Oxidation of 3-(3,4-dihydroxy phenyl)-L-alanine (levodopa) and 3-(3,4,dihydroxy phenyl)-2-methyl-L-alanine (methyl dopa) by manganese(III) in pyrophosphate media: Kinetic and mechanistic study

Article abstract of DOI:10.1002/kin.1041

Manganese(III) (Mn(III)) has been stabilized in weakly acidic solution by means of pyrophosphate and the nature of the complex was elucidated spectrophotometrically. Stoichiometry of Mn(III)-oxidation of levodopa and methyl dopa in pyrophosphate medium wa

Full text of DOI:10.1002/kin.1041

Oxidation of 3-(3,4-
Dihydroxy Phenyl)-
L
-Alanine
(Levodopa) and 3-(3,4-
Dihydroxy Phenyl)-2-
Methyl- -Alanine (Methyl
L
Dopa) by Manganese(III) in
Pyrophosphate Media:
Kinetic and Mechanistic
Study
B. S. SHERIGARA,1 E. V. S. SUBRAHMANYAM,2 K. ISHWAR BHAT,2
B. E. KUMARA SWAMY1
1Department of Industrial Chemistry, Kuvempu University, Jnana Sahyadri, Shankaraghatta—577 451, Karnataka, India
2NGSM Institute of Pharmaceutical Science, Mangalore—573 003, Karnataka, India
Received 9 September 1999; accepted 2 April 2001
ABSTRACT: Manganese(III) (Mn(III)) has been stabilized in weakly acidic solution by means of
pyrophosphate and the nature of the complex was elucidated spectrophotometrically. Stoi-
chiometry of Mn(III)-oxidation of levodopa and methyl dopa in pyrophosphate medium was
established in the pH range 2.5–4.0 by iodometric and spectrophotometric methods. The
reaction shows a distinct variation in kinetic order with respect to [Mn(III)], a first-order de-
pendence in the pH range 1.9–2.6, decreasing to fractional order above pH 3. Other common
features include first-order dependence on [dopa], positive fractional order dependence on
[Hϩ], and inverse first-order dependence on [Mn(III)] in the pH range studied. The effects of
2
Ϫ
varying ionic strength and solvent composition were studied. Added ions such as SO4 and
Ϫ
ClO4 alter the reaction rate, probably due to the change in the formal redox potential of
Mn(III)–Mn(II) couple because of the changes in coordination environment of the oxidizing
species. Evidence for the transient existence of the free radical intermediate is given. Cyclic
voltametric sensing of levodopa and methyl dopa has ruled out the formation of dopaquinones
as oxidation products in the pH range studied. Activation parameters have been evaluated
using the Arrhenius and Erying plots. Mechanisms consistent with the kinetic data have been
proposed and discussed. These studies are expected to throw some light on dopa metabolism.
᭧ 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 449–457, 2001
Correspondence to: B. S. Sherigara (root@shikuv.kar.nic.in)
᭧ 2001 John Wiley & Sons, Inc.

450
SHERIGARA ET AL.
INTRODUCTION
Pharmaceutically pure levodopa and methyl dopa
complying with the pharmacopeial standards (Sun
Pharmaceuticals, Baroda) were obtained.Aqueous
stock solutions of levodopa and methyl dopa (0.05 mol
Levodopa [1] 3-(3,4-dihydroxyphenyl)-L-alanine is a
natural amino acid precursor of dopamine.The dopa-
mine cannot be used as drug because, being poorly
lipid soluble, it is not well absorbed in the gut and
does not penetrate the central nervous system.Levo-
dopa is particularly effective in the treatment of trem-
ors and hyperkinesia [2].It can be called an universal
antiparkinsonian drug, as it improves all the manifes-
tations of parkinsonism.This drug improves the mood
and memory and makes patients more alert and inter-
ested in themselves and in their surroundings.
A great deal of attention has been focused on the
oxidation of drugs and pharmaceuticals by metal ions.
Of these, Mn(III) oxidations are of special significance
because of their biological importance.There are a
number of reports on the kinetics of oxidations of var-
ious substrates by Mn(III) in perchlorate, sulfate, ac-
etate, and pyrophosphate media [4].Kinetics of oxi-
dation of amino acids by various oxidizing agents in
general [5–10] and aquomanganic ions in particular
[11–13] have been reported.Quite recently, we have
3
dmϪ ) were prepared with double-distilled water as re-
quired.All other reagents used were of analytical
grade.
