Light-switchable Janus [2]rotaxanes based on α-cyclodextrin derivatives bearing two recognition sites linked with oligo(ethylene glycol)

Article abstract of DOI:10.1002/asia.201000169

Two Janus [2]rotaxanes, 5a and 5b, with α-cyclodextrin (a-CD) derivatives substituted on the 6-position with two recognition sites (azobenzene and heptamethylene (C7)) that were linked with linkers of different lengths (oligo(ethylene glycol) with a degre

Full text of DOI:10.1002/asia.201000169

DOI: 10.1002/asia.201000169
Light-Switchable Janus [2]Rotaxanes Based on a-Cyclodextrin Derivatives
Bearing Two Recognition Sites Linked with Oligo(ethylene glycol)
Shujing Li,[a] Daisuke Taura,[a] Akihito Hashidzume,[a] and Akira Harada*[a, b]
Abstract: Two Janus [2]rotaxanes, 5a
and 5b, with a-cyclodextrin (a-CD) de-
rivatives substituted on the 6-position
with two recognition sites (azobenzene
and heptamethylene (C7)) that were
linked with linkers of different lengths
(oligo(ethylene glycol) with a degree of
polymerization equal to 2 or approxi-
mately 21) were synthesized and char-
acterized. 2D ROESY NMR spectros-
copy and circular dichroism (cd) spec-
tra demonstrated that the recognition
site of the a-CD moiety was switched
by photoisomerization of the azoben-
zene moiety in 5a and 5b. The differ-
ent size changes of 5a and 5b in hydro-
dynamic radius (RH) owing to the dif-
ferent length of linker between two
recognition sites were observed by
pulse-field-gradient spin-echo NMR
spectroscopy. The kinetic results indi-
cated that the different length of linker
had no or a weak effect for the photo-
Keywords: cyclodextrins
· molec-
ular muscles photochemistry
·
·
rotaxanes · supramolecular chemis-
try
AHCTUNGTRENGNiUN somerization process of 5a and 5b.
Introduction
[2]rotaxane was first reported by Sauvage et al.[4] They syn-
thesized a Janus [2]rotaxane based on a crown ether moiety
containing two CuI metals and demonstrated switching of
the location of the crown ether moiety by extraction of CuI
with KCN and by remetalation with ZnII. Stoddart and co-
workers[5] have synthesized a Janus [2]rotaxane from crown
ether and ammonium moieties and observed that the loca-
tion of the crown ether moiety was switched by changing
the pH value. Stoddart and co-workers[6] also have extended
their Janus [2]rotaxane to a polymeric one by Huisgen [3+2]
cycloaddition by using dangling alkyne groups at both ends
and a diazide. More recently, Grubbs and co-workers[7] have
synthesized a Janus [2]rotaxane carrying azide moieties by
ring-closing metathesis and formed polymers of the Janus
[2]rotaxane units by Huisgen [3+2] cycloaddition with a di-
alkyne. They directly observed a pH-responsive change in
the radius of gyration of the polymer obtained by multi-
angle, laser-light scattering.
Biological systems utilize well-defined supramolecular as-
semblies formed from macromolecules, for example, nucleic
acids and proteins, as molecular machines to maintain living
activities.[1] These biological supramolecular machines have
been inspiring a number of research groups to make their
efforts for construction of highly-functional artificial supra-
molecular machines.[2] One of the most important challenges
toward artificial supramolecular machines is artificial mus-
cles that undergo expansion and contraction as a response
to external stimuli, mimicking the movement of muscle
fibers that utilize sliding of the components.[3]
An important structural unit of artificial muscles is Janus
[2]rotaxanes in which the location of the rotor moiety is
switched by external stimuli. A stimuli-responsive Janus
[a] S. Li, D. Taura, A. Hashidzume, Prof. A. Harada
Department of Macromolecular Science
Graduate School of Science
An important rotor moiety, apart from crown ethers, is cy-
clodextrin (CD). The advantage of CDs is their molecular-
recognition ability in aqueous media. Janus [2]rotaxanes
containing CD as a rotor have been reported independently
by Kaneda and co-workers[8] and our group.[9] A photores-
ponsive Janus [2]rotaxane has been reported by Easton and
co-workers.[10] They utilized a stilbene moiety as a photores-
ponsive moiety and demonstrated photoresponsive switching
of the location of the a-CD moiety through spectroscopic
analysis. We have also previously synthesized a Janus [2]ro-
taxane containing a-CD, successfully switched the location
Osaka University
1-1 Machikaneyama, Toyonaka, Osaka 560-0043 (Japan)
Fax : (+81)6-6850-5445
E-mail: harada@chem.sci.osaka-u.ac.jp
[b] Prof. A. Harada
Core Research for Evolutional Science and Technology (CREST)
(Japan) Science and Technology Agency (JST)
5 Sanbancho, Chiyoda-ku, Tokyo 102-0075 (Japan)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201000169.
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of the a-CD moiety by changing the media, and observed a
change in the hydrodynamic radius RH of the Janus [2]rotax-
ane as determined by pulse-field-gradient spin-echo (PGSE)
NMR spectroscopy.[11]
tion constant of 102 mꢀ1. Preliminary ROESY experiments
for model compounds indicated that the signals owing to the
C3 and C5 protons inside the cavity of a-CD showed corre-
lation signals not only owing to the trans-Azo moiety but
also with signals owing to octamethylene or longer oligo-
methylene moieties. This is indicative of the lower selectivity
of a-CD (data not shown).
