Enantiodifferentiation in the Photoisomerization of (Z,Z)-1,3-Cyclooctadiene in the Cavity of γ-Cyclodextrin-Curcubit[6]uril-Wheeled [4]Rotaxanes with an Encapsulated Photosensitizer

Article abstract of DOI:10.1021/acs.orglett.7b00057

A biphenyl photosensitizer axle was implanted into the cavities of native and capped γ-cyclodextrins through rotaxanation using a cucubit[6]uril-templated azide-alkyne 1,3-dipolar cycloaddition, resulting in the construction of highly defined chiral binding/sensitizing sites. The orientation and interaction of the axle and capping moieties at the ground and excited states were interrogated by NMR, UV-vis, circular dichroism, and fluorescence spectroscopic studies. In situ photoisomerization of (Z,Z)-1,3-cyclooctadiene sensitized in the cavity of these [4]rotaxanes afforded (Z,E)-1,3-cyclooctadiene in up to 15.3% ee, which represents the highest level of enantiodifferentiation obtained to date for this supramolecular photochirogenesis.

Full text of DOI:10.1021/acs.orglett.7b00057

Letter
pubs.acs.org/OrgLett
Enantiodifferentiation in the Photoisomerization of (Z,Z)‑1,3-
Cyclooctadiene in the Cavity of γ‑Cyclodextrin−Curcubit[6]uril-
Wheeled [4]Rotaxanes with an Encapsulated Photosensitizer
Zhiqiang Yan,†,⊥ Qinfei Huang,†,⊥ Wenting Liang,§ Xingke Yu,† Dayang Zhou,∥ Wanhua Wu,†
Jason J. Chruma,†,‡ and Cheng Yang*,†
‡
†Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry and Sino-British Materials
Research Institute, College of Physical Science & Technology, Sichuan University, No. 29, Wangjiang Road, Chengdu 610064, China
§Institute of Environmental Sciences, Department of Chemistry, Shanxi University, Taiyuan 030006, China
∥Comprehensive Analysis Center, ISIR, Osaka University, 8-1 Mihogaoka, Ibaraki Osaka 5670047, Japan
S
* Supporting Information
ABSTRACT: A biphenyl photosensitizer axle was implanted into the cavities of
native and capped γ-cyclodextrins through rotaxanation using a cucubit[6]uril-
templated azide−alkyne 1,3-dipolar cycloaddition, resulting in the construction of
highly defined chiral binding/sensitizing sites. The orientation and interaction of
the axle and capping moieties at the ground and excited states were interrogated by
NMR, UV−vis, circular dichroism, and fluorescence spectroscopic studies. In situ
photoisomerization of (Z,Z)-1,3-cyclooctadiene sensitized in the cavity of these
[4]rotaxanes afforded (Z,E)-1,3-cyclooctadiene in up to 15.3% ee, which represents
the highest level of enantiodifferentiation obtained to date for this supramolecular
photochirogenesis.
