Microcalorimetric and spectrographic studies on host-guest interactions of α-, β-, γ- And Mβ-cyclodextrin with resveratrol

Article abstract of DOI:10.1016/j.tca.2010.07.011

Thermal effects of inclusion processes of α-, β-, γ- and Mβ-cyclodextrin with resveratrol (RES) in aqueous solutions were determined by isothermal titration calorimetry (ITC) with nanowatt sensitivity at the temperature of 298.15 K. Standard enthalpy changes, stoichiometry and equilibrium constants of the inclusion complexes were derived from the direct calorimetric data utilizing nonlinear simulation. The thermodynamic parameters were discussed in the light of weak interactions between the host and the guest molecules combining with UV spectral message. The results indicate that all of the complexes formed in the aqueous solutions are in 1:1 stoichiometry. The binding processes of α-, β- and Mβ-cyclodextrin with the guest are mainly driven by enthalpy, while that of γ-cyclodextrin with the drug is driven by both enthalpy and entropy.

Full text of DOI:10.1016/j.tca.2010.07.011

Thermochimica Acta 510 (2010) 168–172
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Thermochimica Acta
journal homepage: www.elsevier.com/locate/tca
Microcalorimetric and spectrographic studies on host–guest interactions of
␣-, ␤-, ␥- and M␤-cyclodextrin with resveratrol
Hui Li, Xiangyu Xu, Min Liu, Dezhi Sun∗, Linwei Li∗
College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong Province, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Thermal effects of inclusion processes of ␣-, ␤-, ␥- and M␤-cyclodextrin with resveratrol (RES) in aqueous
solutions were determined by isothermal titration calorimetry (ITC) with nanowatt sensitivity at the
temperature of 298.15 K. Standard enthalpy changes, stoichiometry and equilibrium constants of the
inclusion complexes were derived from the direct calorimetric data utilizing nonlinear simulation. The
thermodynamic parameters were discussed in the light of weak interactions between the host and the
guest molecules combining with UV spectral message. The results indicate that all of the complexes
formed in the aqueous solutions are in 1:1 stoichiometry. The binding processes of ␣-, ␤- and M␤-
cyclodextrin with the guest are mainly driven by enthalpy, while that of ␥-cyclodextrin with the drug is
driven by both enthalpy and entropy.
Received 17 May 2010
Received in revised form 8 July 2010
Accepted 9 July 2010
Available online 16 July 2010
Keywords:
Resveratrol
Cyclodextrin
Isothermal titration calorimetry
Inclusion complex
Microcalorimetry
© 2010 Elsevier B.V. All rights reserved.
1. Introduction
of cyclodextrins is their ability to form host–guest inclusion
complexes with a very wide range of compounds by molecular
Resveratrol (3,5,4ꢀ-trihydroxy-trans-stilbene), a polyphenol, has
been found in a wide variety of about 70 plant species, includ-
ing grapes, mulberries, and peanuts [1], which could protect
against a range of illnesses and diseases, e.g., cardiovascular
diseases [2–4], cancer [5,6], viral attacks [7], neurodegenera-
tive diseases [8] and ageing [9]. Furthermore, it could increase
lifespan [10] and physical activity of diverse species [11,12]. Var-
ious studies have also indicated that resveratrol shows several
interesting biological effects such as antioxidant [13–15], anti-
inflammatory [16] and anti-proliferative activities [17]. However,
due to its low water solubility, resveratrol cannot be used for
oral administration. This limitation could be overcome by the
formation of inclusion complexes of the drug with cyclodextrins
[18].
Cyclodextrins (CDs) are the most prominent host molecules
used in supramolecular chemistry up to now [19,20], whose
molecular structures are shown in Scheme 2 as cyclic oligosaccha-
rides composed of glucopyranose units and can be characterized
by a truncated cone structure with hydrophobic interior and
hydrophilic exterior [21]. They have been used in many fields
such as pharmaceutical industry, food technology, biotechnol-
ogy, cosmetics and catalysis [22–24]. The most notable feature
complexation, so that they can enhance the solubility and stability
of some guest molecule [25–27].
