Entropy-Controlled Cu(II)-Catalyzed Oxidation of N-Acetyl-L-Cysteine by Methylene Blue in Acidic Medium

Article abstract of DOI:10.1515/zpch-2016-0853

Kinetics of the oxidation of N-acetyl-L-cysteine (NAC) by methylene blue (MB) catalyzed by Cu(II) have been investigated in presence of HCl. The reaction follows a first order kinetics in MB while the concentration order in NAC is zero. Hydrogen ions retard the rate of reaction. The reaction involves the participation of nanoparticles as revealed by SEM, XRD and FTIR techniques and a gel-like Cu-NAC network acts like the effective catalyst. The reaction conforms to Eley-Rideal mechanism at lower [NAC] while at higher [NAC], the kinetics are explained by extended Eley-Rideal mechanism. The reaction is regulated by the size and morphology of the nanoparticles and is controlled by the entropy of activation.

Full text of DOI:10.1515/zpch-2016-0853

Z. Phys. Chem. 2017; 231(6): 1093–1109
Ranjana Sharma, Mahender Pal and K.K. Mishra*
Entropy-Controlled Cu(II)-Catalyzed
Oxidation of N-Acetyl-L-Cysteine by
Methylene Blue in Acidic Medium
DOI 10.1515/zpch-2016-0853
Received July 14, 2016; accepted October 22, 2016
Abstract: Kinetics of the oxidation of N-acetyl-L-cysteine (NAC) by methylene
blue (MB) catalyzed by Cu(II) have been investigated in presence of HCl. The
reaction follows a first order kinetics in MB while the concentration order in NAC
is zero. Hydrogen ions retard the rate of reaction. The reaction involves the par-
ticipation of nanoparticles as revealed by SEM, XRD and FTIR techniques and a
gel-like Cu-NAC network acts like the effective catalyst. The reaction conforms
to Eley-Rideal mechanism at lower [NAC] while at higher [NAC], the kinetics are
explained by extended Eley-Rideal mechanism. The reaction is regulated by the
size and morphology of the nanoparticles and is controlled by the entropy of
activation.
Keywords: Cu(II) catalysis; Eley-Rideal adsorption; kinetics and mechanism;
methylene blue; N-acetyl-L-cysteine.
1 Introduction
Sulphydryl compounds are known to be essential for regulation of various bio-
logical processes especially for maintaining the reductive environments. This is
manifested by their capability of scavenging intracellular reactive oxygen species
(ROS) during oxidative stress largely due to the fact that unbalanced environ-
ments may cause damage to cells and induce undesired cell death [1]. N-acetyl-L-
cysteine (NAC), the substrate used presently has a wide therapeutic profile and it
is reported to be the most widely used mucolytic agent [2]. It has found enormous
applications in treatment of neurodegenerative diseases such as Parkinson’s and
Alzheimer’s disease [3]. The oxidant methylene blue (MB) is a phenothiazine
*Corresponding author: K.K. Mishra, Department of Chemistry, Rani Durgavati University,
Jabalpur (M.P) 482001, India, e-mail: kkmishra.chem@gmail.com
Ranjana Sharma and Mahender Pal: Department of Chemistry, Rani Durgavati University,
Jabalpur (M.P) 482001, India
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dye that has been used as an inhibitor of plasmodium falciparum malaria [4], as
a model electron receptor for the degradation of surface-confined DNA [5] and
in treatment of Alzheimer’s disease and hepatitis C [6–9]. Metal ion catalysis is
indispensable in biolochemical processes as well as in industry. Transition metal
ions such as palladium, ruthenium either alone or as binary mixtures as catalyst
have been used [10, 11] and thus, the oxidation of a few sulphydryl substrates by
MB in presence of metal ions has been investigated by Mishra and coworkers in
these laboratories [12–16]. In view of this, the interaction of these two biologically
active reactants has been studied in presence of Cu(II), the metal ion known to
be indispensible for sustaining life along with Zn(II) [17]. The reaction is found to
involve the participation of nanoparticles having a bearing on their size and mor-
phology obeying Eley-Rideal mechanism. It may be added here that the photocat-
alytic activities of Cu2O with morphological evolution from truncated octahedral
to spherical structures are found to be dependent on its size and shape [18].
