Host-guest interactions between dapsone and β-cyclodextrin (part I): Study of the inclusion compound by nuclear magnetic resonance techniques

Article abstract of DOI:10.1007/s10847-012-0148-2

Dapsone (4,4′diaminodiphenylsulfone) is a very effective drug to treat leprosy and a broad range of infectious conditions such as Pneumocystis carinii pneumonia, toxoplasmosis and tuberculosis. However, the oral administration of this drug generally is related to serious side effects and treatment failures. It is believed that the inclusion compound of this drug and cyclodextrins would increase the wettability and the solubility of the encapsulated drug for a supported and gradual release, maximizing its biodisponibility over time. The encapsulation of dapsone in β-cyclodextrin was investigated by five nuclear magnetic resonance spectroscopy techniques. The data obtained for the complex in aqueous solution and in solid-state revealed a strong interaction between host and guest, showing that the drug molecule is deeply inserted in the CD cavity. The diffusion experiments (diffusion ordered spectroscopy) showed a high percentage of complexation (86 %) and that the drug molecule is preferentially interacting with the large side of the β-cyclodextrin cavity.

Full text of DOI:10.1007/s10847-012-0148-2

J Incl Phenom Macrocycl Chem (2013) 75:77–86
DOI 10.1007/s10847-012-0148-2
ORIGINAL ARTICLE
Host–guest interactions between dapsone and b-cyclodextrin
(part I): study of the inclusion compound by nuclear magnetic
resonance techniques
•
Adriana Calderini Milene H. Martins
•
Francisco B. T. Pessine
Received: 6 July 2011 / Accepted: 12 March 2012 / Published online: 10 June 2012
Ó Springer Science+Business Media B.V. 2012
Abstract Dapsone (4,40diaminodiphenylsulfone) is
a
DPS
bCD
D
Dapsone
very effective drug to treat leprosy and a broad range of
infectious conditions such as Pneumocystis carinii pneu-
monia, toxoplasmosis and tuberculosis. However, the oral
administration of this drug generally is related to serious
side effects and treatment failures. It is believed that the
inclusion compound of this drug and cyclodextrins would
increase the wettability and the solubility of the encapsu-
lated drug for a supported and gradual release, maximizing
its biodisponibility over time. The encapsulation of dap-
sone in b-cyclodextrin was investigated by five nuclear
magnetic resonance spectroscopy techniques. The data
obtained for the complex in aqueous solution and in solid-
state revealed a strong interaction between host and guest,
showing that the drug molecule is deeply inserted in the
CD cavity. The diffusion experiments (diffusion ordered
spectroscopy) showed a high percentage of complexation
(86 %) and that the drug molecule is preferentially inter-
acting with the large side of the b-cyclodextrin cavity.
b-Cyclodextrin
Diffusion coefficient
Acquisition delay
Diffusion ordered spectroscopy
Freeze-drying
D1
DOSY
FD
FID
Lb
Free induction decay
Line broadening
NMR
nt
Nuclear magnetic resonance
Number of transients
Physical mixture
PM
PW
rOe
Pulse width
Rotating overhauser effect
ROESY Rotating frame overhauser effect spectroscopy
CPMAS Cross-polarization magic angle spinning
Introduction
Keywords Dapsone ꢀ b-Cyclodextrin ꢀ T1 ꢀ ROESY ꢀ
DOSY ꢀ CPMAS
Patients suffering from AIDS are usually affected by
opportunistic diseases such as Pneumocystis carinii pneu-
monia, toxoplasmosis and tuberculosis. One drug of choice
to treat them is dapsone (DPS) (4,40diaminodiphenylsul-
fone), which is cheap and easy to be administered [1]. Also,
the oral administration of DPS is very effective to treat a
broad range of inflammatory conditions [2]. However, the
oral delivery of DPS generally leads to serious adverse
effects, such as the side effects are anemia, stomach upset,
nausea, leg or back pain, headache, dizziness or peripheral
neuropathy and treatment failures [3]. Leprosy is another
important treatment application of DPS although frequently
induces hemolytic anemia and methemoglobinemia [4].
