Published on Web 04/02/2003

Formation Process of Cyclodextrin Necklace-Analysis of
Hydrogen Bonding on a Molecular Level
Koji Miyake,*,†,| Satoshi Yasuda,† Akira Harada,‡ Jun Sumaoka,§
Makoto Komiyama,§ and Hidemi Shigekawa*,†
Contribution from the Institute of Applied Physics, 21st Century COE,
UniVersity of Tsukuba, Tsukuba 305-8573, Japan, the Department of Chemistry,
Graduate School of Science, Osaka UniVersity, Toyonaka, Osaka 560-0043, Japan, andthe Research Center for AdVanced Science and Technology, The UniVersity of Tokyo,
Komaba, Tokyo 153-8904, Japan
Received March 18, 2002; E-mail: koji-miyake@aist.go.jp, hidemi@ims.tsukuba.ac.jp

Abstract: By means of scanning tunneling microscopy (STM), we succeeded for the first time in thequantitative analysis of the intramolecular conformation of a supramolecule, cyclodextrin (CyD) necklace,driven by hydrogen bonding. Contrary to the current model, based on macroscopic analyses, which indicatesthat all CyDs are arranged in head-to-head or tail-to-tail (secondary-secondary or primary-primary hydrogenbonding) conformation, about 20% head-to-tail (primary-secondary hydrogen bonding) conformation was
found to exist in the molecule. In addition, comparing the STM results with the theoretical model of thenecklace formation, the formation ratio of the tail-to-tail and head-to-tail conformations due to the strength
difference between primary-primary and primary-secondary hydrogen bonds of CyDs was directly obtained,
for the first time, to be 2:1.

1. Introduction

Understanding and optimizing the high potential of supramolecules is one of the most intriguing objectives in current
nanoscience and technology1 since supramolecules are one ofthe promising candidates for future molecular devices. For thefurther development of supramolecular materials, it is extremely
important to determine their intramolecular conformations andstructures and the relationship between their conformations andfunctions. In addition, because noncovalent bonding between
component molecules strongly affects the conformational
preferences and functions of a supramolecule, such as molecular
recognition, catalysis, and reactivity, an understanding of theintermolecular interaction between molecules is also important.
In particular, hydrogen bonding has been attracting considerable
attention because of its high selectivity and directionality.
Cyclodextrin(CyD) necklace (molecular necklace) has apolyrotaxane structure; R-cyclodextrins (R-CyDs) consisting ofsix glucose units are threaded on a poly(ethylene glycol) (PEG)
chain (Figure 1a,b). This material has been attracting considerable attention because of its high potential for use in future
molecular devices, such as molecular shuttles, molecularmemory, and molecular machines.2,3
The inclusion of a polymer chain into the cyclodextrin cavity† University of Tsukuba, 21st Century COE. http://dora.ims.tsukuba.ac.jp.
‡ Osaka University.
§ The University of Tokyo.
| Present address: Institute of Mechanical Systems Engineering (IMSE),
National Institute of Advanced Industrial Science and Technology (AIST),
1-2-1 Namiki, Tsukuba, Ibaraki 305-8564, Japan.

(1) Lehn, J.-M. Supramolecular Chemistry; VCH: Weinheim, 1995.
5080 9 J. AM. CHEM. SOC. 2003, 125, 5080-5085

Figure 1. Schematic structures of (a) cyclodextrin, (b) molecular necklace
and molecular tube, and molecular conformations of (c) head-to-head, (d)tail-to-tail, and (d) head-to-tail structures.

