NEW INSIGTHS on the KINETICS and MECHANISM of the ELECTROCHEMICAL OXIDATION of DICLOFENAC in NEUTRAL AQUEOUS MEDIUM

Article abstract of DOI:10.1016/j.electacta.2016.03.094

The diclofenac (DCF) electrochemical oxidation mechanism was studied through: linear voltammetry (LV), chronoamperometry (CA) sampled-current voltammetry (SCV), potentiostatic coulometry (PC) cyclic voltammetry (CV) under stagnant conditions and linear voltammetry under forced convection conditions (FCLV) over a carbon paste electrode (CPE) from an aqueous medium containing 0.1 M phosphate buffer at pH 7. It was found that the DCF electrochemical oxidation involves an EC mechanism, where the electrochemical reaction is carried out through a one electron-exchange while the chemical reaction involves breaking up the DCF through the nitrogen atom, thereby generating the fragments 2,6 dichloroaniline and 2-(2hydroxyprop-2-enyl)phenol. Reverting the potential scan in the cathodic direction at different scan rates and regardless of its rate, after the oxidation peak, it was found that it was possible to reduce only 38% of the DCF oxidized. The spectrophotometric study carried out during different macro-electrolysis periods allowed observing that the current decrease of the oxidation peak coupled to the DCF absorption (at 270 nm), together with the development of a new spectrophotometric absorption maximum (450 nm), all confirm the EC mechanism proposed. With the use of several experimental techniques (CA, LV and FCLV) and theoretical ones using the Stokes-Einstein approach, the DCF diffusion coefficient was determined, this being in average 8.1 × 10^-6 cm² s^-1.

Full text of DOI:10.1016/j.electacta.2016.03.094

Accepted Manuscript
Title: NEW INSIGTHS ON THE KINETICS AND
MECHANISM OF THE ELECTROCHEMICAL
OXIDATION OF DICLOFENAC IN NEUTRAL AQUEOUS
MEDIUM
Author: M.M. Cid-Cer o´ n D.S. Guzm a´ n-Hern a´ ndez M.T.
Ram ´ı rez-Silva A. Galano M. Romero-Romo M.
Palomar-Pardave´
PII:
S0013-4686(16)30634-X
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.electacta.2016.03.094
EA 26924
To appear in:
Electrochimica Acta
Received date:
Revised date:
Accepted date:
28-12-2015
15-3-2016
16-3-2016
´
Please cite this article as: M.M.Cid-Cer o´ n, D.S.Guzm a´ n-Hern a´ ndez, M.T.Ramirez-
Silva, A.Galano, M.Romero-Romo, M.Palomar-Pardav e´ , NEW INSIGTHS ON THE
KINETICS AND MECHANISM OF THE ELECTROCHEMICAL OXIDATION
OF DICLOFENAC IN NEUTRAL AQUEOUS MEDIUM, Electrochimica Acta
http://dx.doi.org/10.1016/j.electacta.2016.03.094
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1
NEW INSIGTHS ON THE KINETICS AND MECHANISM OF THE
ELECTROCHEMICAL OXIDATION OF DICLOFENAC IN NEUTRAL
AQUEOUS MEDIUM
1
1,3
1,*
M.M. Cid-Cerón , D.S. Guzmán-Hernández , M.T. Ramírez-Silva
1
2
2,*
A. Galano M. Romero-Romo , M. Palomar-Pardavé
Universidad Autónoma Metropolitana Iztapalapa, Departamento de Química,
Av. San Rafael Atlixco #186, Col. Vicentina, México, D.F., C.P. 09340.
,
1
2
Universidad Autónoma Metropolitana Azcapotzalco, Departamento de Materiales,
Av. San Pablo #180, Col. Reynosa-Tamaulipas, C.P. 02200, México, D.F.
3
Universidad Autónoma del Estado de Hidalgo, Área Académica de Química
Carretera Pachuca-Tulancingo km 4.5, 42184 Mineral de la Reforma, Hidalgo
*
Corresponding authors E-mail addresses:
mtrs218@xanum.uam.mx (MTR-S) and mepp@correo.azc.uam.mx (MP-P)
1

