Contraction of supramolecular double-threaded dimer formed by α-cyclodextrin with a long alkyl chain

Article abstract of DOI:10.1021/ol063078e

(Figure Presented) A double-threaded dimer bearing a long substituent part and a large stopper group has been prepared and showed a conformational change with increased solvent polarity.

Full text of DOI:10.1021/ol063078e

ORGANIC
LETTERS
2007
Vol. 9, No. 6
1053-1055
Contraction of Supramolecular
Double-Threaded Dimer Formed by
r
-Cyclodextrin with a Long Alkyl Chain
Shouichi Tsukagoshi, Atsuhisa Miyawaki, Yoshinori Takashima,
Hiroyasu Yamaguchi, and Akira Harada*
Department of Macromolecular Science, Graduate School of Science,
Osaka UniVersity, Toyonaka, Osaka 560-0043, Japan
harada@chem.sci.osaka-u.ac.jp
Received December 20, 2006
ABSTRACT
A double-threaded dimer bearing a long substituent part and a large stopper group has been prepared and showed a conformational change
with increased solvent polarity.
Molecular motors and machines in biological systems, such
as dynein, flagellar, myosin, and kinesin, have highly precise
structures and achieve controlled movements by external
stimuli. Molecular motors in biological systems can be
roughly categorized as either linear molecular motors1 or
rotary motors.2 Recently, the subject of nanoscale artificial
molecular muscles and motors has attracted much interest
from researchers.3-5 Sauvage reported that a linear molecular
muscle based on transition metal templates showed expansive
and contractive properties under the action of a chemical
signal.3 Other notable work concerning linear molecular
(2) (a) Berg, H.; Anderson, R. A. Nature 1973, 245, 380-382. (b) Boyer,
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R.; Yoshida, M.; Kinoshita, K. Nature 1997, 386, 299-302. (d) Samatey,
F. A.; Imada, K.; Nagashima, S.; Vonderviszt, F.; Kumasaka, T.; Yamamoto,
M.; Namba, K. Nature 2001, 410, 331-337. (e) Namba, K.; Vonderviszt,
F. Q. ReV. Biophys. 1997, 30, 1-65. (f) Walker, J. E. Angew. Chem., Int.
Ed. 1998, 37, 2308-2319.
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Linke, M.; Sauvage, J.-P. Chem. Soc. ReV. 1999, 28, 293-305. (b) Jime´nez,
M. C.; Dietrich-Buchecker, C.; Sauvage, J.-P.; De Cian, A. Angew. Chem.,
Int. Ed. 2000, 39, 1295-1298. (c) Jime´nez-Molero, M. C.; Dietrich-Bucheck-
er, C.; Sauvage, J.-P. A. Angew. Chem., Int. Ed. 2000, 39, 3284-3287. (d)
Jime´nez-Molero, M. C.; Dietrich-Buchecker, C.; Sauvage, J.-P. Chem. Eur.
J. 2002, 8, 1456-1466. (e) Dietrich-Buchecker, C.; Jime´nez-Molero, M.
C.; Sartor, V.; Sauvage, J.-P. Pure Appl. Chem. 2003, 75, 1383-1393.
(1) (a) Yin, H.; Wang, M. D.; Svoboda, K.; Landick, R.; Block, S. M.;
Gelles, J. Science 1995, 270, 1653-1657. (b) Hirokawa, N. Science 1998,
279, 519-526. (c) Kitamura, K.; Tokunaga, M.; Iwane, A. H. Nature 1999,
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(e) Vale, R. D.; Milligan, R. A. Science 2000, 288, 88-95.
10.1021/ol063078e CCC: $37.00
© 2007 American Chemical Society
Published on Web 02/20/2007

