Jpn. J. Appl. Phys. Vol. 40 (2001) pp. 4419–4422
Part 1, No. 6B, June 2001c2001
The Japan Society of Applied Physics

Interactive Force between Cyclodextrin Inclusion Complexes
Studied by Atomic Force Microscopy
Shigeo OYAMA1 , Koji M IYAKE1, ∗ , Satoshi YASUDA1 , Osamu TAKEUCHI1 , Jun S UMAOKA2 ,Makoto KOMIYAMA2 , Don Norimi F UTABA1,3 , Ryuji M ORITA3 , Mikio YAMASHITA3 and Hidemi S HIGEKAWA1, †1 Institute of Applied Physics, CREST, Japan Science and Technology Corporation (JST), University of Tsukuba, Tsukuba 305-8573, Japan
2 Research Center for Advanced Science and Technology, University of Tokyo, Komaba, Tokyo 153-8904, Japan
3 Department of Applied Physics, CREST, Japan Science and Technology Corporation (JST), Hokkaido University, Sapporo 060-8628, Japan(Received March 13, 2001; accepted for publication April 5, 2001)

Change in the intermolecular interaction between cyclodextrins (CyDs) with guest materials was observed by measuring theadhesion force using atomic force microscopy (AFM) in air. The observed adhesion force with water as the guest material
is weaker for α-CyD (composed of 6 glucose) than β-CyD (7 glucose), contrary to the fact that α-CyD is more hydrophilicthan β-CyD, indicating that the intrinsic interaction of molecules could be obtained separately from the meniscus force evenin air. In addition, the adhesion force depends on the type of guest molecules (H2 O, para-nitrophenol, and triethylendiamine)for α-CyDs, but not for β-CyDs. The observed change was explained well by the change in the dipole moment induced by thestructural deformation due to the guest materials.
KEYWORDS: intermolecular interaction, cyclodextrin, atomic force microscopy, adhesion force, inclusion complexes(a)1. Introduction
Cyclodextrins (CyDs), which are doughnut-shaped
oligosaccharides (Fig. 1), have been attracting considerable
attention because of their significant potential for applications
using their ability to form host-guest compounds. In addition to the well-known development in applications such as
molecular delivery,1) molecular shuttle,2, 3) and indicators for
detecting organic compounds,4) recent success in the formation of film structures of CyD molecules opened up the opportunity for further development of molecular recognition
devices such as ion channels and so on.5, 6) CyD molecules
consist of glucose units linked in a cyclic form. When thenumber of linked glucose units is 6 or 7, they are called αand β-CyD, respectively. Characteristic properties of CyDs
change with their size depending on the number of linked glucose units. For example, the diameters of the cavity are 0.45and 0.7 nm for α- and β-CyDs. Their molecular inclusion selectivity strongly depends on their size.
Recently, structural analysis of self-assembled CyD films
two-dimensionally grown on a highly oriented pyrolyticgraphite (HOPG) surface was performed on an atomic scaleusing scanning tunneling microscopy (STM).7–9) According
to the results, the observed molecular structures strongly depend on the type of inclusion compounds present. For example, STM images of the α- and β-CyDs with H2 O molecules
show similar channel-like structures with two-fold symmetry, but β-CyD is more densely packed than α-CyD. Whenpara-nitrophenol was chosen as the guest material, α-CyD
showed a three-fold symmetric arrangement. Since moleculararrangement depends on the interaction between molecules,
the obtained results indicate a clear change in the interaction
between CyD molecules depending on the kind of inclusion
complexes. In order to deduce and make further use of the potential of this material, analysis of the molecular interaction

H O

H OOOOOO HOO H O H O H

(b)

OO HO
NHOO
para-nitrophenol (p-NP)

N(c)

CCN
triethylendiamine (DABCO)
Fig. 1. Schematics of (a) cyclodextrin, (b) para-nitrophenol, and (c) triethylendiamine molecules.

on an atomic scale is very important and urgently needed.
In consideration of this requirement and the experimental
results regarding CyD molecules mentioned above, we attempted to estimate the intermolecular interaction between
CyD inclusion complexes using atomic force microscopy(AFM) on the self-assembled CyDs. AFM is well known asa promising technique for the measurement of the interaction
between two materials on an atomic scale.10) We succeededin observing the differences in the molecular interaction depending on the type of inclusion complexes.