2
GRAPHICAL ABSTRACT

= 450 nm
0
0
0
.20
.15
.10
1.80
1.75
1.70
1.65
1.60
1.55
2
1
0
.5
2

= 270 nm
0.05
0.00
0
100
200
300
0
100
200
300
t /sec
ox
t /sec
ox
.5
1
DCF electrochemical oxidation in aqueous medium
at pH 7, using CPE
-
E
Cl
O
Cl
a)
Cl
O
-
1e-
OH
NH
N
.5
0
H+
NH2
+
-
O-
Cl
O
-
Cl
Cl
O
O
2
00
300
400
500

/ nm
2

3
HIGHLIGHTS






DCF electrochemical oxidation was studied from aqueous solution with a CPE
Both stagnant and forced convection conditions were considered
We found DCF electrochemical oxidation is a mass transfer‐controlled process
An EC mechanism was found where the electrodic is quasi‐reversible
C reaction provokes the breaking up the DCF through the nitrogen atom
DCF diffusion coefficient was experimental and theoretically calculated
ABSTRACT
The diclofenac (DCF) electrochemical oxidation mechanism was studied through: linear
voltammetry (LV), chronoamperometry (CA) sampled-current voltammetry (SCV),
potentiostatic coulometry (PC) cyclic voltammetry (CV) under stagnant conditions and
linear voltammetry under forced convection conditions (FCLV) over a carbon paste
electrode (CPE) from an aqueous medium containing 0.1 M phosphate buffer at pH 7. It
was found that the DCF electrochemical oxidation involves an EC mechanism, where the
electrochemical reaction is carried out through a one electron-exchange while the chemical
reaction involves breaking up the DCF through the nitrogen atom, thereby generating the
fragments 2,6 dichloroaniline and 2-(2hydroxyprop-2-enyl)phenol. Reverting the potential
scan in the cathodic direction at different scan rates and regardless of its rate, after the
oxidation peak, it was found that it was possible to reduce only 38 % of the DCF oxidized.
The spectrophotometric study carried out during different macro-electrolysis periods
allowed observing that the current decrease of the oxidation peak coupled to the DCF
absorption (at 270 nm), together with the development of a new spectrophotometric
absorption maximum (450 nm), all confirm the EC mechanism proposed. With the use of
several experimental techniques (CA, LV and FCLV) and theoretical ones using the
Stokes–Einstein approach, the DCF diffusion coefficient was determined, this being in
−6
2 −1
average 8.1 × 10 cm s .
Keywords: Diclofenac; CPE; electrochemistry; oxidation; mechanism; kinetics
3

4
1
. INTRODUCTION
The use of pharmaceuticals in society has become vital for treating diverse illnesses. The
non steroidal anti inflammatory drugs (NSAIDS) have analgesic, antipyretic and anti
inflamatory effects. The reason for their popularity is because they do not produce sedation
or addiction and of their unrestricted purchase. Subsequent to isolation of the acetylsalicylic
acid in 1829 the NSAIDS have been used in human medicine because they have been fully
accepted as relatively safe, to the point that no medical prescription is required [1] so that
any person can access the drug, consequently it is one of the most popular drugs consumed.
The (2 - [(2,6-dichlorophenyl) amino] phenyl acetate) or diclofenac (DCF), see Figure 1, is
considered a NSAIDS because of its analgesic, antipyretic and anti inflamatory properties.
[
2]. It is a quick acting, long lasting analgesic that if frequently prescribed in clinical
medicine for treating rheumatoid arthritis, osteoarthritis, non-articular rheumatism and
sport lesions. On consideration of this, different methods have been implemented for its
quantification, although some of them are based on chromatography-mass spectrometry,
liquid chromatography and electronebulization [3] and electrochemical [4-8]. However,
only few studies have duly informed, on relevant features of DCF, like the kinetics and
mechanisms involved during its electrochemical oxidation, the number of electrons lost
during its electrochemical oxidation process and in particular the value of its diffusion
coefficient in aqueous medium. Human indiscriminate disposal of DCF into the sewages
and water bodies has let to its considering as an emerging pollutant, therefore, all
information leading to DCF identification and or its oxidation products is relevant [9,10].
Furthermore, this information would be important for the design of a novel method for
DCF electrochemical quantification [11].
Therefore, this work aims to contribute to the understanding of the mechanism and kinetics
of DCF electrochemical oxidation, through the use of spectroelectrochemistry and different
electrochemical methods.
4

