chapter iii: nucleophilic dephosphorylation of p-nitrophenyl...
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83
CHAPTER III: NUCLEOPHILIC DEPHOSPHORYLATION
OF p-NITROPHENYL DIPHENYL PHOSPHATE IN
CATIONIC MICELLAR MEDIA#.
3.0 INTRODUCTION
The hydrolysis of phosphorous triesters has been proved as classical
reactions of fundamental importance in chemistry and biology1-12
. The widespread
use of toxic phosphates and phosphonates as insecticides, and their use as chemical
weapons, has led to the investigation of fast detoxification and decontamination
methods13
. Most of these compounds are hydrophobic phosphorous (V) esters or
phosphorylating agents. Such compounds are highly toxic to both target and non-
targeted organisms.
As chemical weapons cannot be used by raw hands due to safety and
licensing problems, a well known non-toxic and widely used simulant p-nitrophenyl
diphenyl phosphate (PNPDPP) (I) was employed in the present study.
O
O
P
O
O
NO2
(I)
Over the past years, many research groups14-32
have been used this
simulant for dephosphorylation reaction using different nucleophiles (Table 3.1).
However, there is still need to design and develop new reagents for detoxification. In
the preceding chapter, the nucleophilic substitution reactions of carboxylate ester
have been discussed. In this chapter, a study of the dependence of rate on a series of
-nucleophiles (hydroxamate ions) for the reaction of hydrolysis of PNPDPP have
been undertaken.
# Part of this chapter has been published in Langmuir, 2005, 21, 8664-8669.
84
3.1 REVIEW OF THE EARLIER WORK
Many research groups14-32
have carried out extensive studies on
phosphate ester hydrolysis over the past several years. A partial summary of the
hydrolysis / detoxification of PNPDPP using different nucleophiles are presented in
Table 3.1. A few distinguishing features of this survey are as under:
I. In view of the recognized ability of cationic surfactant micelles to accelerate the
cleavage of carboxylic acids, micellar catalyzed hydrolysis of p-nitrophenyl diphenyl
phosphate (PNPDPP) have been studied.
II. PNPDPP has become the unofficial “standard simulant” permitting comparisons
of the efficacy of many different cleavage reagents.
III. Among the many reagents, the iodosocarboxylates (iodosobenzoate and
iodosonaphthoate) and certain metallomicelles stand out as characterized by rapid
cleavage of PNPDPP and catalytic turnover55
.
IV. The oximate ions (2,3-butanedione monoximate etc.) are believed to act as -
effect super nucleophiles for the cleavage of PNPDPP in the presence of cationic
micelles56
.
V. The CTAB / ClO– system can also work efficiently as turnover catalyst to
decontaminate PNPDPP and other toxic chemical warfare agents21
.
VI. Bhattacharya et al.22-25
developed many effective nucleophiles like
monoperoxyphthalates, dialkylaminopyridine, 1-hydroxytriazoles and tetrazole derivatives
for dephosphorylation reactions.
85
Table – 3.1
Esterolytic Systems for the Cleavage of p-nitrophenyl diphenyl phosphate
PO
O
O O NO2
[CATALYST] (M) CONDITION kobs (s–1) REF.
I
C
O
O
O-
o-iodoxybenzoate
(1.0x 10–4)
1 mM CTACl
pH 8.0
6.45 x 10 –2
14
I
O
O
O-
o-iodosonaphthoate (1.0x 10–4)
5 mM CTACl
pH 8.0
0.26
15
C16H33N+Me2(CH2)2OH
(2.5 x 10-5)
0.01 M NaOH
pH 12.0
≈ 1.5
16
Cu (II) Complex of N, N, N’-trimethyl-
N’-tetradecylethylenediamine
(1.22 x 10–4)
10 mM
N-ethylmorpholine
2.02 x 10-2
17
N+
CHO
H3C
H3C
C12H25
( 8 x 10–3)
pH 9.0
2.00 x 10-2
18
Continued…
86
[CATALYST] (M)
CONDITION
kobs (s–1)
REF.
