Preparation and characterization of two solid supramolecular inclusion complexes of guaiacol with ss- And γ-cyclodextrin

Article abstract of DOI:10.1246/bcsj.80.2185

Solid inclusion complexes of ss- and γ-cyclodextrin (CD) with guaiacol (Gua) were prepared and characterized using elemental analysis, matrix-assisted laser desorption ionization-time of flight mass spectrometry, powder X-ray diffraction, infrared spectro

Full text of DOI:10.1246/bcsj.80.2185

Ó 2007 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 80, No. 11, 2185–2195 (2007) 2185
Preparation and Characterization of Two Solid Supramolecular
Inclusion Complexes of Guaiacol with ꢀ- and ꢁ-Cyclodextrin
ꢀ1
Le Xin Song, Hai Ming Wang,1 Yan Yang,2 and Peng Xu1
1Department of Chemistry, University of Science and Technology of China, Hefei 230026, P. R. China
2Department of Chemical Engineering, Anhui University of Science and Technology, Huainan 232001, P. R. China
Received April 2, 2007; E-mail: solexin@ustc.edu.cn
Solid inclusion complexes of ꢀ- and ꢁ-cyclodextrin (CD) with guaiacol (Gua) were prepared and characterized
using elemental analysis, matrix-assisted laser desorption ionization-time of flight mass spectrometry, powder X-ray
diffraction, infrared spectroscopy, thermogravimetric analysis and nuclear magnetic resonance spectroscopy. Based
1
on the results of elemental analysis and H NMR, the host–guest stoichiometry of the two solid complexes was deter-
mined to be one-to-one. X-ray diffraction patterns of the inclusion complexes gave peak locations consistent with inter-
molecular complexations between CDs and Gua as well as shape and diffraction intensity of these peaks. The solubility
of ꢁ-CD was much less than that of ꢂ-CD in water through the complex formation of CD with Gua. Upon inclusion
the thermal decomposition point of ꢀ-CD or ꢁ-CD as host only slightly increased. However, the thermal stability of
the complexed Gua was obviously higher in Gua–ꢀ-CD than in Gua–ꢁ-CD. The inclusion phenomenon was attributed
to the different strength of intermolecular interactions between host and guest. According to 1H NMR titration measure-
ments, binding constants between Gua and CDs were determined. Furthermore, 1H NMR results indicated that the com-
plexed Gua was likely to have stayed in the wider rim of the cavity of ꢀ- or ꢁ-CD. PM3 calculations clearly showed that
Gua–ꢁ-CD had the most negative interaction energy, whereas Gua was near the secondary hydroxy rim of the cavity of
ꢁ-CD.
Cyclodextrins (CDs, Fig. 1) are cyclic oligosaccharides
consisting of glucose subunits connected through glycosidic
ꢂ-1,4 bond, forming a structure as a hollow truncate with
one ring wider than the other.1,2 The most common CDs are
ꢂ-, ꢀ-, and ꢁ-CD, which are composed of six, seven, and eight
glucose units, respectively. CDs and their derivatives, such as
ꢀ-cyclohepta(2,6-di-O-methyl)-dextrin (DMꢀ-CD), have been
Fig. 1. Structural features of host and guest molecules.
known to form inclusion complexes with a wide variety of
guest molecules via noncovalent bonds.3–6 Many papers have
been published concerning the formation and spectral proper-
ties of guest–CD complexes in aqueous solution using various
analytical methods.7–11
used as an expectorant but also used as a less expensive syn-
thetic flavor chemical in flavor and fragrance industries. More-
over, as one of the most simple phenol derivatives, Gua is also
an important structural unit for use in forming many specific
polysubstituted phenols, such as 4-allyl-2-methoxyphenol and
4-hydroxy-3,5-dimethoxybenzoic acid.
Careful investigations on the formation, structure, character
and stability of solid CD supramolecular complexes will not
only help us to further realize the nature of inclusion phenom-
ena, but also allow us to evaluate the potential application of
CDs in many industries.8,20 For these reasons, Gua was chosen
as a guest, and ꢀ- and ꢁ-CD were selected as hosts in this
study. Their molecular structures are shown in Fig. 1.
In the present work, we examined the preparations of solid
inclusion complexes of ꢀ-CD and ꢁ-CD as well as ꢂ-CD
and DMꢀ-CD with Gua and its derivative 4-hydroxy-3,5-
dimethoxy-benzoic acid in aqueous solution. However, only
two pure complexes, Gua–ꢀ-CD and Gua–ꢁ-CD, were ob-
tained. Under the same experimental conditions, no measur-
able precipitation was observed for the other six host–guest
inclusion systems. The two solid inclusion complexes were
characterized using elemental analysis (EA), nuclear magnetic
In aqueous solution, phenol and its analogs can be included
into the CD cavity.12,13 There have been a few structural re-
ports on the inclusion complexes of CD with substituted phe-
nols based on experimental measurements in aqueous solution
or theoretical calculations in vacuo.14–17 So far, the inclusion
complexes of CDs with many organic guests have been suc-
cessfully utilized in perfume, pharmaceutical, food supplement
industries and other fields.8,18 How to improve water solubility
and thermal stability of aromatic organic guests and to control
release of complexed guest molecules are two of the most
interesting problems concerning the application of solid CD
inclusion complexes in industry.19–21 It should be noted, how-
ever, that less attention is paid to preparation and characteriza-
tion of solid inclusion complexes of CDs with organic guests,
relative to extensive research efforts on CD–guest complexa-
tion interactions in solution.22–24
Guaiacol (Gua), which has disinfectant properties, is an oil
at room temperature due to low melting point. It is not only
Published on the web November 13, 2007; doi:10.1246/bcsj.80.2185

2186 Bull. Chem. Soc. Jpn. Vol. 80, No. 11 (2007)
Complexes of Guaiacol with Cyclodextrins
Fig. 2. Schematic sketches showing the relative positions and the centers of host and guest in two different staring geometries
(L-form, Left; R-form, Right).
air at room temperature for evaporation of the solvent and for
further analysis by MALDI-TOF MS.
resonance (NMR), Fourier transform infrared spectroscopy
(FT-IR), matrix assisted laser desorption ionization-time of
flight mass spectrometry (MALDI-TOF MS), thermogravimet-
ric (TG) and X-ray powder diffraction (XRD) analyses. Bind-
ing constants between Gua and CDs were measured by using
1H NMR titration method in a DMSO-d6 solution. Moreover,
PM3 method was also used to investigate the intermolecular
complexations between Gua and ꢁ-CD both in vacuo and in
water.
