Spectroscopic investigation and reactivities of ruthenium(iii) catalyzed oxidation of anticholinergic drug atropine sulfate monohydrate by hexacyanoferrate(iii) in aqueous alkaline media: A mechanistic approach

Article abstract of DOI:10.1080/15533174.2012.756027

The kinetics of oxidation of an atropine sulfate monohydrate (ASM) by hexacyanoferrate (HCF) (III) has been investigated spectrophotometrically in presence of ruthenium(III) catalyst in aqueous alkaline medium at 25°C. The stoichiometry is 1: 2. The reaction is first order in HCF(III) and has less than unit order in ASM concentrations. The effect of ionic strength and dielectric constants were studied on the rate of reaction. The active species of oxidant and catalyst are Fe(CN)6^3- and [Ru(H2O)5(OH)]²⁺, respectively. A suitable mechanism is proposed. The catalytic constant (KC) was also calculated. The activation parameters and thermodynamic quantities are also determined and discussed.

Full text of DOI:10.1080/15533174.2012.756027

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Spectroscopic Investigation and Reactivities
of Ruthenium(III) Catalyzed Oxidation of
Anticholinergic Drug Atropine Sulfate Monohydrate
by Hexacyanoferrate(III) in Aqueous Alkaline Media: A
Mechanistic Approach
Manjunath D. Meti a , Sharanappa T. Nandibewoor a & Shivamurti A. Chimatadar a
a Karnatak University, P. G. Department of Studies in Chemistry , Dharwad , India
Accepted author version posted online: 20 Sep 2013.Published online: 21 Oct 2013.
To cite this article: Manjunath D. Meti , Sharanappa T. Nandibewoor & Shivamurti A. Chimatadar (2014) Spectroscopic
Investigation and Reactivities of Ruthenium(III) Catalyzed Oxidation of Anticholinergic Drug Atropine Sulfate Monohydrate
by Hexacyanoferrate(III) in Aqueous Alkaline Media: A Mechanistic Approach, Synthesis and Reactivity in Inorganic, Metal-
Organic, and Nano-Metal Chemistry, 44:2, 263-272, DOI: 10.1080/15533174.2012.756027
To link to this article: http://dx.doi.org/10.1080/15533174.2012.756027
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Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 44:263–272, 2014
Copyright ꢀ Taylor & Francis Group, LLC
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ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533174.2012.756027
Spectroscopic Investigation and Reactivities of
Ruthenium(III) Catalyzed Oxidation of Anticholinergic Drug
Atropine Sulfate Monohydrate by Hexacyanoferrate(III) in
Aqueous Alkaline Media: A Mechanistic Approach
Manjunath D. Meti, Sharanappa T. Nandibewoor, and Shivamurti A. Chimatadar
Karnatak University, P. G. Department of Studies in Chemistry, Dharwad, India
metal ions acts as catalysts by one of several different paths,
such as the formation of complexes with reactants or oxida-
tion of the substrate itself or through the formation of free
radicals. The ruthenium(III) catalyzed redox reactions involves
different degrees of complexity, due to the formation of dif-
ferent intermediate complexes and different oxidation states of
ruthenium.
The kinetics of oxidation of an atropine sulfate monohydrate
(ASM) by hexacyanoferrate (HCF) (III) has been investigated spec-
trophotometrically in presence of ruthenium(III) catalyst in aque-
ous alkaline medium at 25◦C. The stoichiometry is 1: 2. The reac-
tion is first order in HCF(III) and has less than unit order in ASM
concentrations. The effect of ionic strength and dielectric constants
were studied on the rate of reaction. The active species of oxidant
and catalyst are Fe(CN)63– and [Ru(H2O)5(OH)]2+, respectively. A
suitable mechanism is proposed. The catalytic constant (KC) was
also calculated. The activation parameters and thermodynamic
quantities are also determined and discussed.
The most common atropine compound[9] used in medicine is
atropine sulfate monohydrate (ASM) (C17H23NO3)2•H2SO4•
H2O, the full chemical name is 1αH, 5αH-Tropan-3-α-ol( )-
tropate(ester), sulfate monohydrate.
Atropine (ASM) is a core medicine in the World Health Or-
ganization’s Essential Drugs List, which is a list of minimum
medical needs for a basic health care system.[10] Although at-
ropine earlier enjoyed widespread use in the treatment of peptic
ulcer, today it is mostly used in resuscitation,[11] anesthesia,[12]
and ophthalmology, usually as the more soluble sulfate salt.
