Hydrolysis of carboxylate and phosphate esters using monopyridinium oximes in cationic micellar media

Article abstract of DOI:10.1002/kin.20590

The reactions of p-nitrophenyl acetate (PNPA) with a series of monopyridinium oximes, viz. 2-PAM (2-hydroxyiminomethyl-1-methylpyridinium iodide), 3-PAM (3-hydroxyiminomethyl-1-methylpyridinium iodide), and 4-PAM (4-hydroxyiminomethyl-1-methylpyridinium iodide) have been studied in the presence of cationic surfactants of same hydrophobic chain length (C ₁₆) within the concentration range of 0.5-6.0 mM at pH 8.0 under the pseudo-first-order condition. The observed rate constant (k_obs) increases with increasing surfactant concentration culminating into a maximum, and this has been analyzed in detail following the concepts of micellar catalysis. The structure-activity relationship of the investigated oximes has been discussed, and 2-PAM was found to be the most reactive among all the three investigated oximes for the cleavage of PNPA. Esterolytic decomposition of p-nitrophenyldiphenyl phosphate with oximate ions (-CH=NO^-) was followed in cetyltrimethylammonium bromide micelles at pH 9.0, and 4-PAM was the most reactive oxime for the micellar hydrolysis of phosphate ester. The apparent acid dissociation constants (pK_a) of the investigated oximes have been determined spectrophotometrically.

Full text of DOI:10.1002/kin.20590

Hydrolysis of Carboxylate
and Phosphate Esters Using
Monopyridinium Oximes in
Cationic Micellar Media
NAMRATA SINGH,1 KALLOL K. GHOSH,1 JAN MAREK,2 KAMIL KUCA2
1School of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur, 492 010, India
2Faculty of Military Health Sciences, University of Defence, Trebesska 1575, Hradec Kralove, Czech Republic
Received 7 February 2011; revised 19 May 2011, 6 June 2011; accepted 15 June 2011
DOI 10.1002/kin.20590
Published online 16 August 2011 in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: The reactions of p-nitrophenyl acetate (PNPA) with a series of monopy-
ridinium oximes, viz. 2-PAM (2-hydroxyiminomethyl-1-methylpyridinium iodide), 3-PAM
(3-hydroxyiminomethyl-1-methylpyridinium iodide), and 4-PAM (4-hydroxyiminomethyl-1-
methylpyridinium iodide) have been studied in the presence of cationic surfactants of same
hydrophobic chain length (C16) within the concentration range of 0.5–6.0 mM at pH 8.0 under
the pseudo-first-order condition. The observed rate constant (kobs) increases with increasing
surfactant concentration culminating into a maximum, and this has been analyzed in detail
following the concepts of micellar catalysis. The structure–activity relationship of the inves-
tigated oximes has been discussed, and 2-PAM was found to be the most reactive among
all the three investigated oximes for the cleavage of PNPA. Esterolytic decomposition of p-
nitrophenyldiphenyl phosphate with oximate ions ( CH NO−) was followed in cetyltrimethy-
lammonium bromide micelles at pH 9.0, and 4-PAM was the most reactive oxime for the
micellar hydrolysis of phosphate ester. The apparent acid dissociation constants (pKa) of the
investigated oximes have been determined spectrophotometrically. ꢀ 2011 Wiley Periodicals,
C
Inc. Int J Chem Kinet 43: 569–578, 2011
struction of OP toxicants are available [3,4], none of
them is suitable to all situations or classes of com-
pounds, thus spurring research into alternative meth-
ods for their destruction. The inhibitory effect of these
OP compounds is based on phosphorylation of a ser-
ine hydroxyl group located at the active site of acetyl-
cholinesterase (AChE), an enzyme that plays an impor-
tant role in modulating cholinergic neurotransmission
[5,6]. Reactivation of inhibited AChE by nucleophiles
such as oximes is an efficient way to attenuate toxic-
ity; it plays a key role in the treatment of OP poison-
ing and has been a subject of extensive investigation
for decades to find more effective reactivators for the
INTRODUCTION
Organophosphorous (OP) compounds are widely used
as pesticides, insecticides, and chemical warfare agents
[1,2] and have a widespread environmental concern.