1H NMR and 13C NMR spectra of the solid complexes were
obtained on a Bruker NMR spectrometer at 300 and 75 MHz,
respectively, at 298.2 K using DMSO-d6 as solvent and TMS as
internal reference. 1H NMR titrations were performed by addition
of stock solutions of CD to a solution of Gua at 298.2 K using
DMSO-d6 as solvent. The chemical shifts of protons in CD and
Gua were monitored with Gua concentration kept constant
(2:00 ꢄ 10ꢃ3 mol dmꢃ3), while the concentration of CD was
gradually increased from 0 to 1:00 ꢄ 10ꢃ1 mol dmꢃ3
.
Experimental and Method
Theoretical Studies of Inclusion Complexation between
Host and Guest. PM3 method25 was chosen to investigate the
inclusion complexation between ꢁ-CD and Gua both in vacuo
and in water. All calculations reported in this paper were per-
formed with the MOPAC software package.26 The initial geome-
try of ꢁ-CD was constructed with the help of the available crys-
tallographic data27 determined by X-ray crystal structure method
and then fully optimized by PM3 without any symmetrical restric-
tions. The guest molecule, Gua, was also fully optimized. PM3
harmonic frequency calculations were performed for the equilibri-
um structures, characterizing them as true minima (all eigenvalues
of the Hessian matrix were positive) on a potential energy surface.
The optimum position of a complexation system was determined
by trying several starting points rather than by a global search.
The glycosidic oxygen atoms of ꢁ-CD were placed onto xy
plane, and the center of its cavity was designated as the origin of
the Cartesian coordinate system (see Fig. 2). The secondary OH
rim of ꢁ-CD was placed pointing toward the positive z-axis.
The benzene ring of the Gua molecule was initially placed along
z-axis as described in Fig. 2.28 As the calculated ꢀEc values of
ꢁ-CD complexes of Gua depend on the starting geometries, two
different starting geometries were considered in the present
work.15,28 Schematic sketches showing the relative positions of
host and guest are depicted in Fig. 2.
Materials. ꢂ-CD was purchased from Nihon Toshin Chemical
Company. ꢀ-CD was purchased from Shanghai Chemical Reagent
Company and recrystallized twice from deionized distilled
water. DMꢀ-CD and ꢁ-CD were kindly donated by Harata. Gua
and 4-hydroxy-3,5-dimethoxy-benzoic acid were obtained from
Shanghai Chemical Reagent Company and used without further
purification. All chemicals were of general purpose reagent grade
unless otherwise stated.
Preparation of Solid Inclusion Complexes. Solid inclusion
complexes were prepared by mixing a guest with ꢂ-, ꢀ-, ꢁ-, or
DMꢀ-CD and stirring for 48 h at 298.2 K. The initial molar ratio
of guests to CDs was 10:1 in deionized water. The separated crys-
talline inclusion complexes were washed using small amounts of
deionized water and alcohol (95%) three times, respectively, and
dried for 24 h at 383.2 K in vacuo. Two pure solid inclusion com-
plexes, Gua–ꢀ-CD and Gua–ꢁ-CD, were obtained in this manner.
However, the solid inclusion complexes of 4-hydroxy-3,5-di-
methoxy-benzoic acid with CDs as well as those of Gua with ꢂ-
CD and DMꢀ-CD were not obtained under the same experimental
conditions.
Instrumentation and Measurement. XRD of the solid com-
plexes was performed on a Philips X’Pert Pro X-ray diffracto-
meter. The samples were irradiated with monochromatized Cu Kꢂ
and analyzed with 5ꢁ ꢂ 2ꢃ ꢂ 40ꢁ. The voltage and current were
40 kV and 40 mA, respectively. EA were carried out on an
Elementar Vario EL III elemental analyzer. FT-IR spectra were
recorded on Bruker EQUINOX55 spectrometer and obtained in
KBr pellets of the injected samples in a frequency range between
4000 and 450 cmꢃ1. TG curves were recorded on a Shimadzu
TGA-50 thermogravimetric analyzer at the heating rate of 10.0
K minꢃ1 under a nitrogen atmosphere. High-resolution MALDI-
TOF mass spectra were recorded on a BIFLEX III TOF-MS from
Bruker (Bremen, Germany) in positive mode. The instrument was
equipped with a nitrogen laser (ꢄ ¼ 337 nm) to desorb and ionize
samples. The sample solutions were prepared by dissolving the
inclusion complexes in DMSO. 2,5-dihydroxybenzoic acid as
matrix was also dissolved in DMSO. Then, the sample solution
of the analyte was pipetted onto the layer of matrix and left in
The host–guest complexation process was simulated by making
Gua penetrate into the cavity of ꢁ-CD from either the wider
(Fig. 2A, L-form) or the narrower (Fig. 2B, R-form) rim side
and letting it pass through the cavity by steps. In every step, the
geometry of the inclusion complex, Gua–ꢁ-CD, was completely
optimized by PM3 without any restrictions.
The formation of the supramolecular inclusion complex (HG)
of Gua (guest, G) and ꢁ-CD (host, H) can be represented by
Eq. 1 as follows:
H þ G ¼ HG:
ð1Þ
The complexation energy (ꢀEc) between G and H is the differ-
ence between the energy of the inclusion complex (ꢀEHG) and
the sum of the energies of Gua (ꢀEe,G) and ꢁ-CD (ꢀEe,H) in their

L. X. Song et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 11 (2007) 2187
Table 1. Preparation of the Solid Inclusion Complexes of ꢀ-CD and ꢁ-CD with Gua
Yield
/%
BPa)
/K
DPa)
/K
Found/%
Calcd/%
Compound
Formulae
C
H
C
H
ꢀ-CD
ꢁ-CD
Gua
Gua–ꢀ-CD
Gua–ꢁ-CD
—
—
—
37.5
51.2
—
—
478.2
—
—
596.0
598.7
—
601.4
603.8
C42H70O35 8H2O
ꢅ
—
—
—
43.10
42.05
—
—
—
6.60
6.80
—
—
—
43.05
42.20
—
—
—
6.63
6.70
C48H80 O40 4H2O
ꢅ
C7H8O2
C49H78O37 6H2O
ꢅ
C55H88O42 8H2O
ꢅ
a) BP and DP represent the boiling point and melting-decomposition point of these compounds,
respectively.
respective optimized equilibrium geometry. Thus, it can be calcu-
lated29 according to Eq. 2:
ture, the results concerning preparation clearly reflected that
the water solubility of supramolecular complexes of different
CDs with the same guest did not depend entirely upon the
solubility of CDs in water. In other words, the water solubility
of ꢁ-CD became much less than that of ꢂ-CD through com-
plex formation with Gua. The yields of the obtained complexes
were calculated on the basis of the initial concentration of host,
and listed in Table 1. Moreover, the thermal decomposition
temperatures, compositions and results of elemental analyses
of these complexes are also summarized in Table 1.
