Oxidation of fursemide by diperiodatocuprate(III) in aqueous alkaline medium-a kinetic study

Article abstract of DOI:10.1007/s10953-009-9492-2

Fursemide is the chemical compound 4-chloro-2-(furan-2-ylmethylamino)-5- (aminosulfonyl) benzoic acid. It was oxidized by diperiodatocuprate(III) in alkali solutions, and the oxidation products were identified as furfuraldehyde and 2-amino-4-chloro-5-(aminosulfonyl) benzoic acid. The reaction kinetics were studied spectrophotometrically. The reaction was observed to be first order in [oxidant] and fractional order each in [fursemide] and [periodate], whereas added alkali retarded the rate of reaction. The reactive form of the oxidant was inferred to be [Cu(H₃IO₆)₂]^-. A mechanism consistent with the experimental results was proposed, in which oxidant interacts with the substrate to give a complex as a pre-equilibrium state. This complex decomposed in a slow step to give a free radical that was further oxidized by reaction with another molecule of DPC to yield 2-amino-4-chloro-5-(aminosulfonyl) benzoic acid and furfuraldehyde in a fast step. This reaction was studied at 25, 30, 35, 40 and 45∈°C, and the activation parameters E _a,ΔH ^#,ΔS ^# and ΔG ^# were determined to be 51 kJ · mol ^-1,48.5 kJ · mol^-1,-63.5 J·K ^-1· mol^-1 and 67 kJ · mol^-1, respectively. The value of log∈₁₀ A was calculated to be 6.8.

Full text of DOI:10.1007/s10953-009-9492-2

J Solution Chem (2010) 39: 165–177
DOI 10.1007/s10953-009-9492-2
Oxidation of Fursemide by Diperiodatocuprate(III)
in Aqueous Alkaline Medium—a Kinetic Study
Mahantesh A. Angadi · Suresh M. Tuwar
Received: 27 May 2009 / Accepted: 28 July 2009 / Published online: 28 January 2010
© Springer Science+Business Media, LLC 2010
Abstract Fursemide is the chemical compound 4-chloro-2-(furan-2-ylmethylamino)-5-
(aminosulfonyl) benzoic acid. It was oxidized by diperiodatocuprate(III) in alkali solu-
tions, and the oxidation products were identified as furfuraldehyde and 2-amino-4-chloro-5-
(aminosulfonyl) benzoic acid. The reaction kinetics were studied spectrophotometrically.
The reaction was observed to be first order in [oxidant] and fractional order each in
[fursemide] and [periodate], whereas added alkali retarded the rate of reaction. The reac-
tive form of the oxidant was inferred to be [Cu(H3IO6)2]−. A mechanism consistent with
the experimental results was proposed, in which oxidant interacts with the substrate to give
a complex as a pre-equilibrium state. This complex decomposed in a slow step to give a free
radical that was further oxidized by reaction with another molecule of DPC to yield 2-amino-
4-chloro-5-(aminosulfonyl) benzoic acid and furfuraldehyde in a fast step. This reaction was
studied at 25, 30, 35, 40 and 45 °C, and the activation parameters Ea, ꢀH#, ꢀS# and ꢀG#
were determined to be 51 kJ·mol−1, 48.5 kJ·mol−1, −63.5 J·K−1·mol−1 and 67 kJ·mol−1
,
respectively. The value of log10 A was calculated to be 6.8.
Keywords Diperiodatocuprate(III) · Fursemide · Oxidation · Kinetics · Periodate · DPC
1 Introduction
Fursemide, 4-chloro-2-(furan-2-ylmethylamino)-5-(aminosulfonyl) benzoic acid, is a loop
diuretic used in the treatment [1, 2] of congestive heart failure and edema. Other synonyms
of fursemide are Furosamide, Frusemid, Furosemida, Furosemid, etc. The diuretic property
of this compound has been most commonly exploited in horses to prevent ‘bleeding’ during
a horse race. An excess dose of this compound in the gastrointestinal system leads to many
adverse effects [3] like gastric irritation, vomiting, diarrhea, constipation, etc. It also affects
the central nervous system causing headache, blurred vision, vertigo, dizziness, hearing loss,
M.A. Angadi · S.M. Tuwar (
)
ꢀ
Department of Chemistry, Karnatak Science College, Dharwad 580 001, India
e-mail: sureshtuwar@yahoo.co.in