CH3CO
CH3
C NO
Butanedione monoximate
(7.5 x 10 –4 M)
pH 9-10
CTAX
0.12
19
C NO
C
H
O
CH3
anti- Pyruvaldehyde-1-oximate
[CTAOX] = 0.01 M
–
56
ClO –
Hypochlorite
pH 8.5
32°C
1.75mM CTABr
20.1 x 10–3
21
N
N
RH3C
(Dialkylamino) pyridine
O
║
R = (CH2)2CNH(CH2)3Me2N+C18H37
N,N-Dimethyl-N-octadecyl-N-[[3-[methyl(4-
pyridyl)amino]propanamido]propyl]ammonium
bromide.
pH 9.0
0.5 mM CTACl
≈ 8.5 x 10–3
22
O
HOO
COOH
Monoperoxyphthalates
(5.4x 10–4)
pH 8.5
1 mM CTACl
2.4 x 10–2
23
87
N
N
N
OH
1-Hydroxybenzotriazoles
(2.5 x 10 –5)
pH 8.2
0.01M CTAB
3.2 x 10 –3
24
N
N
N
OHOH
O
1-hydroxy-1-H-benzo[d] [1,2,3] triazole-
6-
carboxylic acid
pH 8.0
2.5 mM
Me2N
+—(CH2)m—N+–Me2
│ │
C16H33 C16H33
15.2 x 10 –3
25
NH
N
NN
H
Tetrazoles
(1.25 x 10-4 M)
pH 7.0
30.7 x 10–3
26
# The concentrations of catalysts are given in the parentheses.
88
VII. Besides these nucleophiles, many other inorganic oxygen containing
-nucleophiles (NH2OH, BrO–, HOO
–, F
– ions) covering the pKa range from –2 to
13.81 have been used for phosphate esters31,32
.
3.2 PRESENT INVESTIGATION
This chapter describes the systematic study of the hydrolysis of
PNPDPP by different hydroxamate ions (II) using cationic surfactants. The
hydroxamate ions are believed to act as -nucleophiles and are good deacylating and
dephosphorylating agents42-49
. The -nucleophiles possess lone pair of electrons on
an atom adjacent to the nucleophilic centre and show remarkable reactivity as
compared to normal nucleophile (k -nuc / k normal nuc.) with comparable pKa values.
N O
C O
R
R'
(II)
The extent of micellar catalysis is expected to be dependent on the
relative amount of substrate incorporated into the micelles. PNPDPP being highly
lipophilic gets more incorporated into the micelles. Due to biological and
environmental significance, the detoxification reaction is one of the essential aspects.
This chapter reports the esterolytic cleavage of p-nitrophenyl diphenyl phosphate
(PNPDPP) (Scheme I) by different hydroxamic acids (Table 3.2) using cationic
surfactants (Table 3.3).
Biomimetic models such as micelles23,29,33
, reverse micelles34
,
microemulsions35,36
, cyclodextrins13
, liposomes and vesicles37
have been used to
accelerate reactions of phosphate esters with nucleophiles. The quantitative
explanations of reactivity in micelles have been attempted using pseudophase model.
89
Table 3.2
Hydroxamic Acids Used in Present Investigation
R' C N
O OH
R
HYDROXAMIC
ACID
R’ R STRUCTURAL
FORMULA
MOL.
WT.
Acetohydroxamic Acid
(AHA)
CH3
H
C
N
O
OH
H3C
H
75.01
Benzohydroxamic Acid
(BHA)
C6H5
H
C
N
O
OHH
137
Salicylhydroxamic Acid
(SHA)
2-OHC6H4
H
C
OH
N H
O
HO
153.1
N-Phenylbenzo-
hydroxamic acid
(PBHA)
C6H5
C6H5
C
O
NOH
213
p-Fluoro-N-Phenyl-
benzohydroxamic acid.
(p-F-PBHA)
p-F- C6H4
C6H5
C
O
NOH
F
230
90
Table 3.3
Cationic Surfactants Used in Present Investigation.
RN+R’X
–
SURFACTANT R R’ X– STRUCTURE M.W.
