Effect of CTAB micelle on the oxidation of L-Leucine by N-Bromophthalimide: A kinetic study

Article abstract of DOI:10.1524/zpch.2011.0004

The effect of cationic surfactant cetyltrimethylammonium bromide (CTAB) on the oxidation of L-leucine by N-bromophthalimide (NBP) has been studied at 308 K. The reaction exhibits first order dependence on NBP and L-leucine and negative and fractional order dependence on HClO₄. The effects of KCl, KBr, phthalimide and mercuric acetate have also been studied and summarized. The rate of reaction increased with an increase in dielectric constant of the medium. CTAB strongly catalyzes the reaction and typical k _obs and CTAB profile was observed, i.e., with a progressive increase in CTAB, the reaction rate increased and after achieving a peak k_obs decreased at higher concentrations of CTAB. The results are treated quantitatively in terms of "Piszkiewicz" and "Raghvan and Srinivasan's" models. The various activation parameters in presence and absence of CTAB have been also evaluated. A suitable mechanism consistent with the experimental findings has been proposed. The rate constant in micellar phase k_M, cooperativity index (n), binding constant (K₁ and K₂) have been computed. by Oldenbourg Wissenschaftsverlag, Mu?nchen.

Full text of DOI:10.1524/zpch.2011.0004

Z. Phys. Chem. 225 (2011) 107–124 / DOI 10.1524/zpch.2011.0004
© by Oldenbourg Wissenschaftsverlag, München
Effect of CTAB Micelle on the Oxidation
of L-Leucine by N-Bromophthalimide:
a Kinetic Study
By Yokraj Katre1 ∗, Namita Goyal1, and Ajaya Kumar Singh2
,
1
Department of Chemistry, Kalyan Post Graduate College, Bhilai Nagar, Durg,
Chhattisgarh 490006, India
Department of Chemistry, Government Vishwanath Yadav Tamaskar Post Graduate Autonomous
2
College, Durg, Chhattisgarh, India
(Received May 18, 2010; accepted in final form September 9, 2010)
Micellar Kinetics / N-Bromophthalimide / L-Leucine / Oxidation
The effect of cationic surfactant cetyltrimethylammonium bromide (CTAB) on the oxidation of
L-leucine by N-bromophthalimide (NBP) has been studied at 308 K. The reaction exhibits first
order dependence on NBP and L-leucine and negative and fractional order dependence on HClO4.
The effects of KCl, KBr, phthalimide and mercuric acetate have also been studied and summarized.
The rate of reaction increased with an increase in dielectric constant of the medium. CTAB strongly
catalyzes the reaction and typical kobs and CTAB profile was observed, i.e., with a progressive
increase in CTAB, the reaction rate increased and after achieving a peak kobs decreased at higher
concentrations of CTAB. The results are treated quantitatively in terms of “Piszkiewicz” and
“Raghvan and Srinivasan’s” models. The various activation parameters in presence and absence of
CTAB have been also evaluated. A suitable mechanism consistent with the experimental findings
has been proposed. The rate constant in micellar phase kM, cooperativity index (n), binding constant
(K1 and K2) have been computed.
1. Introduction
Micellar induced reactions, due to their unique functional similarities with enzyme-
catalyzed reactions, have established an important place not only in chemical science
but also in biochemical sciences. Study of these micellar reactions, especially the ki-
netic aspects of these reactions, has gained momentum in recent times as these are
useful to varied interests. These surfactants, due to their diverse applications such as
emulsifiers, wetting agents, solubilisers and preservatives, are being exploited in do-
mestic as well as industrial purposes ranging from soap to pharmaceuticals.
* Corresponding author. E-mail: yokrajkatre@gmail.com
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Y. Katre et al.
Oxidation of amino acids, especially that of essential amino acids is of immense im-
portance in the field of metabolism and medical science. This importance arises from
the fact that organism strives to maintain protein balance in body by oxidation of amino
acids. The periodic nature of human nutrition with cycles of fasting and feeding re-
sults in losses and gains of body proteins. This occurs from the response of protein
metabolism i.e. oxidation of amino acids to dietary intake [1]. Also, by modulation
of amino acid oxidation distinct positive effect of Human growth hormone has been
achieved on protein synthesis [2]. Lysine and leucine are ketogenic amino acids which
can be converted into ketone bodies through ketogenesis and give energy. Leucine is
a major component of the sub units in ferritin, astacin and other buffer proteins. Hence,
the mechanisms by which the oxidation of various amino acids is coordinated and ad-
justed to match protein intake is of considerable practical importance and has been
subject of various studies [3–9].
