Revisiting the reactivity of oximate α-nucleophiles with electrophilic phosphorus centers. Relevance to detoxification of sarin, soman and DFP under mild conditions

Article abstract of DOI:10.1039/b609658c

Following a potentiometric determination of the relevant pK_a values of the (R₁R₂)CNOH functionality, the second order rate constants (k^Ox) for reaction of a large set of oximate bases with two model organophosphorus esters, i.e. bis-(4-nitrophenyl) phenylphosphonate (BNPPP) and bis-(4-nitrophenyl)methylphosphonate (BNPMP), and three toxic compounds, i.e., sarin (GB), soman (GD) and diisopropylphosphorofluoridate (DFP), in aqueous as well as a 30: 70 (v/v) H₂O-Me₂SO mixture have been measured. The corresponding Bronsted-type nucleophilicity plots of log k^Ox vs. pK _a^Ox reveal a clear tendency of the reactivity of the oximates to suffer a saturation effect with increasing basicity in aqueous solution. In the case of BNPMP and the three toxic esters, this behaviour is reflected in a levelling off at pK_a ≈ 9 but a more dramatic situation prevails in the BNPPP system where the attainment of maximum reactivity at pK_a ≈ 9 is followed by a clear decrease in rate at higher pK_a's. Interestingly, a number of data reported previously by different authors for the sarin, soman and DFP systems are found to conform rather well to the curvilinear Bronsted correlations built with our data. Based on this and previous results obtained for reactions at carbon centers, it can be concluded that the observed saturation effect is the reflection of an intrinsic property of the oximate functionality. An explanation of this behavior in terms of an especially strong requirement for desolvation of the oximates prior to nucleophilic attack which becomes more and more difficult with increasing basicity is suggested. This proposal is supported by the observed changes in pK_a^Ox and k^Ox brought about by a transfer from H₂O to a 30: 70 H₂O-Me₂SO mixture. The implications of the saturation effect on the efficiency of oximates as nucleophilic catalysts for smooth decontamination are emphasized. Also discussed is the effect of basicity on the exalted (α-effect) reactivity of these bases. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b609658c

SUPPLEMENTARY MATERIAL
Ox
Table S.1: Second order rate constants, k , for nucleophilic substitution of sarin and soman,
as derived from a potentiometric monitoring of the reactions in the presence of an external
a,b
buffer.
Ox
-3
Ox
3
-1 -1
Oxime
pKa
[Ox] , mol dm
External
Buffer
k , dm mol s
0
Sarin
Soman
-
-3
-3
-3
-3
-3
-3
-3
-3
-3
-3
-3
-3
-3
-3
-3
-3
-3
-3
-3
-3
-3
1
a
6.54
2x10
x10
HEPES
HEPES
HEPES
HEPES
HEPES
HEPES
HEPES
HEPES
HEPES
TAPS
0.31
0.33
-
4
0.14
0.25
0.40
0.45
1.45
1.40
-
2
6.98
7.13
2x10
2x10
3
1.52
1.43
4.70
4.86
4.69
8.00
8.10
8.04
6.45
5.05
4.90
8.90
8.70
13.40
13.52
-
4
x10
7
7.75
8.05
2x10
4
8
x10
x10
8
9
2x10
2.25
2.15
-
2
4
x10
x10
HEPES
HEPES
TAPS
8.27
8.30
2x10
4x10
-
1
.d
1.90
-
4
x10
6x10
x10
6x10
x10
6x10
x10
6x10
HEPES
TAPS
1
1
2
3
4
9.30
9.55
9.85
9.95
4.30
4.40
5.34
5.82
5.30
5.70
-
8
TAPS
1
1
1
TAPS
8
TAPS
TAPS
8
TAPS
14.70
13.10
TAPS
-3
(
a) Total HEPES or TAPS concentration of 0.10 mol dm ; 1:1 HEPES (pH=7.49) or TAPS
-3
-3
(
pH=8.30) buffers; [sarin] or [soman] = 10 mol dm ; (b) see ref. 41 for the complete
description of the potentiometric methodology.

Figure S1: Plots illustrating the dependence of kobs on the oximate concentration at constant
pH and T=25°C for the phosphonate BNPPP; upper line: 2,3-butandionemonoxime 1:1
buffers (11, pH=9.30); lower line, CH SCH COCH=NOH 1:1 buffers (1c, pH=8.16 ) in
3
2
-3
aqueous solution; I = 0.1 mol dm KCl.
0
0
0
0
0
0
0
.30,3
11
.25
0,25
.2
0
1c
,2
.15
0,15
.1
0
,1
.05
0,05
0
0
0,002
0.002
0,004
0.004
0,006
0.006
0,008
0.008
0,01
0.01
0,012
0.012
0
-
-
-3
[
Ox ]
[
,
O
m
x]
o
,
l
M
dm

Figure S2: Plot illustrating the dependence of kobs on the oximate concentration at constant
pH for the phosphonate BNPMP in 2-pyridiniumaldoximate 1:1 buffers (7, pH = 9.00) at
2
5°C in 30:70 (v/v) H O-Me SO.
2
2
1
1
1
0
0
0
0
0
.41,4
.21,2
1
.80,8
.60,6
.40,4
.20,2
0
0
0
0,002
0,004
0,006
0,008
0,01
0,012
0,014
0.002 0.004 0.006 0.008 0.01 0.012 0.014
-
-
-3
[
O x ], M
[
Ox ], mol dm

Figure S3: Plot illustrating the dependence of kobs on the oximate concentration at constant
pH for the phosphonate BNPPP reacting in 2-pyridinealdoximate 1:1 buffers (13 , pH = 9.85)
at 25°C in aqueous solution. For avoiding overlap with substitution of the second p-
nitrophenoxide group of BNPPP, the kobs values were determined by monitoring the first
substitution up to 50% release of the first mole of this anion.
0
0
0
0
0
0
.10,1
0,08
.08
.06
0,06
.04
0,04
.02
0,02
0
0
0,001
0.001
0,002
0.002
0,003
0.003
-
0,004
0.004
0,005
0.005
0,006
0.006
0
[
O
-
x], M
-3
[
Ox ], mol dm

Figure S4: Oscilloscope trace illustrating the first order decomposition of soman by the 2-
pyridiniumaldoxime 7 at pH = 7.49 in a 1:1 HEPES buffer, as derived from a potentiometric
-
monitoring of the resulting increase in the F concentration. See text.

Figure S5 : Graph according to eq. (7) illustrating the decomposition of DFP in an external
-3
-3
HEPES buffer containing a total pyridinium aldoxime (7) concentration of 4x10 mol dm
pH = 7.49; T = 25°C).
(

Figure S6: Effect of the oximate concentration on the observed first-order rate constant, kobs,
as measured potentiometrically for the decomposition of DFP in HI-6 buffers (3, pH=7.13) at
2
5°C in aqueous solution.
0
0
0
0
0
0
0
.006
0
,006
.005
0,005
.004
0,004
.
0
0
,
0
0
3
03
02
01
.
0
0
,
0
0
2
.
0
0
,0
0
1
0
0
0.02
0,02
0.04
0,04
0.06
0,06
0.08
0,08
0.1
0,1
0
-
-
[OX]
-3
[
Ox ], mol dm