A mechanistic study on the disproportionation and oxidative degradation of phenothiazine derivatives by manganese(III) complexes in phosphate acidic media

Article abstract of DOI:10.1007/s11243-011-9531-x

The oxidative degradation of phenothiazine derivatives (PTZ) by manganese(III) was studied in the presence of a large excess of manganese(III)-pyrophosphate (P₂O₇ ^2-), phosphate (PO₄ ^3-), and H⁺ ions using UV-vis. spectroscopy. The first irreversible step is a fast reaction between phenothiazine and manganese pyrophosphate leading to the complete conversion to a stable phenothiazine radical. In the second step, the cation radical is oxidized by manganese to a dication, which subsequently hydrolyzes to phenothiazine 5-oxide. The reaction rate is controlled by the coordination and stability of manganese(III) ion influenced by the reduction potential of these ions and their strong ability to oxidize many reducing agents. The cation radical might also be transformed to the final product in another competing reaction. The final product, phenothiazine 5-oxide, is also formed via a disproportionation reaction. The kinetics of the second step of the oxidative degradation could be studied in acidic phosphate media due to the large difference in the rates of the first and further processes. Linear dependences of the pseudo-first-order rate constants (k _obs) on [Mn ^III] with a significant non-zero intercept were established for the degradation of phenothiazine radicals. The rate is dependent on [H⁺] and independent of [PTZ] within the excess concentration range of the manganese(III) complexes used in the isolation method. The kinetics of the disproportionation of the phenothiazine radical have been studied independently from the further oxidative degradation process in acidic sulphate media. The rate is inversely dependent on [PTZ^+.], dependent on [H⁺], and increases slightly with decreasing H⁺ concentration. Mechanistic consequences of all these results are discussed.

Full text of DOI:10.1007/s11243-011-9531-x

Transition Met Chem (2011) 36:767–774
DOI 10.1007/s11243-011-9531-x
A mechanistic study on the disproportionation and oxidative
degradation of phenothiazine derivatives by manganese(III)
complexes in phosphate acidic media
•
Joanna Wisniewska Paweł Rzesnicki
•
´
Adrian Topolski
´
Received: 21 July 2011 / Accepted: 11 August 2011 / Published online: 6 September 2011
Ó The Author(s) 2011. This article is published with open access at Springerlink.com
Abstract The oxidative degradation of phenothiazine
derivatives (PTZ) by manganese(III) was studied in the
presence of a large excess of manganese(III)-pyrophos-
phate (P2O72-), phosphate (PO43-), and H? ions using
UV–vis. spectroscopy. The first irreversible step is a fast
reaction between phenothiazine and manganese pyrophos-
phate leading to the complete conversion to a stable phe-
nothiazine radical. In the second step, the cation radical is
oxidized by manganese to a dication, which subsequently
hydrolyzes to phenothiazine 5-oxide. The reaction rate is
controlled by the coordination and stability of manga-
nese(III) ion influenced by the reduction potential of these
ions and their strong ability to oxidize many reducing
agents. The cation radical might also be transformed to
the final product in another competing reaction. The final
product, phenothiazine 5-oxide, is also formed via a dis-
proportionation reaction. The kinetics of the second step of
the oxidative degradation could be studied in acidic phos-
phate media due to the large difference in the rates of
the first and further processes. Linear dependences of the
pseudo-first-order rate constants (kobs) on [MnIII] with a
significant non-zero intercept were established for the
degradation of phenothiazine radicals. The rate is depen-
dent on [H?] and independent of [PTZ] within the excess
concentration range of the manganese(III) complexes used
in the isolation method. The kinetics of the dispropor-
tionation of the phenothiazine radical have been studied
independently from the further oxidative degradation pro-
cess in acidic sulphate media. The rate is inversely
dependent on [PTZ?.], dependent on [H?], and increases
slightly with decreasing H? concentration. Mechanistic
consequences of all these results are discussed.