Although some very promising methods for the de-
Correspondence to: Kallol K. Ghosh; e-mail: kallolkghosh@
yahoo.com.
Contract grant sponsor: Pt. Ravishankar Shukla University,
Raipur, India.
Contract grant sponsor: Czech Ministry of Defence.
Contract grant number: OVUOFVZ200803.
2011 Wiley Periodicals, Inc.
c
ꢀ

570
SINGH ET AL.
O
C
O
Surfactant
–O
NO2
+ Nu–
+
Nu
R
C
O
NO2
R
R = CH3 p-nitrophenyl acetate (PNPA)
O
O
O
O
O
O
P
Surfactant
–O
NO2
Nu–
+
P
+
NO2
O
Nu
p-Nitrophenyldiphenyl phosphate (PNPDPP)
Scheme 1
treatment of OP pesticide and chemical warfare agent
toxicity. Considerable attention has been directed to-
ward detection and decomposition of organophos-
phates and other toxicants. Most of the cases of poison-
ing can be prevented by better administrative control,
restricted access to OP pesticides, effective measures
of personal protection, and education of OP pesticide
applicators and medical personnel. One strategy to im-
prove the efficacy of reactivators is to characterize their
structural features that accelerate displacement of OP-
bound moiety and introduce them into newly designed
oximes [7].
Oximes (especially oximate anions) are used as po-
tential reactivators of OP-inhibited AChE due to their
unique α-effect nucleophilic reactivity. They are an
important group of drugs used as antidotes in the
treatment of intoxications with highly toxic OP com-
pounds such as pesticides (paraoxon, parathion, chlor-
pyrifos, etc.) and nerve agents (sarin, soman, tabun,
etc.) [8–11]. Scientists worldwide are engaged in de-
signing and developing some potential reactivators of
toxic OP compounds. Kuca et al. [12–15] have made
incessant effort in this field. They have synthesized
many novel and powerful universal reactivators and
performed their reactivation potential in vivo and in
vitro studies. In spite of such efforts, a single reacti-
vator that may be universally potent against all kinds
of nerve agents and OPs is still lacking. For the past
few years, our laboratory has aimed to study and de-
velop some novel promising decontamination agents,
which can detoxify nerve agents. In our recent papers,
various oxime-based compounds were tested with very
promising results [16–18].
ence of three monopyridinium oximes, viz. 2-
hydroxyiminomethyl-1-methylpyridinium iodide (2-
PAM), 3-hydroxyiminomethyl-1-methylpyridinium
iodide (3-PAM), and 4-hydroxyiminomethyl-1-
methylpyridinium iodide (4-PAM) (Scheme 2). The
cleaving efficacy of all three oximes is compared and
discussed. Since it is well known that reactivity of nu-
cleophile increases in the presence of surfactants [19],
the entire kinetic studies are performed in cationic
micellar media with a common hydrophobic chain
length, i.e., cetyl (C16). The use of novel surfactants
in assisting a variety of organic reactions is highly
promising for basic and applied research [20–22].
The application of quantitative data to micellar-
mediated reactions and the implications of different
modes describing such reactions are also topic of con-
tinuing research. The majority of fundamental studies
2
on micellar SN reactions have been conducted in the
presence of cationic micelles of quaternary ammonium
surfactants such as those with trialkylammonium and
quinolinium bromides and chlorides [23,24]. Scheme 1
shows the reaction for the nucleophlic attack of oxi-
mate ions on PNPA and PNPDPP in the presence of sur-
factants. The chemical structures of monopyridinium
oximes and cationic surfactants used in the present in-
vestigation are shown in Scheme 2.
EXPERIMENTAL
Materials
All the three pyridinium oximes (2-PAM, 3-PAM,
and 4-PAM) were prepared in the laboratory of Dr.