ꢀEc ¼ ꢀEHG ꢃ ꢀEe,H ꢃ ꢀEe,G
:
ð2Þ
In this way, a negative value of ꢀEc denotes that the complex
formation is energetically favorable.
The deformation energy (ꢀEfX) of a component (X) in an in-
clusion complex at its optimum position can be calculated from
Eqs. 3 and 4 as follows:30
ꢀEfH ¼ ꢀEe,H ꢃ ꢀEc,H
;
;
ð3Þ
ð4Þ
ꢀEfG ¼ ꢀEe,G ꢃ ꢀEc,G
The host–guest stoichiometries of the two solid supramolec-
ular complexes were determined to be 1:1, based on the results
of EA and further confirmed by comparing the relative integral
areas of the proton signals between host and guest.
X
where ꢀEf corresponds to the energy difference between the
energy of partners of the complex in their respective equilibrium
geometry (ꢀEe,X) and their energy at complex geometry (ꢀEc,X).
Interaction energy (ꢀEi) is the difference between the energy
of the complex and the sum of the energies of both partners at
their complex geometry. Hence, ꢀEi can be calculated as follows:
As shown in Table 1, the yield of Gua–ꢁ-CD (51.2%) is
13.7% higher than that of Gua–ꢀ-CD (37.5%) under the same
conditions, though the solubility of ꢁ-CD in water is signifi-
cantly higher than that of ꢀ-CD. This suggests that there could
exist a strong intermolecular interaction between ꢁ-CD and
Gua. Since Gua is only slightly soluble in water, therefore, it
should be reasonable that in Gua–ꢁ-CD, Gua has no alter-
native but to penetrate only part way into the cavity of ꢁ-
CD. This inclusion phenomenon is proposed to explain the
observed decrease in the water solubility of ꢁ-CD.
Furthermore, as can be seen in Table 1, the thermal decom-
position points (DP) of Gua–ꢀ-CD (601.4 K) and Gua–ꢁ-CD
(603.8 K) are somewhat higher than those of free ꢀ-CD
(596.0 K) and ꢁ-CD (598.7 K), respectively. The increase in
thermal stability of CDs demonstrates that there is an intermo-
lecular complexation between host and guest.
ꢀEi ¼ ꢀEHG ꢃ ꢀEc,H ꢃ ꢀEc,G
:
ð5Þ
Rearranging Eqs. 2, 3, and 4, gives the expresses of ꢀEHG, ꢀEc,H
and ꢀEc,G, then substituting them into Eq. 5 affords Eq. 6:
,
ꢀEi ¼ ꢀEc þ ꢀEe,H þ ꢀEe,G
ꢃ ðꢀEe,H ꢃ ꢀEfHÞ ꢃ ðꢀEe,G ꢃ ꢀEfGÞ:
ð6Þ
Accordingly, this interaction energy (ꢀEc) between Gua and ꢁ-
CD can also be calculated as the sum of the deformation energy
of both molecules (Gua and ꢁ-CD) and the complexation energy
(see Eq. 7).
ꢀEi ¼ ꢀEc þ ꢀEfH þ ꢀEfG:
ð7Þ
In order to further confirm the formation of inclusion
complexes of Gua with ꢀ- and ꢁ-CD, MALDI-TOF MS
was employed. In the case of Gua–ꢀ-CD, two peaks with
m=z ¼ 1281:7 and 1297.7 were clearly observed, which could
be assigned to the Naþ adduct ion of Gua–ꢀ-CD [Gua–
ꢀ-CD + Na]þ and the Kþ adduct ion of Gua–ꢀ-CD [Gua–
ꢀ-CD + K]þ, respectively. Similarly, in the mass spectrum
of Gua–ꢁ-CD, two peaks with m=z ¼ 1443:7 and 1459.5 could
be assigned to the Naþ adduct ion of Gua–ꢁ-CD ([Gua–
ꢁ-CD + Na]þ and Kþ adduct ion of Gua–ꢁ-CD [Gua–
ꢁ-CD + K]þ), respectively.
XRD Analysis of Solid Inclusion Complexes. The crys-
talline diffraction patterns of CDs should change when a guest
molecule is partly or wholly included into CD cavity.22,23,32
The differences in diffraction peak intensities and diffraction
angles (2ꢃ) can show whether there existed an interaction be-
tween CD and guest molecules.7
Solvent effects were also taken into consideration during theo-
retical calculations. The calculations of solvation energy, i.e.,
hydration energy, in the present work were carried out using the
PM3 method. The solvation model was the Conductor-like
Screening Model (COSMO).31 The COSMO algorithm is invoked
using the keyword NSPA = 60 1SCF EPS = 78.4 (water has a
dielectric constant of 78.4 at 298.2 K) and PM3 CHARGE = 0.
Results and Discussion
Preparation Analysis.
Two pure solid CD inclusion
complexes, Gua–ꢀ-CD and Gua–ꢁ-CD, were prepared by a
direct precipitation reaction described above. However, under
the same experimental conditions, no measurable precipitation
was observed for the other complexation systems investigated,
possibly because of the very good solubility of these inclusion
complexes in aqueous solution. Since the solubility of ꢁ-CD in
water is obviously higher than that of ꢂ-CD at room tempera-

2188 Bull. Chem. Soc. Jpn. Vol. 80, No. 11 (2007)
Complexes of Guaiacol with Cyclodextrins
Fig. 3. XRD spectra of (A) ꢀ-CD and Gua–ꢀ-CD, and (B) ꢁ-CD and Gua–ꢁ-CD.
Table 2. Experimental IR and XRD Data of ꢀ-, ꢁ-CD, and Their Complexes of Gua
IR (Wavenumbers/cmꢃ1
)
XRDa) (2ꢃ/degree)
Compounds
ꢅC{O
ꢅC=C
I1
I2
I3
ꢀ-CD
ꢁ-CD
Gua
Gua–ꢀ-CD
Gua–ꢁ-CD
1028.7
1026.8
1024.5
1031.1
1031.7
1079.8
1080.2
1099.6
1086.9
1086.6
1157.4
1158.3
—
1160.4
1161.8
—
—
1260.8
1265.1
1265.2
—
—
1502.6
1506.9
1506.9
—
—
1598.8
1603.6
1603.0
12.6
17.2
—
11.7
7.6
19.3
22.6
—
5.9
16.1
9.1
9.1
—
18.2
22.0
a) I1, I2, and I3 represent the first, second, and third strongest peaks in X-ray diffractograms, respectively.
