Oxidation of psychotropic drugs by Chloramine-T in acid medium: A kinetic study using spectrophotometry

Article abstract of DOI:10.1016/S0022-2860(01)00859-6

The kinetics of oxidation of psychotropic drugs, chlorpromazine hydrochloride (CPH) and fluphenazine dihydrochloride (FPH), by Chloramine-T (CAT) in pH 1.6 buffer medium has been studied spectrophotometrically at λ_max = 570 and 530 nm, respecti

Full text of DOI:10.1016/S0022-2860(01)00859-6

Journal of Molecular Structure 606 (2002) 147±154
www.elsevier.com/locate/molstruc
Oxidation of psychotropic drugs by Chloramine-T in acid medium:
a kinetic study using spectrophotometry
a
R.J.D. Saldanha ,S. Ananda ,B.M. Venkatesha ,N.M. Made Gowda
a
a
b,*
a
Department of Studies in Chemistry, University of Mysore, Manasangangothri, Mysore 570 006, India
b
Department of Chemistry, Western Illinois University, One University Circle, Macomb, IL 61455, USA
Received 7 May 2001; accepted 8 August 2001
Abstract
The kinetics of oxidation of psychotropic drugs,chlorpromazine hydrochloride (CPH) and ¯uphenazine dihydrochloride
(
respectively,at 30 8C. The reaction rate shows a fractional-order dependence on [CAT] and ®rst-order dependence on each
FPH),by Chloramine-T (CAT) in pH 1.6 buffer medium has been studied spectrophotometrically at lmax ˆ 570 and 530 nm,
1
substrate]. The reaction rate also shows an inverse fractional-order in [H ]. Additions of halide ions and the reduction product
[
of CAT, p-toluenesulfonamide,and variation of ionic strength and dielectric constant of the medium do not have any signi®cant
effect on the reaction rate. The activation parameters for the reaction were evaluated. The proposed general mechanism and the
derived rate law are consistent with the observed kinetics. q 2002 Elsevier Science B.V. All rights reserved.
1
. Introduction
[2±5]. Fluphenazine dihydrochloride is also a white
solid used as a tranquilizer and in chemotherapy [5].
Kinetic and spectroscopic studies [6] have shown that
the one-equivalent oxidations of phenothiazine and
phenoxazine (Ar NH) in neutral and acidic CH CN
The N-alkylphenothiazines (NAPs) play a promi-
nent role in chemotherapy these days. Several reviews
1±5] have discussed the synthesis,structure,proper-
ties,and applications of NAPs. These drugs are versa-
tile compounds possessing anticholinergic,
[
2
IV
3
III
solution by Ce and Fe occur via the following
reaction sequence:
antihistaminic,antiamoebic,and antiemetic activities.
The NAPs,such as chlorpromazine hydrochloride
2
2
2
e
2 e
1z
1
Ar NH ! Ar NH ! Ar N ! product
2
2
2
1
2
H
(
CPH) and ¯uphenazine dihydrochloride (FPH),
have also been examined for antibacterial effect on
some bacterial strains in vitro. Chlorpromazine hydro-
chloride is a white solid used for pre-anaesthetic
medication,as a muscle relaxant and in the treatment
of tetanus. It produces also a quieting effect on chil-
dren with behavioral disorders,and it has been tested
for antifungal activities and used in standard assays
Reaction intermediates have been characterized by
uv-visible spectroscopy [6].
A prominent member of the class of N-haloaryl-
sulfonamides is sodium N-chloro-p-toluenesulfona-
mide or chloramine-T (p-CH C H SO NClNa.3H O
3
6
4
2
2
or CAT),which is a by-product in the manufacture
of saccharin [7±10]. Generally,CAT undergoes a
two-electron change in its reactions forming the
reduction products, p-toluenesulfonaminde or PTS
(p-CH C H SO NH ) and sodium chloride. The
*
Corresponding author.
E-mail address: GN-Made@wiu.edu (N.M. Made Gowda).
3
6
4
2
2
0022-2860/02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved.
PII: S0022-2860(01)00859-6