Introduction
Manganese reactivity has attracted particular attention
since its ions are present in the active sites of many
enzymes and participate in very important biological
processes [1, 2]. A key topic in this field is the oxidation
of water into molecular oxygen, which is catalyzed by a
CaMn4 cluster in photosystem II [3]. Although recent
progress in solar energy research has led to an increased
interest in photosynthesis and artificial photosynthesis [4,
5], the structure of this cluster is still unknown [6–9] and
very few manganese-based homogeneous catalysts have
been reported to evolve oxygen upon oxidation [10, 11]—
an observation that, however, has recently been questioned
[12]. The ability to catalyze the heterolytic cleavage of the
O–O bond in hydrogen peroxide and molecular dioxygen
by manganese has been recently intensively studied [13].
Despite the mechanism of these processes catalyzed by
heme oxygenases, such as cytochrome P450, cytochrome
c oxidase, peroxidases, and catalase being known [14–19],
direct observation of the O–O bond cleavage has been
difficult due to the complex catalytic cycles, short-lived
iron intermediates, and required cryogenic conditions.
High-valent manganese oxo intermediates are more stable
and can be functional analogs of heme proteins appearing
in many biological systems using hydrogen peroxide and
molecular dioxygen [13]. Recently, a bridged manga-
nese(V) porphyrin dimer was shown to oxidize water into
dioxygen, [20] and reversible O–O bond cleavage was
observed for a manganese corrole system [21, 22], and the
design of novel, long-lived manganese(III) complexes,
´
´
J. Wisniewska (&) ꢀ P. Rzesnicki ꢀ A. Topolski
Department of Chemistry, Nicolaus Copernicus University,
´
Gagarina 7, 87-100 Torun, Poland
e-mail: wisnia@chem.umk.pl
123

768
Transition Met Chem (2011) 36:767–774
which can be a model of the precursor of the endogenous
high-valent peroxo and oxo intermediates, has been pub-
lished recently [23]. A special emphasis has been focused
on manganese species as effective catalysts in the degra-
dation reactions of many organic species [24, 25]. In this
study, a detailed account of the mechanistic features as
well as the kinetic parameters for the oxidative transfor-
mation of phenothiazines by manganese(III) is provided.
Details of the powerful and environmentally friendly
manganese(III) complexes that act as very efficient oxi-
dants for many oxidative degradation processes, were
sought in an effort to develop new methods for the clean
oxidation of pharmacologically active phenothiazines, and
select the most effective methods with potential applica-
tions in green chemistry for the disposal of this class of
pharmaceuticals.
monitoring the disappearance of the phenothiazines radi-
cals visualized by the decrease in absorbance at 514 nm for
phenothiazines radicals electron transitions in accordance
with literature data: kmax, nm (emax, dm3 mol-1 cm-1):
promazine radical, 513(9200) [27], chlorpromazine radical,
525(10200) [27], promethazine radical, 515(9300) [27],
and trifluoperazine radical, 502(9000) [28]. In the same
visible spectral region, the characteristic electronic transi-
tion of the manganese(III)-pyrophosphate ion is observed,
k
max, nm (emax, dm3 mol-1 cm-1): 513(85). On account of
the marked difference in molar absorption coefficients for
reactants, the changes in absorbance, which were moni-
tored as a function of reaction time and resulted from the
change of oxidant concentration, were low, ca. 0.01. The
reaction rate was determined as a function of the manga-
nese(III) concentration: [PTZ] = 5 9 10-5 M, [MnIII] =
(0.5–4.5) 9 10-3 M, [P2O74-]T = 0.1 M, [Na4P2O7]T =
0.1 M, [H3PO4]T = 1.0 M, [H?] = 0.04 M, I = 0.45 M
(H?, H2PO4-, Na?, H3P2O7-, and H2P2O72-), T =
288–308 K. In another series of experiments, the reaction
Experimental
Materials
rate dependence on the H? concentration was determined:
[PTZ] = 5 9 10-5 M, [MnIII] = 1.5 9 10-3 M, [P2O7
]
4-
Manganese acetate (Mn(CH3COO)3ꢀH2O, Aldrich), pro-
mazine, chlorpromazine, promethazine, trifluoperazine
(Sigma-Aldrich), and all other chemicals were analytical
grade reagents. Water purified in a Millipore Milli-Q
system was used to prepare all the solutions. The stock
solutions of manganese(III) were prepared by dissolving
manganese acetate in 0.1 M Na4P2O7 and 1.0 M H3PO4.
