A redox-switchable α-cyclodextrin-based [2]rotaxane

Article abstract of DOI:10.1021/ja8036146

A bistable [2]rotaxane comprising an α-cyclodextrin (α-CD) ring and a dumbbell component containing a redox-active tetrathiafulvalene (TTF) ring system within its rod section has been synthesized using the Cu(I)-catalyzed azide-alkyne cycloaddition, and the redox-driven movements of the α-CD ring between the TTF and newly formed triazole ring systems have been elucidated. Microcalorimetric titrations on model complexes suggested that the α-CD ring prefers to reside on the TTF rather than on the triazole ring system by at least an order of magnitude. The fact that this situation does pertain in the bistable [2]rotaxane has not only been established quantitatively by electrochemical experiments and backed up by spectroscopic and chiroptical measurements but also been confirmed semiquantitatively by the recording of numerous cyclic voltammograms which point, along with the use of redox-active chemical reagents, to a mechanism of switching that involves the oxidation of the neutral TTF ring system to either its radical cationic (TTF_?+) or dicationic (TTF₂₊) counterparts, whereupon the α-CD ring, moves along the dumbbell to encircle the triazole ring system. Since redox control by both chemical and electrochemical means is reversible, the switching by the bistable [2]rotaxane can be reversed on reduction of the TTF_?+ or TTF₂₊ back to being a neutral TTF. Copyright

Full text of DOI:10.1021/ja8036146

Published on Web 08/02/2008
A Redox-Switchable r-Cyclodextrin-Based [2]Rotaxane
Yan-Li Zhao,† William R. Dichtel,†,§ Ali Trabolsi,‡ Sourav Saha,† Ivan Aprahamian,† and
J. Fraser Stoddart*,†,‡
Department of Chemistry and Biochemistry, UniVersity of California, Los Angeles, California 90095,
Department of Chemistry, Northwestern UniVersity, EVanston, Illinois 60208, and DiVision of Chemistry and
Chemical Engineering, California Institute of Technology, Pasadena, California 91125
Received May 14, 2008; E-mail: stoddart@northwestern.edu
Switchable, mechanically interlocked molecules have attracted
much interest1,2 on account of their ability to alter the relative
positions of their ring and dumbbell components in response to
external stimuli, such as changes in pH, the absorption of light,
and the consecutive addition or removal of electrons. This switching
at a molecular level has been harnessed in a range of devices,
including nanoelectromechanical ones,3 surface-property control-
lers,4 mesoporous nanoparticle-mounted nanovalves,5 and molecular
electronic devices.6 Redox-responsive bistable [2]rotaxanes and
[2]catenanes are of considerable interest because the redox-
responsive switching process is usually rapid and precise and can
be controlled within solid-state devices, as well as on surfaces.
Though cyclodextrins (CDs) have also been introduced7,8 as the
ring components into [2]rotaxanes because of (i) their ability to
interact favorably with hydrophobic units and (ii) their biocom-
patibility, redox-responsive bistable [2]rotaxanes incorporating CD
rings have yet to be investigated. Such systems might be able to
interface with redox-active enzymes or even act as the switching
components in implantable medical devices. Herein, we describe
the template-directed synthesis9 and switching behavior of a bistable
[2]rotaxane 3, wherein an R-CD ring can be induced to move on
Figure 1. 1H NMR spectra of (a) the dumbbell 6 (0.9 mM) in K2CO3 (4.0
mM)/D2O solution, (b) the oxidized dumbbell 6 in the presence of 30%
D2O2/D2O solution ([D2O2] ) 2.2 mM), (c) [2]rotaxane 3 (1.0 mM) in
K2CO3 (4.0 mM)/D2O solution, and (d) the oxidized [2]rotaxane 3 in the
presence of 30% D2O2/D2O solution ([D2O2] ) 2.2 mM) at 25 °C.
account of the redox properties of a tetrathiafulvalene (TTF) unit
Scheme 1. Syntheses of the [2]Rotaxane 3 and the Corresponding
Dumbbell Compound 6
located in the dumbbell component of 3 which was obtained10 from
aqueous solution (Scheme 1) employing a recently developed
threading-followed-by-stoppering approach11 which relies on the
efficiency of the copper (I)-catalyzed azide-alkyne cycloaddition.
