Determination of the hydrolysis kinetics of α-naphthyl acetate in micellar systems and the effect of HPMC (catalyst present)

Article abstract of DOI:10.1002/jps.20800

The change in the hexadecyltrimethylammonium bromide (CTAB) critical aggregation concentration (CAC) was studied in the presence of various concentrations and grades of hydroxypropylmethyl cellulose (HPMC) using surface tension measurement (duNouey ring and Wilhelmy plate) and oil red O solubilization. According to the surface tension methods, the CAC was higher than the CTAB critical micelle concentration (CMC). CAC and CMC were not different when the solubilization method was used. Micellar solutions of CTAB have been found to accelerate the hydrolysis of α-naphthyl acetate (α-NA) by o-iodosobenzoic acid (IBA), a strong nucleophile. Pseudo-first-order kinetics were utilized for rate constant determination. The observed rate constants for the degradation of α-NA in the presence of varying CTAB concentrations with and without HPMC were analyzed according to the pseudophase model. The micellar rate constants and the micellar binding constants for the substrates were obtained. The presence of HPMC retarded the reaction rate, and the rate constant decreased as the polymer concentration increased. However, there was no obvious difference in the observed rate constants among the different grades of HPMC (Methocel E5, Methocel E15, Methocel E50). The decrease in the rate constant was likely due to the polymer-micelle interaction interfering with substrate binding to the CTAB micelles.

Full text of DOI:10.1002/jps.20800

Determination of the Hydrolysis Kinetics of a-Naphthyl
Acetate in Micellar Systems and the Effect of
HPMC (Catalyst Present)
PORNPEN WERAWATGANONE,1 DALE ERIC WURSTER1,2
1Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242
2Obermann Center for Advanced Studies, Oakdale Hall, University of Iowa, Iowa City, Iowa 52242
Received 29 June 2006; revised 21 August 2006; accepted 2 September 2006
Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jps.20800
ABSTRACT: The change in the hexadecyltrimethylammonium bromide (CTAB) critical
aggregation concentration (CAC) was studied in the presence of various concentrations
and grades of hydroxypropylmethyl cellulose (HPMC) using surface tension measure-
ment (duNou¨y ring and Wilhelmy plate) and oil red O solubilization. According to the
surface tension methods, the CAC was higher than the CTAB critical micelle
concentration (CMC). CAC and CMC were not different when the solubilization method
was used. Micellar solutions of CTAB have been found to accelerate the hydrolysis of
a-naphthyl acetate (a-NA) by o-iodosobenzoic acid (IBA), a strong nucleophile. Pseudo-
first-order kinetics were utilized for rate constant determination. The observed rate
constants for the degradation of a-NA in the presence of varying CTAB concentrations
with and without HPMC were analyzed according to the pseudophase model. The
micellar rate constants and the micellar binding constants for the substrates were
obtained. The presence of HPMC retarded the reaction rate, and the rate constant
decreased as the polymer concentration increased. However, there was no obvious
difference in the observed rate constants among the different grades of HPMC (Methocel
E51, Methocel E151, Methocel E501). The decrease in the rate constant was likely due to
the polymer–micelle interaction interfering with substrate binding to the CTAB
micelles. ß 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci
96:448–458, 2007
Keywords: micelle; surfactant; polymer; decomposition kinetics; hydroxypropyl-
methylcellulose; hexadecyltrimethylammonium bromide; hydrolysis; surface tension;
solubility; critical micelle concentration
INTRODUCTION
solutions,1,2 resulting in polymer–surfactant
interactions.3–5 One method that can be uti-
lized to study such interactions is to determine
the effect of polymer addition on the critical
aggregation concentration (CAC), which is the
concentration where surfactant molecules aggre-
gate, or cluster about the polymer molecules.6
In the absence of polymer, the narrow range of
surfactant concentration over which micelles
first become detectable is the critical micelle
concentration (CMC).7 The existence of interac-
tions between a polymer and a surfactant can be
inferred if the CAC and the CMC are different.
Micellar solutions are of widespread interest
due to their varied applications. In some cases,
polymers are introduced into these micellar
Pornpen Werawatganone’s present address is Department
of Pharmacy, Faculty of Pharmaceutical Sciences, Chulalong-
korn University Patumwan, Bangkok 10330, Thailand.
Correspondence to: Dale Eric Wurster (Telephone: 1-319-
335-2137; Fax: 662-218-8401;
E-mail: dale-e-wurster@uiowa.edu)
Journal of Pharmaceutical Sciences, Vol. 96, 448–458 (2007)
ß 2006 Wiley-Liss, Inc. and the American Pharmacists Association
448
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HYDROLYSIS KINETICS OF a-NAPHTHYL ACETATE IN MICELLAR SYSTEMS
449
Surface tension lowering and solubilization are
two techniques that can be used for the determi-
nation of CMC/CAC.7,8 In the surface tension
method, a plot of surface tension as a function of
the logarithm of surfactant concentration is used.
In the solubilization method, the solubility of an
insoluble molecule is plotted as a function of the
logarithm of surfactant concentration. In both
methods, a break is identified and used to deter-
mine the CMC/CAC.