The concentration of a stock solution of manganese(III)
was determined iodometrically. The solution was stable for
a few days when stored at 5 °C. The stability of manga-
nese(III) has been analyzed in different pyrophosphate and
phosphate media by Klewicki [26]. Manganese(III)-pyro-
phosphate is unstable at higher temperatures and undergoes
a disproportionation reaction, which can be facilitated by
OH- ions, as well as by lower than 10 molar ratio of
LT/MnT, where T is a total concentration of pyrophosphate
and manganese, respectively [26]. The desired solutions
of manganese(III) were prepared before each series of
kinetic measurements. Aqueous solutions of chlorproma-
zine (Sigma-Aldrich) and other phenothiazine derivative
were stored in the dark because of their photosensitivity.
= 0.1 M, [H3PO4] = 0.3–1.0 M, [H?] = 0.005–0.04 M,
I = const, T = 298 K. The time scale was 4,800–200 and
5,800–500 s (95%) for chlorpromazine and trifluoperazine,
respectively. The pseudo-first-order rate constants were
calculated using a non-linear fitting procedure to the first-
order absorbance dependence versus time. At least three
kinetic runs were recorded for every set of the reagent
concentrations, and the reported rate constants represent
the average values. The relative standard errors of the
pseudo-first-order rate constants for a single kinetic trace
were ca. 0.5–1%, and relative standard errors of the mean
value were usually ca. 1–2%. Additionally, the kinetic
traces for the first-order and second-order radical decay at
higher pH [ 1 were analyzed by the integral solution
derived from the differential equation of the concentration
derivative of radical dependence versus time using the
Mathematica 7 program.
The kinetics of radical disproportionation were studied
spectrophotometrically at 514 nm in acidic sulphate media.
The phenothiazine radicals were generated in situ in
0.01 M phenothiazine derivatives dissolved in concen-
trated acid solution (95%, Aldrich). This process did not
lead to the complete conversion to the stable phenothiazine
radicals (ca. 25–50% yield). The phenothiazine derivatives
are photosensitive, and free radicals were stabilized by
sulphate or by the H? ion in concentrated acid solution.
The free radicals appear also in non-oxidizing concentrated
HCl acid, but this process proceeds with lower yield than in
the sulphuric acid solution. The concentrated HNO3 acid
oxidized phenothiazines directly to phenothiazine 5-oxide.
The reaction rate in acidic sulphate media was determined
Kinetic measurements
The kinetic measurements were performed on a Shimadzu
UV-1601 PC spectrophotometer equipped with a six-
position cell-holder. Kinetic data were acquired and pro-
cessed using the UVPC personal spectroscopy software.
In all measurements, the solutions were thermostated to
the desired temperature ( 0.1 °C) with an external Julabo
F25 ultrathermostat. The reaction rate was recorded by
123

Transition Met Chem (2011) 36:767–774
769
in dependence of the H? concentration: [PTZ] = 1
9 10-2 M, [PTZ?.] = (0.2–1.2) 9 10-4 M, [H2SO4] =
(0.35–1.65) M, I = const, T = 298 K. In a few cases,
the reaction rate was measured at different concentra-
tions of phenothiazines: [PTZ] = 1 9 10-2 M, [PTZ?.] =
(0.2–1.2) 9 10-4 M, [H2SO4] = 1.0 M, [H?] = 1.2 M,
I = 1.4 M (H?, HSO4-, SO42-), T = 298 K. The second-
order rate constants were calculated by fitting to the linear
inverse of concentration derivative of radical dependence
versus time.
1.0
0.8
0.6
0.4
0.2
0.0
300
400
500
600
Wavelength , nm
Results and discussion
Fig. 1 Spectral changes during chlorpromazine degradation by
manganese(III). Experimental conditions: [PTZ] = 5 9 10-5 M,
The kinetics of the oxidative transformation of phenothia-
zine derivatives by manganese(III) complexes have been
studied in acidic phosphate—pyrophosphate media ([PTZ] =
5 9 10-5 M, [MnIII] = (0.5–4.5) 9 10-3 M, [Na4P2O7]T =
0.1 M, [H3PO4]T = 1.0 M, [H?] = 0.04 M, I = 0.45 M
(H?, H2PO4-, Na?, H3P2O7-, H2P2O72-), T = 288–308 K).