5
2
. EXPERIMENTAL
.1. Chemicals and solutions
2
All reactants were analytical grade, diclofenac (Sigma) and phosphate salts (J.T. Baker);
the solutions were prepared with deionized water from a Milli-Q (Millipore) instrument
displaying 18.0 Mcm resistivity.
2
.2 Measurement methods
The potentiometer was a pH/Ion Analyzer (METTLER TOLEDO). During the experiment
the DCF solutions in the cell were maintained under a nitrogen shroud and precluded from
light at 25 °C constant temperature.
A potentiostat Epsilon BASi was used to perform the electrochemical study aided by a
conventional three electrode cell comprising a carbon paste electrode, CPE (displaying a
2
geometric area of 0.071 cm ) as the working electrode, prepared by mixing graphite powder
(
Johnson Matthey 1 μm, 99.9%) and mineral oil (nujol) from Sigma-Aldrich in 1:1 w/w
relation, the resulting powder is placed in a polyethylene tube (10 cm long and 3 mm
diameter) that contains a piston; the tip of the tube is then placed on a flat surface and
pressure is manually exerted on the piston so as to achieve total elimination of trapped air.
The electric contact is accomplished by a Pt wire soldered to an external Cu wire, more
details can be found in Ramírez et al. [12, 13]. The counter-electrode was a BAS MW-1032
Pt wire while a BAS MF-2052 Ag/AgCl saturated served as reference electrode. The
macro-electrolysis experiments were conducted in a massive electrolysis cell (Princeton
Applied Research Kit 377/16 Stirring Synchronous Motor) using as working electrode a
platinum gauze from BAS (a cylinder 50 mm high and 39 mm diameter with a 50 mm
connecting wire), an electrode bridge glass tube with a platinum wire (Princeton Applied
Research Kit K0030) as reference electrode and a carbon paste electrode as counter
electrode. Spectrophotometric measurements were carried out using a UV–Vis
spectrophotometer Perkin Elmer Lambda 20 and quartz cells, 1 cm optical path length.
5

6
3
. RESULTS AND DISCUSSION
The literature reports that the DCF presents a pKa of 4.15 [14], then, depending on the pH
two species can predominate; the neutral and the anionic species. Figure 2 shows the
predominance zones linear diagram for DCF built on the basis of the method proposed by
Rojas-Hernández et al. [15-18], where it can be observed that for pHs smaller than 4.15 the
neutral species predominates whereas at greater pHs it predominates the anionic species.
The electrochemical DCF quantification has been reported at pH 7 [4-8], therefore, in this
work the characterization is done at pH 7 where the DCF anionic species predominates (see
Figure 2).
3
.1 Electrochemical characterization of DCF
The DCF electrochemical oxidation was studied through linear voltammetry (LV) [19, 20],
in buffer solution at pH 7 (see Figure 3). It can be observed that the DCF displayed an
anodic peak around 0.63 V the current of which increased linearly (ipa = (40.7 ±
1
.9)AV−0.5 s0.5 0.5 – (2.77 ± 0.64)A) as a function of the square root of the potential
scan rate (see inset in Figure 3); therefore, in agreement with the Randles-Sevcik equation
1) [21] the charge transfer in this case is controlled by diffusion.
(
3
1
5
2
0.5
2
ipa  (2.688 10 )n SD C υ
(1)
R
R
Where ipa is the anodic peak current (in A), n is the number of electrons, S the area of the
2
2 −1
electrode (in cm ), D
R
the diffusion coefficient (en cm s ), C is the concentration of the
R
−3
−1
analyte (in mol cm ) and  the potential scan rate (en V s ).
3
.1.1 Estimation of the number of electrons
In order to determine the number of electrons that participate in the electrochemical
NSAIDS reaction in aqueous medium, chronoamperometry has been used (CA) [22].
Figure 4 shows a family of potentiostatic current transients and the inset depicts an example
that the plot of i = f (t−0.5) for the transient obtained at 0.67 V fulfills the prediction from the
6