In one of the study of Heart Research Institute, Sydney [10], it has been estab-
lished that activated eosinophils generate hypobromous acid, which target proteins for
oxidation. This has been implicated in the tissue injury in asthma, allergic reactions
and some infections. We have selected N-bromophthalimide (NBP) for oxidation of
L-leucine as NBP is a strong brominating and oxidative agent and has HOBr as the
active species [11–14]. These species have been shown to decompose under various
conditions to form aldehydes.
Surfactants are extensively employed in pharmaceutical and biotechnological pro-
cesses. From a technological perspective, protein surfactant interactions are important
because they modulate the functional properties of proteins. The surfactants may in-
teract with proteins directly by competing for oil–water or air–water interfaces and
binding to them, thereby, leading to substantial changes in the protein conformation. Al-
terations in the molecular characteristics to globular proteins due to their interactions
with surfactants may lead to changes in their ability to bind other molecules i.e. they
may self associate and be absorbed at intetrfaces thus altering their functional charac-
teristics. However several details in the mode of interaction of surfactants with protein
remain unaswered. Therefore it is very important to understand the origin and nature of
protein surfactant interactions both qualitatively and quantitatively. We find that stud-
ies of amino acids oxidation have been done mostly in the presence of the metal ions
or other catalysts [15–18] and very limited literature is available for studies of amino
acid oxidation in presence of micellar aggregates. Particularly, there is no study on oxi-
dation of L-leucine by NBP in micellar aggregates. This motivated us to take L-leucine
as substrate which is an essential amino acid and is active site residue of enzymes. It
helps in maintaining the correct conformation of enzymes by keeping them in proper
ionic states. Thus study on the oxidation of this may help in understanding enzyme
kinetics.
A micelle, just like, enzyme catalyses a redox reaction in two different ways. First,
it possesses a redox centre, which is involved in the electron-transfer process and thus
reduces the activation barrier. Second, it can increase the encounter probability by con-
centrating substrates at its binding sites and thus causes increase in the rate of reaction.
The former is essentially a chemical factor and the latter is a “concentration effect”, but
essentially a physical one. These interesting features of micelle have generated lot of
interest in recent times and various studies have been done in this field [19–28].
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Reaction Kinetics in Micellar System
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2. Experimental procedures
A standard aqueous solution of CTAB (Sigma Aldrich, 99% purity) and L-leucine
(Sigma Aldrich, 98% purity) was prepared in distilled water. NBP was used as obtained
(Aldrich, 95% purity) and melting point of the sample was found to be 481 K. Solutions
of NBP were prepared in 80% distilled acetic acid and stored in a black-coated flask to
prevent photochemical deterioration. The prepared NBP solution was then standardized
iodometrically [29] against the standard solution of sodium thiosulphate (Qualigens,
AR) using starch as an indicator. A standard aqueous solution of mercuric acetate (Loba
Chemie, GR) was acidified with 20% distilled acetic acid (Sd-Fine, AR). Perchloric
acid (Loba Chemie, G.R.) diluted with distilled water, was standardized by standard so-
lution of NaOH. Water used for the preparation of all aqueous solutions was distilled
three times.
2.1 Kinetic measurements
The reactions were carried out in glass stoppered Pyrex vessel whose outer surface
was black coated to eliminate photochemical effects. These vessels were kept in an
electrically operated thermostatic water bath maintained at a constant temperature. Req-
uisite amounts of the solutions of L-leucine, CTAB, Hg(OAc)2, HClO4, CH3COOH
and water (to keep the total volume constant for all runs) were taken in the vessel and
thermostated at 308 K for thermal equilibrium. A pre-equilibrated amount of the oxi-
dant solution i.e. NBP which was also thermostated at the same temperature was rapidly
added to the reaction mixture. The progress of the reaction was followed by estimating
the amount of unconsumed NBP iodometrically at regular time intervals using freshly
prepared starch as indicator. The course of the reaction was studied for two half-lives.
All the reactions were carried out under pseudo-first order conditions by taking
[L-leucine] ꢀ [NBP]. Each reactant was varied keeping all other reactants constant to
determine pseudo-first order rate constant to study the effects of these reactants on
the kinetics of the reaction. Variations of temperature were also done to determine the
activation parameters.