Kinetic Measurements
A known amount of Mn(III) pyrophosphate solution
was thermally equilibrated at 318 K.It was added to
a mixture of dopa, Mn(II), [P2O7 Ϫ] (for ionic
4
strength), orthophosphoric acid (to maintain pH), and
water (to keep total volume constant) taken from an-
other glass-stoppered bottle also maintained at the
same temperature.The progress of the reaction was
monitored by iodometric estimation of unreacted
Mn(III) pyrophosphate present in known aliquots of
the mixture withdrawn at regular intervals of time.The
course of the reaction was studied to 75% completion.
The rate constants calculated were reproducible within
Ϯ5%.Identical results were obtained when the
reaction was monitored by a spectrophotometric
method.
studied the kinetics of Mn(III) oxidation of
by Mn(III) sulfate in aqueous sulfuric acid [14],
-arginine in pyrophosphate medium [15], -asparatic
acid and -glutamic acid [16] by Mn(III) in pyro-
L-histidine
L
L
L
phosphate and acetate media, and lower ꢀ-amino acids
[17–19] by Mn(III) acetate in aqueous acetic acid.
There seems to be no report in the literature on the
kinetics of oxidation studies that may throw some light
on the mechanism of conversion of the compounds in
biological systems.Hence, as a part of our work on
mechanistic studies on Mn(III) oxidation of organic
and inorganic substrates in general and medicinal
compounds in particular [14–16,20], we have inves-
tigated the stoichiometry and mechanism of oxidation
of levodopa and methyl dopa by Mn(III) in pyrophos-
phate medium.
RESULTS
Stoichiometry and Product Analysis
The stoichiometry of the reaction between Mn(III) py-
rophosphate and levodopa was investigated under ex-
cess oxidant conditions.A known amount of levodopa
solution (5.0 ϫ 10Ϫ mol dmϪ ) was allowed to react
completely with a 10-fold excess of the Mn(II) at 40ЊC
in the presence of orthophosphoric acid to maintain
pH at 4.0. The excess Mn(III) was estimated by io-
dometric method.The product formed was extracted
with ether, the ether was distilled off, and the residue
was identified as the aldehyde by its IR spectra, where
the 9OH stretching frequency was observed in the
2
3
EXPERIMENTAL
Manganese(III) pyrophosphate was prepared by the
literature method [21] and was standardized by the
iodometric method; it was further checked by titrating
against standard Fe(II) using diphenyl sulfonate as an
internal indicator.
A Shimadzu model UV-Visible spectrophotometer
with a 1-cm quartz cell was used for the absorption
measurements under the experimental conditions.The
ꢁmax for the Mn(II) species in a solution of pH 5.0
occurred at 500 nm, which slightly varied as a function
of pH.
range 3400–3500 cmϪ , 9CO stretching frequency
1
of aldehyde was observed in the range 1630–1680
1
cmϪ , and 9CH stretching frequency was observed
in the range 2600–3000 cmϪ .
1
Stoichiometry of the reaction between Mn(III) py-
rophosphate and levodopa was found to be 2:1, both
at low (Ͻ3) and high (Ͼ3) pH.Product analysis was
carried out under substrate excess conditions as fol-
lows.

OXIDATION BY MANGANESE(III) IN PYROPHOSPHATE MEDIA
451
2
Reaction mixtures containing levodopa (5.0 ϫ 10Ϫ
and a plot of log(k) versus log[dopa]0 showed that the
order in [dopa] was unity at both the pH ranges.
3
3
mol dmϪ ) and Mn(III) pyrophosphate (5.0 ϫ 10Ϫ
mol dmϪ ) at pH 4.0 and at 40ЊC were allowed to react
completely.One of the products formed was identified
as the aldehyde [22] by its 2,4-dinitrophenylhydrazone
derivative, which was obtained up to a 90% yield.
The observed stoichiometry can be represented by
the equation
3
Dependence of Rate on pH
The pH of the reaction was varied between 1.9 and
4.0 by varying the orthophosphoric acid concentration
4
at constant [Mn(II)], [P2O7 Ϫ], and [Mn(III)]0.The
rates decreased with an increase in pH.The order with
respect to [Hϩ] was found to be 0.5 both at low and
high pH ranges (Tables III and IV).
