Kinetic control of threading of cyclodextrins onto axle molecules

Article abstract of DOI:10.1021/ja053532u

We report here, for the first time, kinetic control of the face-direction of cyclodextrin (CD) in the construction of a pseudo-rotaxane with an alkyl chain bearing pyridyl end caps. The yields of complexes of CDs with guest alkyl derivatives were controlled by the simple change of the position and the number of methyl groups bound to the pyridyl moiety. Single-substituted pyridyl groups attached to the ends of the alkyl chain regulated the rate for CDs passing them. Two methyl substituents could clearly govern the degree of complex formation of CD with guest molecules and resulted in the distinction of face-direction of CD molecules entering the gates at guest ends. Copyright

Full text of DOI:10.1021/ja053532u

Published on Web 08/10/2005
Kinetic Control of Threading of Cyclodextrins onto Axle Molecules
Tomoya Oshikiri, Yoshinori Takashima, Hiroyasu Yamaguchi, and Akira Harada*
Department of Macromolecular Science, Graduate School of Science, Osaka UniVersity,
Toyonaka, Osaka 560-0043, Japan
Received May 30, 2005; E-mail: harada@chem.sci.osaka-u.ac.jp
Rotaxanes are considered to be a typical prototype of molecular
machines bearing a rotor and an axle in the molecule.1,2 Crown
ethers,3 cyclodextrins (CDs),4 calixarenes,5 and cucurbituril6 have
been used as ring components of rotaxanes. CD has a rigid, well-
defined “nonsymmetric” ring structure. Although there are a few
reports on the isolation of unidirectional pseudo-[2]rotaxane
composed CDs and axle molecules, there are no reports on the
kinetic control of the face-direction of CDs in the complex
formation step.7 We report here, for the first time, the face-direction
control of CD in the construction of a pseudo-rotaxane with an
alkyl chain bearing pyridyl end caps without any purification
procedure. The yields of complexes of CDs with guest alkyl
derivatives were controlled by the simple change of the position
and the number of methyl groups bound to the pyridyl moiety. A
single-substituted pyridyl group attached to the ends of an alkyl
chain regulated the rate for CDs passing them. Two methyl
substituents could clearly govern the degree of complex formation
of CD with guest molecules and resulted in the distinction of the
face-direction of CD molecules entering the gates at guest ends.
Chart 1 shows structures of various kinds of guest molecules
Figure 1. 1H NMR spectra of axle molecules in D2O. (A) 3a in the absence
of CDs, and (B) in the presence of R-CD after 1 day at 30 °C. (C) 3b in
the absence of CDs, (D) in the presence of R-CD after 70 days at 30 °C,
and (E) in the presence of R-CD after 2 days at 70 °C. The arrows indicate
splitting behaviors of each signal on the complexations.
Chart 1. Structures of Axle Molecules
Figure 2. The correlation between time and degree of complex formations
of R-CD with 3b at 70 °C (complex that the primary hydroxyl groups in
the R-CD face the 2-methylpyridine moiety (0) and 3,5-dimethylpyridine
moiety (]). The sum of two isomers (O)).
1c. These results show that the methyl group at the 2-position of
the pyridinium part obviously plays an important role in controlling
the rate of the complex formation. The methyl group at the
2-position of pyridinium part was found to retard the threading of
1
R-CD. The H NMR spectra of 2b and 2c showed no changes on
mixing with R-CD, indicating that axle molecules 2b and 2c cannot
form inclusion complexes with R-CD. The two methyl groups at
the 3-, 5-positions or the 2-, 6-positions of the pyridinium part
prevent R-CD from passing.
used as a dumbbell in this study. Axle molecules have decameth-
ylene units for the recognition site of CDs and pyridinyl units as
the electric and steric trap moieties. Axle molecules were prepared
by the reaction of R,ω-dihalodecane with pyridine derivatives.8
Counteranions of the pyridinium cation in these compounds were
changed to chloride to improve the solubility in water. Dicationic
symmetrical axle molecules, 1a-c and 2a-c, were mixed with 4
molar excess of R-CD in D2O. The 1H NMR spectrum of 1a in the
presence of R-CD (4 molar excess) showed the split in all peaks of
1a and no peaks of free 1a. This result indicates that 1a was
included in R-CD completely. In the case of 1b, with a methyl
group at the 3-position of a pyridinium part, the complexation mode
was similar to that of the R-CD-1a complex. This result indicates
that R-CD could pass through the end caps with methyl groups at
the 3-position of a pyridinium part. The complexation of 1c with
R-CD had the time dependency. The rate of the inclusion of 1c to
R-CD was extremely slow. The complexation between R-CD and
2a, which has methyl groups at the 2- and 5-position of the
pyridinium group, showed a similar behavior to that of R-CD with
1
In the H NMR spectrum of the nonsymmetric axle molecule
(3a), whose 2-position of one pyridyl end and 3-position of the
other end was substituted by a methyl group, both signals of
methylene groups in the vicinity of the 2-methylpyridine side and
the 3-methylpyridine side of 3a in the complex with R-CD shifted
to upfield and downfield (Figure 1B), indicating that each end group
was located in an asymmetric environment; that is, R-CD formed
1
a complex with 3a in the random direction (Figure 4A). The H
NMR spectrum of 3b in the presence of R-CD in D2O showed the
upfield split on the methylene groups in the vicinity of the
2-methylpyridine side and downfield split on the signals in the
vicinity of the 3,5-dimethylpyridine side, respectively (Figure 1D).
Even after 70 days, the complex formation of 3b with R-CD did
not reach an equilibrium state completely. R-CD was found to form
complexes with 3b only from the 2-methylpyridine side and to give
a unique supramolecular structure. The number and position of the
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C O M M U N I C A T I O N S
side of 3b only from the secondary hydroxyl group side of itself
because of comparatively slow molecular dynamics. On the other
hand, R-CD can thread from the terminal group from both hydroxyl
sides of itself because molecular dynamics and equilibrium rate
are faster at high temperature. The complexation of 3b with R-CD
was controlled kinetically at low temperature and dominated by
thermostatics at high temperature. These results mean that the rate
of complexation differs significantly between two isomers.
In conclusion, pseudo-[2]rotaxane was obtained with R-CD
located in a unique direction at a recognition site of dicationic axle
molecule 3b. The methyl group at the 2-position of a pyridinium
group on the end cap of the axle molecule was found to control
the rates of threading of R-CD. This is the first observation that
the terminal group of axle molecules controls the direction of faces
of plural ring components in the rotaxane structure kinetically. The
controlling face of the ring component is expected to be efficient
enough to realize the unidirectional movement in the rotaxane due
to its nonsymmetric structure. We are now studying the dynamics
of R-CD on the axle compounds with multi-stations in detail.
Figure 3. The 2D ROESY NMR spectrum of 3b-R-CD after 21 days in
D2O, at 30 °C.
Acknowledgment. The authors express their special thanks for
the Center of Excellence (21COE) program “Creation of Integrated
EcoChemistry” of Osaka University.
Supporting Information Available: Synthesis and characterization
of axle molecules and T1 measurement. This material is available free
of charge via the Internet at http://pubs.acs.org.
Figure 4. Proposed structures of pseudo-[2]rotaxane 3a-R-CD (A) and
3b-R-CD (B) at room temperature.
methyl groups in the end group of the axle obviously contribute to
the complexation of R-CDs with axle molecules.
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1
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