Scheme 1. Enantiodifferentiating Photoisomerization of
(Z,Z)-1,3-Cyclooctadiene
hiral photochemistry, or photochirogenesis, which allows
for the photogeneration of enantioenriched chiral
C
compounds by activating thermally forbidden processes,
represents one of the greatest challenges in modern photo-
chemistry.1 The short lifetime, weak interactions, and high
reactivity of the electronically excited photosubstrates account
for the poor stereochemical outcome commonly encountered
in photochirogenesis.2 Both internal and external factors, such
as chiral inductors, temperature, solvent, and pressure, have
proven to be crucial factors in photochirogenesis.3 Recently,
supramolecular photochirogenesis has emerged as a promising
tactic, as it benefits from relatively long and strong supra-
molecular interactions exerting their influence on both the
ground and excited states.4 A variety of chiral hosts, including
cyclodextrin (CD) derivatives,5 chiral zeolite supercages,6 chiral
templates,7 chiral cages,8 and biomacromolecules,9 have been
exploited for mediating stereoselective photoreactions. Photo-
sensitization of (Z)-cyclooctene with β-CD tethered to a
sensitizer represents the seminal example of sensitized
supramolecular photochirogenesis10 and produces good to
excellent enantioselectivities for the planar chiral (E)-cyclo-
octene. The enantioselectivity for the photoisomerization
(Z,Z)-1,3-cyclooctadiene 1ZZ to (E,Z)-1,3-cyclooctadiene
1EZ (Scheme 1), in contrast, remains poor, reflecting the
very different stereochemical requirements for these two related
transformations. Very recently, improved ee values of up to
13% were achieved by using a relatively rigid matrix of amyloid-
based nanofibers or hydrogels formed by CD-based poly-
mers.10c,11
While CDs possess the advantages of being readily available,
UV transparent, and inherently chiral, their ability to serve as
enantiodifferentiation agents in photochirogenesis is generally
insignificant. The round shape and hydrophobic interior of
CDs can accommodate a wide variety of binding organic guests,
but with typically poor specificity.12 The negligible stereo-
induction is particularly pronounced for γ-CD due to its
relatively flexible framework and larger cavity. In the present
letter, we describe a new strategy to build up a highly confined
chiral sensitizing cavity by implanting an aromatic sensitizer
into the cavity of γ-CD through rotaxanation. This strategy
takes advantage of the large cavity size of γ-CD to
simultaneously accommodate the photosensitizer and substrate.
Once the biphenyl sensitizer/axle is anchored through
Received: January 7, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b00057
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Organic Letters
Letter
rotaxanation, the remaining space inside the CD cavity no
longer possesses a symmetrically round shape. Accordingly, the
in situ photosensitization is expected to affect chirality transfer
more efficiently than conventional γ-CD derivatives.
Capped γ-CDs W1 and W2 (Scheme 2) were synthesized by
reacting 6A,6C- or 6A,6D-diamino γ-CDs12 with the correspond-
Scheme 2. Supramolecular Chiral Photosensitizers
Figure 1. 1H NMR spectra (400 MHz, D2O, 298 K) of the
hetero[4]rotaxanes (a) Rot1, (b) Rot2, and (c) Rot3.
The UV−vis and circular dichroism spectra of the capped
CDs and [4]rotaxanes were studied in aqueous solutions
(Figure 2). The capped γ-CDs W1 and W2, whose aromatic
ing aromatic dicarboxylic acids, respectively.13 γ-CD-
cucurbit[6]uril (CB[6])-wheeled [4]rotaxanes Rot1−Rot3
were constructed by mixing the appropriate γ-CD, the CB[6]
end caps, the biphenyl-based bis-terminal alkyne “axle” 2, and
the azide “stopper” 3 in an aqueous solution at room
temperature followed by a CB[6]-templated azide−alkyne
1,3-dipolar cycloaddition.14 All rotaxanes were obtained in good
yields, partially due to the supramolecular interactions
organizing all of the components into the appropriate
arrangement.15
The 1H NMR spectra of Rot1−Rot3 clearly show two sets of
proton signals for the CB[6] end caps, corresponding to CB[6]
located at the primary and secondary rims of γ-CD (Figure 1).
Similarly, four unique biphenyl protons were seen with the
rotaxanes due to the loss of symmetry along the longitudinal
axis. Rot1 shows only one set of glucose protons with the
nonanomeric protons all packed in the narrow region between
3.8 and 3.4 ppm, suggesting that the biphenyl axle is centrally
positioned in the CD cavity and exerts relatively equal shielding
and deshielding effects on each glucose unit. Compared to the
1H NMR spectra of Rot1, the nonsymmetrical aryl protons in
the biphenyl units of Rot2 and Rot3 (a, a′, b, and b′) are all
shifted more upfield, as well as being more separated from each
other, as a result of the shielding effect arising from the
aromatic capping moieties on the CD rims (Figure 1b,c).
Moreover, the proton signals in the CD units of Rot2 and Rot3
are distributed over a much wider range versus Rot1, with some
of the nonanomeric protons shifted as far upfield as 2.4 ppm
(Rot2) or 2.2 ppm (Rot3). This can be explained in terms of
the anisotropic shielding and deshielding effects jointly exerted
by the capping moiety and the biphenyl axle. The unequal
shielding and deshielding effects received by the different
glucose units in the CD units of Rot2 and Rot3 suggest that the
biphenyl axle is located off-center of CD cavity, most likely due
to the presence of capping groups.