The free dumbbell compound 6 was also made by a similar route
[see the Supporting Information (SI) and Scheme 1], except that
R-CD was omitted from the reaction mixture. 1H NMR and UV-vis
spectroscopies, together with cyclic voltammetry (CV) and induced
circular dichroism (ICD) experiments, have been employed in
conjunction with one another, to show that the 1,2,3-triazole ring,
which is installed during the synthesis of 3, serves as the second
port of call for the R-CD ring where the TTF unitsthe preferred
resting place for the R-CD ring by farsis oxidized either to its
radical cation or to its dication.
To characterize 3 and establish the nature of the coconformation
adopted by the chiral R-CD on the achiral chromophoric dumbbell
component, ICD experiments (see Figure S5 in the SI) were
performed on both 3 and 6 at 25 °C in K2CO3/H2O solution. As
expected, no ICD signal was observed for 6. The ICD spectrum of
3, however, reveals a positive Cotton effect peak at 311 nm with
a ∆ε value of 9.85 dm-3 mol-1 cm-1. From previous investiga-
tions12 carried out by Harata, Kajta´r, and Nau on the ICD properties
of CD complexes, we can deduce that the TTF unit in the dumbbell
is encircled by the R-CD ring in the [2]rotaxane.13 This deduction
† University of California, Los Angeles.
§ California Institute of Technology.
‡ Northwestern University.
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10.1021/ja8036146 CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Figure 2. 1H NOESY spectrum (600 MHz) of R-CD [2]rotaxane 3 (1.0 mM)
in K2CO3 (4.0 mM)/D2O solution at 25 °C with mixing time ) 150 ms.
Figure 4. 1H NOESY spectrum (600 MHz) of R-CD [2]rotaxane 3 (1.0 mM)
in K2CO3 (4.0 mM)/D2O solution after the addition of 30% D2O2/D2O solution
([D2O2] ) 2.2 mM) at 25 °C with mixing time ) 150 ms.
is confirmed by the fact that the chemical shifts of the TTF
resonances for Hc/f and Hd/e shifted downfield by 0.09 and 0.12
ppm, respectively, relative (Figure 1 a,c) to those obtained for the
equiv of the oxidant, an observation which indicates that the R-CD
ring moves away from the TTF unit immediately after oxidation.
The peak at 595 nm, which corresponds to the presence15 of the
TTF•+ radical cation in the [2]rotaxane, emerges during the course
of addition of 0.2-1.0 equiv of Fe(ClO4)3.
1
analogous protons in 6. In the H NOESY spectrum14 (Figure 2)
of 3, NOE crosspeaks (A-D) between the protons (Hc/f and Hd/
e) of the TTF unit and the protons (H3 and H5) lining the inside of
the R-CD are observed, supporting the conclusion that the neutral
TTF unit is encircled by the R-CD ring in 3.
The location of the R-CD ring in the oxidized forms of 3 can
also be deduced from 1H NMR experiments (Figure 1c,d). The
peaks for Hd/e, which resonate around 6.58 ppm when 3 is dissolved
in K2CO3/D2O solution at 25 °C, shift downfield to 8.36 ppm,
corresponding to TTF2+, after the addition of 30% D2O2/D2O
solution (2 equiv), while the peaks for Hi and Hg move upfield by
0.10 and 0.08 ppm, respectively and the peaks for Hh moves
downfield by 0.02 ppm, suggesting that, on oxidation of the TTF
unit, the R-CD ring moves to the triazole ring system. Since the
oxidized form of 3 is stable in D2O for several hours, we were
able to perform 1H NOESY NMR experiments on the oxidized
rotaxane. They reveal (Figure 4) NOE crosspeaks between the H3/
H5 protons on the inside of the R-CD ring and (i) Hg (crosspeaks
E and F), (ii) Hi (crosspeaks G and H), and (iii) Hh (crosspeak I),
indicating the relocation of the R-CD ring on the triazole unit.