Cetyltrimethylammonium
bromide (CTAB)
C16H33 (CH3)3 Br–
N+Br
364.5
Cetyltrimethylammonium
chloride (CTACl)
C16H33
(CH3)3
Cl–
N+Cl-
320
Tetradecyltrimethylamm-
onium bromide (TTAB)
C14H29
(CH3)3
Br–
N+Br-
336.4
Dodecyltrimethylammo-
nium bromide (DTAB)
C12H25
(CH3)3
Br–
N+
Br-
308.3
Cetylpyridinium bromide
(CPB)
C16H33
C5H5
Br–
N+Br-
384.4
Cetylpyridinium chloride
(CPC)
C16H33
C5H5
Cl–
N+Cl
358
Cetyldimethylethylammo
-nium bromide (CDEAB)
C16H33
(CH3)2
C2H5
Br–
N+Br-
378.5
91
P
O
O NO2 + Nu NO2OP
O
Nu +
Scheme- I
3.3 EXPERIMENTAL
Materials
N-Phenylbenzohydroxamic acid, p-fluoro-N-phenylbenzohydroxamic
acid and benzohydroxamic were prepared by literature method38
.
Salicylhydroxamic acid, acetohydroxamic acid, cetyltrimethylammonium
bromide, tetradecyltrimethylammonium bromide, dodecyltrimethylammonium
bromide, cetylpyridinium bromide and cetylpyridinium chloride were obtained
from Sigma /Aldrich. p-Nitrophenyl diphenyl phosphate was prepared at Defence
Research Development Establishment, Gwalior (Scheme II) by condensation of
diphenyl chlorophosphate with p-nitrophenol in the presence of triethylamine.
P
O
O
O
O Cl HO NO2+
Diphenyl chlorophosphate
p-nitrophenol
Triethylamine
P
O
O
O
O NO2
p-nitrophenyl diphenyl phosphate
Scheme II
A sample of PNPDPP was also obtained from Prof. C. A. Bunton, University of
California, USA.
Solution Preparation
The buffer (Borate 0.01M) solutions were prepared by using single
distilled water. Due to solubility problem, N-substituted hydroxamic acids (PBHA
and p-F-PBHA) were prepared in 20% (v/v) acetonitrile-water mixtures. The
92
solution of PNPDPP was prepared in 50% (v/v) acetonitrile. The pH of the
reaction medium was measured by using Systronics 335 pH meter.
Kinetics
All the reactions were followed at 27 0C ± 0.2
0C with Unicam
UV2-300 spectrophotometer equipped with Techne circulator (C-85A)
thermostated cell holder. The rate of nucleophilic reaction with PNPDPP was
determined by following the increase in absorption of p-nitrophenoxide anion
(400 nm). All the kinetic experiments were performed at an ionic strength of 0.1
M (with KCl). Buffer employed for whole reaction process was borate. For all the
kinetic runs the absorbance/time result fit very well to the first-order rate equation:
ln (A∞ -At) = ln (A∞ -A0) – kt (1)
The pseudo-first order rate constants can be determined by least
square fits. A progressive reaction profile is shown in Figures 3.1 and 3.2. The
spectrum exhibits an increase in absorbance at 400 nm with the formation of
p-nitrophenoxide ion during the course of reaction. The pKa values of hydroxamic
acids were determined pH meterically using Systronics (type-335) pH meter.
3.4 RESULTS AND DISCUSSION
Pseudo-first order rate constant for the reaction of p-nitrophenyl
diphenyl phosphate with hydroxamate ions (Scheme I) have been determined at 27° C
in 4 % (v/v) MeCN aqueous media with the nucleophiles in large excess over the
substrate. pH dependent rate constant increased with increasing pH in the range 6.6 -
11.0 pH. The rate of reaction shows drastic change at the pH where the deprotonation
of hydroxamic acid was found maximum, i.e. pKa of hydroxamic acid (Table 3.4).
The pKa of all the hydroxamic acids were determined in the presence and absence of
93
Figure 3.1 Repeat scans (1-15) every minute for the reaction of PNPDPP with PBHA in
CTAB (1.8mM) micellar media at 8.0 pH.