2 Experimental
2.1 Materials and methods
The samples of N-acetyl-L-cysteine (NAC, RSH) (Lancaster, England; assay 98+%)
and methylene blue (MB) (E. Merck, Germany) were prepared in double distilled
water by dissolving an exactly weighed quantity of the samples. The solution of
Cu(II) was prepared by dissolving CuSO4·5H2O in conformity with the standard
procedure and standardized as described in literature [19]. All the reagents were
E. Merck’s GR grade samples and double distilled water was used throughout
these investigations.
2.2 Instrumentation
The progress of the reaction was followed on Thermospectronic Unicam
UV-530 spectrophotometer by measuring the depletion in absorbance of meth-
ylene blue (εmaxꢀ=ꢀ6.76ꢀ×ꢀ104 M−ꢀ1 cm−ꢀ1 at 664 nm) with time. The ingredients of the
reaction mixture were thermostatted (Julabo, Germany; Model No. F-34E; tem-
perature stability 0.03 °C) in steam washed reaction vessels (Pyrex, England)
coated with Black Japan. The runs showed an identical behavior under aerobic
and anaerobic conditions and thus, the kinetics were studied under aerobic con-
ditions. Further, scattering by the gel-like intermediate is ruled out in the visible
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region as already reported by Okay et al. [20]. This is evinced by the fact that
identical kinetic behavior is noticed when the runs are followed with and without
centrifugation (Kumar Centrifuge, Mumbai, India; 50 000 rpm). The precision of
kinetic data are within 5%. The IR spectra of the samples were recorded on FTIR
spectrometer (Shimadzu, Model. No.8400 S) using KBr pellets. SEM images were
obtained on JEOL/EO JSM-6390 Scanning Electron Microscope while XRD spectra
were recorded on PANalytical Empyrean X-ray diffractometer.
3 Results and discussion
3.1 Stoichiometry of the reaction
The principal reactants interact in a molar ratio of 2 : 1 forming corresponding
disulphide and dihydromethylene blue as the end products. The stoichiometry
of the reaction was determined spectrophotometrically and formation of the
disulphide was confirmed by recording FTIR spectra of the reaction mixture after
completion of the reaction. The spectra show the characteristic frequency of -S-S-
linkage at 550 cm−ꢀ1 [21] which suggests that the chemical reaction is represented
by Scheme 1.
4 Reaction order
4.1 Effect of [NAC]
The concentration of NAC was varied in the range of 2.0ꢀ×ꢀ10−ꢀ3 M–10.0ꢀ×ꢀ10−ꢀ3
M
at a fixed concentration of methylene blue (MB) and hydrochloric acid and at a
fixed ionic strength. It was found that the concentration order in the substrate is
zero as is revealed by the constant values of the initial rate of the reaction meas-
ured at the points where 10% reaction is completed (Table 1). The first order rate
constant, evaluated over the span of the average life period of the reaction (30–
35 min), initially remains almost constant indicating a zero order kinetics in
2RSH
+
LMB
+
MB
RSSR
+
H
Scheme 1:ꢀStoichiometry for the reaction.
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Tab. 1:ꢀEffect of variation of [NAC] on the rate constant.
− 1
−ꢁ1
[NAC]ꢁ×ꢁ103 M
Initial rateꢁ×ꢁ108 Ms
k1ꢁ×ꢁ104 s
3.0
4.0
5.0
6.0
8.0
10.0
1.1
1.3
1.2
1.3
1.3
1.1
6.4
6.7
6.7
6.4
5.0
4.1
[MB]ꢁ=ꢁ2.0ꢁ×ꢁ10−ꢁ5 M; [HCl]ꢁ=ꢁ0.05 M; [CuSO4]ꢁ=ꢁ6.0ꢁ×ꢁ10−ꢁ5 M; Iꢁ=ꢁ0.25 M; Tempꢁ=ꢁ35 °C.
NAC. Subsequently, at higher concentrations of NAC (ca. ꢁ≥ꢁ 6.0ꢀ×ꢀ10−ꢀ3 M), the rate
constant linearly decreases indicating that the order in NAC becomesꢀ−ꢀ1 under
these conditions. The plots were drawn between log k1 and log [NAC] which give
a plateau and subsequently the rate shows a decreasing trend (Figure 1).
