Thermodynamic, IR spectral and X-ray diffraction studies of the "β-cyclodextrin-para-aminobenzoic acid" inclusion complex

Article abstract of DOI:10.1007/s10847-010-9737-0

The inclusion complex with stoichiometric composition 1:1 was formed as a result of intermolecular interactions between para-aminobenzoic acid and β-cyclodextrin. The stability constant of "β-cyclodextrinpara- aminobenzoic acid" inclusion complex at 289,

Full text of DOI:10.1007/s10847-010-9737-0

J Incl Phenom Macrocycl Chem (2011) 69:315–319
DOI 10.1007/s10847-010-9737-0
ORIGINAL ARTICLE
Thermodynamic, IR spectral and X-ray diffraction studies
of the ‘‘b-cyclodextrin-para-aminobenzoic acid’’ inclusion complex
•
Nadiia V. Roik Lyudmila A. Belyakova
Received: 28 October 2009 / Accepted: 11 January 2010 / Published online: 27 January 2010
Ó Springer Science+Business Media B.V. 2010
Abstract The inclusion complex with stoichiometric
composition 1:1 was formed as a result of intermolecular
interactions between para-aminobenzoic acid and
b-cyclodextrin. The stability constant of ‘‘b-cyclodextrin-
para-aminobenzoic acid’’ inclusion complex at 289, 292
and 313 K was calculated by the Ketelar equation. The
influence of temperature on the stability of ‘‘b-cyclodex-
trin-para-aminobenzoic acid’’ inclusion complex was also
examined, and thermodynamic parameters involved in the
complex formation (DG, DH, DS) were calculated. Supra-
molecular complex formation between para-aminobenzoic
acid and b-cyclodextrin was confirmed by X-ray diffraction
and IR spectroscopy studies.
molecules from the inside [4–8]. Solubility, bioavailability,
and stability of various drug molecules can increase due to
its incorporation into the b-CD cavity [4–8].
para-Aminobenzoic acid (p-ABA) is used as an inter-
mediate in bacterial synthesis of folate [9]. p-ABA, as an
antioxidant, provides protection against ozone, smoking,
and other air pollutants which damage cell structures and
membranes through oxidative stress [10, 11]. It has some
therapeutic effect against vitiligo, scleroderma, herpes and
arthritis [9, 12–14]. It was possible to expect that the
therapeutic effect from use of p-ABA as complexes with
cyclodextrins will be enhanced. However the literature data
about conditions of complex formation and its stability are
significantly distinguished [15, 16]. Therefore in this work
interaction between b-CD and p-ABA has been investi-
gated in details by use of UV- and IR-spectroscopy, and
also X-ray diffraction analysis.
Keywords b-Cyclodextrin ꢀ para-Aminobenzoic acid ꢀ
Inclusion complex ꢀ Thermodynamics ꢀ IR spectroscopy ꢀ
X-ray diffraction
Introduction
Experimental
Cyclodextrins (CDs) are cyclic oligosaccharides converted
from starch [1]. b-CD is the most widely used cyclodextrin.
It forms inclusion compounds with organic molecules
which have hydrophobic moieties and suitable geometry
due to hydrophilic exterior and hydrophobic interior of
toroidal b-CD molecule [2, 3]. Organic compounds may
enter partly or entirely into the hydrophobic cavity of b-CD
simultaneously expelling the few ‘‘high-enthalpy water’’
Materials and chemicals
b-CD (from Fluka, purity C 99%), p-ABA (from Merk,
purity C 99%), citric acid, sulfuric acid, sodium hydrox-
ide, disubstituted sodium phosphate (all from Reakhim,
pure analytical) were used without additional purification.
Methods and instruments
UV spectra of p-ABA solutions were recorded in the 220–
350 nm spectral range with a Specord M-40. Quarts cells
with 10 mm pathlength were used. All spectroscopic
measurements were made with temperature-controlled cell
holder and water bath.
N. V. Roik (&) ꢀ L. A. Belyakova
Chuiko Institute of Surface Chemistry of National Academy
of Sciences of Ukraine, 17 General Naumov Str.,
03164 Kyiv, Ukraine
e-mail: roik_nadya@ukr.net
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J Incl Phenom Macrocycl Chem (2011) 69:315–319
pH of p-ABA buffer solutions were measured by an
Ionometer I-120.1.
solution, the values of stability constant were calculated by
the Ketelar relation [17]:
IR spectra of b-CD, p-ABA and inclusion complex
‘‘b-CD-p-ABA’’ were recorded in the frequency range
from 4000 to 1200 cm-1 with a Thermo Nicollet NEXUS
FT-IR spectrophotometer using KBr pelleting.