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J Solution Chem (2010) 39: 165–177
etc. The mechanism of the oxidation of this compound is worth investigation as it may help
to understand the above effects in biological systems.
Copper(III) complexes have occupied a major role in oxidation chemistry due to their
abundance and relevance in biological chemistry [4]. As an analytical reagent, Cu(III) ap-
pears to be surpassing both dichromate and permanganate, particularly as an oxidant in
alkaline medium. It is used in the form of its periodate and tellurate complexes. The former
complex is more stable. Hence, it is also used in kinetic studies of the oxidation of various
inorganic and organic substrates [5]. Previously, copper(II) was used as catalyst in which
case Cu(III) was involved in the transient state for biological electron transfer reactions.
Hence, Cu(III) in the form of diperiodatocuprate(III) (DPC) was used to oxidize fursemide.
Apart from this, reports reveal that [6] among the various forms of DPC, the monoperi-
odatocuprate(III) ion was found to be the reactive species because added OH− had an accel-
erating effect on the reaction rate. However, in the present investigation, kinetic results are
completely different from previous results [6]. To understand the redox chemistry of DPC
and to arrive a suitable mechanism for this new drug, the title reaction has been studied.
2 Experimental
2.1 Materials and Reagents
All chemicals used were of reagent grade. Double distilled water was use throughout this
work. A stock solution of fursemide (Loba Chemie) was prepared by dissolving the appro-
priate amount in aqueous alkali. The purity of the fursemide sample was checked by its
m.p. = 206 °C (literature value. 206 °C).
2.1.1 Preparation of DPC
Diperiodatocuprate(III), DPC, was prepared [7] by oxidizing CuSO4·5H2O dissolved in
aqueous alkaline medium. Copper sulfate (3.54 g), potassium metaperiodate (6.8 g), potas-
sium persulphate (2.2 g) and KOH (9 g) were added to 250 cm3 of water. The mixture was
heated to boiling on a hot plate with constant stirring until it turned dark red, and the boiling
was continued for another 20 min to insure completion of the reaction. The mixture was
then cooled and filtered through a sintered glass crucible (G-4). This filtrate was diluted to
250 cm3 with distilled water. The solution obtained was fairly stable at room temperature,
in the presence of periodate, for several months. The complex was characterized by its UV-
visible spectrum, which exhibits two strong broad absorption bands at 416 nm and 265 nm.
The aqueous solution of copper(III) was standardized by both iodometric and gravimetric
[8] methods.
A periodate solution was prepared by dissolving a known amount of potassium metape-
riodate in hot water and it was kept for 24 hours. Its concentration was ascertained iodo-
metrically [9] at neutral pH maintained by phosphate buffer. Because periodate is present in
excess over DPC, the possibility of oxidation of fursemide by periodate in alkaline medium
at 25 °C was tested by following the reaction iodometrically. No significant reaction was
observed between periodate and fursemide under the experimental conditions employed,
compared to the DPC oxidation of fursemide. Aqueous solutions of KOH and KNO3 (BDH,
AR) were employed in the reacting solutions to maintain the required alkalinity and constant
ionic strength, respectively. The copper(II) solution was prepared by dissolving the required
quantity of CuSO4·5H2O in distilled water.