Manganese(III) ions are more stable in pyrophosphate media
and slowly decompose with rate constants ranging from
3 9 10-7 to 1.5 9 10-8 s-1 and half-lives of 25–530 days in
the pH range 7–9 [26]. The stability decreases with increasing
pH as well as with decreasing the molar ratio of LT/MnT. At
values of LT/MnT lower than 10, decomposition half-lives
decrease to only 5 h at pH = 8 [26]. For pH [9, dispro-
portionation and precipitation of a MnO2 oxide is observed.
At pH \7, stability decreases mainly by protonation of the
ligand and liberation of protonated pyrophosphate resulting
in MnO2 precipitation, which begins to occur after 7 days at
pH = 1–2. There are large discrepancies in stability constants
published in the literature [29, 30], and it is not obvious that
these data can be assumed to be useful in the determination of
molar percentage of manganese(III) ions with pyrophosphate.
Taking into account, the values of the acidity constants for
[MnIII] = 5 9 10-4 M, [Na4P2O7]T = 0.1 M, [H3PO4]T = 1.0 M,
-
pH = 1.4 (phosphate buffer), I = 0.45 M (H?, H2PO4
,
Na?,
H3P2O7-, H2P2O72-), T = 298 K, 2, t = 5,616 s, Dt = 216 s
with the appearance of an intensively colored cationic
radical intermediate. The cationic phenothiazine radical is
known to be very stable in acidic solution [32, 33] and is
only slowly transformed to the final product. The latter
process is consistent with the decrease in absorbance in
the n–p* band at 500–525 nm and is accompanied by the
subsequent increase in absorbance in the p–p* band in the
range 300–400 nm. The final product was characterized on
the basis of the known positions of the electronic transition
band at 340 nm, characteristic for chlorpromazine oxide,
and at 347 nm, for trifluoperazine oxide [34].
Although oxidative degradation of phenothiazines pro-
ceeds in accordance with a two-step consecutive reaction
scheme, the first-order approximation has been applied. It
can be justified by the significant differences in the rates of
the two processes mentioned above. Kinetic measurements
apply mainly to the second, much slower PTZ?. radical
oxidation reaction, leading to PTZ?2, which then hydro-
lyzes to phenothiazine oxide (Scheme 1). Pseudo-first-
order rate constants were calculated from the first-order
dependence of absorbance versus time using a non-linear
least-square method. The relatively low standard deviations
in the determination of rate constants for the single kinetic
trace and the good convergence between experimentally
and theoretically determined absorbance values seem to
confirm the use of this approximation. Pseudo-first-order
rate constants are presented in Table 1; clearly the
dependence of manganese(III) is linear with significant
non-zero intercepts (Fig. 2). The linear regression data are
presented in Table 2 and can be expressed as follows:
pyrophosphoric acid (pK1a = 0.91, pK2a = 2.10, pK3a
=
6.70, and pK4a = 9.32) [31], we could show that the man-
2-
ganese(III) is coordinated with H2P2O7 ion at pH = 1.4
and exists mainly as the [Mn(H2P2O7)2]- ion. The acidity
constants of proton active groups that are present in free
ligands decrease usually after coordination to transition metal
ions.
