Switching of polymerization activity of cinnamoyl-α-cyclodextrin

Article abstract of DOI:10.1039/b818241h

Cinnamoyl α-cyclodextrin (α-CD) has been found to initiate polymerization of δ-valerolactone (δ-VL) to give a polymer in high yield. By the presence of the cinnamoyl group, hydrogen bond was formed between the carbonyl oxygen of δ-VL and the hydroxyl grou

Full text of DOI:10.1039/b818241h

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Switching of polymerization activity of cinnamoyl-a-cyclodextrin†
Motofumi Osaki, Yoshinori Takashima, Hiroyasu Yamaguchi and Akira Harada*
Received 15th October 2008, Accepted 9th January 2009
First published as an Advance Article on the web 4th March 2009
DOI: 10.1039/b818241h
Cinnamoyl a-cyclodextrin (a-CD) has been found to initiate polymerization of d-valerolactone (d-VL)
to give a polymer in high yield. By the presence of the cinnamoyl group, hydrogen bond was formed
between the carbonyl oxygen of d-VL and the hydroxyl group of CD to activate the monomer, which
was observed by FT-IR measurements. However, the cinnamoyl group at the C3- and C6-positions of
a-CD did not affect the polymerization ability. Only that of the C2-position showed high
polymerization activity. The polymerization activity could be switched by the photoisomerization of the
cinnamoyl group attached to the rim of a-CD. Specific monomer recognition and polymerization in the
active site of the a-CD cavity was changed by the photoisomerization.
corresponds to the formation of the inclusion complexes in bulk.
Introduction
After the formation of inclusion complexes, monoester-modified
CD was immediately formed. When monoester-modified CD is
used as an initiator, the monoester-modified CD would be expected
to initiate the polymerization of lactones with high activity. To
observe the difference between the polymerization activity of plain
CD and that of esterified CD, we estimated the polymerization
activity of esterified CD prepared from the intact CD. We chose
a-CD because when intact, it does not initiate the polymerization
of d-VL at all.
The polymerization of d-VL was carried out by heating
mixture of d-VL and a-CD (or esterified a-CD) in bulk at
100 ◦C ([d-VL]/[CD] = 10). Fig. 1 shows time–yield plots for
the polymerization of d-VL initiated by a-CD and 2-O-trans-
cinnamoyl-a-CD (2-trans-CiO-a-CD), respectively. The mixture
of a-CD and d-VL did not give any polymers. On the other hand,
2-trans-CiO-a-CD gave poly(d-VL) in high yield (98% within
Biological molecules change their structures depending on their
external environments.1,2 Structural control of these molecules
leads to principles of molecular recognition and catalytic
activities.3–5 In the field of supramolecular chemistry, control of
molecular recognition and supramolecular structures has been
achieved by using external stimuli.6–15 However, to the best of
our knowledge, there is no report on the control of its catalytic
function by structural changes of supramolecular architectures
using external stimuli. Cyclodextrins (CDs) have been studied
as enzyme models because of their selective inclusion properties
with various guest molecules.16–17 CDs promote many chemical
reactions, such as hydrolysis of activated esters.18–20 We found
that CDs are useful as supramolecular synthetic reagents to give
CD-tethered polyesters with threading CDs, just by mixing CDs
and lactones in bulk without any co-catalyst or solvent.21 The
control of the polymerization activity of the CD was achieved
by the formation of supramolecular complexes.22 Taking the
polymerization mechanism into consideration, we suppose that
not only the monomer recognition by CD in an initial state but
also the ester groups between the CD and the polymer chain are
important for the propagation of the polymerization. Here, we
have studied effects of the ester groups on the polymerization to
improve and to control the polymerization activity. We used a-CD,
which does not have polymerization activity for d-valerolactone
(d-VL) by itself.
Results and discussion
Effect of esterificaton of CD on the polymerization activity
Our previous study indicated that the polymerization of lactones
initiated by intact CDs showed an initial induction period, which
Department of Macromolecular Science, Graduate School of Science, Osaka
University, 1-1 Machikaneyama-cho, Toyonaka, Osaka, 560-0043, Japan.
E-mail: harada@chem.sci.osaka-u.ac.jp; Fax: +81-6-6850-5445; Tel: +81-
6-6850-5445
† Electronic supplementary information (ESI) available: 1H NMR spectra
and MALDI-TOF spectra. CCDC reference number 706467. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/b818241h
Fig. 1 Dependency of yield on time for the polymerization of d-VL
initiated by a-CD or 2-trans-CiO-a-CD in bulk at 100 ◦C. ([d-VL]/[CD] =
10).
1646 | Org. Biomol. Chem., 2009, 7, 1646–1651
This journal is
The Royal Society of Chemistry 2009
©

View Article Online
Table 1 Polymerization of d-VL initiated by a-CD derivatives in bulka
48 h) under the same conditions. Other esterified CDs, such
as 2-O-hydroxybutyrates-a-CD and 2-O-benzyloxypentanoyl-b-
CD,21 have also been found to initiate polymerization. These
results indicate that the esterification of a-CD is important for
the polymerization of d-VL.