Kamil Kuca. PNPA was procured from Fluka (Buchs,
Switzerland), and PNPDPP was prepared in the Ver-
tox Laboratory of the Defence Research Development
In the present investigation, micellar-mediated
hydrolysis of p-nitrophenyl acetate (PNPA)
and
p-nitrophenyldiphenyl
phosphate
(PN-
PDPP) (Scheme 1) was studied in the pres-
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HYDROLYSIS OF CARBOXYLATE AND PHOSPHATE ESTER USING MONOPYRIDINIUM OXIMES
571
OH
N
N
HO
N
OH
N+
N+
I–
CH3
I–
CH3
N+
I–
CH3
2-Hydroxyiminomethyl-
1-methylpyridinium iodide
(2-PAM )
3-Hydroxyiminomethyl-
1-methylpyridinium iodide
(3-PAM )
4-Hydroxyiminomethyl-
1-methylpyridinium iodide
(4-PAM )
Br-
C16H33
Br-
P+
P+
C16H33
Cetyltriphenylphosphonium bromide
(CTPB)
Cetyltributylphosphonium bromide
(CTBPB)
Br-
N
Br-
N+
C16H33
C16H33
Cetylpyridinium bromide
(CPB)
Cetyltrimethylammonium bromide
(CTAB )
N+
Br-
N+
Br-
C16H33
C16H33
HO
HO
Cetyldimethylethanolammonium bromide Cetyldiethylethanolammonium bromide
(CDMEAB)
(CDEEAB)
Scheme 2
Establishment (Gwalior, India). Cetyltriphenylphos-
phonium bromide (CTPB), cetyltributylphosphonium
bromide (CTBPB), cetyldiethylethanolammonium
bromide (CDEEAB), and cetyldimethylethanolam-
monium bromide (CDMEAB) were obtained from
the laboratory of Prof. R. M. Palepu (St. Fran-
cis University, Antigonish, Canada). Surfactants such
as cetyltrimethylammonium bromide (CTAB) and
cetylpyridinium bromide (CPB) were purchased from
Sigma (St. Louis, MO). All the solutions were prepared
in triple-distilled water.
General Synthetic Procedure of
Monopyridinium Oximes
In a typical synthetic procedure, pyridine aldoxime
was dissolved in acetone and to this methyl iodide
was added. The mixture was refluxed for 4 h. The
crystals were filtered and left to dry. The crude prod-
uct was dissolved in a small amount of distilled wa-
ter, and acetone was added to form the crystals. The
solid phase was filtered and dried to obtain a pure
compound.
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572
SINGH ET AL.
Kinetic Measurements
The reactions were studied spectrophotometrically
with a Varian Cary 50 spectrophotometer and Systron-
ics type-118 UV–vis spectrophotometer by monitoring
the appearance of the leaving p-nitrophenoxide ion at
400 nm at 27 0.2◦C. All the kinetic experiments were
performed at an ionic strength of 0.1 M KCl. Phosphate
buffer was employed to control the pH of the media.
All the pH measurements were obtained using a Sys-
tronics pH meter (type 362). All reactions were con-
ducted under pseudo-first-order conditions, i.e., large
excess of oximate anions over the substrate (1:10). For
all the kinetic runs, the absorbance/time result fits very
well with the first-order rate equation. The pseudo-first-
order rate constants (kobs) were determined from the
Figure 1 Absorbance spectra of 4-PAM at different pH
values. [4-PAM] = 5.3 × 10−5 M at 27◦C. Run and pH:
(1) 7.0, (2) 7.3, (3) 7.5, (4) 7.7, (5) 7.9, (6) 8.1, (7) 8.3,
(8) 8.5, (9) 8.7, (10) 8.9, (11) 9.2, (12) 9.4, (13) 9.7. [Color
figure can be viewed in the online issue, which is available
at wileyonlinelibrary.com.]
plots of log(A0 − At/A − At) versus time with A0,
∞
At, and A being the absorbance values at zero, time,
∞
and infinite time, respectively. The substrate (PNPA)
concentration was kept the same for all the reactions.
