A kinetic study of the oxidations of 2-mercaptoethanol and 2-mercaptoethylamine by heteropoly 11-tungsto-1- vanadophosphate in aqueous acidic medium

Article abstract of DOI:10.1007/s11243-015-9998-y

The kinetics of oxidation of 2-mercaptoethanol and 2-mercaptoethylamine by the heteropoly 11-tungsto-1- vanadophosphate anion, [PV^VW₁₁O₄₀]^4-, have been studied spectrophotometrically in aqueous perchloric acid at 25°C. EPR and optical studies show that [PV^VW₁₁O₄₀]^4- is reduced to the one-electron reduced heteropoly blue, [PV^IVW₁₁O₄₀]^5-, whilst the thiols are oxidized to the corresponding disulphides, RSSR. Spectrophotometric titrations show that the stoichiometry of both reactions is 1:1. At constant pH, the reactions show simple second-order kinetics with first-order dependence of rate on both [oxidant] and [thiol]. At constant [thiol], the rate of the reaction increases with increasing pH. Plots of k_obs/[thiol]_t versus 1/[H⁺] are linear with finite intercepts, showing that both the undissociated thiol (RSH) and thiolate ion (RS^-) are reactive species. Generation of RS^· from RSH proceeds via a separated-concerted proton-electron transfer mechanism. The reaction of thiolate ion is a simple outer-sphere electron transfer reaction. By applying the Marcus theory, the self-exchange rate constants for the couples HOCH₂CH₂S^·/HOCH₂CH₂S^- and H₃N⁺CH₂CH₂S^·/H₃N⁺CH₂CH₂S^- were evaluated as 3 × 10⁹ and 2.2 × 10⁸ M^-1 s^-1, respectively, at 25°C.

Full text of DOI:10.1007/s11243-015-9998-y

Transition Met Chem (2016) 41:77–85
DOI 10.1007/s11243-015-9998-y
A kinetic study of the oxidations of 2-mercaptoethanol and
2-mercaptoethylamine by heteropoly 11-tungsto-1-
vanadophosphate in aqueous acidic medium
1
1
1
•
Thangamariyappan Shanmugaprabha
1
•
Karuppaiah Selvakumar
Kasi Rajasekaran
•
Ponnusamy Sami
Received: 10 September 2015 / Accepted: 29 October 2015 / Published online: 12 November 2015
Ó Springer International Publishing Switzerland 2015
Á
þ
Abstract The kinetics of oxidation of 2-mercaptoethanol
and 2-mercaptoethylamine by the heteropoly 11-tungsto-1-
RSH À! RS þ H þ e
ð1Þ
ð2Þ
Á
V 4-
vanadophosphate anion, [PV W O ] , have been studied
2RS À! RSSR
1
1 40
spectrophotometrically in aqueous perchloric acid at 25 °C.
For example, oxidation of the thiol side chain of L-
cysteine forms disulphide linkages that are critical to the
proper folding of many peptides. The thiol/disulphide
couple (RSH/RSSR) acts as a redox buffer. This couple
modulates the activity of biological sites and regulates
metabolism, gene expression, protein conformation and
enzymatic activity [1–4]. Thiol-containing compounds are
effective antioxidants and act as scavengers for reactive
oxygen species (ROS) and thus protect cells, DNA and
proteins from the destructive effects of ROS and other free
radicals [5, 6].
V
EPR and optical studies show that [PV W O ]
4-
is
1
1 40
reduced to the one-electron reduced heteropoly blue,
IV
5-
PV W O ] , whilst the thiols are oxidized to the cor-
11 40
[
responding disulphides, RSSR. Spectrophotometric titra-
tions show that the stoichiometry of both reactions is 1:1. At
constant pH, the reactions show simple second-order kinetics
with first-order dependence of rate on both [oxidant] and
[
thiol]. At constant [thiol], the rate of the reaction increases
?
with increasing pH. Plots of kobs/[thiol] versus 1/[H ] are
t
linear with finite intercepts, showing that both the undisso-
-
ciated thiol (RSH) and thiolate ion (RS ) are reactive spe-
Á
There are diverse mechanisms for the generation of RS
Á
cies. Generation of RS from RSH proceeds via a separated-
from RSH by metal oxidants. When the oxidants are labile
metal complexes, an inner-sphere mechanism is operative
[7–9], in which the thiol proton is rapidly lost with formation
of a thermodynamically stable metal–thiolate complex (M-
SR) prior to the rate-limiting step. The intermediate complex
has been detected spectrophotometrically [7] in some reac-
tions. With substitutionally inert oxidants [10–14], oxidation
of RSH proceeds via an outer-sphere mechanism.
concerted proton–electron transfer mechanism. The reaction
of thiolate ion is a simple outer-sphere electron transfer
reaction. By applying the Marcus theory, the self-exchange
Á
-
rate constants for the couples HOCH CH S /HOCH CH S
2
2
2
2
?
and H N CH CH S /H N CH CH S were evaluated as
Á
?
-
3
2
2
3
2
-1 -1
2
9
9 10 and 2.2 9 10 M
8
3
s
, respectively, at 25 °C.
Á
Introduction
Generation of RS from RSH involves the loss of one
proton and one electron (Eq. 1). These may be transferred to
different molecular centres or to the same centre, either by
stepwise or by concerted processes. In the hydrogen atom
transfer (HAT) mechanism, the proton and electron are both
transferred to the oxidant in a single kinetic step. However, if
the oxidant has no acceptor site for the proton, the proton and
electron will be transferred to different centres. In aqueous
medium, in the absence of bases, the proton is transferred to
water and the electron will be transferred from RSH to the
oxidant. The stepwise pathway (Scheme 1) may involve an
The one-electron oxidation of aliphatic thiols (RSH) gen-
erates a thiyl radical (1), which undergoes dimerization to
form disulphide (2). This is an important reaction in bio-
logical systems.