It is a specific antidote for the treatment of poisoning with
organophosphorus and carbamate insecticides and organophos-
phorus nerve agents. Its degradation by microorganisms has
been reported by several groups.[13,14] and in cases for which the
mechanism has been studied, hydrolysis of the ester linkage to
give the two separate cyclic components is the initial step.[15]
Although some work on oxidation of ASM by various oxi-
dants has been carried out[15] there is a lack of literature on the
oxidation of this drug by hexacyanoferrate(III) in presence of
ruthenium(III). The uncatalyzed reaction of atrofine by hexa-
cyanoferrate(III) has been studied.[16] We have observed that
ruthenium(III) in micro amounts catalyzes the oxidation of
atropine sulfate by hexacyanoferrate(III) in alkaline medium.
Such studies are of much significance in understanding the
mechanistic profile of atropine in redox reactions and provide
an insight into the interaction of metal ions with the substrate
and its mode of action in biological systems. Also, to know the
active species of hexacyanoferrate(III) and to resolve the com-
plexity of the reaction, a detailed study of the reaction becomes
important. Hence, the present investigation is aimed to see the
reactivity of ASM towards hexacyanoferrate(III) in presence of
ruthenium(III) and to arrive at the plausible mechanisms.
Keywords atropine sulfate, hexacyanoferrate(III), kinetics, mecha-
nism, oxidation
INTRODUCTION
Hexacyanoferrate(III) has been widely used to oxidize nu-
merous organic and inorganic compounds in alkaline media.[1,2]
Many transition and nontransition metal ions in their complex
form act as good oxidants in acidic, basic, or neutral medium.
However, oxidation capacity is depending on their redox po-
tential. It is also known that the redox potential of the couple
is depending upon the pH of the medium. For instance, the re-
dox potential[3] of [Fe(CN)6]3−/[Fe(CN)6]4− in acid medium
is +0.360 V and in basic medium is +0.40 V. This indi-
cates that the hexacyanoferrate(III) is a good oxidant[4] in basic
medium.
Ruthenium(III) (Ru(III)) acts as a catalyst in the oxidation of
many organic and inorganic substrates.[5–7] Although the mech-
anism of the catalysis depends on the nature of the substrates,
oxidant and experimental conditions. It has been shown[8] that
Received 27 October 2012; accepted 3 December 2012.
The authors thank the UGC, New Delhi for providing the financial
assistance to carryout this work (Project No: F.NO.39-833/2010).
Address correspondence to Shivamurti A. Chimatadar, P. G. De-
partment of Studies in Chemistry, Karnatak University, Pavate Nagar,
Dharwad 580003, India. E-mail: schimatadar@gmail.com.
263

264
M. D. METI ET AL.
EXPERIMENTAL
Materials and Reagents
All chemicals used were of analytical reagent grade and mil-
lipore water was used throughout the work. The solution of
atropine sulfate (s.d. fine) was prepared by dissolving known
amounts of the samples in millipore water. The purity of the
ASM sample was verified by its melting point 192◦C (Litera-
ture: 194◦C). Solutions of atropine sulfate were always freshly
prepared before use. A stock solution of the oxidant, hexacyano-
ferrate(III), was prepared by dissolving K3Fe(CN)6 (SISCO
CHEM) in millipore water and standardizing the solution iodo-
metrically.[17] The ruthenium(III) stock solution was prepared
by dissolving RuCl3 (s.d. fine) in 0.20 mol dm3 HCl and mer-
cury was added to reduce if any Ru(IV) is formed during the
preparation of the Ru(III) stock solution, and was set aside for
24 h. The ruthenium(III) concentration was assayed by EDTA
FIG. 1. UV-vis spectral change during the oxidation of atropine sulfate by
alkaline hexacyanoferrate(III) at 25◦C, [Fe(CN)63−] = 2.0 × 10−4, [ASM] =
2.0 × 10−3, [OH−] = 0.5, and I = 1.0 mol dm−3 with scanning time interval of
titration.[18] Hexacyanoferrate(II) solution was prepared by dis- 1.0 min.
solving a known amount of K4Fe(CN)6 (s.d. fine) in millipore
water. KOH (Fisher Scientific) and KNO3 (BDH) were used to
ropine sulfate by hexacyanoferrate(III) occurs very slowly, but
maintain the required alkalinity and ionic strength in the reac-
tion solutions. t-Butyl alcohol (SPECTROCHEM) was used to
vary the dielectric constant of the media.
in a measurable quantities. Hence, during the calculation of the
pseudo–first-order rate constants, kC, the uncatalyzed rate has
also been taken in to account. Due to this, in case of each ruthe-
nium(III) mediated kinetic run, a parallel kinetic under similar
conditions in the absence of ruthenium(III) were also carried
out. In both cases the pseudo–first-order rate constants (kC and
kU) were obtained from plots of log (absorbance) versus time.
