudorotaxane topology. ROESY experiments were very
useful in the assignment of the proton signals of 4a⊃1·2a
and revealed close intermolecular contacts as expected from the
described pseudorotaxane topology. DOSY experiments also
supported the formation of the pseudorotaxane-like complex
4a⊃1·2 in solution.28 The values of the diffusion coefficients in
CDCl3 solutions of 2a and 4a are larger (7.5 and 8.2 × 10−10
m2 s−1, respectively) than for 1 (5.0 × 10−10 m2 s−1). This is
expected on the basis of their relative molecular weights and
sizes. A 2D DOSY experiment performed on an equimolar
mixture of 1, 2a, and 4a showed similar diffusion profiles for
the three components, supporting their participation in a
common aggregate. We also determined the diffusion
coefficient value of the formed supramolecular entity 4a⊃1·2
as 4.5 × 10−10 m2 s−1. Not surprisingly, this value is only slightly
lower than the one calculated for the free component 1. This is
because, although the change in molecular weight of 1 vs
4a⊃1·2a is considerable, this is not the case for the values of the
hydrodynamic radii.
Figure 1. Downfield regions of the 1H NMR spectra (500 MHz,
CDCl3, 298 K) of the free linear 2a (a) and cyclic 1 (c) components of
the pseudorotaxanes, its equimolar mixture (b) and the solution
containing the three components 1, 2a, and 4a in a 1:1:1 ratio (d).
Inset: CAChe minimized structure of ion-paired [2]pseudorotaxane
complex 4a⊃1·2a. See Schemes 1 and 2 for proton assignments.
formation of a kinetically stable 1:1 complex between 1 and 2a
with a stability constant higher than 104 M−1 at 233 K.
We assigned a pseudorotaxane topology to the 1·2a complex
on the basis of the chemical shift changes observed at 233 K for
the meso-phenyl protons in free and bound 1. We interpreted
the dissimilar exchange dynamics for the two sets of meso-
phenyl protons as the result of the interweaving geometry
assigned to the 1·2a complex. At 233 K the threading/
dethreading process becomes slow, producing separate signals
for the aromatic protons of free and bound macrocycle 1.
However, the pirouetting process of the linear component 2a
1
occurring at an intermediate rate on the H NMR time scale
within the 1·2a complex produced broadening of the aromatic
protons of bound 1.25,26
The addition of one equivalent of tetrabutylammonium
cyanate 4a to the equimolar CDCl3 solution of 1 and 2a
1
produced a dramatic change in the H NMR spectrum of the
mixture (Figure 1d). All proton signals for 1 and 2a became
sharp and well-defined, and were easily assigned. Two different
and highly downfield-shifted signals for the pyrrole NH protons
(H11 and H19) of 1 indicate participation in distinct hydrogen-
bonding interactions. Four different sets of proton signals were
observed for the aromatic and β-pyrrole protons. These
findings point to an unsymmetrical assembly (Scheme 2 and
Figure 1d). All the proton signals of the bis-amidepyridyl-N-
oxide 2a experienced significant chemical shift changes with
respect to those observed for 2a alone. In addition, the
multiplet of the methylene protons alpha to the nitrogen atom
of the tetrabutylammonium cation in 4a was significantly
downfield shifted.
Isothermal titration calorimetry (ITC) experiments were also
performed to quantify the thermodynamic stability of the
4a⊃1·2a pseudorotaxane-like complex. A CHCl3 solution of N-
oxide 2a ([2a] = 0.6 mM) was added to an equimolar mixture
of 1 and 4a ([1] = [4a] = 0.06 M), and the resulting binding
isotherm (normalized integrated heat vs molar ratio [2a]/[1])
was analyzed using a binding model that considered the
formation of the following species: 4a⊃1·2a, 1·4a, and
1·(4a)2.29 The fit of the titration data returned a stability
Taken together, these observations give strong support for
the quantitative formation of an unprecedented four-
component pseudorotaxane-like complex between macrocycle
1, linear component 2a, and ion-pair 4a. Accordingly, the
ditopic linear component 2a threads into 1 and hydrogen
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constant value K4a⊃1·2a = 9.1× 1010 M−2 for the pseudorotaxane
complex.30
The quantitative assembly of pseudorotaxane 4a⊃1·2 was
also independent of the order of addition of its components.
During the experimental investigations of the different addition
strategies for the assembly of pseudorotaxane 4a⊃1·2a, we also
determined the stability constants of all the intermediate
species.26,29 We performed simulated speciations of the three
possible addition alternatives for a two-step formation of
4a⊃1·2a (SI). In complete agreement with experimental
observations, the simulated profiles showed that working
under strict stoichiometric conditions (1 equiv of each
component) the pseudorotaxane 4a⊃1·2a is quantitatively
assembled independently of the order of addition of the
components. However, the simulated speciation profiles
indicated that when ion-pair component 4a is added
incrementally, pseudorotaxane 4a⊃1·2a disassembles in favor
of the formation of 1·(4a)2 in the presence of more than 1
equiv of the ion-pair. In contrast, self-assembled pseudorotax-
ane 4a⊃1·2a remains stable in the presence of excess of either
of the two other components: macrocycle 1 or N-oxide 2a. The
simulation results were also corroborated experimentally. In the
presence of excess macrocycle 1 or N-oxide 2a, pseudorotaxane
4a⊃1·2a remained intact. We observed a slow chemical
Figure 2. (Top) Single-crystal X-ray structure of 4b⊃1·2a.27 (Bottom)
1
Downfield regions of the H NMR spectra of the CDCl3 solution
containing an equimolar mixture of 1, 2a, and tetrabutylammonium
thiocyanate 4b recorded at 298 and 213 K. [1] = [2a] = [4b] = 4.6×
10−3 M.