The kinetic study was performed at various concen-
trations of surfactant so as to investigate the effect of
surfactant on the cleaving efficiency of oximes.
as a blank. The absorption spectrum was recorded us-
ing a Varian Cary 50 UV–vis spectrophotometer in the
range of 200–400 nm and at different pH values. The
average values of 10 measurements were considered
as the pKa of the compound with respect to oximino
functionality. The spectrophotometric determination of
pKa of oxime 4-PAM is shown in Fig. 1 at the temper-
ature 27◦C. The calculations of pKa were made around
half neutralization using the following equation:
Electrical Conductivity Measurements
The critical micelle concentration (cmc) of the cationic
surfactants was determined by conductance measure-
ments using a Systronics direct reading digital con-
ductivity meter (types 304 and 306). The conductivity
cell was calibrated with KCl solutions in an appro-
priate concentration range. A concentrated surfactant
solution (∼10–20 times the cmc) was progressively
added to a 10-mL medium in a thermostat container
(having a temperature accuracy of 0.01◦C) using a
micropipette. After thorough mixing, the specific con-
ductance was measured. The accuracy of conductivity
measurements was within 0.5%.
Absψ − AbsHox
pKa = pHexp − log
(1)
Absox − Absψ
where AbsHox is the absorbance of unionized form of
compound, Absψ is the absorbance of partially ionized
form of compound, and Absox is the absorbance of
completely ionized form of compound. The absorption
spectrum of 4-PAM is represented in Fig. 1 showing
two characteristic maxima obtained in UV in the region
200–400 nm. The first absorption maxima for 4-PAM
around 341 nm was as a result of absorption of the
nondissociated oxime group (Fig. 1, peak 1), and all
the above peaks were as a result of absorption of the
dissociated oxime group. The sharp isobestic point at
310–312 nm indicates an acid–base equilibrium.
Determination of Acid Dissociation
Constant (pKa)
The acid dissociation constant (pKa) values of all
the monopyridinium oximes were determined spec-
trophotometrically by using the method of Albert and
Sergeant [25]. The method depends on the direct de-
termination of the ratio of molecular species (proto-
nated) to dissociated (deprotonated) species in buffer
solutions. An aliquot (3 mL) of a stock solution (5 ×
10−4 M) of oxime in triple-distilled water was diluted
with a 25-mL phosphate buffer solution. Different pH
values ranging from 6.12 to 9.92 were selected to deter-
mine the pKa values of oximes. The pH of the solution
was measured using Systronics (type-362) pH meter,
and the spectrum was recorded using a buffer solution
RESULTS AND DISCUSSION
First-order rate constants for the nucleophilic substi-
tution reaction of PNPA with monopyridinium oximes
(2-PAM, 3-PAM, and 4-PAM) were determined under
pseudo-first-order condition, i.e., nucleophiles were
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HYDROLYSIS OF CARBOXYLATE AND PHOSPHATE ESTER USING MONOPYRIDINIUM OXIMES
573
in large excess over the substrates in the presence
and absence of surfactants with the same hydropho-
bic chain length (C16) and varying hydrophilic head
groups. Cationic micelles bring reactants closer by
hydrophobically binding of substrate and coulombi-
cally attracting negatively charged nucleophile. Max-
imum rate constants were observed with surfactants
having phosphonium head groups. Since the deproto-
nated oxime was involved in the nucleophilic attack
during the hydrolytic reactions, it is therefore essential
that pKa values be taken into account while studying
their reactivity.
Figure 2 Rate surfactant profile for the reaction of PNPA
with 2-PAM, 3-PAM, and 4-PAM in CTBPB micellar solu-
tions at 27◦C and pH 8.0.