muscles was carried out by Stoddart et al. using palindromic
[3]rotaxane with the redox-active tetrathiafulvalene unit and
cyclobis(paraquat-p-phenylene).4 These designs have been
developed employing a double-threaded dimer, in which the
actuation was inspired by natural muscle, such as that of
the myosin-actin complex. We previously reported that
6-cinnamamide-R-CD and 6-aminocinnamate-R-CD formed
a double-threaded dimer; however, substituent groups on
R-CDs are too short to mimic the contraction and extension
of skeletal muscle.6 In this paper, we have prepared a
modified 6-aminocinnamamide-R-CD and investigated the
formation of the double-threaded dimer. We discuss the
conformational change of the double-threaded dimer by
increased solvent polarity.
mass spectrum of 3 showed the dimer species (Figure S3,
red line). The peaks of the supramolecular polymers having
a degree of polymerization of more than two were not
observed. Compounds 1 and 2 showed only the monomer
species. On the basis of our 1H NMR and MALDI-TOF mass
spectra, formation of a double-threaded dimer (3) is proposed.
The spectrum of 3 in DMSO-d6 showed the ROE correla-
tion between the protons of the cinnamamide group and
protons of R-CD (O(6)-H) and between the hexyl group (the
part of i) and inner protons of R-CD (C(3)-H and C(5)-H)
(Figure 1a). Phenyl protons of the cinnamamide group were
The reaction of 1 with sodium 2,4,6-trinitrobenzene
sulfonate (TNBS) in methanol/pyridine at room temperature
afforded 6-[4-(6-(6-(2,4,6-trinitroanilino)hexylureido)hex-
ylureido)cinnamamido]-R-CD (2) as a model compound in
85% yield because the interaction between the long alkyl
chain and R-CD is very weak in organic solvents. The
double-threaded dimer (3) was prepared in a sodium carbon-
ate buffer at room temperature and confirmed by 1H NMR,
2D-ROESY, MALDI-TOF mass, and circular dichroism
spectroscopies (Scheme 1).
Scheme 1
1
The H NMR spectrum of 1 is similar to that of 2;
however, the spectra of 2 and 3 are different in DMSO-d6
(see Supporting Information, Figure S2). Comparing the 1H
NMR spectra of 2 with that of 3, the peaks of cinnamamide
protons and alkyl protons of 3 shifted to higher magnetic
fields (Figure S2c). Moreover, the chemical shift of the end
group of 3 exhibited a single resonance, indicating formation
of a symmetric supramolecular complex. The MALDI-TOF
Figure 1. ROESY spectra of 3 in (a) DMSO-d6 and (b) DMSO-
d6/H2O. To clarify the illustration, another long alkyl chain was
omitted.
(4) Liu, Y.; Flood, A. H.; Bonvallet, P. A.; Vignon, S. A.; Northrop, B.
H.; Tseng, H.-R.; Jeppesen, J. O.; Huang, T. J.; Brough, B.; Baller, M.;
Magonov, S.; Solares, S. D.; Goddard, W. A.; Ho, H.-M.; Stoddart, J. F. J.
Am. Chem. Soc. 2005, 127, 9745-9759.
(5) Roland, J. T.; Guan, Z. J. Am. Chem. Soc. 2004, 126, 14328-14329.
(6) (a) Miyauchi, M.; Kawaguchi, Y.; Yamaguchi, H.; Harada, A. J. Incl.
Phenom. Macrocycl. Chem. 2004, 50, 57-62. (b) Miyauchi, M.; Takashima,
Y.; Yamaguchi, H.; Harada, A. J. Am. Chem. Soc. 2005, 127, 2984-2989.
not correlated to inner protons of R-CD (C(3)-H and C(5)-
H),7 whereas hexyl protons (the part of i) were correlated to
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Org. Lett., Vol. 9, No. 6, 2007