is entropically unfavorable and is known to be promoted by
the attractive interactions between the chain and the cyclodextrins such as van der Waals and hydrophobic interactions. The
importance of these interactions has been clarified by previous
studies.4,5 According to the recent theoretical study,6 theinclusion behavior becomes cooperative and CyD molecules(2) For cyclodextrin based rotaxanes: (a) Harada, A. Acc. Chem. Res. 2001,
34, 456-464. (b) Shigekawa, H.; Miyake, K.; Sumaoka, J.; Harada, A.;
Komiyama, M. J. Am. Chem. Soc. 2000, 122, 5411-5412. (c) Nepogodiev,
A. N.; Stoddart, J. F. Chem. ReV. 1998, 98, 1959-1976.
10.1021/ja026224u CCC: $25.00 © 2003 American Chemical SocietyFormation Process of Cyclodextrin Necklace

sharply include the polymer chain with increase of the attractive
interaction between adjacent CyDs. Therefore, in addition to
the interaction between CyDs and PEG, interaction between
adjacent cyclodextrins, hydrogen-bonding, on the polymer chain
plays an essential role in the inclusion behavior.
To educe and develop the high potential of the structure ofpolyrotaxanes, it is important to determine the conformation of
the elemental molecules threaded on the molecular chains. In
addition, since the conformation of the R-CyDs in a molecularnecklace directly reflects the formation process, analysis of the
R-CyDs conformation is important to understanding the molecular interaction from both fundamental and practical pointsof view.
Even when the chain PEG molecule is modified with small
end groups such as methyl, dimethyl, and amino groups, theyalso form complexes and their yields are somewhat higher thanthat of unmodified PEG.7 This indicates that the interaction
between OH groups of PEG and R-CyD is not the dominant
driving force for complex formation, and formation of thecomplex is driven by the hydrogen bonding between two
R-CyDs. Namely, the hydrogen-bonding interaction plays animportant role in the threading of another cyclodextrins. As aresult, the hydrogen-bonding interaction between two R-CyDs
is considered to determine the conformation of the R-CyDs in
a molecular necklace. Therefore, in this paper, we focused on
how the hydrogen-bonding interaction determines the conformation of the R-CyDs in a molecular necklace.
R-CyDs are thought to be threaded one by one from the edgeof the PEG chain. Since an R-CyD has two different hydroxyl
groups on the two ends of its cavity, a primary and a secondaryhydroxyl group (Figure 1a), R-CyDs can have three conformations, namely, head-to-head (secondary-to-secondary; Figure 1c),tail-to-tail (primary-to-primary; Figure 1d) and head-to-tail(secondary-to-primary; Figure 1e).
The structure of the molecular necklace was characterized
by nuclear magnetic resonance (NMR), ultraviolet spectroscopy,
and X-ray diffraction,8 and 100% head-to-head and tail-to-tailstructure is concluded. However, the arrangement of R-CyD in
the necklace is still unclear because these methods only give
macroscopic and averaged information about the conformationsof these supramolecules.
Scanning probe microscopy (SPM) is a leading technique forthe analyses mentioned above because of its high potential andhas been applied to the structural analysis of various molecules.9,10 In fact, some molecular conformations such as
chirality have been directly identified.11,12,13 However, thesewere identifications of single molecules, and the determinationof the intramolecular conformation of supramolecules has not
yet been realized, despite its great importance.
Here, we present for the first time, by using STM, thequantitative analysis of the intramolecular conformation of a(3) For other rotaxanes: (a) Pease, A. R.; Jeppesen, J. O.; Stoddart, J. F.; Luo,Y.; Collier, C. K.; Heath, J. R. Acc. Chem. Res. 2001, 34, 433-444. (b)Ballardini, R.; Balzani, V.; Credi, A.; Gandolfi, M. T.; Venturi, M. Acc.
Chem. Res. 2001, 34, 445-455. (c) Schalley, C. A.; Beizai, K.; Vögtle, F.
Acc. Chem. Res. 2001, 34, 465-476. (d) Collin, J.-P.; Dietrich-Buchecker,
C.; Gaviña, P.; Jimenez-Malero, M. C.; Sauvage, J.-P. Acc. Chem. Res.
2001, 34, 477-487.
(4) Ceccato, M.; Nostro, P. L.; Baglioni, P. Langmuir 1997, 13, 2436-2439.
(5) Pozuelo, J.; Mendicuti, F.; Mattice, W. L. Macromolecules 1997, 30, 36853690.