Structure and Properties of Oximes
Figure 2 shows the comparison between the reac-
tivity of different oximes in CTBPB micelles. It
can be inferred from the figure that 2-PAM is far
more reactive than 3-PAM and 4-PAM. Similar trends
can be observed for other surfactants (Tables I–III).
There are some significant structural factors regarding
the activity of monopyridinium oximes, which influ-
ence their affinity toward inhibited AChE and subse-
quent reactivity. The presence of quaternary nitrogen in
the molecule, position of the oxime group in the pyri-
dinium ring, and the number of pyridinium rings in
the structure of the reactivator basically determine the
reactivation potency of the pyridinium-based oximes.
Structure–activity relationships for oxime efficacy are
poorly understood because oxime reactivation has a
complex dependency on the nucleophilicity and orien-
tation of the oxime.
The pyridinium oximes are claimed to react so ef-
fectively with the carboxylate and phosphate esters be-
cause of their relatively low pKa (in the physiological
pH range) that ensures, in neutral aqueous solutions, a
substantial dissociation to oximate anions, which are
powerful α-nucleophiles. The presence of positively
Table I Kinetic Rate Data for the Reaction of PNPA with 2-PAM in the Presence of Different Surfactants
kobs 103 (s−1
)
[Surfactant] (mM)
CTAB
CTPB
CPB
CTBPB
CDMEAB
CDEEAB
0.0
0.5
1.0
3.0
6.0
4.16
–
6.88
6.22
5.20
4.16
5.60
6.78
6.65
4.56
4.16
5.66
6.91
6.01
–
4.16
6.02
8.05
6.41
–
4.16
5.20
7.76
4.18
–
4.16
5.15
2.53
1.87
Experimental conditions: Temperature = 27◦C; pH 8.0; [PNPA] = 0.5 × 10−4 M; [2-PAM] = 0.5 × 10−3 M; ionic strength, μ =
0.1 M KCl.
Table II Kinetic Rate Data for the Reaction of PNPA with 3-PAM in the Presence of Different Surfactants
kobs 103(s−1
)
[Surfactant] (mM)
CTAB
CTPB
CPB
CTBPB
CDMEAB
CDEEAB
0.0
0.5
1.0
3.0
6.0
1.80
–
2.16
1.65
–
1.80
2.50
2.91
2.46
1.96
1.80
2.48
2.63
3.58
3.23
1.80
2.20
2.38
1.50
–
1.80
4.00
4.50
3.50
–
1.80
3.61
4.24
3.70
–
Experimental conditions: Temperature = 27◦C; pH 8.0; [PNPA] = 0.5 × 10−4 M; [3-PAM] = 0.5 × 10−3 M; ionic strength, μ =
0.1 M KCl.
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574
SINGH ET AL.
Table III Kinetic Rate Data for the Reaction of PNPA with 4-PAM in the Presence of Different Surfactants
kobs 103 (s−1
)
[Surfactant] (mM)
CTAB
CTPB
CPB
CTBPB
CDMEAB
CDEEAB
0.0
0.5
1.0
3.0
6.0
3.50
–
4.33
4.01
–
3.50
5.08
5.11
5.01
3.96
3.50
4.30
4.83
4.20
–
3.50
5.86
7.48
4.96
–
3.50
3.80
3.73
2.61
–
3.50
4.40
5.49
4.35
–
Experimental conditions: Temperature = 27◦C, pH 8.0, [PNPA] = 0.5 × 10−4 M, [4-PAM] = 0.5 × 10−3 M, ionic strength, μ =
0.1 M KCl.
CH
NOH
NO–
CH
pK = 7.91
N+
N+
I–
H+
I–
CH3
CH3
Active species
2-PAM
Scheme 3
charged quaternary nitrogen in the pyridinium ring sub-
stantially decreases the pKa value of the oxime. The
electron-withdrawing effect of quaternary nitrogen in
the pyridinium oximes increases the acidity of the hy-
droxyimino group, which is relatively low in nonsub-
stituted aromatic or aliphatic oximes (pKa ≈ 12–13).