These previous studies have utilized two recognition sites
close to each other. To realize a large size change, a longer
linker between the two recognition sites is necessary. In the
preceding study, we have synthesized an a-CD derivative
substituted on its 3-position with azobenzene (Azo) and
heptamethylene (C7) moieties as photoresponsive and non-
responsive recognition sites, respectively, connected by a
longer linker, oligo(ethylene glycol) (OEG; degree of poly-
merization (DP)=~21).[12] We have characterized a doubly
threaded dimer formed from the 3-substituted a-CD deriva-
tive in water by several techniques and observed a photores-
ponsive RH change of the dimer by PGSE NMR spectrosco-
py.[12] However, it was not possible to cap both ends of the
doubly threaded dimer with bulky stoppers to obtain a
Janus [2]rotaxane. Thus, in this study, we have successfully
synthesized Janus [2]rotaxanes by using a-CD derivatives
substituted on the 6-position
Mono(6-amino-6-deoxy)-a-CD[15] (6-NH2-a-CD) was cou-
pled with azobenzene-4,4’-dicarboxylic acid by using N,N’-
dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotria-
zole (HOBt) to give 1. Compound 1 was allowed to react
with excess OEG (DP=2 or ~21) carrying amino groups on
both ends by using (benzotriazol-1-yloxy)-tris(dimethylami-
no) phosphonium hexafluorophosphate (BOP) to give 2.
Compound 2 was allowed to react with tert-butoxycarbonyl-
8-aminooctanoic acid (Boc-Aoc(8)-OH) by using DCC and
HOBt to yield 3. Without purification of 3, the tert-butoxy-
carbonyl group was deprotected with trifluoroacetic acid
(TFA) to produce 4. Compound 4 was capped with 1-ada-
mantanecarboxylic acid by using 4-(4,6-dimethoxy-1,3,5-tria-
with Azo and C7 moieties
linked with OEG linkers of
DP=2 and approximately 21.
Herein, we describe the synthe-
sis of the Janus [2]rotaxanes,
their
photoresponsive
RH
change, and the effect of the
linker length.
Results and Discussion
Synthesis of Janus
[2]Rotaxanes (5a and 5b)
In this study, the Janus [2]rotax-
anes were synthesized accord-
ing to Scheme 1, which is simi-
lar to the previous 3-substituted
analogue. An Azo group and a
C7 moiety have been chosen as
the photoresponsive part and
nonresponsive recognition site,
respectively. It is well known
that the Azo moiety is isomer-
ized from the trans form to the
cis form under irradiation with
UV light and from the cis form
to the trans form under irradia-
tion with visible light.[13] It is
also known that a-CD includes
a trans-Azo moiety with an as-
sociation constant as high as
104 mꢀ1, but it does not interact
with the cis-Azo moiety.[14] On
the other hand, a-CD includes
the C7 moiety with an associa- Scheme 1. Synthesis of Janus [2]rotaxanes 5a, 5b.
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Light-Switchable Rotaxanes
zin-2-yl)-4-methylmorpholinium chloride (DMT-MM) at
08C in an aqueous NaHCO3/Na2CO3 buffer solution in
which 4 formed a doubly threaded dimer, to form the Janus
[2]rotaxane, 5a or 5b. Compounds 1, 2, 4, and 5 were puri-
fied by HPLC and obtained in reasonable yields (30–40%
for each step).
downfield shifts of signals owing to the inner C3 and C5
protons in the a-CD moiety were observed. This is indica-
tive of strong shielding and deshielding effects induced by
the tight inclusion of the trans-Azo moiety facing its p elec-
tron cloud to the B and E glucopyranose units in the a-CD
moiety. The 2D ROESY NMR spectra of 5a and 5b show
correlation signals between the inner protons of the a-CD
moiety and the trans-Azo protons as shown in Figure 2. The
spectra exhibit strong correlation signals between the C3
protons in the a-CD moiety and the c and d protons in the
trans-Azo moiety and between the C5 protons in the a-CD
moiety and the b proton in the trans-Azo moiety, respective-
ly. However, the spectra do not show significant correlation
signals between the inner protons in the a-CD moiety and
the protons in the C7 moiety. These data indicate that the
a-CD moiety selectively includes the trans-Azo moiety from
the narrower rim to form a doubly threaded dimer confor-
mation because of the higher association constant. The con-
formations of 5a and 5b were also investigated by cd spec-
troscopy, as can be seen in Figure 3. These spectra exhibit
the negative- and positive-induced circular dichroism (icd)
bands in the region of n–p* and p–p* transitions of the
trans-Azo moiety. This indicates
The Janus [2]rotaxanes obtained, 5a and 5b, were fully
characterized by matrix-assisted laser desorption ionization
time of flight mass spectrometry (MALDI-TOF-MS), 1D
NMR, 2D NMR (COSY, TOCSY, HMQC, HMBC, and
ROESY), and circular dichroism (cd) spectroscopies. The
MALDI-TOF-MS data showed signals ascribable to the
Janus [2]rotaxanes, 5a and 5b, at m/z=3482.3 and 4864.6–
5571.1, respectively (see Figure S1 in the Supporting Infor-
1
mation). The H NMR spectra for 5a and 5b in D2O exhibit
well-resolved peaks and well-split peaks in the region of CD
protons, indicating that the Azo moiety is included by the a-
CD moiety (see Figures S2 and S3 in the Supporting Infor-
mation). To understand the detailed inclusion fashion of 5a
and 5b, signals of all the protons in the a-CD moiety were
assigned by utilizing COSY, TOCSY, and ROESY NMR
spectroscopy as can be seen in Figure 1. Drastic upfield and
that a-CD includes the trans-
Azo moiety and that the transi-
tion moments of n–p* and p–
p* in the trans-Azo moiety are
perpendicular and parallel to
the axis of the a-CD moiety, re-
spectively.[16]
In the preceding study, it was
not possible to cap the doubly
threaded dimer of the 3-substi-
tuted analogue with 1-adaman-
tanecarboxylic acid under the
same conditions. The 1H NMR
spectrum of the 3-substituted
analogue showed weak but
clear signals owing to the free
monomer,[12]
whereas
the
1H NMR spectra for 4a and 4b
did not exhibit signals owing to
the free monomer, indicating
that the association constants of
the dimerization for 6-substitut-
ed 4a and 4b were much higher
than that for the 3-substituted
analogue. This observation indi-
cates that the higher association
constant is necessary for effi-
cient capping reaction of Janus
[2]rotaxanes.