The observed rates of chemical reactions may
be altered in micellar solutions because of the
distribution of substrates between the micellar
and aqueous phases, in which different environ-
ments exist.8 Therefore, a reaction can be acceler-
ated or inhibited by micelles, depending on the
mechanism of the reaction.9 Berezin et al. pro-
posed an equation (Eq. 1) for the quantitative
analysis of bimolecular reactions occurring in
micellar systems.10 Wurster and Patel utilized
that equation to analyze the hydrolysis of a-
naphthyl acetate (a-NA) in the presence of o-
iodosobenzoic acid (IBA) and CTAB micelles.11
Those authors reported that the rate of hydrolysis
is enhanced in the presence of CTAB micelles and
that the mechanism of the reaction is unchanged,
since the entropy of activation is ꢀ44.9 cal/moleꢁK
in solutions without surfactant, and ꢀ39.3 cal/
moleꢁK in 3 mM CTAB solutions.11 The negative
entropy of activation indicates that the reaction
follows a bimolecular mechanism.
the added viscosity-inducing polymer be deter-
mined. These effects may be on surfactant aggre-
gation behavior, substrate binding to the micelle,
and on the substrate reactivity itself.
The changes in reaction rate of a-NA, a model
substrate, with changing surfactant concentra-
tions and changing polymer concentrations were
studied. In addition, the influence of added
electrolytes on the micellar system was also
studied. Surface tension and solubilization meth-
ods wereused todetermine the CAC of CTAB inthe
presence of HPMC. Oil red O, which is very slightly
soluble in water, was utilized in the solubilization
studies. The reaction kinetics were studied using
fluorescence spectrophotometry, and the reaction
parameters in Equation 1 were calculated using
nonlinear curve fitting software (Kaleidagraph
program).
EXPERIMENTAL SECTION
Materials
Three different grades of HPMC: HPMC E5,
HPMC E15, and HPMC E50 (Methocel E51,
Methocel E151, Methocel E501), were obtained
from The Dow Chemical Company (Midland, MI).
CTAB, oil red O, a-NA, and IBA were purchased
from Sigma Chemical Co. (St. Louis, MO). Mono-
basic sodium phosphate monohydrate, dibasic
sodium phosphate, sodium sulfate, glacial acetic
acid, and sodium acetate trihydrate were pur-
chased from Fisher Scientific (Fair Lawn, NJ). All
HPMC grades were purified using a dialysis
method. A 10% w/w, in water, polymer solution
was placed in a dialysis bag (3500 MWCO) and the
bag was placed in distilled water. The medium
was replaced with fresh distilled water every day
until the conductivity of the medium was not
different from the freshly distilled water. The
other chemicals were used as received.
ꢀ
kb þ kmKNAKIBA
C
kobs
¼
ð1Þ
ð1 þ KNACÞð1 þ KIBACÞ
kobs, observed rate constant; kb, rate constant in
the aqueous phase; KNA, a-NA binding constant;
IBA, IBA binding constant; km, micellar rate
K
constant per molar volume; C, CTAB micelle
concentration.
In this work, the impact of adding a nonionic
polymer, hydroxypropylmethyl cellulose (HPMC),
to CTAB micellar solutions on the hydrolysis of a-
NA inthepresence of IBA is studied thoroughly. As
mentioned earlier, polymers are added to micellar
systems for a variety of different reasons. One of
those reasons is viscosity enhancement so that
topical formulations of micellar systems can be
prepared. This work is part of an ongoing project to
determine the feasibility of making reactive
barriers, for topical application, which could
protect human beings against inadvertent pesti-
cide exposure. If such formulations are to be
successful, it is essential that the exact effects of
Methods
Critical Micelle Concentrations of CTAB, HPMC,
and CTAB—HPMC Mixed Systems
Surface Tension Measurement. A Surface Tensio-
mat 211 (semi-automatic model, Fisher Scientific)
and a KSV Sigma 70 (surface tension/contact angle
meter, Type 100L, KSV instrument, Monroe, CT)
were employed in these studies. A platinum-
iridium duNou¨y ring (circumference 5.910 cm,
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WERAWATGANONE AND WURSTER
R/r 52.94) was attached to the Tensiomat 211 and
a platinum Wilhelmy plate (19.6-mm wide and
0.1-mm thick) was used with the KSV Sigma 70.
The CMC of CTAB was determined in water,
buffer solution (monobasic sodium phosphate
monohydrate and dibasic sodium phosphate),
and HPMC solutions (HPMC E5, HPMC E15,
and HPMC E50). Four concentrations of polymer
solutions, 0.02, 0.1, 0.3, and 0.8% w/v (without
CTAB), were prepared in phosphate buffer solu-
tion. The total buffer concentration and pH value
were controlled at 0.0667 M and 7.40 ꢂ 0.01,
respectively.
Various concentrations of CTAB from 0 to
15 mM were prepared in the aforementioned
solvent solutions. Sample solutions were placed
in a jacketed beaker connected to a circulating
water bath maintained at 308C. Two different
aliquots of each solution were measured. The
surface tension versus log [CTAB] plot was
constructed for each solvent system and the CMC
and/or the CAC was calculated from the profile.
Regarding the critical polymer concentration
(CPC), the surface tensions of solutions having
various concentrations of HPMC E5 were mea-
sured. The CPC was obtained from the plot of
surface tension versus log [HPMC E5].
The oil red O solubilities were also determined
in solutions having various concentrations of
HPMC E5. HPMC E5 aggregation concentration
was determined from the profile of oil red O
solubility versus log [HPMC E5].
Effect of SO24ꢀ Ion on CMC
Phosphate buffer solutions, ionic strength of
0.17 M, and phosphate buffer solutions with
sodium sulfate, ionic strength of 0.30 M, were pre-
pared with a pH of 7.40 ꢂ 0.01. Various concen-
trations of CTAB from 0 to 15 mM were prepared
in these media. The CMC values of CTAB were
determined from both surface tension and oil red
O solubility data using the procedures previously
described.