Cyclodextrins (CDs) are one of host molecules more
extensively studied in supramolecular chemistry, because
Abbreviations
Dd
d
Chemical shift difference
Chemical shift
At
Acquisition time
Cyclodextrin
CD
A. Calderini (&) ꢀ M. H. Martins ꢀ F. B. T. Pessine (&)
Institute of Chemistry, State University of Campinas,
P.O. Box 6154, Campinas, SP CEP 13083-970, Brazil
e-mail: adrianacalderini@yahoo.com.br
F. B. T. Pessine
e-mail: fpessine@iqm.unicamp.br
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J Incl Phenom Macrocycl Chem (2013) 75:77–86
of their advantages: they are biocompatible, produced by
natural enzymatic degradation of starch, they are relatively
cheap and non-toxic, allowing applications in drugs, foods
and cosmetics [5]. CDs are cyclic oligomers of a-D-glucose
connected through glycosidic a-1.4 bonds, crystalline, non-
hygroscopic, and torus-like macrocycles, formed by the
action of the enzyme CD glucosyltransferase (CGTase) on
starch. Due to their intramolecular cavity they have the
ability to include guest molecules altering their physical,
chemical, biological and pharmacological properties
through the formation of inclusion complexes [6, 7]. CD is
often used to increase the aqueous solubility, stability and
bioavailability of drugs [8]. The three most commonly used
CD are aCD (six glucose units), bCD (seven glucose units),
and cCD (eight glucose units) [9]. The size of the cavity of
bCD is just right to interact with a great number of mol-
ecules and, therefore, this CD was used in this study. There
are many techniques that can be applied to study interac-
tions between hosts and CDs molecules but NMR is one of
the most important because association in the CDs inclu-
sion complex is due to non-covalent interactions. Also,
generally CD applications involve the complex in a liquid
solution which again reveals the importance of NMR
spectroscopy in their study [10]. In this way, due to the
DPS uses in many diseases and the properties of this car-
rier, it was decided to study the encapsulation of this drug
in bCD with the goal of increasing the wettability and the
solubility of the encapsulated drug for a supported and
gradual release, maximizing its biodisponibility over time.
One of the main technique to characterize drug:CD is
the nuclear magnetic resonance (NMR) spectroscopy due
to its wide field of applications from structural elucidation
of structures to investigations on intra/inter-molecular. The
simplest experiment of NMR as an indicative of com-
plexation is the observation of the difference in the proton
chemical shifts between the free guest and host species and
the suggested complex. There has been a long time since
Demarco and Thakkar [11] started studies on CDs com-
plexes by observing the chemical shifts changes of the
protons H3 and H5 inside the cavity of aCD when in
presence of aromatic molecules due to the anisotropic
effect of the aromatic ring. When there is a host–guest
interaction, it leads to a change in the d of the hydrogens
due the complexation. This is a first evidence of the guest
inclusion in the CD cavity [10].
between the guest nuclei and the CD inner cavity nuclei
H3, H5 and H6 [14, 15]; and 13C-cross polarization magic
angle spinning (CPMAS) NMR which is a powerful non-
invasive approach to the molecular analysis of starch-
related structures, and provides information on the
molecular organization at shorter distance scales [16].
Therefore, we characterized the inclusion complex of DPS
and bCD by five NMR spectroscopy techniques. Information
on interactions between host and guest were obtained by 1H-
NMR and 13C-CPMAS; measurements of diffusion coeffi-
cients where studied from diffusion ordered spectroscopy
(DOSY) experiments and from T1 relaxation times; structural
information of the complex were from ROESY-1D (rotating
frame overhauser effect spectroscopy).
Experimental
Materials and equipments
´
DPS was supplied by Ecofarma Farmacia Ltd.; bCD was a
gift from ISP Technologies, Inc. and it was used as received;
ethyl alcohol 99.5 % P.A. was purchased from LabSynth
Ltd. Products for Laboratories; 99.9 % deuterium oxide was
purchased from Cambridge Isotope Laboratories, Inc.;
Freeze-dryer FTS systems; NMR spectrometer Bruker
Avance II 300 MHz and Varian 500 MHz; rotary evaporator
RE111, water bath 461 and vacuum pump Bu¨chi Labor-
technik AG.
Preparation of the inclusion complex
The inclusion complex DPS:bCD was prepared by adap-
tation of two methods: co-precipitation and lyophilization.
bCD was dissolved in 70 mL of deionized water, followed
by addition of 20 mL of DPS in ethanolic solution in a
molar ratio 1:1. The mixture was stirred at room temper-
ature for 24 h. After removal of ethanol in a rotatory
evaporator at 40 °C, the suspension was frozen in liquid
nitrogen and lyophilized for 48 h.
Preparation of physical mixture
The physical mixtures (PMs) were prepared using the
molar ratio of bCD and DPS by simply mixing the two
compounds for 2 min.
