Insights into the coordination mode of quercetin with the Al(iii) ion from a combined experimental and theoretical study

Article abstract of DOI:10.1039/c4dt00212a

Combining potentiometric, spectroscopic and theoretical DFT computations we have studied the formation of the Al(iii)-quercetin complex in ethanol solution. The possible complexation sites have been considered on the basis of all the experimental and theoretical tools used. Results supported proposing a 1:1 neutral complex and the possibility to have different isomers in solution.

Full text of DOI:10.1039/c4dt00212a

View Article Online
View Journal
Dalton
Transactions
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: E. furia, T. Marino
and N. Russo, Dalton Trans., 2014, DOI: 10.1039/C4DT00212A.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/dalton

Page 1 of 7
Dalton Transactions
View Article Online
DOI: 10.1039/C4DT00212A
Dalton Transactions
RSCPublishing
ARTICLE
Insights on the coordination mode of quercetin with
Al(III) ion from a combined experimental and
theoretical study
Cite this: DOI: 10.1039/x0xx00000x
Emilia Furia,*
a Tiziana Marinoa and Nino Russoa,b
Received ,
Accepted
Combining potentiometric, spectroscopic and theoretical DFT computations we have studied the
formation of Al(III)ꢀquercetin complex in ethanol solution. The possible complexation sites have been
considered on the basis of all the used experimental and theoretical tools. Results agree in proposing a
1:1 neutral complex and the possibility to have different isomers in solution.
DOI: 10.1039/x0xx00000x
www.rsc.org/
experimental conditions gives stoichiometric ratio of 1:2, metal:
ligand.23,24 Finally, the ability of flavonoids to form chelate
Introduction
complexes with a series of metals has been recently briefly
Flavonoids, the most abundant polyphenolic natural antioxidant
compounds, are found in most plants, concentrating in seeds, fruit
skin or peel, bark and flowers, and in a variety of beverages (tea,
coffee, wines and fruit drinks).1 Flavonoids have been shown to have
a variety of beneficial biological effects, including protection of cells
against oxidative stress and antibacterial, antiꢀinflammatory and
vasodilator activities.2ꢀ4 Polyphenolꢀrich diets have been repeatedly
correlated with a low risk of developing cardiovascular diseases and
cancers, the two major causes of mortality in occidental countries.5
Quercetin (3,3’,4’,5,7ꢀpentahydroxyflavone, H5Que), one of the
most common flavonols present in nature (i.e. in grapes, onions,
berries, green veggies and legumes), has attracted the attention of
many researchers due to its biological properties.6ꢀ10 In addition, it is
well known that quercetin may chelate metal ions preventing the
metalꢀmediated generation of damaging oxidizing radicals and
protecting the biological targets against the oxidative stress.11ꢀ14 In
quercetin structure three chelation sites are possible: the 3ꢀhydroxyꢀ
carbonyl, the 5ꢀhydroxyꢀcarbonyl and the 3’,4’ꢀdihydroxyl functions
(Scheme 1).15,16
reviewed.25
Although the presence of these studies, the composition, structure
and complex formation features are not exhaustively investigated
and sometimes contradictory.17ꢀ21
In this work, we have studied the complexation of quercetin with
Al(III) ion in solution by using a combination of experimental
(potentiometric measurements, IR and UV spectra) and
computational (density functional theory) tools in order to attain
structural and electronic properties of the resulting complex.
With respect to previous work on this subject we underline that in
our investigation we use potentiometric and spectrophotometric
measurements in a wide range of pH and first principle computations
on molar complex ratio of 1:1 (metal: ligand) as indicated by the
experimental data and scarcely investigated previously.
The reason for the choice of aluminium cation is essentially due to
the fact that it is third most abundant element in the Earth’s crust and
often enters in the biotic cycle in many different ways.26 The human
exposure to aluminium is not fully explained but it is well known
that it does not serve any essential function in human biochemistry.26
By contrary, Al(III) cation can enter in the brain where persists for
long time and a small increase seems sufficient to produce
neurotoxicity.27 For this reason, the presence of aluminium in the
human brain has been associated to the Alzheimer’s and other
neurodegenerative diseases.28 Chelation therapy with some ligands
has been demonstrated to reduce some causes of aluminium
toxicity.26,28 In this context, it is interesting to explore the ability of a
natural product as quercetin to coordinate the Al(III) ion.
