Temperature-driven braking of γ-cyclodextrin-curcubit[6]uril-cowheeled [4]rotaxanes

Article abstract of DOI:10.1016/j.cclet.2018.12.002

Several cyclodextrin-cucurbit[6]uril-cowheeled [4]rotaxanes were synthesized through the cucurbit[6]uril-templated azide-alkyne 1,3-dipolar cycloaddition. The intramolecular interaction between the aromatic axle and the capping groups of cyclodextrin moie

Full text of DOI:10.1016/j.cclet.2018.12.002

Accepted Manuscript
Title: Temperature-driven braking of
␥-cyclodextrin-curcubit[6]uril-cowheeled [4]rotaxanes
Authors: Ran Liu, Yuxue Zhang, Wanhua Wu, Wenting Liang,
Qinfei Huang, Xingke Yu, Wei Xu, Dayang Zhou, Narayanan
Selvapalam, Cheng Yang
PII:
DOI:
Reference:
S1001-8417(18)30462-5
https://doi.org/10.1016/j.cclet.2018.12.002
CCLET 4739
To appear in:
Chinese Chemical Letters
Received date:
Revised date:
Accepted date:
8 October 2018
7 November 2018
3 December 2018
Please cite this article as: Liu R, Zhang Y, Wu W, Liang W, Huang Q, Yu
X, Xu W, Zhou D, Selvapalam N, Yang C, Temperature-driven braking of
␥-cyclodextrin-curcubit[6]uril-cowheeled [4]rotaxanes, Chinese Chemical Letters
(2018), https://doi.org/10.1016/j.cclet.2018.12.002
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Communication
Temperature-driven braking of γ-cyclodextrin-curcubit[6]uril-cowheeled
[4]rotaxanes
Ran Liua, Yuxue Zhang a, Wanhua Wua, Wenting Liang a,b, Qinfei Huanga, Xingke Yua, Wei Xua, Dayang
Zhouc, Narayanan Selvapalamd,Cheng Yanga,*
a Key Laboratory of Green Chemistry & Technology, College of Chemistry, State Key Laboratory of Biotherapy, West China Medical Center, and Healthy Food
Evaluation Research Center, Sichuan University, Chengdu 610064, China
b Institute of Environmental Sciences, Department of Chemistry, Shanxi University, Taiyuan 030006, China
c Comprehensive Analysis Center, ISIR, Osaka University, Mihogaoka, Ibaraki 567-0047, Japan
d Center for Supramolecular Chemistry, International Research Center and Department of Chemistry, Kalasalingam University, Krishnankoil, Tamil Nadu
State, India 626126
 Corresponding author.
E-mail address: yangchengyc@scu.edu.cn
Graphical Abstract
A capping moiety, playing a role of the brake, slowed down the rotation speed of the cyclodextrin of a cyclodextrin-cucurbit[6]uril-cowheeled
[3]rotaxane. Lowering the temperature further stopped the rotation at the NMR timescale.
ARTICLE INFO
ABSTRACT
Several cyclodextrin-cucurbit[6]uril-cowheeled [4]rotaxanes were synthesized through the
cucurbit[6]uril-templated azide-alkyne 1,3-dipolar cycloaddition. The intramolecular interaction
between the aromatic axle and the capping groups of cyclodextrin moieties was investigated by
UV-vis, fluorescence, circular dichroism and NMR spectroscopic studies. The rotational kinetic
of the wheel around the axle can be manipulated by adjusting the temperature. The capping group
apparently slowed down the rotation of the wheel, playing a role of the brake, and lowering the
temperature can stop the rotation of the wheel on the NMR timescale.
Article history:
Received
Received in revised form
Accepted
Available online
Keywords:
Temperature-control
Rotational kinetics
Rotaxane
Cyclodextrin
Cucurbit[6]uril
Precisely operating molecular mechanical devices is an intriguing topic of current nanotechnology. The synthesis of molecular motors
has attracted considerable attention and a variety of molecular machines on the basis of interlocked molecules, such as rotaxanes,
catenanes and molecular knots, have been designed and constructed [1]. Several strategies, including electrochemical and photochemical
control, have been applied to drive the motion of molecular motors [2]. Artificial supramolecular chemical structures based on rotaxanes
belong to the most extensively studied molecular machines, because of their interesting mechanical interlocking structures, unique
physical/chemical properties and a wide range of potential applications. The non-covalent interlocked feature makes the ring freely
slidable along the axle, and most studies on the rotaxane-based molecular machines focused on the function arising from the slide motion
of the ring along the axle. On the other hand, the study on controlling the rotational kinetic of the ring around the axle was rarely involved
[3]. Here, we set up a new strategy to control the rotational kinetic of the wheel by introducing a “brake” on the wheel moiety, and
demonstrated that the rotation kinetic of the wheel could be accurately manipulated by temperature variation.