Figure 3.2 Repeat scans (1-20) every minute for the reaction of PNPDPP with BHA in
CTAB (2.74 mM) micellar media at 9.0 pH.
WAVELENGTH (nm)
AB
SOR
BA
NC
E
WAVELENGTH (nm)
AB
SOR
BA
NC
E
94
Table 3.4
pH-dependent pseudo-first order rate constants for the nucleophilic substitution reaction of
p-nitrophenyl diphenyl phosphate with N-phenylbenzohydroxamate (PBHA–) ion in micellar
solution at 270 C.
pH kobsd. 103/s–1
6.6 0.26
7.3 0.92
8.0 1.81
8.5 4.0
10.0 9.0
11.0 10.5
REACTION CONDITIONS
Temp. = 27 °C, = 0.1 M KCl, [PNPDPP] = 0.5 x 10– 4 M, [PBHA] = 0.5 x 10–3 M,
[CTAB] = 1.8 x 10–3 M, Medium = 4% (v/v) MeCN.
CTAB (Table 3.6). The effect of cationic surfactants on the pKa was not significant.
The pKa value, thus determined under micellar condition agreed with the value
determined pH-metrically in 10% (v/v) MeCN medium.
3.4.1 Effect of pH and Determination of pKa
The pH-rate constant profile for the reaction of PNPDPP with
N-phenylbenzohydroxamate ion in cationic micellar solution is typical of pH-
dependent nucleophilic reaction. Hydroxamic acids have been suggested to behave
either as NH or OH acids depending on solvents39-41
. Numerous studies indicate that
hydroxamic acids are OH, rather than NH acids in H2O39
. It is known that the anion
95
of hydroxamic acid (N–O–) acts as a reactive species in the hydrolysis of esters
41-43.
Consequently, the pKa for the conversion of the N–OH to N–O– form play important
role for the cleavage of phosphate esters.
A pH-rate constant profile for the nucleophilic cleavage of 0.05 mM
PNPDPP by 0.5 mM hydroxamate ion in CTAB micellar media (1.8 mM) gave the
apparent pKa values for each hydroxamic acids. Typically, the pseudo-first-order rate
constants for the reaction of PNPDPP were determined at different pH values in
between 6.7 to 11.0. The representative pH-rate constant profile for the cleavage of
0.05 mM PNPDPP by 0.5 mM N-phenylbenzohydroxamic acid in CTAB micellar
media (1.8 mM) at 270 C is shown in Figure 3.3. The plot of log kψ vs pH (Figure 3.3)
gave a break at pH 8.9 which was taken as a systematic pKa for the PBHA under
CTAB micellar conditions.
3.4.2 Effect of Nucleophile Concentrations
In order to investigate the nucleophilic catalysis of hydroxamate ions
for the decomposition of organophosphate, the reaction of PNPDPP in the
presence and absence of hydroxamate ions have been studied. By comparison, the
observed pseudo-first-order rate constant in the presence of hydroxamic acids
(kobs) and in buffer alone (k0), it is apparent that the addition of hydroxamic acids
under these conditions increases the rate of nucleophilic reaction of PNPDPP
significantly.
The nucleophile concentration dependent first order rate constant was
determined for the reaction of PNPDPP with hydroxamic acids in excess. Table
3.5 summarizes the data for the reaction of PNPDPP with different concentration
of N-phenylbenzohydroxamate ion at pH 9.1. Kinetic data provides additional
support for the hypothesis that hydroxamic acid is acting as a nucleophilic
96
Figure 3.3 Plots of first-order rate constants vs. pH for the reaction of
PNPDPP with N-phenylbenzohydroxamate ion.
catalyst for the reaction of PNPDPP. Equation (2) describes the reaction of
PNPDPP with nucleophiles, k0 defined in equation (3) correspond to the intercept
in the kobs versus [Nu] plot. The kH2O term may assume some significance for very
weak nucleophiles and at very low OH–
concentrations. At high pH the intercept,
got dominated by the kOH
– term.
kobs
= k0 + k
Nu [Nu] (2)
k0 = kH2O
+ kOH–[OH
– (3)
Plotting kobs vs. [Nu–] gave a straight line (Figure 3.4) with intercept k0. This
indicates that competition with other nucleophiles i.e. OH–
and H2O is not expected
and hydroxamate ions are very strong -nucleophiles41,43-49
for the nucleophilic attack
at the P center of PNPDPP and kobs is simply given by kobs=kNu
[Nu].