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Figure 2. STM images of R-CyDs on (a) highly oriented pyrolytic graphite(HOPG) (sample bias, Vs ) -30 mV; tunneling current, It ) 0.6 nA, 15
nm × 15 nm) and (b) molybdenum disulfide (MoS2) substrates (Vs ) -200
mV, It ) 1.0 nA, 15 nm × 15 nm). (c) and (d) show the schematics of thelattice matching of R-CyD with HOPG and MoS2, respectively.

supramolecule, CyD necklace,14 driven by the hydrogen bonding
between component CyDs.
2. Analysis Model: Lattice Matching Model

If the structures of supramolecules could be visualizde in real
space, we could directly analyze the structures of supramolecules, such as conformation and stoichiometry. However, it isdifficult to determine which side of the STM image corresponds
to the head or tail of the molecule.
In our previous work, we developed an analysis method bywhich the conformational structure of the molecular necklace
can be determined directly on a molecular level.15 An overview
of the method is given below.
2.1. Cyclodextrins on HOPG and MoS2. Figure 2 shows
typical STM images of R-CyDs on (a) HOPG and (b) MoS2
substrates. Since the surfaces of these substrates are hydrophobic, it is natural for R-CyDs to be lying with their apolar outside
wall on the apolar substrates. This lying conformation is morefavorable than the sitting conformation where the R-CyDs(6) Okumura, Y.; Ito, K.; Hayakawa. R. Polym. AdV. Technol. 2000, 11, 815819.
(7) Harada, A.; Li, J.; Kamachi, M. Macromolecules 1993, 26, 5698-5703.
(8) Harada, A.; Li, J.; Kamachi, M. J. Am. Chem. Soc. 1994, 116, 31923196.
(9) Wiesendanger, R. Scanning Probe Microscopy and Spectroscopy: Method
and Application; Cambridge University Press: New York, 1994.
(10) Bai, C. Scanning Tunneling Microscopy and its Application; Springer
Publishing: New York, 1995.
(11) Lopinski, G. P.; Moffatt, D. J.; Wayner, D. D. M.; Wolkow, R. A. Nature(London) 1998, 392, 909-911.
(12) Fang, H.; Giancarlo, L. C.; Flynn, G. W. J. Phys. Chem. B 1998, 102,
7311-7315.
(13) Jung, T. A.; Schlitter, R. R.; Gimzewski, J. K. Nature (London) 1997, 386,696-702.
(14) Harada, A.; Li, J.; Kamachi, M. Nature (London) 1992, 356, 325-326.
(15) Miyake, K.; Aiso, Y.; Komiyama, M.; Harada, A.; Kamachi, M.; Shigekawa,
H. Jpn. J. Appl. Phys. 1994, 33, 3720-3722.
(16) Shigekawa, H.; Morizumi, T.; Komiyama, M.; Yoshimura, M.; Kawazu,
A.; Saito, Y. J. Vac. Sci. Technol. B 1991, 9, 1189-1192.
(17) Yasuda, S.; Miyake, K.; Goto, Y.; Ishida, M.; Hata, K.; Fujita, M.; Yoshida,M.; Sumaoka, J.; Komiyama, M.; Shigekawa, H. Jpn. J. Appl. Phys. 1998,
37, 3844-3848.
(18) Yasuda, S.; Miyake, K.; Sumaoka, J.; Komiyama, M.; Shigekawa, H. Jpn.
J. Appl. Phys. 1999, 38, 3888-3891.
J. AM. CHEM. SOC. 9 VOL. 125, NO. 17, 2003 5081

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Miyake et al.

