Using acetate anions to induce translational isomerization in a neutral urea-based molecular switch

Article abstract of DOI:10.1002/anie.200702197

Vying for urea: The translational isomerism of a neutral [2]rotaxane can be controlled in solution through the addition and removal of acetate anions. In the absence of acetate ions, the macrocyclic host recognizes a diphenylurea derivative; recognition of acetate ions by the urea-based station causes relocation of the macrocycle to another binding site (see picture). (Figure Presented).

Full text of DOI:10.1002/anie.200702197

Angewandte
Chemie
DOI: 10.1002/anie.200702197
Rotaxanes
Using Acetate Anions To Induce Translational Isomerization in a
Neutral Urea-Based Molecular Switch**
Yi-Lin Huang, Wei-Chung Hung, Chien-Chen Lai, Yi-Hung Liu, Shie-Ming Peng, and
Sheng-Hsien Chiu*
Although the use of cations to switch
interlocked machine-like systems
between different states is quite
common,[1] reports of anion-mediated
interlocked switches are rare. To the
best of our knowledge, only a few
examples of anion-controlled transla-
tional isomerism in interlocked molec-
ular switches have been described:
1) the generation of
a phenoxide
anion on a rotaxane thread to attract
Leighꢀs macrocycle[2] and 2) exchange
of the counteranions of ammonium[3]
or pyridinium[4] ions to affect their
interactions with complementary
crown ether or naphthalene-derived
recognition motifs. Because of their
ability to act as strong Y-shaped
hydrogen-bond donors, urea and its
Scheme 1. Formation of a urea-based pseudorotaxane.
derivatives play key roles in the design of receptors for anions,
including both spherical halide anions and Y-shaped carbox-
ylate anions, in solution.[5] Conceptually, a [2]pseudorotaxane
complex obtained after threading a urea-derived component
through the cavity of a macrocycle should be a suitable system
for constructing anion-controllable molecular switches
because the recognition of anions by the urea recognition
site would encourage relocation of the macrocycle to another
recognition site. We are unaware, however, of any such switch
having been reported to date. Herein, we report a new ditopic
macrocyclic host that is capable of recognizing a dipheny-
lurea-derived thread in a [2]pseudorotaxane fashion in
solution.[6] The controllable translational isomerism of its
corresponding neutral [2]rotaxane was achieved through the
addition and removal of acetate anions.
Previously, we reported that the diethylene glycol linkages
in bis(para-xylyl)-[26]crown-6 (BPX26C6, Scheme 1) located
its two xylene rings at a favorable p-stacking distance and,
thus, helped its complexation to (mono)pyridinium and 4,4’-
bipyridinium ions in solution.[7] Because 2,6-pyridinediamide
is also an excellent spacer for locating aromatic rings at a
suitable p-stacking distance,[8] we designed the ditopic macro-
cycle 1, which possesses two xylyl rings linked by both
diethylene glycol and 2,6-pyridinediamide spacers, as a host
molecule capable of complexing diphenylurea derivatives. We
expected that the corresponding [2]pseudorotaxane com-
plexes (Scheme 1) would be stabilized through the coopera-
tive effects of p stacking (of the two xylyl rings about the
planar p system of the urea center) and N-H···O hydrogen
bonding (between the 2,6-pyridinediamide protons and the
urea carbonyl oxygen atom and between the urea amide
protons and the ethylene glycol oxygen atoms).[9] We
obtained macrocycle 1 in 12% overall yield from the reaction
of 4-bromomethylbenzonitrile with diethylene glycol under
basic conditions (affording the bis(benzonitrile) 2), the
LiAlH4-mediated reduction of 2, and subsequent macro-
[*] Y.-L. Huang, W.-C. Hung, Y.-H. Liu, Prof. S.-M. Peng, Prof. S.-H. Chiu
Department of Chemistry
National Taiwan University
No. 1, Sec. 4, Roosevelt Road, Taipei, Taiwan
Fax: (+886)2-3366-1677
E-mail: shchiu@ntu.edu.tw
Homepage: http://www.ch.ntu.edu.tw/english/efaculty/people/
chiu-eng.html
Prof. C.-C. Lai
Institute of Molecular Biology
National Chung Hsing University and
Department of Medical Genetics
China Medical University Hospital
Taichung, Taiwan
cylization
with
dimethyl
2,6-pyridinedicarboxylate
[**] This study was supported by National Taiwan University (95-R0061-
AN-00-01) and the National Science Council, Taiwan (NSC-95-
2113M-002-016-MY3 and NSC-96-2752-M-002-006-PAE).