Hydrolysis Kinetics of a-NA in Micellar Systems
and the Influence of HPMC
The effect of the interaction between HPMC and
CTAB was studied using the degradation of a-NA
in the presence of a catalyst, IBA. The reaction
was performed in phosphate buffer solution,
0.0667 M and pH 7.40 ꢂ 0.01, in the presence
and absence of the polymers: HPMC E5, HPMC
E15, and HPMC E50. Buffered polymer solutions
were prepared at concentrations of 0.02, 0.1, and
0.3% w/v of each HPMC.
To construct the observed rate constant versus
CTAB concentration profile, various concentra-
tions of CTAB (0–6.5 mM) were prepared in each
reaction medium. The initial concentrations of
reactants were 2.0 ꢃ 10ꢀ4 M of a-NA and 1.0 ꢃ 10ꢀ4
M of IBA at 308C. Samples were taken during the
kinetic runs and were diluted with pH 4.5 acetate
buffer (glacial acetic acid and sodium acetate
trihydrate) to quench the reaction.
The amount of a-NA remaining was analyzed
using a fluorescence spectrophotometer (Kontron
Instruments, Inc., Milano, Italy). The excitation
and emission wavelengths used for the analyses of
a-NA were 278 and 328 nm, respectively. The data
obtained were employed for the determination
of the pseudo-first-order rate constants for the
decomposition of a-NA. Due to the side reaction
between the degradation product, a-naphthol, and
the nucleophile, IBA, only the kinetic data up to
one and one-half half-life periods were used for
the determination of the rate constants.11 The
profile of observed rate constant versus the
concentration of CTAB was constructed for each
solvent mixture.
Solubilization of Oil Red O. Excess amounts of
oil red O were added to screw-cap tubes filled with
phosphate buffer, water, or solvent systems con-
taining different concentrations (0.02, 0.1, 0.3,
0.8% w/v) of the three HPMC grades in phosphate
buffer solution. The samples were rotated end over
end using a sustained-release apparatus (Vander-
kamp1 Sustained Release Apparatus, Model
103906, VanKel Industries, Inc., Edison, NJ) in a
water bath (Vanderkamp1, Model W-1115, Van-
Kel Industries, Inc.) at a controlled temperature of
308C. The samples were allowed to equilibrate for
a period of 48 h, and were then filtered through
0.22 mm Millex1-GV disposable syringe filters
(Millipore, Carrigtwohill, Co. Cork, Ireland). The
first 3 mL of filtrate was discarded and the
collected filtrate was suitably diluted. The con-
centrations of oil red O were assayed using a UV
spectrophotometer (Hewlett Packard HP 8453,
Agilent Technology, Palo Alto, CA) at a wave-
length of 521.4 nm. Each sample was run in dupli-
cate. The data were utilized to prepare an oil red O
solubility versus log [CTAB] plot for each solvent
and the CMC or CAC was indicated by the CTAB
concentration for which the oil red O solubility
increased considerably.
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HYDROLYSIS KINETICS OF a-NAPHTHYL ACETATE IN MICELLAR SYSTEMS
451
Influence of SO24ꢀ Ions on a-NA Hydrolysis
Kinetics in Micellar Systems
Sodium sulfate was added to the buffered reaction
medium to reach 0.3 M ionic strength. The
solutions were controlled at pH 7.40 ꢂ 0.01 and
the total phosphate buffer concentration was kept
constant at 0.0667 M. These solvent mixtures
were used for preparing various concentrations of
CTAB from 0 to 6.5 mM. The initial concentra-
tions of reactants were 2.0 ꢃ 10ꢀ4 M of a-NA and
1.0 ꢃ 10ꢀ4 M of IBA at 308C. Samples were taken
and analyzed during the kinetic runs. These
experiments were done in duplicate.
a-NA Hydrolysis Kinetics in a CTAB-HPMC
Gel System
Figure 1. CMC determination for CTAB in water and
in phosphate buffer solution (pH 7.40 ꢂ 0.01) at 308C:
(*) water using duNou¨y ring, (~) water using Wilhelmy
plate, (^) buffer using duNou¨y ring, (!) buffer using
Wilhelmy plate, and (ꢃ) the CMC.
HPMC gels were prepared from HPMC E50
hydrated in phosphate buffer solution at pH
7.40 ꢂ 0.01 and a total buffer concentration of
0.0667 M. The initial concentrations of reactants
were 2.0 ꢃ 10ꢀ4 M for a-NA and 1.0 ꢃ 10ꢀ4 M for
IBA and the system was controlled at 308C. The
concentration of HPMC E50 was kept constant
at 5% w/v, but the concentration of CTAB was
varied from 0 to 6 mM. Samples were taken and
analyzed during the kinetic runs and a plot of
observed rate constant versus CTAB concentra-
tion was constructed. These experiments were
done in duplicate.
9.34 ꢃ 10ꢀ4 M (Wilhelmy Plate) and 9.36 ꢃ 10ꢀ4
M (duNou¨y Ring) at 308C. Those values are close to
the literature value of 9.2 ꢃ 10ꢀ4 M at 258C.12 In
this case, an increase in temperature is likely to
cause the small change observed. The disruption of
the structured water surrounding the hydrophobic
chain apparently predominated over the decrease
in hydration of the hydrophilic group as tempera-
ture was increased. The CMC for CTAB in the
buffer solution was 6.85 ꢃ 10ꢀ5 M, which is close to
the value reported by Patel of 6.8 ꢃ 10ꢀ5 M.13 The
CMC of CTAB in water was higher than that in
buffer because electrolytes from the buffer reduce
repulsion between the ionic head groups of the
surfactant molecules, thus facilitating micelliza-
tion. In other words, the increased binding of
counterions to the surfactant polar groups causes a
decrease in the CMC of the surfactant.12 A greater
electrolyte effect was found when sodium sulfate
was added to the system.