Cyclodextrins (CDs) are one of the most widely studied host molecules, bearing the advantage of good water solubility, inherent
chirality, versatile binding ability and ready availability [4]. We have demonstrated that chemical modification could significantly
improve the binding and chiral discrimination of CDs [5,6]. Both CDs and curcubit[6]uril (CB[6]) have been applied as the wheels of
rotaxanes due to their round shape and unique complexation ability with organic guests in aqueous solution. γ-CD-CB[6]-cowheeled
[4]rotaxanes R1-R6 were synthesized by mixing γ-CD, CB[6], an alkynyl-terminated aromatic axle 2 or 3, and a bulky azide 1 together
in aqueous solution at room temperature. In rotaxanes R2-R6, capped γ-CD were used as the wheel part. By introducing capping moiety,
the size and shape of CDs as well as their complexation behavior could be significantly varied [7].
CB[6], 6A,6X-dideoxy-6A,6X-diamino--CD and axle molecules were prepared according to the reported procedures [8]. The
[4]rotaxanes were formed in good yield at room temperature as a result of CB[6]-catalyzed click-reaction [9]. We have demonstrated
that the hydrogen bonding formed between CB[6] and CD played an important role in the efficient formation of [4]rotaxane [7b]. The
rotaxanes R1-R3, containing an axle of biphenyl have been used as a supramolecular sensitizer for the chiral photoisomerization of
cyclooctadiene. The capping part can further confine the orientational freedom of the axle part and therefore improved the reaction
selectivity. It occurred to us that the capping moiety may also play a role of brake that can control the rotation kinetic of the axle. The
steric hindrance effect between the cap and the axle molecule may slow down the rotation of the axle molecule along the axis of the CD
cavity. Therefore, we investigated the NMR spectra of R1-R3 in water (Fig. 1). All biphenyl protons should stay in a different
environment if the rotation of the biphenyl group was stopped due to the unsymmetrical structure caused by the introduction of capping
moiety. However, for all these three rotaxanes, only one set of the 1H NMR spectra were observed, indicating that the biphenyl group in
the cavity of γ-CD still can freely rotate on the NMR timescale. We ascribed the failure of braking to the relatively small size of biphenyl
and the internal rotation of two benzene rings around the biphenyl linkage, and therefore focused our investigation on the rotaxanes R4-
R6, in which the relatively bulky naphthalene severs as the axle (Scheme 1).
Scheme 1. Chemical structure of wheels, axles and hetero[4]rotaxanes.
It turned out that the UV-vis spectra of rotaxanes R4-R6 are primarily the result of the UV-vis spectra of the capping moiety and the
axle molecule (Fig. 2). This indicated that the axle part and the capping moiety had not significant electronic interaction at their ground
1
states. R4 and R5 showed positive circular dichroism spectra at the Bb band of naphthalene (Fig. 3). According to the Kajtar’s sector
rule [10], these positive induced circular dichroism is consistent with the parallel orientation of the naphthalene axle along the longitudinal
axis of the CD cavity. However, R6 exhibited strong exciton coupling type circular dichroism (ECCD), due to the close and chiral
orientation of two naphthalenes. The positive ECCD signal (positive peak at 322 nm and a negative peak at 228 nm) indicated a right-
handed helical arrangement of the capping moiety and the axle.

Fig. 1. 1H NMR (400 MHz) of hetero[4]rotaxanes R1 (upper), R2 (middle) and R3 (lower) measured at 25 C in D2O.
The rotaxane R4, wheeled with native γ-CD, showed fluorescence spectrum similar to 3 with a higher intensity, presumably due to
the protection of CD wall. On the contrary, R6 showed only the fluorescence of the capping moiety, and the fluorescence due to the axle
moiety is negligible. We ascribed this to the extremely high efficiency of fluorescence resonant energy transfer from the axle moiety to
the capping naphthalene as a result of the close interlocking of the two moieties. No excimer fluorescence could be seen with R6, for
which the poor orbital overlap between two orthogonal naphthalenes should be responsible. Interestingly, a structureless broad
fluorescence peaked at around 430 nm was observed with R5 in addition to the structural emission of the naphthalene axle (Fig 2, green
line). We assigned the emission to the exciplex fluorescence formed between the naphthalene and the terephthalate. This is presumably
due to that the terephthalate capping in R5 has a smaller size than the naphthalene capping in R6 and is, therefore, more flexible, which
makes it easier forming π-π stacking with the axle.
1.0
0.8
0.6
0.4
0.2
0.0
3
R4
R5
R6
400
300
200
100
0
R4
350
400
450
500
3
R6
R5
350
400
450
500
550
Wavelength / nm
Fig. 2. Fluorescence spectra of 1.0 mol/L of 3 (black), R4 (light blue), R5 (green) and R6 (red) measured in water at 25 ºC, ex = 280 nm.