NH2
&
2Mn(III) ϩ R9CH9COOH ϩ H2O !:
3Mn(II) ϩ RCHO ϩ NH3 ϩ CO2 ϩ 2Hϩ
(1)
Dependence of Rate on Ionic Strength and
[Mn(II)]
where R is
The rate increased with decreasing ionic strength ob-
tained by varying the sodium pyrophosphate concen-
tration.Mn(II) was the reduced product of the oxidant,
and as the initial concentration of added Mn(II) was
increased, the rate progressively decreased and the or-
der with respect to Mn(II) was found to be 1.
HO
CH29
HO
Dependence of Rate on Added Salts
[Mn(III)] and [Levodopa] Dependence
Ϫ
2Ϫ
The effect of added anions like ClO4 and SO4 on
the reaction rate was investigated (Tables V and VI).
A slight enhancement in reaction rate with increasing
The first-order and half-order dependence on Mn(III)
at low and high pH ranges, respectively, were indi-
cated by the linearity by log[Mn(III)] versus time plots
and [Mn(III)]1/2 versus time plots.The values of
pseudo-first-order and pseudo-half-order rate con-
stants were insensitive to changes in initial concentra-
tion of Mn(III) (Tables I and II).
Ϫ
[ClO4 ] may be due to the establishment of a new
Mn(III)/Mn(II) redox couple and also due to ionic
strength considerations.The observed retardation with
increasing [SO4 Ϫ] could be due to reduction in [Hϩ]
2
via formation of HSO4Ϫ as,
At constant [Mn(III)]0, pH, [P2O7 Ϫ], and [Mn(II)],
4
2
Ϫ
SO4 Ϫ ϩ Hϩ !: HSO4
the rate constants increased with increase in [dopa]0
Table I Pseudo-First-Order Rate Constants (kobs) for the Oxidation of Levodopa and Methyl Dopa by Mn(III)
Pyrophosphate at 313 K, pH ϭ 2.2, and [P2O7 Ϫ] ϭ 1.4 ϫ 10Ϫ2 mol dmϪ
4
3
Ϫ
1
k
obs (s )
Ϫ
3
Ϫ
3
Ϫ3
Mn(III) 103 (mol dm
)
[Levodopa] 102 (mol dm
)
Mn(II) 103 (mol dm
)
Levodopa
Methyl Dopa
2.5
5.0
7.5
10.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
2.5
5.0
7.5
10.0
5.0
5.0
5.0
5.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
1.0
2.0
3.0
4.0
3.74
3.64
3.76
3.76
2.4
3.64
5.69
6.90
7.2
3.22
3.15
3.19
3.21
1.96
3.15
5.12
5.12
6.72
4.76
3.15
2.12
5.2
3.64
2.53

452
SHERIGARA ET AL.
Table II Pseudo-Half-Order Rate Constants (kobs) for the Oxidation of Levodopa and Methyl Dopa by Mn(III)
Pyrophosphate at 313 K and pH ϭ 4.0
Ϫ
1
104 kobs (mol1/2 dm3/2
s )
Ϫ
3
Ϫ3
Ϫ3
Mn(III) 103 (mol dm
)
[Sub] (mol dm
)
Mn(III) 103 (mol dm
)
Levodopa
Methyl Dopa
2.5
5.0
7.5
10.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
2.5
5.0
8.0
12.0
5.0
5.0
5.0
5.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
1.0
2.0
3.0
4.0
6.88
7.05
7.05
7.05
3.50
7.05
14.9
21.1
13.9
9.9
6.42
6.51
6.53
6.56
3.05
6.51
14.53
19.67
13.53
9.52
6.51
4.21