(Scheme 2).
To increase the solubility of diphenylurea in less-polar
solvents (i.e., solvents that encourage hydrogen bonding
between their solutes), we synthesized a diphenylurea deriv-
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Scheme 2. Synthesis of macrocycle 1.
Figure 1. Partial 1H NMR spectra (400 MHz, CDCl3, 298 K) of a) an
equimolar mixture of 1 and 3 (10 mm), b) the mixture obtained after
adding TBAA (2 equiv) to the solution in (a), and c) the mixture
ative (3) with two hexyloxy side chains (see the Supporting
Information). The 1H NMR spectrum of an equimolar
mixture of macrocycle 1 and the diphenylurea 3 in CDCl3 at
room temperature displayed significant changes in the
chemical shifts of the protons of the complex relative to
those of its free components (see the Supporting Informa-
tion). The separation of the originally overlapping signals for
the protons of the two methylene groups in the diethylene
glycol unit of macrocycle 1 (d = 3.69 ppm) into two separate
broad signals in the presence of the urea derivative 3 suggests
that hydrogen bonding probably occurred between the host
and guest. The broad, upfield-shifted signals of the protons of
the xylyl groups of macrocycle 1 and of the phenyl groups of 3
in the mixture suggests the likelihood of stacking of the two
components—such that the urea moiety is positioned within
the cavity of the macrocycle, that is, in the form of a
obtained after adding NaBArF (2 equiv) to the solution in (b).
4
#: Signals from NaBArF .
4
addition of 2 equivalents of sodium tetrakis[(3,5-bis(trifluoro-
methyl)phenyl]borate (NaBArF ) to the solution of macro-
4
1
cycle 1, urea derivative 3, and TBAA resulted in a H NMR
spectrum (Figure 1c) similar to that of the original mixture of
1 and 3 (Figure 1a), suggesting that the original complex 1ꢀ3
had been regenerated in solution as a result of the precip-
itation of sodium acetate. Thus, the sequential addition of
TBAA and NaBArF to a solution of 1 and 3 can be used to
4
switch the complex between its non-associated and pseudo-
rotaxane states; that is, this complex behaves as an acetate
anion-controllable molecular switch.
[2]pseudorotaxane assembly 1ꢀ3 (Scheme 1). From
a
1H NMR spectroscopic dilution experiment, we determined
To prove unambiguously that a [2]pseudorotaxane com-
plex between macrocycle 1 and the diphenylurea 3 forms in
solution, we attempted to stopper this complex to form a
corresponding [2]rotaxane. Thus, we synthesized the [2]rotax-
anes 6 and 7 (yields of isolated products: 23 and 20%,
respectively) through reactions of the semirotaxane formed
between macrocycle 1 and the urea derivative 5 with two
different bulky isocyanates (Scheme 3).[15] For these rotax-
anes, we expected that addition of an anion such as TBAA
would cause the interlocked macrocycle to switch between
the urea and carbamate recognition sites, that is, that 6 and 7
would function as molecular switches.
To confirm that the syntheses of molecular switches 6 and
7 resulted from recognition of the amide-based macrocycle 1
to the diphenylurea unit, rather than to the carbonyl group of
the isocyanate motif,[16] we synthesized the symmetrical
rotaxane 9 from the reaction of 1, urea-derivative 8, and
triisopropyl triflate (Scheme 4).[17] We believe that the
relatively low yield (12%) of this reaction is due partially to
the generation of anions during the reaction; these anions
disrupt the hydrogen bonding of the remaining pseudorotax-
ane complexes.
the association constant (Ka) for the formation of this
complex in CDCl3 to be 180mÀ1 [10]
Similar dilution experi-
.
ments gave an association constant (Ka) for binding of the
ester-substituted thread 4 to the macrocycle 1 as greater than
104 mÀ1 [11]
,
which is more than 50-fold higher than for the 1ꢀ3
complexation. We suspect that this result is partly due to the
electron-withdrawing ester substituents of 4 increasing the
[12]
À
hydrogen-bond-donating ability of the N H bonds.