The oxidative degradation of phenothiazine derivatives
proceeds via two consecutive reaction steps, in which
transformation of a PTZ radical is followed by faster oxi-
dation of PTZ to the radical intermediate. In acidic solu-
tion, only one final product was detected, phenothiazine
oxide. As can be seen in Fig. 1, the characteristic spectral
changes in UV–vis. spectra are consistent with a consec-
utive increase in absorbance in the n–p* band at 500 nm
for the trifluoperazine radical and 525 nm for the chlor-
promazine radical. These spectral changes are consistent
kobs ¼ kꢁ0 2 þ k20 ½MnIIIꢂ
in which the intercept and slope have been determined as the
ð1Þ
pseudo-first-order (k0-2) and second-order rate constants
123

770
Transition Met Chem (2011) 36:767–774
k1 , MnIII
-1 , MnII
Scheme 1 The mechanism of
the reaction between
phenothiazine derivatives and
the manganese(III) ion
S
+
S
k
N
R
2
N
R
R
2
R
1
1
k2 , MnIII
k-2 , MnII
S
2+
S
+
N
R
R
2
N
R
2
R
1
1
O
S
H O
2
S
2+
N
R
R
2
N
R
R
2
1
1
O
S
k3 , H O
2
S
S
+
2
+
N
R
N
R
R
N
R
R
2
k-3
2
2
R
1
1
1
Table 1 Observed pseudo-first-
order rate constants for the
reaction between phenothiazine
radicals (kobs) and the
Temp. (K)
288
pH
[MnIII] (M)
103 kobs (s-1
)
103 kobs (s-1
)
Chlorpromazine
0.78 0.01
Trifluoperazine
0.88 0.05
0.90 0.01
1.08 0.02
1.32 0.03
1.56 0.01
1.62 0.08
1.81 0.03
2.31 0.06
2.68 0.08
3.43 0.10
2.47 0.09
3.08 0.10
4.02 0.08
5.47 0.04
5.77 0.10
5.09 0.16
2.84 0.06
2.42 0.05
2.07 0.04
1.61 0.02
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
4.0
2.3
1.8
1.6
1.4
4.0
2.3
1.8
1.6
1.4
0.0005
0.0015
0.0025
0.0035
0.0045
0.0005
0.0015
0.0025
0.0035
0.0045
0.0005
0.0015
0.0025
0.0035
0.0045
0.0015
0.0015
0.0015
0.0015
0.0015
0.0015
0.0015
0.0015
0.0015
0.0015
manganese(III) ion
1.41 0.01
1.99 0.01
2.48 0.01
3.02 0.02
298
308
298
298a
1.54 0.05
2.96 0.03
4.17 0.03
5.87 0.02
7.69 0.14
3.00 0.01
5.82 0.03
8.37 0.15
10.47 0.04
13.41 0.05
6.16 0.21
2.50 0.05
2.36 0.04
Experimental conditions:
[PTZ] = 5 9 10-5 M,
[Na4P2O7]T = 0.1 M,
[H3PO4]T = 1.0 M,
pH = 1.4–4.0 (phosphate
buffer), I = 0.45 M (H?,
2.44 0.03
2.77 0.03
0.58 0.01(157)
0.70 0.01(27.0)
1.01 0.01(19.1)
1.58 0.01(12.5)
2.31 0.01(6.6)
0.57 0.01(220)
0.65 0.01(75.9)
0.70 0.01(47.7)
0.75 0.01(32.3)
0.86 0.01(17.0)
H2PO4-, Na?, H3P2O7
,
-
2-
H2P2O7
a
)
k2, s-1 (k3, M-1 s-1
from Eq. 2
)
(k02), respectively. In fact, the values of the intercepts should
be close to zero as is expected for strong oxidants, for
example, cerium(IV). These data mean that another process
takes place at lower concentration of H? ion and pH [ 1.
Under such conditions, a competing reaction to the oxidation
process might be disproportionation of phenothiazines
123

Transition Met Chem (2011) 36:767–774
771
disproportionation influences only the intercept (Fig. 2) in
the observed rate constant dependence on [MnIII]. In the
case of more reactive radicals like promethazine (data not
shown), the observed rate constants should be fitted by
Eq. 2.
14
12
10
8
However, when the pH is increased, an increasingly
important influence of the disproportionation process is
detected even for the most stable trifluoperazine and
chlorpromazine radicals. In 0.2 M (pH = 4.0) phosphoric
acid solution, the value of the observed first-order rate
constant differs significantly from the other results (Fig. 3).