Scheme 1 Chemical structure of quercetin (H5Que)
Experimental and Theoretical details
Previous experimental and theoretical investigations have been
focused on the complexation of Fe(II) and Fe(III)17,18, Cu(II)19 and
Pb(II)20 with quercetin in solution and with different stoichiometric
ratio. Al(III)ꢀquercetin complex has been previously studied at
theoretical and experimental levels in solid phase21 and in solution
combining spectroscopic UV measurement and semiempirical AM1
theoretical method.22 Furthermore, other two joint experimental and
density functional studies concerns the complex in which the
Computational details
Full optimizations in solution without any symmetry restriction have
been carried out at DFT level employing the M052x29 exchangeꢀ
correlation functional coupled with the 6ꢀ31+G(d) basis set for all
atoms. Solvent effects have been described through a continuum
approach by means of the SMD version of the polarizable continuum
model (PCM).30 The dielectric constant of ethanol has been fixed at
24.85. Vibrational frequencies have been computed on each
This journal is © The Royal Society of Chemistry 2013
Dalton Trans.,| 1

Dalton Transactions
Page 2 of 7
VJieowuArrtnicalelONnlainme e
ARTICLE
DOI: 10.1039/C4DT00212A
optimized structure at the same level of theory of the optimizations, relevant data taken in all titrations are reported in Table S1. The
and zero point vibrational corrections have been added to the general equilibrium can be written as follows:
electronic energies. TDꢀDFT approach31 has been used to obtain the p Al3+ + r H5Que ⇄ AlpH−q(H5Que)r(3p−q) + q H+
βpqr (1).
This formulation takes into account the possible formation of simple
(q=r), mixed (q≠r), mononuclear (p=1) and polynuclear (p>1)
species. The most probable p, q and r values and the corresponding
constants βpqr have been obtained by a least squares fitting of the
potentiometric data.41 In the numerical treatments the first three
acidic constants of quercetin, according to equilibria (2ꢀ4) and
reported with the relative standard deviation, have been maintained
invariant:
vertical excitation energies. In these computations different hybrid
and metaꢀhybrid exchangeꢀcorrelation functionals (M052x,29 M0632
and wB97XD33) have been employed.
All the computations have been performed with the Gaussian (G03)
suite of programs.34
Potentiometric measurements
The perchloric acid stock solution and the sodium hydroxide titrant
solutions have been prepared and standardized as previously
described.35,36 A sodium perchlorate stock solution has been
prepared and standardized according to Biedermann.37
Aluminium(III) perchlorate has been prepared and standardized as
reported by Ciavatta and Iuliano.38 All solutions have been prepared
with ethanol. The cell arrangement was similar to that described by
Forsling and Hietanen.39 Ag/AgCl electrodes have been prepared
according to Brown.40 Glass electrodes, manufactured by Metrohm,
have been of the 6.0133.100 type. They acquired, after the addition
of the reagents, a constant potential within 15 min that remained
unchanged within ± 0.1 mV for several hours. The titrations have
been carried out with a programmable computer controlled data
acquisition switch unit 34970 A supplied by Hewlett Packard. The
EMF values have been measured with a precision of ± 10–5 V using
an OPA 111 low−noise precision DIFET operational amplifier. A
slow stream of nitrogen gas has been passed through three bottles
(a−c) containing: a) 1 M NaOH, b) 1 M H2SO4 and c) 0.16 M
NaClO4, and then into the test solutions, stirred during titrations,
through the gas inlet tube. During the EMF measurements, the cell
assembly has been placed in a thermostat kept at (310.1 ± 0.1) K.
