Volumetric and calorimetric study on complex formation of cyclodextrins with aminobenzoic acids

Article abstract of DOI:10.1016/j.mencom.2009.03.021

A volumetric and calorimetric study on the complex formation of α- and β-cyclodextrins with isomeric aminobenzoic acids in water at 298.15 K revealed the noticeable influence of reagent structure on the driving forces and thermodynamic parameters of bindi

Full text of DOI:10.1016/j.mencom.2009.03.021

Mendeleev
Communications
Mendeleev Commun., 2009, 19, 110–112
Volumetric and calorimetric study on complex
formation of cyclodextrins with aminobenzoic acids
Irina V. Terekhova
Institute of Solution Chemistry, Russian Academy of Sciences, 153045 Ivanovo, Russian Federation.
Fax: +7 4932 33 6237; e-mail: ivt@isc-ras.ru
DOI: 10.1016/j.mencom.2009.03.021
A volumetric and calorimetric study on the complex formation of α- and β-cyclodextrins with isomeric aminobenzoic acids in
water at 298.15 K revealed the noticeable influence of reagent structure on the driving forces and thermodynamic parameters
of binding.
Cyclodextrins (CDs) are naturally occurring cyclic oligosac-
charides consisting of six or more glucose units linked by
glycosidic bond. In supramolecular chemistry, they are known
as macrocyclic ligands that are able to form inclusion complexes
with a variety of guest molecules via noncovalent interactions.1,2
CDs are widely applied as non-toxic encapsulating materials
in pharmaceutical, cosmetic and food industries in order to
improve the physico-chemical properties of biologically active
molecules and to prolong their biological activity.3,4
This work is a continuation of our previous studies5,6 devoted
to the complex formation of native and substituted CDs with
para- and meta-aminobenzoic acids (pABA and mABA, respec-
tively). In particular, the binding mode of CDs with ABAs has
been proposed on the basis of 1H NMR data5 and thermo-
dynamic parameters of mABA complexation with β-CD, and
its methylated and hydroxypropylated derivatives have been
obtained.6 The choice of pABA and mABA as guest molecules
was determined by the following. First, pABA possesses a
biological activity and displays therapeutic effect against typhus.
Moreover, it is known as vitamin H1 and used as a UV filter
in sunscreen cosmetics.7,8 mABA is also of great importance in
the synthesis of analgesics, antihypertensives and vasodilators.9,10
Therefore, encapsulated forms of these biomolecules are of
practical significance. Second, pABA and mABA are structural
isomers, consequently, the opportunity to analyze the influence
of position of the functional groups in the aromatic ring on the
complexation process will appear. In addition, the influence
of CD cavity dimensions on the complex formation can be
considered.
The complex formation of CDs with ABA has been studied
by different experimental techniques.11–18 Stability constants of
1:1 inclusion complexes and other thermodynamic parameters
of their formation are listed in Table 1. Our results obtained
previously5,6 are also presented here. More stable complexes
are formed between α-CD and pABA. Probably, principle of
structural complementarity plays an important role and favours
the binding in this case. The insertion of ABA into CD
cavity was observed in all systems under consideration. Binding
is accompanied by negative enthalpy and entropy changes;
however, the ΔcH and ΔcS values obtained by different authors
considerably differ (Table 1). Therefore, in this work, combina-
tion of calorimetric and volumetric methods was employed for
more particular description of CD complex formation with ABA.
The calorimetric measurements can be useful for accurate
calculation of the thermodynamic parameters of binding. The
results of densimetry allow one to obtain information on the
Table 1 Published data on the complex formation of cyclodextrins with aminobenzoic acids.
Complex
lg K
ΔcG/kJ mol–1
ΔcH/kJ mol–1
TΔcS/kJ mol–1
Method
Ref.
α-CD/mABA
1.7
1.8 0.4
–9.9
—
–32.5 0.3
—
–22.6 0.8
—
circular dichroism
1H NMR
18
5
α-CD/pABA
2.8 0.1
–15.9 0.4
–16.0
—
—
—
–49 2
–43.6 0.8
—
—
—
–33
calorimetry
17
18
15
15
5
2.8
–27.6 2.5
circular dichroism
fluorescence
fluorescence
1H NMR
3.0 0.4a (pH 2.0)
3.15 0.08a (pH 3.5)
3.1 0.6
—
—
—
β-CD/mABA
1.8
–10.3
–12.74
–12.23
–10.03
–17.26
—
–8.7 0.3
–68.0
—
–68.0
—
—
—
1.6 1.3
–55.26
—
–57.97
—
—
—
circular dichroism
UV-VIS
18
11
11
11
11
5
2.2b (pH ~1)
2.1b (pH ~1)
1.8b (pH ~7)
2.0b (pH ~7)
1.8 0.3
fluorimetry
UV-VIS
fluorimetry
1H NMR
1.85 0.03a
—
UV-VIS
6
β-CD/pABA
2.7
–15.4
—
–23.4 0.4
—
–8.0 1.3
—
circular dichroism
fluorescence
fluorescence
UV-VIS
18
15
15
12
12
12
12
5
2.4 0.3a (pH 2.0)
2.8 0.2a (pH 3.5)
1.9b (pH ~1)
2.3b (pH ~1)
1.5b (pH ~7)
2.4b (pH ~7)
2.8 0.6
—
—
—
–11.31
–13.51
–8.81
–13.72
—
–70.75
—
–70.75
—
–59.44
—
–61.94
—
fluorimetry
UV-VIS
fluorimetry
—
—
1H NMR
aAt 293 K. bAt 303 K.