In other cases, kobs values are similar to each other. Due to
the fact that the increase in the value of the observed rate
constant with increasing pH for both trifluoperazine and
chlorpromazine is similar and covers the pH range outside
the pKa of these compounds (9.2 for chlorpromazine) [35],
changes might be attributed to either changes in the coor-
dination sphere of the complex of manganese(III) or a
change in rate of disproportionation. At pH [ 2, manga-
nese(III) undergoes a further coordination reaction with
pyrophosphates; this process causes the blue-shift of the
transition band from 513 to 479 nm (pH = 5.5). An
increasing concentration of the manganese(III) complexes
with two and three coordinated pyrophosphates will cause
a decrease in the redox potential, which at pH = 1.5 is
1.25 V. This will reduce the rate of oxidation reaction
proceeding with an outer-sphere mechanism. Thus, the
changes observed and increase in the overall degradation
rate with increasing pH can be attributed to the increased
rate of disproportionation. The kinetic trace at higher pH
corresponds to the function characterized by the first- and
second-order decay (Eq. 2). The rate constants of oxidative
degradation calculated for kinetic traces at pH = 1.4, do
not differ from the values calculated from the first-order
dependence, while for pH = 4.0 they varied in the same
trend as the redox potential of the MnIII/MnII couple
(Table 2).
6
4
2
0
0.000
0.001
0.002
0.003
0.004
0.005
[MnIII], M
Fig. 2 Plots of kobs versus [PTZ] for the electron-transfer reaction
between chlorpromazine and manganese(III) at different tempera-
tures. Experimental conditions: [PTZ] = 5 9 10-5 M, [Na4P2O7]T
0.1 M, [H3PO4]T = 1.0 M, pH = 1.4 (phosphate buffer), I = 0.45 M
(H?, H2PO4-, Na?, H3P2O7-, H2P2O72-), T = 288 (filled square),
298 (filled circle), 308 (filled triangle) K
=
radicals [32]. In that case, the kinetic traces should be
characterized by the first-order and second-order radical
decay according to the following concentration dependences
versus time:
A ¼ 1=ðð1=AoÞ expðk2tÞ þ ð2k3=k2Þðexpðk2tÞ ꢁ 1ÞÞ
ð2Þ
as a result of integration of the differential equation, d[A]/
dt = -k2[A] - 2k3[A]2, where A is the concentration of
radical, k2 is the first-order, and k3 is the second-order rate
constant for dismutation. Preliminary tests showed that
only at the lowest manganese(III) concentration, small
deviations from first-order kinetics occurred in the first
few percent of conversion; therefore, the highest but sta-
tistically low (ca. 2%) value of standard deviation of the
rate constant for a single kinetic trace has been evaluated.
A statistically significant decreasing trend in standard
deviation was observed for higher oxidant concentrations
(ca. 1%). In the case of more stable radicals, such as
promazine, chlorpromazine, and trifluoperazine, slow
Levy et al. [32] reported the stability of 10-alkylphe-
nothiazine free radicals in response to the Hammett acidity
Table 2 Linear regression data for the plots of kobs versus [MnIII] (Fig. 2) for the reaction between phenothiazine radical and the manganese(III)
ion
Temp. (K)
k02 (M-1 s-1
)
103 k0-2 (s-1
)
k02 (M-1 s-1
)
103 k0-2 (s-1
)
Chlorpromazine
0.55 0.02
1.51 0.07
2.55 0.07
Trifluoperazine
0.18 0.03
0.45 0.05
0.83 0.04
288
0.55 0.04
0.64 0.20
1.85 0.20
0.70 0.07
1.25 0.15
1.95 0.11
293
298
DH= (kJ mol-1
)
46
9
49
6
DS= (J K-1 mol-1
)
-88 30
-87 18
Experimental conditions: [PTZ] = 5 9 10-5 M, [MnIII] = (0.5–4.5) 9 10-3 M, [Na4P2O7]T = 0.1 M, [H3PO4]T = 1.0 M, pH = 1.4 (phos-
phate buffer), I = 0.45 M (H?, H2PO4-, Na?, H3P2O7-, H2P2O7
2-
)
123

772
Transition Met Chem (2011) 36:767–774
Fig. 3 Plots of [PTZ?ꢀ] versus
time for the reaction between
chlorpromazine radical and the
manganese(III) ion.