H5Que ⇄ H4Queꢀ + H+
H4Queꢀ ⇄ H3Que2ꢀ + H+
H3Que2ꢀ ⇄ H2Que3ꢀ + H+
log Ka1 = −8.40 ± 0.01
log Ka2 = −7.83 ± 0.06
log Ka3 = −7.91 ± 0.09
(2)
(3)
(4)
These constants have been determined by potentiometric
measurements in the same experimental conditions used for the
stability constants evaluation between metal and ligand ions (i.e. in
ethanol as solvent at 310.15 K and in 0.16 M NaClO4). The last two
acidic constants of quercetin have not been considered due to the
experimental pH range (i.e. 1.6ꢀ3.6).
+
The equilibrium constants for AlOH2+, Al(OH)2 and Al(OH)4ꢀ have
been kept fixed during the numerical treatment because they are well
known from the literature.42 Various models have been tested by
adding a single species during the elaboration; the best agreement
has been obtained with the neutral complex Al(H)ꢀ3(H5Que), in
which the metalꢀligand stoichiometry is 1:1 and whose stability
constant, log β1,ꢀ3,1, is −5.79 ± 0.06 (the uncertainty represents 3σ)
according to the general equilibrium (1). As no other species
lowered the minimum, this model has been assumed as the best data
fitting, also in consideration that the standard deviation (σ=0.4) is
comparable with the experimental uncertainty (σ=0.2).
The refined equilibrium constant as previously determined has been
used to represent the distribution of the metal in the different species
(see Fig. 1).
Vibrational spectra
The solidꢀstate IR spectra (in KBr pellets) have been recorded on a
PerkinꢀElmer Spectrum One FTꢀIR spectrometer equipped for
reflectance measurements.
100
%
Al3+
Al(H)ꢀ3(H5Que)
Spectrophotometric measurements
The spectrophotometric measurements have been conducted with a
Varian Cary 50 Scan UV visible Spectrophotometer. Absorbance
values between (250 and 550) nm have been measured each 5 nm.
The temperature of the cell holder has been kept at (310.1 ± 0.3) K
by a Grant circulating water bath. Matched quartz cells of thickness
1 cm have been employed. The absorbance, Aλ, has been recorded to
0.001 units. The formulations of the parameters and the acquisition
of the data have been managed with the aid of a computer connected
to the tool.
50
pH
0
1
2
3
4
5
6
7
8
Fig. 1 Distribution of Al(III) species for CL = 5.10ꢀ3 mol/dm3, CM
=
5.10ꢀ3 mol/dm3
As can be seen from Fig. 1, the proposed complex is formed in
appreciable amounts and none of the hydrolytic species reach a
significant percentage. Information regarding the structure and the
coordination sites of the dissolved metal ion complex cannot be
obtained using the employed experimental method but can be
supplied by high level theoretical investigation.
Following the indications coming from the potentiometric
measurements we have considered the complexes with zero total
charge and with the aluminium ion that retains the esaꢀcoordination
(see Scheme 2).
Results and discussion
A sensitive tool to attain information on the formation and
stoichiometry of metal complexes is potentiometric analysis. This
methodology allows to measure potential difference as function of
ion concentration in solution. The complex formation equilibria
between Al(III) and quercetin has been studied, using ethanol as
solvent at 310.15 K and in 0.16 M NaClO4, by measuring with a
glass electrode the competition of the ligand (H5Que) for the
aluminium (III) and H+ ions. The metal (CM) and ligand (CL)
concentrations, ranged from 0.5 to 5 mM (the ligand−to−metal ratio
varied between 1 and 10). The hydrogen ion concentration has been
varied from 25 mM (pH 1.6) to incipient precipitation of basic salts
which takes place in the range [H+] = 1.6ꢀ0.25 mM (pH 2.8ꢀ3.6)
depending on the specific ligand−to−metal ratio. A summary of the
2 | Dalton Trans.,
This journal is © The Royal Society of Chemistry 2012

Page 3 of 7
Journal Name
Dalton Transactions
View Article Online
DOI: 10.1039/C4DTA00R2T12ICALE
OH
OH
OH
OH
HO
O
O
HO
O
O
3
3
OH
5
O
5
OH
O
a4-5eq
or
a3-4eq
or
a3-4ax
a4-5ax
-H+
+ [Al(H2O)2(OH)2]+
b4ꢀ5eq
b3ꢀ4eq
Fig. 2 M052x optimized structures of b3ꢀ4eq and b4ꢀ5eq complexes
OH
OH
OH
OH
The greater stability is reached when a six membered ring is formed
upon the coordination process. From the obtained structures emerges
that the coordination occurs in a planar arrangement in all the
studied species. In Table 2 are reported the geometrical parameters
involving the coordination of metal ion for all the optimized
structures.