The title reaction, as would be seen, is a complex process and involves the
participation of nanoparticles as elaborated later. This results in some surface
phenomena coupled with the kinetic features of the reaction. The kinetics of the
system has been, however, highlighted by giving a typical kinetic run studied
presently (Table S1).
Fig. 1:ꢀA plot of log k1 against log [NAC]. [MB]ꢁ=ꢁ2.0ꢁ×ꢁ10−ꢁ5 M; [HCl]ꢁ=ꢁ0.05 M; [CuSO4]ꢁ=ꢁ6.0ꢁ×ꢁ10−ꢁ5
M; Iꢁ=ꢁ0.25 M; Tempꢁ=ꢁ35 °C.
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Tab. 2:ꢀEffect of variation of [MB] on the rate constant.
−ꢁ1
−ꢁ1
−ꢁ1
[MB]ꢁ×ꢁ105 M
k ꢁ×ꢁ106 M1/2
s
k1ꢁ×ꢁ104 s
k
3/2 × 10 M− 1/2s
½
0.5
1.0
1.5
2.0
2.5
3.0
1.6
6.7
6.7
6.7
0.15
0.13
[NAC]ꢁ=ꢁ5.0ꢁ×ꢁ10−ꢁ3 M; [HCl]ꢁ=ꢁ0.05 M; [CuSO4]ꢁ=ꢁ6.0ꢁ×ꢁ10−ꢁ5 M; Iꢁ=ꢁ0.25 M; Tempꢁ=ꢁ35 °C.
4.2 Effect of [MB]
The concentration of methylene blue (MB) was varied from 0.5ꢀ×ꢀ10−ꢀ5 M to
3.0ꢀ×ꢀ10−ꢀ5 M because Beer-Lambert law is obeyed by MB in this concentration
range. The reaction follows a first order kinetics in methylene blue (MB) but at low
concentrations (ca. 0.5ꢀ×ꢀ10−ꢀ5 M) and at higher concentrations (ca.ꢀ>ꢀ2.5ꢀ×ꢀ10−ꢀ5 M),
the order changes to half and 3/2, respectively (Table 2).
4.3 Effect of [CuSO4]
The rate of reaction increases on increasing [CuSO4] but at higher concentrations
(ca.ꢀ>ꢀ3.0ꢀ×ꢀ10−ꢀ5 M), the rate constant remains unaffected on further increasing
the concentration of Cu(II). Thus, the reaction follows a zero order kinetics in Cu
(II) (Table S2). The order in MB, however, shows a transition from one to 3/2 on
increasing [Cu(II)] beyond 6.0ꢀ×ꢀ10−ꢀ5 M.
It is reported that Cu(II) forms chlorocomplexes in presence of Cl− ions [22–24]
and these complexes rapidly oxidize LMB. However, this occurs at higher con-
centrations of Cu(II) (ca.ꢀ>ꢀ10−ꢀ4 M) as reported by Mills and coworkers whereas
in our case, a lower concentration of Cu(II) (ca. ~ 10−ꢀ5 M) has been employed.
Besides, the rate is not affected on varying [Cu(II)] beyond 3.0ꢀ×ꢀ10−ꢀ5 M which
again confirms that the kinetics of the reaction are not influenced by the partici-
pation of chlorocomplexes of Cu(II).
Further, the maximum concentration of Cl− ions in our system was 0.25 M and
according to Mills and coworkers, the prominent Cu(II) complexes are expected
+2
+
to be Cu (aq) and CuCl (aq) (50% and 48% respectively) [22–24]. Since the con-
centration of Cu(II) in our system is relatively low; the concentration of these
complexes will be very small and their participation in a mass law term seems
insignificant.
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4.4 Effect of [HCl]
The concentration of hydrochloric acid was varied from 0.04 M to 0.16 M at
constant concentrations of NAC, MB, Cu (II) and keeping the ionic strength fixed
+
(ca. 0.32 M). The rate initially increases but it decreases on increasing [H ] beyond
0.08 M. A plot of log [HCl] and log k0 gives a straight line with a slope ofꢀ−ꢀ2.2. It is
also reported that Cl− ions accelerate the oxidation of LMB [22] but such a possibil-
ity in the present case is ruled out on the grounds that at higher concentrations of
HCl (ca.ꢀ>ꢀ0.08 M), [Cl−] would be large and an increase in rate is expected under
these conditions. The results, however, are just opposite. Moreover, the ionic
strength was maintained at a fixed level by adding KCl to the reaction system
and thus, it seems that the kinetic influence of Cl− is minimized due to its larger
+
concentration and the rate is solely a function of [H ].