&
Ponnusamy Sami
sami_rishi@yahoo.com
1
Department of Chemistry, VHNSN College,
Virudhunagar 626001, India
123

7
8
Transition Met Chem (2016) 41:77–85
ET-PT
+
used as such. For kinetic isotope studies, D O (99 % atom)
2
RSH + Y + B
RSH + Y + B
-
e
purchased from Aldrich was used. Deuterated 2-mercap-
toethylamine was obtained by equilibration of 2-mercap-
-H+
+
s-CPET
(
-H , -e)
toethylamine with D O. Doubly distilled water was used
2
RS + Y + BH+
for the preparation of all the solutions. Stock HClO4
solutions were standardized using carbonate-free sodium
hydroxide solution.
Scheme 1 Sequential and concerted mechanisms for the oxidation of
aliphatic thiols. ET–PT Electron transfer followed by proton transfer,
s-CPET separated-concerted proton-coupled electron transfer, Y oxi-
dant, B base that accepts a proton
Kinetics and instrumentation
initial slow electron transfer followed by fast proton transfer
Fresh solutions of thiols were always prepared just before
the kinetic experiments. All the kinetic measurements were
(
ET–PT). If the proton and electron are transferred to dif-
ferent molecular centres in a single kinetic step (Scheme 1),
this is termed as separated-concerted proton-coupled elec-
tron transfer (s-CPET) [15, 16].
made under pseudo-first-order conditions ([thiol] [ [oxi-
t
dant]) in aqueous medium at 25 °C. The course of the
reaction was monitored by measuring the decrease in
absorbance of the oxidant with time at 360 nm. The
pseudo-first-order rate constant, kobs, was evaluated from
Alkyl thiols have poor solubility in water, and this
limits the understanding of their aqueous chemistry. The
simple aliphatic thiol 2-mercaptoethanol, HOCH CH SH
2
the slope of plots of log(A -A ) versus time (A = ab-
t ? t
2
(
HORSH), has better solubility in water. The thiol and
sorbance at time; A? = absorbance at the completion of
reaction) by the method of least squares.
alcohol moieties are not too near to each other, and hence, it
may serve as a reasonable model of aqueous thiol chemistry.
UV–visible spectra were measured on a Shimadzu-1800
UV–visible spectrophotometer. Kinetic measurements
were made using a Shimadzu-1601 UV–visible spec-
trophotometer fitted with thermostatic cell holder. For pH
measurements, a Systronics digital pH meter was used.
X-band EPR spectra were recorded on a Bruker EMX plus
spectrophotometer. GC–MS spectra were recorded on an
Agilent-7820A GC system with 5977E MSD (DB-5
column).
2
-Mercaptoethylamine, H NCH CH SH, (H NRSH), is
2 2 2 2
analogous to L-cysteine and can therefore serve as a model
compound to understand the redox chemistry of L-cysteine.
3
-
Kinetic studies onthe oxidation of H NRSH by[Fe(CN) ]
6
,
2
III
5-
[
[
Co W O ] [17, 18] and on the oxidation of HORSH by
12 40
4
?
0
Mn -(l-O) (bipy) ] (bipy = 2,2 -bipyridine), [Mn -(l-
4
6
6
4
3
?
O) (phen) (H O) ]
4
IV 7-
heteropoly 13-vanadomanganate(IV) [Mn V O ] [19–
(phen = 1,10-phenanthroline) and
4
2
2
1
3 38
2
1] show that in all these reactions, in the rate-determining
step, an electron is transferred from the thiol to the oxidant. In
the oxidation of HORSH by {l-amido-l-superoxo-bis(te-
Results and discussion
Products
4
?
traamminecobalt(III)} , a HAT mechanism has been sug-
gested [22]. The bridging superoxide ligand accepts a
hydrogen atom from the thiol and gets reduced to a
VI-
V
4-
hydroperoxo complex. With the powerful oxidant [Fe
The UV–visible spectrum (Fig. 1) of [PV W O ] in
11 40
-2
2
-
O ] , oxidation of thiols proceeds through an ET–PT
2 9 10 M HClO shows an intense band at 258 nm
4
4
4
-1
-1
mechanism [23]. Previous studies from this laboratory have
shown that the heteropoly 11-tungsto-1- vanadophosphate
(e = 3.64 9 10 M cm ) and shoulders at 360 nm
3
-1
-1
(e = 2.5 9 10 M cm
)
and 410 nm (e = 1.45 9
V 4-
anion, [PV W O ] , acts as outer-sphere oxidant. It
3
-1
-1
10 M cm ). The band at 258 nm is assigned to
O ? W(VI) charge transfer transition (CTT) and the
shoulders at 360 and 410 nm to O ? V(V) CTT. Smith
and Pope [27] have reported a band at 262 nm
1
1 40
resists protonation in weakly acidic media [24] and does not
degrade after oxidation. Employing this oxidant, we have
now studied the kinetics of oxidation of 2-mercaptoethanol
and 2-mercaptoethylamine in aqueous medium with a view
to understand the mechanism of these electron transfer
reactions. The results of our studies are reported in this paper.