148
R.J.D. Saldanha et al. / Journal of Molecular Structure 606 (2002) 147±154
oxidation potential of the CAT-PTS couple varies
with the pH of the medium (1.139 v at pH 0.65,
tube whose outer surface was coated black. The tube
was thermostatted in a water bath at a given tempera-
ture. To this solution was added a measured amount of
pre-equilibrated CAT solution to give a desired
overall concentration. The reaction mixture was peri-
odically shaken for uniform concentration. The course
of the reaction was monitored spectrophotometrically
by measuring absorbance at the lmax (570 nm for CPH
and 530 nm for FPH) at regular time intervals for at
least three half lives. The pseudo-®rst-order rate
0
.778 v at pH 7.0 and 0.614 v at pH 9.7). The existing
chemistry of CAT and other N-haloarylsulfonamides
has been reviewed by Campbell and Johnson [10].
Since compounds such as hypochlorite and CAT can
act as sources of chlorine,they are used in the disin-
fection of drinking water [11,12]. As a result, CAT
can ®nd its way into the animal stomach,including
that of the human [12]. Ingested NAP drugs such as
CPH and FPH can react with CAT under acidic condi-
tions in the stomach. Therefore,there was a need for
understanding the oxidation mechanism of the drug in
acidic medium so that the study could throw some
light on the fate of the drug in the biological systems
in vivo.
0
constants, k ,calculated were reproducible within
^3%.
2.2. Stoichiometry and product analysis
Reaction mixtures containing different composi-
tions of CPH or FPH and Chloramine-T were equili-
brated at 308C in an acidic buffer of pH 1.6 for 24 h.
The iodometric determination of unreacted CAT in
the reaction mixture showed that 1 mole of NAP
consumed 4 moles of CAT (CPH) or 6 moles of
CAT (FPH).
After reviewing the literature,we found that there
was no information available on the oxidation of the
two substrates,CPH and FPH,by N-haloamines. In
this paper,we report the spectrophotometrically-
monitored kinetics of oxidation of CPH and FPH by
CAT in pH 1.6 buffer medium in order to elucidate the
reaction mechanism.
2
. Experimental
Chloramine-T (CAT) (E. Merck) was puri®ed by
ꢀ
1†
the method of Morris et al. [13]. An aqueous solution
of CAT was prepared,standardized periodically by
the iodometric titration and stored in brown bottles
to prevent its photochemical deterioration [13].
Aqueous solutions of CPH and FPH were prepared.
Standard buffer systems [14,15] were prepared (e.g.
for pH 1.6,a mixture of 0.20 M 50.0 ml KCl and
Of the reaction products,PTS was isolated and
recrystallized from dichloromethane and petroleum
2
6.3 ml 0.20 M HCl was diluted to 200 ml) and
used. All other chemicals were of analytical grade.
Triply distilled water was used for preparing aqueous
solutions.
ether and identi®ed by TLC (R ˆ 0.26 with dichlor-
f
omenthane solvent and iodine developing agent)
[16,17]. Furthermore, the mass spectrum showed an
1
M peak at 171 amu con®rming PTS. The conditions
2
.1. Kineticmeasurement
used in the GC-MS study for PTS were reported
earlier [17]. The other products,sulfoxides of CPH
and FPH,were identi®ed through UV spectral studies.
Kinetic runs were performed under pseudo-®rst
order conditions with a large excess of the oxidant
over the substrate (CPH or FPH) at 308C. For each
run,requisite amounts of solutions of CPH or FPH,
3. Results and discussion
NaClO (to maintain a constant ionic strength) and a
4
buffer of known pH and of given component concen-
trations [14,15] were mixed in a stoppered Pyrex glass
Under pseudo-®rst-order conditions of [CAT] @
o
[CPH]o or [FPH]o at constant [CAT] ,pH,and
o