HO
O
O
HO
O
4
-2H+
3
3
O
+ [Al(H2O)3(OH)]+2
5
OH
5
O
b3-4eq
or
b3-4ax
OH
O
b4-5eq
or
b4-5ax
Table 2 Main geometrical parameters of the investigated structures
by using two different protonation states of quercetin. Distances are
in Å and angles are in degrees (°)
Scheme 2 Formation of the investigated Alꢀcomplexes starting from
the considered deprotonated forms of quercetin
Species
H4QueAl(H2O)2(OH)2
The considered complexes include structures in which quercetin is
deprotonated in 3 or 5 positions and with Al ion biꢀcoordinated with
quercetin and surrounded by two water molecules and two OH
groups (see a3ꢀ4 and a4ꢀ5 species in Scheme 2), or deprotonated in
both 3 and 5 positions and linked to the Al(H2O)3(OH) moiety (see
b3ꢀ4 and b4ꢀ5 species in Scheme 2). Since the experimental solution
pH, the complex resulting from neutral ligand has not been
considered. In all cases both the equatorial (a3ꢀ4eq, a4ꢀ5eq and b4ꢀ
5eq, b4ꢀ5eq) and axial (a3ꢀ4ax, a4ꢀ5ax and b4ꢀ5ax, b4ꢀ5ax)
topologies for the OH groups have been considered. The energetic
data are collected in Table 1.
Alꢀ
O3
Alꢀ
O4
Alꢀ
O5
Alꢀ
Ow
Alꢀ
OH
O3ꢀ
Alꢀ
O4
81.7
83.3
ꢀ
O4ꢀAlꢀ
O5
1.896 1.982
1.902 1.957
ꢀ
ꢀ
ꢀ
ꢀ
2.045 1.811
1.999 1.836
ꢀ
ꢀ
a3ꢀ4eq
a3ꢀ4ax
a4ꢀ5eq
a4ꢀ5ax
1.957 1.891 2.026 1.820
1.952 1.882 1.998 1.827
H3QueAl(H2O)3(OH)
88.5
91.0
ꢀ
1.857 1.910
1.860 1.903
ꢀ
ꢀ
ꢀ
ꢀ
1.987 1.787
1.966 1.797
84.4
ꢀ
b3ꢀ4eq
b3ꢀ4ax
b4ꢀ5eq
b4ꢀ5ax
85.2
ꢀ
1.865 1.848 1.987 1.799
1.868 1.838 1.982 1.801
ꢀ
ꢀ
93.2
93.8
Table 1 Total (hartree) and relative (kcal/mol)
energies for the neutral species
In the most stable structure (a4ꢀ5ax) the AlꢀO5 distance is 1.882 Å
while the AlꢀO4 one is 1.952 Å reflecting the fact that the CꢀO5
bond is 1.309 Å versus the 1.273 Å of C=O4 carbonyl bond. This
behaviour is similar in all other studied structures. The O4ꢀAlꢀO5
angle is 91° in a4ꢀ5ax while assumes a smaller value when the
coordination occurs with the oxygen atoms that lie in the same ring
(e.g. 81.7° in a3ꢀ4eq). Since the pH of the experimental solution and
according to the equilibria (3) and (4), we can reasonably
hypothesize that both the O3ꢀH and O5ꢀH groups, that have very
similar pKa (7.83±0.06 and 7.91±0.09), undergo deprotonation. In
this situation it is interesting to further consider the corresponding
complexes b3ꢀ4eq and b4ꢀ5eq even if exhibit a slightly reduced
energetic stability. These two complexes differ in energy by only 0.8
kcal/mol and can be both populated in the experimental conditions.