2.2 CMC determination
The concentration at which surfactant molecules assemble to form a cluster in solution
is called the critical micelle concentration (CMC) and can be determined from plots
of the specific conductivity vs. surfactant concentration. Conductometric measurements
were carried out with a digital conductivity meter, model 611E at 308 K. The values of
CMC of surfactants are sensitive to the nature of the reactants and also depend upon
reaction conditions. The break point of nearly two straight-line portions in the plot is
taken as an indication of micelle formation, and this corresponds to the CMC of sur-
factant. The obtained values of CMC in different experimental conditions are reported
in Table 1. The difference among the literature and the observed values of CMC arises
from the well-known effect of added electrolyte, which lowers the CMC by causing
a decrease in the repulsion between the polar head groups at the micelle surface. Our
results of decrease in CMC value are in accord with the earlier observations of micelle
formation at relatively low surfactant [30–32].
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Table 1. Critical micelle concentration (CMC) values of CTAB in different experimental conditions.
Solution
CMC× 104 mol dm−3
Water
9.6 (9.2, 9.8)a
Water + NBP
9.0
4.1
5.0
3.5
1.0
Water + L-leucine
Water + L-leucine + H+
Water + L-leucine + H+ + Hg2+ + 50% CH3COOH
Water + L-leucine + H+ + Hg2+ + 50% CH3COOH + NBP
Experimental conditions [NBP] = 1.0×10−4 mol dm−3, [L-leucine] = 1.0×10−3 mol dm−3, [H+] = 1.0 ×
10−2 mol dm−3, [Hg2+] = 2.0×10−4 mol dm−3, temperature = 308 K.
a: Literature values [33] at different temperatures (25 and 35 ◦C respectively) are given in parentheses.
2.3 Stoichiometry and product analysis
Various sets of experiments were performed with different [NBP]: [L-leucine] ratios,
under the condition of [NBP] ꢀ [L-leucine]. The stoichiometry of the reaction was es-
tablished by equilibrating the mixture consisting of NBP, L-leucine, CTAB, Hg(OAc)2,
CH3COOH and HClO4 for 72 h. After completion of the reaction, the unconsumed NBP
was estimated and it was found that 1 mol of L-leucine is oxidized by 1 mol of NBP i.e.
stoichiometry of 1 : 1. The stoichiometry of equation may be formulated as (Eq. 1):
(CH3)2CHCH2CH(NH2)COOH+NBP+H2O →
(CH3)2CHCH2CHO+NHP+CO2 +HBr+NH3
(1)
where NHP is phthalimide.
The main product of oxidation, aldehyde was detected by spot test [34] and NH3
and CO2 were detected by their standard test.
3. Results and discussion
To study the effects of concentration of different reactants on the kinetics of the oxi-
dation reaction and with a view to ultimately propose a suitable reaction mechanism,
concentration of each reactant was varied keeping concentration of other reactants con-
stant. Pseudo-first order rate constant has been determined in each experimental set to
establish the dependence of reaction rate on each reactant and the order of the reaction.
The results of these variations have been reported in Table 2. Any intervention arising
out of kinetics due to molecular bromine has been prevented by the addition of mer-
cury(II) ions, which removed Br− ions either as HgBr2 or as HgBr42−. So basic function
of mercuric acetate was to act as a scavenger.
3.1 Test for free radicals
The oxidation of L-leucine by NBP under nitrogen atmosphere fails to induce polymer-
ization of added acrylonitrile, thus ruling out of radical oxidation.
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Reaction Kinetics in Micellar System
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Table 2. Effect of [oxidant], [substrate], [Hg2+], CH3COOH (%) and [H+] on the oxidation reaction rate.
[NBP]
[L-leucine]
[Hg2+
]
CH3COOH
%
[H+]
kobs
×104 mol dm−3
×103 mol dm−3
×104 mol dm−3
×102 mol dm−3
×104 s−1
1.0
2.0
3.0
4.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.5
1.0
1.5
2.0
2.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
4.0
6.0
8.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
50
50
50
50
50
50
50
50
50
50
50
50
30
40
50
60
50
50
50
50
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.25
0.50
1.0
1.25
3.30
3.33
3.31
3.28
1.72
3.30
5.82
7.71
9.20
3.31
3.32
3.31
5.88
4.76
3.30
1.78
5.71
4.22
3.30
2.71
Experimental conditions: temperature = 308 K and [CTAB] = 4.0×10−4 mol dm−3
.
3.2 Effects of varying [L-leucine]
The substrate, L-leucine, was varied in the range of 0.5×10−3 to 2.5 ×10−3 mol dm−3
at 308 K keeping all other reactant concentrations and conditions constant. The plot of
log kobs vs. log[L-leucine] was found to be linear and the slope was found to be almost
unity, indicating first order dependence on L-leucine (Table 2).