To confirm the existence of the supramolecular inclusion
complexes of CDs with Gua, X-ray powder diffraction of the
two solid samples was performed. The powder X-ray diffrac-
tion patterns of ꢀ-, ꢁ-CD, and their inclusion complexes with
Gua are shown in Fig. 3. Because Gua is an oleaginous liquid
at room temperature, there is no powder X-ray diffraction data
available.
and widths also increased.
Furthermore, the morphological shape difference in the
XRD diffraction diagrams, as can be seen in Fig. 3, is smaller
between ꢁ-CD and its complex of Gua than that between ꢀ-
CD and its complex of Gua, suggesting relative small effects
of host–guest complexation on the molecular arrangement of
ꢁ-CD in solid state before and after inclusion.7
As shown in Fig. 3A and Table 2, the 2ꢃ values of the top
three peaks in free ꢀ-CD at 9.1, 12.6, and 19.3ꢁ become 5.9,
11.7, and 18.2ꢁ in Gua–ꢀ-CD, respectively. The main peaks
of Gua–ꢀ-CD shifted towards lower 2ꢃ angles compared to
those of free ꢀ-CD. On the whole, there are considerable
differences in the XRD diffraction spectra of free ꢀ-CD and
Gua–ꢀ-CD, including shapes, numbers and locations of dif-
fraction peaks. Obviously, inclusion complexation decreases
the numbers of diffraction peaks and increases the width in
main peaks, clearly reflecting that Gua–ꢀ-CD is more amor-
phous than free ꢀ-CD.33
Figure 3B displays the XRD spectra of ꢁ-CD and its inclu-
sion complex of Gua. The free ꢁ-CD has a characteristic pat-
tern of multiple diffraction peaks at 9.1, 17.2, and 22.6ꢁ. The
peak at 9.1ꢁ is characteristic of the two free hosts. However,
the other two main peaks of ꢁ-CD are quite different from
those of free ꢀ-CD, reflecting a structural difference in the
conformation of macrocyclic ring skeleton as well as in the
molecular stacking in solid state between free ꢀ-CD and ꢁ-
CD.7,34
FT-IR Spectroscopic Analysis of Solid Inclusion
Complexes. FT-IR spectra are usually used to probe intermo-
lecular interaction between host and guest. Exiguous spectra
changes in the characteristic absorption bands of CD and
guest, upon complexation, can be used to confirm the forma-
tion of a supermolecule as a new compound, though in general,
the changes in IR spectra is quite small, because an inclusion
interaction does not lead to the formation or rupture of chemi-
cal bonds.23 FT-IR spectra of ꢀ-CD, ꢁ-CD, Gua, and their in-
clusion complexes are shown in Fig. 4. As can be seen from
Fig. 4, the positions and intensities of many spectroscopic
bands of the Gua inclusion complexes of CDs show subtle
changes in comparison with those of the same specific bands
of free Gua and CDs.
In Fig. 4A, free ꢀ-CD shows prominent peaks at 3417.6 and
1028.7 cmꢃ1, contributing to ꢅOH and ꢅC{O of ꢀ-CD. There
were a series of peaks at 720–1250 cmꢃ1, which is due to the
ꢅC{C stretching vibrations of ꢀ-CD in the fingerprint region. In
the FT-IR spectra of Gua, the ꢅC=C stretching vibrations of the
aromatic moiety of Gua give two sharp peaks at 1502.6 and
In the Gua–ꢁ-CD spectrum, its top three peaks were ob-
served at 2ꢃ values of 7.6 (I1), 16.1 (I2), and 22.0ꢁ (I3), all of
which are rather different from those of free ꢁ-CD. Upon
inclusion with Gua, the three strongest peaks of ꢁ-CD obvi-
ously shifted towards lower 2ꢃ angles, and their intensities
1598.8 cmꢃ1
.
As for Gua–ꢀ-CD, there were two peaks at 1506.9 (sharp)
and 1603.6 (moderate) cmꢃ1, belonging to the ꢅC=C stretching
vibrations of Gua, and one small sharp peak at 1265.1 cmꢃ1
,
belonging to the ꢅC{O stretching vibrations of Gua. The posi-

L. X. Song et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 11 (2007) 2189
Fig. 4. FT-IR spectra of (A) 1. ꢀ-CD; 2. Gua; 3. Gua–ꢀ-CD and (B) 4. ꢁ-CD; 5. Gua; 6. Gua–ꢁ-CD.
Fig. 5. TG curves of hosts and their complexes of Gua: (A) ꢀ-CD, (B) Gua–ꢀ-CD, (C) ꢁ-CD, and (D) Gua–ꢁ-CD.
tions and intensities of these peaks exhibited large changes
relative to those of pure Gua, despite that there were no new
covalent bonds formed between host and guest. The character-
istic peaks of host and guest, as shown in Table 2, slightly
shifted to higher wavenumbers. Furthermore, the intensities
of these peaks obviously decrease upon inclusion, indicating
that Gua has been introduced into the cavity of ꢀ-CD after
complexation.22
In Fig. 4B, the stretching vibrations of ꢅC{O in IR spectra
of ꢁ-CD were observed at 1026.8, 1080.2, and 1158.3 cmꢃ1 re-
spectively. The ꢅC{C stretching vibrations of ꢁ-CD lie within a
given range of 709–1250 cmꢃ1 in fingerprint region.
Gua–ꢁ-CD, gave weak absorptions at 1506.9 and 1603.0
cmꢃ1. These results show that there exist distinct intermolecu-
lar interactions between Gua and ꢁ-CD.23
Consequently, FT-IR spectroscopic analyses of these host–
guest systems suggest the formation of the two solid inclusion
complexes Gua–ꢀ-CD and Gua–ꢁ-CD. It should be noted that
IR spectra of Gua–ꢀ-CD and Gua–ꢁ-CD are very similar,
whereas their XRD spectra were quite different, because many
characteristic peaks of Gua in the IR spectra are overlapped by
those of CDs.
TG Analysis of Solid Inclusion Complexes. Thermal
analysis methods are widely used in host–guest chemistry for
the thermodynamic investigation of inclusion complexations
between CDs and organic guests.23,35 Figure 5 displays the
TG curves of ꢀ-CD, ꢁ-CD, Gua–ꢀ-CD, and Gua–ꢁ-CD.
