Cyclic voltammetry and computational chemistry studies on the evaluation of the redox behavior of parabens and other analogues

Article abstract of DOI:10.1590/S0103-50532012000300025

Parabens are antimicrobial preservatives widely used in pharmaceutical, cosmetic and food industries. The alkyl chain connected to the ester group defines some important physicochemical characteristics of these compounds, including the partition coefficient and redox properties. The voltammetric and computational analyses were carried out in order to evaluate the redox behavior of these compounds and other phenolic analogues. A strong correlation between chemical substituents inductive effects of parabens with redox potentials was observed. Using cyclic voltammetry and glassy carbon working electrode, only one irreversible anodic peak was observed around 0.8 V for methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BP), benzylparaben (BzP) and p-substituted phenolic analogues. The electrodonating inductive effect of alkyl groups was demonstrated by the anodic oxidation potential shift to lower values as the carbon number increases and, therefore the parabens (and other phenolic analogues) oxidation processes to the quinonoidic forms showed great dependence on the substituent pattern.

Full text of DOI:10.1590/S0103-50532012000300025

J. Braz. Chem. Soc., Vol. 23, No. 3, 565-572, 2012.
Printed in Brazil - ©2012 Sociedade Brasileira de Química
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Article
A
Cyclic Voltammetry and Computational Chemistry Studies on the Evaluation of the
Redox Behavior of Parabens and other Analogues
Eric de S. Gil,*,a Carolina H. Andrade,a Núsia L. Barbosa,a Rodolpho C. Bragaa and
Sílvia H. P. Serranob
aFaculdade de Farmácia, Universidade Federal de Goiás, 1ª Av. c/ Praça Universitária,
74605-220 Goiânia-GO, Brazil
bInstituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748,
Cidade Universitária, 05508-000 São Paulo-SP, Brazil
Os parabenos são conservantes antimicrobianos amplamente utilizados na indústria
farmacêutica, cosmética e alimentícia. A cadeia alquila ligada ao grupo éster define algumas
características físico-químicas destes compostos, incluindo coeficiente de partição e propriedades
redox.A voltametria e estudos computacionais foram realizados a fim de avaliar o comportamento
redox desses compostos fenólicos e de outros análogos. Uma forte correlação entre os potenciais
redox e os efeitos indutivos dos substituintes químicos dos parabenos foi observada. Usando
voltametria cíclica e eletrodo de trabalho de carbono vítreo, foi observado um único pico de natureza
irreversível, em torno de 0,8 V para metilparabeno (MP), etilparabeno (EP), propilparabeno (PP),
butilparabeno (BP), benzilparabeno (BzP) e análogos fenólicos p-substituídos. O efeito indutivo
eletrodoador de grupos alquila foi demonstrado pela mudança do potencial de oxidação para valores
menos positivos conforme o aumento do número de carbonos e, portanto, o processo de oxidação
dos parabenos (e outros análogos fenólicos) às formas quinonoídicas mostrou forte dependência
do padrão de substituição.
Parabens are antimicrobial preservatives widely used in pharmaceutical, cosmetic and food
industries. The alkyl chain connected to the ester group defines some important physicochemical
characteristics of these compounds, including the partition coefficient and redox properties. The
voltammetric and computational analyses were carried out in order to evaluate the redox behavior of
these compounds and other phenolic analogues.A strong correlation between chemical substituents
inductive effects of parabens with redox potentials was observed. Using cyclic voltammetry and
glassy carbon working electrode, only one irreversible anodic peak was observed around 0.8V for
methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BP), benzylparaben
(BzP) and p-substituted phenolic analogues. The electrodonating inductive effect of alkyl groups
was demonstrated by the anodic oxidation potential shift to lower values as the carbon number
increases and, therefore the parabens (and other phenolic analogues) oxidation processes to the
quinonoidic forms showed great dependence on the substituent pattern.