R.J.D. Saldanha et al. / Journal of Molecular Structure 606 (2002) 147±154
149
Table 1
Table 2
24
Effects of varying reactant concentrations on the reaction rate.
Buffer pH ˆ 1.6; m ˆ 0.10 M; T ˆ 308C; lmax ˆ 570 nm (CPH)
and 530 nm (FPH); NAP ˆ CPH or FPH
Effects of pH on the reaction rate. [CPH]
o
or [FPH]
o
ˆ 5.00 £ 10
2
3
M; [CAT]
o
ˆ 2.00 £ 10 M; m ˆ 0.10 M; T ˆ 308C
a
0
3
21
pH
k £ 10 (s
)
3
4
0
3
21
[
CAT]
o
£ 10 (M)
[NAP]
o
£ 10 (M)
k £ 10 (s
)
CPH
FPH
CPH
FPH
1
.0
0.960
1.32
1.68
2.34
3.22
4.05
5.65
1.52
1.95
2.52
3.26
4.28
5.32
6.98
0
1
2
3
5
7
2
2
2
2
2
.50
.00
.00
.00
.00
.00
.00
.00
.00
.00
.00
5.00
5.00
5.00
5.00
5.00
5.00
1.00
3.00
5.00
7.00
10.0
1.23
1.68
2.34
2.66
3.53
3.84
2.36
2.32
2.34
2.30
2.34
1.65
2.38
3.26
4.06
5.37
6.12
3.24
3.20
3.26
3.24
3.26
1.2
1.4
1.6
1.8
2.0
2.2
a
Procedure in Ref. [5] was used to prepare each buffer and its pH
was veri®ed using pH meter.
increased with increasing [CAT] (Table 1). Further-
o
0
more,a plot of log k vs log[CAT] was linear with a
o
temperature,the substrate (NAP) concentration was
varied. For each run,the plot of ln( A /A ) vs time
slope showing a fractional-order dependence on
[CAT] (Fig. 1). The reaction rate increased with
increasing pH of the medium (Table 2). A plot of
0
t
was linear indicating a ®rst-order dependence of the
reaction rate on [CPH] and [FPH]. A and A are absor-
0
1
logk vs log[H ] was linear with a negative slope
o
t
1
showing an inverse fractional-order in [H ]. An addi-
bances of the reaction mixture at time intervals of zero
and t,respectively. The pseudo-®rst-order rate
constant obtained at 308C is independent of [CPH]o
-
tion of Cl or Br ions in the form of NaCl or NaBr at
-
1
constant [H ] and ionic strength did not affect the
and [FPH] further con®rming the ®rst-order depen-
o
rate. An addition of p-toluenesulfonamide or the
variation of the ionic strength of the medium by
dence on [NAP] (Table 1). At constant pH,[CPH] or
o
[
FPH] ,ionic strength,and temperature,the rate
o
adding NaClO had no effect on the reaction rate.
4
Also,the variation of the solvent composition using
MeOH did not affect the rate. The reaction was
studied at varying temperatures,25±40 8C. The acti-
vation parameters,namely energy of activation ( E ),
a
±
enthalpy of activation (DH ),and entropy of activa-
±
tion (DS ),were obtained from the Arrhenius and
0
0
Eyring plots of lnk vs 1/T and ln(k /T) vs 1/T. The
kinetic and activation data obtained are presented in
Table 3.
The existence of similar equilibria in acid and alka-
line solutions of N-metallo-N-haloarylsulfonamides
has been reported by Pryde and Soper [18],Morris
et al. [13],and Bishop and Jennings [19]. Chlora-
mine-T behaves as a strong electrolyte in aqueous
solutions forming different species as shown in Eqs.
(2)±(7).
2
ArSO NClNa O ArSO NCl 1 Na
1
ꢀ2†
ꢀ3†
2
2
0
24
Fig. 1. Plots of logk vs log[CAT]
2
o
. [CPH]
o
or [FPH]
23
o
ˆ 5.00 £ 10
3
2
1
mol dm ; buffer pH ˆ 1.6; m ˆ 0.10 mol dm ; T ˆ 308C.
ArSO NCl 1 H O ArSO NCl
2 2