7
Cottrell equation (2) [21], thereby corroborating that the DCF electrochemical oxidation
process is limited by diffusion.
1
2
0.5 -0.5
i  nFSD R C 
t
(2)
R
Where F is the Faraday constant.
From the family of potentiostatic current transients in Figure 4 it is possible to build plots
of i = i (E), for different times sampled (see Figure 5(a)). From these plots and using the
equation of Heyrovsky-llkovic (see equation 3) [23, 24] the plots E = E (log (i -i/i)) were
l
obtained, for different sampling times, see Figure 5b and Table 1. It is important to note
that all the plots in Figure 5(a) depict the characteristic features of a one-electron reversible
wave in sample-current voltammetry, where the wave rises from base line to the diffusion-
controlled limit over a fairly narrow potential region (ca 200 mV), see for instance Figure
5
.4.1 in [21]. Figure 5b shows an example that the equation 3 describes adequately the
experimental data obtained for a sampling time of 0.095 s (the fitting plot was: E = (0.658 ±
.003)V-(0.056 ± 0.006) V log(i -i/i)). From the value of the slope it is possible to
0
l
determine the number of electrons that participate in the electrochemical reaction. Table 1
shows the values of n for each value of the sampling time considered and the value of the
half wave potential (0.66 V). The number of electrons transferred during the oxidation of
DCF is practically 1 for all cases. Moreover, from coulometric experiments, see Figure S1
in the supporting information of this work, it was confirmed that n = 1 and that the
oxidation of DCF in this potential range is a reversible process; another important feature
that support this outcome is that for all the plots in Figure 3, the average of the differences
between the peak potential, E , and the corresponding half-peak potential Ep/2, is 62 mV,
p
which is quite close with the predicted (56.6 mV) for a one-electron reversible process, see
equation 6.2.22 in [21]. This value contrasts with the value of n = 2 reported by Goyal et al.
[4], from the variation of the potential as a function of pH (in the 2 to 11 range) using an
“edge plane pyrolytic graphite” electrode. Furthermore, based on this Goyal et al. [4],
proposed a mechanism (also reported by Goodarzian et al. [8]) where the DCF oxidation
process starts with the completely protonated molecule. However, at pH 7 the DCF
predominating species would be the deprotonated one (see Figure 2), therefore, the
7

8
mechanism described is incorrect as well as the form in which to determine the number of
electrons using the potential variation as a function of pH, given that within the interval
selected by Goyal et al. [4], there would be a change in the DCF predominating species
(pKa = 4.15). In agreement with the DCF predominating species at pH 7 in aqueous
solution and the number of electrons that we have found based on electrochemical
techniques, the electrochemical reaction would be that described in Figure 7.
RT
nF
il  i
i
E  E1/2

2.203 log(
)
(3)
Where E is the electrode potential (in V), E1/2 is the half wave potential (in V), i
l
is the
limiting current, i the current measured at each potential, R the gas constant and T the
temperature.
Figure 6a shows a family of cyclic voltammograms, CVs, obtained during the DCF
electrochemical oxidation (during the forward potential scan) and reduction (during the
backward potential scan) process. The presence of an oxidation peak is readily noted during
the direct scan and a reduction one during the reverse. The former has already been
analyzed in the study by means of LV, whereas in the latter case (see Figure 6b) it is
straightforward that the current also varies linearly (ipc = (-(15.4 ± 0.6))AV−0.5 s0.5 0.5
1.14 ± 0.21)A) with the square root of the scan rate. However, the absolute value of the
ratio of both peaks current, as a function of the potential scan rate, see the inset in Figure
a, is pretty much less than unity, which can be explained if the DCF oxidation process
–
(
6
takes place via an Electrochemical (E)-Chemical (C) mechanism (EC).
Considering the information obtained through cyclic voltammetry, Figure 7 shows the EC
mechanism involved in the DCF electrochemical oxidation process via transfer of one
electron (E) and C would be due to what happens after the DCF molecule losses one
electron and one proton, the nitrogen resonates between the formation of a double bond and
formation of a radical, which may be able to react with the medium thus producing the
8