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© 2009 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2009, 19, 110–112
Table 2 Thermodynamic parameters of the complex formation of cyclodextrins with aminobenzoic acids in water at 298.15 K.
Densimetry
Calorimetry
Complex
VF,c(ABA)/ ΔVF,c(ABA)/ VF,c(CD)/
ΔVF,c(CD)/
lg K
lg K
ΔcG0/kJ mol–1
ΔcH0/kJ mol–1
TΔcS0/kJ mol–1
cm3 mol–1 cm3 mol–1
cm3 mol–1 cm3 mol–1
α-CD/mABA 1.7 0.2
82.3 1.9 –11.5 0.9
595.0 0.5 –8.3 0.7
732.4 0.9 27.2 0.6
1.8 0.2
1.8 0.1
–10.3 1.1
–10.2 0.5
–21.9 0.6
–2.2 0.1
–11.6 1.5
8.0 0.8
β-CD/mABA 1.8 0.2 111.8 0.9
α-CD/pABA 2.8 0.2 93.7 0.8
β-CD/pABA 2.8 0.2 117.4 0.8
18.0 0.8
–9.1 0.9
14.6 0.9
596.5 0.5 –6.8 0.6
728.1 1.0 22.9 0.5
3.2 0.2
2.9 0.1
–18.3 1.1
–16.6 0.6
–41.0 0.4
–14.2 0.2
–22.7 1.6
2.4 0.1
nature of solute–solute interactions and structural rearrangements
in solution occurring upon inclusion complex formation. Note
that densimetry is not so common for investigation of CD
complexation as spectroscopy, calorimetry, solubility and other
methods. As a consequence, the number of volumetric studies
of CD complex formation is limited in the literature.19
The densities of solutions were measured at 298.15 0.01 K
using a vibrating-tube digital densimeter (DMA 4500 model,
Anton Paar, Austria) with a precision of 1×10–5 g cm–3. The
densimeter was calibrated with dry air and freshly prepared
twice distilled water. The operation of the densimeter was
checked by measuring the density of aqueous solutions of NaCl
(Fluka, > 99.99%). A good agreement with the literature data20
was detected. All the solutions were prepared by weight using
twice distilled water and commercial mABA (Aldrich), pABA
(Fluka), α-CD (Fluka) and β-CD (Fluka). α-CD and β-CD
were stable crystal hydrates with water contents of 10 and
12.3%, respectively.
tions. The thermodynamic parameters of complex formation
summarized in Table 2 are in a good agreement with the data
reported by Lewis et al.17 and Harata18 (Table 1). The observed
in the other cases discrepancy can be caused by the different
experimental conditions (temperature, pH).
It was detected in our previous works5,6 and in the litera-
ture11–18 that 1:1 complex formation of CDs with ABA takes
place. This process is described by the equation:
CD + ABA
CD·ABA.
(3)
According to the Young rule,21 for 1:1 complexation mode, the
VF, which is separately determined for each reagent, contains
the contributions from volumes of free and complexed species
presented in the system:
VF = (1 – ac)VF,f + acVF,c
,
(4)
where ac is the fraction of the complexes; VF,f and VF,c are
the volumes of free and fully complexed species, respectively.
Contributions due to ionization/protonation of ABA were con-
sidered as negligible in the concentration ranges under study
since the measured pH of solutions (pH 3.6 for pABA and
pH 3.9 for mABA) corresponded to the predominant existence
of neutral (or zwitterionic) structures of ABA.22,23 CDs do not
dissociate under experimental conditions.1,2
The apparent molar volumes (V ) were calculated on the
F
basis of the following relation:
VF = M/d + 103(d – d0)/mdd0,
(1)
where M is the solute molar mass; m is the molality; d0 and d
are the densities of solvent and solution, respectively. For binary
systems (CD + H2O) or (ABA + H2O), water was the reference
solvent with d0 = 0.99704 g cm–3. For ternary systems (CD +
+ ABA + H2O), the reference solvents were aqueous solutions
of CD or ABA. The two sets of experiments were carried out.
The apparent molar volumes of CDs [VF (CD)] were determined
at constant CD concentration (0.005 mol kg–1) and variable ABA
concentration (0–0.04 mol kg–1) and vice versa the apparent
molar volumes of ABA [VF (ABA)] were determined at constant
ABA concentration (0.005 mol kg–1) and changeable CD con-
centration (0–0.08 mol kg–1). As an example, concentration
dependences of VF are plotted in Figure 1.