Keywords: preservatives, electroanalysis, computational chemistry, substituent pattern,
phenolic compounds
Introduction
Their biological properties as antibacterial and
antifungal activity4 increase synergistically if associations
are employed. Thus, while the antimicrobial activity
increases as function of the chain length of the ester
group, the water solubility decreases. As consequence,
the most common preservative system contains 0.3% MP
(methylparaben) and 0.1% PP (propylparaben).5
Parabensarecompoundscommonlyusedasantimicrobials
preservatives in foodstuffs, cosmetics, pharmaceutical and
personal care.1,2 They are esters of p-hydroxybenzoic acid,
with low molecular weight, relatively high lipophilicity, and
are easily absorbed through the skin.3
The use of these preservatives have become very
popular due to their low toxicity, effective activity and
*e-mail: ericsgil@gmail.com

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Cyclic Voltammetry and Computational Chemistry Studies
J. Braz. Chem. Soc.
broad spectra, as well as worldwide regulatory acceptance
and low cost.5,6 Parabens are completely absorbed through
the skin and from gastrointestinal tract, being completely
metabolized and rapidly excreted in the urine.7,8 The
metabolism involves hydrolysis to p-hydroxybenzoic acid
with further conjugation and, none of these compounds or
their metabolites are accumulated in the body.5 Another
interesting property is their antioxidant activity, which
arouses great interest due to parabens´ importance in
biological and industrial processes.9
The alkyl chain of the ester group defines the
lipophilicity of alkyl parabens, which is responsible for
the first step of antimicrobial activity, the cell membrane
penetration.9 Furthermore, the donor character of alkyl
chain have shown some influence on the phenol oxidation
to correspondent quinone.10,11
chloride were purchased from Merck S.A, Vetec Ltda and
Impex Ltda and were of analytical grade.All solutions were
prepared by direct dissolution of the salts on purified water
from Milli-Q plus system (Millipore). Stock solutions of
phenolic compounds in the concentration of 10-2 mol L-1
were prepared using 1:1 (v/v) water:ethanol.
Apparatus
The electrochemical analyses were performed using a
potentiostat/galvanostat μAUTOLAB TYPE III from Eco
Chemie BV coupled to GPES software for acquisition and
treatment of voltammetric data. Glassy carbon electrode
(∅ 2 mm2), Hg/Hg2Cl2,KCl(sat) and platinum wire were used
as working, reference and auxiliary electrodes, respectively.
All pH measurements were made using a combined
glass electrode (type BlueLine; Shott) coupled to a digital
pHmeter (Labmeter) model PHS-3B.
In the light of the great importance of these preservatives,
the quantitative analysis and the investigation of their
physicochemical properties are very useful.
Most of the analytical methods reported in the literature
are based on high performance liquid chromatography
(HPLC) and other chromatographic techniques, which
are very appropriate for quantitative purposes and could
also provide some valuable information about the hydro/
lipophilicity.12,13 However, these techniques are expensive
and time consuming, and cannot provide information
regarding the antioxidant properties.
In spite of the high sensitivity and selectivity of
electroanalytical methods, few studies have been conducted
on the application of voltammetry to establish correlations
between the electrochemical behavior and the chemical
structural pattern.9,14,15
Therefore, the present study aims to investigate the
electrochemical behavior of alkyl parabens and other
phenolic analogues such as cresol, p-nitrophenol and
p-chlorophenol and compute relevant electronic properties
through quantum-chemical calculations, in order to evaluate
the eventual correlations. The results will help to better
understand the redox behavior of paraben compounds.
Procedures
Voltammetric measurements were carried out as
follows. A 10 mL aliquot of phosphate buffer (0.1 mol L-1)
was placed in the voltammetric cell and, the required aliquot
of sample solution, was added into the voltammetric cell in
order to get a phenolic concentration of 0.25 mmol L-1. The
solution was stirred during 2 min and the voltammogram
recorded in the range of –0.25 to 1.25V (or 1.25 to –0.25V)
using variable scan rate in the range of 10 to 100 mV s-1.
The pH influence on the electrochemical behavior
was evaluated adjusting the pH solution in the range of
3.0 ≤ pH ≤ 8.0 with NaOH or HCl 0.1 mol L-1. The ionic
strength influence was evaluated in the range of 0.01 to
0.5 mol L-1 by varying the buffer solution concentrations.
Moreover, the influence of the supporting electrolyte on the
anodic peak potentials was also evaluated by changing the
phosphate buffer electrolyte solution for other salt solutions
using different anions (PO43−, CH3COO−, SO4−, Cl− and
NO3−) and different cations (K+, Li+, Na+ and NH4+).