Isothermal titration calorimetry (ITC) is an extremely power-
ful and highly sensitive technique that is capable of determining
the interaction of reacting species in solution and has hitherto
been used with great success in the study of interaction between
biomolecules in dilute aqueous solutions both from thermody-
namic and from kinetics points of view [28]. In a word, it is of
significance to study the interactions of CDs with resveratrol in
aqueous system using the method of ITC. In the present work, heat
effects caused by interactions of several CDs with resveratrol were
determined by ITC and thermodynamic parameters were calcu-
lated based on the calorimetric data and were discussed according
to the weak interactions between the host and the guest molecules.
In order to verify the results acquired from ITC, UV spectra were also
determined and analyzed.
2. Experimental
2.1. Materials
Resveratrol was purchased from Xi’an Sino-Herb Bio-
technology Company and the stated purity was better than
98%, which was dried under reduced pressure at the temperature
of 350 K in order to remove the impurity (mainly ethanol). The
molecular structure of resveratrol is provided in Scheme 1. ␣-
and ␥-CD were obtained from Aldrich Company and were also
∗
Corresponding authors. Tel.: +86 635 8230614; fax: +86 635 8239196.
E-mail addresses: sundezhisdz@163.com, dzsun@eyou.com (D. Sun),
lilinwei@lcu.edu.cn (L. Li).
0040-6031/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.tca.2010.07.011

H. Li et al. / Thermochimica Acta 510 (2010) 168–172
169
2.3. UV–vis spectrum determination
An Hp8453 UV–vis spectrophotometer (USA) was used for
absorbance determination of solutions. The temperature of the
sample was controlled at 298.0 0.1 K. Four kinds of CDs with the
concentration of 4.00 × 10−4 mol L−1 were added into the resvera-
trol solution in which the concentration of resveratrol was always
at 4.34 × 10−5 mol L−1
.
3. Results and discussion
3.1. Thermodynamic data analysis
Scheme 1. Molecular structure of resveratrol.
3.1.1. Analysis process
To evaluate the standard enthalpy of formation for inclusion
complex of drug with cyclodextrin in aqueous medium, ꢀHi◦
apparent equilibrium constants ˇi for overall reactions have been
defined as follows:
,
≥98% pure. ␤- and M␤-CD were purchased from Shanghai Chem-
ical Reagent Company and purified twice by recrystallization in
redistilled water. All of the CD samples were dried under reduced
pressure at 358 K for 24 h prior to use. Double distilled water used
in the experiment was prepared in the presence of basic potassium
permanganate. Mass of each sample was weighed using a Mettler
Toledo AG 135 analytical balance with a precision of 0.01 mg.
M + iL = MLi
[MLi]
[M][L]i
ˇi =
ꢀHi◦
(1)
2.2. Microcalorimetric measurement
where i = 1, 2, 3. In Eq. (1), M or L can represent either guest (Resver-
atrol) or host (CD), so there are five possible reaction models. The
total concentrations of L and M can be obtained according to the
following formulas:
Titration calorimetric measurement was performed by a 201
nanowatt scale isothermal titration microcalorimeter supported
by Thermal Activity Monitor TAM 2277 (Thermometric, Sweden),
which was controlled by Digitam 4.1 software. This instrument
can be electrically calibrated with a precision better than 1% that
was verified by measuring the dilution enthalpy of a concentrated
sucrose solution with the literature method [29]. In the experiment,
the reaction cell and reference cell of the calorimeter were initially
loaded with 500 ␮L resveratrol solution at 5.21 × 10−4 mol L−1 and
750 ␮L pure water, respectively; the titrant solution was injected
into the stirred sample vessel in 30 aliquots of 12 ␮L using a Hamil-
ton syringe controlled by a 612 Lund Pump. The concentrations
of ␣-, ␤-, ␥- and M␤-cyclodextrins as titrants were, respectively,
1.46 × 10−3, 1.43 × 10−3, 1.40 × 10−3 and 8.42 × 10−4 mol L−1. The
interval between two injections was 40 min, which was suffi-
ciently long for the signal to return to the baseline. The system
was stirred at 30 rpm with a gold propeller. All experiments
were performed at the temperature of 298.15 0.01 K and were
started after the baseline became stable so that the heat pro-
duced by stir can be automatically deducted. To deduct the
dilution heats of resveratrol and CD solution, titration experi-
ments were performed for each of CD solution titrated into the
solvent (pure water) and the solvent into resveratrol solution,
respectively. All of the dilution heats were found to be negligi-
ble.