The addition of HPMC to the CTAB solution
increased the observed concentration of CTAB at
the breakpoint in the plot of surface tension versus
log [CTAB]. This breakpoint was defined earlier
as the CAC and it gives an indication of the
interaction between CTAB and HPMC. These
interactions caused a redistribution of the CTAB
molecules, from the surface to the bulk phase.
Since more CTAB molecules distributed to the
bulk phase when HPMC was added, more CTAB
RESULTS AND DISCUSSION
CMC/CAC Values for CTAB, HPMC, and
CTAB—HPMC Mixed Systems
Surface Tension Measurement
The CMC of CTAB was determined in water and
in buffer solution by measuring the surface
tensions of a series of CTAB solutions having
different concentrations. As the CTAB concen-
tration increased, the surface tension rapidly
dropped to a minimum value and then remained
constant. Figure 1 is a typical plot for CMC/CAC
determination using the surface tension method.
The CMC and CAC values of CTAB in solutions
of different HPMC grades and concentrations,
which were determined from their surface tension
versus log [CTAB] profiles, are reported in
Table 1. CPC was observed at 2.66 ꢃ 10ꢀ6 g/ml.
Regarding the surface tension method, the
CMC for CTAB in water was found to be
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Table 1. CMC or CAC of CTAB in Various Media Using Surface Tension and Solubilization Methods at 308C
CMC or CAC, M
Surface Tension Method
System
duNou¨y Ring
Wilhelmy Plate
Solubilization Method
Water
9.36 ꢃ 10ꢀ4
6.85 ꢃ 10ꢀ5
—
9.34 ꢃ 10ꢀ4
6.83 ꢃ 10ꢀ5
6.11 ꢃ 10ꢀ5
5.04 ꢃ 10ꢀ4
1.20 ꢃ 10ꢀ4
1.02 ꢃ 10ꢀ4
Phosphate buffer (pH 7.40 ꢂ 0.01)
Na2SO4 in phosphate buffer (pH 7.40 ꢂ 0.01)
HPMC E5 (% w/v)
0.02
0.1
0.3
0.8
1.26 ꢃ 10ꢀ4
1.20 ꢃ 10ꢀ4
1.17 ꢃ 10ꢀ4
1.10 ꢃ 10ꢀ4
1.14 ꢃ 10ꢀ4
1.23 ꢃ 10ꢀ4
1.22 ꢃ 10ꢀ4
1.25 ꢃ 10ꢀ4
1.10 ꢃ 10ꢀ4
1.13 ꢃ 10ꢀ4
1.10 ꢃ 10ꢀ4
1.10 ꢃ 10ꢀ4
HPMC E15 (% w/v)
0.02
0.1
0.3
0.8
1.33 ꢃ 10ꢀ4
1.12 ꢃ 10ꢀ4
1.04 ꢃ 10ꢀ4
1.10 ꢃ 10ꢀ4
1.19 ꢃ 10ꢀ4
1.03 ꢃ 10ꢀ4
8.44 ꢃ 10ꢀ5
1.01 ꢃ 10ꢀ4
1.20 ꢃ 10ꢀ4
1.20 ꢃ 10ꢀ4
1.20 ꢃ 10ꢀ4
1.20 ꢃ 10ꢀ4
HPMC E50 (% w/v)
0.02
0.1
0.3
0.8
1.05 ꢃ 10ꢀ4
1.08 ꢃ 10ꢀ4
1.09 ꢃ 10ꢀ4
1.24 ꢃ 10ꢀ4
1.17 ꢃ 10ꢀ4
1.06 ꢃ 10ꢀ4
1.06 ꢃ 10ꢀ4
1.18 ꢃ 10ꢀ4
1.20 ꢃ 10ꢀ4
1.20 ꢃ 10ꢀ4
1.20 ꢃ 10ꢀ4
1.20 ꢃ 10ꢀ4
molecules were needed to reach the CMC. This
explanation was supported by the effect of HPMC
on the surface tension. The initial decrease in
surface tension upon CTAB addition was more
rapid in the absence of HPMC than in the presence
of HPMC. Lundqvist et al. also observed a CAC
higher than the CMC in a study of CTAB-starch
polysaccharides binding.14 Similar behavior was
also observed in the presence of Carbopol and
Tween 80.15 The initial slope of surface tension
versus log [Tween 80] was less in the presence of
0.25% Carbopol, since the surface excess of Tween
80 at the air/water interface was decreased as the
surfactant was adsorbed by the polymer and
drawn into the bulk solution. According to the
Gibbs adsorption equation, the relationship
between change in surface tension (dg) and the
surface excess (G1) of a surfactant is given by:
Table 2. Surface Excesses of CTAB in Various Media
Surface Excess,
Mole/cm2 (1011ꢃ)
duNou¨y
Ring
Wilhelmy
Plate
System
Water
Phosphate buffer
9.01
14.3
10.8
12.5
(pH 7.40 ꢂ 0.01)
Na2SO4 in phosphate
—
13.1
buffer (pH 7.40 ꢂ 0.01)
HPMC E5 (% w/v)
0.02
0.1
0.3
0.8
5.54
6.66
5.90
5.74
5.63
5.40
5.36
5.05
HPMC E15 (% w/v)
0.02
0.1
0.3
0.8
6.20
7.46
6.60
6.21
6.09
6.11
6.48
5.90
dg ¼ ꢀ2RTG1d ln C
where, T and C represent the absolute tempera-
ture and the surfactant concentration, respec-
tively, and R is the gas constant.