1
exchange on the H NMR time scale between bound and
free component added in excess. In contrast, the addition of
excess of 4a induced the emergence of proton signals assigned
to 1·(4a)2 at the expense of those corresponding to 4a⊃1·2a.
Other tetrabutylammonium salts of polyatomic anions were
investigated as templates for the quantitative assembly of
related pseudorotaxanes (i.e., azide 4c, thiocyanate 4b, and
nitrate 4d). In the case of the azide pair 4c, the results
paralleled those observed for 4a (cyanate anion). Conversely,
the addition of 1 equiv of thiocyanate 4b or nitrate 4d to an
tetrabutylammonium cyanate 4a or azide 4c with 1 and 2a
induces the quantitative formation of the ion-paired pseudor-
otaxane-like complex 4a,c⊃1·2a independently of the addition
order of the components. We are currently involved in
exploiting this methodology of assembly of pseudorotaxanes
in the synthesis of mechanically interlocked molecules (i.e.,
rotaxanes) through a capping approach.
1
ASSOCIATED CONTENT
* Supporting Information
equimolar CDCl3 solution of 1 and 2a did not produce H
■
NMR spectra with sharp or well-resolved signals. Several
proton signals in 1 and 2a were not even observable due to
broadening. However, lowering the temperature at 213 K for
4b and 243 K for 4d generated 1H NMR spectra containing the
diagnostic proton signals expected for the quantitative assembly
of the pseudorotaxane-like complexes 4b⊃1·2a and 4d⊃1·2a.
Most likely, hydrogen-bonding characteristics, and the shape
and size of the polyatomic anions are key parameters for the
quantitative assembly of the 4⊃1·2 aggregates at room
temperature. Ion-pairs 4b and 4d did template the partial
formation of the corresponding 4b,d⊃1·2 complexes. The
exchange dynamics that exist between free and bound
components resulted in broadening of the proton signals. At
low temperature the thermodynamic and kinetic stability of the
4b,d⊃1·2a complexes is increased, enabling their detection as
the predominant species in solution. Interestingly, the
interweaving structure of the 4b⊃1·2a complex was confirmed
in the solid-state from X-ray diffraction of a single crystal grown
from an equimolar CDCl3 solution of 1, 2a, and 4b (Figure 2).
The use of linear component 2b in combination with 4a was
also effective in the quantitative assembly of 4a⊃1·2b at 298 K.
In combination, these results demonstrate the generality of the
described assembly strategy in the preparation of pseudorotax-
ane-like motifs.
S
Experimental procedures for synthesis and binding studies,
spectral data for new compounds, methods for the
mathematical analysis of the titration curves, simulated
speciation profiles, 2D ROESY and DOSY spectra of
4a⊃1·2a, and X-ray crystallographic files of 1, 1·2a and
4b⊃1·2a.This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
pballester@iciq.es
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by Spanish Ministries MICINN and
MINECO (CTQ2008-00222 and CTQ2011-23014), General-
itat de Catalunya (2009SGR00686), and the ICIQ Foundation.
We dedicate this work to Prof. Miquel A. Miranda, Instituto de
́
́
Tecnologia Quimica UPV-CSIC, Valencia, on the occasion of
his 60th anniversary.
REFERENCES
In conclusion, we have synthesized homoditopic calix[4]-
pyrrole macrocycle 1 and used it in a general strategy for the
quantitative self-assembly of pseudorotaxane-like complexes. At
298 K in CDCl3 solution, an equimolar combination of
■
(1) Kay, E. R.; Leigh, D. A. Pure Appl. Chem. 2008, 80, 17−29.
(2) Kay, E. R.; Leigh, D. A.; Zerbetto, F. Angew. Chem., Int. Ed. 2007,
46, 72−191.
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(3) Dietrichbuchecker, C. O.; Sauvage, J. P. Chem. Rev. 1987, 87,
795−810.
(4) Breault, G. A.; Hunter, C. A.; Mayers, P. C. Tetrahedron 1999, 55,
5265−5293.
(30) The stability constants values of the complexes involving ion-
pair 4a should be considered as apparent because ion-pair dissociation
and ion-paired complex formation equilibria are not taken into
consideration in the mathematical analysis of the titration data.
(5) Gavina, P.; Tatay, S. Curr. Org. Synth. 2010, 7, 24−43.
(6) Qu, D. H.; Tian, H. Chem. Sci. 2011, 2, 1011−1015.