The pseudo–first-order plots were linear over three half-lives.
Thus, the total rate constant (kT) is equal to the sum of the rate
constants in presence (kC) and in absence (kU) of catalysts. That
is, kT = kU + kC and kC = kT – kU.
Instruments Used
First, for kinetic measurements, a Peltier Accessory (tem-
perature control) attached Varian CARY 50 Bio UV-vis spec-
trophotometer (Varian, Victoria-3170, Australia) was used.
Second, for product analysis, the QP-2010S Shimadzu gas
chromatograph mass spectrometer and Nicolet 5700-FT-IR
1
spectrometer (Thermo, USA), 300 MHz H NMR spectropho-
tometer (Bruker, Switzerland) were used.
Therefore, the rate constants, kC obtained in this way were
reproducible within 5% and are the average of at least four
independent kinetic runs (Table 1).
In view of the modest concentrations of alkali used in the
reaction medium, attention was also given to the effect of the
surface of the reaction vessels on the kinetics. Use of poly-
thene/acrylic ware and quartz or polyacrylate cells gave the
same results as glass vessels and cells indicating that the sur-
faces play no important role on the rate of reaction.
The effect of dissolved oxygen on the rate of reaction was
checked by preparing the reaction mixture and following the
reaction in an atmosphere of nitrogen. No significant difference
between the results obtained under nitrogen atmosphere and in
the presence of air was observed. In view of the ubiquitous con-
tamination of carbonate in the basic solutions, added carbonate
up to 1.0 × 10−3 mol dm−3 showed no effect on the reaction
rate. However, fresh solutions were used while performing the
experiments.
Kinetic Measurements
The ruthenium(III) (5.0 × 10−6 mol dm−3) catalyzed ox-
idation of atropine sulfate by hexacyanoferrate(III) was fol-
lowed under pseudo–first-order conditions at 25.0
0.1◦C
where [ASM]>[Fe(CN)63−], unless otherwise specified. The re-
action in the presence of the ruthenium(III) catalyst was initiated
by mixing hexacyanoferrate(III) with the ASM solution which
also contained the required concentrations of KNO3, KOH, and
Ru(III) catalyst. The progress of reaction was monitored spec-
trophotometrically at 420 nm by measuring the decrease in the
absorbance of hexacyanoferrate(III). The extinction coefficient
was determined under experimental conditions and was found
to be ε = 1070
10 dm3 mol−1cm−1. The spectral changes
during the chemical reaction for the standard condition at 25◦C
are shown in Figure 1. It is evident from the figure that the con-
centration of hexacyanoferrate(III) decreases at 420 nm. It was
also verified that there were no interference from other species
in the reaction mixture at this wavelength (420 nm). The kinetic
runs were followed more than 80% completion of the reaction
and good first-order kinetics were observed. During the kinetic
Stoichiometry and Product Analysis
Different sets of reaction mixtures containing varying ra-
studies it was observed that, under the present experimental tios of hexacyanoferrate(III) to ASM in the presence of con-
conditions in the absence of ruthenium(III), the oxidation of at- stant amount of OH−(0.50 mol dm−3), KNO3(0.50 mol dm−3),

ANTICHOLINERGIC DRUG ASM BY HCF(III)
265
TABLE 1
Effect of variation of hexacyanoferrate(III), atropine sulfate, and OH− on the ruthenium(III) catalyzed oxidation of atropine
sulfate by hexacyanoferrate(III) in aqueous alkaline medium at 25◦C
[Fe(CN)63−] ×
[ASM] × 103 [OH −] (mol dm [Ru(III)] × 106
−3
104 (mol dm −3
)
(mol dm −3
)
)
(mol dm −3
)
kT × 103 (s−1
)
kU × 103 (s−1
)
kC × 103 (s−1
)
0.50
1.0
2.0
3.0
5.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
0.50
1.0
2.0
3.0
5.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
0.5
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
0.0
3.0
5.0
8.0
10.0
20.0
4.66
4.78
4.72
4.08
4.24
1.33
2.32
4.72
5.98
7.74
2.20
3.81
4.72
5.91
8.20
—
1.09
1.03
1.05
1.07
1.08
0.31
0.65
1.05
1.56
2.08
0.45
0.81
1.05
1.48
1.71
1.05
1.05
1.05
1.05
1.05
1.05
3.57
3.75
3.70
3.01
3.15
1.0
1.70
3.70
4.40
5.70
1.80
3.0
3.70
4.40
6.50
—
1.80
3.70
5.10
5.70
15.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.10
0.30
0.50
0.70
1.0
0.5
0.5
0.5
0.5
0.5
0.5
2.90
4.72
6.15
6.82
16.1
Ru(III) (5.0 × 10−6 mol dm−3) and at constant ionic strength of
1.0 mol dm−3 were allowed to react for about 5 h at 25◦C.