Degree of
b
Entry CD
Yield/% Mn
polymerizationc
1
2
3d
4
5
6
7
a-CD
0
82
58
7
1
0
—
5200
8100 125.0
1900
1500
0
0.0
41.3
2-trans-CiO-a-CD
Product of entry 2
3-trans-CiO-a-CD
6-trans-CiO-a-CD
2-trans-CiO-a-CD …CiOMe
2-cis-CiO-a-CD
To validate the difference in the polymerization activity, FT-IR
spectroscopy was carried out.23 Fig. 2 shows the FT-IR spectra
of d-VL in the presence and absence of CDs. d-VL shows a
3.7
3.6
0
strong band due to C O stretching at 1731.8 cm-1 (Fig. 2(a)). The
=
=
12
2100
8.1
C O stretching band of the mixture of a-CD and d-VL in bulk
a [d-VL]/[CD] = 20. The mixtures of CD and d-VL were heated at 100 ◦C
for 48 h. b The molecular weights were calibrated by GPC calculated with
polystyrene standard (eluent: THF). c Determined by the 1H NMR value
of the polymer chain. d Before the polymerization, the polymer product of
entry 2 was included into native a-CDs to form poly-pseudo-rotaxane.20c
showed similar wavenumber to that of d-VL (Fig. 2(b)), indicating
that there is no intermolecular interaction between the carbonyl
group of d-VL and the hydroxyl group of a-CD. In contrast, the
=
C O stretching band in the mixture of 2-trans-CiO-a-CD and
d-VL shifted to lower wavenumber (1700.4 cm-1), indicating that
hydrogen bonds between the hydroxyl group of 2-trans-CiO-a-CD
and the carbonyl group of d-VL are formed.
addition of d-VL, the product (which still has a polymerization
activity) gave a longer polyester with Mn of 8100. The degree of
the polymerization was more than 120, as determined by NMR
spectroscopy (entry 3 in Table 1).
(1)
(2)
Although 2-trans-CiO-a-CD showed high polymerization ac-
tivity for d-VL, 3-trans-CiO-a-CD and 6-trans-CiO-a-CD showed
significantly lower polymerization activity, respectively (eqn 3 and
4, entries 4 and 5 in Table 1). These results indicate that the
esterifications at C3 and C6 do not affect the polymerization
ability. The ester group at C2 of a-CD is thus essential for the
polymerization. The secondary hydroxyl groups (at C2 and C3)
of CD have higher basicity than those of primary ones (at C6).
Moreover, whereas 3-trans-CiO-a-CD has the ester group of the
cinnamoyl substituent at the C3-carbon orientating outside the
CD cavity, that of 2-trans-CiO-a-CD locates nearby the CD cavity,
which was characterized by single crystal X-ray analysis.‡
Fig. 2 FT-IR spectra of d-VL (a), the mixture of d-VL and a-CD (b),
and the mixture of d-VL and 2-trans-CiO-a-CD (c).
Okamoto24 and Penczek25 reported that activated heterocyclic
monomers are generated by hydrogen bond formation or pro-
tonation. The formation of a hydrogen bond between CD and
monomer activates the carbonyl carbon of d-VL for nucleophilic
attack. Therefore, 2-trans-CiO-a-CD should show polymerization
activity, whereas a-CD should not initiate the polymerization.
Relationship between polymerization activity and
substitution positions
To understand the relationship between the esterification of a-CD
and the enhancement of the polymerization activity, we studied
the effects of the position of the cinnamoyl group on a-CD.
trans-Cinnamic acid is able to be selectively attached to various
positions on a-CD. The reactionof m-nitrophenyltrans-cinnamate
and a-CD in a basic aqueous solution gave regioisomers of
a-CD modified with the cinnamoyl group – 3-trans-CiO-a-CD
and 2-trans-CiO-a-CD. The other isomer, 6-trans-CiO-a-CD, was
prepared according to a literature method.26
(3)
‡ The data were collected on a Rigaku RAXIS-RAPID diffractomer. A
crystal, of dimensions 0.25 ¥ 0.25 ¥ 0.15 mm, was selected and mounted on
a 0.30 mm MicroMount and immediately placed on the goniometer head
in a 100.1 K N2 gas stream. Data integration, reduction, collections for
absorption and polarization effects were all performed using PROCESS-
AUTO and CrystalStructure software. Space group determination, struc-
ture solution and refinement were obtained using Crystalstructure ver.