Figure 1. Assignments of 5a (A) and 5b (B) before UV irradiation based on COSY, TOCSY, ROESY,
HMBC, and HMQC measurements (left) in D2O, and proposed inclusion fashion of the Azo group (right).
Sugar units are labeled clockwise from A to F (viewed from the wider rim), beginning with the altrose unit.
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Figure 3. Circular dichroism spectra variations of 2ꢁ10ꢀ4 m 5a (A) and
5b (B) before (c) and after UV irradiation (g) in water.
Figure 2. Partial ROESY NMR spectra for 3.0 mm 5a (A) and 5b (B)
before UV irradiation measured in D2O at 308C (the mixing time=
200 ms).
Photoisomerization of the Janus [2]Rotaxanes (5a and 5b)
Photoisomerization properties of the Janus [2]rotaxanes, 5a
and 5b, were investigated in detail by UV/Vis absorption
spectroscopy. Figure 4A shows a typical example of time-de-
pendent UV/Vis absorption spectra for 5a and 5b under ir-
radiation with UV light at 365 nm. With elapse of irradia-
tion time (t), the absorption band around 340 nm attributa-
ble to the trans-Azo moiety decreases, whereas the broad
absorption band around 440 nm ascribable to the cis-Azo
moiety increases. To understand the kinetics of trans-to-cis
photoisomerization of 5a and 5b, ln
N
U
values were plotted against t as shown in Figure 5A assum-
ing a pseudo-first-order reaction[17] in which A0, At, and Aeq
are the initial absorbance, the absorbance at t, and the ab-
sorbance in the photostationary state of the Azo moiety at
340 nm, respectively. Figure 5 shows a good linear relation-
ship, indicating that the trans-to-cis photoisomerization
obeys the pseudo-first-order kinetics. From the slopes of the
straight lines in Figure 5A and Equation (1), the pseudo-
first-order rate constants of trans-to-cis photoisomerization
Figure 4. UV/Vis spectra variations of 2ꢁ10ꢀ5 m trans-to-cis of 5a (A),
and cis-to-trans of 5a (B) in water under photoirradiation at 365 nm.
(ktc) were determined to be 5.0ꢁ10ꢀ3 and 4.9ꢁ10ꢀ3 sꢀ1 for
5a and 5b, respectively, as listed in Table 1.
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Light-Switchable Rotaxanes
À
Á
Á
Aeq ꢀ A0
À
In
¼ kctt
ð2Þ
Aeq ꢀ At
The kct values for 5a and 5b are almost the same, indicative
of no or a weak effect of the linker length. It should be
noted here that the kct values for 5a and 5b are smaller than
that (0.23 sꢀ1) for the reference, 4b, indicating that the re-
stricted structure inhibits the cis-to-trans photoisomeriza-
tion. The similar result of cis-to-trans photoisomerization
has been reported for restricted systems, for example, Lang-
muir–Blodgett membranes.[18] The excellent reversibility was
confirmed as can be seen in Figure S4 in the Supporting In-
formation.
In water, the cis content of the Janus [2]rotaxanes under
the photostationary state was as low as 40%, presumably
not only because of the restricted structure but also because
of the stable inclusion complex of the a-CD and trans-Azo
moieties. Thus, the trans-to-cis photoisomerization was car-
ried out in methanol, in which the inclusion complex was
less stable, to obtain the cis form in as high as approximately
85%. As we did not further purify the Janus [2]rotaxanes
after UV irradiation, because the cis-Azo moiety would be
thermally converted back to the trans isomer even in the
dark,[19] the photoisomerization product should be a mixture
of cis–cis, cis–trans, and trans–trans isomers. However, it
may be possible to characterize the cis–cis isomer as the
main component. In the following, the mixtures, which were
recovered by evaporation of methanol followed by dissolu-
tion in water, were used for characterization of the cis–cis
isomer of 5a and 5b.
Figure 5. The pseudo-first-order plots for the trans-to-cis (A) and cis-to-
trans photoisomerizations (B) of 5a, 5b, and 4b in water.
Table 1. Pseudo-first-order rate constants of trans-to-cis and cis-to-trans
photoisomerization (ktc and kct) for 5a, 5b and 4b.
Rate constant
5a
5b
4b
kts ꢁ103 sꢀ1
kct ꢁ101 sꢀ1
5.0
1.7
4.9
1.5
12
2.3
ðA0 ꢀ AeqÞ
ln
¼ ktct
ð1Þ
ðAt ꢀ AeqÞ
Characterization of the cis–cis Isomer of the Janus
These data are indicative of either no or a weak effect of
the linker length. It is noteworthy that ktc (1.2ꢁ10ꢀ2 sꢀ1) for
the stopper-free, doubly threaded dimer, 4b, is considerably
larger than those for 5a and 5b. This observation indicates
that the restricted structure of the mechanically interlocked
Janus [2]rotaxanes retards the trans-to-cis photoisomeriza-
tion. Notably, the cis contents for 5a and 5b in the photosta-
tionary state (approximately 40%) were considerably lower
than that for 4b (approximately 80%), indicating that the
mechanically interlocked structure makes the cis form less
stable in water.
Similar kinetic studies on the cis-to-trans photoisomeriza-
tion for the Azo moiety in 5a and 5b were also investigated
upon irradiation with visible light at 430 nm, as can be seen
in Figure 4B. Prior to the experiments, the solution was irra-
diated by UV light at 365 nm for 20 min to ensure that the
sample had been in a photostationary state. Similar to the
trans-to-cis photoisomerization, the plots in Figure 5B show
good linear relationships, which is indicative of the pseudo-
first-order kinetics. From the slopes of the straight lines in
Figure 5B and the following Equation (2), the pseudo-first-
order rate constants of cis-to-trans photoisomerization (kct)
were determined to be 0.17 and 0.15 sꢀ1 for 5a and 5b, re-
spectively, as listed in Table 1.