9
irreversible DCF rupture into two products: a) 2,6 dichloroaniline and b) 2-(2hydroxy prop-
2
-enyl)phenol, see Figure 7.
In order to corroborate the electrochemical oxidation described in Figure 7, it became
necessary to carry out a spectro-electrochemical study [25, 26] recording simultaneously
the UV-Vis absorption spectra of the DCF solution after different potentiostatic
macroelectrolysis periods (at 640 mV), see the experimental section for more details,
during which process there were obtained, after certain period, the respective LVs, see
Figure 8a and the UV-Vis absorption spectra, see Figure 8b. It can be seen, that the DCF
oxidation peak current, see inset Figure 8a, and the absorption measured at 270 nm wave
length (see corresponding inset in Figure 8b) diminish with increasing electrolysis time.
Furthermore, it can be clearly noted the formation of an absorption peak at 450 nm, which
was absent at the start of the experiment, that increases with increasing electrolysis time.
Also, it is relevant to mention that before the electrolysis the DCF solution was transparent
and it became gradually yellow, with an intensity dependent on electrolysis time. This
second absorption peak generated after the DCF electrochemical oxidation is congruent
with that corresponding to the substituted anilines like the o-nitro aniline [27] or that of the
2
,6 dichloroaniline. This experimental evidence gives stronger support to the mechanism
proposed in Figure 7. Is important to mention that Vogna et al., [28] carried out the DCF
oxidation by means of ozone and UV/H treatments and identified, through GC-MS (Gas
chromatography–mass spectrometry) analyses, formation of 2,6 dichloroaniline and 2-
2hydroxy prop-2-enyl)phenol, see route c in scheme 1 of the reference [28].
2
O
2
(
0
.5
From the slope of the variation of ipc vs. v , see Figure 6b, and the value of the diffusion
coefficient of the DCF estimated in this work (see below) the value of n was calculated as
1
.02 electrons, which is in strong agreement with the mechanism proposed in Figure 7.
3
.1.2 DCF electrochemical oxidation under forced convection conditions
Figure 9 shows the effect of the electrode rotation speed on a family of LVs obtained
during the DCF electrochemical oxidation. It can be seen that the limiting currents (i ),
formed at each value of the angular velocity, vary linearly (i
= (0.099 ± 0.003)A rpm−0.5
L
L
9

1
0
0.5
+ (1.17 ± 0.06)A) with the square root of the rotation speed, see inset in Figure 9, in
agreement with the Levich equation (4) [21]. Since these LVs do not depict the typical S-
shape, we have repeated this sort of experiments but using a lower potential scan rate,
namely 10 mV/s and a lower DCF concentration, see Figure S2a in the supporting material
0
.5
in this work. The LVs in Figure S2a depicts the S-shape and the corresponding i vs. 
L
plot, see Figure S2b, was linear with the following equation: i
L
(A)= (3.57 ± 0.23)E-08
0
.5
0.5
(
A/(rpm) ) + (3.05 ± 0.30)E-07(A) and R² = 0.9737.
2
3
-1/6 1/ 2
i  0.2nFSD C 

(4)
L
R
R
2
-1
Where  is the kinematic viscosity (in this case 0.01 cm s ) and  the angular rotation
speed (in rpm).
3
.1.3 Experimental evaluation of the DCF diffusion coefficient
Once determined the electron number involved during the DCF electrochemical oxidation
and that this reaction follows equations (1) of Randles-Sevcik, (2) of Cottrell and (4) of
Levich, the DCF diffusion coefficient can be estimated from these different methodologies,
see Table 2. As can be appreciated the values of the DCF diffusion coefficient estimated
through this work, following different techniques, are indeed close among them. It is
−6
2
−1
worthy of mention that Goodarzian et al. [8], reported a value of 5.9 × 10 cm s for the
DCF diffusion coefficient using an ionic liquids-modified electrode and CNT, although, the
−6
2
values estimated in this work are clearly at variance with that reported of 0.94 × 10 cm
−1
s by Hajijizadeh et al. [7], which is practically an order of magnitude smaller.
3
.1.4 Theoretical estimation of the diffusion coefficient
All the electronic calculations were performed with Gaussian 09 package of programs [29].
The M05-2X functional [30] was used for geometry optimizations and frequency
calculations in conjunction with the 6-311+G(d,p) basis set and the continuum solvation
model based on density (SMD), [31] using water as solvent. Local minima were identified
1
0