Our
hypothesis that this [2]pseudorotaxane was stabilized pre-
dominantly through hydrogen-bonding interactions between
the two components is supported by our observation of only
negligible shifts in the positions of the various signals in the
1H NMR spectrum recorded from an equimolar mixture of 1
and 3 in CD3CN (i.e., a more-polar solvent).[13]
1
The H NMR spectrum in Figure 1b indicates that the
addition of 2 equivalents of tetrabutylammonium acetate
(TBAA) to an equimolar mixture of macrocycle 1 and the
urea derivative 3 caused the reappearance of the signals of the
free macrocycle and the appearance of signals of the complex
formed between 3 and the acetate anion; that is, the addition
of TBAA led to dissociation of the complex 1ꢀ3.[12,14] The
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bonded bridge between the amide
protons of the urea unit and the
oxygen atoms of the diethylene
glycol chain.
We employed [2]rotaxane 7 to
demonstrate the acetate anion con-
trollable switching behavior in solu-
tion while minimizing potential signal
overlap in the aromatic region, which
would complicate analysis of the
spectra. 2D COSY and NOSY experi-
ments helped us to identify most of
1
the signals in the H NMR spectrum
of the [2]rotaxane 7 in CDCl3/CD3CN
(1:1) at 298 K (Figure 3); we con-
firmed that, under these conditions,
the macrocycle resided on the urea
station (see the Supporting Informa-
tion), as it did for 6 in the solid state
(Figure 2). The addition of 5 equiva-
lents of tetramethylammonium ace-
tate (TMAA) to the [2]rotaxane 7 in
CDCl3/CD3CN (1:1) induced signifi-
cant changes in the 1H NMR spec-
trum (Figure 3b)—upfield shifts of
protons Hl’ and Hj’’ and a downfield
shift for proton Hg’—after the addi-
tion of TMAA, suggesting that the
macrocyclic component had moved
from the urea station toward the
carbamate station (Scheme 5). The
2D NOSY spectrum of this mixture
displayed (see the Supporting Infor-
mation) cross-signals of the xylyl
protons (Hc’ and Hd’) of the macro-
cycle and the amide protons of the
Scheme 3. Syntheses of molecular switches.
Scheme 4. Synthesis of a symmetrical [2]rotaxane.
We grew single crystals suitable for X-ray crystallography
through liquid diffusion of hexane into a solution of rotaxane
6 in CH2Cl2. The solid-state structure[18,19] (Figure 2) reveals
the expected interlocked nature of the [2]rotaxane; macro-
cycle 1 resides on the diphenylurea unit with its two amide
protons hydrogen bonded to the oxygen atom of the urea
center. Interestingly, one water molecule acted as a hydrogen-
Figure 2. Ball-and-stick representation of the solid-state structure of
[2]rotaxane 6. Atom labels: C gray, H pink, O orange, N blue. The
hydrogen bonding geometries X···O, H···O [Š], and X-H···O [8] are
a) 2.88, 2.05, 164.6; b) 2.91, 2.08, 161.7.
Figure 3. Partial 1H NMR spectra (400 MHz, CDCl3/CD3CN (1:1),
298 K) of a) molecular switch 7, b) the mixture obtained after adding
TMAA (5 equiv) to the solution in (a), and c) the mixture obtained
after adding NaClO4 (5 equiv) to the solution in (b).
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Communications
recognition system could be adapted for the preparation of
biological detectors or sensors. Currently, we are studying
electrochemically and photochemically controllable molec-
ular switches based on this recognition system.
Received: May 18, 2007
Published online: July 30, 2007
Keywords: anion recognition · host–guest systems ·
.
molecular switches · rotaxanes · urea
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1
solution resulted in a H NMR spectrum (Figure 3c) similar
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conditions.[20] Therefore, we could operate the translational
isomerism of the interlocked molecular switch 7 reversibly
through the sequential addition and removal of acetate anions
(Scheme 5). Unlike previously reported systems, which
required ion-pairing compounds to exchange the counter-
anions or the creation of negative charge (through deproto-
nation) on the molecular switch itself, we operated our
[2]rotaxane-based molecular switch 7 through the compet-
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nition site, which allowed the [2]rotaxane to remain neutral
throughout the switching process.
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[2]pseudorotaxane complexes, stabilized through intermolec-
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polarity solvents. We exploited the fact that macrocycle 1
recognizes urea moieties to prepare a unique set of molecular
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[19] Crystal data for 6: C79H86O9N6·CH2Cl2·H2O, Mr = 1366.48,
¯
triclinic, space group P1, a = 13.0119(4), b = 14.1602(4), c =
20.4104(6) ꢁ, V= 3662.43(19) ꢁ3, 1calcd = 1.239 gcmÀ3
,
m-
(MoKa) = 0.152 mmÀ1
, T= 295(2) K, colorless cubes; 12883
independent measured reflections, F2 refinement, R1 = 0.0708,
wR2 = 0.1624.
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