Experimental
Computational studies
Chemicals and solutions
The redox reactivity of phenolic compounds (ArOH),
such as paraben, follows at least two mechanisms, which
may occur in parallel:16,17 a one-step hydrogen atom transfer
(HAT, equation 1) and/or a single-electron transfer and
proton transfer (SET-PT, equation 2):
All phenolic compounds: methylparaben (MP),
ethylparaben (EP), propylparaben (PP), butylparaben
(BP), benzylparaben (BzP), p-chlorophenol, p-nitrophenol,
p-cresol and p-hydroxybenzoic acid (HBzA) were
purchased from SIGMA S.A. Phosphate buffer, ethanol,
sodium sulfate, sodium nitrate, sodium phosphate, sodium
chloride, potassium chloride, lithium chloride, ammonium
ArOH + R• → ArO• + RH
(1)
(2)
R• + ArOH → R−+ ArOH•+ → ArO• + RH

Vol. 23, No. 3, 2012
Gil et al.
567
The reactivity of ArOH can be estimated for the first
case by O−H bond dissociation enthalpy (BDE), or by
adiabatic ionization potential (IP) value and reactivity of the
ArOH•+ cation, for the second mechanism.16,17 In equation 1,
the reactivity of ArOH can be estimated by the calculated
O−H bond dissociation enthalpy (BDE) value, whereas in
equation 2, by the calculated adiabatic ionization potential
(IP) value and by the reactivity of the ArOH•+ cation.16,17
The BDE and IP are important molecular descriptors for
studying the redox behavior of phenolic compounds since
that low values for these parameters are related with ease of
O−H bond breaking and ease of electron transfer process,
respectively, which makes the electron abstraction easier.18
The oxidation behavior of the paraben compounds
has been investigated by means of post-Hartree-Fock
approach (second order Møller-Plesset perturbation
theory, MP2). All calculations were carried out using the
ORCA program package19,20 in our local cluster (36 Intel®
Xeon® Processors). Geometry optimizations were done
using the recently developed second-order Möller-Plesset
perturbation (RIJCOSX-MP2) method21 in combination
with a triple-ζ quality plus polarization functions TZVP
basis set.22 The density fitting and chain of spheres
(RIJCOSX) approximations23 were used to accelerate
the calculations in combination with the auxiliary basis
sets TZVP/J and TZVP/C used from TurboMole library24
developed by the Karlsruhe group.
which Hr is the enthalpy of radical generated through
H-atom abstraction, Hh is the enthalpy of hydrogen atom
[−0.49765 hartree] and Hn is the enthalpy of neutral
molecule.27 The adiabatic ionization potential (IP) was
calculated from the Koopmans’ theorem (orbital energy
consideration represented by subscript O): IPO = −EHOMO
and from the total energies denoted with subscript E:
IPE = Ecation − Eneutral, where Ecation is the energy of the
molecule derived from electron-transfer (radical cation)
and Eneutral is associated to the neutral molecule.28
Results and Discussion
The alkyl paraben compounds: MP, EP, PP and BP, as well
as the arylparaben, BzP are oxidized to the corresponding
quinonoidic forms as represented in Figure 1.
Figure 1. Proposed electrochemical oxidation mechanism for paraben
compounds.
Using cyclic voltammetry and glassy carbon electrodes,
only one irreversible anodic peak was observed around
0.8 V for all parabens, Figure 2.
Single-point calculations employing the orbital-
optimized second-order Möller-Plesset perturbation
theory (OO-MP2)25 were performed using the extensively
polarized basis sets of triple-ζ quality including high
angular momentum polarization functions (def2-TZVPP).26
The RIJCOSX23 in combination with the def2-TZVPP/J and
def2-TZVPP/C auxiliary basis sets,26 was used to accelerate
the calculations. Frequency calculations were done at
the same level of theory for both ArOH neutral molecule
and ArO• and ArOH+• species. These values were used to
characterize the stationary points on the potential surface
and obtain the zero point energies (ZPE) at a 298.15 K and
1 atm using unscaled vibrations. ZPE values were included
in all BDE and IP relative energies.