X-ray diffraction spectra were registered by use of a
diffractometer DRON-4-02 (emission of Cu Ka, k =
1
1
1
¼
þ
;
ð1Þ
A ꢁ Ao
a
aKs½b ꢁ CDꢂo
where A and Ao—p-ABA absorbance with and without b-
CD, respectively; a—the constant which is the difference
between extinction coefficients of ‘‘b-CD-p-ABA’’ com-
plex and p-ABA at the same wave length; Js—stability
constant (binding constant) of ‘‘b-CD-p-ABA’’ complex;
[b-CD]o—the starting concentration of b-CD in a solution.
Good linear relationship (R = 0.997–0.999) between
spectral characteristics of p-ABA and b-CD content in the
coordinates 1/(A - Ao) = f (1/[b-CD]o) was obtained. It
confirms the formation of a 1:1 complex between p-ABA
and b-CD over studied temperature interval. The stability
constants of ‘‘b-CD-p-ABA’’ complex formation at vari-
able temperatures were calculated from the tangent of the
slope of the straight lines (Table 1).
˚
1.54178 A) with nickel filter.
Procedure of study of interaction
between b-CD and p-ABA
Aliquots (on 1 mL) of p-ABA (1.0 9 10-4 mol L-1
)
solution were placed into a 10 mL volumetric flasks and
an appropriate amounts of b-CD solution (1.0 9
10-2 mol L-1) prepared in pH = 3.60 buffer solution were
added. The obtained solutions were diluted up to constant
volume (10 mL) with buffer solution (mixture of 0.2 M
Na2HPO4 and 0.1 M citric acid solutions with pH = 3.60).
The starting concentration of b-CD was varied from 0.0012
to 0.0072 mol L-1. Then the prepared solutions were
shaken at 289, 292 and 313 K for 24 h up to attainment of
equilibrium. The solutions were prepared just before taking
measurements. Twice-distilled water was used for prepa-
ration of aqueous solutions. The reference solutions con-
tained the same concentration of reagents, but no p-ABA.
Complex thermodynamics
The temperature dependence of binding constants was used
for calculation of thermodynamic parameters involved in
the complex formation: changes of the Gibbs free energy
(DG), enthalpy (DH), and entropy (DS) [18]. The values of
the Gibbs free energy change at various temperatures were
found by the van’t Hoff equation [18]:
Procedure of synthesis of inclusion complex
DG ¼ ꢁRT ln Ks:
ð2Þ
of p-ABA with b-CD
The values of entropy and enthalpy changes depending on
the variation of the stability constant with the temperature
were calculated graphically from the intercept and tangent of
the slope, respectively, by use of the equation [18]:
Batches of b-CD and p-ABA were weighed in a 1:1 M
ratio and dissolved singly in twice-distilled water. Then the
b-CD solution was gradually dropped to the p-ABA solu-
tion and continuously stirred with an electromagnetic stir-
rer at 293 K for 24 h. The binary solution was stored at
277 K for 48 h. The white precipitate was filtered, washed
with twice-distilled water and dried in an oven at 333 K for
24 h.
DS DH
ln Ks ¼
ꢁ
:
ð3Þ
R
RT
The obtained thermodynamic parameters are given in
Table 1.
The negative values of DG testify that the complex
formation is a spontaneous and thermodynamically favored
process. Four driving forces for the inclusion of the
‘‘guest’’ molecules into cyclodextrins were proposed [19]
including the hydrogen binding between the hydroxyl
groups of cyclodextrins and the ‘‘guest’’, van der Waals
forces between ‘‘host’’ and ‘‘guest’’ molecules, hydropho-
bic interactions, and the release of ‘‘high-enthalpy water’’
molecules from the inner CD-cavities to bulk water. The
value of negative enthalpy change (Table 1) is typical for
low-energy interactions [19]. As the change of entropy is
also negative, the complex formation is entropically unfa-
vourable [18]. The negative entropy changes are attribut-
able to decrease in translational and rotational degrees of
Results and discussion
Stability constant of ‘‘b-CD-p-ABA’’ complex
It has been known [15, 16] that b-CD produces complexes
with molecular, anionic and cationic forms of p-ABA.
However complex of b-cyclodextrin with uncharged form
of para-aminobenzoic acid is firmer [16]. Therefore com-
plex formation between p-ABA and b-CD was studied in
buffer solutions at pH = 3.60, where p-ABA exists pref-
erably in molecular form. As p-ABA absorbs in the same
interval of waves lengths as complex formed in the
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317
Table 1 Stability constant and
Temperature (K)
Js (L mol-1
)
DG (kJ mol-1
)
DH (kJ mol-1
)
DS (J mol-1 K-1
)
thermodynamic parameters of
‘‘b-CD-p-ABA’’ complex
289
176 28
158 25
97 15
-12.4
-12.3
-11.8
-19.3
-24
292
313
freedom of complex formation molecules as compared
with the free ones on giving more ordered system [19].