The remaining hexacyanoferrate(III) concentration was esti-
mated by measuring the absorbance at 420 nm spectrophoto-
metrically. The results indicated 1:2 stoichiometry as given in
Eq. 1.
After the completion of the reaction (as observed by con-
stancy of the absorbance at different time intervals) the reaction
mixture was acidified, concentrated, and extracted with ether.
The ethereal layer was subjected to column chromatography us-
ing hexane and ethyl acetate in 8:2 (v/v) and the fractions were
subjected to spectral investigations. The main reaction products
SCH. 1. Stoichiometry of ruthenium(III) catalyzed oxidation of atropine sulfate by alkaline hexacyanoferrate(III).

266
M. D. METI ET AL.
FIG. 2. 1H NMR spectra of tropine, the oxidation product of atropine sulfate by hexacyanoferrate(III) in alkaline medium.
were identified as tropine and benzaldehyde. The products were RESULTS
1
characterized and confirmed by FT-IR, GC-MS, and H NMR
Reaction Orders
spectral studies. The IR spectrum of tropine showed a broad
band at 3245 cm−1 assigned to –OH stretching. The GC-MS
mass spectrum of tropine showed the base peak at 124 amu and
molecular ion peak at 141 amu. The 1H NMR spectral analysis
of tropine showed a broad singlet for –OH at δ 12.36 ppm (D2O
exchangeable), singlet for proton adjacent to –OH group at δ
3.89 ppm, multiplets for the protons of -CH2 are observed in
the range δ 2.50–3.89 ppm. Methyl protons attached to nitrogen
appear at δ 3.64 ppm and a singlet for the proton on the carbon at-
tached to the –OH group appeared at δ 3.92 ppm (Figure 2), thus
confirming the product tropine. Another product benzaldehyde
was confirmed by its GC-MS spectrum that showed a molecular
ion peak at 106 amu and also confirmed by its hydrozone deriva-
tive.[19] The byproducts were identified as methyl alcohol, which
was confirmed by sodium test[19] and CO2 was qualitatively de-
tected by bubbling nitrogen gas through the acidified reaction
mixture and passing the liberated gas through tube containing
limewater.
The reaction orders have been determined from the slopes of
log kC versus log(concentration) plots by varying the concen-
trations of atropine sulfate, OH−, ruthenium(III), in turn, while
keeping the others constant.
Effect of [Hexacyanoferrate(III)]
The oxidant hexacyanoferrat(III) was varied in the concen-
tration range 0.50 × 10−4 to 5.0 × 10–4 mol dm−3 at constant
concentrations of ASM, OH−, Ru(III) at constant ionic strength
of 1.0 mol dm−3. The fairly constant kC value (Table 1) indicate
that order with respect to hexacyanoferrate(III) concentration
was unity. This was also confirmed by the linearity of the plots
of log(absorbance) versus time plots up to 80% completion of
the reaction.
Effect of [Atropine Sulfate]
The effect of atropine sulfate was studied in the concen-
tration range 0.5 × 10−3 to 5.0 × 10−3 mol dm−3 at constant

ANTICHOLINERGIC DRUG ASM BY HCF(III)
267
concentration of hexacyanoferrate(III), OH−, Ru(III), and a con-
stant ionic strength of 1.0 mol dm−3 at 25◦C. The rate constants
increased with the increase in concentration of atropine sulfate
(Table 1). The order with respect to atropine sulfate concentra-
tion was obtained from the plot of log kC versus log[atropine
sulfate] and was found to be less unity (0.73). This was also
confirmed by the plot of kC versus [ASM]0.73, which is linear
rather than the direct plot of kC versus [ASM].
Effect of [Alkali]
The effect of alkali was studied in the concentration range
0.10–1.0 mol dm−3 at constant concentrations of hexacyano-
ferrate(III), atropine, Ru(III), and at constant ionic strength of
1.0 mol dm−3. The rate constants increased with the increase in
[alkali] (Table 1) and the order was found to be less than unity
(i.e., 0.53). This less than unit order is also confirmed by the
plot of kC versus [OH−]0.53, which is linear rather than the direct
plot of kC versus [OH−].
FIG. 3. Effect of ionic strength and dielectric constant on the ruthenium(III)
catalyzed oxidation of ASM by hexacyanoferrate(III) in alkaline media at 25◦C.