1
1
by the absence of imaginary frequencies. Thermodynamic corrections at 298.15 K were
included in the calculation of relative energies. All the calculated thermochemical data is
reported using the 1M standard state. The diffusion coefficient was estimated from the
Stokes–Einstein approach [32, 33]:
k T
B
D 
(5)
6a
where k
B
is the Boltzmann constant, T is the temperature (298.15 K), η denotes the
-4
viscosity of the solvent, in our case water (η = 8.91 x 10 Pa s) and a is the radius of the
solute. The value of a (5.05 Å) was estimated using the Gaussian 03 package [29], with the
option volume = tight. The geometry used for this estimation was previously optimized at
M052X/6-311+G(d,p) [30] level of theory, in water solution using the SMD continuum
−6
2
model [31]. It is important to note that the D value, theoretically estimated, 4.85 x 10 cm
−1
s , is quite similar to those values experimentally estimated under both stagnant and forced
convection hydrodynamic conditions.
CONCLUSIONS
For the first time it is shown, from a spectro-electrochemical study, that the DCF
electrochemical oxidation in aqueous media at pH 7, where the anionic form of DCF
predominates, involves an EC mechanism, where the electrochemical reaction is reversible
and occurs through the loss of one electron. Furthermore, the chemical reaction provokes
the DCF breaking up through the nitrogen atom, thereby generating the fragments 2,6
dichloroaniline and 2-(2hydroxyprop-2-enyl)phenol. This chemical reaction is not so fast
because after reverting the potential scan in the cathodic direction at different scan rates,
and regardless of its rate, it was possible to reduce 38 % of the DCF oxidized.
ACKNOWLEDGMENTS
MMCC and DSGH thank CONACyT for the grant given to pursue Ph.D. studies and
postdoctoral research respectively. MTRS thanks CONACyT for support through project
2
37327. MTRS, AG, MRR, DSGH and MEPP like to thank SEP PRODEP for financial
support through the RedNIQAE. DSGH, MTRS, AG, MRR and MPP wish to thank the
SNI for the distinction of their membership and the stipend received.
1
1

1
2
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[18] A. Rojas-Hernández, M.T. Ramírez, I. González. Equilibria among condensed phases
and a multi-component solution using the concept of generalized species: Part II. Systems
with polynuclear species. Anal. Chim. Acta 278 (1993) 335-347.
[19] D.K. Gosser Jr., Cyclic Voltammetry Simulation and Analysis of Reaction
Mechanisms, VCH, Weinheim, 1993.
[
20] Joseph Wang, Analytical Electrochemistry, Wiley-VCH, Hoboken, New Jersey, 2006.
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[
Interscience, New York, 2000.
[22] D.S. Guzmán-Hernández, M.T. Ramírez-Silva, M. Palomar-Pardavé, S. Corona-
Avendaño, Annia Galano, A. Rojas-Hernández, M. Romero-Romo. Electrochemical
characterization of tenoxicam using a bare carbon paste electrode under stagnant and forced
convection conditions. Electrochim. Acta 59 (2012) 150-155.
[23] A.J. Bard, G Inzelt, F. Scholz. Electrochemical Dictionary, 2nd edition, ed. Springuer,
p 540 2012.
[
24] P.H. Rieger. Electrochemistry, second edition, ed. Champman & Hall, pp. 212, 1994.
25] M.T. Ramírez-Silva, D.S. Guzmán-Hernández, A. Galano, A. Rojas-Hernández, S.
[
Corona-Avendaño, M. Romero-Romo, M. Palomar-Pardavé. Spectro-electrochemical and
DFT study of tenoxicam metabolites formed by electrochemical oxidation. Electrochim.
Acta 111 (2013) 314-323.
[26] W. Kaim, J. Fiedler. Spectroelectrochemistry: the best of two worlds. Chem. Soc. Rev.
3
8 (2009) 3373-3382.
[27] P. Nalawade, T. Mukherjee, S. Kapoor. Green Synthesis of Gold Nanoparticles Using
Glycerol as a Reducing Agent. Advances in Nanoparticles. 2 (2013) 78-86.
[
28] D. Vogna, R. Marotta, A. Napolitano, R. Andreozzi, M. d’Ischia. Advanced oxidation
of the pharmaceutical drug diclofenac with UV/H and ozone. Water Research 38 (2004)
14-422.
2
O
2
4
1
4