4.5 Effect of ionic strength, dielectric constant, and the
disulphide
Addition of KCl and NaCl increases the rate while it remains almost unaffected on
adding K2SO4 and KNO3 to the reaction system. The rate of reaction increases on
increasing the dielectric constant of the reaction system. The rate remains almost
unaffected on adding the corresponding disulphide.
4.6 The possible role of dihydromethylene blue (LMB) and the
effect of addition of LMB
The leucobase (LMB) is known to be oxidized by O2 [22] but in the present case,
the rate is found to be similar under aerobic as well as anaerobic conditions. This
indicates that the reacting species and the reaction products especially LMB do
not interact with O2 under the prevailing conditions. Further, the rate is margin-
ally influenced by the addition of LMB which shows its participation in an irre-
versible step.
4.6.1 Determination of activation parameters
The activation parameters viz. ∆H*, ∆S* and ∆G* were determined by making the
runs at different temperatures at lower [NAC] (ca. 5.0ꢀ×ꢀ10−ꢀ3 M) and at higher [NAC]
(ca. 1.0ꢀ×ꢀ10−ꢀ2 M) (Table 3a and b). At lower [NAC], ∆H*, ∆S* and ∆G* are found
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Tab. 3:ꢀEffect of variation of rate constant with temperature.
(a) At lower [NAC]
Temperature (K)
−ꢁ1
−ꢁ1
−ꢁ1
k1/2ꢁ×ꢁ106 M1/2
s
k1ꢁ×ꢁ104 s
k2ꢁ×ꢁ10 M−ꢁ1s
298
303
308
313
0.85
3.4
6.7
7.4
[NAC]ꢁ=ꢁ5.0ꢁ×ꢁ10−ꢁ3 M; [MB]ꢁ=ꢁ2.0ꢁ×ꢁ10−ꢁ5 M; [HCl]ꢁ=ꢁ0.05 M; [CuSO4]ꢁ=ꢁ6.0ꢁ×ꢁ10−ꢁ5 M; Iꢁ=ꢁ0.25 M.
(b) At higher [NAC]
−ꢁ1
Temperature (K)
k1ꢁ×ꢁ104 s
308
313
4.1
7.5
[NAC]ꢁ=ꢁ1.0ꢁ×ꢁ10−ꢁ2 M; [MB]ꢁ=ꢁ2.0ꢁ×ꢁ10−ꢁ5 M; [HCl]ꢁ=ꢁ0.05 M; [CuSO4]ꢁ=ꢁ6.0ꢁ×ꢁ10−ꢁ5 M; Iꢁ=ꢁ0.25 M.
to be 105.6 kJ mol−ꢀ1, 17.6 J deg−ꢀ1 mol−ꢀ1 and 95.2 kJ mol−ꢀ1, respectively. At higher
[NAC] (ca. 1.0ꢀ×ꢀ10−ꢀ2 M) the values are 96.7 kJmol−ꢀ1, 0.7 JK−ꢀ1 mol−ꢀ1 and 96.4 kJmol−ꢀ1,
respectively. It may be pointed out that these parameters have a limited signifi-
cance in a complex chemical process. However, it is seen that there is a marked
difference in the value of ∆S* on varying [NAC] which indicates that the process
is entropy controlled.