150
R.J.D. Saldanha et al. / Journal of Molecular Structure 606 (2002) 147±154
Table 3
o
Temperature dependence and activation parameters for the oxidation of CPH and FPH by CAT in acidic buffer medium. [CPH] or
2
4
23
[
FPH]
o
ˆ 5.00 £ 10 M; [CAT]
o
ˆ 2.00 £ 10 M; m ˆ 0.10 M; buffer pH ˆ 1.6
0
3
21
±
21
± 21
DS (Jk mol
21
21
Substrate
k £ 10 (s
)
DH (kJ mol
)
)
a
E (kJ mol )
298 K
303 K
308 K
313 K
CPH
FPH
1.44
2.61
2.34
3.26
3.91
4.37
5.89
5.66
70.9
38.1
2 61.3
2 166.9
73.5
40.6
ArSO NHCl 1 H O O ArSO NH 1HOCl
2
ꢀ4†
ꢀ5†
ꢀ6†
ꢀ7†
species involved in the mechanism of CPH and FPH
oxidation. Thus the following reaction mechanism is
proposed (Scheme 1):
2
2
2
2
ArSO NHCl O ArSO NH 1ArSO NCl
2
2
2
2
2
The total effective concentration of the substrate,
[substrate] ,from Scheme 1 is given by
1
HOCl 1 H O H OCl
1
t
2
HOCl 1 HCl O Cl 1H O
2
‰SŠt ˆ ‰SŠ 1 ‰XŠ
This equation leads to the rate law below,
ꢀ9†
2
In acid solutions,the probable oxidizing species
are the conjugate free acid (ArSO NHCl),dichlora-
2
K K k ‰CATŠ‰SŠ ‰H OŠ
1
mine-T (ArSO NCl ),HOCl,H OCl ,and molecular
1
2
1
3
t
2
Rate ˆ
ꢀ10†
2
2
2
‰
H Š 1 K K ‰CATŠ
1
2
chlorine. As Eq. (4) indicates a slow hydrolysis,if
HOCl were the primary oxidizing species,a ®rst-
order retardation of the rate by the added ArSO NH
which is in good agreement with the experimental
data,including a ®rst-order in substrate,a frac-
tional-order in CAT and an inverse fractional-
2
2
would be expected,contrary to the experimental
results. If ArSO NC1 were the reactive species,the
1
2
2
order in [H ].
Since the reaction was studied under pseudo-®rst-
rate law would predict a second-order dependence on
CAT] and a rate retardation by ArSO NH [Eq. (5)],
which are contrary to the experimental observations.
[
2
2
1
Similarly,if H OCl [Eq. (6)] or molecular chlorine
2
[
Eq. (7)] were the reactive species,there would be a
positive effect of [HCl] on the rate,which did not
occur. Narayanan and Rao [20] and Subhashini et al.
[
21] have reported that monohaloamines can be
further protonated at pH # 2 as shown in Eq. (8) for
Chloramine-B (CAB,Ar ˆ C H ) and CAT (Ar ˆ
6
5
CH C H ).
4
3
6
1
ArSO NHCl 1 H KArSO N H Cl
1
ꢀ8†
2
2
2
0
The second protonation constants, K ,for CAB
2
1
and CAT are 61 ^ 5 and 102 M ,respectively,
at 258C. Gupta [22] has suggested that the value
could be lower than those reported by the above
workers.
In the present case,an inverse fractional-order
1
in [H ] suggests that the deprotonation of
0
1
Fig. 2. Plots of 1/k vs [H ]. [CPH]
24
o
or [FPH]
23
o
ˆ 5.00 £ 10 mol
1
ArSO N H Cl results in the regeneration of
2
dm ; [CAT]
3
23
23
2
2
o
ˆ 2.00 £ 10
mol dm ; m ˆ 0.10 mol dm
;
ArSO NHCl,which is the most likely active oxidant
2
T ˆ 308C.

R.J.D. Saldanha et al. / Journal of Molecular Structure 606 (2002) 147±154
151
Scheme 1.
Scheme 2.