Experimental conditions:
[PTZ] = 5 9 10-5 M,
[MnIII] = 1.5 9 10-3 M,
I = const (H?, H2PO4-, Na?,
H3P2O7-, H2P2O72-),
0,000030
0,000025
0,000020
0,000015
0,000010
0,000005
0,000000
A
C
0,00005
0,00004
0,00003
0,00002
0,00001
0,00000
0
1000
2000
3000
4000
0
1000
2000
3000
4000
T = 298 K, A pH = 4.0, 1st
order fit, Chi2 = 6 9 10-13
k2 = 0.0041 0.0001;
Time , s
Time , s
,
0,000030
0,000025
0,000020
0,000015
0,000010
0,000005
0,000000
B
D
0,00005
0,00004
0,00003
0,00002
0,00001
0,00000
B pH = 4.0, 1st ? 2nd order
fit, Chi2 = 1 9 10-14
k2 = 0.00058 0.00001,
,
k3 = 157 1; C pH = 1.4,
Chi2 = 6 9 10-14
,
k2 = 0.0026 0.00001;
D pH = 1.4,
Chi2 = 2 9 10-14
,
0
1000
2000
3000
4000
0
1000
2000
3000
4000
k2 = 0.00231 0.00002,
k3 = 6.6 0.3
Time , s
Time , s
(see Table 3). It may be a consequence of the reversibility
of the disproportionation process, and the reverse com-
proportionation reaction takes place. Thus, the observed
rate constant is expected to be the sum of the second-order
rate constant for disproportionation and the second-order
rate for the reverse process with regeneration of reactant
in the reaction mixture. The second-order rate constants,
calculated from linear regression data (first few experi-
mental points), at [H?] = 0.04 M, in which the reaction
with manganese(III) has been studied, are 8.8 and
9.2 M-1 s-1 for chlorpromazine and trifluoperazine radi-
cal, respectively. These variables are close to the values of
k0-2/[PTZ?ꢀ] for the reaction with manganese(III), which
were estimated as 12.8 and 25 M-1 s-1, respectively. The
similarity of these quantities confirms the hypothesis that
the oxidative degradation proceeds simultaneously with the
disproportionation as a competing reaction. Nevertheless,
this latter process should proceed with a higher rate in
phosphate than in sulphate media.
function in sulphuric acid solutions [36]. Because the
Hammett function is more convenient for concentrated acid
solutions and no detailed data for more dilute solutions are
available, we decided to measure the rate of the dispro-
portionation reaction of these phenothiazine derivatives
in sulphuric acid solution in the range of 0.35–1.65
M. Phenothiazine free radicals were produced directly in
concentrated sulphuric acid (95%), in which they are very
stable. The choice of acidic sulphate media resulted in the
highest yield of phenothiazine free radicals. The second-
order rate constants were calculated from the reciprocal
of concentration versus time according to the following
equation:
1=A ꢁ 1=Ao ¼ 2k3t
ð3Þ
where A, as before, is concentration of radical and Ao, is
initial concentration at time t = 0. The second-order rate
constants are presented in Table 3. The rate of radical
disproportionation decreases with increasing H? concen-
tration, and phenothiazine radicals are more stable at
higher acid concentration. The plot of the second-order rate
constants versus [H?] is non-linear (Fig. 4). This charac-
teristic trend is not affected by ionic strength because the
positively charged radicals should react with a higher rate
at increased ionic strength. The hydrogen ion concentration
increases the stability of the free radical and decreases
the rate of the disproportionation not directly, but probably
via interaction of cationic radicals with sulphate or other
negatively charged ions of electrolyte present in aqueous
solution. The second-order rate constants were found to be
inversely proportional to the initial concentration of free
radical, although this tendency was not so significant as for
the decreasing rate dependence on the H? concentration
The reaction with manganese(III) proceeds according to
an outer-sphere mechanism. This conclusion is supported
by the fact that the rate of the electron-transfer process
?ꢀ
can be correlated with the reduction potential, E
?ꢀ
PTZ/
= 0.6 V and E
?ꢀ
= 1.0 V for chlorpromazine
?ꢀ
PTZ
PTZO/PTZ
and E
perazine [37]. The very similar reactivities of phenothia-
= 0.7 V and E
= 1.0 V for trifluo-
PTZ/PTZ
PTZO/PTZ
zine free radicals with manganese(III) are consistent with
?ꢀ
the similar values of reduction potential of E
.