4.7 Proposed mechanism of the reaction
It has been reported by Odriozola and coworkers that salts of the coinage metals
such as Au(III), Ag(I) and Cu(II) form supramolecular hydrogel with bioactive
substrates specifically glutathione and N-acetyl-L-cysteine [25]. It has also been
mentioned by these workers that Cu-NAC derivative is very unstable and decom-
poses within hours making its characterization and handling difficult. Such an
instability can be attributed to the in situ oxidation of Cu(I) to Cu(II). Moreover,
in case of the hydrogel formed by the interaction of NAC and Ag(I), the strength of
the gel was found to decrease at higher concentrations of NAC(ca.ꢀ>ꢀ1.2ꢀ×ꢀ10−ꢀ3 M)
[26]. Incidentally, in our investigations the concentration of NAC employed is
in the range of 2.0ꢀ×ꢀ10−ꢀ3 M–1.0ꢀ×ꢀ10−ꢀ2 M. Moreover, the concentration of Cu(II)
employed in our system (ca. 6.0ꢀ×ꢀ10−ꢀ5 M) is much smaller than that used by
Odriozola and coworkers; thus, it is evident that in our reaction system, the
possibility of the formation of Cu-NAC hydrogel is very remote and the reaction
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is perhaps regulated by Cu-NAC intermediate. The spectral interference by the
intermediate is overruled on the grounds that an identical behavior is noticed
when the kinetic runs are followed with and without centrifugation. Moreover,
the compound formed due to interaction of Cu(II) with NAC is found to show
maximum absorbance at 303 nm in the UV region. Incidentally, the surface reac-
tions catalyzed by metal nanoparticles have been frequently monitored by UV-
Visible spectrophotometer [27].
This contention is further supported by recording FTIR spectra of NAC and
those of the reaction system recorded after completion of the reaction (Figures S1
and S2). It is seen that the bands obtained at 1732, 1558, 1520, 1404, 1212, 1045,
745 and 617 cm−ꢀ1 for the reaction mixture correspond to the prominent bands
obtained for NAC. Moreover, the bands obtained for the reaction mixture at 3443
and 1645 cm−ꢀ1 correspond with those obtained by Odriozola and coworkers [25]
for Cu-NAC hydrogel but the prominent bands obtained at 3064 and 2922 cm−ꢀ1 are
absent in our system. This observation is very significant because the stretching
vibration of –SH group occurs in the region 2500–3000 cm−ꢀ1 and thus, it seems
that the mode of binding of –SH group to Cu(II) is different in the present case.
5 Reaction scheme
The entropy of activation of the reaction is positive which indicates that the
process involves the adsorption of reactants on the surface leading to an increase
in entropy [28]. Since the thiol itself is a reducing agent; therefore, it can reduce
metal ion to nanoparticles [29, 30] and thus, it seems that Cu-NAC intermediate or
gel like network adsorbs Cu nanoparticles and this moiety behaves as the effec-
tive catalyzing species. The kinetic results obtained for the influence of [NAC] on
the rate reveal two important features:
(i) In terms of the initial rate, the reaction follows a zero order kinetics in NAC.
This indicates that the reaction site becomes saturated with NAC and thus, a
further increase in its concentration does not affect the rate which is a char-
acteristic of Eley-Rideal mechanism reported for surface reactions even in
homogeneous domain [31].
(ii) The value of the first order rate constant k1 remains almost constant and
finally, the rate constant decreases linearly as is expected from the Langmuir-
Hinshelwood mechanism.
It appears that methylene blue is preadsorbed on Cu-NAC intermediate or gel like
network which entraps Cu nanoparticles. It is known that Cu(II) interacts with
sulphydryl substrates to form the complexes as shown below:
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Entropy-Controlled Cu(II)-Catalyzed Oxidation of N-Acetyl-L-Cysteineꢂ
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K1
II
−
+
+
ꢀꢀꢁ
Cu(II)+RSH
[Cu (RS )] + H
ꢂꢀꢀ
(1)
(2)
(C1 )
K2
II
−
+
II
−
+
ꢀꢀꢁꢀ
[Cu (RS )] +RSH
[Cu (RS ) ]+ H
ꢂꢀꢀ
2
C2
The values of the equilibrium constants K1 and K2 are reported to be
(4.5 1.1)ꢀ×ꢀ103 M−ꢀ1 and (2.1 0.6)ꢀ×ꢀ103 M−ꢀ1, respectively [32]. The complexes C1
and C2 subsequently react with MB to produce the end products RSSR and LMB
regenerating the catalyst.