3.3 Effects of varying [NBP]
The NBP concentration was varied in the range of 1.0×10−4 to 4.0 ×
10−4 mol dm−3 and the linearity of plots of log[NBP] vs. time in each case indicated
a reaction order in NBP as unity. Also in all the variations of NBP pseudo-first order rate
constant kobs was almost same which confirmed the first order dependence of reaction
rate with respect to oxidant (Table 2).
3.4 Effect of varying [CTAB]
The CTAB concentration was varied in the range of 0.5×10−4 to 5.0 ×
10−4 mol dm−3 and the rate constant values first increased from 2.66×10−4 s−1 to
11.53×10−4 s−1 and after that it decreased on further increasing the Surfactant concen-
tration (Fig. 1). The results are presented in Table 3. The increase in kobs was observed
even at [CTAB] < CMC. This fact is usually interpreted as reactants inducing micelle
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Y. Katre et al.
Fig. 1. Effect of variation of [CTAB] on rate constant with reaction conditions as [NBP] = 1.0 ×
10−4 mol dm−3
,
[L-leucine] = 1.0×10−3 mol dm−3
,
[Hg2+] = 2.0×10−4 mol dm−3
,
[H+] = 1.0 ×
10−2 mol dm−3, [CH3COOH] = 50%, temperature = 308 K.
formation (surfactant molecules start aggregating below CMC). This catalysis below
CMC is termed as submicellar catalysis or pre-micellar catalysis. The feasibility can be
sought in the fact that small aggregates of the surfactants (dimers, trimers, tetramers,
etc.) exist below CMC; these small submicellar aggregates can interact physically with
the reactants forming catalytically active entities.
The maxima in the rate-surfactant profile is produced by two opposite effects. Bind-
ing of reactants in the stern layer begins as soon as the micelle formation starts and
these reactants are transfered into a small volume of the micellar pseudophase. There
is thus a concentration effect which is responsible for acceleration. This concentra-
tion effect is opposed by the counterions dilution of the reactants within the micellar
pseudophase with increasing surfactant concentration. The former effect is predominant
at lower surfactant concentrations whereas the latter becomes at higher concentration
of surfactant, resulting in maximum in rate-surfactant profile followed by drop in the
rate.
This micellar effect on the reaction in terms of pseudophase models has been dis-
cussed separately later on.
3.5 Effect of varying [Hg(OAc)2]
It has been reported earlier that Hg(II) can act as a homogeneous catalyst, co-catalyst
and oxidant [35]. So it became necessary to establish the real role of Hg(OAc)2 in
our experimental set-up i.e. whether it is playing any role of oxidant and/or catalyst
in our case and thus interfering with the role of intended oxidant (NBP) and/or cata-
lyst (CTAB). Several experiments were performed with different initial concentrations
of Hg(OAc)2 in the presence of NBP under similar experimental conditions (Table 2).
The kinetic observations showed that the reaction rate was almost constant with the
variation in concentration of Hg(OAc)2 ruling out its role as catalyst or co-catalyst
in the reaction. Similarly, experiments were carried out with different variations of
Hg(OAc)2 without using NBP and it was found that these reactions did not proceed
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Reaction Kinetics in Micellar System
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Table 3. Effect of [CTAB] and inorganic electrolytes on the reaction rate.
[CTAB]
[KCl]
[KBr]
kobs
×104 mol dm−3 ×107 mol dm−3 ×107 mol dm−3
×104 s−1
0
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
1
3
5
7.5
2.30
2.66
2.91
3.31
4.42
5.94
7.21
9.20
11.53
10.88
8.24
6.13
4.51
3.32
3.08
2.91
2.51
2.02
1.75
1.50
1.21
2.31
1.82
1.50
1.21
1.00
0.50
0.75
1.00
1.25
1.50
1.75
2.00
2.25
2.50
2.75
3.00
3.50
4.00
4.50
5.00
–
–
–
–
–
–
–
–
–
1
3
5
7.5
10
–
–
–
–
–
–
10
Experimental conditions T = 308 K, [NBP] = 1.0×10−4 mol dm−3
,
,
,
[L-leucine] = 1.0×10−3 mol dm−3
[CTAB] = 4.0×10−4 mol dm−3],
[CH3COOH] = 50%.