In this investigation, the more relevant electronic
properties for phenolic compounds, such as O−H bond
dissociation enthalpy (BDE), HOMO (highest occupied
molecular orbital) and LUMO (lowest unoccupied
molecular orbital) energies of neutral, radical and radical-
cation species, energy gap (DE = ELUMO – EHOMO) and
ionization potential (IP), have been studied. The O–H
BDEs in gas phase were obtained at 298.15 K using the
sum of electronic and thermal enthalpies. The BDEs
were calculated as follows: BDE = Hr + Hh − Hn in
Figure 2. Cyclic voltammograms obtained at glassy carbon electrode
in 0.1 mol L-1 phosphate buffer, pH 7.0, containing 0.25 mmol L-1 MP
solution. Experimental conditions: scan range from –0.25V to 1.25V, scan
rate of 100 mV s-1. Inset: voltammograms obtained for MP, EP, PP, BP
and BzP, from 0.5V to 1.1V and the same other experimental conditions.
It can be also observed that the anodic peak potentials
shift to less positive values with the increase of the chain
length in the R substituent. Such effect may be attributed
to the electron donating character of the alkyl chain,

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Cyclic Voltammetry and Computational Chemistry Studies
J. Braz. Chem. Soc.
which may balance the electron withdrawn effect of ester
group. This may facilitate the phenolic moiety oxidation,
being that the longer the alkyl chain length, the stronger
this effect will be.
By plotting the anodic peak potential vs. molecular
weight, a linear relationship was obtained, Figures 2 and 3.
The reactivity of phenolic compounds (ArOH) can
be estimated by calculating the O−H bond dissociation
enthalpy (BDE) which the smaller value should improve the
biological activity. The parabens calculated BDEs values,
and the enthalpies of the neutral and radical species are
presented in Table 1.
In the hydrogen atom transfer (HAT) mechanism, a
spontaneous H atom is abstracted from the phenolic hydroxyl
group and transported to the free radical. In this mechanism,
the breaking of O−H bond is, in nature, homolytic. The
BDE physicochemical parameter governs this mechanism
since a weaker O−H bond implies in a greater reaction
velocity, which contributes to the oxidation process. As
seen in Table 1, the lowest value for BDE gas-phase was of
92.807 kcal mol-1 for BzP, and 95.763 kcal mol-1 for BP. The
results indicated that the alkyl chain side affects the BDE
values, and therefore, a greater amount of energy is required
to break the OH bonds on MP and EP.
Table 1. Entalpy and bond dissociation enthalpy (BDE) computed in the
gas phase for the paraben compounds at OO-MP2/def2-TZVPP level
of theory
Figure 3. Ep,a vs. MW plots for paraben compounds (r = 0.9895).
Experimental conditions as described on Figure 2.
HAT Mechanism
In phenolic compounds, the behavior of the OH groups
is mostly influenced by the neighboring groups as well
as by the geometry of the molecule. Figure 3 reinforces
the hypotheses that the withdrawn effect of ester group
is diminished, as the alkyl chain increases. As a result,
the electron density on the aromatic ring is enhanced,
which may contribute to the electron loss. It is noteworthy
that in the case of paraben series, the chain length also
determines the steric conformations, which exert important
influence over the electron density of hydroxyl group. In
order to confirm these assumptions we conducted some
computational chemistry studies.
Paraben
MP
Hn / Haa
−534.460
−573.673
−612.881
−652.103
−764.578
Hr / Hab
−533.800
−573.019
−612.229
−651.453
−763.932
BDE / (kcal mol-1)c
102.032
EP
98.428
PP
96.858
BP
95.763
BzP
92.807
aHn = enthalpy of neutral molecule, in hartree; bHr = enthalpy of radical
generated through H-atom abstraction, in hartree; cBDEs computed with
zero point energy (ZPE).