[2]Rotaxane (5a and 5b)
The cis–cis isomers of 5a and 5b were also fully character-
ized by 1D NMR and 2D ROESY NMR and cd spectrosco-
1
py. The H NMR spectra exhibited signals owing to protons
in the cis-Azo moiety and new signals ascribable to protons
in the C7 moiety, as can be seen in Figures S5 and S6 in the
Supporting Information. Figure 6 shows the ROESY spectra
for the cis–cis isomers of 5a and 5b. These spectra show
strong correlation signals between the inner protons of the
a-CD moiety and the protons in the C7 and adamantane
moieties but do not show significant correlation signals be-
tween the inner protons of the a-CD moiety and the protons
in the cis-Azo moiety. As shown in Figure 3, the cd spectra
exhibit the very weak icd bands ascribable to the residual
trans-Azo moiety in a complex, which is indicative of almost
no interaction of the a-CD moiety with the cis-Azo moiety.
These observations indicate that the location of the a-CD
moiety is switched from the Azo moiety to the C7 moiety
by trans-to-cis photoisomerization of the Azo moiety, as il-
lustrated in Figure 7.
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A. Harada et al.
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ents, d the gradient length, and t the 908–1808 pulse dis-
tance. By using these D values and the Stokes–Einstein
equation (shown in Equation (4)), RH values were calculated
as listed in Table 2.
RH ¼ kBT=6phD
ð4Þ
In Equation (4), h is the viscosity coefficient and kB is the
Boltzmann constant. In both cases of 5a and 5b, RH of the
trans–trans isomer was larger than that of the cis–cis isomer
by approximately 20% (3.0 and 2.6 nm for the trans–trans
and cis–cis isomers of 5a, respectively, and 4.4 and 3.6 nm
for the trans–trans and cis–cis isomers of 5b, respectively).
The effect of the linker length on RH is not so strong. This
may be because the OEG linker is very flexible and the
Janus [2]rotaxanes take a random-coil conformation. It is
promising that dense accumulation of the Janus [2]rotaxane
units make the linker more rigid, like polymer brushes.[20]
Conclusions
In summary, with the aim of constructing a molecular
muscle caused by a different size change in the Janus [2]ro-
taxane, 5a and 5b with two recognition sites (the Azo and
C7 site, linked with OEG; DP=2 or approximately 21),
were synthesized and characterized. 2D NMR spectroscopy,
cd spectra, and PGSE NMR spectroscopy demonstrated
that the recognition site of the a-CD moiety was switched
by photoisomerization of the Azo moiety in 5a and 5b,
causing a different size change in RH owing to the different
length of linker between the two recognition sites. Polymer
formation and polymer reaction utilizing the terminal amine
moieties of 4a and 4b are in progress to construct a molecu-
lar muscle showing macroscopic size changes.
Figure 6. Partial ROESY NMR spectra for 3.0 mm 5a (A) and 5b (B)
after UV irradiation measured in D2O at 308C (tm =200 ms).
Experimental Section
Comparison of the Hydrodynamic Radii for the trans–trans
and cis–cis Isomers of the Janus [2]Rotaxanes (5a and 5b)
Materials
N,N-Dimethylformamide (DMF) was purified by using a GlassContour
solvent dispensing system. Azobenzene-4,4’-dicarboxylic acid, BOP, 1-
adamantanecarboxylic acid, and diethylene glycol bis(3-aminopropyl)
ether (oligo(ethylene glycol) (OEG), DP=2) were obtained from Tokyo
Chemical Industry Co., Ltd. p-Toluenesulfonyl chloride, 28% ammonia
solution, DCC, HOBt, and TFA were obtained from Nacalai Tesque Inc.
(OEG, DP=~21, number average molecular weight of 1.0ꢁ103) was ob-
tained from NOF corporation. Boc-Aoc(8)-OH was obtained from Wata-
nabe Chemical Industry Co., Ltd. DMT-MM was obtained from Wako
Pure Chemical Industries. a-CD was obtained from Junsei Chemical Co.,
Ltd. These reagents were used without additional purification. 6-p-Tolue-
nesulfonyl-a-CD[21] and 6-NH2-a-CD[15] were prepared according to the
literature.
The trans–trans and cis–cis isomers of the Janus [2]rotax-
anes, 5a and 5b, were characterized by PGSE NMR to esti-
mate the RH value in water. Figure 8 shows a typical exam-
ple of the plots of the logarithm of the ratio of the observed
spin-echo intensities with and without field gradients (lnACTHNUTRGNE(UNG I/
I0)) versus the square of the gradient strength (G2) for the
trans–trans and cis–cis isomers of 5a and 5b. Figure 8 indi-
cates good linear relationships, which is indicative of unimo-
dal relaxations. From the slopes of the straight lines and
Equation (3), the self-diffusion coefficients (D) were deter-
mined, as listed in Table 2.
Synthesis of Janus [2]Rotaxanes, 5a and 5b
ln ðI=I0Þ ¼ g2G2d2ðDꢀd=3ꢀt=2ÞD
1: 6-NH2-a-CD (0.49 g, 0.50 mmol) and azobenzene-4,4’-dicarboxylic acid
(0.14 g, 0.50 mmol) were dissolved in DMF (50 mL). DCC (0.15 g,
0.75 mmol) and HOBt (0.10 g, 0.75 mmol) were added to the solution
with cooling at 08C. After stirring for 1 h at 08C, the solution was stirred
at room temperature for an additional 8 h. The solvent was evaporated
ð3Þ
In Equation (3), g is the gyromagnetic ratio, G the gradient
strength, D the delay between the midpoints of the gradi-
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Light-Switchable Rotaxanes
Figure 7. Conceptual illustration of photoresponsive structural changes for the Janus [2]rotaxane of 5a and 5b.
Table 2. The D and RH values for the trans–trans and cis–cis isomers of
5a, 5b.