Figure 2. Circular dichroism (top) and UV−vis (bottom) spectra of
10 μM W1 (black), W2 (red), Rot1 (blue), Rot2 (green), and Rot3
(brown) measured in water at 25 °C.
caps are fixed in a trans-annular manner on the primary rim of
the CDs, show positive induced circular dichroism (ICD)
signals at the main UV−vis absorption bands. According to the
“sector rule” proposed by Kajtar and co-workers,16 such an ICD
implies that the aromatic planes are more parallel to the
longitudinal axis of the CD ring. Negative exciton coupling
circular dichroism (ECCD) was seen at the short wavelength of
Rot1, suggestive of a left-handed screw arrangement for the two
conjoined benzene rings in the biphenyl axle. Rot2 showed a
circular dichroism spectrum very similar to that of Rot1, rather
than a simple sum of Rot1 and W1. Rot3, on the other hand,
has a circular dichroism spectrum significantly deviating from
the sum of Rot1 and W2, and it shows an improved positive
B
DOI: 10.1021/acs.orglett.7b00057
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Organic Letters
Letter
signal at longer wavelengths and negative signals below 250 nm.
Moreover, the UV−vis spectrum of Rot3 is broadened with a
significant bathochromic shift compared to W2. These results
indicate an alternation of capping moiety’s orientation in the
rotaxanes and an electronic interaction between the biphenyl
axle and the capping moieties at the ground state.
with association constants of 2130, 2510, 3820, 8170, and
10330 M−1 for W1, W2, Rot1, Rot2, and Rot3, respectively.
The remarkably improved binding affinity observed for the
rotaxanes Rot2 and Rot3 versus the capped CDs W1 and W2
clearly demonstrates a more intimate interaction jointly
originating from the CD wall, the biphenyl axle, and the
aromatic capping moieties.
Photoisomerization of 1ZZ using 280 nm light was carried
out in an aqueous solution of a CD-based chiral sensitizers
under a nitrogen atmosphere. The enantioselectivity varied
considerably with the chiral host employed. With the capped γ-
CDs W1 and W2, the observed enantioselectivity was negligible
even though the sensitizer moiety was rigidly fixed on the
primary rim of CD (Table 1). This result confirms that the
The fluorescence emission of the biphenyl unit in Rot1 is
stronger than that of the free biphenyl unit 2 (Figure 3); this
Table 1. Enantiodifferentiating Photoisomerization of 1ZZ
a
Sensitized by Chiral Hosts
host
temp (°C)
1EZ/1ZZ
1EZ % ee
W1
25
25
25
0.5
25
0.5
25
0.5
0.16
0.14
0.09
0.06
0.08
0.05
0.06
0.04
1.1
0.8
W2
Rot1
3.9
4.7
Rot2
Rot3
12.8
15.3
8.3
Figure 3. Fluorescence spectra of 10 μM 2 (black), W2 (red), Rot1
(blue), Rot2 (green), and Rot3 (brown) in water at 25 °C, λex = 280
nm.
9.2
a
Irradiation at 280 nm under nitrogen in a methanol−water mixture
for 30 min; [1ZZ] = 0.5 mM; [host] = 0.1 mM.
can be attributed to protection from the CD wall. Fluorescence
from the biphenyl unit in Rot3 was not observed. Instead, only
fluorescence emission at a longer wavelength closer to that of
W2 was observed, suggesting an efficient energy transfer from
the higher energy biphenyl axle to the naphthalene capping
moiety. Interestingly, the fluorescence spectra of Rot2
contained two fluorescence peaks, one at 310 nm and a very
broad emission at the longer wavelength of 433 nm. The
former, having a lifetime (7.7 ns) similar to that for Rot1 (7.6
ns), corresponds to emission from the biphenyl axle. The latter
signal is assigned as the exciplex fluorescence between the
terephthalamide cap on the CD rim and the biphenyl axle. The
formation of this rarely observed benzene−biphenyl exciplex
could be ascribed to the noncovalent interlocked nature of the
rotaxane, which leads to a high local concentration of the two
components with adjustable stacking via slipping of the wheel
along the axle. Two lifetime decays of 2.7 and 8.9 ns,
respectively, were observed with the exciplex fluorescence,
suggesting the presence of conformational isomers of the
exciplex. The above results indicate that the capping moiety and
the axle interact with each other in both the ground and excited
states and therefore are expected to further confine the binding
sites.