4
-1
-1
(e = 3.75 9 10 M cm ) and shoulders at 355 nm
3
-1
-1
(e = 2.6 9 10 M cm
)
and 410 nm (e = 1.5 9
10 M cm ) for the UV–visible spectrum of [PV W
3
-1
-1
V
1
1
4
-
O ] at pH 2.2.
4
0
-
Excess thiol HORSH/H NRSH, (1 9 10 M), was
1
2
V
added to a solution containing [PV W O ]
4-
Experimental
(1 9
1
1 40
-
3
-2
M) and HClO (2 9 10 M), and the mixture was
10
4
V
K [PV W O ]Á2H O was prepared and characterized as
kept until completion of reaction (24 h). The resulting
solution was extracted with chloroform to remove the
organic product and then analysed by optical and EPR
4
11 40
2
reported in our earlier papers [25, 26]. 2-Mercaptoethanol
and 2-mercaptoethylamine, purchased from Aldrich, were
1
23

Transition Met Chem (2016) 41:77–85
79
0
0
0
.6
.4
.2
0
2
1
0
2
00
300
400
500
Wavelength (nm)
3
20
420
520
620
Wavelength (nm)
V
4-
-4
(1.6 9 10 M) in
Fig. 3 X-band EPR spectrum of one-electron reduced heteropoly
IV
Fig. 1 UV–visible spectrum of [PV W11
O
40
]
5-
V
obtained by the reduction of [PV W11-
-2
blue [PV
W
11
-3
O
40
]
perchloric acid (2 9 10 M) medium (Insert is the UV–visible
4-
4-
-1
V
spectrum of a dilute solution of [PV W11
-5
(4 9 10 M) in
40 2 4
O ] (1 9 10 M) by HORSH/H NRSH (1 9 10 M) in HClO
O
40
]
-
(1 9 10 M) recorded at room temperature
2
-2
perchloric acid (2 9 10 M))
spectroscopy. The UV–visible spectrum (Fig. 2) of the
aqueous layer showed a shoulder at 400 nm and a band at
one electron from the thiol to form V(IV), and the odd
electron is localized on vanadium. Altenau et al. [29] have
-
1
-1
-4
reported giso = 1.952 and Aiso = 90.7 9 10 cm for the
-1
5
00 nm (e = 800 M cm ) for intervalence charge
transfer, V(IV) ? W(VI), and shoulders at 680 and
30 nm for d–d transition of V(IV). This spectrum is
characteristic of the one-electron reduced heteropoly blue,
IV
one-electron reduced heteropoly blue, [PV W O ]
5-
.
1
1 40
8
In order to identify the organic product, a solution
4-
V
containing [PV W O ]
-3
-3
(1 9 10 M), HORSH/H
2
-2
1
1
40
IV
5-
[
PV W O ] . Smith et al. [28] have reported a shoul-
1
NRSH (1 9 10 M) and HClO (2 9 10 M) was kept
1
40
4
-
1
-1
der at 400 nm, a peak at 500 nm (e = 750 M cm ) and
shoulders at 690 and 833 nm for the optical spectrum of
IV 5-
PV W O ] at pH 2.0.
until completion of the reaction (24 h) in a closed vessel to
avoid direct oxidation of thiol by air. The reaction mixture
[
containing H NRSH was neutralized with NaOH. Both
2
1
1
40
The EPR spectrum (Fig. 3) shows a typical eight-line
1 51
pattern expected for V(IV) with d configuration ( V,
solutions were extracted with chloroform. The chloroform
layer was dried over anhydrous magnesium sulphate, and
its UV–visible spectrum was recorded. A band at 245 nm
indicates that the product of oxidation is the disulphide,
HOCH CH SSCH CH OH or H NCH CH SSCH CH
2-
I = 7/2, 100 %) with g = 1.951 and Aiso = 91.1 9
iso
-4
0
-1
cm . The V(V) present in the oxidant has accepted
1
2
2
2
2
2
2
2
2
1
NH . The UV–visible spectrum of H NRSSRNH is shown
2 2 2
in Fig. 4. For the chloroform extract of the reaction mixture
0.8
0.6
0.4
0.2
0
1
.5
1
0.5
2
00
400
600
800
1000
Wavelength (nm)
0
200
300
400
500
Fig. 2 UV–visible spectrum of one-electron reduced heteropoly blue,
Wavelength (nm)
IV
5-
V
obtained by reduction of [PV W11
-1
4-
[
(
(
PV
1 9 10 M) with HORSH/H
W
11
-
O
40
]
O
40
]
NRSH (1 9 10 M) in HClO
3
2
4
2 2
Fig. 4 UV–visible spectrum of the disulphide H NRSSRNH in
-
2 9 10 M)
2
V
4-
CHCl
3
obtained by the oxidation of H
2 40
NRSH by [PV W11O ]
123

8
0
Transition Met Chem (2016) 41:77–85
with H NRSH, the GC–MS spectrum was recorded. In the
2
0.8
mass spectrum (Fig. 5), prominent peaks (m/z) were
observed at 121 (32 %), 119 (97 %), 117 (100 %), 83
(
41 %), 85 (26.4 %) plus a small peak at 55. There was no
0
0
0
.6
peak corresponding to the molecular ion (m/e = 152), and
all of the observed peaks occur at odd mass number. This
indicates that in all the fragment ions, only one nitrogen
atom is present (nitrogen rule). The pairs of peaks (121,
.4
1
19), (119, 117) and (85, 83) differ by 2 mass units and
correspond to loss of two hydrogen atoms. The peaks (117,
5) differ by 32 mass units due to loss of one sulphur atom.
8
.2
The peaks (119, 55) differ by 64 mass units, which cor-
respond to loss of two sulphur atoms, consistent with the
disulphide linkage. The various fragment ions are
?