Sample
D [10ꢀ11 m2 sꢀ1
]
RH [nm]
trans–trans 5a
cis–cis 5a
trans–trans 5b
cis–cis 5b
7.5
8.7
5.1
6.2
3.0
2.6
4.4
3.6
vent. Yield: 0.23 g, 38%. 1H NMR (500 MHz, [D6]DMSO): d=12.1 (s,
1H, COOH) 8.55 (t, J=6.0 Hz, 1H, -NH-), 8.05 (d, J=8.4 Hz, 2H, Azo-
H), 7.97 (q, J=6.0 Hz, 4H, Azo-H), 7.64 (d, J=8.5 Hz, 2H, Azo-H),
5.58–5.40 (m, 12H, OH of CD), 4.97 (d, 1H, C(1)H of CD), 4.84–4.79
(m, 5H, C(1)H of CD), 4.60–4.55 (1H, OH of CD), 4.44–4.36 (m, 5H,
OH of CD), 3.92–3.20 ppm (m, 30H, CH of CD). Positive ion MALDI-
TOF-MS: m/z=1248.6 [M+Na]+; elemental analysis: calcd (%) for
C50H69O32N3·7H2O: C 44.48, H 6.20, N 3.11; found: C 44.32, H 6.12,
N 3.07.
2a and 2b: Compound 1 (0.49 g, 0.40 mmol), OEG (DP=2, 0.2 mL,
2.0 mmol), or OEG (DP=21, 2.0 g, 2.0 mmol), and BOP (0.50 g,
1.2 mmol) were dissolved in anhydrous DMF (30 mL). TEA (1.4 mL)
was added into the solution and the mixture was stirred for 3 days. After
evaporation of the solvent, the product, 2a or 2b, was purified by LC/MS
by using a mixed solvent of water and methanol as eluent and recovered
by evaporation of the solvent.
Figure 8. PGSE NMR spectroscopic data for 3.0 mm the trans–trans and
the cis–cis isomers of 5a (A) and 5b (B) in D2O at 308C.
2a: Yield: 0.23 g, 40%. 1H NMR (500 MHz, [D6]DMSO): d=8.63 (t, J=
5.3 Hz, 1H, -Azo-NH-DEG-), 8.55 (t, J=5.3 Hz, 1H, -CD-NH-Azo-),
8.06 (q, J=8.6 Hz, 4H, Azo-H), 7.98 (q, J=8.6 Hz, 4H, Azo-H), 7.55
(2H, -NH2), 5.58–5.40 (m, 12H, OH of CD), 4.97 (d, 1H, C(1)H of CD),
4.84–4.79 (m, 5H, C(1)H of CD), 4.60–4.55 (1H, OH of CD), 4.44–4.36
and then the residue obtained was dissolved in water. The insoluble solid
was filtered off and then the solvent was evaporated under reduced pres-
sure to obtain the crude product. The product, 1, was purified by liquid
chromatography/mass spectrometry (LC/MS) by using a mixed solvent of
water and methanol as eluent and recovered by evaporation of the sol-
Chem. Asian J. 2010, 5, 2281 – 2289
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2287

A. Harada et al.
FULL PAPERS
(m, 5H, OH of CD), 3.92–3.20 (m, -O-CH2- of DEG, CH of CD, -NH-
CH2-CH2-, -CH2-CH2-NH-), 1.79 (m, J=6.7 Hz, 2H, -NH-CH2-CH2-),
1.60 ppm (m, J=6.7 Hz, 2H, -CH2-CH2-NH2). Positive ion MALDI-
TOF-MS: m/z=1426.3 [M+H]+.
2b: Yield: 0.32 g 36%. 1H NMR (500 MHz, [D6]DMSO): d=8.63 (t, J=
5.3 Hz, 1H, -Azo-NH-OEG-), 8.55 (t, J=5.3 Hz, 1H, -CD-NH-Azo-),
8.06 (q, J=8.6 Hz, 4H, Azo-H), 7.98 (q, J=8.6 Hz, 4H, Azo-H), 7.55
(2H, -NH2), 5.58–5.40 (m, 12H, OH of CD), 4.97 (d, 1H, C(1)H of CD),
4.84–4.79 (m, 5H, C(1)H of CD), 4.60–4.55 (1H, OH of CD), 4.44–4.36
(m, 5H, OH of CD), 3.92–3.20 (m, -O-CH2- of OEG, CH of CD, -NH-
CH2-CH2-, -CH2-CH2-NH-), 1.79 (m, J=6.7 Hz, 2H, -NH-CH2-CH2-),
1.60 ppm (m, J=6.7 Hz, 2H, -CH2-CH2-NH2). Positive ion MALDI-TOF
MS (n: the number of ethylene glycol unit in OEG): m/z 2129.7 [M-
5a. Yield: 49 mg, 32%. 1H NMR (500 MHz, [D6]DMSO): d=8.39 (t, J=
5.3 Hz, 1H, -Azo-NH-DEG-), 8.31 (t, J=5.3 Hz, 1H, -CD-NH-Azo-),
7.99 (t, J=7.45 Hz, 2H, Azo-H), 7.90 (q, J=7.45 Hz, 2H, Azo-H), 7.80
(t, J=6.2 Hz, 2H, Azo-H), 7.67 (t, J=6.2 Hz, 2H, Azo-H), 7.45 (t, J=
5.3 Hz, 1H, -CH2-NH-CO-), 7.25 (t, 1H, -CH2-NH-CO-Ad), 5.58–5.40
(m, 12H, OH of CD), 4.97 (d, 1H, C(1)H of CD), 4.84–4.79 (m, 5H,
C(1)H of CD), 4.60–4.55 (1H, OH of CD), 4.44–4.36 (m, 5H, OH of
CD), 3.92–3.20 (m, -O-CH2- of DEG, CH of CD, -NH-CH2-CH2-, -CH2-
CH2-NH-, -(CH2)6-CH2-NH-), 2.02 (t, J=7.3 Hz, 2H, -CO-CH2-(CH2)6-),
1.95 (m, 3H, Ad-H), 1.86 (m, J=6.7 Hz, 2H, -NH-CH2-CH2-), 1.76–1.57
(m, 14H, Ad-H, -CH2-CH2-NH-), 1.47 (m, J=6.9 Hz, 2H, -CH2-CH2-
(CH2)5-), 1.37 (m, J=6.9 Hz, 2H, -(CH2)5-CH2-CH2-), 1.23 ppm (m, 6H,
-CH2-(CH2)3-CH2-). Positive ion MALDI-TOF MS: m/z=3482.3
[M+Na]+.