In this study, RIJCOSX-MP2 level of theory, with a
triple-ζ quality plus polarization functions, TZVP basis set,
were used. Despite all recent progress, it would be useful
to have a wave-function-based ab initio method, with the
same QCISD (Quadratic Configuration Interaction with
Single and Double Excitation) or CCSD (Coupled-Cluster
Singles and Doubles) reliably of results at a low cost. In this
context, the results of MP2 for open-shell molecules can be
improved both in accuracy and stability, if the orbitals are
optimized alongside the double excitation amplitudes.29,30
The orbital-optimized MP2 method (OO-MP2) was chosen
for single point calculations for it improves the results for
open-shell molecules, reactions barriers and radicals, and
it reduces the spin contamination in electronically difficult
situations (unrestricted Hartree-Fock) with OO-MP2 over
MP2 substantial benefits.29
The calculated electronic properties for paraben
compounds such as HOMO and LUMO energies, energy
gap (DE = ELUMO – EHOMO) and ionization potential (IP)
are listed in Table 2, which also shows the experimental
oxidation potential (E°’) for the paraben molecules.
Electron donation of the selected compounds was also
studied. Adiabatic IPs were calculated in the gas phase for
the most stable structure of neutral form of the compounds
as the difference between the electronic energy of the
corresponding ionized form (radical cation) and that of
the neutral species corrected with ZPE. According to
one electron transfer (SET-PT) mechanism, the removal
of an electron from the HOMO of the neutral compound
generates radical cation species.

Vol. 23, No. 3, 2012
Gil et al.
569
Table 2. Molecular descriptors calculated from the total energies and the
orbital energies obtained at OO-MP2/def2-TZVPP level of theory and
the experimentally obtained oxidation potentials (E°’) for the paraben
molecules
Molecular descriptorsa and oxidation potentials
Paraben
MP
EHOMO
−9.007
−9.006
−8.995
−8.989
−8.969
ELUMO
2.558
2.557
2.568
2.562
ΔEb
IPE
IPO
E°’/ Vc
0.778
0.769
0.754
0.744
0.725
11.565
11.563
11.562
11.551
11.447
8.936
8.754
8.579
8.261
7.473
9.007
9.006
8.995
8.989
8.969
EP
PP
BP
BzP
2.478
b
c
aAll values are in eV. ΔE = Energy gap = ELUMO – EHOMO. Oxidation
potential (E°’), experimentally observed, in Volts (V). IPE = Ionization
potential calculated from total energy; IPO = Ionization potential calculated
from orbital consideration.
Figure 4. Correlation graph between the experimental oxidation potentials
(E°’) and the ionization potential (IPE) for the paraben compounds,
calculated at the OO-MP2/def2-TZVPP level of theory.
accurately.33 Koopman’s theorem is valid only when there
is no difference between the orbital of neutral and ionized
compounds, which in turn is not possible. The molecular
orbital theory provides just an approximation that is not
quantitatively reliable, since Koopman’s theorem does
not consider the effects of electron correlation and orbital
relaxation.
The energy of the lowest unoccupied molecular
orbital (ELUMO) and the energy of the highest occupied
molecular orbital (EHOMO) can be used as measurement
of the molecular ability to accept or donate an electron,
respectively. The molecular electron donating ability has
been also characterized by the HOMO energy values:
the higher the HOMO energy, the easier the oxidation
process. The computed HOMO energy values of paraben
compounds are −9.007 eV for MP, −9.006 eV for EP,
−8.995 eV for PP, −8.989 eV for BP and −8.969 eV for
BzP. Benzylparaben which records a higher HOMO energy
value, exhibits a facilitated oxidation process.
The energy gap is the necessary energy to promote an
electron from the highest occupied molecular orbital to
the lowest unoccupied molecular orbital. This molecular
descriptor gives a crude estimate of the relative ability a
molecule has to act as a reducing or oxidizing agent. The
higher the reactivity the inferior is the energy gap between
the HOMO and LUMO. Although quite subtle, there is a
small difference in the energy gap between the paraben
compounds (Table 2). The energy gap is smaller for
parabens with larger side chains, such as propyl and butyl.
Moreover, BzP shows a smaller gap, demonstrating its easy
oxidation process. Therefore, the correlation between the
reactivity of the paraben compounds and their chain length
was achieved, since the greater the length the smaller the
energy gap.
The IP properties that are displayed in Table 2 were both
obtained from the total energies denoted with subscript E
and from the orbital energies through Koopman’s theorem.
The orbital energies are represented by the subscript O.
