Using oppositely charged ions to operate a three-station [2]rotaxane in two different switching modes

Article abstract of DOI:10.1021/ol203401d

A [2]rotaxane undergoes switching of its bis-p-xylyl-[26]crown-6 (BPX26C6) component away from its guanidinium station toward its 2,2′-bipyridyl and carbamate stations upon the addition and removal of Zn²⁺ and PO ₄^3- ions,

Full text of DOI:10.1021/ol203401d

ORGANIC
LETTERS
2012
Vol. 14, No. 4
1046–1049
Using Oppositely Charged Ions To
Operate a Three-Station [2]Rotaxane in
Two Different Switching Modes
Ya-Ching You,† Mei-Chun Tzeng,† Chien-Chen Lai,‡ and Sheng-Hsien Chiu*,†
Department of Chemistry and Center for Emerging Material and Advanced Devices,
National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei, Taiwan, 10617,
R.O.C., and Institute of Molecular Biology, National Chung Hsing University and
Department of Medical Genetics, China Medical University Hospital, Taichung,
Taiwan, R.O.C.
shchiu@ntu.edu.tw
Received December 20, 2011
ABSTRACT
A [2]rotaxane undergoes switching of its bis-p-xylyl-[26]crown-6 (BPX26C6) component away from its guanidinium station toward its 2,20-bipyridyl
and carbamate stations upon the addition and removal of Zn2þ and PO43ꢀ ions, respectively.
The development of new methods and protocols for
the operation of rotaxane-type molecular switches
and actuators has attracted much attention because
such systems have potential applicability in sensing,1
organogelation,2 drug delivery,3 fluid transportation,4
and molecular memory.5 For molecular switches that are
operated chemically, the external stimuli are frequently
cationic species (e.g., metal ions, protons)6 because the
ionꢀdipole and/or hydrogen bonding interactions intro-
duced by these additives can be sufficiently strong to invert
the interlocked macrocyclic unit’s preference for the bind-
ing sites. In contrast, anion-controllable interlocked mo-
lecular switches are relatively rare7 because the larger sizes,
unique shapes, and higher solvation energies of anions in
solution, relative to cations, complicate the molecular
design for the recognition process. Although simultaneous
recognition of cations and anions in a macrocyclic host is
possible,8 it remains a challenge to operate interlocked
molecular switches in different switching modes through
the application of ions of opposite charges. In theory,
such a dual-mode molecular switch could be constructed
by adding two more recognition stations to the thread
component of a [2]rotaxane, allowing the interlocked
macrocyclic moiety to migrate specifically in the presence
of a particular charged species (see abstract image);
† National Taiwan University.
‡ National Chung Hsing University and China Medical University Hospital.
(1) (a) Chmielewski, M. J.; Davis, J. J.; Beer, P. D. Org. Biomol.
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Wojcik, A.; Kamat, P. V.; Smith, B. D. Chem.;Eur. J. 2010, 16, 2916–
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Stoddart, J. F. J. Am. Chem. Soc. 2008, 130, 6348–6350. (b) Hsueh,
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r
10.1021/ol203401d
Published on Web 01/31/2012
2012 American Chemical Society