(7) Fuller, A. M.; Leigh, D. A.; Lusby, P. J.; Oswald, I. D. H.; Parsons,
S.; Walker, D. B. Angew. Chem., Int. Ed. 2004, 43, 3914−3918.
(8) Hancock, L. M.; Beer, P. D. Chem. Commun. 2011, 47, 6012−
6014.
(9) Cheng, H. M.; Leigh, D. A.; Maffei, F.; McGonigal, P. R.; Slawin,
A. M. Z.; Wu, J. J. Am. Chem. Soc. 2011, 133, 12298−12303.
(10) Voignier, J.; Frey, J.; Kraus, T.; Budesinsky, M.; Cvacka, J.;
Heitz, V.; Sauvage, J. P. Chem.Eur. J. 2011, 17, 5404−5414.
(11) Vickers, M. S.; Beer, P. D. Chem. Soc. Rev. 2007, 36, 211−225.
(12) Lankshear, M. D.; Beer, P. D. Acc. Chem. Res. 2007, 40, 657−
668.
(13) Gong, H. Y.; Rambo, B. M.; Karnas, E.; Lynch, V. M.; Keller, K.
M.; Sessler, J. L. J. Am. Chem. Soc. 2011, 133, 1526−1533.
(14) Hunter, C. A. J. Am. Chem. Soc. 1992, 114, 5303−5311.
(15) Altieri, A.; Aucagne, V.; Carrillo, R.; Clarkson, G. J.; D’Souza, D.
M.; Dunnett, J. A.; Leigh, D. A.; Mullen, K. M. Chem. Sci. 2011, 2,
1922−1928.
(16) Schalley, C. A.; Reckien, W.; Peyerimhoff, S.; Baytekin, B.;
Vogtle, F. Chem.Eur. J. 2004, 10, 4777−4789.
(17) Wyman, I. W.; Macartney, D. H. J. Org. Chem. 2009, 74, 8031−
8038.
(18) Wenz, G.; Han, B. H.; Muller, A. Chem. Rev. 2006, 106, 782−
817.
(19) Amabilino, D. B.; Stoddart, J. F. Chem. Rev. 1995, 95, 2725−
2828.
(20) Brown, A.; Beer, P. D. Dalton Trans. 2012, 41, 118−129 and
references cited therein.
(21) Kim, S. K.; Sessler, J. L. Chem. Soc. Rev. 2010, 39, 3784−3809.
(22) Verdejo, B.; Gil-Ramirez, G.; Ballester, P. J. Am. Chem. Soc.
2009, 131, 3178−3179.
(23) For other examples of N-oxides used as linear components in
the assembly of [2]pseudorotaxane see ref 8 and Chen, M. J.; Han, S.
J.; Jiang, L. S.; Zhou, S. G.; Jiang, F.; Xu, Z. K.; Liang, J. D.; Zhang, S.
H. Chem. Commun. 2010, 46, 3932−3934.
(24) Ballester, P.; Costa, A.; Deya, P. M.; Frontera, A.; Gomila, R. M.;
Oliva, A. I.; Sanders, J. K. M.; Hunter, C. A. J. Org. Chem. 2005, 70,
6616−6622.
(25) An interwoven structure for the 1·2a complex was also observed
in the solid-state. 2a is threaded through 1, showing disorder between
two equivalent positions.
1
(26) Using H NMR titrations we determined at 298 K the stability
constant values for K1·2a = 800 M−1, K2a·4 = 3 × 103 M−1, and a
dimerization constant value Kd = 100 M−1 for 2a.
(27) The cyanate and thiocyanate anions are ambidentate. Probably
in solution, the sandwiched anion rotates freely within the complex.
(28) We attempted the characterization of the pseudorotaxane-like
complex 4a⊃1·2a in the gas phase using ESI-TOF-MS with negative
mode detection. We could not detect the ion peak corresponding to
[NCO⊃1·2a]− (1476.7 m/z). Instead, we observed a cluster of
monocharged negative ions at 1479.7, 1496.7, 1529.9, 1546.9, and
1563.9 m/z (Figure S18 [SI]). These molecular masses and their
corresponding isotopic distribution patterns coincide with those
calculated for molecular formulas [NCO⊃1·2a + H2 + H]−•
,
[NCO⊃1·2a + H2 + H2O]−, [NCO⊃1·2a + 2H2 + H2O
+CH3O]−•, [NCO⊃1·2a + 2H2 + H2O +CH3OH + HO]− and
[NCO⊃1·2a + 2H2 + H2O +CH3OH + 2HO]−•, respectively. Most
likely, the anionic or anion−radical complex NCO⊃1·2a reacted with
solvent molecules or ions/radicals derived from them in the ionization
process.
(29) The values of the stability constants and enthalpies for
formation for 1·4a and 1·(4a)2 were fixed during the mathematical
analysis of the titration data. K1·4a = 1 × 10−5 M−1, ΔH1·4a = −5 kcal/
mol; K1·4a↔1·(4a) = 1 × 10−6 M−1, ΔH1·4a↔1·(4a) = −8 kcal/mol.
2
2
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