The increased acidity of pyridinium aldoximes and ke-
toximes (pKa ≈ 8–10) provides a sufficient concentra-
tion of the nucleophilic oximate anion even in neutral
solutions.
The oxime group ( CH NOH) dissociates and
forms oximate anion ( CH NO), which now acts
as an α-nucleophile and cleaves the bond at the car-
bon center. Furthermore, the position of the oxime
group is one of the most important structural factors
responsible for the activity of oximes. 2-PAM is a
well-known antidote for the reactivation of inhibited
AChE in organophosphate poisoning [26,27]. The po-
sition of the oxime group can affect the dissociation
constant lowering the pKa. 2-PAM is the most reac-
tive among all the oximes (Fig. 2) due to the pres-
ence of the oxime group at second position, where
as 3-PAM is the least reactive oxime for the hydrol-
ysis of PNPA. This can be accounted for by the fact
that the acid dissociation constant (pKa) of 2-PAM is
less than the oximes substituted at 3- and 4-positions.
(The pKa values of 2-PAM, 3-PAM, and 4-PAM were
calculated as 7.91, 9.53, and 8.36, respectively.) Dis-
sociation of 2-PAM into active species is depicted in
Scheme 3.
To study the effect of investigated oximes on the
hydrolysis of phosphate ester, first-order rate constants
for the reaction of PNPDPP with 2-PAM, 3-PAM, and
4-PAM in CTAB at pH 9.0 were determined. The re-
sults are summarized in Table IV. The same trend was
not obtained when the substrate was changed. For the
hydrolysis of PNPDPP, 4-PAM was found to be the
most reactive and the reactivity order of oximes can be
presented as 4-PAM > 3-PAM > 2-PAM. The reactiv-
ity order of oximes may be explained on the basis of
steric hindrance for the cleavage of bond at phospho-
rus center. 4-PAM possesses the least steric hindrance
and for this reason it is most reactive for the hydrol-
ysis of PNPDPP. However, the position of the oxime
Table IV Kinetic Rate Data for the Reaction of PNPDPP
with 2-PAM, 3-PAM, and 4-PAM in the Presence of CTAB
kobs 103 (s−1
)
[CTAB] (mM)
2-PAM
3-PAM
4-PAM
0.0
0.5
1.0
3.0
0.40
0.53
0.43
0.40
0.48
0.56
0.53
0.50
0.43
0.76
0.65
0.60
Experimental conditions: Temperature = 27◦C; pH 9.0; [PN-
PDPP] = 0.5 × 10−4 M; [PAM] = 0.5 × 10−3 M; ionic strength,
μ = 0.1 M KCl.
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HYDROLYSIS OF CARBOXYLATE AND PHOSPHATE ESTER USING MONOPYRIDINIUM OXIMES
575
was observed that first-order rate constant increases
sharply with increasing the concentration of the sur-
factant in the reaction medium, reaches a maximum,
and then decreases smoothly upon further addition of
the surfactant in the presence of nucleophiles for most
of the kinetic runs. The rate–surfactant concentration
profiles obtained with surfactants are characteristic of
the micelle-catalyzed reaction.
However, in a few cases, this trend was not found
and a rate maximum was observed even below the ex-
pected cmc in water. The rate constant increases with
an increase in the [surfactant] below the cmc, and it
has been already established [29–31] that at the con-
centrations below the cmc hydrophobic substrates in-
duce the formation of submicellar aggregates where
the reaction takes place. One consequence of such ag-
gregation of cationic surfactants is the generally ob-
served rate acceleration of nucleophilic processes in
this region. Savelli et al. also encountered similar rate
maxima below the cmc of surfactant for the hydroly-
sis of methylnaphthalene-2-sulfonate, and they termed
it as substrate-induced premicellization [32]. In a few
of the cases, especially for the esterolytic cleavage of
PNPDPP at the fixed concentration of CH NO− ions
of 2-PAM, 3-PAM, and 4-PAM, the rate maximum was
achieved even before the cmc in water of the CTAB.