,
[Hg2+] = 2.0×10−4 mol dm−3
[H+] = 1.0×10−2 mol dm−3
at all. Therefore, the role of Hg(OAc)2 as oxidant is also ruled out in our case. Hence
it is established that the role of Hg(OAc)2 is limited to act as a Br− scavenger only
due to formation of the complex [HgBr4]2− and thus to prevent any intervention of
molecular bromine. Therefore, all the experiments were carried out in the presence of
Hg(OAc)2.
3.6 Effect of varying [HClO4]
With an increasing [H+] from 0.25×10−2 mol dm−3 to 1.25×10−2 mol dm−3, the rate
constant values decreased. The retardation by [H+] may be mainly attributed to the
conversion of the more reactive neutral species of L-leucine to the less reactive proto-
nated form. The plots of log kobs vs. log[H+] produced a straight line with negative slope
(−0.44) indicating that order with respect to [H+] ion is negative fractional value. The
results are presented in Table 2.
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Y. Katre et al.
Fig. 2. The plot of log kobs vs. 1/ε with reaction conditions as [NBP] = 1.0×10−4 mol dm−3, [Hg2+] =
2.0×10−4 mol dm−3
,
[L-leucine] = 1.0×10−3 mol dm−3
,
[CTAB] = 4.0 × 10−4 mol dm−3
,
[H+] = 1 ×
10−2 mol dm−3, temperature = 308 K.
3.7 Effect of initially added product
The effect of phthalimide, added initially, was studied. Addition of phthalimide brought
about a substantial decrease in the rate of reaction. The retardation of reaction rate on
the addition of phthalimide suggests a pre-equilibrium step involving a process in which
phthalimide is one of the products.
NBP+H2O HOBr+phthalimide
(2)
According to above equilibrium, rate is an inverse function of phthalimide concentra-
tion.
3.8 Effect of varying dielectric constant
To study the effect of dielectric constant (polarity) of the medium on the rate of reaction,
the micellar catalyzed oxidation of L-leucine by NBP was studied in various compo-
sition of acetic acid (Table 2). The results clearly reveal that the rate decreases with
increase in the percentage of acetic acid, i.e. with decreasing dielectric constant of the
medium.
The effect of dielectric constant of the medium on the rate constant of a reaction
between two ions has been described by the well known equation [36] given below.
ZA ZB e2 N
2.303(4πε0)dAB RT ε
1
log kobs = log K0ꢁ −
(3)
where K0ꢁ is the rate constant in a medium of infinite dielectric constant, ZA and
ZB are the charges of reacting ions, dAB refers to the size of activated complex, and
T is absolute temperature and ε is the dielectric constant of the medium. Plot has
been made between log kobs and 1/ε, which gave a straight line having slope equal to
−ZA ZB e2 N/2.303(4πε0)dAB RT (Fig. 2).
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Reaction Kinetics in Micellar System
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Table 4. Temperature effect and activation parameters for uncatalyzed and CTAB catalyzed reactions of
oxidation of L-leucine by NBP.
Parameters
Without
surfactant
With surfactant
[CTAB]
kobs ×104 s−1
kobs ×104 s−1
303 K
308 K
1.40
2.30
2.41
3.32
313 K
3.32
4.81
318 K
5.70
7.40
Ea (kJ mol−1
)
73.31
70.75
−76.72
94.38
8.80
59.78
57.22
−117.60
93.44
6.66
ΔH (kJ mol−1
)
ΔS (J K−1 mol−1
)
ΔG (kJ mol−1
log PZ
)
Experimental conditions: [NBP] = 1.0×10−4 mol dm−3, [L-leucine]
= 1.0×10−3 mol dm−3, [Hg2+] = 2.0×10−4 mol dm−3, [CTAB] =
4.0×10−4 mol dm−3
,
[H+] = 1.0×10−2 mol dm−3
,
CH3COOH =
50%.
The rate constant of the reaction decreased with increasing acetic acid from 30
to 60% (Table 2). The rate of oxidation was found to depend on the polarity of the
medium.
3.9 Effect of inorganic electrolytes
The salt effect on the L-leucine-NBP reaction was studied in the presence of CTAB
micelles (4.0×10−4 mol dm−3) at 308 K, keeping other variables constant. It was
found that the micellar catalysis is retarded by addition of these inorganic electrolytes
(Table 3). The rate retarding effect largely depends upon the nature of counterions and
the inhibition increases as the hydrophilic character of the salt increases. The coun-
terions from the added electrolyte compete with the reactive counterions for micellar
binding.
The inhibition of micellar catalysis by the added electrolytes may also be inter-
preted by considering the change of size of the micelles in the presence of salts. The
presence of salts increases the aggregation number (and consequently the shape and
size) of the micelles. An increase in aggregation number will reduce the number of
micelles and as a result the catalytic efficiency of the micelle decreases.