However, upon inclusion the characteristic peaks, attributed
to the ꢅC{O stretching vibrations of ꢁ-CD, shifted to 1031.7,
1086.6, and 1161.8 cmꢃ1. The C=C stretching vibrations of

2190 Bull. Chem. Soc. Jpn. Vol. 80, No. 11 (2007)
Complexes of Guaiacol with Cyclodextrins
Table 3. Thermal Decomposition Details of CDs and Their Inclusion Complexes
Stage a
TR/K
Stage a0
TR/K
Stage b0
Stage b
TR/%
Stage c
Compound
TP/K
TP/K
TR/K
WL/%
RW/%
ꢀ-CD
Gua–ꢀ-CD
ꢁ-CD
356.6
373.5
357.8
357.8
323.5–383.2
340.1–452.4
329.6–393.7
329.6–385.8
—
551.1
—
—
—
—
—
573.0–623.3
560.6–632.0
565.2–631.3
571.3–655.5
61.23
62.00
65.12
57.43
16.80
10.18
10.88
9.79
467.4–560.5
—
393.8–470.0
Gua–ꢁ-CD
453.2
474.6–562.2
Fig. 6. A consecutive mechanism depicting the formation (A) and decomposition (B–E) of the inclusion complex of ꢀ-CD with Gua.
In Fig. 5A, the first weight loss of ꢀ-CD in the range from
323.5 to 383.2 K was about 10.90% (Stage a), corresponding
to the release of about eight water molecules from ꢀ-CD cavi-
ty (calc. 7.71), with a maximum rate of mass loss at 356.6 K.
No further change is observed until around 573.0 K after which
ꢀ-CD begins to melt and decompose. The maximum rate of
melting-decomposition was recorded at 596.0 K, correspond-
ing to decomposition point (DP) of ꢀ-CD, as shown in
Table 1. The melting-decomposition of ꢀ-CD appeared in the
narrow range of 573.0–623.3 K with a weight loss of 61.23%
in this stage (Stage b). Even though the free solid ꢀ-CD was
subsequently heated up to 773.2 K, a residual weight of
16.80% (Stage c) could still be observed in the TG curve.
The TG curve of Gua–ꢀ-CD is significantly different
from that of pure ꢀ-CD. When solid Gua–ꢀ-CD was heated
from room temperature to 452.4 K, a weight loss of 7.89%
(Stage a) occurred, corresponding to the release of six water
molecules (calc. 6.00). In this stage, a continuous weight loss
measurement, as in Fig. 5B, clearly showed slow and gradual
releases of water from the ꢀ-CD complex in the broad temper-
ature range from 340.1 to 452.4 K, which is rather different
from the release of water molecules in free ꢀ-CD, indicating
the difference in numbers of complexed and uncomplexed
water molecules between the host–guest supermolecule (main-
ly containing complexed water) and the free host (mainly con-
taining uncomplexed water).35 In addition, one guest molecule
(calc. 0.98) released from the complex in the temperature
range of 467.4–560.5 K with a weight loss of 8.85% (Stage a0).
It is worth stressing that the molecular numbers of both
water and guest based on the TG curve are exactly in accord
with the measurement results of elemental analyses of the solid
sample. A relatively rapid weight loss of complexed Gua oc-
curred at around 551.1 K, due to its rapid boiloff. When the
temperature was further increased to 560.0 K, the complexed
Gua disappears entirely from its inclusion complex of ꢀ-CD.
It should also be noted that until about 467.4 K, Gua is not
released, and the two temperatures, 551.1 and 560.6 K, are
markedly higher than the boiling point (478.2 K) of free Gua.
These observations strongly suggest that the intermolecular
interactions between Gua and ꢀ-CD significantly improve the
thermal stability of Gua. Above 560.0 K, a very large weight
loss of 62.00% in the TG curve of Gua–ꢀ-CD was recorded
in the temperature range of 560.6 to 632.0 K (Stage b, DP =
601.4 K, see Table 1), attributing to the melting-decomposi-
tion of the complexed ꢀ-CD. The residual weight of the inclu-
sion complex of ꢀ-CD at 773.2 K was about 10.18% (Stage c).
The temperature ranges (TR, K) of the thermal release and
decomposition of the supramolecular inclusion complexes as
well as the decomposition temperature points (TP, K), corre-
sponding to a rapid weight loss (WL, %) process, and the
residual weight (RW, %) at 773.2 K are all summarized in
Table 3.
According to the findings in Fig. 5B and Table 3, a consecu-
tive mechanism (A–E) concerning the formation and thermal
decomposition of solid supramolecular inclusion complex of
ꢀ-CD with Gua is suggested in Fig. 6. The formation of a
hydrated inclusion complex, Gua–ꢀ-CD 6H2O, is regarded as
ꢅ
process A. Next the release of six water molecules and Gua in
this complex early or late refer to processes B (Stage a) and C
(Stage a0), respectively, and the melting-decomposition or
carbonization of the complexed ꢀ-CD is regarded as process
D (Stage b). Process E represents further incineration of the
carbonized remains (Stage c).
It should be noted that there are very small differences in
temperature range of decomposition and degradation of free
ꢀ-CD (573.0–623.3 K) and complexed ꢀ-CD (560.6–632.0 K)
as shown in Table 3. The melting-decomposition point (DP,
601.4 K) of the inclusion complex also is only slightly higher
than that of free ꢀ-CD (DP, 596.0 K). However, at temper-
atures > 632.0 K, more residual weight is always recorded in
the TG curve of ꢀ-CD compared to that of Gua–ꢀ-CD.
As shown in Fig. 5C, the TG curve of ꢁ-CD indicated the
loss of hydrated water (Stage a, 5.62%, 4.10 water molecules)
up to 393.7 K. In the temperature range from 565.2 to 631.3 K,
ꢁ-CD melted and decomposed (Stage b, 65.12%). The maxi-
mum rate of the thermal decomposition was recorded at
598.7 K (DP). The residual weight of ꢁ-CD at 773.2 K was
about 10.88% (Stage c). However, as can be seen in Fig. 5,
the TG curve of Gua–ꢁ-CD is significantly different from that
of ꢁ-CD or Gua–ꢀ-CD. Because the weight loss processes of
Gua–ꢀ-CD and ꢁ-CD can be divided easily into three and
four stages respectively; however, a five-stage thermal decom-
position process for Gua–ꢁ-CD can be seen very clearly in
Fig. 5D.

L. X. Song et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 11 (2007) 2191
ꢀ-CD > Gua–Gua > Gua–ꢁ-CD.
During the first stage, a weight loss of 9.46% should be as-
cribed to the release of about eight water molecules (Stage a,
calc. 8.22) from the hydrated supermolecule of ꢁ-CD with
Gua.
NMR Spectral Analysis of Solid Inclusion Complexes.
NMR has been widely used to gain important information
about the location of a guest in its complex of CD by chemical
shift changes from protons of CD and guest in solution,23,36 be-
cause the insertion of a guest molecule into the hydrophobic
cavity of CD from two different rims will result in different
chemical shift changes of the interior protons (H-3 close to
the wider rim and H-5 close to the narrower rim) of the CD
cavity.22,37
1H NMR spectra of free Gua and its complexes of ꢀ- and ꢁ-
CD in DMSO-d6 are displayed in Fig. 7. The 1H and 13C NMR
chemical shifts (ꢆ) of Gua, ꢀ-CD and ꢁ-CD as well as the
chemical shift changes (ꢀꢆ) of their solid inclusion complexes
in DMSO-d6 are also listed in Table 4.