The variation of rate constants below the cmc is diffi-
cult to quantify due to reactant-induced micellization
and the interaction with micellized surfactants. The
maxima below the cmc in water can be attributed to
the highly hydrophobic character of PNPDPP. Rate
maxima below the cmc for the degradation of PNPA
were observed in two systems: PNPA-2-PAM at 0.5
mM of CDEEAB (Table I) and PNPA-4-PAM at 0.5
mM of CDMEAB (Table III). This may be accounted
for on the basis of kinetic cmc, i.e., deviation in cmc
of the surfactant from aqueous medium to the reac-
tion medium. To support this conclusion, cmc of the
investigated surfactants was also determined conducto-
metrically in a buffer medium of pH 8.0 in the presence
of nucleophile, [2-PAM] = 1 × 10−3 M. As depicted
in Table V, a reduction in cmc values was observed
for all the cationic surfactants and thus the formation
of micelles or premicellar aggregates in the reaction
medium can be assumed [33]. Also, it has been doc-
umented that with a rise in pH, cmc of surfactants
generally decreases [34,35]. However, it is likely that
the extent of attack of oximate ions at the carbon cen-
ter (C O) is influenced by a number of factors apart
from lipophilicity, including the nucleophilicity of the
α-effect nucleophile, structure of the surfactant, and
polarity of the medium [36]. Cationic micelles speed
up the reaction providing a reaction environment that
is less polar than water.
Figure 3 Rate surfactant profile for the reaction of PNPA
with 4-PAM in various concentrations of different cationic
surfactants at 27◦C and pH 8.0.
group and the ability to reactivate to some extent also
depends on the type of the substrate used [28].
Effect of Cationic Surfactants
Table I shows the kinetic rate data for the hydrolysis of
PNPA with 2-PAM in the presence of different cationic
surfactants at pH 8.0 and temperature 27◦C. It is clearly
depicted that as the surfactant concentration increases,
the observed rate constant first increases and reaches
maximum and then decreases at a higher concentration
of surfactants. Similar trends are observed for the ki-
netic study with 3-PAM and 4-PAM, as presented in
Tables II and III. The efficacy of 4-PAM toward the
hydrolysis of ester in cationic micellar media is also
depicted in Fig. 3, which shows the observed rate con-
stants for the cleavage of PNPA with 4-PAM in the
presence of surfactants. Micelles are known to amplify
the kinetic benefits by bringing together a small vol-
ume of the reactant species, and this is particularly
relevant when they are marked lipophilic and hence
sparingly soluble in a bulk solution. In the present in-
vestigation, cationic micelles are used because they
are known to lower the pKa values of acidic func-
tions (oximate nucleophiles). Furthermore, hexadecyl
chain length provides a lower critical micelle concen-
tration to the surfactants and thus a kinetic study be-
comes easier under such conditions. The kinetic runs
were performed at different surfactant concentrations
within the range of 0.5–6.0 mM, i.e., well above and
below the cmc of the surfactants used, and the rate
enhancement of ester cleavage in micelles was com-
pared with that of only buffer systems (the absence
of surfactant). For the reaction of 2-PAM with PNPA
at 1.0 mM of CTBPB, the rate acceleration was 1.93
folds with respect to only buffer system (Table I). It
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SINGH ET AL.
N+
Br-
O
CH3
N
O2N
O
C
O-
CH
N+
N+
I–
CH3
Br–
Scheme 4 Orientation of PNPA in CTAB for nucleophilic attack at C [38].
head groups of the surfactants at the micellar surface
and the increase in the concentration of the nucleophilic
anions. This enhanced concentration of the reactants
accounts for the higher rate of reaction (Scheme 4).
Subsequent addition of the cationicsurfactant after cmc
caused a gradual decrease in the reaction rate, and this
may be due to the decrease in the catalyst concentration
in the micellar pseudophase. The excess of unreactive
counterions competes with oximate ions for available
sites in the Stern layer. Decrease in the observed reac-
tion rates after maxima is due to the dilution of cata-
lysts in the Stern layer of micelles [39]. The rate en-
hancement in the phosponium- and pyridinium-based
cationic surfactants is greater than in alkyl ammonium
head groups due to their bulky head group [22,40].