3.10 Activation parameters
Activation parameters are believed to provide useful information regarding the environ-
ment in which chemical reactions take place. The effect of temperature on rate constant
was studied in the temperature range of 303–318 K. From Arrhenius plots, the values
of activation energy (Ea) were calculated and the values of ΔS and ΔG were computed
from Eyring equation and are reported in Table 4. A lower value of Ea in presence of
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CTAB shows the catalytic effect on the rate of reaction. The larger negative value of ΔS
in the presence of surfactant indicates that more ordered activated complex is formed.
The fairly positive values of ΔH and ΔG indicate that the transition state is highly sol-
vated. Nearly same value of ΔG in absence as well as in presence of the surfactant has
been observed which indicates the same reaction mechanism in aqueous and micellar
medium.
The difference in the activation parameters for the catalyzed and uncatalyzed reac-
tion explains the catalytic effect on the reaction. The catalyst alters the reaction pathway
by lowering the energy of the barrier i.e. it provides an alternative pathway with lower
activation parameters for the reaction involving the formation of an intermediate com-
plex as proposed.
3.11 Mechanism
N-halo compounds have been used in organic synthetic methodology especially in the
oxidation and bromination reactions. In most cases these reagents are converted to ph-
thalimide in the end of reactions, as a nontoxic chemical. It has been reported earlier
by several researchers [11–14] that NBP is oxidizing and brominating agent because of
large polarity of > N−Br bond. NBP is capable of producing Br+ reasonably shows that
NBP, like other similar N-halo imides, may exist in various forms in acidic medium,
that is, free NBP, protonated NBP, Br+, HOBr, (H2OBr)+, as per the following equilib-
ria:
NBP+H+ NHP+Br+
NBP+H+ (NBPH)+
NBP+H2O HOBr+NHP
HOBr+H+ (H2OBr)+
(4)
(5)
(6)
(7)
Addition of phthalimide in the reaction mixture decreases the rate of oxidation in acidic
media. This suggests that the pre-equilibrium step involves a process in which phthal-
imide is one of the products. When NBP or (NBPH)+ is assumed as the reactive species,
the derived rate laws fail to explain the negative effect of phthalimide. Hence neither of
these species can be considered as the reactive species. When (H2OBr)+ is taken as the
reactive species, the rate law obtained shows first order kinetics with respect to hydro-
gen ion concentrations, contrary to our observed negative fractional order with respect
to HClO4. Although Eq. (4) fully explains the negative effect of phthalimide, but the
contrary findings of HClO4 dependence rules out the possibility of cationic bromine
(Br+) as reactive species. Thus, the only choice left is HOBr, which, when considered
as the reactive species of NBP, leads to a rate law capable of explaining all the kinetic
observations and other effects. In the light of kinetic observations, HOBr can safely be
assumed to be the main reactive species of NBP for the present reaction. On the basis
of above experimental findings Scheme 1 can be proposed for kinetics of oxidation of
L-leucine by NBP in acidic medium.
On the basis of Scheme 1, it is evident that step c is the rate determining step. Let
[X−] be the intermediate formed out of the step (b) which acts as reactant in step (c) of
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Scheme 1. Proposed scheme for oxidation reaction of L-leucine by NBP.
Scheme 1. Then rate shall be:
Rate = k[X−]
(8)
From step a and b, K1 and K2 shall be
[NHP][HOBr]
K1 =
(9)
[NBP]
[X−][H+]
K2 =
(10)
[L-Leu][HOBr]
From Eqs. (9) and (10), Eq. (8) can be rewritten as
kK1 K2[L-Leu][NBP]
rate =
(11)
[H+][NHP]
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At any time, total NBP will be the sum of following forms:
[NBP]T = [NBP]+[HOBr]+[X−]
(12)
(13)
Again with the help of Eqs. (9), (10) and (12) rate is derived as:
kK1 K2[L-Leu][NBP]T
rate =
[NHP][H+]+ K1[H+]+ K1 K2[L-Leu]
In the above rate law it is assumed that K1[H+] is very very greater than K1 K2[L-Leu].
The above rate law is in good agreement with our experimental findings i.e. addition
of [H+] decreases the rate, addition of [NHP] decreases the rate and increasing [L-Leu]
increases the rate. This confirms the validity of the proposed mechanism.