∗ Present address: Tribology group, Institute of Mechanical Systems Engi-neering, National Institute of Advanced Industrial Science and Technology(AIST), 1-2-1 Namiki, Tsukuba, Ibaraki 305-8564, Japan.
† Corresponding author, E-mail address: hidemi@ims.tsukuba.ac.jp
http://dora.ims.tsukuba.ac.jp4419

Jpn. J. Appl. Phys. Vol. 40 (2001) Pt. 1, No. 6B

3. Results and Discussion
In order to measure the interaction between CyDs, theinteraction between the AFM tip and the CyDs must bestronger. The Si3 N4 tip surface is covered with an oxide film.
CyD molecules have many hydroxyl groups on both sides ofthe cavity, which are called primary and secondary hydroxyl
groups, as shown in Fig. 1(a). Therefore, hydrogen bond interaction is expected to exist between hydroxyl groups of thetip oxide and those of CyD molecules. When CyD molecules
are adsorbed on the tip during the force curve measurementson the CyD film, the adhesion force between the tip and theclean HOPG is supposed to change before and after the force
curve measurements on the CyD thin film. Figure 2 shows theforce distributions measured on freshly cleaved HOPG surface (a) before and (b) after force curve measurements on aCyD thin film surface. After force curve measurements on
the CyD thin film surface, the average value of the adhesion
force was 3.4 nN, larger compared to that before the measurements, 2.9 nN, as expected.
Then, in order to consider the effect of the meniscus force
first, we compared the adhesion force between α- and βCyD in the case of the guest molecule of water. Since CyD
molecules are solable in water, measurements were carriedout in air. However, when the adhesion force is measured inair, the influence of the meniscus force caused by the waterlayer adsorbed on the sample surface is critical for the analysis of the intrinsic interaction between CyD molecules. If
the meniscus force is dominant in the measurement, the hydrophilicity of samples is reflected in the adhesion force. Figure 3 shows the force distributions obtained for (a) α- and (b)β-CyDs. The average values of the adhesion forces between
α- and β-CyDs were about 6.1 nN and 7.2 nN, respectively.
It is well known that the solubility in water (g/100 ml) of(a) Clean tipFrequency1501005000510Force (nN)

1510Force (nN)

15(b) Tip with CyDs
120100806040200Frequency

Self-assembled films of CyD molecules were prepared bydropping the aqueous solution of α- or β-CyDs with guest
molecules onto a freshly cleaved HOPG substrate.9) The concentration of the solution was 1 mM. Three types of moleculesof different sizes were used as guest molecules; water (H2 O),
para-nitrophenol ( p-NP), and triethylendiamine (DABCO).
When no additional molecule exists in the solution, water
is included in CyDs. The schematic structures of p-NP andDABCO molecules are shown in Figs. 1(b) and 1(c), respectively. β-CyD includes all guest molecules, but α-CyD does
not in the case of DABCO, because the size of the DABCO
molecule is larger than that of the α-CyD cavity.
We focused on the change in the magnitude of adhesion
force depending on the guest molecules. The force curveon the freshly cleaved HOPG surface was used as a reference. After all force curve measurements on the CyD thinfilm surfaces, we measured the force curves on the freshly
cleaved HOPG surface again in order to check the tip condition. All experiments were performed in air at room temperature. V-shaped silicon nitride (Si3 N4 ) cantilevers (OlympusCo., Japan) with a leg length of 200 µm and leg width of 20µm were used in this study. The spring constants of each cantilever were about 0.08 N/m. The force curves were measured
within the range from 500 nm to −100 nm of tip-sample distance.

α- and β-CyD molecules is 14.5 and 1.85, respectively, i.e.,
α-CyD is more hydrophilic than β-CyD. Therefore, more water is adsorbed on the α-CyDs compared to the β-CyDs. Thevalue of the adhesion force is expected to be larger for α-CyD
than β-CyD. However, the measured values of the adhesion

05Fig. 2. Force distributions measured on fleshly cleaved HOPG surface (a)before and (b) after force curve measurements on a CyD thin film surface.

(a) -CyD
100
Frequency

2. Experiments

S. OYAMA et al.

80
60
40
2000510Force (nN)15510Force (nN)

15(b) -CyD
80
Frequency

442060402000Fig. 3. Force distributions measured on (a) α-CyD and (b) β-CyD
self-assembled film surface.

Jpn. J. Appl. Phys. Vol. 40 (2001) Pt. 1, No. 6B

S. OYAMA et al.

force for α- and β-CyDs showed opposite results to those described above. Namely, besides the effect of the meniscus
force, the intrinsic adhesion forces between CyDs could beobserved. In fact, as mentioned above, according to the STM
images, β-CyDs are more densely packed than α-CyD,7) indicating that the interaction between β-CyDs is stronger thanthat of α-CyDs.
Next, in order to analyze the interaction between CyDs
more in detail, we analyzed the influence of guest molecules.
Figures 4 and 5 show the force distributions of α- and βCyDs with guest molecules of (a) p-NP and (b) DABCO, respectively. Schematics of the molecular structures used arealso shown in Figs. 4 and 5. The obtained values are summarized in Table I. In the case of α-CyD, the average valueof the adhesion force increased with p-NP (∼ 7.2 nN), whilethat with DABCO decreased (∼ 5.8 nN) compared to the casewith H2 O (∼ 6.1 nN). (In the case of DABCO, there was another small peak at ∼ 12.3 nN. Since the adhesion force of thepure DABCO was greater than that of α-CyDs, the small peak
was considered to be influenced by pure DABCO such as byits clusters.) Namely, the adhesion forces changed drasticallydepending on the guest molecules. On the other hand, in thecase of β-CyD, the average value of the adhesion force did