J Solution Chem (2010) 39: 165–177
167
Fig. 1 Spectroscopic changes
occurring during the oxidation of
fursemide by
[diperiodatocuprate(III)] at 25 °C,
−4
−3
[DPC] = 1.0 × 10 mol·dm
,
−3
−3
[Fur] = 1.0 × 10 mol·dm
,
−
−3
[OH ] = 0.1 mol·dm , and
−3
I = 0.5 mol·dm with scanning
time intervals of: (1) 0.5, (2) 1.0,
(3) 1.5, (4) 2.0, (5) 2.5, (6) 3.0,
(7) 3.5, and (8) 4.0 min
2.2 Kinetic Measurements
The kinetics of oxidation of fursemide by DPC was followed at 25 0.1 °C under pseudo-
first order reaction condition where [fursemide] was in excess over [DPC]. The reaction was
initiated by mixing the required quantities of previously thermostatted solutions of DPC
and fursemide that also contained appropriate quantities of KOH, KNO3 and IO−4 needed to
maintain the required concentrations of alkali, ionic strength, and periodate, respectively. In
the reaction mixture, the total concentration of OH− was calculated by considering the KOH
present in DPC as well as the KOH added. Similarly, the total metaperiodate concentration
was calculated by considering both the metaperiodate present in the DPC solution and any
additionally added.
The reaction course was followed spectrophotometrically by measuring the decrease in
absorbance of DPC in the reaction mixture as a function of time, in a 1 cm quartz cell in a
thermostatted compartment of a Hitachi U3310 spectrophotometer, at its ‘λmax’ = 416 nm.
Previously, it was verified that there is negligible interference from other species present
in the reaction mixture at this wavelength. That the absorbance by DPC obeys Beer’s law
at its ‘λmax’ = 416 nm was verified earlier, and the molar absorbency index ε was found
to be 6250 50 dm3·mol−1·cm−1 (literature value [9] ε = 6500 50 dm3·mol−1·cm−1).
The first-order rate constants, kobs, were obtained from the slopes of plots of log10(a − x)
versus time, where ‘a’ and ‘x’ denote the initial concentration and change in concentration
of DPC at time t, respectively. These plots are linear up to 40% completion of the reaction
(the non-linearity of these above 40% was due to the retarding effect of Cu(II), as explained
elsewhere), and the rate constants were reproducible to within 5%. The spectral changes
during the reaction are shown in Fig. 1 in which [DPC] decreases during the reaction.
2.3 Stoichiometry and Product Analysis
Different sets of reaction mixtures containing different concentrations of fursemide and
DPC, at constant ionic strength and [alkali], were kept in a closed vessel for ca. 6 h at
25 0.1 °C under an inert atmosphere (to avoid any potential reaction between oxygen and
fursemide). When [DPC] was in excess over [fursemide], the unreacted DPC was estimated
spectrophotometrically by measuring the absorbance at 416 nm. The results indicated that

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J Solution Chem (2010) 39: 165–177
two moles of DPC were consumed by one mole of fursemide as shown in reaction (1):
(1)
Fursemide and its reaction products have various functional groups, viz., aromatic chlo-
rine, primary amine, sulfonyl amine, aldehyde and aromatic carboxylic acid. It was found
that the functional groups: sulfonyl amine, chlorine and benzoic acid were unaffected by
the oxidation. These groups were identified by the following methods. The presence of the
5-(amino sulfonyl) group was tested for by boiling the above solution with sodium hypochlo-
rite, which gave a canary yellow precipitate [10]. Anthranilic acid was tested for by heating
the reaction mixture with sodium sulfanillate in the presence of α-naphtalamine in ethanol;
the appearance of an intense red color [11] indicated the presence of anthranilic acid. The
benzoic acid functional group was confirmed [11] from a buff-colored precipitate in the pres-
ence of neutral FeCl3 solution. Another product was detected, furfuraldehyde. Its presence
was confirmed by a spot test as follows: a drop of the reaction mixture was placed in a micro
crucible that was covered with a disk of filter paper moistened with 10% aniline solution
containing 10% acetic acid. This moistened paper was placed on a watch glass, and a red
strain appeared on the filter paper upon heating at 40 °C [12]. The amount of furfuraldehyde
was also estimated quantitatively as its 2,4-DNP derivative.
3 Results and Discussion
3.1 Reaction Order
The reaction orders with respect to [fursemide], [alkali] and [periodate] were determined
from plots of log10 kobs versus log10 (concentration) for each of these reagents. These reac-
tion orders were obtained by varying the concentration of fursemide, periodate and alkali,
each in turn, while keeping the concentrations of the others constant. In view of the non-
linearity of the first order rate plots above 40% of reaction, these orders were also confirmed
by the initial rate method and found to be identical for both methods.
3.2 Effect of [Diperiodatocuprate(III)]
The concentration of DPC was varied over the range 1.0 × 10−5 to 2.0 × 10−4 mol·dm−3 at
fixed [fursemide], [OH−], [IO4−] and ionic strength. The lack of variation in the pseudo-first
order rate constants at various concentrations of DPC indicates that the order in [DPC] is
unity (Table 1). This was also confirmed from the linearity of plots of log10 [DPC] versus
time up to about 40% completion of reaction.