R-CyD has an anisotropic shape and the positions of S atoms
on the MoS2 surface are shifted by a/2 along the [110] direction.
Therefore, L and L′ depend on the relative conformations of
the two adjacent R-CyDs. For example, when two R-CyD
molecules are closely located along the [11h0] direction of MoS2
without shifting in the [110] direction (m ) 0), the lattice
matching conditions of the head-to-tail and head-to-head (tailto-tail) arrangement are maintained for l ) even (Figure 3b)
and l ) odd (Figure 3c), respectively.
In consideration of this lattice matching, the relative conformation of the two adjacent R-CyDs can be determined bymeasuring L and L′ between two adjacent R-CyDs in STM
images, namely, the arrangement of two adjacent R-CyDs ishead-to-head (or tail-to-tail) and head-to-tail for (l + m) being
even and odd, respectively.
3. Experimental: STM Imaging of the Cyclodextrin
Necklace

Figure 3. (a) CyDs with head-to-head (tail-to-tail) and head-to-tailconformations on a MoS2 surface. (b) Lattice matching between an R-CyD
and S atoms on a MoS2 substrate.

hydroxyl residues are contacting the apolar substrates. In thecase of HOPG substrate, the interaction between CyDs andsubstrate is weak. Therefore, self-assembled R-CyD layers(Figure 2a) in the two-dimensional growth mode are formedby the interaction between adsorbed CyDs when the CyDs are
sufficiently dense to form the monolayer.16-18 However, it isdifficult to stabilize individual CyD molecules given the low
concentration of the solution. On the other hand, individual
R-CyDs can be observed on the MoS2 substrate stably as shownin Figure 2b, even when the concentration of R-CyD in thesolution was diluted. Therefore, MoS2 is appropriate for theobservation of the individual R-CyD molecules.
This difference in interaction comes from the difference inlattice matching between an R-CyD molecule and the substrate.
Parts c and d of Figure 2 show the schematics of R-CyD on
HOPG and MoS2, respectively. On HOPG substrate, there exist
many equivalent physisorption sites for R-CyD. Therefore,
R-CyD molecules can easily move to the neighboring stablesites on HOPG substrate. This, however, makes it difficult toobserve the individual R-CyDs on HOPG substrate. On the other
hand, the arrangement of sulfur atoms of the MoS2 surface iscommensurate with the contour of R-CyD molecules.
The commensurability between R-CyD and HOPG and MoS2
is used to determine the relative orientation of adjacent R-CyDs
in the molecular necklace as described below.
2.2. Lattice Matching Model for the Analysis of theRelative Conformation of r-CyD on MoS2. By use of thelattice constants of S atoms on the MoS2 surface (d and a shownin Figure 3a), the interstice L between two adjacent R-CyDs in
the [110] direction and the shift of the axis L′ between two
adjacent R-CyDs along the [11h0] direction of MoS2 can be
described as

L)ld

(1)

L′ ) m(a/2)(2)

where d ) ∼0.27 nm, a ) ∼0.32 nm, and l and m are integers.
5082 J. AM. CHEM. SOC. 9 VOL. 125, NO. 17, 2003