In the inclusion complex Gua–ꢀ-CD, the H-a proton signals
of Gua were shifted downfield by 0.029 ppm. However, no
obvious chemical shift changes of these protons of phenolic
hydroxy and methoxy groups of Gua were observed. More-
over, among the CH or CH2 protons of ꢀ-CD, the signals of
H-3 and H-5 protons located inside ꢀ-CD cavity, were shifted
slightly more downfield (0.019 and 0.010 ppm, respectively)
than those of the other protons outside the cavity. In addition,
The second weight loss process is a two-step Gua–ꢁ-CD
decomposition process (Stage a0 and Stage b0): the first step
showed a weight loss of 7.81% from 393.8 to 470.0 K, corre-
sponding to the gradual evaporation of the complexed Gua
(Stage a0, calc. 0.99), and the second step showed a weight loss
of 8.66% from 474.6 to 562.2 K (Stage b0), corresponding to
the slow melting and evaporation of the remaining complex,
which was mainly ꢁ-CD. It is worth stressing that the phase
change temperature (448.4 K) of Gua after inclusion is signifi-
cantly lower than the boiling point (478.2 K) of free Gua.
Moreover, even if the experimental temperature is below
470.0 K, complexed Gua can still be released entirely from
the complex. In addition, due to the latent heat effects resulting
from the phase changes of the first step, i.e., Stage a0, the re-
maining sample, mainly containing ꢁ-CD, had a lower melting
point than free ꢁ-CD and lost 8.66% of its total weight in
the broad temperature range of 474.6–562.2 K, due to a slow
evaporation rate. The results described above are completely
different from those found in free ꢁ-CD and Gua–ꢀ-CD, be-
cause the initial onset temperature of the thermal decomposi-
tion of both free ꢁ-CD and residual of Gua–ꢀ-CD are greater
than 565.2 K. In addition, further heating would result in an
abrupt weight loss of 57.43% in the temperature range from
571.3 to 655.5 K (Stage b) with the maximum rate of weight
loss occurring near 603.8 K. The residual weight of complexed
ꢁ-CD at 773.2 K was about 9.79% (Stage c).
The above results indicate that, upon inclusion, the thermal
decomposition point of ꢀ-CD or ꢁ-CD as host only slightly in-
creases. Gua after inclusion exhibits entirely different thermal
behavior in its two CD complexes, Gua–ꢀ-CD and Gua–
ꢁ-CD, i.e., the thermal stability of the complexed Gua is obvi-
ously higher in the former than in the latter. Clearly, this inclu-
sion phenomenon can be attributed to the effects of the differ-
ent strength of interactions between Gua and CDs as well as
between Gua itself. It is reasonable that the intermolecular
interactions in the solid state decreases in the order: Gua–
Fig. 7. 1H NMR spectra (300 MHz, DMSO-d6, 298.2 K) of
Gua, Gua–ꢀ-CD and Gua–ꢁ-CD.
Table 4. 1H and 13C NMR Chemical Shifts (ꢆ, ppm) of Gua, ꢀ-CD, and ꢁ-CD, and the Chemical Shift Changes
(ꢀꢆ, ppm) of Their Solid Inclusion Complexes in DMSO-d6
ꢀ-CD
ꢁ-CD
Gua
Position
Position
Free/ppm ꢀꢆ/ppm Free/ppm
ꢀꢆ/ppm
Free/ppm ꢀꢆꢀ-CD/ppm ꢀꢆꢁ-CD/ppm
H-1
H-2
H-3
H-4
H-5
H-6
4.810
3.322
3.657
3.294
3.598
3.631
0.005
0.008
0.019
0.004
0.010
0.007
4.859
3.306
3.755
3.327
3.567
3.627
0.029
0.005
ꢃ0:004
0.015
0.006
H-a
H-b
H-c
6.756
6.891
3.748
0.029
0.004
ꢃ0:008
0.011
0.027
0.003
0.010
C-1
C-2
C-3
C-4
C-5
C-6
102.300
72.410
73.470
81.900
72.730
60.320
ꢃ0:262
ꢃ0:292
ꢃ0:337
ꢃ0:264
ꢃ0:297
ꢃ0:233
102.220
73.010
73.430
81.410
72.680
60.540
ꢃ0:374
ꢃ0:300
ꢃ0:399
ꢃ0:343
ꢃ0:389
ꢃ0:425
C-1
C-2
C-3
C-4
C-5
C-6
C-7
146.619
147.701
115.616
119.229
120.953
112.600
55.574
0.020
0.066
0.030
0.140
0.103
0
0.011
0.084
0.076
0.066
0.103
0
0.075
0.121

2192 Bull. Chem. Soc. Jpn. Vol. 80, No. 11 (2007)
Complexes of Guaiacol with Cyclodextrins
Fig. 9. Chemical shift changes (ꢀꢆ) in the H-a protons
of Gua (2:00 ꢄ 10ꢃ3 mol dmꢃ3) upon addition of ꢁ-CD
(0{1:00 ꢄ 10ꢃ1 mol dmꢃ3).
As shown in Fig. 9, the chemical shift changes of H-a proton
of Gua upon addition of ꢁ-CD in the concentration range from
0 to 1:00 ꢄ 10ꢃ1 mol dmꢃ3 exhibited highly nonlinear charac-
teristics. Therefore, the binding constant between Gua and ꢁ-
CD can be calculated. If the formation of ꢁ-CD inclusion
complex of Gua in solution is shown in Eq. 1, the relationship
among the observed chemical shift changes of H-a proton
signal in Gua, the initial molar concentration of Gua and ꢁ-
CD, and the value of K can be described by Eq. 8,38,39
Fig. 8. Chemical shifts (ꢆ) of the protons of benzene ring
and methoxy groups in Gua for the 1H NMR titration of
the inclusion system of Gua and ꢁ-CD. The values of R
represent the molar concentration ratios of ꢁ-CD to Gua.
the chemical shift change of H-3 proton is larger than that of
H-5 proton. However, in the case of Gua–ꢁ-CD, the signals
of the H-3 and H-5 protons of ꢁ-CD as well as the proton
signals of methoxy groups of Gua showed only very small
lateral shifts.