PTZO/PTZ
These similarities result from the similar electronic struc-
tures of the radicals as seen from the ionization energy of
HOMO orbitals. As can be seen, the relevant electron-
transfer reaction proceeds with a similar negative entropy
of activation. The negative values of DS= indicate that this
123

Transition Met Chem (2011) 36:767–774
773
Table 3 Selected second-order
rate constants for
[H2SO4]
[H?] (M)
104 [PTZ] (M)
104 [PTZ?.] (M)
k3 (M-1 s-1
)
disproportionation of
phenothiazine free radicals in
acidic sulphate media
Promethazine
0.35
0.43
0.55
0.67
0.90
1.14
1.38
1.2
2
1.1
1.1
1.1
1.1
1.1
1.1
0.7
0.5
0.35
0.2
191.0 1.2
164.5 0.6
146.2 0.9
105.1 0.6
84.9 0.3
75.3 0.2
69.2 0.1
82.5 0.1
98.8 0.2
140.5 0.6
0.45
2
0.55
2
0.75
2
0.95
2
1.15
2
1.0
2.0
1.5
1.0
0.5
1.0
1.2
1.0
1.2
1.0
1.2
Chlorpromazine
0.35
0.43
0.55
0.67
0.90
1.14
1.38
1.2
2
1.3
1.3
1.3
1.3
1.3
1.3
0.95
0.7
0.5
0.2
6.08 0.04
5.79 0.03
5.30 0.03
4.39 0.02
3.43 0.01
3.01 0.01
3.18 0.01
3.36 0.01
3.93 0.01
4.11 0.01
0.45
2
0.55
2
0.75
2
0.95
2
1.15
2
1.0
2.0
1.5
1.0
0.5
1.0
1.2
1.0
1.2
1.0
1.2
Trifluoperazine
0.85
1.02
1.14
1.26
1.50
1.74
1.98
1.2
5
1.2
1.2
1.2
1.2
1.2
1.2
1.1
0.8
0.55
0.3
5.68 0.07
5.33 0.05
4.82 0.06
3.76 0.04
3.30 0.02
2.69 0.02
1.79 0.01
1.96 0.01
2.30 0.01
3.28 0.01
0.95
5
1.05
5
1.25
5
1.45
5
1.65
5
1.0
2.0
1.5
1.0
0.5
1.0
1.2
Experimental conditions:
1.0
1.2
(a) [PTZ] = 1 9 10-2 M,
[PTZ?.] = (1.1 - 1.3) 9 10-4
M, [H2SO4] = (0.35 - 1.65)
M, I = const, T = 298 K for
the k3 dependence of [H?];
(b) [PTZ] = 1 9 10-2 M,
[PTZ?.] = (1.3 - 0.2) 9 10-2
M, [H2SO4] = 1.0 M,
1.0
1.2
Promazine
0.35
0.43
0.55
0.67
0.90
1.14
1.38
2
2
2
2
2
2
1.6
1.6
1.6
1.6
1.6
1.6
1.71 0.01
1.57 0.01
1.34 0.01
1.02 0.01
0.75 0.01
0.40 0.01
0.45
0.55
0.75
[H?] = 1.2 M, I = 1.4 M (H?,
HSO4-, SO42-), T = 298 K for
0.95
1.15
the k3 dependence of [PTZ?ꢀ
]
process is accompanied by extensive solvation related to
charge creation in the activation process and with similar
changes of charge and solvation effects for creating a
2? cationic phenothiazine transient in the activation
process.
processes, and can be useful in an effort to develop new
methods for the clean oxidation of pharmacologically
active phenothiazines, and selecting the most effective
and environmentally friendly manganese(III) oxidants with
potential applications in green chemistry for the disposal of
this class of pharmaceuticals. Compared to manganese(III)-
pyrophosphate, the green oxidants, such as oxygen or
Manganese(III)-pyrophosphate complexes act as very
efficient oxidants for phenothiazine derivative degradation
123

774
Transition Met Chem (2011) 36:767–774
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