ꢀ
ꢂ
ꢁ
[M]0 = [M] 1 +
ˇi[L]i
(2)
(3)
ꢀ
ꢂ
ꢁ
[L]0 = [L] 1 + [M]
iˇi[L](i−1)
The relationship between the overall equilibrium constants, ˇi, and
the stepwise equilibrium constants, Ki, is given by
ꢃ
ˇi =
Ki
(4)
ꢀHi◦ and ˇi (or Ki) can be obtained by the multi-nonlinear regres-
sion equation analysis with the Ligand Binding program of the
Digitam 4.1 software. By comparing the congruousness between
the simulation curve and the experiment point, the most rea-
sonable result can be obtained as final result. Furthermore, the
standard changes of Gibbs free energy (ꢀG◦) and entropy effect
(TꢀS◦) of the combination can be derived using the following ther-
modynamic formulas [30]:
ꢀGi◦ = −RT ln ˇi
ꢀGi◦ = ꢀHi◦ − TꢀSi◦
(5)
Scheme 2. Molecular structure of CDs.

170
H. Li et al. / Thermochimica Acta 510 (2010) 168–172
Table 1
Thermodynamic parameters of the complexation of host (␣-, ␤-, ␥-, M␤-CD) with guest (RES) in aqueous solution at 298.15 K.
Host
Reaction model
ˇi (L/mol)
ꢀH◦ (kJ/mol)
ꢀG◦ (kJ/mol)
TꢀS◦ (kJ/mol)
␣-CD
␤-CD
␥-CD
M + L = ML
M + L = ML
M + L = ML
M + L = ML
877.24
952.29
−27.18
−26.16
−1.50
−16.80
−17.00
−26.69
−19.89
−10.38
−9.16
25.19
−0.47
4.74 × 104
M␤-CD
3054.10
−20.36
3.1.2. Thermodynamic parameters
As shown by the data in Table 1, the four host–guest complexes
are all in 1:1 stoichiometry (M + L = ML). The cause might be that the
concentrations of CD and resveratrol are rather low in the solution,
so there is little opportunity for the host and the guest to form
complexes in other stoichiometry. From the values of ˇi (=ˇ1), it
could be observed that the inclusion complex of ␥-CD with the drug
is much more stable than those of other CDs with the drug. This
phenomenon can be attributed to the different inner sizes of the
hydrophobic cavity of the CDs. The molecular dimension of ␥-CD is
the largest, so it might be just right for the guest molecule entering
into the cavity of ␥-CD molecule.
It can be seen from Table 1 that the standard formation
enthalpies (ꢀH◦) of all the CD complexes are negative, i.e., the heat
effect is beneficial to the formation of host–guest supramolecu-
lar structure. The negative heat effects include the energy released
by transferring of water molecules from the holes of completely
hydrated CD molecules into the bulk aqueous phase and that caused
by hydrophobic interaction between the CD and the drug molecules
[31,32]. Assuming that the volume of a water molecule is ∼30 a˚ 3,
the number of water molecules that per molecule of ␣-, ␤-, and
␥-CD can accommodate are 6, 9 and 14, respectively [33,34]. It was
proposed [35] that they are not able to develop a full hydrogen
bonded network inside the cavity, probably due to the high cur-
vature of the inside of the cavity. When the water molecules are
released, the hydrogen bonds reform, which leads to a release of
heat. ꢀH◦ is less negative for the inclusion compounds formed by
the drug with ␤-CD and M␤-CD than that formed by the drug with
␣-CD and much negative than that with ␥-CD. This phenomenon
may be caused by the incomplete intramolecular hydrogen-bond
belt in ␣-CD molecule, since one glucopyranose unit is in a dis-
torted position [36]. Consequently, the molecular conformation of
␣-CD can alter to combine with the drug molecule more tightly. So,
binding between the interior of ␣-CD molecule with the hydropho-
bic part of the drug molecule releases a larger amount of energy.