Fig. 3. 1H NMR (400 MHz) of hetero[4]rotaxanes R4 (upper), R5 (middle) and R6 (lower) measured at 25 C in D2O.
R5
R3
Fig. 4. Partial 1H NMR spectra (600 MHz, D2O:CD3OD=3:7) of hetero[4]rotaxane R3 (left) and R5 (right) recorded at -20 ºC, -10 ºC, -5 ºC, 10
ºC and 25 ºC.
The 1H NMR spectra of rotaxanes R4-R6 were measured in D2O at 25 C. As shown in Fig. 3, all three rotaxanes showed two sets
of CB[6]’s proton signals, as a result that two CB[6] positioned at the secondary and primary rims of γ-CD, respectively. The 1H NMR
spectra of R4 exhibited one set of aromatic proton signals, and the H2, H3, H4, H5 and H6 proton signals of the γ-CD were congested
in a narrow region of 3.4-3.8 ppm. This is reasonable as the large cavity of γ-CD should allow the naphthalene axle to freely rotate. For
1
R5, the H NMR of CD exhibited a much wider distribution, giving an upfield shift up to 2.5 ppm. This indicated that the aromatic
capping and the axle exerted unequal shielding and deshielding effects on each glucose unit of the CD. However, totally only one set of
proton signals were seen for R5, suggesting that the rotation of the naphthalene axle is still fast on the NMR timescale.
The 1H NMR spectra of R6 showed even significant upfield shift, with some CD protons shifted as far as 2.1 ppm (Fig 3). Interestingly,
the aromatic and CD proton signals of R6 were clearly broadened at 25 C, implying that the rotation of the axle was slow. To confirm

this, the VT NMR of rotaxanes were performed in a mixture of D2O and CD3OD, which allowed us to measure the NMR spectra at a
temperature lower than 0 C. As illustrated in Fig. 4, both R3 and R5 showed only one set of protons even at -20 C, suggesting a fast
rotation of the wheel. Nevertheless, the proton signals became broad when lowering the temperature to -10 C and -20 C. This
observation raveled that the rotation speed slowed down with decreasing the temperature. In contrast, R6 showed broad and overlapped
1
1H NMR signals at 25 C (Fig. 5), and raising the temperature to 40 C led to an even broader and featureless H NMR spectrum. The
broad and coalesced proton signals become sharper and differentiable with further increasing the temperature, to show a relatively clear
1
1H NMR spectrum at 55 C and 80 C. Interestingly, the H NMR signals of R6 also became clear and sharp when lowering the
temperature. The signals divided into two sets of proton signals at -20 C. The two sets of 1H NMR signals indicated that the naphthalene
axle for R6, in which both the capping and the axle moieties constituted with relatively bulky naphthalene group, should cause strong
steric interaction and therefore the two conformations of R6 interconvert slowly at low temperature (Scheme 2).
Scheme 2. Two rotational conformations of R6.
-20℃
-10℃
-5℃
10℃
25℃
40℃
55℃
80℃
Fig. 5. Partial 1H NMR (600 MHz, D2O:CD3OD = 3:7) spectra of R6 at -20 ºC, -10 ºC, -5 ºC, 10 ºC, 25 ºC, 40 ºC, 55 ºC and 80 ºC.
In summary, we have synthesized a series of CB[6] and γ-CD co-wheeled [4]rotaxanes through a CB[6]-templated azide-alkyne 1,3-
dipolar cycloaddition. The aromatic capping moiety on the primary rim of γ-CD can interact with the aromatic axle at the ground and/or
excited states. The rotaxanes having a naphthalene axle showed exciton coupling-type circular dichroism when wheeled with a
1
naphthalene-capped γ-CD or exciplex fluorescence when wheeled with a terephthalate-capped γ-CD. Variable temperature H NMR
proved that the rotation speed of the axle was affected by both the geometry of capping groups and the temperature. The rotaxane with
naphthalene groups on the capping and axle moieties showed rotation kinetics slower than NMR timescale at low temperature, due to
the steric interaction. The braking effect caused by capping groups in the present study established a new strategy to control the rotational
kinetics of rotaxanes, and thus opens a new window for building intelligent molecular mechanical devices.
Acknowledgments
We acknowledge the support of this work by the National Natural Science Foundation of China (Nos. 21871194, 21572142, 21372165,
21402129 and 21402110), National Key Research and Development Program of China (No. 2017YFA0505903), Science & Technology
Department of Sichuan Province (No. 2017SZ0021), and Comprehensive Training Platform of Specialized Laboratory, College of
Chemistry, Sichuan university. The kind assistance on the fluorescence measurements from Prof. Peng Wu in Analytical & Testing
Center, Sichuan University was greatly appreciated.

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