Enthalpies of CD solution in pure water (ΔHw) and in aqueous
solutions of ABA at concentrations of 0–0.04 mol kg–1 (ΔH)
were determined at 298.15 K using the isothermal ampule
calorimeter of solution. The calorimeter was described pre-
viously.6 Enthalpies of transfer of CDs from water to aqueous
solutions of ABAs (ΔtrH) were get by the following way:
Some mathematical rearrangements of equation (4) result in
VF = (VF,f + KVF,cm)/(1 + Km),
(5)
where K is stability constant of 1:1 complexes and m is the
solute concentration. Analytical solution of equation (5) by
nonlinear least-squares fitting gives VF,c for each of reagents
and K, the values of which are summarized in Table 2. The
values of VF,f preliminarily determined for binary systems
(CD + H2O) and (ABA + H2O) were 603.3, 705.2, 102.8 and
93.8 cm3 mol–1 for α-CD, β-CD, pABA and mABA, respec-
tively. They are in a good agreement with values reported by
Spildo et al.24 for α-CD (604 2 cm3 mol–1), Milioto et al.25 for
β-CD (706.5 0.3 cm3 mol–1) and Hyncica et al.26 for pABA
(103.61 cm3 mol–1). No partial molar volumes of mABA were
found in the literature.
The change in the molar volumes (ΔVF,c) induced by complex
formation can be calculated as
ΔtrH = ΔH – ΔHw.
(2)
ΔVF,c = VF,c – VF,f
.
(6)
Concentration dependences of ΔtrH are presented in Figure 2.
K and ΔcH were calculated on the basis of these dependences
using a nonlinear least-squares method. Subsequently, ΔcG and
ΔcS were evaluated from the well-known thermodynamic equa-
According to the above experiment, the values of ΔVF,c were
estimated for CDs and ABAs (Table 2).
It can be seen in Table 2 that transfer of mABA and pABA
from water to aqueous solutions of α-CD is accompanied by
pABA
0
–4
0
–10
–20
–30
–40
725
720
715
710
705
100
95
β-CD/mABA
β-CD/pABA
pABA
mABA
α-CD/mABA
α-CD/pABA
90
–8
mABA
85
80
–12
0.00 0.02 0.04 0.06
mα-CD/mol kg–1
0.00 0.01 0.02 0.03 0.04
0.00 0.01 0.02 0.03 0.04
0.00 0.01 0.02 0.03 0.04
mABA/mol kg–1
mABA/mol kg–1
mABA/mol kg–1
Figure 2 Isotherms of binding of ABA with CDs.
Figure 1 Concentration dependences of VF.
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Mendeleev Commun., 2009, 19, 110–112
negative volume changes [ΔVF,c(ABA) < 0]. The same character
system is generally entropically driven. Thus, the obtained
results point out that solvent reorganization plays an important
role in β-CD complex formation.
of volume changes was obtained for transfer of α-CD to
aqueous solutions of both mABA and pABA [ΔVF,c(α-CD) < 0].
The opposite behaviour of ΔVF,c was observed for β-CD
complex formation. In these cases, an increase in the apparent
molar volumes of ABA and β-CD was found (Table 2).
The ΔVF,c values can be interpreted on the basis of the
reorganization of solvent (water) molecules during complex
formation.24,25,27–29 It is known that cavity of α-CD or β-CD con-
tains 2 or 6.5 water molecules, respectively, which are partially
or completely replaced by the guest molecules upon binding.30,31
This process gives the positive contribution to the ΔVF,c
values.24,27,28 In addition, complex formation is accompanied by
the partial destruction of hydration shells of ABA and CD.
Restructurization of the hydration shells of the solutes can be
explained using a cosphere overlap model proposed by Friedman
and Krishnan.29 According to this model, hydrophilic–hydro-
Analysis of thermodynamic parameters listed in Table 2
allows one to emphasize the following points. Firstly, complex
formation of CDs with ABA is determined by the position of
the NH2 group. In particular, binding of pABA with both CDs
results in formation of more stable inclusion complexes. Secondly,
the CD cavity dimensions influence only the enthalpy of complex
formation and have no influence on the complex stability.
Binding of ABA with α-CD was found as more enthalpically
favourable.
Finally, the author is grateful to N. A. Obukhova for her
assistance in calorimetric measurements.
References
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,
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As found previously,5 the deeper penetration of ABA into
β-CD cavity takes place. The positive ΔVF,c values (Table 2)
observed for β-CD complex formation are related to release
of more water molecules from β-CD cavity than from α-CD
cavity. This fact is also confirmed by less negative ΔcH and
positive ΔcS obtained for β-CD complexation (Table 2). Note
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hydrophobic interactions, which contribute negatively to ΔVF,c
,
as provided by the cosphere overlap model.29 However, the
positive ΔVF,c values detected for β-CD complex formation
(Table 2) testify that hydrophobic interactions are not the driving
force of β-CD binding with ABA. Comparison of thermodynamic
parameters of β-CD complex formation with isomeric ABA
allows one to note that inclusion of mABA is accompanied by
more intense dehydration and, as consequence, binding in this
Received: 22th July 2008; Com. 08/3187
– 112 –