The complex C1 interacts with the network and site S1 on the network is
covered by complex C1. If θ1 is the fraction of the surface area of the network
which is covered then,
θ = k [C ]⋅(1−θ )
′
(3)
1
1
1
(where k′ denotes the rate constant for the adsorption of C1 on Cu-NAC network)
θ1
1 −θ1
(4)
or,
= k [C ]
′
1
k [C ]
′
1
Hence, θ1 =
(5)
1 + k [C ]
′
1
The effective concentration (Cx) accounting for the interaction of the principal
reactants will then be given by-
Cx = θ1 ⋅[MB]
k [C ]
(6)
(7)
′
1
or, Cx =
⋅[MB]
1 + k [C ]
′
1
Thus, the rate of reaction will be given as-
d[MB]
−
= ks ⋅Cx
(8)
(9)
dt
k [C ]
1+ k [C ]
′
d[MB]
dt
1
or,−
= ks[MB]⋅
′
1
(where ks denotes the specific rate constant)
K1[Cu(II)][RSH]
[H+ ]
Since, [C1 ]=
;
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thus,
k k K [Cu(II)][RSH][MB]
′
d[MB]
s
1
−
=
(10)
(11)
[H+ ](1+ k K [Cu(II)][RSH]/[H+ ])
dt
′
1
k k K [Cu(II)][RSH][MB]
′
d[MB]
dt
s
1
or, −
=
[H+ ]+ k K [Cu(II)][RSH]
′
1
This equation explains the retarding influence of hydrogen ions as has been
noticed. It may again be pointed out that an exact relationship between the rate
+
and [H ] could not be established in the present case largely due to its complex
nature as already reported [33].
+
Since K1 is comparatively very large, thus [H ] is expected to be smaller; then
k k K [Cu(II)][RSH][MB]
′
d[MB]
dt
s
1
−
=
(12)
k K [Cu(II)][RSH]
′
1
d[MB]
= ks[MB]
dt
or, −
(13)
Equation (13) explains the zero order kinetics in NAC and Cu(II) and a first order
kinetics in MB.
The validity of the proposed mechanism could be checked by evaluating the
first order rate constant ks from the values of the initial rate as predicted by Equa-
tion (13). It will be seen from Table 1 that the average value of the initial rate is
found to be 1.3ꢀ×ꢀ10−ꢀ8 Ms−ꢀ1. Thus, the rate constant ks is found to be 6.5ꢀ×ꢀ10−ꢀ4 s−ꢀ1
when [MB] is 2.0ꢀ×ꢀ10−ꢀ5 M. It can also be seen from the table that the average value
of the first order rate constant is found to be 6.6ꢀ×ꢀ10−ꢀ4 s−ꢀ1 in the concentration
range of NAC where a zero order kinetics in the substrate has been observed. This
excellent agreement between the experimental and theoretical values of the rate
constant lends credence to the proposed mechanistic model.
In the foregoing discussion, the complex C1 is postulated to interact with
MB adsorbed on Cu-NAC network in the initial stages of the reaction. It is known
that complex C1 further reacts with thiol molecule to form the complex C2. It is
evident, therefore, that in the later stages of the reaction, there will be a competi-
tion between complexes C1 and C2 to interact with preadsorbed MB. Since K1 is
larger than K2, the system will have a residual concentration of C1 along with C2
and thus, both may compete for the same reaction site.
Suppose S1 and S2 are the sites for C1 and C2 to be adsorbed on MB-adsorbed
network and θ1 is the fraction of the surface area having S1 covered with C1 and θ2
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is the fraction having S2 covered with C1. Then, the fraction which simultaneously
has S1 covered by C1 and S2 covered by C2 is θ1. (1–θ2) as pointed out by Laidler and
Hoare [34]. If the adsorption process conforms to Langmuir adsorption isotherm;
then θ1 and θ2 may be evaluated as follows.
θ = k [C ]⋅(1−θ )
′
(14)
1
1
1
k [C ]
′
1
or, θ1 =
(15)
1 + k [C ]
′
1
k [C ]
′′
2
and θ2 =
1−θ2 =
(16)
(17)
1 + k [C ]
′′
2
Thus,
1
1+ k [C ]
′′
2
where k′ and k″ denote the rate constants for the adsorption of complexes C1 and
C2 on Cu-NAC network, respectively.