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ACHTUNGTRENNUNG
5b. Yield: 69 mg, 30%. 1H NMR (500 MHz, [D6]DMSO): d=8.39 (t, J=
5.3 Hz, 1H, -Azo-NH-OEG-), 8.31 (t, J=5.3 Hz, 1H, -CD-NH-Azo-),
7.99 (t, J=7.45 Hz, 2H, Azo-H), 7.90 (q, J=7.45 Hz, 2H, Azo-H), 7.80
(t, J=6.2 Hz, 2H, Azo-H), 7.67 (t, J=6.2 Hz, 2H, Azo-H), 7.45 (t, J=
5.3 Hz, 1H, -CH2-NH-CO-), 7.25 (t, 1H, -CH2-NH-CO-Ad), 5.58–5.40
(m, 12H, OH of CD), 4.97 (d, 1H, C(1)H of CD), 4.84–4.79 (m, 5H,
C(1)H of CD), 4.60–4.55 (1H, OH of CD), 4.44–4.36 (m, 5H, OH of
CD), 3.92–3.20 (m, -O-CH2- of OEG, CH of CD, -NH-CH2-CH2-, -CH2-
CH2-NH-, -(CH2)6-CH2-NH-), 2.02 (t, J=7.3 Hz, 2H, -CO-CH2-(CH2)6-),
1.95 (m, 3H, Ad-H), 1.86 (m, J=6.7 Hz, 2H, -NH-CH2-CH2-), 1.76–1.57
(m, 14H, Ad-H, -CH2-CH2-NH-), 1.47 (m, J=6.9 Hz, 2H, -CH2-CH2-
(CH2)5-), 1.37 (m, J=6.9 Hz, 2H, -(CH2)5-CH2-CH2-), 1.23 ppm (m, 6H,
-CH2-(CH2)3-CH2-). Positive ion MALDI-TOF-MS (n: the number of
G
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E
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4a and 4b: 2a (0.17 g, 0.13 mmol) or 2b (0.28 g, 0.13 mmol) and Boc-
Aoc(8)-OH (0.16 g, 0.60 mmol) were dissolved in DMF (10 mL). DCC
(0.036 g, 0.17 mmol) and HOBt (0.024 g, 0.17 mmol) were added to the
solution with cooling at 08C. After stirring for 1 h at 08C, the solution
was stirred at room temperature for an additional 8 h. The solvent was
evaporated and then the residue obtained was dissolved in water. The in-
soluble solid was filtered off and then the crude product, 3a or 3b, was
recovered by lyophilization from the solution. The crude compound, 3a
or 3b, was dissolved in an aqueous solution of TFA (H2O/TFA, 1:9 (v/v),
6.0 mL) with cooling at 08C and stirred for 30 min. The solvent was then
evaporated to dryness under reduced pressure. The obtained residue was
dissolved in water (10.0 mL), and was neutralized with 0.50m ammonia
solution. The product, 4a or 4b, was purified by LC/MS by using a mixed
solvent of water and methanol as eluent and recovered by evaporation of
the solvent.
ethylene glycol unit in OEG): m/z 4864.6 [M
(n=19)+H]+, 5039.9 [M(n=20)+H]+, 5128.7 [M
(n=22)+H]+, 5304.1 [M(n=23)+H]+, 5394.5 [M
(n=25)+H]+, 5571.1 [M(n=26)+H]+).
ACHTUNGTRENNUNG
A
U
ACHTUNGTRENNUNG
A
U
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
1
4a. Yield: 0.075 g, 40%. H NMR (500 MHz, [D6]DMSO): d=8.63 (t, J=
Measurements
5.3 Hz, 1H, -Azo-NH-DEG-), 8.55 (t, J=5.3 Hz, 1H, -CD-NH-Azo-),
8.06 (q, J=8.6 Hz, 4H, Azo-H), 7.98 (q, J=8.6 Hz, 4H, Azo-H), 7.55 (t,
J=5.3 Hz, 1H, -CH2-NH-CO-), 5.58–5.40 (m, 12H, OH of CD), 4.97 (d,
1H, C(1)H of CD), 4.84–4.79 (m, 5H, C(1)H of CD), 4.60–4.55 (1H, OH
of CD), 4.44–4.36 (m, 5H, OH of CD), 3.92–3.20 (m, -O-CH2- of DEG,
CH of CD, -NH-CH2-CH2-, -CH2-CH2-NH-, -(CH2)6-CH2-NH2), 2.03 (t,
J=7.3 Hz, 2H, -CO-CH2-(CH2)6-), 1.79 (m, J=6.7 Hz, 2H, -NH-CH2-
CH2-), 1.60 (m, J=6.7 Hz, 2H, -CH2-CH2-NH-), 1.48 (m, J=6.9 Hz, 4H,
-CH2-CH2-(CH2)5- and -(CH2)5-CH2-CH2-), 1.26 ppm (m, J=6.7 Hz, 6H,
-CH2-(CH2)3-CH2-). Positive ion MALDI-TOF-MS: m/z=1567.6
[M+H]+.