The IP properties from the total energies are based on the
difference of total electronic energies, when an electron
is removed with reference to the neutral compound and
are called energy-vertical (EE). The IP properties from the
orbital energies are based on the difference between the
HOMO and LUMO energies of the neutral compound and
are known as orbital-vertical (EO). The lowest gas-phase IP
value from energy-vertical is 7.473 eV for BzP, followed
by 8.261 eV for BP suggesting that the BzP and BP may be
more efficient electron donors than MP, EP and PP.
Moreover, a correlation between oxidation electrode
potentials and ionization potentials has been found. Several
of these correlations have been previously reported for
other systems.31,32 The correlation graph between calculated
ionization potentials (IP) and oxidation potentials (E°’) is
shown in Figure 4. A good linear relationship is observed
between the IP and E°’ (R2 = 0.95). IP and E°’ decrease
with the increasing of the alkyl chain length of the paraben
compounds. The lowest values of IP and E°’ were found
for BzP and BP, meaning that these compounds are easier
oxidized than PP, EP and MP, showing that the electron
donating character of the alkyl side chain contributes
slightly to the oxidation process. These results are in
accordance to the electrochemical data.
It is noteworthy that the IP for BzP from the orbital-
vertical method (EO) is higher than the energy-vertical
method (EE) by 1.89 eV (Table 2). The same is observed
with the other compounds, but to a lesser extent. In
previous investigations, it has been found that for most of
the commonly used exchange-correlation functional such
as B3LYP, B3PW91, Koopman’s theorem is not satisfied
The electrostatic potential maps (EPM) of the methyl,
butyl and benzyl paraben molecules in their neutral and

570
Cyclic Voltammetry and Computational Chemistry Studies
J. Braz. Chem. Soc.
radical forms are shown in Figure 5. The analysis of
these maps have indicated that electronic density of the
phenolic hydroxyl group increases with the increasing
of the alkyl chain length of the paraben compounds in
their neutral forms (Figure 5, top), which facilitates the
oxidation process. Moreover, the EPM also indicated
that the electrons in the oxidized paraben forms are
delocalized (Figure 5, bottom) and a significant negative
potential is on the electronegative oxygen atoms in the
paraben molecules.
Figure 6. Cyclic voltammograms obtained at glassy carbon electrode in
phosphate buffer 0.1mol L-1 (pH 7.0) containing 0.25 mmol L-1 MP (––),
…
. .
p-cresol (- - -), p-nitrophenol ( ) and p-chlorophenol (– – ). Scan range
from –0.25 V to 1.25 V; n = 100 mVs-1.
Figure 5. Electrostatic potential maps for MP, BP and BzP in their neutral
(top) and radical (bottom) forms. The color code is in the range of −55.0
(deepest red) to +100.0 (deepest blue) kcal mol-1 (see online).
The results obtained using the computational chemistry
approach are in accordance with the electrochemical data,
demonstrating a stabilization of paraben radical by the
side chain of the ester group. Thus, the oxidation of the
parabens herein studied has shown to be dependent on the
substitution pattern of the side chain of the ester moiety.
Figure 6 presents the cyclic voltammograms obtained
for p-nitrophenol, p-chlorophenol and p-cresol solutions in
the same conditions as those used for MP. The remarkable
differences between electron donor/withdrawn character
of these different substituents resulted in higher potential
shifts than those observed for different parabens. For
instance, the Ep,a value of p-cresol was 300 mV lower than
that one observed for MP, showing clearly that higher
electron donor character makes easier the oxidation process.
Moreover, the p-nitrophenol has exhibited the highest value
of anodic potential peak. It is easily explained by its great
withdrawing character (negative inductive effect, I−, and
resonance withdrawing effect, R−), which makes electron
loss during the oxidation process more difficult.
Furthermore, the p-chlorophenol has presented the
anodic peak inside the range of parabens group, fact
which was attributed to the opposite effects of the chloro
substituent, as electron donation by resonance (R+)
dominates the inductive effect (I−) (Figure 7). Herewith,
the electron withdrawing effect over the oxidized hydroxyl
group decreases in the following order: nitro > methyl-ester
(MP) > chloro > methyl, and can be explained by means of
inductive and resonance effects (Figure 7).