because these ions cannot be added to the solution without
complementary counterions, however, fine-tuning of the
energetics would be required to maintain the orthogonality
of the two operating modes. Herein, we report a three-station
[2]rotaxane in which 2,20-bipyridyl and carbamate units
serve as additional recognition stations that allow the bis-p-
xylyl-[26]crown-6 (BPX26C6)9 component to migrate away
from its originally occupied guanidinium station upon the
addition and removal of Zn2þ and PO43ꢀ ions, respectively.
To ensure solubility of the necessary salts, the desired
molecular switch would have to be operated in a quite
polar solvent (e.g., CH3CN) or a mixture with a less polar
one (e.g., CHCl3, CH2Cl2). Because the affinities of these
charged species to their binding sites in the [2]rotaxane
would be significantly weakened through high solvation in
polar solvents, the binding affinity of the macrocyclic
component to the original recognition station should not
be too strong under such conditions to ensure facile ion-
driven switching. Thus, we selected the guanidinium ion,
which is also solvated well in more polar solvents but
capable of threading through BPX26C6 in CH2Cl2,7g as a
recognition site for assembling the molecular switch. A
readily accessible monopyridinium ion would not be a
suitable secondary station for the anion-mediated switch-
ing process because its binding affinity to BPX26C6 is
higher than that of a guanidinium ion in CD3CN.7g There-
fore, we chose a carbamate unit as the second station, with
the expectation that [NꢀH O] hydrogen binding of its
3 3 3
NH proton to the oxygen atoms of BPX26C6 and its
weaker interaction with anions, relative to that of the
guanidinium ion, would allow it to host the macrocycle
in the presence of competing anions in solution. In a
previous study, we found that the interlocked BPX26C6
macrocyclic moiety and the 2,20-bipyridyl unit of the
thread component of a [2]rotaxane can interact orthogon-
ally to induce the recognition of specific metal ions,
thereby providing a 1H NMR spectroscopic probe for the
simultaneous identification of physiologically important
metal ions in a solution mixture.10 It seemed reasonable to
expect that the interlocked BPX26C6 component might
move to the 2,20-bipyridyl station from the guanidinium
station if we were to introduce suitable metal ions into the
solution.
Scheme 1
Scheme 2
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(8) For recent examples, see: (a) Zhu, K.; Li, S.; Wang, F.; Huang, F.
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D. E.; Lee, C.-H.; Kim, J. S.; Lynch, V. M.; Delmau, L. H.; Hay, B. P.
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Org. Lett., Vol. 14, No. 4, 2012
1047