ꢀ
ðꢆHG ꢃ ꢆGÞ
ꢆ ꢃ ꢆG ¼
½Hꢆ0 þ ½Gꢆ0 þ ð1=KÞ
2
ꢁ
qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
2
ꢃ
ð½Hꢆ0 þ ½Gꢆ0 þ ð1=KÞÞ ꢃ 4½Hꢆ0½Gꢆ0
;
ð8Þ
As 13C NMR chemical shifts extend over a much larger
scale than 1H NMR does, it is particularly suitable for identify-
ing the formation of inclusion complexes. The 13C NMR data
of ꢀ-CD, ꢁ-CD, Gua, and their inclusion complexes are given
in Table 4. Upon complexation, all of the signals of carbon
atoms of ꢀ-CD and ꢁ-CD shifted upfield, and the chemical
shift changes of C-3 (ꢀꢆ, ꢃ0:337 ppm for ꢀ-CD and ꢃ0:399
ppm for ꢁ-CD) in the two complexes of Gua are bigger than
of those of C-5 (ꢀꢆ, ꢃ0:297 ppm for ꢀ-CD and ꢃ0:289 ppm
for ꢁ-CD). Moreover, the signals of the carbon atoms, espe-
cially C-4 atom (ꢀꢆ, 0.140 ppm for ꢀ-CD) and C-5 atom
(ꢀꢆ, 0.103 ppm for ꢁ-CD), in benzene ring of Gua aside from
C-6 atom were shifted downfield.
where ꢆG, ꢆHG, ꢆ represent chemical shift of Gua, inclusion
complex of Gua, and observed chemical shift, respectively.
Hence, the difference between ꢆ and ꢆG is the observed chemi-
cal shift changes (ꢀꢆ) in the H-a proton signal in Gua with and
without ꢁ-CD. [H]0 and [G]0 represent the initial molar con-
centration of ꢁ-CD and Gua, respectively. As can be seen in
Fig. 9, the nonlinear relationship between the experimental
data points and the fitted curve appears to be rather good. A
correlation coefficient (r2) of 0.997 was obtained, confirming
that ꢁ-CD interacts with Gua to form an inclusion complex
of 1:1 stoichiometry. The calculated binding constant between
Gua and ꢁ-CD was 6:22 ꢄ 103 molꢃ1 dm3. The inclusion
system of Gua and ꢀ-CD was similarly treated, and the bind-
ing constant between Gua and ꢀ-CD was determined to be
5:74 ꢄ 103 molꢃ1 dm3, which is smaller than that between
Gua and ꢁ-CD, indicating that there is a stronger intermolec-
ular interaction between Gua and ꢁ-CD than between Gua and
ꢀ-CD in DMSO solution.
As can be seen in Fig. 8, a progressively increasing down-
field shift of the benzene ring protons (H-a and H-b) in Gua
with increasing molar fractions of ꢁ-CD in sample solutions
was clearly observed. This result is attributed to the formation
of ꢁ-CD inclusion complex of Gua in DMSO solution. The
maximum ꢀꢆ values of the H-a, H-b, and H-c protons were
0.051, 0.047, and 0.031 ppm, respectively. Therefore, upon
complexation, the benzene ring protons are more affected than
the protons of the methoxy group in Gua. For the inclusion
system of Gua and ꢀ-CD, a similar phenomenon was also
It is noted that the observed ꢀꢆ values of the complexes
dissolved in DMSO solution were very small. Their maxima
were 0.029 ppm for proton and ꢃ0:425 ppm for carbon. This
means that the solid inclusion complexes decompose in DMSO
solution. In order to further investigate the complex geometries
and the intermolecular complexation between Gua and CDs in
1
solution, H NMR titration measurements were carried out.
NMR Titration Measurements. 1H NMR titrations were
performed by adding stock solutions of CDs to a solution of
Gua at 298.2 K using DMSO-d6 as solvent. The continuous
chemical shift changes in the protons of CD and Gua were
observed with an increase in the concentration ratio of CD to
Gua. Typical 1H NMR spectra at each titration point of the
inclusion system of Gua and ꢁ-CD are shown in Fig. 8.
Quantitative analysis of the NMR titration data allows us to
determinate the binding constants (K) between Gua and CDs.

L. X. Song et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 11 (2007) 2193
Fig. 10. Relationships between the chemical shift changes (ꢀꢆ) of protons H-3 ( ) and H-5 ( ) of CDs and the concentrations of
CDs. The concentration of Gua is kept constant at 2:00 ꢄ 10ꢃ3 mol dmꢃ3. (A) inclusion system of Gua with ꢀ-CD and (B) inclu-
sion system of Gua with ꢁ-CD.
observed. These findings suggest that the benzene ring of Gua
is deeply embedded into the CD cavity and the methoxy group
of Gua might project outside the cavity.
Table 5. Complexation Energies (ꢀEc), Deformation Ener-
gies (ꢀEf) and Interaction Energies (ꢀEi) in kJ molꢃ1 of
the Inclusion Complex of ꢁ-CD with Gua at Two Differ-
ent Starting Geometries (L- and R-forms) in Vacuo and in
Water
Intermolecular complexation between Gua and CD should
lead to the chemical shift changes (ꢀꢆ) in the protons (H-3
and H-5) of the inner cavity of CD. As shown in Figs. 10A
and 10B, a markedly nonlinear increase of the ꢀꢆ values in
the H-3 and H-5 protons of CDs with an increase in the relative
concentration of CDs was observed. The maximum ꢀꢆ values
of the H-3 and H-5 protons of Gua–ꢀ-CD were ꢃ0:075 and
ꢃ0:052 ppm, respectively. For the Gua–ꢁ-CD inclusion sys-
tem, these values were ꢃ0:059 and ꢃ0:041 ppm, respectively.
In other words, after complexation with Gua, due to the ring
current effect, both H-3 and H-5 protons of CDs showed con-
siderably large upfield shifts. These observations are in good
agreement with those already published by other groups for
the inclusion systems of ꢀ-CD and phenolic compounds.11,37
However, the ꢀꢆ values are significantly larger than those
listed in Table 4 for the solid inclusion complexes in DMSO
solution. This is because complexation induced shifts corre-
sponding to 100% complexation can be obtained by using
NMR titration.
In both case, the ꢀꢆ value of H-3 protons located in the
large end side is always bigger than that of H-5 protons located
in the small end side of CD cavity. It is known that, if H-3
undergoes a shift in the presence of substrate, then the cavity
penetration is shallow, whereas, when the H-5 resonance of
CD also shifts, the penetration will be deep.40 Therefore, ac-
cording to the results from NMR titration experimental, it is
reasonable to presume that the benzene ring of Gua in solution
is likely to have stayed near the wider rim of the cavity of ꢀ-
or ꢁ-CD with its methoxy group projecting outside. In order
to further investigate the details of complexation process and
evaluate the stability of the geometry of CD inclusion com-
plexes of Gua, PM3 calculations were carried out.