Effect of [Ruthenium(III)]
The ruthenium(III) concentration was varied from 1.0 × 10−6
to 10.0 × 10−6 mol dm−3 range, at constant concentrations of
hexacyanoferrate(III), atropine sulfate, OH−, and at constant
ionic strength of 1.0 mol dm−3. As the catalyst, ruthenium(III),
concentration increases the rate of reaction also increases (Ta-
ble 1). The order in [Ru(III)] was found to be unity from the
linearity of the plot of kC versus [Ru(III)].
Effect of Temperature
The influence of temperature on the rate of reaction was
studied at 15, 25, 35, and 45◦C. It was observed that, as the
temperature increases the rate of reaction also increases. The
rate constants (k) of the slow step of Scheme 2 were obtained
from the intercepts of the plots of 1/kC versus 1/[ASM] and 1/kC
versus 1/[OH−] at the four different temperatures. The values
are given in Table 2. The energy of activation was obtained
from Arrhenius plot, log k versus 1/T. The enthalpy of activa-
tion, ꢀH= and entropy of activation ꢀS=, were obtained by the
Eyring equation[20] and are given in Table 2.
Effect of Ionic Strength (I) and Dielectric Constant (D)
The effect of ionic strength was varied by varying KNO3
concentration between 0.60 and 1.40 mol dm−3. The rate was
found to increase with increase in the ionic strength. A plot of
1
2
log kC versus I was linear with positive slope (Figure 3). The
dielectric constant of the medium varied by varying the t-butyl
alcohol and water percentage (v/v) from 0% to 30%. The D
values were calculated from the equation D = DWVW+DBVB,
where DW and DB are dielectric constants of pure water and
t-butyl alcohol, respectively, and VW and VB are the volume
fractions of components water and t-butyl alcohol, respectively,
in the total mixture. It was found that as the percentage compo-
sition of t-butyl alcohol increases in the reaction medium, the
rate of reaction decreases and the plot of log kC versus 1/D was
linear with negative slope (Figure 3).
Test for Free Radicals (Polymerization Study)
The intervention of the free radicals in the reaction was exam-
ined as follows: the reaction mixture, to which known quantity
of acrylonitrile monomer (scavenger) had been added initially,
was kept for 2 h in an inert atmosphere. On diluting the re-
action mixture with methanol, a white precipitate was formed,
indicating the intervention of free radicals during the reaction.
The blank experiments of either Fe(CN)63− or ASM alone with
acrylonitrile did not induce any polymerization under the same
condition as those induced for the reaction mixture. Initially
added acrylonitrile decreases the rate also indicating the free
radical intervention in the reaction.[21]
Effect of Initially Added Products
The initially added products, hexacyanoferrate(II), tropine,
and benzaldehyde did not have any significant effect on the rate
of reaction.
Thus, from the observed experimental results, the rate law
for ruthenium(III) catalyzed reaction is
Catalytic Activity
It has been pointed out by Moelwyn-Hughes[22] that in the
presence of catalyst, the uncatalyzed and catalyzed reactions
proceed simultaneously, so that
ꢀ
ꢁ
Rate = kC Fe(CN)63− 1.0[ASM]0.73[OH−]0.53[Ru(III)]1.0 [2]
kT = kU + KC[Ru(III)]x
[3]

268
M. D. METI ET AL.
SCH. 2. Detailed scheme for ruthenium(III) catalyzed oxidation of atropine sulfate by alkaline hexacyanoferrate(III).
Here kT is the total rate constant; kU is the pseudo–first-order equation:
rate constant for the uncatalyzed path; KC is the catalytic con-
stant and x the order of the reaction with respect to catalyst.
kT − kU
kC
(Where, kT − kU= kC) [4]
[Ru(III)]x [Ru(III)]
KC =
=
In the present investigations, the x value was found to be
unity. Then, the value of KC is calculated using the following

ANTICHOLINERGIC DRUG ASM BY HCF(III)
269
TABLE 2
Activation parameters and thermodynamic quantities for the ruthenium(III) catalyzed oxidation of ASM by hexacyanoferrate(III)
in aqueous alkaline medium with respect to the slow step of Scheme 2 at 25◦C
(A) Effect of temperature and activation parameters
Temperature(K)
k × 10−5 (dm3 mol−1 s−1
)
Parameters
Values
288
298
308
318
0.65
1.30
2.60
5.20
Ea (kJmol−1
)
)
36
33
3
3
ꢀH#(kJmol−1
ꢀS# (JK−1 mol−1
)
–70
54
4
3
ꢀG# (kJmol−1
)
log A
9.6 0.2
(B) Effect of temperature on first and second equilibrium step of Scheme 2
Temperature (K)
K1 × 101 (dm3 mol−1
)
K2 × 102 (dm3 mol−1
)
288
298
308
318
1.12
2.46
3.46
5.34
5.10
4.68
4.28
3.86
(C) Thermodynamic quantities with respect to K1 and K2
Thermodynamic quantities
Values from K1
Values from K2
ꢀH (kJmol−1
)
38
135
–2.0
–7
–27
–15
ꢀS (JK−1 mol−1
ꢀG298 (kJmol−1
)
)
(D) Values of catalytic constant (KC) at different temperatures and activation parameters calculated using KC values
Temperature (K)
KC × 10−3
Parameters
Values
288
298
308
318
0.36
0.74
1.08
2.68
Ea (kJmol−1
)
48
46
3
3
ꢀH# (kJmol−1
)
ꢀS# (JK−1 mol−1
)
–35
56
3
3
ꢀG#(kJmol−1
)
log A
11 0.4
[Fe(CN)63−] = 2.0 × 10−4 mol dm−3, [ASM] = 2.0 × 10−3 mol dm−3, [OH−] = 0.50, [Ru(III)] = 5 × 10−6 mol dm−3, I = 1.0 mol dm−3
.