Other important experiments include: T1 measurement,
which is directly related to the relaxation phenomenon
[12]; the DOSY experiment, where the molecular diffusion
in solution is a phenomenon related to the molecular
dynamics in biological and chemical systems [13]; the
ROESY experiment, which is widely applied for structural
elucidation of guest:CD inclusion complexes, which are
done through the internuclear NOE enhancement measures
NMR spectroscopy experiments
All experiments with liquid samples were run on a Varian
INOVA-500 spectrometer (BO = 11 T), operating at
500 MHz for 1H, keeping the temperature at 297.6 0.1 K.
The chemical shifts were referenced against the HOD
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J Incl Phenom Macrocycl Chem (2013) 75:77–86
79
resonance (d = 4.67 ppm). The samples were prepared by
dissolving of 2–4 mg of the complex in approximately
0.6 mL of D2O. The data were acquired using standard
Varian software and processed using the program VNMR
inferred that the guest molecule was inside the cavity.
Thus, the chemical displacement of the CD signals induced
by the presence of the guest is a first evidence of its
inclusion in the CD cavity [10]. The protons of DPS and
bCD and the NMR spectra of DPS, bCD and the inclusion
complex DPS:bCD were illustrated in Fig. 1.
The chemical shifts of the main protons of each mole-
cule and their shifts in the complex are summarized in
Tables 1, 2.
1
of the equipment. The conditions to obtain the H NMR
spectra were PW = 6.1 s At = 3.3 s and D1 = 3.0 s. The
accumulated number of transients (nt) was 32 scans and
Lb = 0.2 Hz.
DOSY
According to Greatbanks and Pickford [17], when Dd
H3 [ Dd H5 the inclusion of the guest molecule inside the
cavity is partial and when Dd H3 B Dd H5 the guest mol-
ecule is included more deeply inside the cavity. As it is
observed in Table 1 one can conclude that DPS is totally
included in the CD cavity due to the high affinity between
the rings of DPS with the hydrophobic environment of this
cavity. Also, in Table 1, we observe that even though all
protons have Dd when DPS is included in the cavity of CD,
the signals of the protons localized in the inner cavity of CD
(H3 and H5) undergo the strongest shift [18]. One inter-
esting characteristic that can be observed is that all the bCD
protons had a variation on their chemical shifts. This fact
can be explained by the strong intermolecular interaction of
the drug and its high hydrophobicity, what leads the
encapsulated and the free drug not only interact with the
protons of the bCD cavity but also with its external protons.
Also, as we have seen in other studies, the –SO2 group of
DPS interacts with the hydroxyl group of bCD (Table 3).
The pulse sequence used for the DOSY experiments was
gradient compensated stimulated echo with spin lock
(DOSY GCSTESL). In all the analyzes 25 different pulsed
gradient amplitudes were used, D1 = 6.1 s, At = 3.3 s,
nt = 32, and Lb = 0.2 Hz.
T1 measurements
1
The samples were prepared as usual. For H-NMR, a 90°
pulse was typically of 15 ls, and the recycling time was set
to 15 s. Longitudinal relaxation times were obtained by the
conventional inversion-recovery method.
ROESY
ROESY experiments were carried out using the parameters
At = 1.0 s; D1 = 3.0 s; nt = 128 scans; Lb = 1.0 Hz. It
a sequence of 180°–90° sel.—spin lock-FID pulses was
applied with a mixing time of 500 ms, FIDs acquired
through the sequence of 90° sel.—spin lock-FID pulses. A
modulator generated the selective pulses and automatically
attenuated the power and duration of the pulse.
Diffusion ordered spectroscopy
DOSY is an important NMR technique that gives the dif-
fusion coefficients of different molecules in only one
experiment. The diffusion coefficients (D) supply impor-
tant information on molecular organization and phase
structure. This technique is non-invasive and can provide
individual multi component translational D with good
precision. The sequence used was gradient compensated
stimulated echo spin lock (GCSTESL), which is adequate
when there is no exchange effect and modest gradients are
enough for the acquisition. After correction of the base line
and selection of the points, the D were processed auto-
matically and the value of each D was calculated as the
average of all the listed coefficients. The guest population
(p) involved in the complexation was calculated from the
observed D of each component in the complexed and in the
free form through Eqs. 1–3 [19, 20].
13C-CPMAS
All 13C-CPMAS spectra of lyophilized samples, PM, DPS
and bCD were run on a Bruker 300 MHz, at 298 K and
10 kHz.