For ␤-CD or M␤-CD molecule, they have smaller curvature inside
their cavity, to which the water molecules can better adapt. All
water molecules are expected to be expelled upon complexation
of both ␤-CD and M␤-CD with the guest. However, the minimum
of the binding enthalpies of ␥-CD with drug can be attributed to
the retention of the water in the inclusion complex cavity allowing
for a ‘looseness’ of the guest molecule fits into the ␥-CD cavity. In
a word, the foregoing trend can be well understood by considering
all of the factors together.
Fig. 1. Variation of heat-flow/electrical power as a function of time, titrant: ␤-CD
(1.43 × 10−3 mol L−1); titrand: RES (5.21 × 10−4 mol L−1).
The relationship between the enthalpy of formation (ꢀH◦i) and the
apparent equilibrium constant (ˇi) can be shown by Eq. (6).
ꢀHi◦ = −RT ln ˇi + TꢀS◦
(6)
The thermodynamic parameters for the resveratrol complexes
with several CDs are listed in Table 1, and a typical calorimetric
titration plot and a typical fitting curve of the binding complex
system are shown in Fig. 1 and Fig. 2, respectively.
The entropy effect (TꢀS◦) of ␣-, ␤-, ␥- and M␤-CD–guest com-
plexes are −10.38, −9.61, 25.19 and −0.47 kJ mol−1, respectively,
which are all negative values except for ␥-CD–drug complex. In
order to explain this tendency, structural factors governing the
entropy effect should be taken into account. As mentioned above,
the drug molecule possesses hydrophobic groups, benzene ring
and hydrocarbyl chain, which can drive water molecules from
the molecular cavity of CD to the bulk solvent, this transport of
water molecules can cause increase in entropy. Furthermore, col-
lapse of the iceberg structure formed by water molecules around
each hydrophobic group also causes the entropy increase when the
hydrophobic groups combine with the CD molecule. If only these
two entropy-increasing factors were considered, formation of CD
Fig. 2. Rate of change in the heat caused by the host–guest interaction versus the
ratio of concentrations [L]/[M]. L and M, respectively, represent ␤-CD and RES, the
points are gotten from experiment and the line is the result of calculated. The con-
centrations of the titrant and the titrand are, respectively, the same as those in
Fig. 1.

H. Li et al. / Thermochimica Acta 510 (2010) 168–172
171
Fig. 3. Influence of CD on the UV–vis spectrum of RES, (a): ␣-CD; (b): ␤-CD; (c): ␥-CD; (d): M␤-CD. Curve (1): aqueous solution of RES at 4.34 × 10−5 mol L−1; Curve (2):
aqueous solution of RES at 4.34 × 10−5 mol L−1 in coexistence with CD at 4.00 × 10−4 mol L−1
.
Table 2
complex with the drug would be an entropy-increasing process.
However, there is an important factor causing entropy decrease,
that is the directly hydrophobic interaction of molecular hole of
CD with the included part of the drug molecule, which makes
negative contribution to entropy. From the values of TꢀS◦, we
can deduce that the former influence surpass the later one for
the interaction of ␥-CD with the drug, while the later influence
become dominant for the interactions of ␣-, ␤- and M␤-CD with
the drug. The values of TꢀS◦ also indicate that the order of the
contribution of entropy to the formation of inclusion complex is
that: ␥-CD–drug > M␤-CD–drug > ␤-CD–drug > ␣-CD–drug, which
is opposite to the tendency of the enthalpy change. This tendency
might be mainly decided by the transfer of water molecules from
molecular cavity of CD to the bulk medium. The larger the inner cav-
ity of CD molecule is, the more the water molecules can be driven
from the host cavity.
The changes in absorbance at the peak wavelength (ꢀA) caused by the CDs at
the concentration about 10 times of the guest concentration, the concentrations of
resveratrol and each of the CDs are 4.34 × 10−5 and 4.00 × 10−4 mol L−1, respectively.