The effect would correspond to a general decrease in
the polarity of the head group region that would there-
fore increase the rate of the nucleophilic substitution
[16,41]. Another possible explanation is the steric ef-
fects by the phenyl rings in the head group region that
would activate the bound substrate toward substitution
[33]. The rate enhancement for the hydrolytic reactions
in cationic micelles may also be explained on the basis
of reduction in the acid dissociation constants (pKa) of
monopyridinium oximes due to the micellar environ-
ment. It has been well proved that cationic micelles are
very often responsible for lowering of the pKa values
of different nucleophilic species and thus may be used
as efficient decontaminating systems for toxic esters
[42–44].
Kinetic Rate Constants above the cmc
According to the previous discussion, rate maxima for
PNPA hydrolysis with oximate ions in micelles were
obtained above the cmc of surfactants and this was due
to the micelle-catalyzed reactions. Initially, an increase
in the surfactant concentration generates more cationic
micelles and an increase in the reaction rate occurs.
With increasing micelles in the solution, a stage ap-
pears where all the substrates are almost entrapped in
the micellar phase. Further addition of surfactant in-
creases the number of micelles to such an extent that
the oximate anions are bound in the “Stern layer”; thus
the rate of reaction falls since the substrate in one mi-
celle cannot react with nucleophile in another [37]. The
reactants are microcompartmentalized in the micelles
by electrostatic and hydrophobic interactions; the cat-
alytic enhancement results from both the localized con-
centration of the reactants and the physicochemical
properties of the micellar environment, which is quite
different from those of the bulk solvent.
According to Buncel et al. [38], micellar kinetics is
governed by the electrostatic attraction of the cationic
Table V Cmc of the Cationic Surfactants in Aqueous
and Buffer Medium (pH 8.0) at Temperature 27◦C
cmc (mM)
Surfactant
Aqueous
Buffera
CTAB
CTPB
CPB
CTBPB
CDMEAB
CDEEAB
0.90
0.16
0.95
0.20
0.84
0.87
0.55
0.09
0.70
0.15
0.50
0.45
CONCLUSIONS
A significant objective of the present investigation was
to study in detail the structure–activity relationship of
monopyridinium oximes and their role in hydrolysis of
model substrates of OP compounds and nerve agents in
aExperimental conditions: pH 8.0 (phosphate buffer); [2-PAM]
= 0.5 × 10−3; KCl = 0.1 M KCl; temperature = 27◦C.
International Journal of Chemical Kinetics DOI 10.1002/kin

HYDROLYSIS OF CARBOXYLATE AND PHOSPHATE ESTER USING MONOPYRIDINIUM OXIMES
577
the micellar medium. It can be concluded that the reac-
tivation potency of oxime depends not only on its struc-
ture but also on the kind of substrate used. Cationic mi-
celles showed a tremendous enhancement in the rate of
spontaneous hydrolysis of esters and assisted the rate of
reaction. The observed rate constants were found to in-
crease with increasing surfactant concentration, which
further decreases at a higher surfactant concentration,
showing the nature of micellar-catalyzed reactions. 2-
PAM was found to be the most reactive among all the
investigatedoximesfor thehydrolysis at C O, whereas
4-PAM was most effective oxime for the hydrolysis at
the P O center. Monopyridinium oximes are a par-
ticularly appealing class of α-nucleophiles to examine
since they have pKa values in the range 7–10, which
makes them ideal candidates for decontamination in
the environment, but their structural requirements still
need to be explored. Results of this investigation will
enrich our understanding about reactivators of AChE
and their action and a promising role in detoxification
purposes. Most significantly, results of this investiga-
tion are useful in developing an effective mechanism
for the degradation of chemical and biological warfare
agents under mild conditions.
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