J Solution Chem (2010) 39: 165–177
169
Table 1 Effect of varying [DPC]
and [Fur] on the alkaline
4
3
3
−1
)
10 × [DPC]
10 × [Fur]
10 × k (s
obs
−3
−3
a
b
(mol·dm
)
(mol·dm
)
Exptl.
Calc.
diperiodatocuprate(III) oxidation
of fursemide at 25 °C, where
−
−3
[OH ] = 0.1 mol·dm
,
0.1
0.2
0.4
0.8
1.0
2.0
1.0
1.0
1.0
1.0
1.0
1.0
9.00
8.88
8.89
8.69
8.71
8.73
–
–
–
–
–
–
−
−3
−3
,
[IO ] = 1.0 × 10 mol·dm
4
−3
and I = 0.5 mol·dm
a
Experimental value
1.0
1.0
1.0
1.0
1.0
1.0
0.5
0.8
1.0
2.0
4.0
5.0
5.92
8.13
8.71
4.30
b
Calculated value; these values
6.00
6.70
of k
were calculated by using
obs
−2 −1
k = 1.87 × 10
s
,
11.2
10.1
13.1
14.0
3
−1
K = 1.88 dm ·mol
,
1
2
3
−3
15.1
16.1
K = 1.32 mol·dm and
3
3
−1
K = 2.4 × 10 dm ·mol
in (6)
Table 2 Effect of the variation
−
−
3
3
−1
−
−
[OH
]
10 × [IO
]
10 × k (s
)
obs
of [OH ] and [IO ] on the
4
4
−3
−3
a
b
alkaline diperiodatocuprate(III)
oxidation of fursemide at 25 °C,
where
(mol·dm
)
(mol·dm
)
Exptl.
Calc.
0.05
0.08
0.10
0.20
0.40
0.50
1.0
1.0
1.0
1.0
1.0
1.0
13.1
10.5
10.0
−4
−3
[DPC] = 1.0 × 10 mol·dm
,
7.90
6.70
4.30
2.44
2.01
−3
−3
[Fur] = 1.0 × 10 mol·dm
,
−3
8.71
and I = 0.5 mol·dm
6.03
3.72
3.16
a
Experimental value
0.1
0.1
0.1
0.1
0.1
0.1
0.5
0.8
1.0
2.0
4.0
5.0
5.36
7.48
8.71
4.31
6.02
6.70
b
Calculated value; these values
of k
were calculated by using
obs
−2 −1
k = 1.87 × 10
s
,
11.6
10.1
3
−1
K = 1.88 dm ·mol
,
1
2
3
−3
13.0
15.0
12.8
13.6
K = 1.32 mol·dm and
3
3
−1
K = 2.4 × 10 dm ·mol
in (6)
3.3 Effect of [Fursemide]
The concentration of the substrate, [fursemide], was varied from 5.0 × 10−4 to 5.0 ×
10−3 mol·dm−3 at 25 °C keeping all other reactant concentrations constant (Table 1). The
kobs values increased with increasing concentration of fursemide and its order was found to
be 0.4 (Table 1).
3.4 Effect of [Alkali]
The effect of [alkali] on the rate of reaction was studied at constant concentrations of
fursemide, DPC and IO−4 at a constant ionic strength of 0.5 mol·dm−3. The rate constants
decreased with increasing [alkali] with an order of −0.6 (Table 2).