7.05
4.68
Table III Effect of Variation of [P2O7 Ϫ] and Methyl Dopa by Mn(III) Pyrophosphate at [Mn(III)] ϭ 5.0 ϫ 10Ϫ3 mol
4
3
3
dmϪ3, [Mn(II)] ϭ 3.0 ϫ 10Ϫ mol dmϪ3, and [Dopa] ϭ 5.0 ϫ 10Ϫ2 mol dmϪ
Ϫ1
102 kobs (s
)
4
Ϫ
[P2O7
]
Temperature
(K)
102 (mol dm
)
pH
Levodopa
Methyl Dopa
Ϫ
3
0.76
0.92
1.40
2.00
1.40
1.40
1.40
1.40
1.40
1.40
2.2
2.2
2.2
2.2
1.9
2.0
2.6
2.2
2.2
2.2
313
313
313
313
313
313
313
303
308
323
5.98
5.29
3.64
2.83
6.60
5.29
1.69
1.70
2.69
7.43
5.46
4.83
3.15
2.37
6.17
4.76
1.28
1.61
2.22
6.92
Table IV Effect of Variation of [SO4 Ϫ] and Solvent Effects on the Rate of Oxidation of Levodopa and Methyl Dopa
2
3
by Mn(III) Pyrophosphate at 313 K, pH ϭ 4.0, [Mn(III)] ϭ 5.0 ϫ 10Ϫ3 mol dmϪ3, [Mn(II)] ϭ 3.0 ϫ 10Ϫ3 mol dmϪ
,
4
2
3
[P2O7 Ϫ] ϭ 1.4 ϫ 10Ϫ mol dmϪ3, [Sub] ϭ 5.0 ϫ 10Ϫ3 mol dmϪ
kobs kobs
kobs
Ϫ
Ϫ
1
Ϫ
Ϫ
1
Ϫ
Ϫ1
(mol1/2 dm 3/2 s
)
(mol1/2 dm 3/2 s
)
(mol1/2 dm 3/2 s
)
Percentage
2Ϫ
SO4
Methyl ClO4 ϫ 102
Methyl of Absolute Dielectric
Dopa
Methyl
Dopa
Ϫ
3
Ϫ3
(mol dm
)
Levodopa
Dopa
(mol dm
)
Levodopa
Alcohols
Constant
Levodopa
5.0
10.0
17.4
6.5
6.1
5.8
6.01
5.63
5.41
5.0
10.0
16.7
7.5
7.8
8.2
7.15
7.38
7.76
3.0
5.0
10.0
76.7
75.2
72.9
6.9
6.4
6.1
6.51
6.01
5.9

OXIDATION BY MANGANESE(III) IN PYROPHOSPHATE MEDIA
453
Table V Effect of Variation of [SO4 Ϫ] and Solvent on the Oxidation of Dopa by Mn(III) Pyrophosphate at 313 K,
2
3
pH ϭ 2.2, [Mn(III)] ϭ 1.4 ϫ 10Ϫ2 mol dmϪ3, [Dopa] ϭ 5.0 ϫ 10Ϫ2 mol dmϪ
kobs
kobs
kobs
Ϫ
Ϫ
1
Ϫ
Ϫ
1
Ϫ
Ϫ1
(mol1/2 dm 3/2 s
)
(mol1/2 dm 3/2 s
)
(mol1/2 dm 3/2 s
)
Percentage
2Ϫ
SO4
Methyl ClO4 ϫ 102
Dopa
Methyl of Absolute Dielectric
Dopa
Methyl
Dopa
Ϫ
3
Ϫ3
(mol dm
)
Levodopa
(mol dm
)
Levodopa
Alcohols
Constant
Levodopa
5.0
10.0
17.4
3.2
2.5
2.3
2.78
2.16
1.97
5.0
10.0
16.7
3.9
4.2
4.6
3.51
3.77
4.26
3.0
5.0
10.0
76.7
75.2
72.9
6.9
6.4
6.1
6.51
6.01
5.9
Dependence of Rate on Temperature
The variation in reaction rate with the dielectric
constant of the reaction mixture was investigated by
adding ethanol to the solvent.The observed decrease
in rate with the decrease in dielectric constant is in
conformity with Amis [23] and other theories [24,25]
(i.e., it indicates the importance of specific solvent–
solute interactions) (Tables IV and V).
The reaction was carried out at 303, 308, 313, and 323
K at constant ionic strength, pH, and Mn(III), both at
low (2.2) and high (4.0) pH. Arrhenius and Erying
plots of log k versus 1/T gave good straight lines.From
the slopes and intercepts, the values of the activation
parameters for both levodopa and methyl dopa were
calculated (Table VII).