152
R.J.D. Saldanha et al. / Journal of Molecular Structure 606 (2002) 147±154
linear with
1
‰
H Š
1
slope ˆ
and intercept ˆ
K K k ‰H OŠ
k ‰H OŠ
1
2
3
2
3
2
0
1
Also,from Eq. (12),a plot of 1/ k vs [H ] at
constant [CAT] , [S] ,and temperature is linear
o
o
(
Fig. 2) with
1
slope ˆ
K K k ‰CATŠ‰H OŠ
1
2
3
2
1
and intercept ˆ
k ‰H OŠ
3
2
2
3
21
21
The values of k (4.76 £ 10
M
s
and
23
3
2
3
21
21
8
.00 £ 10
M
s
for CPH and 8.30 £ 10
2
1
21
22
21 21
M
s
and 1.00 £ 10
M
s
for FPH) have
been calculated from the intercepts of the above
plots. Narayanan and Rao [20],Subhashini et al.
[
(
21],and Gupta [22] have reported the value of K
1
2
3
9.80 £ 10 M) for other substrate oxidations by
2
3
CAT. A value of K (6.59 £ 10 M for CPH and
1
2
3
9
.80 £ 10 M for FPH) obtained from Eq. (12) is
similar to the one reported previously [20±22].
Hence this K1 value indirectly supports the
proposed Scheme 1.
Fig. 3. UV spectra of Chlorpromazine Hydrochloride (CPH) and
4
2
23
dm ;
CPH 1 CAT.
CAT]
[CPH]
3
o
ˆ 4.00 £ 10
mol
2
23
[
o
ˆ 2.00 £ 10 mol dm ; buffer pH ˆ 1.6.
The activation energies and rate constants (Table 3)
show that the oxidation of FPH is faster than that of
CPH. Several structure±activity relationship studies
have shown that the pharmacological effects of NAP
compounds in living systems depend on the nature of
the N-alkyl side chain (R) and the aromatic ring
0
order conditions of [S] , [CAT] ,rate ˆ k [S] .
o
o
t
Therefore,Eq. (10) becomes,
0
substituent (R ) (structure I,Scheme 2) [2 3, ]. Quanti-
tative changes depend on the electron-withdrawing or
K K k ‰CATŠ‰H OŠ
k0 ˆ k
ˆ
1
2
3
2
ꢀ11†
obs
1
‰
H Š 1 K K ‰CATŠ
1
2
0
electron-donating power of R group,particularly at
the 2-position,while the qualitative effects are
directed by the steric and electronic nature of R
group [2,3]. Therefore, in the present kinetic study,
the difference in reactivities of FPH and CPH is
mainly due to the inductive effects of the electron-
Eq. (11) can be transformed into the following
forms:
1
1
‰H Š 1 K K ‰CATŠ
1
2
0
ˆ
ˆ
or
withdrawing R group in the NAP molecule. As
expected,the FPH molecule with a stronger elec-
0
k
K K k ‰CATŠ‰H OŠ
1
2
3
2
ꢀ
12†
1
tron-attracting CF group has a greater reactivity
3
1
‰H Š
K K k ‰CATŠ‰H OŠ
1
1
0
than CPH,which has a weaker electron-attracting Cl
±
k
k ‰H OŠ
1
2
3
2
3
2
group. The negative values of DS suggest the forma-
tion of a more ordered and rigid transition state for
each NAP reaction (Table 3).
The absorption and ESR spectral studies have
0
1
A plot of 1/k vs 1/[CAT] at constant [S] ,[H ],
o
and temperature from Eq. (12) was found to be

R.J.D. Saldanha et al. / Journal of Molecular Structure 606 (2002) 147±154
153
2
4
23
23
Fig. 4. UV spectra of Fluphenazine Dihydrochloride (FPH) and FPH 1 CAT. [FPH]
2
o
ˆ 4.00 £ 10 mol dm ; [CAT] ˆ 2.00 £ 10 mol
o
3
dm ; buffer pH ˆ 1.6.
shown how the oxidation of NAP molecules occurs in
acidic aqueous solutions [1±6,23]. Scheme 2 shows
general structures of species involved in the NAP
oxidation sequence.
The spectral data suggest that the oxidation
proceeds through two single-electron steps from
neutral molecule (I) to the free-radical cation (II)
and then to the dication (III) [2,3]. The change in
color from colorless to pink is due to the formation
of a radical cation (II),which undergoes dismutation
to form a mixture of I and III. A possible alternative
route for the formation of III is an one-electron oxida-
tion of II. The dication III exhibits absorption maxima
exhibit a lmax at 205 nm [24]. Examination of the uv
spectral data obtained after completion of the NAP±
CAT reaction showed additional peaks at 270,302
and 336 nm,which correspond to the general sulf-
oxide product structure (V) shown in Scheme 2,
consistent with the reported data [3±6,23,25].
The uv spectral data also suggest that the N±R bond
(structure I in Scheme 2) remained intact when the
radical cation (II) was oxidized to dication (III)
since the loss of R group would have led to the
formation of product VI [3,4,25,26].
(
lmax) at 570 nm for CPH and 530 nm for FPH. The
hydrolysis of III followed by deprotonation of IV
leads to the formation of sulfoxide product V [3].
The uv spectra of free CPH and FPH,and of their
reaction mixtures in aqueous solutions were recorded
(
Figs. 3 and 4). Absorption maxima in aqueous
medium appear at 254 and 306 nm for CPH and 256
and 308 nm for FPH [3,4]. Aqueous solutions of CAT
The expected lmax values of 225,and 326 nm were
not observed in the reaction mixture of NAP and