3.7 and SHELXL software. Crystal data: C45H66O31·12.6245H2O, M =
d-VL was added to these a-CD derivatives and heated to 100 ◦C
in bulk. The results are summarized in Table 1. a-CD did not react
with d-VL after 48 h (eqn (1), entry 1 in Table 1). 2-trans-CiO-
a-CD gave poly(d-VL) with molecular weight (Mn, determined
by GPC with polystyrene standard) of 5200 in 82% yield (eqn
(2), entry 2 in Table 1) under the same conditions. After further
˚
1330.36, orthorhombic, a = 15.5665(4), b = 23.5385(5), c = 33.1929(9) A,
◦
◦
◦
3
˚
a = 90 , b = 90 , g = 90 , U = 12162.3(5) A , T = 100.1 K, space group
P212121, Z = 8, m(Cu-Ka) = 1.54187 mm-1, 99451 reflections collected,
21089 unique, (Rint = 0.043), R = 0.0698, wR2 = 0.2154.
This journal is
The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 1646–1651 | 1647
©

View Article Online
d-VL to shorter wavenumber (1700.4 cm-1) (Fig. 4(c)), indicating
that the inclusion and the activation of the monomer took place in
the CD cavity via hydrogen bond formation. On the other hand,
the mixture of d-VL and 2-cis-CiO-a-CD did not show such a shift
(Fig. 4(e)), suggesting that 2-cis-CiO-a-CD and d-VL did not show
this interaction. These results suggest that d-VL was included only
in the cavity of 2-trans-CiO-a-CD and that the CD cavity functions
as the active site for the polymerization. The aromatic ring of
the cinnamoyl group of 2-cis-CiO-a-CD significantly inhibits the
formation of the inclusion complex.
(4)
The product obtained from the mixture of 2-trans-CiO-a-CD
and d-VL was characterized by 1H NMR and MALDI-TOF mass
spectroscopy (Figs. S1 and S2†). The product obtained from the
mixture of 2-trans-CiO-a-CD and d-VL has a single poly(d-VL)
chain propagated from the ester bond at the C2-position of 2-
trans-CiO-a-CD.
The polymerization ability of 2-trans-CiO-a-CD is improved
by the following. (i) The cinnamoyl group of 2-trans-CiO-a-CD
is activated by the formation of hydrogen bonds between the
carbonyl oxygen of the trans-cinnamoyl group and the secondary
hydroxyl groups of CD. (ii) The hydroxyl group at the end of
monomer might be easily attached to the carbonyl carbon of the
cinnamoyl group at C2 and thus propagate from C2 because the
ester group of the cinnamoyl group is located adjacent to the
included monomer.
We investigated the inhibition of the initiation reaction of d-VL
by using a competitive guest. Methyl trans-cinnamate (CiOMe;
association constant Ka = 1200 M-1 for the a-CD cavity27) was
used as a competitive guest for d-VL (Ka = 10 M-1 for a-CD).
The inclusion complex of 2-trans-CiO-a-CD with CiOMe (2-trans-
CiO-a-CD…CiOMe) showed no polymerization activity (entry 6
in Table 1). It should be considered that d-VL was not included
in the cavity of 2-trans-CiO-a-CD because CiOMe is strongly
included in the cavity. These observations suggest that the cavity
of 2-trans-CiO-a-CD is the active site for the polymerization of
d-VL.
Fig. 4 FT-IR spectra of d-VL (a), 2-trans-CiO-a-CD (b), a mixture of
d-VL and 2-trans-CiO-a-CD (c), 2-cis-CiO-a-CDs (d), and a mixture of
d-VL and 2-cis-CiO-a-CD (e). (KBr-disc method).
Switch of polymerization activity
We supposed that control of the molecular recognition might lead
to control of the initiation reaction – inhibition of the monomer
binding in the a-CD cavity would lead to the inhibition of the poly-
merization. We investigated the control of the polymerization by
using 2-trans-CiO-a-CD. The initiation step would be prevented
by the photoisomerized cinnamoyl group if the photoisomerized
substituent acted as a ‘ledge’, restricting monomer inclusion at the
rim of the a-CD cavity. In aqueous solution, 2-trans-CiO-a-CD
was irradiated by UV light (l = 280 nm) to give 2-cis-CiO-a-CD
(Fig. 3), which was purified by preparative reverse-phase HPLC. A
mixture of 2-cis-CiO-a-CD and d-VL gave only 12% of poly(d-
VL) with lower Mn under the same conditions (entry 7 in Table 1),
indicating that the polymerization activity of 2-CiO-a-CD was
restricted by using the photoisomer of the cinnamoyl a-CD. Thus,
the cis-cinnamoyl group seems to inhibit the binding of monomer
in the 2-CiO-a-CD cavity.