In order to have further insights on this possibility we have
considered the interconversion process that can occur throughout the
rotation of the Al(H2O)3(OH) fragment around the CꢀO bond (Ψ
angle in Fig. 3). Along this path we have located a transition state
that lies at 5.8 kcal/mol above the lowest minimum (Fig. 3). This
result suggests that the interconversion between to the two b3ꢀ4eq
and b4ꢀ5eq isomers is kinetically possible and both species should
be present in solution.
Species EZPE
ꢁE
H4QueAl(H2O)2(OH)2
ꢀ1650.390618 2.9
ꢀ1650.389227 3.6
ꢀ1650.393320 1.2
ꢀ1650.395214 0.0
a3ꢀ4eq
a3ꢀ4ax
a4ꢀ5eq
a4ꢀ5ax
H3QueAl(H2O)3(OH)
ꢀ1650.387088 5.1
b3ꢀ4eq
b3ꢀ4ax
b4ꢀ5eq
b4ꢀ5ax
ꢀ1650.383435 7.4
ꢀ1650.385786 5.9
ꢀ1650.383394 7.4
Results show that the complex in which the metal is coordinated to
the positions 4 and 5 between the rings A and C (a4ꢀ5ax) is the most
stable.
In the next lying minimum, at 2.9 kcal/mol, the Al ion coordinates to
the C=O moieties in 3 and 4 positions inside of the ring C (a3ꢀ4eq).
The zero charge complexes derived by the deprotonation of both the
3 and 5 OꢀH groups are higher in energy by 5.1 kcal/mol (b3ꢀ4eq)
and 5.9 kcal/mol (b4ꢀ5eq), respectively (see Table 1). The structures
of the two complexes have been reported in Fig. 2.
This journal is © The Royal Society of Chemistry 2012
Dalton Trans.,| 3

Dalton Transactions
Page 4 of 7
View Article Online
ARTICLE
Journal Name
DOI: 10.1039/C4DT00212A
Fig. 4 UVꢀvis spectra of the quercetin 0.1 mM (line 1) and of the
complex formed between quercetin and Al(ClO4)3 0.1 mM (line 2)
Quercetin exhibits a strong absorption band at 368 nm. Upon
addition of Al(ClO4)3 to quercetin in solution (1:1 ratio of Al(III)
salt:H5Que) the UVꢀvis data showed a 60 nm bathochromic (red)
shift in absorbance (of the corresponding peak for quercetin)
indicating that the complexation occurs (Fig. 4, line 2). Moreover an
isobestic point has been observed at 392 nm, confirming the
presence of two species in equilibrium and therefore the formation of
the complex.
In order to obtain further information on the origin of the UVꢀvis
spectra we have computed the excitation energies for quercetin and
the two more probable complexes (a3ꢀ4eq and b4ꢀ5eq) by using
different exchangeꢀcorrelation functionals in the framework of timeꢀ
dependent density functional theory.31 Results are reported in Table
4.
Table 4 Excitation energies (nm) and oscillator strength in
parenthesis for a3ꢀ4eq, b4ꢀ5eq and quercetin in ethanol computed by
using different exchangeꢀcorrelation functionals
a3ꢀ4eq
b4ꢀ5eq
M052x
quercetin
Fig. 3 Potential energy profile for the interconversion process as a
function of the rotation around the CꢀO bond (Ψ angle) between b3ꢀ
4eq and b4ꢀ5eq isomers
396 (0.50)
245 (0.54)
416 (0.63)
251 (0.48)
M06
312 (0.59)
232 (0.49)
The computed and experimental vibrational spectra of metallated
complexes have been reported in Figures S1 and S2 respectively,
while the main stretching modes that can be affected by the complex
formation, are given in Table 3. We underline that the obtained
experimental spectra concern the solid phase while the simulated
ones are referred to the liquid phase. Since our work is mainly
devoted to the complexation process in solution we think that the
comparisons can be regarded with cautions.