3.12 Quantitative treatment of micellar catalysis
The experimental data obtained by variation of surfactant (Table 3) may be applied to
some models developed for micellar catalysis reactions. These models explain the catal-
ysis and inhibition of reaction by Surfactant and give some quantitative characteristics
of Surfactant for the reaction.
3.12.1 Piszkiewicz’s model or co-operative model
Micelle-catalyzed reactions resemble with enzyme-catalyzed reactions in many ways.
For example, micelle-catalyzed reactions exhibit a sigmoid shaped curve for the plot
of rate constant vs. surfactant concentration, which is typical to enzyme-catalyzed re-
actions. This means that after attaining a rate maximum, the rate decreases at the higher
concentration of the surfactant. For enzyme-catalyzed reactions, Hill model [37] is in
vogue for a very long time which is based on positive cooperativity. Taking a cue from
Hill model, Piszkiewicz developed a kinetic model to explain the micellar effect [38].
This model considers that the substrate (S) and n molecules of detergent (D) aggre-
gate to form the active micelle (DnS) as per the Scheme 2, which causes rate to increase.
After a point, further aggregation of surfactant molecules produce kinetically inactive
(DnDpS) with p molecules of surfactant. This explains the retarding effect of surfactant
at the higher concentration.
From the Scheme 2, rate constant is obtained as:
n
kM[D] +kW KD
kobs
=
(14)
n
n
p
KD +[D] + KP[D] [D]
where kM = rate constant in micellar phase, kW = rate constant in aqueous phase.
At low concentration of surfactant, Eq. (14) reduces to Eq. (15):
n
kM[D] +kW KD
kobs
=
(15)
(16)
n
KD +[D]
The above equation can be rewritten as
ꢀ
ꢁ
kobs −kW
kM −kobs
log
= n log[D]−log KD
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Reaction Kinetics in Micellar System
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Scheme 2. Scheme for reaction steps for Piszkiewicz’s model.
It is easy and practically possible to determine the values of kW by proceeding the reac-
tion without micelle i.e. reaction is taking place only in aqueous phase. But practically,
it is not possible to attain absolute or total micellar phase to determine kM and that is
why this phase is often referred as pseudo-phase.
It is interesting to note how different researchers have dealt with kM. It is practical
to take kM as zero for the surfactants which inhibit the reaction as in the pseudo-micellar
phase of this reaction i.e. in absence of any reaction in aqueous phase, the surfactant will
supposedly inhibit the reaction to the extent that reaction will not proceed at all i.e. kM
can be reasonably taken as zero.
But for the surfactants, which catalyze the reaction, such simple assumptions are
not feasible. Although some researchers are tempted to treat highest observed rate con-
stant as kM, in our opinion, such assumption is erratic as in the reaction of the highest
rate constant, reaction in aqueous phase is also contributing to the overall reaction rate
constant. To come out of this intriguing scenario, we have taken help of Menger and
Portnoy’s Model [39] which gives fairly reasonable value of kM. This model gives fol-
lowing equation:
1
1
1
=
+
(17)
kW −kobs
kW −kM (kW −kM)KS[D]n
Using this equation, we have computed the value of kM for our experimental data as
27.55×10−4 s−1. This value of kM is much higher than the highest observed rate con-
stant i.e. 11.53×10−4 s−1. The explanation of this very high kM is as following:
“In the micellar catalyzed reactions, at low surfactant concentrations, overall reac-
tion rate is governed by reactions taking place in pseudo-micellar phase and aqueous
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Fig. 3. Graph showing linearity for Piszkiewicz model. Exp. conditions: T = 308 K, [CH3COOH] = 50%,
[NBP] = 1.0×10−4 mol dm−3, [L-leucine] = 1.0×10−3 mol dm−3, [Hg2+] = 2.0×10−4 mol dm−3, [H+] =
1.0×10−2 mol dm−3
.
Table 5. Parameters of surfactant and different constants calculated from models.
Parameter
Value
n
3.16
log KD
−11.283
5.21×10−12
1.92×1011
1.67×1011
1.11
KD (mol dm−3
1/KD
)
K1 (mol−1 dm3)
K2 (mol−1 dm3)
phase by following equation:
kobs = [fraction of micellar phase]×kM +[fraction of aqueous phase]×kW
Since concentration of surfactant is low and kW is much lower than the highest kobs
value of kM shall be much higher than the highest kobs.”
(18)
,
However above equation is not valid at higher surfactant concentrations as at higher
concentrations, formation of kinetic inactive micelle starts, which is responsible for
retardation of reaction.