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J Solution Chem (2010) 39: 165–177
3
Table 3 Effect of variation of
the Cu(II) product concentration
and ionic strength on the alkaline
diperiodatocupprate(III)
oxidation of fursemide at 25 °C,
where
4
10 × [Cu(II)]
Ionic strength
10 × k
obs
−3
−3
−1
(mol·dm
)
(mol·dm
)
(s
)
0.4
0.5
0.7
1.0
2.0
0.5
0.5
0.5
0.5
0.5
7.83
4.41
3.69
3.22
2.30
−4
−3
[DPC] = 1.0 × 10 mol·dm
,
−3
−3
[Fur] = 1.0 × 10 mol·dm
,
−
−3
and [OH ] = 0.1 mol·dm
–
–
–
–
–
–
0.2
0.4
0.5
0.7
0.9
1.2
12.9
9.90
8.71
7.40
6.10
4.90
Fig. 2 Effect of ionic strength
on the oxidation of fursemide by
diperiodatocuprate(III) in
aqueous alkaline medium at
25 °C (conditions are the same as
in Table 3)
3.5 Effect of [Periodate]
The effect of [IO−4 ] on the rate of reaction was also studied by varying its concentration from
5.0×10−4 to 5.0×10−3 mol·dm−3 at constant concentrations of DPC, fursemide, alkali and
constant ionic strength (Table 2). The rate constants increased with increasing [IO−4 ] and the
order was found to be 0.8 (Table 2).
3.6 Effect of Ionic Strength and Solvent Polarity
The effect of ionic strength was studied by varying the KNO3 concentration in the reaction
medium. The ionic strength was varied from 0.2 to 1.2 mol·dm−3 at constant concentrations
of oxidant, reductant, IO−4 and alkali (Table 3). It was observed that, as the ionic strength
√
increased, the rate of reaction decreased. The plot of log10 kobs versus I was linear (Fig. 2)
with unit negative slope.

J Solution Chem (2010) 39: 165–177
171
The relative permittivity (εT ) effect was studied by varying the t-butyl alcohol and water
content in the reaction mixture while all other conditions were held constant. The εT values
of the mixtures were computed from those of the pure liquids [13]. It was previously found
that there was no reaction between solvent and oxidant under the experimental conditions
used. Varying the t-butyl alcohol + water composition of the reaction medium had no effect
on the rate of reaction.
3.7 Effect of Initially Added Products
The effect of adding the product Cu(II) was studied over the concentration range of 4.0 ×
10−5 to 2.0 × 10−4 mol·dm−3 when all other reactant concentrations were kept constant.
The kobs values decrease with increasing [Cu(II)] with an order of −0.4 (Table 3). The other
product, furfuraldehyde, did not alter the rate of reaction.
3.8 Polymerization Study
DPC is a single equivalent oxidant. Hence, intervention of a free radical, generated from the
organic compound, was expected. In view of this, acrylonitrile was used as a free radical
scavenger and tested in the reaction mixture as follows. The reaction mixture was mixed
with acrylonitrile monomer and kept for 24 h under an inert atmosphere. Upon dilution with
methanol, a white precipitate of polymer formed, indicating that free radicals occurred dur-
ing the reaction. Separate experiments with either DPC or fursemide with acrylonitrile alone
did not induce polymerization under conditions similar to those used with the reaction mix-
tures. Initially added acrylonitrile decreases the reaction rate thus indicating a free radical
intervention [14].
3.9 Effect of Temperature
The rate of reaction was measured at different temperatures at constant concentrations of
reactants with other conditions being constant (Table 4a). From the slope of the Arrhenius
plot, the activation energy Ea was calculated. It was then used to calculate other activation
parameters ꢀH#, ꢀS#, ꢀG# and log10 A (Table 4b).
It has been reported that the water soluble sodium-potassium salt of Cu(III) periodate
is Na7KH(Cu(IO6)2) [6], in which periodate is unprotonated. However, in aqueous alkaline
solutions periodate occurs as a mixture of H3IO26− and H2IO36− monomers and the H2I2O14−0
dimer [15]. The dimeric species H2I2O140− has been reported to occur at higher [IO−4 ]. Thus,
under our experimental conditions the occurrence of polymeric form of periodates may be
ignored. Consequently only the monomers H3IO26− and H2IO63− are important in the present
study. By considering the periodate species present in copper(III) periodate, the species of
Table 4a Effect of temperature
on the alkaline
3
−1
)
Temperature (°C)
10 × k (s
obs
diperiodatocuprate(III) oxidation
of fursemide at 25 °C, where
25
30
35
40
45
8.71
12.6
17.7
24.0
31.6
−4
−3
[DPC] = 1.0 × 10 mol·dm
,
−3
−3
[Fur] = 1.0 × 10 mol·dm
,
−
−3
[OH ] = 0.1 mol·dm , and
−3
I = 0.5 mol·dm