438 (0.37)
270 (0.37)
460 (0.55)
261 (0.24)
wB97D
426 (0.58)
251 (0.32)
Exp
350 (0.48)
258 (0.21)
400 (0.50)
247 (0.59)
317 (0.56)
234 (0.51)
429,269
429,269
368,255
For quercetin, although all the employed exchangeꢀcorrelation
functionals well reproduce the experimental data, better agreement
has been found in the M06 values. For this system, the main bands at
255 and 368 nm are due to a HOMOꢀLUMO+1 (42%) and
HOMOꢀLUMO (69%) orbital transition, respectively. In the a3ꢀ
4eq and b4ꢀ5eq species, the two main transitions are originated by
the HOMOꢀ4ꢀLUMO (about 70%) and HOMOꢀLUMO (about
60%) excitations. The M06 excitation energies for the considered
complexes give results closer to the experimental absorption for the
a3ꢀ4eq species, while the other two functionals seem to privilege the
Table
3
Selected calculated and experimental vibrational
frequencies (cmꢀ1) of Al(III)ꢀquercetin complex
Mode
C3ꢀO3
C4ꢀO4
C5ꢀO5
b3ꢀ4eq
1634
b4ꢀ5eq
1576
1582
1540
1390
1371
Exp
1638, 1596, 1579, 1545, 1514, 1374, 1328
Table 3 clearly show that the considered CꢀO vibrational modes in agreement with the b4ꢀ5eq complex. In any case the differences
the b4ꢀ5eq assume values lower than that in the corresponding b3ꢀ between the experimental and theoretical absorption spectra support
4eq complex. Looking at the experimental values in the frequency the possibility that both the a3ꢀ4eq and b4ꢀ5eq isomers can
range that include the CꢀO vibrational modes we note that the 1579, contribute to the experimental UVꢀvis spectrum.
1545 and 1374 cmꢀ1 well fits with the three CꢀO stretching computed Since the presence of the complex (see Fig. 1) at physiological pH
ꢀ
for the b4ꢀ5eq structure.
and the presence of Al(OH)4 hydrolytical species in absence of the
To gain additional insight on the complex formation, we have ligand (see Figure S3) that indicate as the ligand is able to
compared the UVꢀvis spectra of the free and bound quercetin. quantitatively sequester the metal, our results can be related to the
Absorption spectrum of quercetin 0.1 mM in ethanol solution is aluminium toxicity in living organism since highlight the properties
presented in Fig. 4 (line 1).
and the formation process of Al(III)ꢀquercetin complex that can bind
to the DNA affecting its transcription and, consequently, inhibiting
growth of cancer cells.25 In addition, our results can be related also
to the reduction of toxic metal bioavailability, since the formation of
Al(III)ꢀquercetin complex reduces the excess aluminium in diet
thereby reducing the role of the aluminium in neurological
disorders.20,21,25
2
1
Conclusions
4 | Dalton Trans.,
This journal is © The Royal Society of Chemistry 2012

Page 5 of 7
Journal Name
Dalton Transactions
View Article Online
ARTICLE
DOI: 10.1039/C4DT00212A
In this work we have investigated the formation of Al(III)ꢀquercetin
complex in solution by using a combination of experimental
(potentiometric measurements, IR and UV spectra) and
computational (density functional theory and timeꢀdependent density
functional theory) tools. From our results the following conclusions
can be drawn:
7
8
P. Hollman, M. Hertog, M. Katan, Food. Chem., 1996, 57, 43.
A.J. Moreira, C. Fraga, M. Alonso, P.S. Collado, C. Zetller, C.
Marroni, N. Marroni, J. GonzálezꢀGallego, Biochem. Pharmacol.,
2004, 68, 1939.
9
M. Leopoldini, T. Marino, N. Russo, M. Toscano, Theor. Chem.
Acc., 2004, 111, 210.