The values of KC were evaluated for ruthenium(III) catalyst medium has a stoichiometry 1:2. Ruthenium(III) acts as an ef-
at four different temperatures. Further, plots of log KC versus ficient catalyst in many redox reactions, particularly in an alka-
1/T were linear and the values of activation parameters with line medium.[23] In the present study, it is quite probable that
reference to catalytic constant were calculated and the results the [Ru(H2O)5OH]2+ species might assume the general form
are summarized in Table 2.
[Ru(III)(OH)x]3–x. The x value always be less than six because
there are no definite reports of any hexahydroxy ruthenium
species. The remainder of the coordination sphere would be
filled by water molecules. Hence, under the conditions employed
(e.g., [OH−]ꢁ[Ru(III)]) ruthenium(III) is mostly present[24] as
hydroxylated species, [Ru(H2O)5OH]2+. Based on the experi-
mental results, a mechanism can be proposed in which all the
observed orders in each constituent such as [oxidant], [reduc-
tant], [catalyst], and [OH−] may be well accommodated. Oxida-
tion of atropine sulfate by hexacyanoferrate(III) in alkali media
is a noncomplementary reaction.[25]
DISCUSSION
For the variation of the concentrations of the oxidant (hex-
acyanoferrate(III)), substrate (atropine sulfate), catalyst (ruthe-
nium(III)), and alkali, while keeping others constant, it was
found that the reaction is first order with respect to oxidant
and catalyst concentrations and less than unit order in alkali
and substrate concentrations. The ruthenium(III) catalyzed ox-
idation of atropine sulfate by hexacyanoferrate(III) in alkaline

270
M. D. METI ET AL.
The results indicate that the alkali combines first with at-
ropine sulfate to give the anionic form of atropine(I) in a prior
equilibrium step, which is also supported by the observed frac-
tional order in [OH−] and [ASM]. The anionic form of atropine
sulfate(I) reacts with ruthenium(III) species to give a complex
(II), which decomposes in the presence of the hexacyanofer-
rate(III) species in a slow step to give a 2-phenyl ethanol free rad-
ical species (III) and one of the final product tropine(IV) derived
4−
from atropine sulfate and byproduct CO2(V) and Fe(CN)6
with regeneration of the catalyst, ruthenium(III). K2 is the equi-
librium constant comprising the equilibrium to bind atropine
sulfate to ruthenium(III). The intermediate free radical species
(III) further reacts with another mole of hexacyanoferrate(III) in
a fast step to form the final products such as benzaldehyde(VI),
methyl alcohol(VII). and Fe(CN)64−. All these results may be
interpreted in a detailed mechanistic pathway as in Scheme 2.
Spectroscopic evidence for the complex formation between
Ru(III) and ASM was obtained from UV-vis spectra of [ASM]
(2.0 × 10−3 mol dm−3), [Ru(III)] (5.0 × 10−6 mol dm−3), [OH−]
(0.5 mol dm−3), and a mixture of both. A bathochromic shift
of about 6 nm from 240 to 246 nm in the spectra of ASM to
mixture of Ru(III) and ASM was observed. Michaelis-Menten
plot (Figure 4) proved the complex formation between a catalyst
and substrate, which explains less than unit order in [ASM].
From Scheme 2, the rate law (5) can be derived as follows:
Rate
[Fe(CN)36−
k K1 K2 [ASM] [OH−] [Ru(H2O)5OH]2+
= kC=
]
K1[OH−] + (1 + K1 K2 [ASM] [OH−]
[5]
Equation 5 can be rearranged to the following form (Eq. (6))
and is used for verification.