The complexation of 1ZZ with the rotaxanes Rot1−3 was
studied by circular dichroism and fluorescence titration.
Addition of 1ZZ did not cause an apparent change in the
circular dichroism spectra, suggesting that no significant
conformational changes occurred in the rotaxanes. Binding of
1ZZ by the rotaxanes did result in fluorescence quenching in
the latter, most likely due to energy transfer from the excited
biphenyl axle to the introduced diene 1ZZ. Job’s plots
consistently demonstrated a 1:1 stoichiometry for the complex-
ation of 1ZZ with the various modified CDs and rotaxanes,
cavity of γ-CD is too large to realize efficient chiral delivery.
With Rot1, 1ZZ should be coincluded with the biphenyl
sensitizer in the cavity of γ-CD during sensitization. However,
the modest enantioselectivity (4.7% ee) obtained suggests that
the chiral cavity thus formed is still not specific enough for
efficient chirality transfer. On the other hand, the enantiose-
lectivity was significantly improved with the rotaxanes wheeled
with capped γ-CDs W1 and W2. Thus, the ee values were
improved to 12.8% and 8.3% with Rot2 and Rot3, respectively,
at 25 °C. This unambiguously demonstrated the effect of the
capping moiety on further confining the complex. Since both
the capping moieties and the biphenyl axle could play the role
of a sensitizer, they individually are expected to contribute to
the photoisomerization, though it is not immediately clear
which part dominates the photosensitization. For all of the
rotaxane-based sensitizers investigated, lowering the temper-
ature led to a further increase in enantioselectivity. At 0.5 °C,
Rot2 afforded 1EZ in 15.3% ee, which is the highest value
obtained to date for the supramolecular photoisomerization of
1ZZ.
In summary, we have established a new strategy to construct
highly confined chiral cavities by implanting a biphenyl species
into the round and large chiral cavity of γ-CD via rotaxanation.
Capping the inner rim of the CD host with rigid aromatic rings,
which interact with the biphenyl axle at both ground and
excited states, induced increased conformational restraint in the
chiral cavity. The enantioselective sensitized photoisomeriza-
tion of 1ZZ with these rotaxanes gives 1EZ with an enhanced
ee of up to 15.3%. This study opens a new window for building
highly specific chiral binding sites from naturally occurring
chiral hosts
C
DOI: 10.1021/acs.orglett.7b00057
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b00057.
■
S
Experimental details and analytical data (NMR, ESI-
HRMS, fluorescence lifetime analyses) (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: yangchengyc@scu.edu.cn.
ORCID
Cheng Yang: 0000-0002-2049-1324
Author Contributions
⊥Z.Y. and Q.H. contributed equally.
(11) Fukuhara, G.; Imai, M.; Yang, C.; Mori, T.; Inoue, Y. Org. Lett.
2011, 13, 1856.
(12) Yang, C.; Fukuhara, G.; Nakamura, A.; Origane, Y.; Fujita, K.;
Yuan, D.-Q.; Mori, T.; Wada, T.; Inoue, Y. J. Photochem. Photobiol., A
2005, 173, 375.
Notes
The authors declare no competing financial interest.
(13) For details, see the Supporting Information.
ACKNOWLEDGMENTS
■
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This work was supported by the National Natural Science
Foundation of China (Nos. 21572142, 21372165, 21321061,
21402110, 21402129, and 21372159), the State Key Laboratory
of Polymer Materials Engineering (Grant No. sklpme2014-2-
06), and the Comprehensive Training Platform of Specialized
Laboratory, College of Chemistry, Sichuan University.
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DOI: 10.1021/acs.orglett.7b00057
Org. Lett. XXXX, XXX, XXX−XXX