0
2
4
6
8
10
12
6 7 8 9 10 11 12
pH
ko
bs.
103/s
-1(A
)
-4
-3
-2
-1
0
(A)
(B)
log
kψ
(B
)
97
Table 3.5
Nucleophile concentration dependent first-order rate constants for the reaction
of PNPDPP with N-phenylbenzohydroxamate ion in micellar media.
[PBHA] x 10–3
M kHA
obsd.103/s–1
0.0 0.19
0.25 4.30
0.50 7.75
0.75 11.2
1.00 13.8
REACTION CONDITIONS
Temp.= 27oC, pH = 9.12, μ = 0.1 M KCl, [PNPDPP] = 0.5 x 10–4 M , [CTAB] = 1.80 x 10–3 M
0
2
4
6
8
10
12
14
16
0 0.25 0.5 0.75 1 1.25
[PBHA] 10-3
M
kH
Aobsd.1
03/s
-1
Figure 3.4 Kinetic plot of kHA
obs.103/s
–1 versus concentration of PBHA in the
micellar media.
98
3.4.3 Kinetic Studies in Micelles
The rate constant data for the nucleophilic substitution reaction of
PNPDPP with N-phenylbenzohydroxamate ion at 9.12 pH are given in Table 3.6. The
results follow typical biphasic pattern. Cationic micelle catalyzed the reaction and kψ
passed through maxima with increasing surfactant concentration. The rate maxima are
independent of the type of surfactants but the magnitude of rate constant depends on
type of surfactants. The rate-surfactant concentration profiles obtained with various
surfactants / catalysts are characteristic of micelle catalyzed reaction50
. The variation
increasing alkyl chain lengths of the surfactants, i.e. with increasing aggregation
number of micelle. The rate constants below the cmc is difficult to quantify due to
reactant induced micellization and interaction with non-micellized surfactants. The
reaction was slightly faster when the counterion was chloride than bromide ion
(Table 3.6). The fractional ionic dissociation, α, of micelle is often little affected by
the nature or the concentration of the counterion. In other words, the micellar surface
appears to be saturated with counterions, and the fractional coverage β = 1 – α, is
constant. If β is constant, the rate of reaction should increase as substrate is taken up
by the micelles, but once substrate is fully bound, the rate should be independent of
added surfactant or counterion.
Kinetic results indicate that CTAB is more reactive than TTAB. The
effect of DTAB is insignificant. The kψ values increase with increase in the order is
mainly due to the increase in electrical surface potential of the micelle and partially
due to an increase of hydrophobicity of palisade layer of micelle. The hydroxamate
ion concentration in the vicinity of the micellar surface is expected to increase with
increasing the aggregation number. The electrostatic attraction of the cationic head
groups of the surfactants at the micelle surface to the nucleophilic anion counterions
leads to augmentation of the local concentration of the nucleophile, while
99
Table 3.6
Kinetic rate data for the nucleophilic substitution reactions of p-nitrophenyl diphenyl phosphate with
N-phenylbenzohydroxamate ion in cationic micellar solutions.
[Surfactant]
x 103 / M
kobs. x 103 / s
–1
CPC CPB CTACl CTAB CDEAB TTAB DTAB
0 0.13 0.13 0.13 0.13 0.13 0.13 0.13
0.36 8.50 6.98 6.15 4.09 5.70 3.70 –
0.90 8.90 8.50 7.00 7.46 6.60 4.70 –
1.80 9.33 9.13 7.68 7.73 7.24 5.22 0.40
3.60 9.20 8.85 7.40 7.22 6.90 5.16 –
5.40 8.40 8.10 6.90 5.98 6.10 4.75 0.90
7.00 7.61 7.30 6.10 4.85 5.30 4.45 –
8.00 7.00 6.70 5.70 4.10 4.80 4.25 –
9.00 6.40 6.10 5.22 3.32 4.31 4.13 2.12
REACTION CONDITIONS:
pH = 9.12, [PNPDPP] = 0.5 x 10– 4 M, [PBHA] = 0.5 x 10–3 M, Medium = 4.0% MeCN, μ = 0.1 M KCl
100
incorporation of the substrate in the micelle leads to a higher local concentration of
the substrate50-53
.