4b. Yield: 0.10 g 35%. 1H NMR (500 MHz, [D6]DMSO): d=8.63 (t, J=
5.3 Hz, 1H, -Azo-NH-OEG-), 8.55 (t, J=5.3 Hz, 1H, -CD-NH-Azo-),
8.06 (q, J=8.6 Hz, 4H, Azo-H), 7.98 (q, J=8.6 Hz, 4H, Azo-H), 7.55 (t,
J=5.3 Hz, 1H, -CH2-NH-CO-), 5.58–5.40 (m, 12H, OH of CD), 4.97 (d,
1H, C(1)H of CD), 4.84–4.79 (m, 5H, C(1)H of CD), 4.60–4.55 (1H, OH
of CD), 4.44–4.36 (m, 5H, OH of CD), 3.92–3.20 (m, -O-CH2- of OEG,
CH of CD, -NH-CH2-CH2-, -CH2-CH2-NH-, -(CH2)6-CH2-NH2), 2.03 (t,
J=7.3 Hz, 2H, -CO-CH2-(CH2)6-), 1.79 (m, J=6.7 Hz, 2H, -NH-CH2-
CH2-), 1.60 (m, J=6.7 Hz, 2H, -CH2-CH2-NH-), 1.48 (m, J=6.9 Hz, 4H,
-CH2-CH2-(CH2)5- and -(CH2)5-CH2-CH2-), 1.26 ppm (m, J=6.7 Hz, 6H,
-CH2-(CH2)3-CH2-). Positive ion MALDI-TOF-MS (n: the number of
The 1H NMR spectra were recorded on a JEOL ECA500 NMR spec-
trometer. Chemical shifts were referenced to the solvent values
(2.49 ppm for DMSO or 4.70 ppm for HOD) at 308C. 2D NMR (g-
COSY, TOCSY, HMQC, HMBC, and ROESY) spectra were recorded
on a VARIAN INOVA 600 NMR spectrometer at 308C.
LC–MS experiments were carried out on Waters 2545 and Waters 515 as
the binary and makeup pumps equipped with a SunFire Prep C18 OBD
column (19ꢁ150 mm) by using the gradient program of water and metha-
nol as eluent at a flow rate of 10 mLminꢀ1. Waters SFO and Waters 2767
were used as the switching valve and the injector/fraction collector. 3100
Mass Detector and Waters 2996 Photodiode Array Detector were also
used as MS and UV detectors. The LC, MS, and mass-directed fraction
collection were controlled by Masslynx version 4.1 with Fractionlynax.
The positive-ion MALDI-TOF-MS experiments were performed by using
a Shimadzu/KRATOS Axima CFR Ver.2.2.3 mass spectrometer with di-
hydroxylbenzoic acid (DHBA) as a matrix.
UV/Vis absorption spectra were recorded on a JASCO V-650 spectrome-
ter with a 1 cm quartz cell at room temperature.
Circular dichroism spectra were recorded on a JACSO J820 spectrometer
with a 0.1 cm quartz cell at 308C.
ethylene glycol unit in OEG): m/z 2270.8 [M
(n=19)+H]+, 2358.5 [M(n=20)+H]+, 2402.8 [M
(n=22)+H]+, 2490.5 [M(n=23)+H]+, 2534.4 [M
(n=25)+H]+, 2622.2 [M(n=26)+H]+).
ACHTUNGTRENNUNG
Photoisomerization
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Solutions of compounds 4b, 5a, and 5b were photoirradiated by an
Asahi Spectra Compact Xenon Light Source MAX-301. HQBP 365 and
HQBP 430 (Asahi Spectra Co.) band-pass filters were used for the wave-
lengths of 365ꢁ10 and 430ꢁ10 nm, respectively. The distance between
the sample cell and the optical filter was fixed at 1.0 cm.
E
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ACHTUNGTRENNUNG
5a and 5b: 4a (70 mg, 45 mmol) or 4b (108 mg, 48 mmol) was dissolved in
an Na2CO3/NaHCO3 buffer solution (0.1m, 5 mL) with cooling at 08C
and stirred for 1 h to form the doubly threaded dimer. 1-Adamantanecar-
boxylic acid (18 mg, 90 mmol) and the coupling reagent DMT-MM
(25 mg, 90 mmol) were added to the solution. The solution was stirred at
08C for an additional 8 h and then dialyzed by using a dialysis membrane
of a molecular-weight cut off=500 against pure water for 3 days to
remove the salt. The crude compound was recovered by freeze drying
and the product, 5a or 5b, was purified by LC/MS by using a mixed sol-
vent of methanol and water as eluent.
Determination of Self-Diffusion Coefficients
PGSE NMR spectra were recorded at 600 MHz in D2O on a VARIAN
INOVA 600 NMR spectrometer at 308C. The bipolar pulse pair stimulat-
ed echo (BPPSTE) sequence was applied.[22] The strength of pulsed gra-
dients was increased from 6.36ꢁ10ꢀ1 to 43.1 gausscmꢀ1. The time separa-
tion of pulsed field gradients and their duration were 0.10 and 1.0ꢁ10ꢀ3 s,
2288
www.chemasianj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2010, 5, 2281 – 2289

Light-Switchable Rotaxanes
respectively. The sample was not spun and the airflow was disconnected.
The shape of the gradient pulse was rectangular, and its strength varied
automatically during the course of the experiments.
[8] T. Fujimoto, Y. Sakata, T. Kaneda, Chem. Commun. 2000, 2143–
2144.
[9] T. Hoshino, M. Miyauchi, Y. Kawaguchi, H. Yamaguchi, A. Harada,
J. Am. Chem. Soc. 2000, 122, 9876–9877.
[10] R. E. Dawson, S. F. Lincoln, C. J. Easton, Chem. Commun. 2008,
3980–3982.
[11] S. Tsukagoshi, A. Miyawaki, Y. Takashima, H. Yamaguchi, A.
Harada, Org. Lett. 2007, 9, 1053–1055.
Acknowledgements
[12] S. Li, D. Taura, A. Hashidzume, Y. Takashima, H. Yamaguchi, A.
Harada, Chem. Lett. 2010, 39, 242–243.
The authors would like to thank Mr. Seiji Adachi for 2D NMR measure-
ments and helpful discussions.
[13] a) G. S. Kumar, D. C. Neckers, Chem. Rev. 1989, 89, 1915–1925;
b) J.-i. Anzai, T. Osa, Tetrahedron 1994, 50, 4039–4070.