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J Solution Chem (2010) 39: 165–177
Values
Table 4b Activation parameters
for the oxidation of fursemide by
alkaline diperiodatocuprate(III)
at 25 °C
Activation parameters
−1
E /kJ·mol
51 0.5
a
#
−1
ꢀH /kJ·mol
48.5 0.5
#
−1
−1
ꢀS /J·K ·mol
−63.5
2
2
#
−1
ꢀG /kJ·mol
67
log
A
6.8 0.2
10
DPC occuring in alkaline medium is either [Cu(H3IO6)2]− or [Cu(H2IO6)2]3−. Neverthe-
less, Lister [16] proposed that Cu(III) periodate occurs in three different forms: diperioda-
tocuprate(III) (DPC), monoperiodato cuprate(III) (MPC), and tetrahydroxocuprate(III) in
aqueous alkali solutions. The later species can be ruled out [17] because its equilibrium
constant for formation [16] is 8.0 × 10−11 at 40 °C. Hence, in the present study, copper(III)
periodate occurs either as DPC, MPC or their mixture. However, reports in the literature [18]
reveal that the actual molecular formulae of DPC and MPC are not known except in a single
case [6].
Based on the active form of periodate, the enhancing effect of [IO−4 ] and retarding effect
of [OH−], the plausible forms of MPC and DPC are given in (2) and (3):
K
1
[Cu(H2IO6)(H2O)2] + H3IO26− ꢀ [Cu(H2IO6)(H3IO6)]2− + 2H2O
[Cu(H2IO6)(H3IO6)]2− + H2O ꢀ [Cu(H3IO6)2]− + OH−
(2)
(3)
K
2
In (2), water molecules from the coordination sphere have been replaced by the biden-
date ligand H3IO26− to give the deprotonated diperiodatocopper(III) complex (DDPC), which
then undergoes hydrolysis to give a protonated diperiodatocopper(III) (DPC) as shown
in (3). Similar complexes have been reported for Ni(IV) periodate [19, 20] and Ag(III) pe-
riodate [21, 22]. However, these results are in conflict with the reported result [6] that OH−
had an accelerating effect, and periodate had a retarding effect, on the rates of reaction.
Fursemide posseses both –NH2 and –COOH groups. Thus, it is expected [17] to occur in
a zwitterionic or anionic form at the [OH−] used in the present study:
(4)
The positive test for intervention of free radicals in the reaction, the first order reaction
rate in [DPC], and the positive fractional orders in [fursemide] and in [periodate] can be
accommodated as shown in Scheme 1. Scheme 1 also includes (2) and (3), which account
for the positive fractional order in [IO−4 ] and the negative fractional order in [OH−].
Scheme 1 shows that protonated diperiodatocuprate(III) reacts with fursemide to give a
complex that, in turn, decomposes to give a free radical by the abstraction of an α-hydrogen

J Solution Chem (2010) 39: 165–177
173
Scheme 1
atom of alkyl group from the furfuryl moiety attached to the imino group of the benzene ring.
This free radical then reacts with another molecule of DPC in a fast step to give products.
Scheme 1 leads to the following rate laws given by (5) and (6):
d[DPC]
−
= rate
dt
kK1K2K3[Cu(III)]T[Fur][H3IO62−
]
=
(5)
(6)
[OH−]+K1[OH−][H3IO62−] + K1K2[H3IO26−] + K1K2K3[H3IO26−][Fur]
kK1K2K3[Fur][H3IO62−
]
kobs
=
[OH−]+K1[OH−][H3IO62−] + K1K2[H3IO26−] + K1K2K3[H3IO26−][Fur]