154
R.J.D. Saldanha et al. / Journal of Molecular Structure 606 (2002) 147±154
CAT,showing the absence of phenothiazine sulfoxide
VI amongst the oxidation products [6,26].
tion of tricyclic neuroleptics and antidepressants,in: I.S.
Forrest,C.J. Carr,E. Usdin (Eds.),The Phenothiazines and
Structurally Related Drugs,Raven Press,New York,1974,
pp. 5±13.
The TLC analysis of the crude oxidation-reaction
mixture indicated the presence of ®ve to six products,
but they were not separated. Therefore,as observed in
the stoichiometry,more than two equivalents of the
oxidant were consumed. Experiments are presently
underway to separate the individual oxidation
products.
[
3] P.C. Huang,S. Gabay,Isolation and charcterization of
phenothiazine±copper complexes,in: I.S. Forrest,C.J. Carr,
E. Usdin (Eds.),The Phenothiazines and Structurally Related
Drugs,Raven Press,New York,1974,pp. 97±109.
4] J. Balsek,Die Pharozie 3 (1967) 129.
[
[
5] N.C. Wood,K.M. Nugent,Antimicrob. Agents Chemother. 27
(
1985) 692.
6] J.T. Kemp,P. Moore,G.R. Quick,J. Chem. Soc.,Perkin II
1980) 291.
[
[
(
4
. Conclusion
7] D.S. Mahadevappa,K.S. Rangappa,N.M. Made Gowda,B.T.
Gowda,J. Phys. Chem. 85 (1981) 3651.
The kinetic study involving the oxidation of CPH
and FPH by CAT in acidic buffer medium has led to
the following conclusions:
[8] D.S. Mahadevappa,K.S. Rangappa,N.M. Made Gowda,B.T.
Gowda,Int. J. Chem. Kinet. 14 (1982) 1183.
[
9] B.T. Gowda,D.S. Mahadevappa,J. Chem. Soc.,Perkin Trans.
II (1983) 323.
[
[
10] M.M. Campbell,G. Johnson,Chem. Rev. 78 (1978) 65.
11] N.M. Made Gowda,N.M. Trieff,G.J. Stanton,Appl. Environ.
Microbiol. (USA) 32 (1981) 469.
1
. the oxidation stoichimetries of the two NAPs deter-
mined under similar experimental conditions
differ: a mol-to-mol ratio of 1:4 for the CPH±
CAT reaction and a mol-to-mol ratio of 1:6 for
the FPH±CAT reaction;
[12] N.M. Made Gowda,N.M. Trieff,G.J. Stanton,Water
Research (UK) 20 (7) (1986) 817.
[
13] J.C. Morris,J.A. Salazar,M.A. Wineman,J. Amer. Chem.
Soc. 70 (1948) 2036.
2
. the oxidation of FPH occurs at a faster rate than
that of CPH,which is attributable to the electron-
withdrawing ability of the aromatic ring substi-
[
14] A. Findley,Practical Physical Chemistry,Longmans,London,
UK,1952,p. 268.
[15] G. Gomori,S.P. Colowick,N.O. Kaplan,Methods Enzymol. 1
1955) 138±146.
0
(
tuent,R ,in the NAP molecule;
[
16] H. Ramachandra,D.S. Mahadevappa,K.S. Rangappa,N.M.
Made Gowda,Int. J. Chem. Kinet. 29 (1997) 773.
3
4
. the two NAPs follow the same general reaction
mechanism as proposed in Scheme 1;
. the values of deprotonation constant, K ,of
[
17] R. Ramachandrappa,S.M. Puttaswamy,N.M. Mayanna,Made
Gowda,Int. J. Chem Kinet. 30 (1998) 407.
1
1
ArSO N H Cl determined from the oxidation of
2
[18] B.G. Pyrde,F.G. Soper,J. Chem. Soc. (1926) 1582.
19] E. Bishop,V.J. Jennings,Talanta 1 (1958) 197.
2
23
23
[
CPH (6.59 £ 10 M) and FPH (9.80 £ 10 M)
2
3
[20] S.S. Narayanan,V.R.S. Rao,Radio Chem. Acta. 32 (1983)
211.
agree with the reported value of 9.80 £ 10
M
0
21
(1/K ˆ K ˆ 102 M ) from other substrate oxida-
tions [20±22] supporting the proposed mechanism.
1
[
[
[
[
21] M. Subhashini,M. Subramanian,V.R.S. Rao,Talanta 32
1985) 1082.
(
22] Y.K. Gupta,Private Communication,Jodhpur University,
India,1988.
23] P.H. Sackett,J.S. Mayausky,T. Smith,S. Kalus,R.L.
McGreery,J. Med. Chem. 24 (1981) 1342.
24] N.M. Made Gowda,V.M.S. Ramanujam,N.M. Trieff,Micro-
chem. J. 25 (1980) 93.
References
[
[
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