[Ru(III)
kC
1
1
1
k
=
+
+
[6]
k K1 K2 [ASM] [OH−] k K2 [ASM]
According to Eq. (6), other conditions being constant, plots
of [Ru(III)]/kC versus 1/[ASM], and 1/[OH−] should be linear
and are found to be so (Figure 4). The slopes and intercepts of
such plots lead to the values of K1, K2, and k (Table 2).
FIG. 4. Verification of rate law (5) in the form of Eq. (6) for the ruthe-
nium(III) catalyzed oxidation of atropine sulfate by hexacyanoferrate(III) in
alkaline medium.
The effect of ionic strength and dielectric constant of medium
on the rate explains qualitatively the reaction between ions hav-
ing the same charge, as seen in Scheme 2. The thermodynamic
quantities for the different equilibrium steps, in Scheme 2 can of ꢀS# (–70 JK−1 mol−1) suggests that the intermediate com-
be evaluated as follows. The [ASM] and [OH−] (Table 1) were plex (C) is more ordered than the reactants.[26] The observed
varied at four different temperatures. From the slopes and in- modest enthalpy of activation and higher rate constants for the
tercepts of the plots, [Ru(III)]/kC versus 1/[ASM], [Ru(III)]/kC slow step indicate that the oxidation presumably occurred via
versus 1 [OH−] the values of K1, K2, and k were calculated an inner sphere mechanism. This conclusion is supported by
at different temperature and are given in Table 2. van’t Hoff literature.[27,28] The activation parameters evaluated for the cat-
plot was made for the variation of K1 and K2 with temperature alyzed reactions explain the catalytic effect on the reaction. The
(logK1 versus 1/T and K2 versus 1/T). The values of enthalpy catalyst, ruthenium(III) forms the complex (C) with substrate,
of reaction ꢀH, entropy of reaction ꢀS and free energy of re- which enhances the reducing property of substrate than that
action ꢀG were calculated for the first and second equilibrium without catalyst. Further, the catalyst ruthenium(III) modifies
steps. These values are given in Table 2. The negative value the reaction path by lowering energy of activation.

ANTICHOLINERGIC DRUG ASM BY HCF(III)
271
CONCLUSION
hexacyanoferrate(III) in aqueous alkaline media: a mechanistic approach.
J. Solution. Chem. 2013.
Spectroscopic investigation of ruthenium(III) catalyzed oxi-
dation of atropine sulfate monohydrate by hexacyanoferrate(III)
in aqueous alkaline media has been made. The active species
of ruthenium(III) is found to be [Ru(H2O)5OH]2+. Oxidation
products were identified. Rate constant of slow step and other
equilibrium constants involved in the mechanism are evaluated
and activation parameters with respect to slow step of reaction
were computed. The overall sequence described here is con-
sistent with all experimental including the product, spectral,
mechanistic, and kinetic studies.
17. Jeffery, G. H.; Bassett, J.; Mendham, J.; Denny, R. C. Vogel’s Text Book of
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anism of uncatalyzed and Ru (III) catalyzed oxidation of allyl alcohol by
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19. Furniss, B. S.; Hannaford, A. J.; SmithPeter, W. G.; Tatchell, A. R. Vogel’s
Textbook of Practical Organic Chemistry, 5th edn.; Pearson Education,
London, 2004.
20. Byadagi, K. S.; Naik, D. V.; Savanur, A. P.; Nandibewoor, S. T.; Chimatadar,
S. A. Ruthenium (III) mediated oxidation of thiamine hydrochloride by
cerium (IV) in perchloric acid medium: a kinetic and mechanistic approach.
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21. Jagadeesh, R. V.; Puttaswamy Ru(III), Os(VIII), Pd(II), and Pt(IV) catal-
ysed oxidation of glycyl-glycine by sodium N-chloro-p-toluenesulfona-
mide: comparative mechanistic aspects and kinetic mod-eling. J. Phys.
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J. Am. Chem. Soc. 1960, 82, 4187–4191.
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of ruthenium(III) catalysed hexacyanoferrate(III) by atenolol in alkaline
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of Reactions in Techniques of Chemistry; Wiley, New York, 1974.
27. Martinez, M.; Pitarque, M. A.; Eldik, R. V. Outer-sphere redox reactions
of [CoIII(NH3)5(HxPyOz)](m– 3)- complexes. A temperature- and pressure-
dependence kinetic study on the influence of the phosphorus oxoanions.
J. Chem. Soc. Dalton. Trans. 1996, 2665–2671.
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APPENDIX
From Scheme 2, the rate law (10A) can be derived as follows:
ꢀ
ꢁ
d Fe(CN)36−
ꢀ
ꢁ
10. World Health Organization. WHO Model List of Essential Medicines; World
Rate = −
= k Complex] [Fe(CN)63−
[1A]
Health Organization, Geneva, 2005.