?
?
C S NH (121), C S NH
3
?
C NSH (85), C NSH (83) and C NH (55). The results
(119), C S NH (117),
3 2 3
2
7
3
2
?
5
0
.0000
0.0005
0.0010
0.0015
0.0020
0.0025
?
3
3
3
3
5
V
4-
[
PV W O ] / M
1
1 40
of these spectroscopic studies show that the oxidation
V
4-
products of the thiols by [PV W O ] are their corre-
-
3
1
1
40
2
Fig. 6 Spectrophotometric titration of H NRSH (1 9 10 M) in
perchloric acid medium (2 9 10 M) with [PV W11O ]
40
-
2
V
4-
sponding disulphides.
Stoichiometry
various time intervals (Fig. 7). The absorbance at 360 nm
decreases and absorbance at 500 nm increases with time.
There is a well-defined isosbestic point at 455 nm. Similar
observations were reported [24, 25] in the oxidation of phenol
The stoichiometry of both the reactions was determined by
spectrophotometric titration. In a typical experiment, a
solution of 2-mercaptoethylamine/2-mercaptoethanol (1 9
V
4-
and thiourea by [PV W O ] . The results indicate an
1
1 40
-
3
-2
1
0
M) in HClO4 (2 9 10 M) was titrated spec-
4-
V
4-
IV
equilibrium involving the [PV W O ] /[PV W O ]
5-
1
1
40
11 40
V
trophotometrically with [PV W O ]
-3
(5 9 10 M).
1
1 40
couple.
The absorbance of the oxidant was monitored at 500 nm.
The spectrophotometric titration plot for 2-mercaptoethy-
lamine (Fig. 6) shows that the stoichiometry of the reaction
is 1:1. For the oxidation of 2-mercaptoethanol also, 1:1
stoichiometry was observed in a similar manner. The title
reactions can therefore be represented as
Kinetics
All the kinetic runs were carried out under pseudo-first-
order conditions ([thiol] ꢀ [oxidant]) in aqueous medium
at 25 °C. The course of the reaction was followed by
measuring the decrease in absorbance at 360 nm of the
V
4À
IV
þ RSH À! 2½PV W11O40Š
5À
2
½PV W11O40Š
þ
þ RSSR þ 2H
2
Spectrophotometric changes
a
1
0
.5
1
V
To a solution containing [PV W O ] (1 9 10 M) in
4-
-3
1
1 40
k
-2
-2
HClO (2 9 10 M), 2-mercaptoethylamine (1 9 10 M)
4
was added and the UV–visible spectrum was recorded at
k
.5
0
a
300
500
700
900
1100
Wavelength (nm)
V
4-
Fig. 7 Spectral changes of [PV W11
O
40
]
on reduction with
-mercaptoethylamine at a time interval of 300 s. (conditions:
2
V
4-
-3
= 1 9 10 M; [H
-2
Fig. 5 GC–MS spectrum of the disulphide H
V
2
NRSSRNH
2
obtained
[PV W11
O
40
]
2 4
NRSH] = 1 9 10 M; [HClO ] =
4-
-2
2 40
by the oxidation of H NRSH by [PV W11O ]
2 9 10 M; t = 25 °C)
1
23

Transition Met Chem (2016) 41:77–85
81
oxidant. The linearity of plots of log (A -A ) versus time
t
?
2
-Mercaptoethanol
(
At = absorbance at time t; A = absorbance at comple-
?
2-Mercaptoethylamine
6
4
2
tion of reaction) shows that the order of the reaction with
respect to [oxidant] is one. The pseudo-first-order rate
constant, kobs (evaluated from the slope of these plots by
the method of least squares), increases with an increase of
?
thiol] at constant [H ]. A plot of k
[
(
versus [thiol]t
t
obs
Fig. 8) is linear for both thiols and passes through the
origin. The order of the reaction with respect to [thiol] is
t
also one. At constant pH, the reaction shows simple sec-
ond-order kinetics, and the experimental rate law for the
reaction is
Àd½oxidantŠ=dt ¼ k½oxidantŠ½thiolŠt
where k is the apparent second-order rate constant.
The rates of the reactions were also measured at various
ð3Þ
1
.2
1.4
1.6
pH
1.8
2.0
?
H ] keeping [thiol] and [oxidant] at constant value. The
[
t
Fig. 9 pH-rate profiles for the oxidation of thiol. (conditions:
V
PV W11
4-
-3
= 1 9 10 M; [thiol]
-2
= 1 9 10 M; t = 25 °C)
pH-rate profiles (Fig. 9) show that the reaction is retarded
?
by increasing [H ]. The observed dependence of the rate
?
on [H ] is discussed below.
[
O
40
]
t
2-Mercaptoethylamine has two dissociable protons, as per
Kinetic isotope effect
Eqs. 4 and 5.
þ
þ
À
ðBÞ
þ
N H3CH2CH2SH ꢀ N H3CH2CH2S þ H
Ka1
Ka2
ð4Þ
ð5Þ
The rate of oxidation of deuterated 2-mercaptoethylamine
ðAÞ
(
RSD) in D O was measured and compared with the rate of
2
oxidation of RSH in H O. At pH 1.7, kH2O
=
þ
À
À
þ
2
N H3CH2CH2S ꢀ NH2CH2CH2S þ H
-
2
-1 -1
s
2
D O
-2
-1 -1
s
2
.7 9 10
M
and
k
= 1.9 9 10
M
.
ðBÞ
ðCÞ
The kinetic isotope effect (kH2O=kD2O) is therefore 1.4.