3.1. Sample Preparation for STM Observation. For the analysisof the conformation of the CyD necklace, STM imaging of a single
molecular necklace on MoS2 substrate was performed. CyD necklace
molecules are insoluble in water but are soluble in 0.1 M NaOH.
Therefore, these molecules were dissolved in 0.1 M NaOH, and theaqueous solution was added dropwise onto fleshly cleaved MoS2
substrates. The samples were dried in air at room temperature, andthen STM was performed in air at room temperature. The concentrationof CyD necklace was sufficiently diluted to enable observation of an
isolated chain of R-CyDs.
To confirm that the obtained STM images correspond with themolecular necklaces we used, two kinds of molecular necklaces, whichhave different molecular weights (MWs) of the polymer chain, wereused in this experiment. One is prepared from PEG of MW ) 3350,
which has about 22 R-CyDs on a PEG chain (MN-3350). This
corresponds to a molar ratio of 3.9, that is, more than half of the polymer
chain is covered with R-CyDs. The other has about 15 R-CyDs on a
PEG chain that is prepared from PEG of MW ) 1450 (MN-1450).
The molar ratio of ethylene glycol units to R-CyDs is 2.3. This indicatesthat the complex is almost stoichiometric, i.e., the CyDs are packed
from end to end of a polymer chain. The number of R-CyDs in themolecular necklace and the molar ratio of ethylene glycol units to
R-CyDs were estimated from the results of NMR measurement.19
3.2. STM Images of Cyclodextrin Necklace. Figure 4 shows the
STM images of the molecular necklaces, in which the molar ratios of
ethylene glycol units to R-CyDs are (a) 3.9 (MN-3350) and (b) 2.3(MN-1450), respectively. The molar ratio of PEG to R-CyDs wasdetermined by the 1H NMR.19 In both cases, an MoS2 substrate wasused. The molecular necklaces were stably observed during STM scan.
Regularly aligned R-CyDs were clearly observed as shown in Figure
4. In the case of MN-3350, R-CyDs were observed separately in theirlinear forms and an interstice between two adjacent R-CyDs on the
PEG chain was observed, as shown in Figure 4a. On the other hand,closely packed R-CyD molecules were observed in the case of MN1450, as shown in Figure 4b. The observed structures were in good
agreement with the molecular structures previously proposed, in which
R-CyDs were threaded on a PEG chain. In addition, the molar ratios
of MN-3350 and MN-1450 estimated from STM images were about 4
and 2, which also agree well with the results of NMR measurement.19

4. Determination of the Relative Orientation of Adjacentr-CyDs

4.1. Measurement Procedure. The structure and molar ratioof the CyD necklace were visualized in real space at the(19) Harada, A.; Li, J.; Nakamitsu, T.; Kamachi, M. J. Org. Chem. 1993, 58,7524-7528.

Formation Process of Cyclodextrin Necklace

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Figure 6. STM image (Vs ) -200 mV, It ) 1.0 nA) of a molecularnecklace (a) and its magnification of the squared part in (a) with the contrast
focused on the MoS2 lattice (b) (Vs ) -130 mV, It ) 1.0 nA).

Figure 4. STM images of molecular necklaces, where the molar ratio of
ethylene glycol units to R-CyDs is (a) 3.9 (MN-3350) (Vs ) -250 mV, It) 2.0 nA) and (b) 2.3 (MN-1450) (Vs ) 200 mV, It ) 0.9 nA), respectively.

Figure 5. Determination procedure of the relative orientation of adjacent
R-CyDs.