Scheme 1 shows a proposed propagation mechanism for the
polymerization of d-VL by 2-CiO-a-CDs. First, 2-trans-CiO-a-
CD includes d-VL in its cavity, then the hydroxyl group of CD
attacks the carbonyl carbon of d-VL to open the ring. The
generated hydroxyl group of the monomer immediately attacks
the ester bond of 2-trans-CiO-a-CD to insert d-VL into the ester
bond between the cinnamoyl group and a-CD, so as to give a single
poly(d-VL) chain attached to a-CD at the C2-position. Another
new d-VL is accepted by the cavity to continue the propagation step
to produce poly(d-VL) chain from the CD moiety (Scheme 1(A)).
However, it should be noted that the 2-trans-CiO-a-CD…CiOMe
inclusion complex showed no polymerization activity due to
the inhibition of monomer recognition (Scheme 1(B)). After
the photoisomerization, 2-cis-CiO-a-CD did not initiate the
polymerization. The substituent of 2-cis-CiO-a-CD might limit
monomer inclusion, acting as a ‘ledge’ at the rim of active site of
the CD cavity. The approach of d-VL is inhibited by the presence
of bulky cis-cinnamoyl group (Scheme 1(C)).
Conclusions
In conclusion, a-CD modified with ester groups at C2-position
has been found to show polymerization activity for d-VL, whereas
free a-CD did not initiate the polymerization. The polymerization
takes place in the CD cavity. We have succeeded in switching the
Fig. 3 Schematic illustration of photoisomerization of 2-CiO-a-CD.
The FT-IR spectra of the mixture of d-VL and 2-trans-CiO-a-
CD showed a large shift of the band for the carbonyl group of
1648 | Org. Biomol. Chem., 2009, 7, 1646–1651
This journal is
The Royal Society of Chemistry 2009
©

View Article Online
G3000HXL and G2000HXL column (eluent: THF, detector:
refractive index and UV absorbance (l = 256 nm)). Isothermal
titration calorimetry (ITC) was performed using a MicroCal VP-
ITC MacroCalorimeter to determine the association constant of
CDs.
Preparation of trans-cinnamoyl-a-CDs (trans-CiO-a-CDs)
6-trans-CiO-a-CD was prepared by
a previously reported
method.22 2- and 3-trans-CiO-a-CD were prepared by the fol-
lowing method.
(i) Preparation of m-nitrophenyl cinnamate (m-NPC). trans-
Cinnamic acid (6.1 g, 41 mmol), m-nitorphenol (5.8 g, 41 mmol),
and N,N¢-dicyclohexyl-carbodiimide (8.5 g, 41 mmol) were dis-
solved in THF (37 mL), and stirred for 24 h at room temperature.
After removal of the undissolved residue by filtration, the filtrate
was poured into 800 mL water. The resulted precipitate was
washed with a saturated aqueous solution of sodium hydrogen
carbonate once and recrystallized twice from n-butanol. 1H NMR
(DMSO-d6, 20 ◦C, 500 MHz): d 6.90 (d, J = 16.1 Hz, 1H,
Scheme 1 Proposed mechanisms of the propagation step by 2-trans-CiO-
a-CD (A) and the inhibition of the propagation by 2-trans-CiO-
a-CD…CiOMe (B) and 2-cis-CiO-a-CD (C).
=
=
-CH CH-Ph), 7.44–7.50 (m, 3H, -CH CH-3,4,5-Ph), 7.71–7.78
=
(m, 3H, 6-Ph-NO2), 7.79–7.85 (m, 2H, -CH CH-2,6-Ph), 7.91
=
(d, J = 16.1 Hz, 1H, -CH CH-Ph). Elemental Anal. Calcd for
initiation activity of the polymerization by the photoisomerization
of the cinnamoyl group at the C2-position. This polymeriza-
tion system showed specific substrate recognition, releasing the
products from the active site, and is similar to those of enzymes
having highly sophisticated functions. Application of this system
to polymerization of other molecules are now under investigation.
C15H11NO4: C, 66.91; H, 4.12; N, 5.20. Found: C, 66.79; H, 3.96;
N,5.21.
(ii) Preparation of cinnamoyl-attached a-cyclodextrins (CiO-a-
CDs). a-CD (1.5 g, 1.6 mmol) was dissolved in 300 mL of
0.40 mM sodium carbonate solution containing 180 mL of
acetonitrile. m-NPC (0.60 g, 2.2 mmol) dissolved in 30 mL of
acetonitrile was gradually added to the a-CD solution with
stirring. The pH of the reaction medium was adjusted to 8–9
by the addition of 0.10 M NaOH solution at room temperature.