Table I. Average values of the adhesion force obtained for the inclusion
complexes (nN).
Guest
H2 O
6.1
7.2

α-CyDβ-CyD

p-NP
7.3
7.3

DABCO—
7.4(a) β-CyD with p-NP
OHNOONO

6040O

2000510Force (nN)

10Force (nN)

1008060NCC
N

20515(b) β-CyD with DABCO

10040015(b) α-CyD with DABCOFrequency

OH120
10080

Frequency

Frequency(a) α-CyD with p-NP
120
10080
60
40200

not change as much (∼ 7.2 nN for H2 O, ∼ 7.3 nN for p-NP,
and ∼ 7.4 nN for DABCO).
In order to understand the effect of the guest molecules on
the CyDs, characteristic structures of the α- and β-CyDs are
summarized first. As is well known, CyD molecules have intramolecular hydrogen bonds between O-2 hydroxyl groups
of a glucose molecule and O-3 hydroxyl groups of the adjacent glucose molecule.11) In the case of β-CyD, the distance
between O-2 and O-3 on the adjacent two glucose molecules
is short enough to form a hydrogen bond, and a rigid roundstructure is maintained without distortion. However, in thecase of α-CyD, the CyD ring is distorted from the regularpolygonal symmetry to form the hydrogen bond because theoriginal distance between O-2 and O-3 on the adjacent two
glucose molecules is too great. As a result of the distortion,
two intramolecular hydrogen bonds in α-CyD are disrupted
because of the inclination of the related glucose units.
When α-CyD includes p-NP, the distortion of the CyD
structure is eliminated and the structure becomes more symmetric. According to the recent results of theoretical calculation, CyD molecules have a large dipole moment.9, 12)
Also, an electrostatic potential gradient is present in the cavity of α-CyD molecules.13) Therefore, electrostatic interaction exists between α-CyD molecules and guest molecules
when they form the inclusion complexes. In addition, when
they include large guest molecules such as p-NP, the guest
molecules change the inclination of the glucose units and theCyDs take the symmetric macrocyclic structure. The theoretical calculation shows that the direction and magnitude of thedipole moment of α-CyD molecules is changed by the guest
inclusion.9, 12) This change must influence the intermolecularFrequency

Host4421

NCCN80604020000510Force (nN)

15Fig. 4. Force distributions measured on self-assembled film surfaces of αCyDs with guest molecules ((a) p-NP and (b) DABCO). Insets are theschematics of each inclusion complex.

0510Force (nN)

15Fig. 5. Force distributions measured on self-assembled film surfaces of βCyDs with guest molecules ((a) p-NP and (b) DABCO). Insets are theschematics of each inclusion complex.

4422

Jpn. J. Appl. Phys. Vol. 40 (2001) Pt. 1, No. 6B

interaction of the CyDs.
On the other hand, the structure of β-CyD is symmetricand very rigid from the beginning, and inclusion of p-NP andDABCO does not have a significant influence on the structure.
β-CyD molecules have a large dipole moment, however, little
electrostatic potential gradient is present in the cavity of theβ-CyD molecules.12) Therefore, β-CyDs interact less electrostatically with guest molecules even if they form inclusion
complexes. Accordingly, it is considered that the change inthe dipole moment induced by guest inclusion, which is observed for α-CyD, does not occur in the case of β-CyD. On
the basis of the above discussion, the change in the dipole moment induced by the structural change of host CyD molecules
is considered to be the major factor in the observed difference
between the observed adhesion forces. This is in good agreement with the STM results which show that the structural arrangement of the CyD inclusion complexes can be explainedon the basis of the change in the dipole moment induced bythe guest molecules.
When DABCO molecules were mixed with α-CyD
molecules, they did not form inclusion complexes becauseof the steric hindrance between the size of the cavity of αCyD and DABCO molecules. Therefore, DABCO molecules
are considered to prevent the interaction between α-CyD
molecules, and the adhesion force of the mixture of α-CyDand DABCO molecules was reduced compared to the complexes of α-CyD with H2 O and p-NP molecules.
4. Conclusions
Change in the intermolecular interaction between CyDs
with guest materials was observed by measuring the adhesion
force using AFM in air. The observed adhesion force withwater as the guest material is weaker for α-CyD than for βCyD, contrary to the fact that α-CyD is more hydrophilic thanβ-CyD, indicating that the intrinsic interaction of molecules

S. OYAMA et al.

could be obtained separately from the meniscus force evenin air. In addition, the adhesion force depends on the typeof guest molecules (H2 O, para-nitrophenol, and triethylendiamine) for α-CyDs, but not for β-CyDs. The observed change
was explained well by the change in the dipole moment induced by the structural deformation due to the guest materials.
Acknowledgement
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.

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