ð2Þ
HPMC E50 (% w/v)
0.02
0.1
0.3
0.8
7.11
7.29
6.31
6.62
6.11
6.44
6.22
6.02
Surface excesses from the experiments are
reported in Table 2. The results confirmed that
the surface excess of CTAB was lowered when
HPMC was added to the system. In buffer solution,
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the surface excess increased because the effective
charge of the hydrophilic groups on the CTAB
molecules was decreased by the buffer salts,
leading to an increase in the efficiency of adsorp-
tion of CTAB at the surface.12
Neither HPMC concentration nor grade
affected the CAC. This result was surprising, and
the explanation is not definitively known. One
possible explanation is that the lowest HPMC
concentration used in this work, 0.02%, was large
enough to satisfy the possible interactions with
CTAB. Therefore, further increase in HPMC
concentration had no impact.
hydrophobic and hydrophilic regions in the mole-
cular structure.16
The solubilization results confirmed that the
CMC of CTAB in water was higher than that in
buffer. Using the solubilization method, the CMC
of CTAB in buffer was 1.2 ꢃ 10ꢀ4 M, which was
higher than that obtained from the surface tension
method (6.8 ꢃ 10ꢀ5 M). This difference may be real
or it may be an artifact. It may be that, when the
number of micelles was small, oil red O solubility
changes could not be detected.
Effect of SO24ꢀ Ion on CMC
The CMC of CTAB in a buffered sodium sulfate
Solubilization of Oil Red O
solution was determined to be 6.11 ꢃ 10ꢀ5 M using
The solubility of oil red O in CTAB solution
dramatically increased above the CMC. Figure 2
shows typical solubility profiles obtained from
this study. The CMC was defined as the point
where the solubility abruptly increased. In buffer
solution, the introduction of HPMC into the
system did not alter the break point of the profile.
The CMC or CAC values for CTAB in the different
solvent systems using the solubilization method
are reported in Table 1. According to solubility
studies (not shown in Tab. 1), the HPMC (only)
solutions did not dissolve oil red O at any of the
tested concentrations.
surface tension measurement and 1.02 ꢃ 10ꢀ4
M
using the solubilization technique. For experi-
ments involving water without electrolytes, the
CMC from the solubilization method was less
than that obtained from the surface tension
methods. In most cases, the decrease in the CMC
caused by the introduction of a solubilizate is
attributed to changes in the activity of the
surfactant and, consequently, in the concentra-
tion of monomeric surfactant in the bulk phase.12
The solubilizate influence was not observed in the
buffer solution because the reduction of the CMC
due to the electrolyte effect was more dominant
than the increase in the CMC due to the
solubilizate effect.
HPMC is surface active and reduces the surface
tension of aqueous systems, but the HPMC solu-
tions did not dissolve oil red O at any of the tested
concentrations. The reason is that HPMC does not
form micelles. Micelle formation requires both
Hydrolysis Kinetics of a-NA in Micellar
Systems and the Influence of HPMC
Throughout this work, excellent correlations were
observed between log [a-NA] and time, which
supports pseudo-first-order kinetics.11 The pre-
sence of 2.65 mM CTAB enhanced the IBA-
catalyzed a-NA hydrolysis as much as 68 times
compared to the same system without CTAB
micelles. The catalytic effect of micellar media
on bimolecular reactions can occur in two ways:
(1) concentrating reactants in a small volume and
providing a concentration advantage to the reac-
tion, and (2) providing a medium effect to change
the activities of substrates. Micelles may provide
a medium effect that changes the reactivities of
both the substrate and the reactive ion. This effect
arises from a combination of orientation, micro-
viscosity, polarity, and charge effects.17 Since the
microviscosity of micelles is much higher than
the viscosity of the surrounding homogeneous
solvent, substrate molecules incorporated in
Figure 2. CMC determination for CTAB using the
solubilization method at 308C: (*) water, (^) phosphate
buffer solutions, and (ꢃ) the CMC.
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micelles have less translational and rotational
freedom and this is reflected in their reactivities.
For some reactions, electrostatic and hydrophobic
interactions between the substrate and micelle
may influence the activation energy.8
Typical observed rate constant versus CTAB
concentration profiles in the presence and absence
of HPMC are presented in Figures 3 and 4. The
shapes of all of the plots follow the same pattern as
the system without HPMC. Regarding Equation 1,
the pseudophase parameters were obtained using
nonlinear curve fitting and the results are tabu-
lated in Tables 3–5.
As seen in Figures 3 and 4, a maximum in the
observed rate constant versus surfactant con-
centration profile was reached. The reason is that,
as CTAB micelle concentration was increased,
a concentration was reached for which essentially
all of the reactants were bound to micelles.
After this point, an increase in the number of
CTAB micelles decreased the micellar concentra-
tions of substrates, causing lower observed rate
constants.
Figure 4. Observed rate constant for a-NA hydrolysis
versus CTAB concentration with added HPMC at
different concentrations in pH 7.40 ꢂ 0.01 phosphate
buffer at 308C: (~) 0.02% HPMC E5, (ꢃ) 0.02% HPMC
E15, (&) 0.02% HPMC E50, (~) 0.1% HPMC E5, (})
0.1% HPMC E15, ( ) 0.1% HPMC E50, (!) 0.3% HPMC
E5, (*) 0.3% HPMC E15, and (&) 0.3% HPMC E50.