Thus, negative values of thermodynamic parameters indi-
cate that complex is formed as a result of p-ABA incor-
poration into the cavity of b-CD.
IR spectral study
Inclusion complex formation may be confirmed by IR
spectroscopy because bands resulting from the incorpo-
rated ‘‘guest’’ molecule are generally shifted or their
intensities are altered.
In the IR spectrum of p-ABA (Fig. 1, curve 1) the valence
vibrations of the N–H bonds in the primary amino group and
the C–H bonds in the aromatic ring with maxima at 3460,
3362, 3231 and 3051 cm-1, respectively, are registered. The
band of valence vibrations of the C=O bond in the carboxyl
group is observed at 1661 cm-1. The absorption bands with
maxima at 1600, 1573 and 1524 cm-1 belong to the valence
vibrations of the C=C bonds in the benzene ring. The
absorption band of the valence vibrations of the C–N bond in
the amino group connected with the benzene ring is
observed at 1310 cm-1. The bands of the deformation
vibrations of the N–H bonds in the amino group and the C–H
bonds in the benzene ring are registered at 1625, 890 cm-1
and 1173, 1131, 844 cm-1, respectively [20].
In the IR spectrum of b-CD (Fig. 1, curve 2) the wide
band is registered with the absorption maximum at
3320 cm-1, which is caused by the valence vibrations of
the O–H bonds in the primary hydroxyl groups (C-6–OH
group) connected by the intermolecular hydrogen bonds or
in the secondary hydroxyl groups connected by the intra-
molecular hydrogen bonds (the C-2–OH group of one
glucopyranose unit and C-3–OH group of adjacent gluco-
pyranose unit) [2]. Also, in the IR spectrum of b-CD the
absorption band with maximum at 2926 cm-1 is observed.
It belongs to the valence vibrations of the C–H bonds in the
CH and CH2 groups. In the region 1400–1200 cm-1 the
absorption bands of the deformation vibrations of the C–H
bonds in the primary and secondary hydroxyl groups of
b-CD (1411, 1368, 1335, 1301, 1246 cm-1), and in the
region 1200–1030 cm-1 the absorption bands of the
valence vibrations of the C–O bonds in the ether and
hydroxyl groups of b-CD (1080 and 1027 cm-1) are reg-
istered. The absorption bands in the region 950–700 cm-1
belong to the deformation vibrations of the C–H bonds and
the pulsation vibrations in glucopyranose cycle.
Fig. 1 IR spectra of p-ABA (1), b-CD (2) and ‘‘b-CD-p-ABA’’
inclusion complex (3)
The IR spectrum of the inclusion complex of b-CD with
p-ABA differs from the IR spectra of p-ABA and b-CD
(Fig. 1, curve 3). The band of the valence vibrations of the
C=O bond in the carboxyl group of p-ABA is shifted to
higher frequency in spectral pattern of the inclusion com-
plex (1676 cm-1). At the same time, the band of the
deformation vibrations of the N–H bonds in the amino
group is shifted to lower frequency—1634 cm-1. The
absorption bands of the valence vibrations of the C–O
bonds in the ether and hydroxyl groups of b-CD are
slightly broadened. Moreover, the absorption bands of the
valence vibrations of the C=C bonds in the benzene ring
are shifted to 1609, 1576 and 1518 cm-1; the peak at
1246 cm-1 in the spectrum of b-CD which belongs to the
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X-ray diffraction study
Diffraction patterns of the ‘‘b-CD-p-ABA’’ inclusion
complex and individual compounds are different. Encap-
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12.39, 19.28 and 20.54 2H in comparison with precursors
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In this work spectrophotometric study of intermolecular
interactions between para-aminobenzoic acid and b-
cyclodextrin was carried out. The complexation behavior
of p-ABA in citric buffer solution has been investigated
with and without b-CD. The Ketelar equation was used to
calculate the stability constant of ‘‘b-CD-p-ABA’’ complex
at 289, 292 and 313 K. The stability constant decreases
from 176 to 97 L mol-1 with increase in temperature.
Calculation of the thermodynamic parameters involved in
the complex formation was made by the van’t Hoff equa-
tion. Negative values of thermodynamic parameters (DG,
DH, and DS) indicate that the complex is formed as the
result of p-ABA incorporation into the cavity of b-CD.
From the results obtained by IR spectroscopy it may be
concluded that vibrations and bends of the included
‘‘guest’’ molecule are restricted due to encapsulation of p-
ABA into the b-CD cavity. Interaction between p-ABA and
b-CD gave rise supramolecular complex with new crys-
talline structure.
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