Table VI Effect of Variation of [P2O7 Ϫ], pH and Temperature on the Rate of Oxidation of Levodopa and Methyl
Dopa by Mn(III) Pyrophosphate at [Mn(III)] ϭ 5.0 ϫ 10Ϫ4 mol dmϪ3, [Sub] ϭ 5.0 ϫ 10Ϫ2 mol dmϪ3, and [Mn(II)] ϭ
4
3
3
3.0 ϫ 10Ϫ mol dmϪ
Ϫ
Ϫ1
k
obs (mol1/2 dm 3/2 s
)
[P2O7 ] 102
Temperature
(K)
4
Ϫ
Ϫ
3
(mol dm
)
pH
Levodopa
Methyl Dopa
0.76
0.92
1.40
2.00
1.40
1.40
1.40
1.40
1.40
1.40
1.40
1.40
4.0
4.0
4.0
4.0
3.0
3.5
3.8
4.0
4.0
4.0
4.0
4.0
313
313
313
313
313
313
313
313
303
308
313
323
11.5
10.71
7.05
6.10
20.14
10.70
8.51
7.50
2.40
5.10
7.50
14.10
10.97
10.23
6.51
5.63
19.92
10.24
7.91
6.51
1.98
4.67
6.51
13.52
Table VII Activation Parameters of Levodopa and Methyl Dopa at High and Low pH
Levodopa
Methyl Dopa
pH ϭ 4.0
pH ϭ 2.2
pH ϭ 4.0
pH ϭ 2.2
Ϫ
1
Ea (kJ mol
log A
)
53.99
5.85
55.52
128.09
40.036
57.44
8.15
58.01
Ϫ87.65
27.376
47.78
4.74
47.86
42.50
5.59
43.27
ꢂH# (kJ mol
)
Ϫ
1
ꢂS (JK 1 mol
)
Ϫ153.40
74.96
Ϫ135.71
42.43
Ϫ
Ϫ
1
ꢂG# (kJ mol
)
Ϫ
1

454
SHERIGARA ET AL.
DISCUSSION
range 0.91–1.45 was carried out recently [18] in
pyrophosphate medium.It was shown that the rate
of oxidation decreases with an increase in pH.At
pH Ͼ 2, the reaction becomes extremely slow; there-
fore, kinetics of oxidation of phenylalanine at higher
pH could not be carried out as a comparative study.
Also, now it can be inferred that the two 9OH groups
present in levodopa activate the oxidation of amino
acid moiety.
Kinetics of another methylated derivative of levo-
dopa, methyl dopa, was studied under identical exper-
imental conditions.The rate of oxidation of methyl
dopa was found to be slower than that of levodopa,
probably due to the steric effect of the 9CH3 group
present in the amino acid chain.
Electrochemical Studies
The electrochemical oxidation of levodopa with plat-
inum electrode in pyrophosphate buffer (pH ϭ 1.25)
shows a well-defined anodic peak at Epa ϭ 0.571 V
(Fig.1) and a complementary cathodic peak appearing
at Epc ϭ 0.381 V. The electrooxidation product of lev-
odopa has been identified to be the dopaquinone, the
oxidation of catechol moiety.The peak current in-
creases with sweep rate and also with concentration of
dopa.The anodic peak potential shifts on lowering pH,
probably due to the involvement of protons in the elec-
trochemical oxidation of levodopa. Epa increases from
0.54 to 1.0 V as the pH changes from 1.01 to 9.8 (Fig.
2).This suggests that as the pH is increased oxidation
of catechol moiety of dopa to dopaquinone becomes
more difficult.Similar dependence of half-wave po-
tential on pH was reported by investigation of levo-
dopa with a polycarbazole electrode [26].Therefore,
it is inferred that Mn(III) oxidation of dopa takes place
directly through decarboxylation and deamination of
amino acid and catechol moiety does not get oxidized
to quinone in the pH range studied.Further, separate
experiments were performed, in which Mn(III) pyro-
phosphate was made to react with catechol by main-
taining the experimental condition, and oxidation of
the catechol was found to be negligible.
The observed results of first- and half-order depen-
dence on Mn(III), first-order dependence on [dopa],
and fractional-order dependence on [Mn(II)] can be
accounted for by the mechanism given.
Oxidation at Low pH Range (1.9–2.6)
In acidic medium, Mn(III) pyrophosphate can be con-
sidered to be a metal chelate (a coordinated compound
with a ring structure) anion having the composition
Mn(H2P2O7)3 Ϫ.The observed results of first-order
3
3Ϫ
dependence each on [dopa] Mn(H2P2O7)3 and in-
verse fraction-order dependence each on Mn(II)
[(H2P2O7)3 Ϫ] and [H2P2O7 Ϫ] can be explained with
the proposed mechanism.