The proton dissociation equilibrium constants are
pKa1 = 8.27 and pKa2 = 10.53 corresponding to the –SH
þ
Mechanism and rate law
and N H3 groups, respectively [30]. For 2-mercaptoethanol,
To propose a mechanism, knowledge of the reactive
species present under the kinetic conditions is needed.
there is only one dissociable proton in the pH range up to
14.
À
ðBÞ
þ
HOCH CH SH ꢀ HOCH CH S þ H
Ka1
ð6Þ
2
ðAÞ
2
2
2
The pK value of the –SH group is 9.5 [31].
a
VI 2-
Oxidation of L-cysteine by [Fe O ] has been studied
12
2-Mercaptoethanol
-Mercaptoethylamine
4
2
[
23] in the pH range 7.6–11.3, and the kinetic results
showed that the completely deprotonated form,
–
9
6
3
0
–
OOCCH(NH )CH S , does not contribute to the rate even
2
2
at high pH. The completely deprotonated form of 2-mer-
-
captoethylamine (NH CH CH S ) will exist only at
2
2
2
pH [ 12. Kinetic studies on the oxidation of H NRSH/
2
HORSH were carried out in the pH range 1.3–2.0. There-
-
fore, the contribution of H NCH CH S to the rate can be
2
2
2
excluded. For both thiols, only two reactive forms, namely
þ
þ
À
2
H N CH CH SH and H N CH CH S for 2-mercap-
3
2
2
3
2
-
toethylamine and HOCH CH SH and HOCH CH S for
2
2
2
2
0
1
2
3
2
2-mercaptoethanol, may contribute to the overall rate of the
reaction. For both of these thiols, the rate of the reaction
1
0 [Thiol] / M
t
?
decreases with increasing [H ]. A similar inverse depen-
V
(conditions: [PV W11-
Fig. 8 Variation of
k
obs with [thiol]
t
.
4
-
-3
= 1 9 10 M; [HClO
-2
?
dence of rate on [H ] has been reported for the oxidation of
O
40
]
4
] = 2 9 10 M; t = 25 °C)
123

8
2
Transition Met Chem (2016) 41:77–85
0
2
glutathione [32–34] by a Ru(III) complex, [IrCl ] and
-
K
have not been reported, but this value can be calcu-
6
ass
III
III
5?
[
(NH ) Co (l-O )Co (NH ) ] . A mechanism involv-
lated from the K value of thiol group using Eq. 14.
a
3
5
2
3 5
ing deprotonation of thiol group prior to the rate-limiting
step was suggested by these authors.
0
K
¼ KassKa
Using the K
ð14Þ
ass
-
9
In acidic medium, both of the present substrates will
exist predominantly in the thiol form with minor amounts
of thiolate ion. Even though its concentration may be very
small, the thiolate form will probably be more reactive than
the thiol form. The concentration of thiolate form will
values of L-cysteine (6.6 9 10 ) and
a
0
2-mercaptoethanol (3.2 9 10 ), Kass values were calcu-
-
lated as 5.9 9 10 and 5.4 9 10 , respectively, for L-
-
10
5
-7
cysteine and 2-mercaptoethanol. The disulphide radical
Á-
anion, (RSSR) is a powerful reducing agent [35]. It is
?
decrease with increasing [H ], accounting for the observed
?
dependence of the rate on [H ].
rapidly and irreversibly oxidized to RSSR by another
molecule of oxidant (Eq. 12). This will be the predominant
Based on these kinetic and spectrophotometric obser-
path at higher pH. At lower pH, Eq. 11 is unfavourable
0
(since the value of Kass is small), and hence, dimerization
vations, the mechanism shown in Eqs. (7)–(13) can be
þ
Á
of RS by Eq. 13 could become significant. The fast reac-
envisaged for the oxidation of both thiols (R = H N
3
tions given in Eqs. 10–13 occur after the rate-limiting steps
and hence will not affect the kinetics.
For the mechanism shown in Eqs. (7)–(13), the rate law
is,
CH2CH2 for 2-mercaptoethylamine and R = HOCH CH2
2
for 2-mercaptoethanol).
fast
RSH ꢀ RS þ H
À
þ
Ka
ð7Þ
þ RS þ Hþ
þ À1Þ½oxidantŠ½thiolŠt
Àd½oxidantŠ 2ðk þ k K ½H Š
Â
Ã
Â
Ã5À
a
b
a
4À
slow
V
IV
Á
¼
ð15Þ
PV W11O40
þ RSH À! PV W11O40
þ
dt
ð1 þ Ka½H ŠÞ
ka
?
If K [H ] \ 1, Eq. 15 reduces to Eq. 16.
a
ð8Þ
kobs
2kbKa
½HþŠ
Â
Ã
Â
Ã5À
4À
slow
¼ 2k þ
ð16Þ
V
þ RS À! PV W11O40 þ RSÁ kb
À
IV
a
PV W11O40
½thiolŠt
ð9Þ
ð10Þ
ð11Þ
?
For both the thiols, plots of kobs/[RSH] versus 1/[H ]
t
fast
RS þ RS ꢁ ðRSSRÞ
fast
are linear with finite intercept on the y-axis (Figs. 10, 11).