Results and discussion
1H-NMR
In this experiment, the behavior of the chemical shifts of
the protons inside the cavity was observed. Thakkar and
Demarco [11] initiated NMR studies of CD complexes
observing changes in the chemical displacements of the H3
and H5 protons inside the cavity of aCD in the presence of
an aromatic substrate, due to the anisotropic effect of the
aromatic ring. Since the NMR signals of the external H1,
H2 and H4 protons did not show any variation, they
Dobserved ¼ pfree Dfree þ pcomplexed Dcomplexed
where
ð1Þ
pfree þ pcomplexed ¼ 1
Then
ð2Þ
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J Incl Phenom Macrocycl Chem (2013) 75:77–86
Fig. 1 The molecular structures of a DPS and b bCD; 1H NMR partial spectrum of c DPS protons and d bCD protons at 500 MHz, in D2O and
1
297.6 K; e the H NMR spectra of bCD:DPS inclusion complex in aqueous medium at the same conditions
absence bCD; pcomplexed is the completely complexed DPS
pfree ¼ 1 ꢁ pcomplexed
ð3Þ
population and Dcomplexed is the completely complexed
DPS diffusion coefficient. Substituting Eq. 3 in 1,
considering that the completely complexed DPS diffusion
Dobserved is the DPS diffusion coefficient with bCD in
the medium; Dfree is the DPS diffusion coefficient in the
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J Incl Phenom Macrocycl Chem (2013) 75:77–86
81
Table 1 1H NMR chemical shifts of bCD protons in D2O and their
the D of DPS in presence of bCD decrease approximately
to the same value as that of bCD alone indicating that the
drug is located inside the bCD cavity. In Fig. 2, it is
observed a bi-dimensional plot of the data obtained from
DOSY experiment from DPS, bCD and the DPS:bCD
inclusion complex. The plot of each data has as axes the
chemical shifts and the D values. Analyzing this figure, we
can observe that the D of the DPS protons is differently
located in the 2D-plot when bCD is present.
change due to the presence of DPS (Dd = dcomplexed - dfree) obtained
1
1
from the inclusion complex H NMR spectra and the bCD H NMR
spectra alone
H
dbCD
dDPS:bCD
D(dDPS:bCD - dbCD)
H1
H2
H3
H4
H5
4.961
3.551
3.856
3.475
3.757
4.922
3.512
3.784
3.416
3.678
-0.039
-0.039
-0.072
-0.054
-0.079
T1 measurement
Table 2 1H NMR chemical shifts of DPS protons in D2O and their
change due to the presence of bCD (Dd = dcomplexed - free) obtained
from the inclusion complex H NMR spectra and the DPS H NMR
spectra alone
The application of the B1 field at the resonance frequency
results in a lowering of the magnetization in the z direction
owing to the energy absorption and the conversion of some
?1/2 spins into -1/2 spins. This relaxation returns the
system to equilibrium with time constant T1, called spin–
lattice or longitudinal relaxation. The major source of these
magnetic fields is the magnetic nuclei in motion which
depends on the molecular surroundings. Therefore, longi-
tudinal relaxation times (T1) give information about the
nucleus mobility in solution and the interaction between
host and guest molecules [21].
d
1
1
H
dDPS
dDPS:bCD
D(dDPS:bCD - dDPS)
H10
H20
6.731
7.519
6.690
7.458
-0.039
-0.061
Table 3 Free and complexed DPS and bCD diffusion coefficients,
and percent values of the DPS population complexed with bCD
obtained from the DOSY experiment using the pulse sequence
GCSTESL and performed at 500 MHz, 297.6 K in D2O
The spin–lattice T1 were measured for free and com-
plexed DPS and bCD hydrogens. The values for each
sample are summarized in Tables 4, 5. One can observe
that all T1 values decrease in the inclusion compounds
approximately to the same value as that of bCD alone,
same observed by DOSY experiment, indicating that the
drug is located inside the bCD cavity, and so, it becomes
with the same behavior as the host. Grillo et al. [22]
showed that T1 decreases of the host and guest are strong
evidence of the interaction between both molecules.
Sample
Molecule
D (910-10 m2/s)
pcomplexed
bCD
bCD
DOH
DPS
DOH
DPS
bCD
DOH
3.2 0.3
14.8 0.3
5.2 0.3
17.2 0.6
3.0 0.1
2.6 0.1
17.1 0.3
84.6 %
DPS
DPS:bCD
ROESY-1D
coefficient is approximately the same as the completely
complexed coefficient of bCD and assuming that the
observed bCD diffusion coefficient is almost the same as
when it is in its free form.