This enhanced concentration of the reactants accounts for the higher rate
of reaction. Implicit in this explanation is the requirement that the reactive site of the
PNPDPP be situated in close proximity to the nucleophile, that is, at the micelle-water
interface, the Stern layer. The subsequent addition of the cationic surfactant after cmc
caused a decrease in the reaction rate possibly due to the decrease in the catalyst /
reagent concentration in the micellar pseudophase. The excess of unreactive
counterions (X–) compete with hydroxamate ions for available sites in the stern layer.
The rate of the nucleophilic reaction of anionic nucleophile depends on
the binding of the substrate molecule hydrophobically and electrostatically attraction
of anionic nucleophlies in to the micelle50,54
. Kinetic rate data for the reaction of
PNPDPP with various hydroxamate ions in micellar solution of cetylpyridinium
bromide shows that the rate of reaction increases with increasing hydrophobicity of
the nucleophiles. By comparing the reaction rate of N-substituted and unsubstituted
hydroxamate ions in aqueous media (Table 3.7), it can be concluded that the micellar
system shows differential reactivity than bulk aqueous media.
Table 3.7 shows the rate data for the reaction of PNPDPP with various
hydroxamate ions of different hydrophobicity. In aqueous media, reactivities of
p-F-PBHA and PBHA are comparable and slightly lower than SHA, BHA and AHA.
In aqueous micellar media p-F-PBHA and PBHA shows higher reactivity than SHA,
BHA and AHA. The solubility of PBHA and PNPDPP in pure buffered aqueous
solution was quite low. However, they are readily soluble in CTAB micelles. Since
these hydrophobic substrates also partition into the micellar pseudophase, increased
localization of catalysts and substrates lead to rate acceleration in the cleavage of
phosphate esters.
101
Table 3.7
Kinetic rate data for the reaction of p-nitrophenyl diphenyl phosphate with hydroxamate ions in cationic
micellar solutions of cetylpyridinium bromide at 270 C
a.
[CPB] / mM
kobs. x 103/s–1
p-F-PBHA PBHA SHA BHA AHA
(8.7)b (8.9)
b (7.2)
b (8.6)
b (9.2)
b
0 0.10 0.13 0.19 0.15 0.12
0.36 7.25 6.98 0.72 0.52 –
0.90 8.71 8.50 1.20 0.81 0.50
1.80 9.60 9.13 1.59 1.28 0.70
3.60 9.30 8.85 1.50 1.19 –
5.40 8.30 8.10 1.41 1.00 0.65
7.00 7.10 7.30 1.10 0.80 –
8.00 6.30 6.70 0.91 0.75 –
9.00 5.44 6.10 0.73 0.71 0.63
REACTION CONDITIONS:
pH = 9.12, [HA] = 0.5 x 10-3 M, [PNPDPP] = 0.5 x 10–4 M, a
μ = 0.1 M KCl .
b The pKa of nucleophiles in micelles are given in parentheses.
102
Similar observations have also been made for the reaction of Paraoxon
with hydroxamate ions42
. Paraoxon is less hydrophobic than PNPDPP therefore the
reactivity of hydroxamate ions in micellar solution is not significant (data not shown).