1
5
[
29] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman,
et al. Gaussian 09. Wallingford, CT, USA: Gaussian, Inc.; 2009.
[30] Y. Zhao, N.E. Schultz, D.G. Truhlar. Design of density functionals by combining the
method of constraint satisfaction with parametrization for thermochemistry,
thermochemical kinetics, and noncovalent interactions. J. Chem. Theory. Comput. 2 (2006)
3
64-382.
[31] A.V. Marenich, C.J. Cramer, D.G. Truhlar. Universal solvation model based on solute
electron density and on a continuum model of the solvent defined by the bulk dielectric
constant and atomic surface tensions. J. Phys. Chem. B 113 (2009) 6378-6396.
[32] A. Einstein, Ann. Phys. (Leipzig), 1905, 17, 549.
[
33] G.G. Stokes, Mathematical and Physical Papers (Cambridge University Press,
Cambridge, 1903), Vol. 3 (esp. Sect. IV).
1
5

1
6
FIGURE CAPTIONS
Figure 1. Molecular structure of fully protonated diclofenac.
Figure 2. DCF´s Linear Predominance Zones Diagram constructed following the
methodology proposed by Rojas-Hernández et al. [12-15].
Figure 3. Typical experimental LVs obtained from the system CPE / DCF 142 M, (PBS
0
.1M, pH 7) varying the electrode potential in the anodic direction, starting at 0.3 V at
different potential scan rates indicated in the Figure. The inset shows the variation of the
anodic peak current (ipa) as a function of the square root of the potential scan rate (). The
broken line depicts the linear regression of the experimental data (markers).
Figure 4. Family of potentiostatic current transients obtained from the system CPE / DCF
6
4 M, (PBS 0.1M, pH 7) applying different potential steps from 0.3V up to the different
potentials shown in the Figure. The inset in the Figure depicts the plot of i = f (t−0.5) for the
transient obtained at 0.67 V.
Figure 5. (a) Plots of i = f (E ) obtained from Figure 4 using different sampling times
indicated in the Figure. (b) Plot of E = f (log (i -i/i)) for a sampling time of  ms.
l
Figure 6. a) Typical experimental CVs obtained in the CPE / DCF 142 M system, (PBS
.1M, pH 7) after varying the electrode potential in the anodic direction, starting at 0.2 V)
0
at different potential scan rates indicated in the Figure. The inset shows the variation of the
ratio of the cathodic (ipc) to the anodic (ipa) peak currents as a function of the potential scan
rate (). b) Variation of the cathodic peak current (ipc) as a function of the square root of the
potential scan rate (). The broken line is the linear regression of the experimental data
(
markers).
Figure 7. EC mechanism proposed involved during the DCF electrochemical oxidation in
aqueous medium at pH 7, using CPE.
1
6

1
7
−1
Figure 8. Family of a) LVs, applying 100 mV s potential scan rate and b) UV-vis spectra
recorded in the Pt mesh / DCF 209 M system, (PBS 0.1M, pH 7) after different oxidation
times, at 640 mV. The dependence of the current peaks of the voltammograms and the
absorbance at 270 and 450 nm of the UV-vis spectra, with the oxidation time are also
depicted in the insets in Figures a and b, respectively.
Figure 9. Typical experimental LVs obtained in the CPE / DCF 142 M system, (PBS
0
.1M, pH 7) the potential scan started at 0.3 V at a 20 mVs−1 rate applying different
rotation speeds to the electrode, indicated in the Figure. The inset shows the variation of the
anodic limiting current (i ) as a function of the electrode’s rotation rate square root (). The
line corresponds to the linear regression and the markers to the experimental data.
L
1
7