CV experiments, carried out (Figure 5) on both 3 and 6,
demonstrate that, while the latter exhibits two one-electron revers-
ible oxidation processes at +0.17 and +0.54 V (in the potential
The preferred encirclement of the TTF unit can also be monitored
by UV-vis spectroscopy. The UV-vis spectra of 3 and 6, recorded
(see Figure S6 in the SI) in K2CO3/H2O solution at 25 °C, show
that the absorption peak at 432 nm for the TTF unit in the dumbbell
compound 6 is decreased in intensity and red-shifted to 457 nm in
the [2]rotaxane 3. Also, the peak observed at 595 nm for the TTF•+
radical cation15 after partial oxidation of 6 is attenuated relative to
that in 3, following its oxidation, showing that the encirclement by
the R-CD ring prevents the oxidization of the TTF unit in the
[2]rotaxane under these conditions. When the oxidization of 3 was
monitored (Figure 3) by UV-vis spectroscopy, following the
addition of Fe(ClO4)3 solutions, the peak for the TTF unit at 457
nm shifts back to one centered on 432 nm after the addition of 0.2
Figure 3. UV-vis spectral changes of [2]rotaxane 3 (1.1 mM) in 4.0 mM
K2CO3/H2O upon addition of Fe(ClO4)3 ·6H2O (0∼1.0 mM from concentra-
tion a to f) aqueous solution at 25 °C.
Figure 5. Cyclic voltammetry of [2]rotaxane 3 (black, 1.1 mM) and dumbbell
6 (red, 1.1 mM) in 0.1 M LiClO4/H2O at scan rate ) 100 mV s-1
.
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C O M M U N I C A T I O N S
range between -0.2 and +0.8 V at a scan rate of 100 mV s-1) for
the first and second oxidization peaks16 of the TTF unit, the former
reveals that the first oxidization peak for the [2]rotaxane shifts
dramatically to +0.32 V, whereas the second oxidization peak at
+0.55 V is very similar to that observed for the dumbbell. These
observations support those obtained from UV-vis spectroscopy,
that is, the R-CD ring moves away from the TTF unit in the
[2]rotaxane just as soon as it is oxidized to the TTF•+ radical cation.
In the reducing cycle, the first reduction peaks of the TTF2+ dication
at +0.46 and +0.48 V for 3 and 6, respectively, are almost identical.
The fact that the separation between the second reduction peaks
for 3 and 6 is 0.14 V seems to suggest that the R-CD ring is already
close enough to the TTF unit in the [2]rotaxane to influence the
reduction of the TTF•+ radical cation back its neutral form.17 The
R-CD ring might also be facilitating the desolvation of the TTF•+
radical cation in aqueous solution.18
In a nutshell, we have demonstrated the operation of a redox-
switchable R-CD-based [2]rotaxane using both spectroscopic and
electrochemical probes. The R-CD ring in the [2]rotaxane moves
between a TTF unit, the more preferred19 station, and a triazole
ring system, the less preferred19 station, under redox control. This
dynamic property has consequences for the design, synthesis, and
fabrication of nanoscale systems and devices. These findings have
implications for the production of mechanized nanoparticles5 that
can be used for drug delivery where the stimulus is a unique redox
state often present within diseased cells but not in healthy cells.
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(10) Since the TTF unit has two cis-trans constitutional isomers and the R-CD
ring has a primary and a secondary face, four isomeric [2]rotaxanes can
be, in principle, formed as
a consequence of the dumbbell being
constitutionally unsymmetrical. We have employed an orange cylinder to
represent the R-CD ring in the different isomeric forms of 3, whether it be
a structural formula or a graphical representation. On the basis of the ratio
of two TTF methine proton peaks (Hd and He) in the 1H NMR spectrum
of the [2]rotaxane, we have calculated that the ratio of the cis and trans
TTF units-based constitutional isomers in the [2]rotaxane is ca. 3:2.
(11) (a) Aucagne, V.; Ha¨nni, K. D.; Leigh, D. A.; Lusby, P. J.; Walker, D. B.
J. Am. Chem. Soc. 2006, 128, 2186–2187. (b) Dichtel, W. R.; Miljanic´, O.
Acknowledgment. We acknowledge support from the Micro-
electronics Advanced Research Corporation and its Focus Center
Research Program, the Center on Functional Engineered Nano-
Architectonics, and the Center for Nanoscale Innovation for
Defense.
Supporting Information Available: Experimental details and
spectral characterization data. This material is available free of charge
via the Internet at http://pubs.acs.org.
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