The hydrolysis reaction for PNPDPP proceeding via the steps outlined
in Scheme III. A point of interest was whether the catalysts were consumed as the
reaction proceeded or were regenerated and indeed a true catalyst. When the
concentration of PNPDPP was in large excess, the release of p-nitrophenoxide ion
also followed pseudo-first order kinetics and yielded a consistent kobs value. With
such a small proportion of the catalyst, the kinetics could only be first order if the
catalyst was not consumed during the course of reaction. There is no direct
experimental evidence for the complete regeneration of hydroxamic acids. Other
α-nucleophiles like o-iodosylcarboxylates55
, oximate56
, hydroperoxide57
and
hydroxybenzotriazoles24,25
rapidly cleaved phosphate esters with turnover in micelle.
P
O
PhO
PhO
O NO2 R' C N
O O
R+ P
O
PhO
PhO
ONO2Nu +
+ H2O
OHNO2P
PhO
PhOO
O
++Nu
Scheme- III
103
3.4.4 Quantitative Treatment of Rate Data in Micelles
The Pseudophase Model:
Rate effects on bimolecular reactions in association colloids are
rationalized by the pseudophase model51,58
, in which the aggregates and bulk solvent,
typically water, are regarded as distinct reaction regions. The overall reaction rate is
the sum of the rate in each pseudophase and depends upon the rate constants and
reactant concentrations in each pseudophase. A crucial requirement of this model is
that component distributes them much faster than the reaction.
The influence of cationic micelles on the reaction rate can be
quantitatively analyzed according to the model of the micellar pseudophase59,60
. We
assume that the presence of cationic surfactant does not change the pKa of the
hydroxamic acids in water. Under these experimental conditions, scheme IV can be
proposed for applying pseudophase model.
In this scheme IV subscript w and m indicates aqueous and micellar
pseudophases, respectively and Dn represents the micellized surfactant, that is
[Dn] = [DT] – cmc, where [DT] is the stoichiometric surfactant concentration and cmc
the critical micellar concentration, obtained under the experimental conditions as the
minimum surfactant concentration required to observe any kinetic effect.
Scheme IV considers the distribution of PNPDPP between the aqueous
and micellar pseudophases, KmPNPDPP
. This association constant of PNPDPP in
micellar systems with the value of KmPNPDPP
= 7000 M–1
, is agreed with literature
value56
. The distribution of the hydroxamate ion, HA, between both pseudophases is
considered through the distribution constant KmHA
. The different reactivities in the
104
aqueous and micellar pseudophases have been taken into account through the
corresponding second order rate constants: k2w and k2
m. The values of k2w have been
obtained by studying the reaction in the absence of the surfactants.
PNPDPP Dn+w PNPDPPm
+
HAmHAm + Dn
PRODUCTSk2mk2w
Km PNPDPP
Km HA
The hydroxamate concentration in the micellar pseudophase has been
defined as the local, molar concentration within the micellar pseudophase: [HA]T =
[HA]m / [DnV], where V is the molar volume in dm3 mol
–1 of the reaction region and
[Dn]V denotes the micellar fractional volume in which the reaction occurs. V was
assumed equal to the partial molar volume of the interfacial reaction region in the
micellar pseudophase, determined by Bunton59
as 0.14 dm3 mol
–1. Micellar binding
of both substrate, PNPDPP and hydroxamate ions HAs, is governed by hydrophobic
interactions and the equilibrium constants KmPNPDPP
and KmHA
are expressed by
referring these concentrations to the total volume of the observed rate constants, kobs,
based on scheme IV and on the above considerations, is given by the following
equation:
Scheme-IV
105
kobs. =
k2w
+k2
m
VKm
PNPDPPKm
HA[Dn]
Km
PNPDPP( 1 + [Dn] ) Km
HA( 1 + [Dn] )
[HA]T
Second order rate constants at the micellar interface and association
constants of the hydroxamate ions to the cationic micelles were obtained by fitting
equation 4 to the experimental data and listed in Tables 3.8 and 3.9. In Figures 3.5 and
3.6, the kψ calculated values with this treatment are shown by solid lines.
The results presented in Table 3.8 allow us to study the influence of the
nature of the micelle for the reaction of PNPDPP with N-phenylbenzohydroxamate
ion. From the fitting equation 4, k2w = 0.13 x 10
–3 M
–1 s
–1 was obtained in aqueous
medium. Likewise we obtained value of k2m
= 4.20 x 10–2
M–1
s–1
, for the highly
reactive CPB-PBHA combination. The CPB-PBHA system shows 323 fold micellar
catalysis (k2m
/ k2w) for the cleavage of PNPDPP.