The ROESY experiment in its 1D version with selective
pulses leads to a direct, fast and easily quantified analysis
[23]. The ROESY spectrum provided information about
which bCD proton has an intermolecular correlation when
the DPS H10 and H20 protons were selectively irradiated.
The spectra are in Figs. 3, 4. Analyzing both figures, we
observe one can conclude that the H10 proton is deeply
located in the cavity of CD because when it was irradiated,
the experiment generated a strong signal in all CD protons.
These results are also indicative of a high association
constant between the DPS and the bCD [24].
DbCD complexed ꢂ DbCD observed free ꢂ DbCD free
Substituting Eq. 4 in 1:
ð4Þ
À
Á
Dfree ꢁ Dcomplexed
À
Á
pcomplexed
¼
ð5Þ
Dfree ꢁ DbCD observed
The diffusion coefficients and percentages of the DPS
population complexed with bCD are given in Table 5 and
the NMR spectra are shown in Fig. 5. It can be observed
that the values of the D for HOD, bCD and the DPS
population are quite distinct and their magnitudes are
coherent, since D is directly related with the molecular
weight of each molecule. Moreover, one can observe that
13C cross polarization magic angle spinning NMR
The inclusion complex of DPS:bCD were also investigated
by solid-state 13C-CPMAS NMR spectroscopy. This
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J Incl Phenom Macrocycl Chem (2013) 75:77–86
Fig. 2 Bi-dimensional plot of
DOSY/NMR spectra of a DPS;
b bCD; c DPS:bCD inclusion
complex obtained from the
pulse sequence GCSTESL with
25 different pulsed gradient
amplitudes, D1 = 6.1 s,
At = 3.3 s, nt = 32, and
Lb = 0.2 Hz (500 MHz; D2O;
297.6 K)
Table 5 Values of longitudinal relaxation times (T1, s) of bCD
hydrogens isolated and in presence of DPS in the inclusion complex
obtained by the conventional inversion-recovery method
Table 4 Values of longitudinal relaxation times (T1, s) of DPS
hydrogens isolated and in presence of bCD in the inclusion complex
obtained by the conventional inversion-recovery method
Proton
T1bCD (s)
T1DPS:bCD (s)
Proton
T1DPS (s)
T1DPS:bCD (s)
H1
H3
H5
H4
1.2 0.1
1.56 0.13
0.63 0.03
0.91 0.06
0.73 0.07
1.48 0.07
0.39 0.03
0.81 0.04
H10
H20
2.78 0.54
3.11 0.17
1.02 0.16
1.73 0.22
technique allows distinguishing between the free host and
the inclusion complex, since the chemical environment
chemical shift patterns are different [25]. Therefore, one
can obtain the spectra of DPS, crystalline and lyophilized
free bCD, their PM and their lyophilized complex.
between these two species is different and as result the 13
C
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J Incl Phenom Macrocycl Chem (2013) 75:77–86
83
Fig. 3 ROESY-1D spectrum of
DPS:bCD inclusion complex
obtained when the H10 proton at
6,731 ppm of DPS was
selectively irradiated, showing
the NOE effects in the bCD
hydrogens signals with mixing
time of 0.5 s (500 MHz; D2O)
Fig. 4 ROESY-1D spectrum of
DPS:bCD inclusion complex
obtained when the H20 proton at
7,519 ppm of DPS was
selectively irradiated, showing
the NOE effects in the bCD
hydrogens signals with mixing
time of 0.5 s (500 MHz; D2O)
The use of 13C-CP/MAS NMR in CD characterization
provides information on the molecular organization at
shorter distance scales [26]. The comparison of the
lyophilized and non-lyophilized bCD spectra is necessary
because some changes in their pattern can occur when one
compares the spectrum of the isolated molecules with the
inclusion compound due to the freeze-drying process,
which leads to amorphization of its structure, with no
indication of the host–guest interaction. The carbon reso-
nances of the spectra of bCD were assigned as previous
reported [18]. Figure 5 shows the attributions of each
carbon in the molecule of DPS and the 13C-CP/MAS NMR
spectra of DPS, non freeze-dried and freeze-dried bCD, the
PM and the suggested inclusion compound of DPS:bCD
(Fig. 6).
larger than in the PM. Also, peak broadening occurs in the
inclusion complex spectrum. Both facts suggest that DPS is
encapsulated into the CD cavity. Moreover, it is evident
that the PM spectrum is a combination of the spectrum of
bCD and DPS and no interaction occurs.