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J Solution Chem (2010) 39: 165–177
Fig. 3 Verification of the rate law (6) for oxidation of fursemide by diperiodatocuprate(III) at 25 °C (condi-
tions are the same as in Tables 1 and 2)
Equation (6) can be verified in the following form:
1
kobs
[OH−]
[OH−]
1
1
=
+
+
+
(7)
kK1K2K3[Fur][H3IO62−
]
kK2K3[Fur] kK3[Fur]
k
Plots of 1/kobs versus 1/[H3IO26−], 1/[fursemide], and [OH−] should be linear (Fig. 3).
From the slopes and intercepts of such plots, the constants k, K1, K2 and K3 are calculated
to be 1.87 ( 0.04) × 10−2 s−1, 1.88 ( 0.04) dm3·mol−1, 1.32 ( 0.03) mol·dm−3, and 2.4
( 0.07) × 103 dm3·mol−1, respectively. The magnitudes of K1 and K2 are in the neighbor-
hood of literature [6] values, which supports the proposed mechanism. Further, these data
are used in (6) to reproduce the kobs for different experimental conditions. The kcal and kobs
values are in reasonably agreement with each other (Tables 1 and 2).
The retarding effect of added Cu(II) on the rate of reaction may be attributed to the
formation of a complex between Cu(II) and fursemide, because Cu(II) is better at form-
ing complexes with ligands having a nitrogen donor atom. The literature [23] reveals that
Cu-amine or -amino acid complexes with copper in the mono and bivalent state are quite
common. Complexes of Cu(III) with amines and amino acids are rare [23] and appear only
as transient species. Such complexes have been proposed as intermediates in the Cu(II) cat-

J Solution Chem (2010) 39: 165–177
175
alyzed oxidation of amines by hydrogen peroxide. Hence, in the present study, a complex
between Cu(II) and fursemide is expected as evidenced by its UV-Vis spectra. The spectra
reveal that adding fursemide to 0.005 mol·dm−3 Cu(II) leads to a hypsochromic shift from
668 nm to 658 nm and hyperchromicity from 0.228 to 0.238. This complex might be less
reactive compared with the Cu(III) complex.
The diamagnetic (dsp2) square planar structure of Cu(III) periodate in the form of DPC,
DDPC, and MPC, and the paramagnetic (sp3) complex of Cu(II) and fursemide can be
formulated as shown below. Similar structures have been reported in other studies [6].
The decreasing rate of reaction with increasing ionic strength is in the expected direc-
tion [24], as negatively charged DPC interacts with a polar group of fursemide in the pre-
equilibrium step of the rate determining step, or a singly negatively charged DPC reacts
with another positive part of fursemide that is generated in a zwitterionic state. This is also
√
evidenced by the unit negative slope from the graph of log10 kobs versus I. This supports
the mechanism shown in Scheme 1. Dealing with the activation parameters for the reaction
is complicated, as it involves both the retarding effect of Cu(II) and other pre-equilibrium
steps involving various forms of Cu(III) periodate. However, the moderately negative value
of the entropy of activation [25], and the high positive value of ꢀG#, can be explained by
the loss of degrees of freedom in the activated complex which might be considered to be a
rigid sphere.
The negative value of ꢀS# (−63.5 J·K−1·mol−1) indicates that two species, either two
polar species or a polar and an ionic species, combine in the rate determining step to give
a single intermediate complex that is more ordered [26, 27] than the reactants (Scheme 1).
The magnitudes of ꢀH# and ꢀS# are both favorable for an electron absorption process. The
favorable enthalpy change was due to release of energy on neutralization of charges in the
transition state. The value of ꢀS# is within the range for radical reactions that have been
ascribed [28] to the nature of electron pairing and un-pairing processes, and to the loss of
degrees of freedom (formerly available to the reactants) on formation of a rigid transition
state.
The moderate value of the entropy of activation and the decrease in reaction rate with
increasing ionic strength clearly envisage an electron transfer from substrate to oxidant with
an outer sphere mechanism. This conclusion is also supported by the fact that the derived
small rate constant, k = 1.87 × 10−2
s
−1, and moderately large value of frequency factor,
log10 A = 6.8, support an outer sphere mechanism.

176
J Solution Chem (2010) 39: 165–177
4 Conclusions
Among various species of DPC occurring in alkaline medium, diperiodatocuprate (DPC) is
considered to be the active species for the title reaction. One of the products, Cu(II), had
a retarding effect on the rate of reaction. The reaction proceeds through the intervention of
free radicals. Equilibrium constants involved in the mechanism and activation parameters of
the reaction were evaluated. The overall mechanistic sequence described here is consistent
with the identified products, mechanistic studies, and kinetic studies.
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