À
Á
ÁÀ
Kass
From the intercepts and slopes of the plots, it was found
-
3
that 2k = (4.9 ± 1.0) 9 10
4
10 M
and 2k = (6.8 ± 0.4) 9
b
a
-1 -1
RSH þ RS ꢁ ðRSSRÞ þ Hþ
Á
ÁÀ
0
K
ass
s
for 2-mercaptoethylamine and for 2-mercap-
-
3
Â
Ã
Â
Ã5À
toethanol 2k
a
= (11.0 ± 3.3) 9 10
-1 -1
and 2k
= (1.8 ±
b
PV W11O40 Àþ ðRSSRÞÁÀ À! PV W11O40 þ RSSR
4
fast
V
IV
6
.2) 9 10 M
0
s . From the magnitudes of these values,
-
it is obvious that RS is more reactive than RSH.
ð12Þ
fast
Á
Á
RS þ RS À! RSSR
In this mechanism, K is the acid dissociation constant
ð13Þ
0
0
.07
.06
a
of the thiol group and k and k are the second-order rate
a
b
constants for oxidation of the thiol and thiolate forms,
Á
respectively. Thiyl radical (RS ) is generated from RSH
-
and RS in the rate-determining steps (Eqs. 8 and 9) by
0.05
reaction with the oxidant. There are two routes for the
formation of disulphide product (RSSR). In the first route,
0
0
.04
.03
Á
RS undergoes rapid direct dimerization to RSSR (Eq. 13).
Á
-
In the second route, RS first combines with RS or RSH to
Á-
form the disulphide radical anion, (RSSR) (Eqs. 10 and
0
1
1), with formation constants Kass and K , respectively.
ass
Á-
0.02
Radiolysis studies have shown the formation of (RSSR)
from thiols in aqueous medium upon irradiation [35–37].
20
40
60
/ [H+]
80
100
The equilibrium constant, K , has been reported as
ass
1
3
.9 9 10 and 1.7 9 10 M
3
-1
8
for L-cysteine [36] and
?
versus 1/[H ] for oxidation of 2-mer-
2
-mercaptoethanol [37], respectively. However, Kass value
Fig. 10 Plot of kobs/[thiol]
t
V
captoethanol by [PV W11
4-
O
40
]
at 25 °C
is not available for 2-mercaptoethylamine. The values of
1
23

Transition Met Chem (2016) 41:77–85
83
+
pK = 8.27
+
a
H NCH CH S + H+
-
H NCH CH SH
3
2
2
3
2
2
0
0
0
0
.04
.03
.02
.01
E0 = 1.35 V
E0 = ?
E0 = 0.87 V
+
+
+
+ H+
H NCH CH S
3 2 2
H NCH CH SH
3
2
2
pK = ?
a
Scheme 3 EMF diagram for 2-mercaptoethylamine
0
For 2-mercaptoethylamine, suitable E values are not
0
available. However, for most aliphatic thiols, E of the
Á
-
RS /RS ) couple [31] is almost independent of the struc-
(
2
0
40
60
/ [H+]
80
100
ture of R and equal to 0.74 V. We assume that this value
1
-
Á
2
also pertains to the NH CH CH S /NH CH CH S couple.
2
2
2
2
2
0
Protonation of the amine shifts E to a more positive value,
?
versus 1/[H ] for the oxidation of
Fig. 11 Plot of kobs/[thiol]
t
V
-mercaptoethylamine by [PV W11
4-
2
O
40
]
at 25 °C
which can be calculated using Eq. 19.
ꢀ
ꢁ
þ
þ
0
À
Á
0
À
Á
E
N H3RS = N H3RS ¼ E ðH2NRS =H2NRS Þ
þ 0:059ðpKa2À pKa1Þ
Details of k path
a
ð19Þ
The title reactions involve outer-sphere electron transfer.
0
The difference in E values of the oxidant and reductant gives
where pKa1 is the dissociation constant of the SH group and
þ
an idea about the magnitude of the driving force of the
0
reaction. The E value of the oxidant [29] is 0.80 V (NHE).
0
Experimental determination of E values for thiols is very
pKa2 is the dissociation constant of the NH3 group of
0
-mercaptoethylamine. The evaluated E value of the
2
þ
þ
À Á
N H3RS /N H3RS ) couple is 0.87 V. Using this value, E
0
(
difficult. Schemes 2 and 3 show EMF diagrams for 2-mer-
captoethanol and 2-mercaptoethylamine, respectively.
The equilibrium constant of the thiyl radical with
þ
þ
Á
þ
of the (N H3RS ; H /N H3RSH) couple is evaluated as
1
.35 V via Eq. 20.
ꢀ
?
chlorpromazine (ClPz ) has been determined experimen-
ꢁ
ꢁ
þ
þ
0
Á
þ
tally [35] by generating thiyl radical by pulse radiolysis;
E
N H3RS ; H = N H3RSH
Á
þ
þ
ꢀ
HOCH2CH2RS þ ClPz þ H ꢀ HOCH2CH2SH
þ
þ
0
À
Á
2
þ
¼ E N H RS = N H RS þ 0:059pK ðSHÞ
ð20Þ
3
3
a
þ ClPz
Using the E value of the ClPz /ClPz
ð17Þ
couple
0
?
2?
These results are summarized in the EMF diagrams of
-mercaptoethanol and 2-mercaptoethylamine (Schemes 2
and 3). For L-cysteine, Wang and Stanbury [10] calculated
0
Á
?
(
0.83 V), the E value of the (HORS , H /HORSH) couple
2
is evaluated as 1.33 V. The pKa of the SH group in
0
-mercaptoethanol is 9.5. The E value of the (HORS /
Á
0
-
?
Á -
?
2
the E value of the OOC( NH )CHCH S / OOC( NH )
3
3
2
-
HORS ) couple calculated using Eq. 18 is 0.77 V.