Hosts
␣-CD
␤-CD
␥-CD
M␤-CD
ꢀA
0.160
0.123
0.147
0.116
with a CD, the absorption peak becomes higher at almost the same
wavelength, this indicate that the host–guest inclusion complex is
formed [20]. There is nearly no influence of each of the CDs on the
peak wavelength of the drug (Fig. 3), which means that the inter-
action between the host and the guest is quite weak. The changes
in absorbance at the peak wavelength (ꢀA) caused by the CDs at
the concentration about 10 times of the guest concentration are
shown in Table 2. The value of ꢀA corresponding to the formation
of the ␣-CD complex with the drug is the largest, showing that its
inner surface is most near to the hydrophobic part of the guest, in
other words, association force between ␣-CD and resveratrol is the
strongest. This is in accordance with the largest negative formation
enthalpy value (Table 1).
The values of standard Gibbs free energy changes (ꢀG◦), which
are decided by enthalpy changes as well as entropy changes, indi-
cate that all of the inclusion complexes can spontaneously form in
aqueous solution. Combining with the values of ꢀH◦ and TꢀS◦, we
can deduce that the complexation processes of ␣-, ␤- and M␤-CD
with the drug were shown to be enthalpy favored, while the for-
mation of ␥-CD–drug was synergistically driven by enthalpy and
entropy.
4. Conclusions
3.2. Ultraviolet absorption spectra
Calorimetric measurement for the interactions of ␣-, ␤-, ␥- and
M␤-CD with resveratrol at 298.15 K have shown that all of the sto-
ichiometry of the host–guest complex is in 1:1. The complexation
processes of ␣-, ␤- and M␤-CD–drug are predominantly enthalpy
favored. While ␥-CD–drug is mainly enthalpy and entropy driven.
The UV–vis spectra can be regarded as evidence for the formation
of inclusion complexes.
Fig. 3(a)–(d), respectively, shows the UV spectra of resveratrol
in the presence of ␣-, ␤-, ␥- and M␤-cyclodextrin. From these
figures we can see that the typical absorption peaks of resver-
atrol center at 306 nm, which is in good accordance with that
reported in the literature [18]. When the drug is in coexistence

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H. Li et al. / Thermochimica Acta 510 (2010) 168–172
Acknowledgements
[16] X.H. Shu, H. Li, Z. Sun, M.L. Wu, J.X. Ma, J.M. Wang, Q. Wang, Y. Sun, Y.S. Fu, X.Y.
Chen, Q.Y. Kong, J. Liu, Identification of metabolic pattern and bioactive form of
resveratrol in human medulloblastoma cells, Biochem. Pharmacol. 79 (2010)
1516–1525.
The authors are grateful to the National Natural Science Foun-
dation of China (No. 20773059) for financial support.
[17] B. Billack, V. Radkar, C. Adiabouah, In vitro evaluation of the cytotoxic and
antiproliferative properties of resveratrol and several of its analogs, Cell Mol.
Biol. Lett. 13 (2008) 553–569.
[18] V. Bertacche, N. Lorenzi, D. Nava, E. Pini, C. Sinico, Host–guest interaction study
of resveratrol with natural and modified cyclodextrins, J. Incl. Phenom. Macro.
55 (2006) 279–287.
[19] R. Villalonga, R. Cao, A. Fragoso, Supramolecular chemistry of cyclodextrins in
enzyme technology, Chem. Rev. 107 (2007) 3088–3116.
[20] S.H. Gellman, Introduction: molecular recognition, Chem. Rev. 97 (1997)
1231–1734.
[21] N. Li, L. Xu, Thermal analysis of ␤-cyclodextrin/Berberine chloride inclusion
compounds, Thermochim. Acta 499 (2010) 166–170.
References
[1] P. Saiko, A. Szakmary, W. Jaeger, T. Szekeres, Resveratrol and its analogs:
defense against cancer, coronary disease and neurodegenerative maladies or
just a fad? Mutat. Res. 658 (2008) 68–94.