Gua–ꢁ-CD-L
Gua–ꢁ-CD-R
in vacuo
ꢃ60:5
6.59
2.79
9.38
ꢃ51:1
in water
in vacuo
ꢃ33:5
6.34
2.98
9.32
ꢃ24:2
in water
ꢀEc
ꢀEfH
ꢀEfG
ꢀEf
ꢀEi
ꢃ51:2
6.72
2.81
9.53
ꢃ41:7
ꢃ25:9
7.03
2.54
9.57
ꢃ16:3
in Table 5.
The calculated energies of CD–guest complexes depend on
the starting geometries. The optimum position for guest into
CD at different starting geometries can be determined accord-
ing to complexation energy. The most stable structure can be
obtained by comparing the characteristic energies of the com-
plexes between different starting geometries at the optimum
position. The detailed results of the inclusion processes of Gua
with ꢁ-CD and the most stable structure of Gua–ꢁ-CD are
shown in Fig. 11.
As can be seen in Fig. 11A, Gua–ꢁ-CD with the starting
geometry shown in Fig. 2A, Gua–ꢁ-CD-L (L represents left),
had the most negative ꢀEc near the secondary hydroxy rim
(Z ¼ 200 pm, ꢀEc ¼ ꢃ60:5 kJ molꢃ1). Figure 11B shows the
other structural form (Gua–ꢁ-CD-R, R represents right) of
Gua–ꢁ-CD with the starting geometry in Fig. 2B. Its most
negative complexation energy was near the center region of
ꢁ-CD cavity (Z ¼ ꢃ100 pm, ꢀEc ¼ ꢃ33:5 kJ molꢃ1). Clearly,
the supramolecular structure of Gua with ꢁ-CD described in
Fig. 11A has
a
much lower complexation energy
(ꢀꢀEc ¼ ꢃ27:0 kJ molꢃ1).
Calculated Results of Inclusion Complexation between
ꢁ-CD and Gua. ꢀEi is a reflection of the stability of a supra-
molecular complex. A negative value of ꢀEi means that the
complex formation is energetically favorable. Theoretically
speaking, if the value of ꢀEi of an inclusion complex is more
negative, the complex should be more thermodynamically
stable. ꢀEc, ꢀEf, and ꢀEi values of the inclusion complex
Gua–ꢁ-CD with two different starting geometries are listed
This phenomenon is attributed to the formation of inter-
molecular hydrogen bonds between the polar substituents
(–OH or –OCH3) in Gua and the hydroxys of ꢁ-CD. The PM3
optimized structures of the two structural forms of Gua–ꢁ-CD
are illustrated with color photographs in Fig. 12. The hydrogen
bond between –OH in Gua and a secondary hydroxys group of
ꢁ-CD (hydroxy group at C-3) is clearly shown in Fig. 12A.
However, as shown in Fig. 12C, no intermolecular hydrogen

2194 Bull. Chem. Soc. Jpn. Vol. 80, No. 11 (2007)
Complexes of Guaiacol with Cyclodextrins
Fig. 11. PM3 complexation energy [ꢀEc/kJ molꢃ1] curves of the host–guest inclusion complexations, (A) migration of Gua into
ꢁ-CD cavity from the secondary OHs rim and (B) migration of Gua into ꢁ-CD cavity from the primary OHs rim.
tence of the rigid benzene ring on the guest backbone.
In general, interaction of water with host or guest is impor-
tant for making an inclusion complex in aqueous solution.3 As
can be found in Table 5, when solvent effects were taken into
consideration during theoretical calculations, the values of
ꢀEc of Gua–ꢁ-CD-L or Gua–ꢁ-CD-R were obviously differ-
ent between in vacuo and in water (ꢀꢀEc > 7:5 kJ molꢃ1),
but the ꢀEf values of Gua–ꢁ-CD were scarcely affected
(ꢀꢀEf < 0:3 kJ molꢃ1).
The structural form, Gua–ꢁ-CD-L, of the inclusion complex
has a relatively lower complexation energy (ꢀꢀEc ¼ ꢃ9:3
kJ molꢃ1) in vacuo than in water. For the other structural form,
Gua–ꢁ-CD-R, a similar energy difference of ꢃ7:6 kJ molꢃ1 is
also found. However, there is only slight difference between
the calculated ꢀEf values of Gua as well as ꢁ-CD in vacuo
and in water. In other words, in the present work the deforma-
Fig. 12. PM3 optimized structures of Gua–ꢁ-CD-L and
Gua–ꢁ-CD-R, (A) top view and (B) side view of the
optimized structure of Gua–ꢁ-CD-L; (C) top view and
(D) side view of the optimized structure of Gua–ꢁ-CD-R.
tion of both host and guest molecule is not affected by the
water environment around them.
The sufficiently large negative values of ꢀEi especially the
extremely large negative ꢀEi value (ꢃ51:1 kJ molꢃ1 in vacuo,
ꢃ41:7 kJ molꢃ1 in water) of the structural form Gua–ꢁ-CD-L
clearly demonstrate that Gua forms a stable complex with
ꢁ-CD near the secondary hydroxy rim. The results also
suggest a significant intermolecular interaction between ꢁ-
CD and Gua.
bonds form between Gua and ꢁ-CD in the optimized structure
of Gua–ꢁ-CD-R. The side view of the optimized structure of
Gua–ꢁ-CD-L or Gua–ꢁ-CD-R (see Figs. 12B and 12D) shows
that the benzene ring of Gua is accommodated into the cavity
of ꢁ-CD. Furthermore, for either the two structural forms of
the complex, when Gua is far from the center region of cavity
of ꢁ-CD, the host–guest inclusion system would become
unstable (see Fig. 11).
The molecular inclusion of a guest molecule into CD cavity
is sure to be accompanied by the deformation of both the guest
and host molecules. Unlike ꢂ- and ꢀ-CD, ꢁ-CD has a more
flexible structure;1 therefore, deformation of ꢁ-CD during
the complexation process cannot be neglected. Between the
structural forms of Gua–ꢁ-CD-L and Gua–ꢁ-CD-R in vacuo,
the ꢀEfH values of ꢁ-CD were 6.59 and 6.34 kJ molꢃ1, respec-
tively.
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4
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As can be seen in Table 5, there is no significant difference
H
between the two calculated ꢀEf values of ꢁ-CD under two
10 R. Ficarra, P. Ficarra, M. R. Di Bella, D. Raneri, S.
Tommasini, M. L. Calabro, M. C. Gamberini, C. Rustichelli,
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different conditions, i.e., Gua enters ꢁ-CD cavity from the sec-
ondary OHs rim or from the primary OHs rim. From Table 5,
G
in any case the ꢀEf values of Gua are always obviously
H
smaller than the ꢀEf values of ꢁ-CD, because of the exis-

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