-
CHCH S couple as 0.88 V in a similar manner. Oxidation
2
0
Á
À
0
Á
þ
of the thiol form of the substrate may proceed either through
the sequential ET–PT mechanism or via the s-CPET
mechanism. In the ET–PT mechanism (shown below), a
E ðHORS =HORS Þ ¼ E ðHORS ; H =HORSHÞ
À 0:059 pKaðSHÞ
ð18Þ
Á þ
thiol radical cation (RSH) will be formed in the rate-limiting
step by transfer of one electron from RSH to the oxidant.
pK = 9.5
a
HOCH CH S + H+
-
Á þ
Â
Ã
Â
Ã5À
4À slow
HOCH CH SH
2
2
V
IV
À! RSH þ PV W O
0
k
2
2
RSH þ PV W O
1
1
40
11 40
a
Á þ
fast
RSH À! RS þ H
E0 = 1.33 V
Á
þ
E0 = ?
E0 = 0.77 V
fast
RS þ RS À! RSSR
Á
Á
+
+ H+
S
HOCH CH
SH
HOCH CH2
2
2
2
The thiyl radical cation will rapidly decompose to a thiyl
Á?
pK = ?
a
radical by loss of a proton. The pK value of (RSH) and
a
0
E of the (RSH) /RSH) couple are not available. However,
Á?
Scheme 2 EMF diagram for 2-mercaptoethanol
123

8
4
Transition Met Chem (2016) 41:77–85
-1 -1
s ,
0
the relevant E value will be higher than 1.5 V (since the
5
22 were evaluated as 2.8 9 10 and 5.2 9 10 M
5
Á?
pKa of (RSH) \ 0). The ET–PT mechanism will be
highly endergonic and unfavourable.
respectively. These values are less than the diffusion-con-
-1 -1
s ) calculated from
9
trolled rate constant (6.6 9 10 M
In the s-CPET mechanism (shown below), there is a
concerted transfer of one proton and one electron from
RSH to different molecular centres (R = HOCH CH for
the Debye equation. Therefore, the reaction of thiolate
anion with this oxidant proceeds via an activation-con-
trolled outer-sphere electron transfer reaction.
2
2
?
2
-mercaptoethanol; R = N H CH CH for 2-mercap-
3 2 2
toethylamine). The proton is transferred to a solvent
molecule, and the electron is transferred to the oxidant in a
single kinetic step.
Marcus theory
The Marcus theory [38, 39] can be used to calculate the
rate constant of a cross-electron transfer reaction pro-
ceeding through an outer-sphere mechanism. The func-
tional form of the Marcus equation is
Â
Ã
Â
Ã5À
4À
slow
V
Á
þ
IV
PV W11O40
þ RSHÀ!RS þH þ PV W11O40
ka
fast
Á
Á
RS þRS À! RSSR
1
=2
For the ET–PT mechanism, the S–H bond is not broken
in the rate-limiting step, and hence, no kinetic isotope effect
KIE) will be observed. The reverse is true of the s-CPET
mechanism. For the oxidation of 2-mercaptoethanol by
k12 ¼ ðk11k22K12f12Þ
ð23Þ
ð24Þ
2
ðlog K12Þ
(
log f12 ¼ 4
2
logðk11k22=z Þ
4
?
[
Mn -(l-O) (phen) (H O) ] , KIE was observed [20].
3
4
4
2
2
where k12 is the rate constant for the cross-electron transfer
reaction and k11 and k22 are the self-exchange rate con-
stants for the oxidant and reductant, respectively; K12 is the
equilibrium constant for the cross-electron transfer reaction
Similarly for the oxidation 2-mercaptoethylamine, a KIE
was observed in the present study. Therefore, it is highly
probable that the oxidation of HORSH and H NRSH pro-
2
1
1
ceeds through an s-CPET mechanism.
and z is the collision frequency (1 9 10 ). The equilib-
rium constant K12 can be calculated from the reduction
potentials of the oxidant and reductant. Direct experimental
determination of k11 and k22 is very difficult. Very often,
Details of k path
b
such constants are evaluated using the Marcus equation.
V-
V 4-
The reaction of thiolate with [PV W O ] is a simple
1
1
40
The self-exchange rate constant (k ) of the couple [PV
5-
11
4
-
IV
-1 -1
outer-sphere electron transfer process. Equations 9, 10 and
2 contribute to the mechanism. Further insight into the
W O ] /[PV W O ] was evaluated as 84 M s
11 40 11 40
0
1
from this laboratory [25]. Using an E value of 0.77 V for
Á
HORS /HORS , the self-exchange rate constant (k ) of
22
-
mechanism can be gained by consideration of the driving
force of the electron transfer reactions. The relevant reac-
tions can be written as shown in Eqs. 21 and 22.
-
Á
the HORS /HORS
9
3 9 10 M
couple was calculated as
-1 -1
s
by an iterative procedure using a com-
Â
Ã
kb
puter program together with Eqs. 23 and 24. A self-ex-
change rate constant of this magnitude is not unreasonable
in view of the electronic structure of the thiyl radical, in
which the unpaired electron resides on sulphur. Hence,
there will be minimal changes in the C–S bond length
accompanying electron transfer and a correspondingly
small internal reorganization energy.