molecular level by using STM. However, as mentioned in
section 3, since the primary and secondary hydroxyl groups
cannot be discriminated in the STM image, it is difficult todetermine the conformation of adjacent CyDs in the molecularnecklace. The conformations are determined by using the lattice
matching model.
We determined the relative orientations of adjacent R-CyDs
from STM images by the following procedures (Figure 5).
1. Highest positions of the two R-CyD molecules were
determined as the reference points ((1) and (1′)).
2. Four straight lines passing through the two reference pointsof the molecules were drawn along the [110] and [11h0] direction(four red dotted lines). And the two intersections were marked((2) and (2′)).
3. The values L′ can be determined by measuring the distance,(1)-(2) or (1′)-(2′).
4. On the other hand, in the case of L, the rim-to-rim distanceis necessary. Therefore, the size of a R-CyD molecule ()0.70nm) was subtracted from the measured distance of (1)-(2′) or(1′)-(2).
5. From eqs 1 and 2, the integers l and m were obtained by
dividing L and L′ by d ()0.27 nm) and a/2 ()0.16 nm),respectively.
6. Then, when (l + m) became odd (even), the arrangementof the two adjacent R-CyDs was determined as head-to-heador tail-to-tail (head-to-tail).
4.2. Example of Conformational Analysis and Statistics.
Figure 6a is a STM image of a molecular necklace. A
magnification of the square part in Figure 6a is shown in Figure
6b with the contrast focused on the MoS2 lattice. Following
the procedure described in 4.1, the values L and L′ were
measured as 2.20 and 2.75 nm, respectively. And l and m were
determined as 8 (L/d ) 2.20/0.27 ∼ 8.15) and 17 (L′/(a/2) )2.75/(0.32/2) ∼ 17.19), respectively. Therefore, (l + m) is 25,
namely, odd, in this case, and indicates that the conformationof the two adjacent R-CyD molecules is head-to-tailThis result also indicates that there must exist eight sulfur
rows along the [110] direction between adjacent CyD molecules.
Here, since contrast is focused on the MoS2 lattice, the existenceof the eight sulfur rows can actually be observed between CyD
molecules.
We measured L and L′ for about 100 CyD molecular pairs,
and the results are summarized in Figure 7a. The head-to-headand head-to-tail conformations are represented by [ and 9,
respectively. Figure 7b and c show the histograms of theJ. AM. CHEM. SOC. 9 VOL. 125, NO. 17, 2003 5083

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Miyake et al.

Figure 7. (a) Experimentally obtained values of L′ and L′. (b) (c) Histograms of the difference between the measured values of L or L′ and the ideal integer
multiples of the elementary lattice constants of the axes, respectively.

Figure 8. Number of head-to-head (or tail-to-tail) and head-to-tailconformations determined from STM measurements.

difference between the measured values of L or L′ and the ideal
integer multiples of the elementary lattice constants of the axes,
respectively. As shown in the figures, δL and δL′ are within
0.05 nm, resulting in the differences from the integers as δl <∼0.2 and δm < ∼0.3, respectively. These values are sufficient
to determine the relative orientations by using our model.
4.3. Results of the Relative Orientation of Adjacentr-CyDs. Figure 8 summarizes the numbers of head-to-head (ortail-to-tail) and head-to-tail conformations determined from STM
measurements. As shown in Figure 8, about 80% of theconformation is head-to-head or tail-to-tail, contrary to the model
proposed on the basis of the macroscopic analyses. Namely,
20% head-to-tail conformations were found microscopically, forthe first time, to exist.
5. Analysis of Formation Process

5.1. Formation Process and Observed Structures. Now let
us examine the inclusion process in detail. From comparison
5084 J. AM. CHEM. SOC. 9 VOL. 125, NO. 17, 2003

between a theoretical model with the result shown in Figure 8,
the formation ratio of the tail-to-tail and head-to-tail conformations is analyzed. CyDs are included from the left side here,
following the schematic model shown in Figure 9. If thesecondary-secondary interaction is sufficiently strong comparedto the secondary-primary interaction, only the secondarysecondary (head-to-head) conformation is realized when the left
end of the threaded CyDs is the secondary side (Figure 9a).
Therefore, the primary-secondary (head-to-tail) conformation
is introduced only when the left end of the threaded CyDs is
the primary side (Figure 9c). In this case, the primary-secondary(head-to-tail) conformation has a single orientation; the primaryhydroxyl of the head-to-tail unit (tail side) is oriented toward
the left side, as indicated by solid triangles in Figure 9d. In
fact, the experimentally observed head-to-tail CyD units are in
the expected single orientation extending over ∼10 CyDs fromeach end (approximately the center from either edge of amolecular necklace).
5.2. Model for the Analysis. To reproduce the experimental
results in Figure 8 by calculation, we adopt the following
conditions. When the end of the threaded CyD molecules is
the secondary side, it forms a hydrogen bond with the following
CyD by secondary-secondary (head-to-head) conformation(Figure 9a). On the other hand, when the last end is the primaryside, both tail-to-tail and head-to-tail conformations are realized.
Because CyDs are included from the left side in this model,hydroxyl groups on the right-hand side form hydrogen bonds
with an included CyD at first. Therefore, we focused on theconformation of the right-hand side of each CyD. When theconformations of the right-hand side of CyD are head-to-head,
tail-to-tail, and head-to-tail, they are called h-h, t-t, and h-t,respectively. On the basis of this assumption, the total number
of CyD molecules in a single CyD necklace (Ntotal) can be
represented byFormation Process of Cyclodextrin Necklace