Figure 7. Electronic effects of different phenolic substituents. Positive
inductive effect (I+), negative inductive effect (I−), electron donation by
resonance (R+) and electron withdrawing by resonance (R−).
The cyclic voltammograms obtained with glassy carbon
electrode for 0.25 mmol L-1 MP in different electrolytes
show one pH dependent oxidation peak. Moreover, it was
observed that the oxidation of phenol group is facilitated
at low proton concentration, Figure 8.
Additionally, for pH values higher than 7.0 the parabens
suffer alkaline hydrolysis giving 4-hydroxybenzoic acid.
Probably the calculated pK values represent the pK of the
4-hydroxybenzoic acid and their derivatives and therefore
will be very similar. Besides, the linear equation of the
E
p,a versus pH curve (57.6 mV/pH), shows clearly that
the same number of electron and proton are involved in
the electrochemical electrode process as expected for the
oxidation of phenol group.34
Finally, the influence of supporting electrolyte on
the anodic peak potentials was also evaluated. The
voltammetric behavior of MP was anion dependent while
the cation influence was negligible, Figure 9.
The small potential was obtained for experiments
carried on sodium phosphate, while the highest potential
for sodium nitrate. The decreasing order of the anodic
peak potentials, PO43− < CH3COO− < SO42− < Cl− ≤ NO3−,
suggests stronger interaction of some oxygenated anions
with ester groups or, eventually, stabilization of phenoxyl
radical, intermediate reactive specie during the oxidation

Vol. 23, No. 3, 2012
Gil et al.
571
Figure 8. (A) Cyclic voltammograms obtained for 0.25 mmol L-1 of MP
at glassy carbon electrode in different pH solutions: 8.0 (– – ), 7.0 (– –),
Figure 9. Cyclic voltammograms obtained at glassy carbon electrode
containing 0.25 mmol L-1 of MP in supporting electrolyte different
. .
..
−
−
6.0 ( ), 5.0 (- - -), 4.0 (– –) and 3.0 (––). Scan range from -0.25 to 1.25V;
0.1 mol L-1 (pH 7.0). (A)Anion: PO43−(––), CH3COO (– –), NO3 (– – ),
…
.. . .
. .
−
+
+
+
scan rate of 100Vs-1. (B) Ep,a vs pH curve obtained for MP. Linear equation:
Ep,a (V) = 1.18 (V) – 0.0576 pH. Other conditions such as Figure 8(A).
SO42− (- - -), Cl ( ). (B) Cation: K ( ), Na (––), Li , (– – ), NH4+ (- - -),
…
…
Cl− salts. Einitial = -0.25 V; El = 1.25 V; Efinal = − 0.25 V and n = 100 mVs-1.
of phenol to the respective quinonoidic form. Moreover,
the peak current levels can be correlated to the mobility of
the different cations in the solution, being more intense for
K+. Indeed, both the ions mobility of and the ionic strength
exert positive effect on current signal.
in good agreement with the calculated values for the
electronic descriptors. The energies calculated for the
formation of the radical forms of parabens indicate that the
BzP and BP are oxidized more easily than PP, EP and MP,
showing that the electron donating character of the alkyl
side chain contributes slightly to the oxidation process and
is not negligible. Therefore the oxidation of parabens and
other phenolic analogues to the quinonic forms showed
great dependence on the substituent pattern. The results
also showed high stability (high anodic potentials) and
irreversible behavior, which limits the application of these
compounds as antioxidants.
Conclusions
Using cyclic voltammetry and glassy carbon electrodes,
only one irreversible anodic peak was observed around
0.8 V for all parabens. Increasing the alkyl chain length,
the overall electron donating character of alkyl side chain
slightly contributed to the oxidation process due to the
increasing of electron density over the aromatic ring, which
facilitated the phenolic group oxidation. This positive
inductive effect of alkyl groups was evidenced by the
potential shift to lower potentials as the carbon number
increases. At the same time, the oxidation potentials are
Acknowledgments
The authors would like to thank Fundação de Amparo
à Pesquisa do Estado de Goiás (FAPEG), Fundação de
Amparo à Pesquisa do Estado de São Paulo (FAPESP)

572
Cyclic Voltammetry and Computational Chemistry Studies
J. Braz. Chem. Soc.
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