Taking all of these factors into consideration, we de-
signed the [2]rotaxane 1-H PF6;featuring guanidinium,
bipyridyl, and carbamate units as three stations for the
interlocked BPX26C6 component;as a dual cation/
anion-operated molecular switch (Scheme 1).
upfield shift for the former sample, consistent with the
BPX26C6 component residing at the bipyridinium station
under these conditions (see the SI). The presence of cross
peaks for the signals of the aromatic (HAr) and diethylene
glycol protons of BPX26C6 with the signals for the
3
0
bipyridinium protons (HR, HR , Hβ) in the 2D NOSY
spectrum of a 2:1 mixture of TFA and the [2]rotaxane 1-
H PF6 (see the SI) confirmed the encircling of the macro-
3
cyclic component around the bipyridinium station under
these conditions. The addition of Et3N (3 equiv) to the
solution of the [2]rotaxane 1-H PF6 and TFA resulted in a
3
1H NMR spectrum (Figure 1c) similar to that of the original
(untreated) [2]rotaxane 1-H PF6 (Figure 1a), suggesting
3
that the BPX26C6 unit had moved back to encircle the
guanidinium ion. Thus, the [2]rotaxane 1-H PF6 can be
3
operated as an acid/base-controllable molecular switch, in
which the interlocked BPX26C6 component can be posi-
tioned selectively at the bipyridyl and guanidinium stations
through sequential additions of TFA and Et3N, respectively.
After having proven that the interlocked BPX26C6 unit
in the [2]rotaxane 1-H PF6 could be moved from the
3
guanidinium ion to the 2,20-bipyridyl station through the
addition of protons, we suspected that a similar migration
would also be possible when driven by the addition of
appropriate metal ions. Figure 2 reveals that the addition
of Zn(ClO4)2 to a solution of the [2]rotaxane 1-H PF6 led
1
to significant migrations of the signals in the H NMR
3
Figure 1. Partial 1H NMR spectra (400 MHz, CD3CN, 298 K) of
(a) the [2]rotaxane 1-H PF6, (b) the mixture obtained after
adding TFA (2 equiv) to the solution in (a), and (c) the mixture
obtained after adding Et3N (3 equiv) to the solution in (b).
3
spectrum. The shifts of the signals of the xylene units (HAr)
of the interlocked BPX26C6 component and of the methy-
lene groups adjacent to the guanidinium ion (Hc, Hd) for 1-
H PF6 in the presence of Zn2þ ions were similar to those
3
We synthesized the threadlike guanidinium salt 2-H
obtained above after adding TFA to the [2]rotaxane, imply-
ing that the interlocked BPX26C6 moiety had again migrated
to the bipyridyl station. The appearance of cross peaks
between the signals of the aromatic protons (HAr) of the
BPX26C6 unit and the signals of the bipyridyl protons
3
PF6 in nine steps from 5,50-dibromo-[2,20]bipyridyl (see the
Supporting Information (SI)). Because the protonated
form of 2,20-bipyridyl can also form complexes with
BPX26C6, thereby increasing the efficiency of the assem-
bly of the [2]rotaxane,9d,10 we reacted the macrocycle
BPX26C6, 1-isocyanato-3,5-di-tert-butylbenzene,2b,7d and
0
(HR, HR ) in the 2D NOSY spectrum of a mixture of the
[2]rotaxane 1-H PF6 and Zn(ClO4)2 (see the SI) was con-
3
the threadlike guanidinium salt 2-H PF6 under acidic
3
sistent with the BPX26C6 component encircling the bipyridyl
station under these conditions. The signals of the protons of
the [2]rotaxane 1-H PF6 shifted back (Figure 2c) to their
conditions, followed by ion exchange and neutralization
of the (presumably) protonated 2,20-bipyridyl station, to
affordthedesired[2]rotaxane1-H PF6 anditscorrespond-
3
original positions [i.e., prior to the addition of Zn(ClO4)2]
after the introduction of 1 equiv of N,N,N0,N0-tetrakis-
(2-pyridylmethyl)ethylenediamine (TPEN), a tight sequestering
agent for Zn2þ ions,11 suggesting that the BPX26C6 moiety
had returned to encircle the guanidinium ion after removing
3
ing dumbbell-shaped threadlike salt 3-H PF6 in 9% and
45% yields, respectively (Scheme 2).
3
Because BPX26C6 can form complexes with protonated
2,20-bipyridyl units, we suspected that the [2]rotaxane 1-
H PF6 would function as an acid/base-controllable mole-
the complexed metal ion. Thus, the [2]rotaxane 1-H PF6 can
3
3
cular switch. After the addition of 2 equiv of trifluoroacetic
acid (TFA) to a CD3CN solution of the [2]rotaxane, the 1H
NMR spectrum revealed significant upfield and downfield
shifts of the signal of the xylene protons (HAr) of BPX26C6
and of the signals of the methylene groups adjacent to the
guanidinium ion (Hc, Hd), respectively, suggesting that the
macrocycle BPX26C6 had moved away from the guanidi-
nium station to stack with the aromatic motifs of the
bipyridyl unit of the threadlike component. A compari-
son of the signals of the bipyridinium protons in the
be switched not only through pH control but also through
metal ion control, with the interlocked BPX26C6 component
residing at the bipyridyl and guanidinium stations upon the
addition and removal of Zn2þ ions, respectively.
Having demonstrated that the migration of the BPX-
26C6 unit between the guanidinium and bipyridyl stations
in the [2]rotaxane 1-H PF6 could be controlled using
3
either Hþ or Zn2þ cations, we turned our attention to the
(11) (a) Kawabata, E.; Kikuchi, K.; Urano, Y.; Kojima, H.; Odani, A;
Nagano, T. J. Am. Chem. Soc. 2005, 127, 818–819. (b) Blindauer, C. A.;
Razi, M. T.; Parsons, S.; Sadler, P. J. Polyhedron 2006, 25, 513–520.
[2]rotaxane with those in the dumbbell-shaped salt 3-H
PF6 in the presence of TFA revealed a more significant
3
1048
Org. Lett., Vol. 14, No. 4, 2012