ꢀ
ꢀ
ꢀ
in the considered pH range only complexes with 1:1
stoichiometric ratio between metal and ligand are possible;
the best fit of the potentiometric data indicates that the
formed species should be neutral;
DFT computations on the possible hydrated complexes
indicate that the preferred complexation site of quercetin
should be the deprotonated 3 and 5 positions of the A and
C ring, respectively. Moreover, the transition between the
a4ꢀ5ax and a3ꢀ4eq requires a low barrier indicating that
both species can be present in solution;
the UVꢀvis experimental and theoretical spectra indicate
the possible coexistence of the two isomers in the ethanol
solution;
at physiological pH quercetin is able to efficiently
sequestrate the aluminium ion.
10
11
12
M. Leopoldini, T. Marino, N. Russo, M. Toscano, J. Phys. Chem.
A, 2004, 108(22), 4916.
I. B. Afanas’ev, A.I. Dorozhko, A.V. Brodskii, V.A. Kostyuk, A.I.
Potapovitch, Biochem. Pharmacol., 1989, 38, 1763.
M. Melidou, K. Riganakos, D. Galaris, Free Radical Biol. Med.,
2005, 39, 1591.
13
14
15
16
B.A. Halliwell, M.C. Gutteridge, Biochem. J., 1984, 219, 1.
G. Minotti, S.D. Aust, Chem. Biol. Interact., 1989, 71, 1.
J.E.N. Dolatabadi, Int. J. Biol. Macromol., 2011, 48, 227.
M. Leopoldini, N. Russo, M. Toscano, J. Agric. Food Chem.,
2006, 54, 3078.
ꢀ
ꢀ
17
18
19
20
A. Torreggiani, M. Tamba, A. Trinchero, S. Bonora, J. Mol.
Struc., 2005, 744, 759.
M. Leopoldini, N. Russo, S. Chiodo, M. Toscano, J. Agric. Food
Chem., 2006, 54, 6343.
Acknowledgements
J. Ren, S. Meng, C.E. Lekka, E. Kaxiras, J. Phys. Chem. B, 2008,
112, 1845.
We gratefully acknowledge Dipartimento di Chimica
e
Tecnologie Chimiche, Università della Calabria and PON R&C
(Programma Operativo Nazionale Ricerca e Competitività
2007–2013) project PON01_00293 “Spread Bio Oil” for
J.P. Cornard, L. Dangleterre, C. Lapouge, J. Phys. Chem. A, 2005,
109, 10044.
financial support. N.R. thanks UAM for Càtedra Dr. Raùl 21
Remigio Cetina Rosado.
A. Ahmedova, K. Paradoska, I. Wawer, J. Inorg. Biochem., 2012,
110, 27.
22
J.P. Cornard, J.C. Merlin, J. Inorg. Biochem., 2002, 92, 19.
L. Dangleterre, J.P. Cornard, C. Lapouge, Polyhedron, 2008, 27,
1581.
Notes and references
23
a Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria,
24
Y.A. Davila, M.I. Sancho, M.C. Almandoz, S.E. Blanco,
Spectrochim. Acta Part A: Mol. And Biomol. Spectros., 2012, 95,
1.
b
P Bucci, Iꢀ87036Arcavacata di Rende, Italy; Departamento de Quimica,
Division de Ciencias Basicas
e Ingenieria, Universidad, Autonoma
MetropolitanaꢀIztapalapa, Av. San Rafael Atlixco No. 186, Col. Vicentina,
CP 09340 Mexico D.F., Mexico. Eꢀmail: emilia.furia@unical.it
Electronic Supplementary Information (ESI) available: The primary data
comprise 4 titrations with 65 data points, and summary of the relevant data
taken in all titrations have been reported in Table S1. The computed and
experimental vibrational spectra of metallated complexes have been reported
in Figures S1 and S2, respectively. The distribution diagram of Al(III) ion in
the hydrolytical species has been reported in Figure S3.
25
M. Symonowicz, M. Kolanek, Biotech. and Food Sci., 2012,
76(1), 35.
26
27
28
29
C. Exley, Environ. Sci.: Processes Impacts, 2013, 15, 1807.
R.A. Yokel, Curr. Inorg. Chem., 2012, 2, 54.