Regarding the pseudophase parameters before
the addition of HPMC, the micellar rate constant,
km, was found to be 1.4 ꢃ 10ꢀ4 minꢀ1, assuming
that the molar volume of CTAB in the micellar
form was 0.25 Mꢀ1. This micellar rate constant
was less than that observed for the reaction
conducted in the absence of the surfactant, kb,
which was 6.2 ꢃ 10ꢀ4 minꢀ1. The enhancement of
reaction rate is, therefore, due to the increased
concentration of the reactants in the micellar
pseudophase and not due to an enhancement of
the reactivity in the micellar environment. The
lowering of the reaction rate constant in the
micellar pseudophase, compared to the bulk
phase, is normally attributed to such factors as
microviscosity or orientational effects.
Patel13 reported that the activation energy of
the reaction was 11.5 kcal/mole in the system
without any surfactant present (pH 7.5), and 11.1
kcal/mole in the system with 3 mM CTAB (same
pH). These two activation energies are essentially
equal. This information further supports the
notion that the acceleration in reaction rate
afforded by the micellar solution is due to a
concentration effect.
Nardviriyakul studied the degradation of dicap-
thon in a micellar CTAB system in the presence
of IBA (258C). The reported substrate binding
constants for IBA and dicapthon were 120 and
2749 Mꢀ1, respectively.18 In these current studies,
the degradation of a-NA in a micellar CTAB
system containing IBA was studied at 308C. The
substrate binding constants were found to be 174
and 541 Mꢀ1 in phosphate buffer solution. Based
on this information, it can be deduced that 174 and
541 Mꢀ1 were for IBA and the a-NA binding
constants, respectively. The difference between
the IBA binding constant found in this work and
the previously reported value might be due to a
Figure 3. Observed rate constant for a-NA hydrolysis
versus CTAB concentration with added HPMC E5 in pH
7.40 ꢂ 0.01 phosphate buffer at 308C: (*) buffer, (~)
0.02% HPMC E5, (~) 0.1% HPMC E5, and (!) 0.3%
HPMC E5.
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455
Table 3. Summary of the Parameter Estimates Obtained From the Analysis of the Rate Constant Versus
Surfactant Concentration Data in the System With HPMC E5
Concentration of HPMC E5, % w/vb
Pseudophase
Parameters
0% HPMC
0.02% HPMC
0.1% HPMC
0.3% HPMC
KIBA (Mꢀ1
)
174 (14)
541 (35)
151 (12)
517 (33)
146 (12)
494 (31)
120 (11)
455 (30)
KNA (Mꢀ1
km(M/min)
)
5.7 ꢃ 10ꢀ4 (0.2 ꢃ 10ꢀ4
)
)
6.4 ꢃ 10ꢀ4 (0.2 ꢃ 10ꢀ4
)
)
5.6 ꢃ 10ꢀ4 (0.2 ꢃ 10ꢀ4
)
)
5.9 ꢃ 10ꢀ4 (0.2 ꢃ 10ꢀ4
)
)
k
m (minꢀ1 a
)
1.4 ꢃ 10ꢀ4
1.6 ꢃ 10ꢀ4
1.4 ꢃ 10ꢀ4
1.5 ꢃ 10ꢀ4
kb (minꢀ1
Copt (M)c
R2
)
6.2 ꢃ 10ꢀ4 (0.1 ꢃ 10ꢀ4
3.2 ꢃ 10ꢀ3
7.0 ꢃ 10ꢀ4 (0.0 ꢃ 10ꢀ4
3.5 ꢃ 10ꢀ3
5.4 ꢃ 10ꢀ4 (0.1 ꢃ 10ꢀ4
3.7 ꢃ 10ꢀ3
8.0 ꢃ 10ꢀ4 (0.0 ꢃ 10ꢀ4
4.2 ꢃ 10ꢀ3
0.993
0.991
0.991
0.991
aAssuming a molar volume for CTAB in the micellar form of 0.25 Mꢀ1
bThe number between brackets is the standard error.
cCTAB concentration at the highest rate constant.
.
change in either the reaction components or the
temperature, or both. Temperature, for example,
alters micelle formation and increases the dis-
sociation constant of weak acids.12,19
range of 1.4 ꢃ 10ꢀ4 to 1.6 ꢃ 10ꢀ4 minꢀ1 for HPMC
E5 concentrations of 0.02, 0.1, and 0.3% w/v. When
the results from different grades of HPMC were
compared, the observed rate constants did not
seem to be influenced by HPMC grade (Fig. 4).
The aforementioned results indicate that the
decrease in the observed reaction rate constants
upon the addition of HPMC was due to decreased
substrate binding. Therefore, substrate concen-
trations in the micellar pseudophase were lower
than before the addition of polymer, but the
reactivity in the micellar environment was not
decreased. Furthermore, the viscosity increase in
the bulk phase resulting from the addition of the
polymer was not responsible for the decrease in the
reaction rate constant. If that had been the case,
then the observed rate constants should have
decreased more when HPMC E15 or HPMC E50
was added than when HPMC E5 was added, since
Upon HPMC addition, the cationic surfactant
still had an effect on the hydrolysis of a-NA.