3
2
The kinetics of oxidation of L-phenylalanine at pH
Ϫ
1
Figure 1 Cyclic voltametric curve of levodopa in pyrophosphate buffer at platinum electrode.Sweep rate ϭ 50 mV s
pH ϭ 1.25, temp. ϭ 298 K, concentration of levodopa ϭ 2 mM, and electrolyte ϭ 20 mM pyrophosphate.
,

OXIDATION BY MANGANESE(III) IN PYROPHOSPHATE MEDIA
455
Figure 2 Effect of pH on anodic peak potential of levodopa in pyrophosphate buffer at platinum electrode.Sweep rate ϭ 50
Ϫ
mV s 1, pH ϭ 1.25, temp. ϭ 298 K, concentration of levodopa ϭ 2 mM, and electrolyte ϭ 20 mM pyrophosphate.
K1
R9CH9COOꢄ ꢃ Hꢃ
R9CH9COOH
(fast)
NH3
NH3
ꢃ
ꢃ
(S)
(SHꢃ)
(2)
(3)
K2
(fast)
Mn(H2P2O7)33ꢄ ꢃ R9CH9C9OH
R9CH99C9OH ꢃ Hꢃ
NH3
O
NH3
O
ꢃ
(SHꢃ)
Mn(H2P2O7)3
3ꢄ
(x)
K3
2ꢄ
R9CH99C9OH
R9CH9C9OH ꢃ Mn(H2P2O7)22ꢄ ꢃ H2P2O7
(fast)
NH3
O
NH2 Oꢃ
ꢅ
3ꢄ
Mn(H2P2O7)3
(x)
(y)
(4)
(5)
k4
ꢅ
R9CH9C9OH
R9CH ꢃ CO2 ꢃ Hꢃ
(slow)
NH2
O
NH2
ꢃ
ꢃ
ꢅ
(y)
(z)

456
SHERIGARA ET AL.
fast
ꢅ
3ꢄ
2ꢄ
2ꢄ
Mn(H2P2O7)3
ꢃ H2O
R9CHO ꢃ Mn(H2P2O7)2 ꢃ NH4ꢃ ꢃ H2P2O7
ꢃ R9CH
NH2
(z)
(6)
SHϩ represent the mono cationic forms of the sub-
strate, levodopa, X is Mn(III)–substrate complex an-
ion, Y is the free radical cation, and Z is the free rad-
ical.
The existence of a transient free radical interme-
diate was indicated by the positive test involving po-
lymerization of olefinic monomers.The evidence for
the in situ formation of transition metal–substrate
complex species is available in the literature [27].
The rate of dopa oxidation is given by
Oxidation at High pH Range (3.0–4.5)
An explanation for half-order kinetics involves a fast
reversible dissociation step preceding the rate-deter-
mining step.One possibility is that all the Mn(III) is
essentially in the form of polymeric species
Mn2(H2P2O7)6 Ϫ, with a small amount of kinetically
6
active monomeric species Mn(H2P2O7)3 Ϫ.This is sup-
3
ported by the strong tendency of Mn(III) pyrophos-
phate in pyrophosphate medium to form polymers/
oligomers.
The following scheme accounts for the observed
kinetics:
3
Rate ϭ Ϫd[Mn(H2P2O7)3 Ϫ]/dt ϭ k4[Y]
(7)
Applying the steady-state approximation to the in-
termediate species, X and Y, solving for Y and substi-
tuting in eq.(7),
K1
6
3Ϫ
Mn2(H2P2O7)6 Ϫ E
RF Mn(H2P2O7)3
2
Ϫ
obs ϭ K1k2K3k4[S][Hϩ]/{k2[Mn(H2P2O7)2
]
K2
k
S ϩ Hϩ E F SHϩ
R
[Hϩ][H2P2O7 Ϫ] ϩ K3k4 (8)
2
K3
Mn(H2P2O7)3 ϩ SHϩ E F X1 ϩ Hϩ
R
3
Ϫ
The plots of kobs versus [S] are linear passing though
the origin, supporting the rate law.