After 2 h, the reaction solution was adjusted to pH 3 with
1.0 M HCl solution. The reaction mixture was lyophilized to
give colorless powder. The crude powder was washed with water
(200 mL) to get rid of the insoluble compounds. The contaminants
in the filtrate were removed by the extration with 600 mL of
ether. The aqueous layer was lyophilized to give 2-trans-CiO-a-
CD and 3-trans-CiO-a-CD. Reversed-phase preparative HPLC
(colomn: SunFire C18-SemiPrep, solvent: water–acetonitrile) was
performed to separate these isomers. The lyophilized powder
was dissolved in 50 mL of distilled water and an aliquot of
the solution (5.0 mL) was injected onto HPLC system. 2-trans-
Experimental section
General procedures
All manipulations were carried out using standard Schlenk
techniques under an argon atmosphere. Tetrahydrofuran (THF)
was dried and deoxygenated by distillation over sodium benzophe-
none ketyl under an argon atmosphere. N,N-Dimethylformamide
(DMF) was dried and deoxygenated by distilling from BaO under
reduced pressure. a-Cyclodextrin (a-CD) was obtained from
Junsei Chemical Co., Ltd. d-Valerolactone (d-VL) was obtained
from Nacalai Tesque. Cyclodextrins were used after drying under
vacuum at 80 ◦C. Lactones were distilled over CaH2 under
˚
an argon atmosphere and dried over molecular sieves (4 A).
The photoisomerization was performed using an Asahi Spectra
Compact Xenon Light Source MAX-301 (300 W) with l = 280 nm
band pass filter ( 10 nm).
CiO-a-CD: H NMR (D2O, 20 ◦C, 600 MHz): d 7.88 (d, J =
1
=
=
16.0 Hz, 1H, -CH CH-Ph), 7.86 (d, J = 6.6 Hz, 2H, -CH CH-
=
2,6-Ph), 7.65 (t, J = 7.5 Hz, 2H, -CH CH-3,5-Ph), 7.51 (t, J =
B
=
7.4 Hz, 1H, -CH CH-4-Ph), C (2)H), 6.82 (d, J = 16.0 Hz,
Measurements
A
F
E
=
1H, -CH CH-Ph), 5.29 (C (1)H), 5.07 (C (1)H), 5.01 (C (1)H),
5.00 (CB(1)H), 4.98 (CC(1)H), 4.91 (CD(1)H), 4.67 (CA(2)H), 4.67
(CA(3)H), 4.11 (CE(3)H), 4.03 (CB(3)H), 3.93 (CA(3)H), 3.89
(CE(4)H), 3.47–3.98 (CA-F(5)H, CA-F(6)H, CB(4)H, CC(3–4)H),
3.84 (CC(3)H, CF(3)H), 3.62 (CC(4)H, CE(2)H), 3.60 (CF(2)H),
1H (500 and 600 MHz) and 13C (125 and 150 MHz) NMR
spectra in DMSO-d6 were measured on JEOL JNM-LA500 and
VARIAN INOVA 600 spectrometers. Assignments of 1H and 13
C
NMR peaks for some complexes were supported by 2D H–1H
NOESY, 2D 1H–1H COSY, 2D TOCSY, 2D HMQC and 2D
HMBC spectra. MALDI-TOF mass spectra measurements were
performed on a Shimadzu/KRATOS AXIMA-CFR spectrome-
ter. FT-IR spectra were measured on a JASCO FT/IR-410 spec-
trometer with KBr discs. Gel-permeation chromatography (GPC)
was performed using a TOSOH GPC system with a TOSOH
1
3.53 (CF(4)H, CC(2)H), 3.52 (CA(4)H, 3.51 (CD(2)H). 13C NMR
(D2O 20 C, 150 MHz): d 168.9 (-O-C O), 146.6 (-CH CH-Ph),
134.4 (-CH CH-1-Ph), 130.7 (-CH CH-4-Ph), 129.5 (-CH CH-
3,5-Ph), 128.8 (-CH CH-2,6-Ph), 117.4 (-CH CH-Ph), 99.0,
82.1, 73.6, 71.5, 70.5, 60.5, (CA(1–6) of CD moiety), 101.9, 101.8,
101.7, 81.7, 81.4, 73.9, 73.4, 73.3, 73.1, 72.6, 72.4, 72.3, 72.2,
◦
=
=
=
=
=
=
=
This journal is
The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 1646–1651 | 1649
©

View Article Online
72.1, 71.9, 71.8, 71.7, 60.9, 60.7, 60.3 (CB–F(1–6) of CD moiety).
MALDI-TOF MS; m/z = 1126.1 ([C45H66O31 + Na]+ = 1125.4),
1142.2 ([C45H66O31 + K]+ = 1141.3). Elemental Anal. Calcd for
C45H66O31(H2O)6: C, 44.63; H, 6.49. Found: C, 44.81; H, 6.28.
3-trans-CiO-a-CD: 1H NMR (D2O, 20 ◦C, 600 MHz): d 8.06
(d, J = 13.0 Hz, 1H, -CH CH-Ph), 6.11 (d, J = 13.0 Hz, 1H,
=
=
-CH CH-Ph), 5.35–5.69 (m, 11H, O(2,3)H), 5.02 (C(1¢¢)H), 4.84
(C(1¢)H), 4.79 (m, 4H, C(1)H), 4.38–4.58 (m, 6H, O(6)H), 4.06
(C(2¢)H), 3.52–3.88 (m, 22H, C(3)H, C(5)H and C(6)H), 3.16
(C(6¢)H), 3.20–3.49 (m, C(2)H and C(4)H overlapped with HOD).