The effective concentration involved in the electron transfer reaction on the
surface
Cx = θ1 ⋅(1−θ2 )⋅[MB]
(18)
(19)
Thus,
k [C ]
′
1
Cx =
⋅[MB]
(1+ k [C ])(1+ k [C ]
′′
′
1
2
At the later stage (C1) will be relatively smaller; thus,
k [C ]
′
1
Cx =
⋅[MB]
(20)
(21)
(22)
(1+ k [C ]
′′
2
k K [Cu(II)[RSH][MB]
′
1
or, Cx =
[H+ ](1+ k K K [Cu(II)][RSH]2 )/[H+ ]2 )
′′
1
2
k K [Cu(II)][RSH][MB][H+ ]
′
1
or, Cx =
([H+ ]2 + k K K [Cu(II)][RSH]2 )
′′
1
2
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Hence, the rate of reaction will be given as
d[MB]
−
= v = ks ⋅Cx
(23)
(24)
dt
k K [Cu(II)][RSH][MB][H+ ]
′
1
or, v = ks ⋅
([H+ ]2 + k K K [Cu(II)][RSH]2 )
′′
1
2
+
In Equation (24), if [H ]2 is smaller, then –
k k [MB][H+ ]
′
s
v =
(25)
k K [RSH]
′′
2
This expression explains a first order kinetics in MB, zero order kinetics in Cu(II)
andꢀ−ꢀ1 order in NAC. It also predicts a linear relationship between the rate and
+
[H ] which has not been found experimentally. But such an observation on pH
dependence of the oxidation of thiols is quite prevalent in literature.
Prima facie, this interpretation seems to be identical to the Langmuir-Hin-
shelwood mechanism but its close examination indicates that MB is preadsorbed
and C1 and C2 compete for interaction with MB. In principle, therefore, it is an
extension of Eley-Rideal mechanism and the deviations may be attributed to the
accumulation of more than one reactive species viz. C1 and C2 with the passage of
time in the reaction system.
This contention is verified by rearranging Equation (25) which gives the
observed first order rate constant k1 as-
k k [H+ ]
′
s
k1 =
(26)
k K [RSH]
′′
2
k k k1K2[RSH]
′
s
or,
=
(27)
[H+ ]
k
′′
k k
′
s
Since K2ꢀ=ꢀ2.1ꢀ×ꢀ103 M−ꢀ1; thus from Equation (27), the value of
calculated for different [RSH] as given in Table 4.
can be
k
′′
If we plot ks k′/k″ against [RSH] (Figure 2), it is seen that the value initially
increases and then tends to become constant-a characteristic shown by Eley-
Rideal mechanism.
In order to understand the mode of interaction of Cu(II) with NAC in the reac-
tion system, the reaction mixture was allowed to dry in air and the residue was
subjected to SEM, XRD and FTIR studies. These studies indicate that the reaction
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Entropy-Controlled Cu(II)-Catalyzed Oxidation of N-Acetyl-L-Cysteineꢂ
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Tab. 4:ꢀValues of ksk′/k″ at different [RSH].
[RSH]ꢁ×ꢁ103 M
ks k′/k″
3.0
4.0
5.0
6.0
8.0
10.0
0.0806
0.1125
0.1407
0.1612
0.1680
0.1720
[MB]ꢁ=ꢁ2.0×10−ꢁ5 M; [HCl]ꢁ=ꢁ0.05 M; [CuSO4]ꢁ=ꢁ6.0×10−ꢁ5 M; I= 0.25 M; Tempꢁ=ꢁ35 °C.
Fig. 2:ꢀA plot of ks k′/k″ against [RSH]. [NAC]ꢁ=ꢁ5.0ꢁ×ꢁ10−ꢁ3 M; [HCl]ꢁ=ꢁ0.05 M;
[CuSO4]ꢁ=ꢁ6.0ꢁ×ꢁ10−ꢁ5 M; Iꢁ=ꢁ0.25 M; Tempꢁ=ꢁ35 °C.
involves the participation of nanoparticles and it is regulated by their size and
morphology.
5.1 Participation of nanoparticles
5.1.1 SEM images
SEM images of the reaction system indicate that the surface morphology of the
nanoparticles appreciably depends on [NAC] as well as on temperature. SEM
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Fig. 3:ꢀSEM images of the reaction system (a) [NAC]ꢁ=ꢁ5.0ꢁ×ꢁ10−ꢁ3 M at 35 °C
(b) [NAC]ꢁ=ꢁ1.0ꢁ×ꢁ10−ꢁ2 M at 35 °C (c) [NAC]ꢁ=ꢁ5.0ꢁ×ꢁ10−ꢁ3 M at 40 °C. [MB]ꢁ=ꢁ2.0ꢁ×ꢁ10−ꢁ5 M;
[HCl]ꢁ=ꢁ0.05 M; [CuSO4]ꢁ=ꢁ6.0ꢁ×ꢁ10−ꢁ5 M; Iꢁ=ꢁ0.25 M; Tempꢁ=ꢁ35 °C.
images of the reaction system reveal the participation of cube shaped nanoparti-
cles (Figure 3) while at higher [NAC] and temperature, the morphology of nano-
particles changes to nanorods and nanoplates, respectively (Figure 3).