Further,
k4
R
2
Ϫ
2Ϫ
X1 E
F Y1 ϩ (H2P2O7)2 ϩ H2P2O7
(13)
k5
Y1 E
R
F Z1 ϩ Hϩ
(14)
(15)
2
Ϫ
1
1
[Mn(H2P2O7)2 Ϫ][H2P2O72
]
slow
ϭ
(fast)
kobs K1K3k4
[S]
3
Z1 ϩ Mn(H2P2O7)3 Ϫ E
RF products
1
ϩ
(9)
K1k2[S][Hϩ]
proof of 1/kobs versus 1/[Hϩ] was linear with the in-
tercepts on the ordinate axis.These observations
support the derived rate low and hence the mechan-
ism.
X1 and Y1 are the transient intermediate and Z1 is the
free radical.
By solving for X1 and Y1 with the application of
steady-state approximation, one gets
K1K21/2 k3k4k5[Mn2(H2P2O7)6 Ϫ]1/2[S][Hϩ]
6
k5[Y1] ϭ
(16)
2
kϪ [Mn(H2P2O7)2 Ϫ][H2P2O72Ϫ] ϩ {kϪ [Hϩ] ϩ k4} Ϫ kϪ
4
3
4
[Mn(H2P2O7)2 Ϫ][H2P2O72Ϫ] Ϫ kϪ {kϪ [Hϩ] ϩ k4}
2
5
3

OXIDATION BY MANGANESE(III) IN PYROPHOSPHATE MEDIA
457
7.Gopalakrishnan, G;.Hog, J.L.J Org Chem 1985, 50,
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8. Rajanna, K.C;. Saiprakash, P.K.Indian J Chem 1979,
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Chem 1984, 23A, 197–199.
The negative value of entropy of activation both at low
and high pH might be due to the associative process
involved.The transition state might involve an asso-
ciated species formed by solvation, consequently low-
ering entropy of activation.
10. Gowda, B.T;. Mahadevappa, D.S.J Chem Soc, Perkin
Trans 1983, 2, 323–334 (see also references therein).
11.Beg, M.A;. Kamaluddin Indian J Chem 1975, 13,
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CONCLUSION
12.Kamaluddin Indian J Chem 1980, 19A, 431–434.
13. Ramachandran, M. S.; Vivekanandam, T. S.; Kadar, S.
S.Indian J Chem 1984, 23A, 379–382.
14. Pinto, I;. Sherigara, B.S;. Udupa, H.V.K.Bull Chem
Soc Jpn 1994, 63, 1105–1119.
15. Subrahamanyam, E.V.S;. Ishwar Bhat, K;. Sherigara,
B.S.Samyak Journal of Chemistry 1997, 1, 32–34.
16. Sherigara, B. S.;Ishwara Bhat, K. ; Pinto, I.; Made-
gowda, N.M.Int J Chem Kinet 1995, 27, 675–690.
17. Chandraju, S.; Sherigara, B. S.; Madegowda, N. M. Int
J Chem Kinet 1994, 26, 1105–1119.
18. Chandraju, S.; Mahadevappa, D. S.; Rangappa, K. S.
Indian J Chem 1997, 36A, 974.
19. Chandraju, S.; Rangappa, K. S.; Mahadevappa, D. S.
Trans Met Chem 1996, 21, 519.
20. Sherigara, B. S.; Ishwar Bhat, K.; Pinto, I. Aminoacids
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and Green: London, 1958; p 708.
Kinetics of Mn(III) oxidations of ꢀ-amino acids have
been investigated in sulfuric, perchlorate, acetic acid,
and pyrophosphate media by our group [14–17,20]
and by others [11–13,18,19].The order in [amino
acid] obtained was generally one in all cases, while
inverse dependencies on [Hϩ] and [Mn(II)] are the
other common features.Kinetic order in [Mn(III)]
1
is found to be ⁄
2, 1, and 2 in different situations.In
the present study, the half- and first-order kinetics ob-
served might be due to kinetically active oxidizing
species, Mn2(H2P2O7)6 Ϫ and Mn(H2P2O7)3 Ϫ, respec-
tively.Comparison of cyclic voltametric behavior of
levodopa in pyrophosphate media [28] and this study
has shown that the oxidative pathways of electrochem-
ical and chemical processes are diametricallydifferent.
6
3
23.Amis, E.S.Solvent Effects on Reaction Rates and
Mechanism; New York: Academic Press, 1996.
24. Entelis, S.G.; Tiger, R.P.Reaction Kinetics in the Liq-
uid Phase; New York: Wiley, 1976.
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