[2] D. Colin, A. Lancon, D. Delmas, G. Lizard, J. Abrossinow, E. Kahn, B. Jannin,
N. Latruffe, Antiproliferative activities of resveratrol and related compounds
in human hepatocyte derived HepG2 cells are associated with biochemi-
cal cell disturbance revealed by fluorescence analyses, Biochimie 90 (2008)
1674–1684.
[22] A. Avci, S. Dönmez,
A novel thermophilic anaerobic bacteria producing
cyclodextrin glycosyltransferase, Process Biochem. 44 (2009) 36–42.
[23] A. Gunaratne, H. Corke, Effect of hydroxypropyl ␤-cyclodextrin on physical
properties and transition parameters of amylose–lipid complexes of native and
acetylated starches, Food Chem. 108 (2008) 14–22.
[3] D. Delmas, B. Jannin, N. Latruffe, Resveratrol: preventing properties against
vascular alterations and ageing, Mol. Nutr. Food Res. 49 (2005) 377–395.
[4] B. Olas, B. Wachowicz, Resveratrol, A phenolic antioxidant with effects on blood
platelet functions, Platelets 16 (2005) 251–260.
[24] F.B. Sousa, A.M.L. Denadai, I.S. Lula, J.F. Lopes, H.F.D. Santos, W.B.D. Almeida,
R.D. Sinisterra, Supramolecular complex of fluoxetine with ␤-cyclodextrin: an
experimental and theoretical study, Int. J. Pharm. 353 (2008) 160–169.
[25] M.B. Jesus, L.M.A. Pinto, L.F. Fraceto, Y. Takahata, A.C.S. Lino, C. Jaime, E. Paula,
Theoretical and experimental study of a praziquantel and ␤-cyclodextrin inclu-
sion complex using molecular mechanic calculations and 1H-nuclear magnetic
resonance, J. Pharm. Biomed. Anal. 41 (2006) 1428–1432.
[26] H.R. Zhang, G. Chen, L. Wang, L. Ding, Y. Tian, W.Q. Jin, H.Q. Zhang, Study on the
inclusion complexes of cyclodextrin and sulphonated azo dyes by electrospray
ionization mass spectrometry, Int. J. Mass Spectrom. 252 (2006) 1–10.
[27] A.C. Illapakurthy, C.M. Wyandt, S.P. Stodghill, Isothermal titration calorime-
try method for determination of cyclodextrin complexation thermodynamics
between artemisinin and naproxen under varying environmental conditions,
Eur. J. Pharm. Biopharm. 59 (2005) 325–332.
[28] I. Jelesarov, H.R. Bosshard, Isothermal titration calorimetry and differential
scanning calorimetry as complementary tools to investigate the energetics of
biomolecular recognition, J. Mol. Recognit. 12 (1999) 3–18.
[29] G.Y. Bai, Y.J. Wang, H.K. Yan, Thermodynamics of interaction between cationic
Gemini surfactants and hydrophobically modified polymers in aqueous solu-
tions, J. Phys. Chem. B 106 (2002) 2153–2159.
[5] C.S. Yang, J.M. Landau, M.T. Huang, H.L. Newmark, Inhibition of carcinogenesis
by dietary polyphenolic compounds, Annu. Rev. Nutr. 21 (2001) 381–406.
[6] M. Nielsen, R.J. Ruch, O. Vang, Resveratrol reverses tumor-promoter-induced
inhibition of gap-junctional intercellular communication, Biochem. Biophys.
Res. Commun. 275 (2000) 804–808.
[7] V. Krishnan, S.L. Zeichner, Host cell gene expression during human immun-
odeficiency virus type 1 latency and reactivation and effects of targeting
genes that are differentially expressed in viral latency, J. Virol. 78 (2004)
9458–9473.
[8] J.A. Parker, M. Arango, S. Abderrahmane, E. Lambert, C. Tourette, H. Catoire, C.
Neri, Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and
mammalian neurons, Nat. Genet. 37 (2005) 349–350.
[9] C.A. de la Lastra, I. Villegas, Resveratrol as an anti-inflammatory and anti-aging
agent: mechanisms and clinical implications, Mol. Nutr. Food Res. 49 (2005)
405–430.