4
À
À
Ã
À
V
Á
HORS þ PV W11O40
ꢀ HORS
kÀb
ð21Þ
ð22Þ
Â
Ã
5
IV
þ PV W11O40
Kb
þ
Â
kb
þ
4
À
À
V
Á
H3 N RS þ PV W11O40
ꢀ H3 N RS
kÀb
Â
Ã
5
À
IV
þ PV W O
0
K
11
40
b
0
Similarly using an E value of 0.87 V, the self-exchange
þ
22
0
b
The equilibrium constants K and K were calculated as
b
À
rate constant (k ) of the couple H3 N CH2CH2S =
-
.2 and 6.5 9 10 , respectively, from the E values of the
2
0
3
þ
Á
8
H3 N CH2CH2S was evaluated as 2.2 9 10 M
-1 -1
s .
oxidant and reductant. This corresponds to a free energy
0
-1
change (DG ) of -2.9 and 8.7 kJmol for the electron
Since this compound is similar to L-cysteine, this value can
be compared with the self-exchange rate constant of the L-
cysteine radical. From kinetic studies on the oxidation of L-
þ
-
transfer reactions of HORS and N H RS , respectively.
À
3
Qualitatively this result implies that the intrinsic barriers to
þ
V
V
5-
cysteine by [PV V W O ] , the self-exchange rate
1
0 40
-
-
electron transfer from HORS /N H3RS to [PV W
À
V
?
Á –
-1 -1
constant of the couple OOCCH( NH )CH S / OOCCH
3
?
( NH )CH S was reported as 1.7 9 10 M
1
1-
2
4
O ] should be rather small. From the calculated values
-
-
7
s
by
4
0
3
2
0
b
of the equilibrium constants K and K and the experi-
b
Sami et al. [13]. The k22 value obtained for
?
Á ?
NH CH CH S / NH CH CH S is higher than that of
3 2 2 3 2 2
-
mentally determined k values, the rate constants (k-b) for
b
the back electron transfer reactions shown in Eqs. 21 and
the cysteinyl system, perhaps due to a reduction in
1
23

Transition Met Chem (2016) 41:77–85
85
electrostatic repulsion; the overall charge is zero for
?
9. Paul PC, Tracey AS (1997) J Biol Inorg Chem 2:644
10. Wang X, Stanbury DM (2008) Inorg Chem 47:1224
-
NH CH CH S but -1 for OOCCH( NH )CH S .
-
?
-
3
2
2
3
2
1
1. Hung M, Stanbury DM (2005) Inorg Chem 44:3541
2. Sami P, Venkateshwari K, Mariselvi N, Sarathi A, Rajasekaran K
2009) Transit Met Chem 34:733
13. Sami P, Venkateshwari K, Mariselvi N, Sarathi A, Rajasekaran K
2010) Transit Met Chem 35:137
1
(
Conclusion
(
1
1
4. Saha B, Hung M, Stanbury DM (2002) Inorg Chem 41:5538
5. Costentin C, Evans DH, Robert M, Sav e´ ant JM, Sing PS (2005) J
Am Chem Soc 127:12490
The one-electron oxidation of the aliphatic thiols, 2-mer-
captoethanol and 2-mercaptoethylamine, generates the
corresponding thiyl radicals and one-electron reduced
16. Bonin J, Costentin C, Louault C, Robert M, Routier M, Save
JM (2010) Proc Natl Acad Sci USA 107:3367
´
ant
IV
5-
heteropoly blue, [PV W O ] . The thiyl radicals
1 40
1
1
1
7. Kapoor RC, Chohan RK, Sinha BP (1971) J Phys Chem 75:2036
8. Ayoko GA, Olatunji MA (1983) Polyhedron 2:577
combine with thiolate anion to give thiolate anion radical
in a fast equilibrium step. Subsequently, the thiolate anion
radical is irreversibly oxidized to the corresponding disul-
phide by another molecule of the oxidant. In the pH range
19. Chakraborty M, Mandal PC, Mukhopadhyay S (2012) Polyhe-
dron 45:213
2
0. Chakraborty M, Mandal PC, Mukhopadhya S (2013) Inorg Chim
Acta 398:77
1. Chakrabarty S, Banerjee R (2014) Int J Chem Kinetics 47:13
employed for the present kinetic studies, both the thiol
2
-
RSH) and the thiolate (RS ) forms are reactive. For the
(
[
22. Mishra R, Mukhopadhyay S, Banerjee R (2010) Dalton Trans
39:2692
V 4-
PV W O ] –RSH reaction,
a separated-concerted
1
1 40
2
3. Sharma VK, Luther GW III, Millero FJ (2011) Chemosphere
2:1083
proton-coupled electron transfer mechanism has been
suggested.
8
2
4. Vairalakshmi M, Raj V, Sami P, Rajasekaran K (2011) Transit
Met Chem 36:875
Acknowledgments The authors P.S and K.S thank the University
Grants Commission, New Delhi, India, for the award of major
research project (F. No. 42-349/2013(SR)) and financial assistance.
We also thank Sophisticated Analytical Instrumentation Facility,
CECRI Karaikudi, for EPR facilities and Managing Board, Virud-
hunagar Hindu Nadars’ Senthikumara Nadar College, Virudhunagar
for infrastructural facilities.
25. Sami P, Mariselvi N, Venkateshwari K, Vairalakshmi M, Sarathi
A, Rajasekaran K (2010) Transit Met Chem 35:563
26. Sami P, Anand TD, Premanathan M, Rajasekaran K (2010)
Transit Met Chem 35:1019
27. Smith DP, Pope MT (1993) Inorg Chem 12:331
28. Smith DP, So H, Bender J, Pope MT (1973) Inorg Chem 12:685
29. Altenau JJ, Pope MT, Prados RA, So H (1975) Inorg Chem
1
4:417
3
0. Edsall JT, Wyman J (1958) Biophysical chemistry. Academic
Press Inc, New York
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