C. Exley, J. Inorg. Biochem., 1999, 76, 133.
Y. Zhao, N.E. Schultz, D.G. Truhlar, J. Chem. Theory Comput.,
2006, 2, 364.
30
31
A.V. Marenich, C.J. Cramer, D. G. Truhlar, J. Phys. Chem. B,
2009, 113, 6378.
See DOI: 10.1039/b000000x/
M.E. Casida, Recent Advances in Density Functional Methods,
Part I, D.P. Chong, Ed.; World Scientific: Singapore, 1995.
Y. Zhao, D.G. Truhlar, Theor. Chem. Acc., 2008, 120, 215.
J.ꢀD. Chai, M. HeadꢀGordon, Phys. Chem. Chem. Phys., 2008, 10,
6615; J.D. Chai, M. HeadꢀGordon, J. Chem. Phys., 2008, 128,
84106.
1
2
K. Herrmann, J. Food Tech., 1976, 11, 433.
C.L.M. Chantal, V.M. France, T. Muriel, S.M. Helene, M.
Jacques, S.W. Marc, Toxicology, 1996, 114, 19.
32
33
3
4
P.C.H. Hollman, M.B. Katan, Food Chem. Toxicol., 1999, 37,
937.
C. Polissero, M.J.P. Lenczowski, D. Chinzl, C.B. Davail, J.P.
Sumpter, A. Fostier, J. Steroid Biochem. Mol. Biol., 1996, 57, 215.
B. Alluis, O. Dangles, Helvetica Chimica Acta, 2001, 84, 1133.
T. Leighton, C. Ginther, L. Fluss, W. Harter, J. Cansado, V.
Notario, Phenolic Compounds in Foods and their Effects on
Health II, 1992, T. Huang, C.T. Ho, C.Y. Lee, Eds.; ACS
Symposium Series 507; American Chemical Society: Washington,
DC, 220.
34
M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A.
Robb, J.R. Cheeseman, J.A. Montgomery, Jr., T. Vreven, K.N.
Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar, J. Tomasi, V.
Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A.
Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R.
Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O.
Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian, J.B.
Cross, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O.
5
6
This journal is © The Royal Society of Chemistry 2012
Dalton Trans.,| 5

Dalton Transactions
Page 6 of 7
ARTICLE
VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C4DT00212A
Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y.
Ayala, K. Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg,
V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O.
Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B.
Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J.
Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I.
Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. AlꢀLaham, C.Y.
Peng, A. Nanayakkara, M. Challacombe, P.M.W. Gill, B.
Johnson, W. Chen, M.W. Wong, C. Gonzalez, J.A. Pople,
Gaussian 03, Revision A.1, Inc., Pittsburgh PA, 2003.
35
36
E. Furia, G. Sindona, J. Chem. Eng. Data, 2012, 57, 195.
E. Furia, D. Aiello, L. Di Donna, F. Mazzotti, A. Tagarelli, H.
Thangavel, A. Napoli, G. Sindona, Dalton Trans., 2014, 43, 1055.
G. Biedermann, Svensk. Kem. Tidsk., 1964, 76, 362.
37
38
39
40
41
L. Ciavatta, M. Iuliano, Ann. Chim., 1996, 86, 1.
W. Forsling, S. Hietanen, Acta Chem. Scand., 1952, 6, 901.
A.S. Brown, J. Am. Chem. Soc., 1934, 56, 646.
P. Gans, A. Sabatini, A. Vacca, J. Chem. Soc., Dalton Trans.,
1985, 6, 1195.
42
E. Furia, G. Sindona, J. Chem. Eng. Data, 2010, 55, 2985.
6 | Dalton Trans.,
This journal is © The Royal Society of Chemistry 2012

Page 7 of 7
Dalton Transactions
View Article Online
DOI: 10.1039/C4DT00212A
TABLE OF CONTENTS
Manuscript ID DT-ART-01-2014-000212
Title: Insights on the coordination mode of quercetin with Al(III) ion from a combined
experimental and theoretical study
%
Al3+
Al(H)-3(H5Que)
pH
Taking into account the importance of aluminium it is interesting to explore the ability of
quercetin to coordinate it.
%