5.1.2 XRD studies
The size of the particles was determined by XRD analysis (Figure 4a and b) with
the help of Scherrer equation [35] and was found to vary between 32.42 and
325.46 nm with an average size of 131.42 nm at low [NAC]. At higher [NAC], the
particle size lied between 29.12 and 339.82 nm with an average size of 164.99 nm.
XRD parameters of the reaction system under varying conditions have been given
in Table S3.
It is seen from the above table that the number of facets (200), (210) and (211)
increases on increasing [NAC]. It shows that the surface properties of the nano-
particles undergoes a change and affects the time dependence of rate on [NAC].
It would be pertinent to mention here that metal nanoparticles are electron
donors while in the present case, MB and the complex C1 are cationic in nature.
Thus, a favorable columbic interaction is indicated when MB and C1 interact on
the surface of Cu-NAC network. On the other hand, the complex C2 is electri-
cally neutral and its interaction should involve an energy barrier. The energy of
activation, however, is found to be almost identical and thus, the reaction does
not seem to be activation-controlled under these conditions. ∆S*, on the other
hand, differs markedly and it is more positive at lower [NAC] (17.6 J K−ꢀ1 mol−ꢀ1) as
compared to that obtained at higher [NAC] (0.7 JK−ꢀ1 mol−ꢀ1). This indicates that at
lower [NAC], adsorption is more favored. This contention is also justified on the
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ꢂ1107
Fig. 4:ꢀXRD spectra of the reaction system at (a) [NAC]ꢁ=ꢁ5.0ꢁ×ꢁ10−ꢁ3 M (b) [NAC]ꢁ=ꢁ1.0ꢁ×ꢁ10−ꢁ2 M.
[MB]ꢁ=ꢁ2.0ꢁ×ꢁ10−ꢁ5 M; [HCl]ꢁ=ꢁ0.05 M; [CuSO4]ꢁ=ꢁ6.0ꢁ×ꢁ10−ꢁ5 M; Iꢁ=ꢁ0.25 M; Tempꢁ=ꢁ35 °C.
grounds that the size of the nanoparticles is smaller at lower [NAC] resulting in
the larger surface area and thus, an easy interaction between preadsorbed MB
and the complex C1 will be facilitated. Larger nanoparticles obtained at higher
[NAC], will have a smaller surface area for adsorption to take place and secondly,
the species C1 and C2 simultaneously compete for the same reaction site. Inciden-
tally, in spite of surface reactions, we have obtained normal Arrhenius plots in
conformity with the observations of Laidler and Hoare [34], Wunder et al. [27] and
Das et al. [31]. It seems therefore that the morphology and size of the nanoparti-
cles play a very vital role in facilitating electron transfer reaction between NAC
and MB in presence of Cu(II) resulting in a specific mode of adsorption leading to
deviating kinetic features.
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6 Conclusions
The oxidation of NAC by methylene blue catalyzed by Cu(II) involves the partici-
pation of nanoparticles and is regulated by Cu-NAC gel-like network acting as
the effective catalyst. The reaction conforms to Eley-Rideal mechanism at lower
[NAC] while at higher [NAC], the kinetics are explained by invoking an extended
Eley-Rideal mechanism encompassing the features of Langmuir-Hinselwood
mechanism. Kinetic and FTIR studies overrule the possibility of the formation of
hydrogel in the reaction system. The reaction is influenced by the size and mor-
phology of the nanoparticles and is entropy-controlled.
Acknowledgments: The authors are grateful to University Grants Commission,
India for financial support for this project (No. F-37-522/2009 SR) and to Maulana
Azad National Institute of Technology (MANIT) Bhopal for availing SEM facil-
ity, Model Government Science College Jabalpur for FTIR and Indian Institute of
Science Education and Research (IISER) Bhopal for XRD analysis, respectively.
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