[10] K.T. Howitz, K.J. Bitterman, H.Y. Cohen, D.W. Lamming, S. Lavu, J.G. Wood,
R.E. Zipkin, P. Chung, A. Kisielewski, L.L. Zhang, B. Scherer, D.A. Sinclair,
Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan,
Nature 425 (2003) 191–196.
[11] J.A. Baur, K.J. Pearson, N.L. Price, H.A. Jamieson, C. Lerin, A. Kalra, V.V. Prabhu,
J.S. Allard, G. Lopez-Lluch, K. Lewis, P.J. Pistell, S. Poosala, K.G. Becker, O. Boss, D.
Gwinn, M. Wang, S. Ramaswamy, K.W. Fishbein, R.G. Spencer, E.G. Lakatta, D. Le
Couteur, R.J. Shaw, P. Navas, P. Puigserver, D.K. Ingram, R. de Cabo, D.A. Sinclair,
Resveratrol improves health and survival of mice on a high-calorie diet, Nature
444 (2006) 337–342.
[12] M. Lagouge, C. Argmann, Z. Gerhart-Hines, H. Meziane, C. Lerin, F. Daussin,
N. Messadeq, J. Milne, P. Lambert, P. Elliott, B. Geny, M. Laakso, P. Puigserver,
J. Auwerx, Resveratrol improves mitochondrial function and protects against
metabolic disease by activating SIRT1 and PGC-1alpha, Cell 127 (2006)
1109–1122.
[13] M. Sengottuvelan, K. Deeptha, N. Nalini, Resveratrol ameliorates DNA damage,
prooxidant and antioxidant imbalance in 1,2-dimethylhydrazine induced rat
colon carcinogenesis, Chem.–Biol. Interact. 181 (2009) 193–201.
[14] S. Fabris, F. Momo, G. Ravagnan, R. Stevanato, Antioxidant properties of resver-
atrol and piceid on lipid peroxidation in micelles and monolamellar liposomes,
Biophys. Chem. 135 (2008) 76–83.
[30] V. Karlsen, E.B. Heggset, M. Sølie, The use of isothermal titration calorimetry
to determine the thermodynamics of metal ion binding to low-cost sorbents,
Thermochim. Acta 501 (2010) 119–121.
[31] D.Z. Sun, L. Li, X.M. Qiu, F. Liu, B.L. Yin, Isothermal titration calorimetry and 1
H
NMR studies on host–guest interaction of paeonol and two of its isomers with
␤-cyclodextrin, Int. J. Pharm. 316 (2006) 7–13.
[32] Q. Zhao, X.Y. Xu, X.J. Sun, M. Liu, D.Z. Sun, L.W. Li, A calorimetric study on
interactions of colchicine with human serum albumin, J. Mol. Struct. 931 (2009)
31–34.
[33] V.J. Smith, N.M. Rougier, R.H. de Rossi, M.R. Caira, E.I. Buján, M.A. Fernández, S.A.
Bourne, Investigation of the inclusion of the herbicide metobromuron in native
cyclodextrins by powder X-ray diffraction and isothermal titration calorimetry,
Carbohyd. Res. 344 (2009) 2388–2393.
[34] M. Nilsson, A.J.M. Valente, G. Olofsson, O. Soderman, M. Bonini, Thermodynamic
and kinetic characterization of host–guest association between bolaform sur-
factants and ␣- and ␤-cyclodextrins, J. Phys. Chem. B. 112 (2008) 11310–11316.
[35] T. Loftsson, M. Masson, M.E. Brewster, Self-association of cyclodextrins and
cyclodextrin complexes, Pharm. Sci. 93 (2004) 1091–1099.
[15] B. Fauconneau, P. Waffo-Teguo, F. Huguet, L. Barrier, A. Decendit, J.M. Merillon,
Comparative study of radical scavenger and antioxidant properties of phenolic
compounds from Vitis vinifera cell cultures using in vitro tests, Life Sci. 61 (1997)
2103–2110.
[36] J. Szejtli, Introduction and general overview of cyclodextrin chemistry, Chem.
Rev. 98 (1998) 1743–1754.