MALDI-TOF MS; m/z = 1125.7 ([C45H66O31 + Na]+ = 1125.4).
Elemental Anal. Calcd for C45H66O31(H2O)7: C, 43.97; H, 6.56.
Found: C, 43.68; H, 6.26.
=
(d, J = 16.0 Hz, 1H, -CH CH-Ph), 7.88 (d, J = 16.0 Hz, 2H,
=
=
-CH CH-2, 6-Ph), 7.59 (t, J = 7.4 Hz, 2H, -CH CH-3, 5-Ph),
=
7.53 (t, J = 7.4 Hz, 1H, -CH CH-4-Ph), 6.70 (d, J = 16.0 Hz,
A
A
F
=
1H, -CH CH-Ph), 5.66 (C (3)H), 5.13 (C (1)H), 5.01 (C (1)H),
5.08 (CE(1)H), 5.06 (CD(1)H), 4.94 (CB(1)H), 4.91 (CC(1)H), 4.14
(CD(3)H), 4.01 (CA(5)H), 3.37–4.05 (CB, E, F(6)H, CC(3–6)H), 3.91
(CA(4)H, CF(4)H), 3.89 (CE(5)H), 3.87 (CA(2)H), 3.85 (CA(6)H),
3.84 (CF(3)H), 3.83 (CE(3)H), 3.82 (CD(5)H), 3.66 (CD(2)H),
3.65 (CD(6)H), 3.64 (CB(5)H, CF(5)H), 3.62 (CD(4)H), 3.60
(CE(2)H), 3.58 (CF(2)H), 3.53 (CE(4)H, CC◦(2)H), 3.51 (CB(3)H),
3.41 (CB(2)H, CB(4)H). 13C NMR (D2O 20 C, 150 MHz): d 170.0
Preparation of 2-trans-CiO-a-CD…CiOMe inclusion complex
2-trans-CiO-a-CD (22 mg, 20 mmol) was dissolved in water (2 mL),
and 3.2 mg (20 mmol) of methyl cinnamate (CiOMe) was added to
the solution. After stirring 10 min, the solution was lyophilized
and dried at 50 ◦C to remove excess amount of CiOMe and
to obtain 1 : 1 inclusion complex of 2-trans-CiO-a-CD…CiOMe.
(Yield 22 mg, 87%). H NMR (DMSO-d6, 30 ◦C, 500 MHz):
1
=
=
=
=
(-O-C O), 147.0 (-CH CH-Ph), 135.1 (-CH CH-1-Ph), 131.1
(-CH CH-4-Ph), 129.7 (-CH CH-3,5-Ph), 129.3 (-CH CH-2,6-
Ph), 118.2 (-CH CH-Ph), 101.8, 81.6, 79.7, 75.6, 73.7, 71.4,
=
d 7.72–7.65 (m, 6H, -CH CH-2,6-Ph (2-trans-CiO-a-CD and
=
=
=
CiOMe)), 7.41–7.44 (m, 6H, -CH CH-3,4,5-Ph (2-trans-CiO-a-
=
=
CD and CiOMe)), 6.69 (d, J = 16.0 Hz, 1H, -CH CH-Ph of
(CA(1–6) of CD moiety), 102.3, 102.2, 102.1, 102.0, 82.1, 82.0,
81.9, 81.8, 74.3, 73.8, 73.5, 73.3, 72.9, 72.7, 72.6, 72.5, 72.3, 72.2,
71.5, 61.2, 61.1, 61.0, 60.8 (CB–F(1–6) of CD moiety). MALDI-
TOF MS; m/z = 1125.4 ([C45H66O31 + Na]+ = 1125.4), 1142.3
([C45H66O31 + K]+ = 1141.3). Elemental Anal. Calcd for Calcd for
C45H66O31(H2O)5: C, 45.30; H,6.42. Found: C, 45.02; H, 6.35.
=
2-trans-CiO-a-CD), 6.63 (d, J = 16.0 Hz, 1H, -CH CH-Ph
of CiOMe), 5.33–5.72 (m, 11H, O(2,3)H), 5.03 (C(1¢¢)H), 4.84
(C(1¢)H), 4.79 (m, 4H, C(1)H), 4.34–4.60 (m, 6H, O(6)H), 4.06
(C(2¢)H), 3.51–3.89 (m, 22H, C(3)H, C(5)H and C(6)H), 3.21–
3.51 (m, C(2)H and C(4)H overlapped with HOD), 3.17 (C(6¢)H).
Elemental Anal. Calcd. for C55H76O33(H2O)11: C, 45.14; H, 6.75.
Found: C, 44.79; H, 6.38.