inner protons of R-CD in the ratio of H2O/DMSO-d6 ) 1:1
(Figure 1b). These results indicate that R-CD moved from
the site of the cinnamamide group to that of the hexyl group.
Double-threaded dimer 3 showed a negative exciton
coupling at the maximum absorption wavelength of the
cinnamamide group (331 nm) in DMSO (Figure 2a). The
site of R-CD was found to change with the solvent polarity.
Considering the results of our ROESY NMR and circular
dichroism spectral data, R-CD of 3 moves to the hexyl site
in the axle guest parts in 1:1 H2O/DMSO-d6.
To estimate the size of the double-threaded dimer 3 in
DMSO-d6 and H2O/DMSO-d6 (1:1), the pulse field gradient
spin-echo (PFGSE) NMR technique was used and the
diffusion coefficients (D) and hydrodynamic radii (RH)12,13
of the supramolecular complexes were determined. The
apparent volume of double-threaded dimer 3 in DMSO-d6
and H2O/DMSO-d6 (1:1) was 8.142 and 8.641 nm3 in diluted
solution (5 mM), respectively. The change of length of 3 is
estimated to be about 0.66 nm calculated by molecular
modeling. These results are conconsistent with the hydro-
dynamic radii and indicate that 3 forms a complex with a
larger size or a stretched state in H2O/DMSO-d6.
In conclusion, double-threaded dimer 3 bearing a long
substituent part and a large stopper group has been prepared.
Upon addition of water to a solution of 3, the conformation
of 3 was found to change, as revealed by 1H NMR, ROESY,
and circular dichroism spectroscopies. Changes in molecular
size as a function of solvent polarity have been demonstrated
by PFGSE-NMR. As a general property of CDs, slightly
apolar cavity of CD is substituted by nonpolar guest
molecules in aqueous media, which are energetically
favored.10-11 On the basis of the characteristics of CDs, we
have demonstrated that double-threaded CD dimer (3)
undergoes a contractile motion when the solvent polarity is
increased. We are currently expanding these studies to the
synthesis of supramolecular polymers based on double
threaded dimer units.
Acknowledgment. The authors thank Dr. Akihito Hash-
idzume and Mr. Seiji Adachi, Department of Chemistry,
Graduate School of Science, Osaka University, for 2D-NMR
experiments. This work has been partially supported by Grant
in-Aid no. S14103015 for Scientific Research and has been
conducted with financial support from the 21st Century COE
(Center of Excellence) program of the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
Figure 2. Circular dichroism spectra of 3 in (a) DMSO and (b)
DMSO/H2O at 25 °C.
potential reason for this exciton coupling is that two
cinnamamide groups are located in close proximity. How-
ever, double-threaded dimer 3 exhibited a negative induced
circular dichroism band at 331 nm (no exciton coupling) in
1:1 H2O/DMSO-d6 (Figure 2b).8 This result indicates that
the cinnamamide moiety was located outside the R-CD cavity
with an orientation perpendicular to R-CD.9 The inclusion
Supporting Information Available: Selected NMR data
(1D NMR and ROESY spectrum). This material is available
free of charge via the Internet at http://pubs.acs.org.
OL063078E
(11) (a) ComprehensiVe Supramolecular Chemistry, Cyclodextrins; At-
wood, J. L., Davies, J. E. D., MacNicol, D. D., Vo¨gtle, F., Eds.;
Pergamon: Oxford, 1996; Vol. 3, pp 189-203. (b) Szejtli, J. Chem. ReV.
1998, 98, 1743-1753.
(12) The viscosity of the DMSO/water mixture is necessary to determine
the diffusion coefficient. The viscosity of the DMSO/water mixture refers
to the following paper. Catalan, J.; Diaz, C.; Garcia-Blanco, F. J. Org. Chem.
2001, 66, 5846-5852.
(13) Hydrodynamic radius (RH) was estimated by the following equa-
tion: RH ) kBT/6πηD where η is the viscosity coefficient and kB is the
Boltzmann constant.
(7) The 1H NMR spectrum of (TNA-HUHU-CiNH-R-CD)2 in D2O was
not measured because the solubility of (TNA-HUHU-CiNH-R-CD)2 in D2O
is very low.
(8) (a) Kodaka, M.; Fukaya, T. Bull. Chem. Soc. Jpn. 1989, 62, 1154-
1157. (b) Kodaka, M. J. Am. Chem. Soc. 1993, 115, 3702-3705.
(9) Bender, M. L.; Komiyama, M. Cyclodextrin Chemistry; Springer-
Verlag: Berlin, 1978.
(10) Szejtli, J. Cyclodextrins and their Inclusion Complexes; Akade¨miai
Kiado¨: Budapest, 1982.
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