However, HPMC addition resulted in a decrease
in the observed rate constant at any given CTAB
concentration. The higher the HPMC concentra-
tion, the lower was the rate constant. The reason is
that the binding constants of both IBA and a-NA
decreased systematically as the concentration of
HPMC increased. For example, the IBA and the
a-NA binding constants decreased from 174 to 120
M
ꢀ1 and from 541 to 455 Mꢀ1, respectively, when
the concentration of HPMC E5 was increased from
0.0 to 0.3% w/v. On the other hand, the micellar
rate constant, km, did not appear to be affected by
the addition of HPMC and it remained within the
Table 4. Summary of the Parameter Estimates Obtained From the Analysis of the Rate Constant Versus
Surfactant Concentration Data in the System With HPMC E15
Concentration of HPMC E15, % w/vb
Pseudophase
Parameters
0% HPMC
0.02% HPMC
0.1% HPMC
0.3% HPMC
KIBA (Mꢀ1
)
174 (14)
541 (35)
166 (14)
537 (37)
148 (6)
492 (16)
120 (12)
451 (34)
KNA (Mꢀ1
km(M/min)
)
5.7 ꢃ 10ꢀ4 (0.2 ꢃ 10ꢀ4
)
)
5.6 ꢃ 10ꢀ4 (0.0 ꢃ 10ꢀ4
)
)
5.5 ꢃ 10ꢀ4 (0.1 ꢃ 10ꢀ4
)
)
6.0 ꢃ 10ꢀ4 (0.2 ꢃ 10ꢀ4
)
)
k
m (minꢀ1 a
)
1.4 ꢃ 10ꢀ4
1.4 ꢃ 10ꢀ4
1.4 ꢃ 10ꢀ4
1.5 ꢃ 10ꢀ4
kb (minꢀ1
Copt (M)c
R2
)
6.2 ꢃ 10ꢀ4 (0.1 ꢃ 10ꢀ4
3.2 ꢃ 10ꢀ3
7.0 ꢃ 10ꢀ4 (0.0 ꢃ 10ꢀ4
3.3 ꢃ 10ꢀ3
6.0 ꢃ 10ꢀ4 (0.0 ꢃ 10ꢀ4
3.7 ꢃ 10ꢀ3
7.0 ꢃ 10ꢀ4 (0.0 ꢃ 10ꢀ4
4.3 ꢃ 10ꢀ3
0.993
0.990
0.997
0.987
aAssuming a molar volume for CTAB in the micellar form of 0.25 Mꢀ1
bThe number between brackets is the standard error.
cCTAB concentration at the highest rate constant.
.
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Table 5. Summary of the Parameter Estimates Obtained From the Analysis of the Rate Constant Versus
Surfactant Concentration Data in the System With HPMC E50
Concentration of HPMC E50, % w/vb
Pseudophase
Parameters
0% HPMC
0.02% HPMC
0.1% HPMC
0.3% HPMC
KIBA (Mꢀ1
)
174 (14)
541 (35)
165 (15)
544 (40)
144 (12)
487 (29)
126 (10)
470 (27)
KNA (Mꢀ1
km(M/min)
km (minꢀ1 a
kb (minꢀ1
)
5.7 ꢃ 10ꢀ4 (0.2 ꢃ 10ꢀ4
)
)
5.7 ꢃ 10ꢀ4 (0.4 ꢃ 10ꢀ4
)
)
5.7 ꢃ 10ꢀ4 (0.4 ꢃ 10ꢀ4
)
)
5.5 ꢃ 10ꢀ4 (0.1 ꢃ 10ꢀ4
)
)
)
1.4 ꢃ 10ꢀ4
1.4 ꢃ 10ꢀ4
1.4 ꢃ 10ꢀ4
1.4 ꢃ 10ꢀ4
)
6.2 ꢃ 10ꢀ4 (0.1 ꢃ 10ꢀ4
3.2 ꢃ 10ꢀ3
7.0 ꢃ 10ꢀ4 (0.0 ꢃ 10ꢀ4
3.3 ꢃ 10ꢀ3
6.7 ꢃ 10ꢀ4 (0.4 ꢃ 10ꢀ4
3.7 ꢃ 10ꢀ3
7.1 ꢃ 10ꢀ4 (0.1 ꢃ 10ꢀ4
4.1 ꢃ 10ꢀ3
C
opt (M)c
R2
0.993
0.988
0.990
0.992
aAssuming a molar volume for CTAB in the micellar form of 0.25 Mꢀ1
bThe number between brackets is the standard error.
cCTAB concentration at the highest rate constant.
.
the same concentration of HPMC E15 or HPMC
E50 provides higher viscosities than HPMC E5.
indicated by the decrease in the CMC. Moreover,
the addition of electrolytes to a micellar solution
will cause competition between ionic species
having the same charge, including reactive coun-
terions in the Stern layer.17 Thus, nonreactive
counterions can interfere with the binding of
reactive counterions causing rate inhibition.13,18
The calculated binding constants for the sub-
strates from the pseudophase model supported
this explanation. Sodium sulfate reduced the IBA
binding constant from 174 to 98 Mꢀ1. Conversely,
the a-NA binding constant increased from 541 to
763 Mꢀ1. The decrease in the IBA binding constant
could be explained as follows. The anionic form of
IBA (IBAꢀ) had to compete with SO24ꢀ to bind to the
polar head groups of the CTAB molecules. Since
SO24ꢀ carries a higher charge than IBAꢀ, it
competes very effectively. SO24ꢀ also compres-
sed the electrical double layer surrounding the
positively-charged head groups of CTAB and
increased the aggregation number. The higher
aggregation number should result in a greater
volume in the palisade region of the micelle. This
would likely increase the available region for
solubilization of a-NA, a neutral substrate.