Polymerization of lactones initiated by CDs in bulk
All the procedures of the polymerization of lactones by CDs were
carried out by the following method. 2-trans-CiO-a-CD (9.1 mmol,
10.0 mg) was dried in vacuo at 80 ◦C for 24 h. Then, d-valerolactone
(180 mmol, 18 mg) was added to 2-trans-CiO-a-CD under an
argon atmosphere. The reaction tube was sealed under an argon
atmosphere, and kept at 100 ◦C with stirring. After the prescribed
reaction time, the polymerization was terminated by adding a
large amount of dry DMF (1.0 mL). The resulting powder was
dissolved in DMF. The resultant polymer solution was added to
THF (10.0 mL) to precipitate free CD. The filtrate was evaporated
Acknowledgements
The authors thank Dr. A. Hashidzume and Mr. S. Adachi of
Osaka University for helpful advice and for performing the NMR
experiments. This work has been partially supported by Grant
in-Aid No. A19205014 for Scientific Research and has been
conducted with financial support from the “Stress and Symbiosis
on Supramolecules” program of the Ministry of Education,
Culture, Sports, Science and Technology, Japan. M.O. thanks
the Japan Society of the Promotion of Science (JSPS) Research
Fellowships for Young Scientists.
1
in vacuo to obtain polyester (Yield: 82%). H NMR (DMSO-d6,
30 ◦C, 500 MHz): d 7.57 (m, 1H, p-cinnamate), 7.53 (d, J =
8.2 Hz, 1H, a-cinnamate), 7.39 (d, J = 8.2 Hz, 2H, o-cinnamate),
7.23 (m, 2H, m-cinnamate), 6.54 (m, 1H, b-cinnamate), 5.49 (br,
11H, O2,3H), 4.79 (br, 5H, C1H), 4.46 (br, 6H, O6H), 4.36 (br,
1H, C1’H), 4.00 (br, 4H, d-polymer), 3.76 (br, 12H, C6H), 3.63
(br, 12H, C35H), 3.37 (br, 12H, C4,2H), 2.27 (br, 4H, a-polymer),
1.55 (br, 8H, g - and b-polymer). To show detailed structure of
terminal cinnamoyl unit, the NMR sample was prepared by HPLC
to obtain lower molecular weight moiety. IR (KBr): 3396, 2932,
1704, 1643 cm-1.
References
1 D. M. Spencer, T. J. Wandless, S. L. Schreiber and G. R. Crabtree,
Science, 1993, 262, 1019.
2 P. J. Belshaw, D. M. Spencer, G. R. Crabtree and S. L. Schreiber, Chem.
Biol., 1996, 3, 731.
3 K. C. Nicolaou, F. Roschangar and D. Vourloumis, Angew. Chem. Int.
Ed., 1998, 37, 2014.
4 A. R. Minter, B. B. Brennan and A. K. Mapp, J. Am. Chem. Soc., 2004,
126, 10504.
5 Y. Kwon, H. D. Arndt, Q. Mao, Y. Choi, Y. Kawazoe, P. B. Dervan and
M. Uesugi, J. Am. Chem. Soc., 2004, 126, 15940.
6 F. M. Raymo and J. F. Stoddart, Molecular Switches, ed. B. L. Feringa,
section 7, “Switchable Catenanes and Molecular Shuttles”.
7 S. Shinkai, K. Shigematsu, M. Sato and O. Manabe, J. Chem. Soc.
Perkin, Trans 1, 1982, 2735.
8 A. Mulder, A. Jukovic, F. W. B. van Leeuwen, H. Kooijman, A. L.
Spek, J. Huskens and D. N. Reinhoudt, Chem. Eur. J., 2004, 10, 1114.
9 W.-Y. Yang, J.-H. Ahn, Y.-S. Yoo, N.-K. Oh and M. Lee, Nat. Mater.,
2005, 4, 399.
10 D. S. Sidhaye, S. Kashyap, M. Sastry, S. Hotha and B. L. V. Prasad,
Langmuir, 2005, 21, 7979.
11 F. Rakotondradany, M. A. Whitehead, A.-M. Lebuis and H. F. Sleiman,
Chem. Eur. J., 2003, 9, 4771.
Preparation of 2-cis-CiO-a-CD (photoisomerization)
2-trans-CiO-a-CD (50 mg) was dissolved in water (20 mL). The
solution was irradiated by Asahi Spectra Compact Xenon Light
Source MAX-301 (wavelength: l = 280 10 nm) in ice bath for
24 h. The solution was lyophilized to obtain white powder, then
2-cis-CiO-a-CD was isolated with reverse-phase HPLC. (Yield:
32 mg, 64%) H NMR (DMSO, 30 ◦C, 500 MHz): d 7.65 (d,
1
=
=
2H, -CH CH-2,6-Ph), 7.34–7.36 (t, 2H, -CH CH-3,4,5-Ph), 6.97
1650 | Org. Biomol. Chem., 2009, 7, 1646–1651
This journal is
The Royal Society of Chemistry 2009
©

View Article Online
12 T. Hirose, K. Matsuda and M. Irie, J. Org. Chem., 2006, 71, 7499.
13 (a) M. Mu¨ller and R. Zentel, Macromolecules, 1994, 27, 4404; (b) G.