Applying this value of kM to Eq. (16), we have calculated the value of n and log KD,
Fig. 3 which are given in Table 5. The value of n is 3.16, which is an indication of
positive coperativity. KD is dissociation constant of micelle back to its free compon-
ent.
3.12.2 Raghvan and Srinivasan’s model
For bimolecular micellar catalyzed reactions Raghvan and Srinivasan [40] developed
a model, which considers distribution of the reactant as well as nucleophile i.e. oxi-
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Reaction Kinetics in Micellar System
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Scheme 3. Scheme for reaction steps for Raghvan and Srinivasan’s model.
dant in both phases i.e. aqueous and micellar phases and may be used for evaluating
the binding constants of both the reactants. The product formation is assumed to result
from decomposition of ternary complex involving substrate, nucleophile and micelle.
The analysis of the data on the basis of the model showed that almost all the nucleophile
was present in the bulk phase. A similar idea has also been given by Romsted [41] and
Reeves [42]. The model is represented in Scheme 3.
Where D, S and N refer to detergent monomer, substrate and the nucleophile, re-
spectively, while DnS and DnSN refer to binary and ternary complexes, respectively.
In present investigation NBP has been considered as N. The products are assumed to
result from reactions in aqueous medium as well as surfactant medium. According to
above model the observed rate constant in presence of surfactant is given by following
equation:
n
kW +kM K1 K2[D]
kobs
=
(19)
n
1+ K1[D] {1+ K2[S]T}
This equation is identical to those derived by Berezin et al. [43] and Bunton et al. [44].
Further, the above equation may be rearranged in the following form:
ꢀ
ꢁ
kobs −kW
1
kM
×
= K1 K2
− K1{1+ K2[S]T}
(20)
n
kobs
[D]
kobs
n
The equation predicts a linear relationship between [(kobs −kW)/kobs]/[D] vs. (kM/kobs).
We have applied this model in our system using the value of n obtained from
n
Piszkiewicz’s cooperativity model. The plots of [(kobs − kW)/kobs]/[D] vs. (kM/kobs
)
was found to be fairly linear, Fig. 4. The values of K1 and K2 (binding constants) have
also been evaluated with the help of intercept and slope of this linear plot. The values
of intercept and K1 are almost the same in magnitude as K2[S]T ꢂ 1. The values of
intercept, K1 and K2 obtained from the model are reported in Table 5.
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Y. Katre et al.
Fig. 4. Graph for manifestation of Raghvan and Srinivasan’s model. Exp. conditions: T = 308 K,
[CH3COOH] = 50%, [NBP] = 1.0×10−4 mol dm−3, [L-leucine] = 1.0×10−3 mol dm−3, [Hg2+] = 2.0 ×
10−4 mol dm−3, [H+] = 1.0×10−2 mol dm−3
.
The evaluated K1 values are also in good agreement with obtained from the
Piszkiewicz’s model (in which the dissociation constant KD which is reciprocal of bind-
ing constant is reported), Table 5. The low value of K2 (K1 ꢀ K2) also suggest the NBP
is present almost in full of the bulk phase. Thus, it is apparent that phenomena results by
formation of an aggregate between the surfactant and substrate and NBP residing in the
bulk phase.
4. Conclusion
In the light of kinetic observations for the micellar effect on the oxidation of L-leucine
by N-bromophthalimide in the presence of perchloric acid, the following conclusions
can easily be drawn: Oxidation products were identified and activation parameters were
evaluated for the catalyzed as well as uncatalyzed reactions. The critical micelle con-
centration values are much lower than those given in the literature for aqueous solutions
of CTAB without added electrolyte. In the presence of catalyst, the rate of oxidation
first increased and after attaining a peak it decreased with increasing concentration
of CTAB. Application of different kinetic models confirms the behavior of micellar-
catalyzed oxidation reaction. The micellar effect can be correlated with the nature of
the reducing substrate and the reaction conditions. These results are of relevance to var-
iety of applications such as understanding of important biochemical mechanisms and
functioning of pharmaceutical formulations involving amino acids. Interestingly, in the
present study the reactive species of oxidant NBP is found to be HOBr and not NBP it-
self. This HOBr is of relevance to life sciences as HOBr targets proteins for oxidation
and is responsible for tissue injury, asthma and other infections. As such the results can
be utilized in studies for prevention of these diseases. These micellar effects are quite
important to understand and to substantiate the proposed mechanistic pathways.
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Acknowledgement
One of the authors (YRK) thanks the University Grants Commission, New Delhi for
the Minor Research Project Grant. We also thank the annoymous reviewers for their
valuable feedback and suggestions for corrections and improvement in this article.
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