Influence of SO24ꢀ Ions on a-NA Hydrolysis Kinetics
in Micellar Systems
The plots of observed rate constant versus
micellar CTAB concentrations are presented in
Figure 5. Nonlinear curve fitting was employed to
calculate the pseudophase parameters reported in
Table 6.
The addition of sodium sulfate caused a
decrease in the observed rate constant at any
CTAB concentration. The effect was not due to a
change in reaction rate constant in the bulk phase,
kb, or the micellar rate constant, km. Sodium
sulfate changed CTAB micelle formation, as
For one and one-half half-lives, the a-NA
degradation (in the presence of IBA) was found to
follow pseudo-first-order kinetics. Thus, a change
in the amount of a-NA in the reaction region
should not affect the reaction rate constant. On the
other hand, the observed rate constant was
dependent on the amount of IBA in the reaction
region. The smaller the amount of IBA in the
reaction region, the lower was the observed rate
constant. The ionic strength of the system with
sodium sulfate was 0.3 M, whereas that of the
phosphate buffer solution alone was 0.17 M.
Figure 5. Observed rate constants for a-NA hydro-
lysis with CTAB-sodium sulfate and CTAB-HPMC gel at
308C: (*) buffer, (þ) sodium sulfate in buffer, and (*)
5% HPMC E50.
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HYDROLYSIS KINETICS OF a-NAPHTHYL ACETATE IN MICELLAR SYSTEMS
457
Table 6. Summary of the Parameter Estimates Obtained From the Analysis of the Rate Constant Versus
Surfactant Concentration Data in Sodium Sulfate and CTAB-HPMC Gel Systems
Systemb
Pseudophase
Parameters
Sodium Sulfate in
Phosphate Buffer
CTAB-HPMC (5% w/v HPMC
E50) Gel in Phosphate Buffer
Phosphate Buffer
KIBA (Mꢀ1
KNA (Mꢀ1
km(M/min)
)
)
174 (14)
541 (35) .
98 (9)
763 (48)
84 (17)
448 (56)
5.7 ꢃ 10ꢀ4 (0.2 ꢃ 10ꢀ4
)
)
5.5 ꢃ 10ꢀ4 (0.1 ꢃ 10ꢀ4
)
)
3.8 ꢃ 10ꢀ4 (0.2 ꢃ 10ꢀ4
)
)
k
m (minꢀ1 a
)
1.4 ꢃ 10ꢀ4
1.4 ꢃ 10ꢀ4
9.5 ꢃ 10ꢀ5
kb (minꢀ1
Copt (M)c
R2
)
6.2 ꢃ 10ꢀ4 (0.1 ꢃ 10ꢀ4
3.2 ꢃ 10ꢀ3
6.1 ꢃ 10ꢀ4 (0.0 ꢃ 10ꢀ4
3.6 ꢃ 10ꢀ3
7.2 ꢃ 10ꢀ4 (0.2 ꢃ 10ꢀ4
5.0 ꢃ 10ꢀ3
0.993
0.990
0.971
aAssuming a molar volume for CTAB in the micellar form of 0.25 Mꢀ1
bThe number between brackets is the standard error.
cCTAB concentration at the highest rate constant.
.
Changes in ionic strength result in changes in the
activity coefficients of the substrates and of the
substrates in the transition state (gNA, gIBA, and
the micellar pseudophase, the high concentration of
HPMC E50 diminished the concentration advan-
tage, as evidenced by the decreased substrate
binding constants and the lowered reaction rate
constant, km. Moreover, the decrease in km implied
that the high concentration of the polymer might
have impeded the bimolecular reaction, possibly
through environmental effects. This could occur
through orientation effects on the substrates.
g
NA–IBA). However, this reaction involves a neutral
species and an ion, which means that the primary
salt effect on the rate constant is not important.
gNA is approximately unity and gIBA and gNA–IBA
decrease to approximately the same extent. Addi-
tionally, there were no significant differences
between the observed rate constants with and
without sodium sulfate when no CTAB was added.
Changes in ionic strength also caused the pKa of
IBA to change (secondary salt effect). Using the
Davies equation, the difference in the apparent
pKa of IBA was approximately 0.035 pH units
lower, which is small. Therefore, sodium sulfate
retarded the catalytic ability of CTAB by decreas-
ing the IBA binding constant without, apparently,
changing the reaction environment.
CONCLUSION
The formation of CTAB micelles was facilitated by
the addition of electrolytes. According to the
surface tension experiments, the surface tension
became lower when HPMC was added to the
surfactant solutions. The CAC was found to be
higher than the CMC when surface tension was
measured. The solubilization method did not
show a difference between the CAC and the
CMC. The a-NA degradation with IBA present
was accelerated in the micellar environment due
to the concentration effect. When either HPMC or
sodium sulfate was introduced into the solutions
containing micellar CTAB, the observed reaction
rate constant decreased. In both cases, this was
due to a decrease in the binding constants of the
reactants to the micelles. In the first case, the
addition of sodium sulfate decreased IBA binding.
In the second case, HPMC decreased both a-NA
and IBA binding.
a-NA Hydrolysis Kinetics in a
CTAB-HPMC Gel System
The observed rate constant profile in the CTAB-
HPMC gel system was compared to that of the
buffer samples (without polymer), as presented in
Figure 5. The bimolecular reaction equation for
the pseudophase model was fit to the rate
constant data and the parameters are reported
in Table 6.
HPMC E50 was selected for preparing gel-like
samples. Since the difference in the rate constants
between the HPMC gel system without CTAB and
the buffer solution without CTAB was not large,
gel conditions were not likely to disturb the
reaction in the bulk phase. However, gel conditions
did seem to disturb the micellar pseudophase. In
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