11. Field, J. M.; Hazinski, M. F.; Sayre, M. R. Part 1: executive summary 2010
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241–249. (b) Thomas, C. C. Toxicology: Symptoms and Treatments, 3rd
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13. Berends, F.; Ro¨rsch, A.; Stevens, W. F. Atropine esterase from a Pseu-
domonas strain. Proceedings of the Conference on the Structure and Re-
actions of DFP-Sensitive Enzymes, Research Institute National Defence,
Stockholm 1967, 45, 6.
dt
From the second step of Scheme 2, we have
[Complex]
K2 =
[Anionic form of ASM] [Ru(H2O)5OH]2+
[Complex] = K2 [Anionic form of ASM] [Ru(H2O)5OH]2+
[2A]
14. Ro¨rsch, A.; Berends, F. A.; Bartlema, H. C.; Stevens, W. F.; Winsinck, F.
Proc. K Ned. Akad. Wet. Ser. C 1971, 74, 132.
15. Byadagi, K. S.; Hosahalli, R. V.; Nandibewoor, S. T.; Chimatadar, S. A. Ox-
idation of a anticholinergic drug atropine sulfate monohydrate by alkaline
copper(III) periodate complex: a kinetic and mechanistic study. Z. Phys.
Chem. 2012, 226, 1–17.
Substituting equation (1A) in equation (2A), we have
Rate = k K2 [Anionic form of ASM ] [Ru(H2O)5OH]2+
16. Meti, M. D.; Nandibewoor, S. T.; Chimatadar, S. A. Spectroscopic investiga-
ꢀ
ꢁ
tion and oxidation of anticholinergic drug atropine sulfate monohydrate by
× Fe(CN)36−
[3A]

272
M. D. METI ET AL.
From the first step of Scheme 2, we have
[Anionic form of ASM]
Similarly,
[OH−]T = [OH−] + [Anionic form of ASM]
[OH−]f =
K1=
[ASM][OH−]
[OH−]T
1 + K1[ASM]
Therefore,
[Anionic form of ASM] = K1[ASM][OH−]
[4A]
In the view of low concentration of atropine sulfate used in the
reaction, the term 1+K1 [ASM] is neglected.
Therefore total concentration of OH − is given by
Substituting equation (4A) in equation (3A) we get,
Rate = kK2K2 [ASM] [OH−] [Ru(H2O)5OH]2+[Fe(CN)36−
[OH−]f = [OH−]T
[7A]
[5A]
Similarly,
The total concentration of atropine sulfate is given by
[ASM]T= [ASM]f+[Anionic form of ASM] + [Complex]
where T and f refers to total and free concentrations
[Ru(H2O)5OH]2T+ = [Ru(H2O)5OH]2f ++C
[Ru(H2O)5OH]2T+
[Ru(H2O)5OH]2f +
=
[8A]
(1 + K1K2[ASM][OH−])
Substituting the equations (6A), (7A), (8A) in equation (5A)
and omitting t and f we get,
= [ASM]f+K1[ASM][OH−] + K2[Anionic form of ASM]
[Ru(H2O)5OH]2+
k K1 K2 [ASM] [OH−] [Ru(H2O)5OH]2+ [Fe(CN)63−
Rate =
= [ASM]f+K1[ASM][OH−] + K1K2[Anionic form of ASM]
(1 + K1 [OH−]) (1 + K1 K2 [ASM] [OH−])
[OH−] [Ru(H2O)5OH]2+
k K1K2 [ASM] [OH−] [Ru(H2O)5OH]2+ [Fe(CN)63−
(1 + K1 K2 [ASM] [OH−] + K1 [OH−] + K12 K2[ASM] [OH−]2)
= [ASM]f [1 + K1[OH−] + K1K2[OH−] [Ru(H2O)5OH]2+
Rate =
[9A]
Therefore
The term, K1 K2[ASM] [OH−]2 in the denominator of equation
2
(9A) is negligibly small compared to unity in view of the low
concentration of atropine sulfate used. Therefore the equation
(9A) can be written as,
[ASM]T
[ASM]f=
[1 + K1[OH−] + K1K2[OH−] [Ru(H2O)5OH2+
In view of low concentration of [OH−], hence above Eq. K1 K2
[OH−] [Ru(H2O)5OH]2+
Rate
[Fe(CN)36−
= kC
]
k K1 K2 [ASM] [OH−] [Ru(H2O)5OH]2+
[ASM]T
1 + K1[OH−]
[ASM]f =
[6A]
=
K1 [OH−] + (1 + K1 K2 [ASM] [OH−])
[10A]