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Figure 9. Three different conformations appearing in the inclusion process of a molecular necklace formation: (a) secondary-secondary, (b) primaryprimary, and (c) secondary-primary and (d) CyD conformations in a molecular necklace.

Ntotal ) Nh-h + Nt-t + Nh-t + 1(3)

where Nh-h, Nt-t, and Nh-t are the numbers of h-h, t-t, and h-t
CyDs; i.e., they correspond to the numbers of head-to-head,
tail-to-tail, and head-to-tail conformations, respectively. Herethe term +1 corresponds to the first included CyD molecule inthe molecular necklace.
The ratio of the head-to-tail conformation r can be expressedasr ) Nh-t/(Nh-h + Nt-t + Nh-t)(4)Here, supposing that the head-to-tail conformation is introduced with a probability of 1/n, it can be written as

1/n ) Nh-t/(Nt-t + Nh-t)(5)

When Ntotal is constant, Nh-h and Nt-t have the relationshipNh-h ) Nt-t + c (c ) (1 or 0)(6)

When the left end of the CyD included first is the secondaryside as shown in Figure 10a, the value of c becomes 0 or 1 forthe orientation of the last CyD molecule to be the same as(Figure 10a) or opposite to (Figure 10b) the first one, respectively. On the other hand, when the left end of the CyD included
first is the primary side as shown in Figure 10c, the value of cbecomes 0 or -1 for the orientation of the last CyD molecule
to be the same as (Figure 10c) or opposite to (Figure 10d) the
first one, respectively.
From eqs 3, 4, 5, and 6, r is expressed as

r)

(

c
1
12n - 1
Ntotal - 1)(7)

Since CyD molecules are randomly included, the averagevalue of c becomes 0. Therefore, the average value of r becomesjr )12n - 1Figure 10. Four conformations of the CyDs in a molecular necklace andthe corresponding values of c appearing in eq 6: (a) and (c) CyD moleculeswith both ends having the same orientation (c ) 0). (b) CyD moleculeswith both ends having the tail-to-tail conformation (c ) 1). (d) CyD
molecules with both ends having the head-to-head conformation (c ) -1).

(8)

5.3. Results of Analysis. Using eq 8, jr becomes 0.20 for n) 3, which corresponds to the experimental result (∼0.2, Figure
8).

This result indicates that the primary-secondary (head-totail) hydrogen bonding is 2 times more difficult to realize thanthe primary-primary (head-to-head) configuration during theinclusion process. This is the first quantitative determinationof the hydrogen bonding between CyDs during the supramolecular formation process.
6. Conclusion

The intramolecular structure of the molecular necklace wasanalyzed on a molecular level for the first time. The role ofhydrogen bonding in the formation process was confirmed.
Contrary to the current model that is based on macroscopic
analyses, indicating that all CyDs are arranged in head-to-headand tail-to-tail conformations, about 20% head-to-tail conformation was found to exist in the molecule. From the analysis of
this result with a stochastic model, the formation ratio of thetail-to-tail and head-to-tail conformations due to the primaryprimary and primary-secondary hydrogen bonding of CyDs,
was quantitatively evaluated, for the first time, to be 2:1.
Acknowledgment. This work was supported by a Grant-inAid for Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
JA026224U

J. AM. CHEM. SOC. 9 VOL. 125, NO. 17, 2003 5085