Figure 3. Partial 1H NMR spectra (400 MHz, CD3CN, 298 K) of
(a) the [2]rotaxane 1-H PF6, (b) the mixture obtained after adding
(TBA)3PO4 (2 equiv) to the solution in (a), and (c) the mixture
obtained after adding Ba(ClO4)2 (3 equiv) to the solution in (b).
Figure 2. Partial 1H NMR spectra (400 MHz, CD3CN, 298 K) of
(a) the [2]rotaxane 1-H PF6, (b) the mixture obtained after
adding Zn(ClO4)2 (1 equiv) to the solution in (a), and (c) the
mixture obtained after adding TPEN (1 equiv) to the solution in
(b). Asterisks: Signals from Zn2þ-complexed TPEN.
3
3
of the ethylene glycol loops of the BPX26C6 component in
the 2D NOSY spectrum, suggested that the macrocycle
resided on the carbamate station after the addition of
(TBA)3PO4. Addition of Ba(ClO4)2 (3 equiv) to this
anion-mediated switching of this system. We suspected
that 1-H PF6 would function as an anion-controllable
3
molecular switch, with the interlocked BPX26C6 compo-
nent migrating between the guanidinium and carbamate
stations, if a tightly binding anion were to be introduced to
compete with the macrocycle for the guanidinium station
(Scheme 1). The singly charged anions Clꢀ, Fꢀ, Brꢀ, and
OAcꢀ failed to provide clean and clear switching in the
3ꢀ
mixture removed the PO4 anions from the solution by
forming a precipitate of the less-soluble Ba3(PO4)2; accord-
ingly, the macrocycle reverted to its original guanidinium
station, as evidenced by the restoration of the signals in the
1H NMR spectrum back to their original positions prior
to the addition of the PO43ꢀ anions (Figure 3c). Thus, the
operation of the [2]rotaxane 1-H PF6, presumably be-
3
cause these anions and the guanidinium ion were highly
solvated in the polar solvent, thereby weakening their
interactions. Because highly charged anionic species com-
plex more tightly with guanidinium-based anion receptors
through stronger electrostatic interactions,12 we suspected
that the PO43ꢀ anion might, unlike the tested monovalent
anions, be capable of displacing the interlocked BPX26C6
unit to reside at the carbamate station. The addition
of (TBA)3PO4 (2 equiv) to a CD3CN solution of the
[2]rotaxane 1-H PF6 also functions as an anion-controlla-
3
ble molecular switch, with the interlocked macrocycle itin-
erating between the carbamate and guanidinium stations
through the simple addition and removal of PO43ꢀ anions.
We have constructed a three-station [2]rotaxane in
which the macrocyclic component can migrate not only
between the guanidinium and 2,20-bipyridyl stations of the
threadlike unit through the addition and removal of
suitable cations (Hþ, Zn2þ) but also between the guanidi-
nium and carbamate motifs through the addition and
removal of PO43ꢀ anions. We believe that such dual-mode
molecular switches, which can be controlled orthogonally
through the application of oppositely charged ions, will aid
in the development of complicated molecular actuators
and sensors for specific ion pairs.
1
[2]rotaxane 1-H PF6 resulted in a H NMR spectrum
3
revealing the clean and clear migration of the macrocyclic
component (Figure 3b). We used 2D COSY and NOSY
spectra to identify the signals of the [2]rotaxane 1-H PF6
3
before and after the addition of (TBA)3PO4. The negligible
1
shifts of the signals of the 2,20-bipyridyl unit in the H
NMR spectra suggested that it was not involved in the
complexation of the BPX26C6 moiety under these condi-
tions. The significant upfield and downfield shifts of the
benzylic protons adjacent to the carbamate (Hi) and
guanidinium (Hc, Hd) stations, respectively, in the H
NMR spectrum, together with the cross signals between
the protonsnearthe carbamate units (Hj, Hh, Hi) and those
Acknowledgment. We thank the National Science Council
(Taiwan) for financial support (NSC-100-2119-M-002-026).
1
Supporting Information Available. Synthetic proce-
dures and characterization data for the [2]rotaxane 1-H
3
PF6. This material is available free of charge via the
Internet at http://pubs.acs.org
(12) Dietrich, B.; Fyles, D. L.; Fyles, T. M.; Lehn, J.-M. Helv. Chim.
Acta 1979, 62, 2763–2787.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 4, 2012
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