1
8
Figure 1
Cl
NH
Cl
OH
O
1
8

1
9
Figure 2
Cl
Cl
NH
NH
Cl
OH
O-
Cl
O
O
pH
4.15
Figure 3
1
1
1
1
1
8
20
1
5
0
5
0
6
4
2
0
8
6
4
2
0
1
/ Vs-1
0.02
0.04
0
0.1
0.2
0.5
0.3
/Vs-1
0.4
0.5
0
.06
0.1
0
0
0
0
.12
.16
.18
.2
0
.3
0.4
0.5
0.6
0.7
0.8
E / V
1
9

2
0
Figure 4
0
0
.016
.014
0
0
0
0
0
0
0
0
.14
.12
.10
.08
.06
.04
.02
.00
0.012
.010
0.008
0
E /V
0
0
0
0
0
0.7
0
0.76
.56
.58
.61
.64
.67
0.55
0.59
0.62
0.65
0.68
0.71
0.74
0.77
0.8
0.57
0.6
0
0
0
0
.006
.004
.002
.000
0.63
0.66
0.69
0.72
0.75
0.78
0.81
0.84
0
3
5
8
10
13
15
.73
t-0.5 / sec-0.5
0
0
0
.79
.82
.85
0.83
0
10
20
30
40
50
60
70
80
90
t / msec
2
0

2
1
Figure 5
3
2
2
1
1
0
5
0
5
0
5
0
a)

/ msec
1
1
5
7
8
9
9
0
9.95
9.95
9.95
9.95
4.95
5.05
0.54
0.64
0.74
0.84
E / V
2
1

2
2
0.72
0.67
0.62
0.57
b)
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
0.8
1
log (i -i / i )
l
2
2

2
3
Figure 6
1
1
1
1
1
8
a)
6
4
2
0
8
6
4
2
0
2
4
6
8
0
0
0
0
0
.40
.38
.35
.33
.30

/ Vs-1
0.02
0
.04
.06
0
0.1
0
0.05
0.1
/Vs-1
0.15
0.2
0.12

0.16
0.18
0.2
-
-
-
-
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
E / V
2
3

2
4
b)
0
2
4
6
0
0.2
0.4
0.6
-
-
-
0.5
/(V/s)0.5
2
4

2
5
Figure 7
E
Cl
N
Cl
-
-
1e-
H+
NH
O-
O-
Cl
Cl
O
O
+
H O
2
C
-
O
b)
a)
Cl
Cl
O
OH
NH2
+
2
5

2
6
Figure 8
1
1
1
1
1
8.0
6.0
4.0
2.0
0.0
a)
16.0
14.0
12.0
10.0
8
6
4
2
0
.0
.0
.0
.0
.0
0
100
200
300
t /sec
ox
0
.50
0.55
0.60
0.65
0.70
0.75
0.80
0.85
E / V
2
6

2
7
1.80
1.75
1.70
1.65
1.60
1.55
 = 270 nm
2
1
0
.5
2
b)
0
100
200
300
t /sec
 = 450 nm
ox
.5
1
0.20
0.15
0.10
0.05
0.00
.5
0
0
100
200
300
t /sec
ox
200
300
400
500

/ nm
2
7

2
8
Figure 9
4
3
2
1
0
rpm
80
4
3
2
1
0
140
160
200
260
340
400
0
5
10
0.5
15
/ (rpm)0.5
20
25
0
.5
0.6
0.7
E / V
0.8
0.9
2
8

2
9
Table 1. Estimates of the number of electrons, n, and the half wave potential, E1/2, involved
during the DCF electrochemical oxidation process in aqueous medium (pH 7) by means of
the sampled-current voltammetry (see Figure 5b).
t / ms
60
80
90
94
95
Slope / V
-0.074
0.664
0.800
-0.068
0.667
0.873
-0.060
0.656
0.991
-0.060
0.660
0.993
-0.056
0.658
1.056
E1/2 / V
n
Table 2. Comparison of the diffusion coefficient obtained for the DCF anionic species (pH
7
) obtained through different electrochemical techniques and that reported.
6
2 −1
Technique
10 D / cm s
*
Chronoamperometry: stagnant conditions
7.88 ± 0.04
*
* Linear Voltammetry: forced convection conditions
** Linear Voltammetry: stagnant conditions
8.13 ± 0.33
8.19 ± 0.28
*
Using equation *(2), ** (4) and *** (1) and the respective experimental data.
2
9