Maxein and R. Zentel, Macromolecules, 1995, 28, 8438; (c) M. Mu¨ller
and R. Zentel, Macromolecules, 1996, 29, 1609; (d) S. Mayer, G. Maxein
and R. Zentel, Macromolecules, 1998, 31, 8522.
14 (a) F. Ciardelli, D. Fabbri, O. Pieroni and A. Fissi, J. Am. Chem. Soc.,
1989, 111, 3470; (b) O. Pieroni, A. Fissi, A. Viegi, D. Fabbri and F.
Ciardelli, J. Am. Chem. Soc., 1992, 114, 2734.
15 (a) P. Kuad, A. Miyawaki, Y. Takashima, H. Yamaguchi and A. Harada,
J. Am. Chem. Soc., 2007, 129, 12630; (b) K. Yamauchi, Y. Takashima,
A. Hashidzume, H. Yamaguchi and A. Harada, J. Am. Chem. Soc.,
2008, 130, 5024.
Bioorganic Chemistry of Enzymatic Catalysis, Wiley, New York, 1984;
(c) V. D’Souza and M. L. Bender, Acc. Chem. Res., 1987, 20, 146;
(d) R. L. VanEtten, J. F. Sebastian, G. A. Clowes and M. L. Bender,
J. Am. Chem. Soc., 1967, 89, 3242; (e) R. L. VanEtten, J. F. Sebastian,
G. A. Clowes and M. L. Bender, J. Am. Chem. Soc., 1967, 89, 3253.
20 Y. Takashima, Y. Kawaguchi, S. Nakagawa and A. Harada, Chem.
Lett., 2003, 12, 1122.
21 (a) Y. Takashima, M. Osaki and A. Harada, J. Am. Chem. Soc., 2004,
126, 13588; (b) M. Osaki, Y. Takashima, H. Yamaguchi and A. Harada,
Macromolecules, 2007, 40, 3154.
22 M. Osaki, Y. Takashima, H. Yamaguchi and A. Harada, J. Am. Chem.
Soc., 2007, 129, 14452.
16 J. L. Atwood, J. E. D. Davies, D. D. MacNicol and F. Vo¨gtle, Com-
prehensive Supramolecular Chemistry, Vol. 3. Cyclodextrins, Pergamon,
Oxford, 1996.
23 (a) Y. Nakai, K. Yamamoto, K. Terada and K. Akimoto, Chem. Pharm
Bull., 1984, 32, 685; (b) K. Moribe, E. Yonemochi, T. Oguchi, Y. Nakai
and K. Yamamoto, Chem. Pharm. Bull., 1995, 43, 666.
24 (a) Y. Okamoto, Polym. Prepr. Am. Chem. Soc. Div. Polym. Chem.,
1984, 25, 264; (b) Y. Okamoto, Makromol. Chem. Macromol. Symp.,
1991, 42/43, 117.
25 (a) K. Brzezin´ska, R. Szyman´ski, P. Kubisa and S. Penczek, Makromol.
Chem. Rapid Commun., 1986, 7, 1; (b) R. Tokar, P. Kubisa and S.
Penczek, Macromolecules, 1994, 27, 320.
17 Special Issue: Cyclodextrins, Chem. Rev., 1998, 98(5).
18 (a) M. F. Czarniecki and R. Breslow, J. Am. Chem. Soc., 1978, 100,
7771; (b) R. Breslow, M. F. Czarniecki, J. Emert and H. Hamaguchi,
J. Am. Chem. Soc., 1980, 102, 762; (c) R. Breslow, G. L. Trainor and A.
Ueno, J. Am. Chem. Soc., 1983, 105, 2739; (d) R. Breslow, Acc. Chem.
Res., 1991, 24, 317; (e) B. Zhang and R. Breslow, J. Am. Chem. Soc.,
1997, 119, 1676; (f) R. Breslow, X. Zhang and Y. Huang, J. Am. Chem.
Soc., 1997, 119, 4535–4536.
26 T. Hoshino, M. Miyauchi, Y. Kawaguchi, H. Yamaguchi and A.
Harada, J. Am. Chem. Soc., 2000, 122, 9876.
19 (a) M. L. Bender and M. Komiyama, Cyclodextrin Chemistry, Springer,
Berlin, 1978; (b) M. L. Bender, R. J. Bergeron and M. Komiyama, The
27 T. W. Rosanske and K. A. Connors, J. Pharm. Sci., 1980, 69,
564.
This journal is
The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 1646–1651 | 1651
©