Therefore, in view of all results exposed above, we can
suppose that the inclusion compound DPS:bCD present the
following structure, where the aromatic ring of DPS is
located inside the bCD cavity.
Conclusions
In summary, NMR spectroscopy was applied to charac-
terize all the substances and the complex between DPS and
bCD. First, a suggested inclusion compound of DPS:bCD
was prepared successfully by a modified co-precipitation/
freeze-drying method in a 1:1 molar ratio. Also, its PM was
prepared in the same molar ratio in such a way so that one
Chemical shifts of each carbon of bCD, DPS, PMs and
complex are in Tables 6, 7, and 8.
Upon analysis of these spectra and tables, one can
observe that the Dd when DPS is complexed with bCD is
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Fig. 5 a Attributions of each
carbon in the molecule of DPS.
b 13C-CP/MAS NMR spectra of
DPS. c 13C-CP/MAS NMR
spectra of nature bCD (non
freeze-dried) and e freeze-dried
bCD (10 kHz, 298 K) and
d 13C-CP/MAS NMR spectra of
PM and f inclusion compound
of DPS:bCD (10 kHz, 298 K)
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J Incl Phenom Macrocycl Chem (2013) 75:77–86
85
could compare the interaction between both molecules by
the two methods. The data obtained by the NMR tech-
niques clearly indicate the formation of the inclusion
compound. In simplest experiment, 1H-NMR, the presence
of both molecules induces strong chemical shifts in the
protons H3 and H5. Also, according to Greatbanks and
Pickford [17], as Dd H3 B Dd H5 the DPS molecule is
included more deeply inside the cavity. In solution, the
techniques of DOSY and T1 indicates a high association
constant between host:guest, because the D and the T1 of
DPS became similar in magnitude to those of D and T1 of
CD. Moreover, DOSY provide a percentage of association
of 84.6 %, indicating the only approximately 15.4 % of
DPS molecules are not interacting with bCD. The ROESY
results confirm how the drug molecule is spatially located
inside the bCD cavity, i.e., the aromatic ring is located
inside the cavity with its protons H10 and H20 interacting
with the CD protons, because in the ROESY spectra is
observed that the proton from the aromatic region of DPS
present correlations with the protons from the bCD cavity.
The results of 13C-CPMAS also confirm that there are
interactions between the two components in the solid-state,
not only by the induced chemical shifts observed, but also
by the differences presented in the spectrum of the inclu-
sion complex and the PM, in which no chemical shifts
occurred. In the second part of this work, the DAP:bCD
inclusion compound was characterized by other important
techniques, infrared spectroscopy, differential scanning
calorimetry, thermal gravimetric analysis and X-ray dif-
fractometry. Also, the stoichiometry of this complex was
determined by a job plot. The stability constant and the
thermodynamics properties were obtained by fluorescence
spectroscopy.
Fig. 6 Suggested structure of the inclusion compound DPS:bCD
Table 6 13C-CP/MAS NMR chemical shifts of bCD non-freeze
dried and their changes in the presence of DPS (Dd = dPM - dfree
)
C
dbCD
dDPS:bCD - PM
D(dDPS:bCD - dbCD)
C1
102.5
73.6
81.6
63.7
102.3
73.6
81.5
63.8
0.2
0
C2,3,5
C4
0.1
C6
-0.1
Table 7 13C-CP/MAS NMR chemical shifts of bCD freeze dried and
their changes in the presence of DPS (Dd = dcomplexed - dfree
Acknowledgments The authors gratefully acknowledge the finan-
cial support from CAPES, ISP Technologies Inc. for supplying the
)
ˆ
bCD and the technicians Sonia Fanelli and Anderson S. Pedrosa for
C
d
dDPS:bCD
D(dDPS:bCD - dbCD - FD)
bCD - FD
their assistance with the NMR work, and Guilherme L. Alexandrino
with his help to optimize the suggested structure of the inclusion
compound.
C1
102.5
73.7
81.4
63.8
106.4
76.5
84.9
64.1
4.4
2.8
3.5
0.3
C2,3,5
C4
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d
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C
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- PM-dbCD
)
- PM
C10
C20,40 130
C30
152.8 153
130.2
115.5 115.2
0.2
0.2
155.5
133.1
118.6
2.7
3.1
3.1
-0.3
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