[14] a) F. Cramer, H. Hettler, Naturwissenschaften 1967, 54, 625–632;
b) P. Bortolus, S. Monti, J. Phys. Chem. 1987, 91, 5046–5050.
[15] J. Boger, R. J. Corcoran, J.-M. Lehn, Helv. Chim. Acta 1978, 61,
2190–2218.
[16] a) K. Harata, H. Uedaira, Bull. Chem. Soc. Jpn. 1975, 48, 375–378;
b) M. Kodaka, T. Fukaya, Bull. Chem. Soc. Jpn. 1989, 62, 1154–
1157; c) M. Kodaka, J. Phys. Chem. 1991, 95, 2110–2112; d) M.
Kodaka, J. Am. Chem. Soc. 1993, 115, 3702–3705.
[1] a) D. Voet, J. G. Voet, Biochemistry, Wiley, New York, 1995; b) L.
Stryer, Biochemistry, W. H. Freeman, New York, 1995; c) B. Alberts,
A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, Molecular Biol-
ogy of the Cell, Garland Publishing Inc., New York, 2008.
[2] a) V. Balzani, A. Credi, S. Silvi, M. Venturi, Chem. Soc. Rev. 2006,
35, 1135–1149; b) H. Murakami, A. Kawabuchi, R. Matsumoto, T.
Ido, N. Nakashima, J. Am. Chem. Soc. 2005, 127, 15891–15899;
c) R. J. Coulston, H. Onagi, S. F. Lincoln, C. J. Easton, J. Am. Chem.
Soc. 2006, 128, 14750–14751; d) D. H. Qu, Q. C. Wang, H. Tian,
Angew. Chem. 2005, 117, 5430–5433; Angew. Chem. Int. Ed. 2005,
44, 5296–5299; e) X. Ma, D. H. Qu, F. Y. Ji, Q. C. Wang, L. L. Zhu,
Y. Xu, H. Tian, Chem. Commun. 2007, 1409–1411.
[17] a) S. L. Sin, L. H. Gan, X. Hu, K. C. Tam, Y. Y. Gan, Macromole-
cules 2005, 38, 3943–3948; b) N. Ma, Y. Wang, B. Wang, Z. Wang,
X. Zhang, G. Wang, Y. Zhao, Langmuir 2007, 23, 2874–2878; c) Q.
Bo, Y. Zhao, Langmuir 2007, 23, 5746–5751.
[18] a) T. Kawai, J. Umemura, T. Takenaka, Langmuir 1989, 5, 1378–
1383; b) H. Menzel, Macromolecules 1993, 26, 6226–6230.
[19] a) Y. Morishima, M. Tsuji, M. Kamachi, K. Hatada, Macromolecules
1992, 25, 4406–4410; b) Y. Morishima, M. Tsuji, M. Seki, M. Kama-
chi, Macromolecules 1993, 26, 3299–3305; c) H. Knoll, CRC Hand-
book of Organic Photochemistry and Photobiology, 2nd ed., 2004, 89/
81–89/16; d) J. Dokic, M. Gothe, J. Wirth, M. V. Peters, J. Schwarz,
S. Hecht, P. Saalfrank, J. Phys. Chem. A 2009, 113, 6763–6773.
[20] a) S. Lata, J. Piehler, Anal. Chem. 2005, 77, 1096–1105; b) C. E.
McNamee, S. Yamamoto, K. Higashitani, Langmuir 2007, 23, 4389–
4399.
[3] a) V. Bermudez, N. Capron, T. Gase, F. G. Gatti, F. Kajzar, D. A.
Leigh, F. Zerbetto, S. W. Zhang, Nature 2000, 406, 608–611; b) C. A.
Nijhuis, B. J. Ravoo, J. Huskens, D. N. Reinhoudt, Coord. Chem.
Rev. 2007, 251, 1761–1780; c) B. Champin, P. Mobian, J.-P. Sauvage,
Chem. Soc. Rev. 2007, 36, 358–366; d) S. Bonnet and J. P. Collin,
Chem. Soc. Rev. 2008, 37, 1207–1217; e) A. Credi, Aust. J. Chem.
2006, 59, 157–169.
[4] a) M. C. Jimꢂnez, C. Dietrich-Buchecker, J.-P. Sauvage, Angew.
Chem. 2000, 112, 3422–3425; Angew. Chem. Int. Ed. 2000, 39, 3284–
3287; b) M. C. Jimenez-Molero, C. Dietrich-Buchecker, J.-P. Sauv-
age, Chem. Eur. J. 2002, 8, 1456–1466.
[5] J. Wu, K. C.-F. Leung, D. Benꢃtez, J.-Y. Han, S. J. Cantrill, L. Fang,
J. F. Stoddart, Angew. Chem. 2008, 120, 7580–7584; Angew. Chem.
Int. Ed. 2008, 47, 7470–7474.
[6] L. Fang, M. Hmadeh, J. Wu, M. A. Olson, J. M. Spruell, A. Trabolsi,
Y.-W. Yang, M. Elhabiri, A.-M. Albrecht-Gary, J. F. Stoddart, J. Am.
Chem. Soc. 2009, 131, 7126–7134.
[21] L. D. Melton, K. N. Slessor, Carbohydr. Res. 1971, 18, 29–37.
[22] a) E. O. Stejskal, J. E. Tanner, J. Chem. Phys. 1965, 42, 288–292;
b) J. E. Tanner, E. O. Stejskal, J. Chem. Phys. 1968, 49, 1768–1777;
c) P. Stilbs, Prog. Nucl. Magn. Reson. Spectrosc. 1987, 19, 1–45.
[7] P. G. Clark, M. W. Day, R. H. Grubbs, J. Am. Chem. Soc. 2009, 131,
13631–13633.
Received: March 3, 2010
Published online: July 28, 2010
Chem. Asian J. 2010, 5, 2281 – 2289
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
2289