A very important aspect to take into account when dealing with
nucleophilic nucleophilic reactions in micelles is the incorporation of different
nucleophiles into the micelle. Table 3.8 lists the substrate and nucleophile distribution
constants in cetylpyridinium bromide micelle. As stated earlier, N-substituted
hydroxamic acids are more hydrophobic, associate with CPB micelle through
hydrophobic interactions (Kmp-FPBHA
= 86.2 M–1
; KmPBHA
= 73.7 M–1
). The N–OH
groups are considerably ionized as N–O– at pH 9.1 and therefore also bind to
quarternary ammonium headgroup through electrostatic attractions. N-substituted
hydroxamate ions, p-F-PBHA and PBHA shows 351 and 323 fold micellar catalysis
(k2m
/k2w) towards reaction of PNPDPP, whereas SHA, BHA, and AHA shows around
36, 44 and 31 fold catalysis respectively.
(4)
106
Figure 3.5 Simulated rate-surfactant profiles for the reaction of p-nitrophenyl diphenyl
phosphate with N-phenylbenzohydroxamate ion (solid lines are predicted
values with model).
Fig.3.6 Simulated rate-surfactant profiles for the reaction of p-nitrophenyl
diphenyl phosphate with hydroxamate ions in cetylpyridinium bromide
micellar solutions (solid lines are predicted values with model).
○ CPC
● CPB
■ CTACl
■ CTAB
▲ CDEAB
▲ TTAB
○ p-F-PBHA
● PBHA
■ SHA
■ BHA
▲ AHA
k
ob
s. s
–1
ko
bs.
s–1
107
Table 3.8
Kinetic parameters obtained by applying pseudophase model for the Nucleophilic reaction of PNPDPP with
N-phenylbenzohydroxamate ions in the presence of cationic micelles.
wk2 /(M-1
·s-1
) PNDPP
mK /(M-1
) HA
mK /(M-1
) mk2 /(M-1
·s-1
)
PBHA (CPyCl) 0.13x10-3
7000 86.2 (3.930.15)x10-2
PBHA (CPyBr) 0.13x10-3
7000 73.7 (4.200.11)x10-2
PBHA (CTACl) 0.13x10-3
7000 73.4 (3.560.10)x10-2
PBHA (CTAB) 0.13x10-3
7000 118.6 (2.160.22)x10-2
PBHA(CDEAB) 0.13x10-3
7000 96.8 (2.590.09)x10-2
PBHA (TTAB) 0.13x10-3
7000 43.9 (3.790.07)x10-2
108
Table 3.9
Kinetic parameters obtained by applying pseudophase model for the Nucleophilic reaction of PNPDPP with
hydroxamate ions in the presence of CPB (Cetylpyridinium bromide) micelles.
wk2 /(M-1
·s-1
) PNDPP
mK /(M-1
) HA
mK /(M-1
) mk2 /(M-1
·s-1
)
p-F-PBHA 0.10x10-3
7000 94.1 (3.510.17)x10-2
PBHA 0.13x10-3
7000 73.7 (4.200.11)x10-2
SHA 0.19x10-3
7000 67.5 (6.780.92)x10-3
BHA 0.15x10-3
7000 50.5 (6.620.93)x10-3
AHA 0.12x10-3
7000 5.2 (3.670.47)x10-2
109
The study was undertaken with a view to develop a hydroxamate
function based ‘hydrolysing nucleophile’ in micellar medium to detoxify the toxic
phosphorus esters. For this purpose, PNPDPP was selected as simulant of nerve
agents as huge kinetic data are available in open literature on this substrate with other
nucleophiles, which could be compared with the data obtained with hydroxamic acids
(HAs). To achieve this target, the HAs and surfactants with varying structures were
selected for kinetic study and the best combination of ‘HA-Surfactants’ was
formulated as potential esterolytically detoxifying system against nerve agents.
110
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