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

Abstract

Following a potentiometric determination of the relevant pKa values of the (R1R2)C=NOH 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 Brønsted-type nucleophilicity plots of log k(Ox)vs. pKa(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 pKa approximately 9 but a more dramatic situation prevails in the BNPPP system where the attainment of maximum reactivity at pKa approximately 9 is followed by a clear decrease in rate at higher pKa'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 Brønsted 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 pKa(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 (alpha-effect) reactivity of these bases.

Characteristic features of the change in reactivity of supernucleophilic functional surfactants in acyl group transfer processes

“…The special interest in study of the reactivity of typical representatives of this class of reagents, oximate ions (Ox -), is first of all due to the fact that effective antidotes are found among them: re-activators of the acetylcholinesterase inhibited by organophosphorus compounds, the search for which is being vigorously pursued at the moment [4]. There is no doubt that the level of biological activity of the antidotes is directly connected with the high reactivity of Ox -ions [4][5][6][7]. Detailed kinetic analysis of their behavior suggests that the nucleophilicity of Ox -ions cannot be described in terms of a single Brönsted equation [4][5][6][7].…”

Hydroxylamines and Oximes: Biological Properties and Potential Uses as Therapeutic Agents

“…These calculations assumed that the Brønsted linear equation holds for the kinetic scheme for reactivation shown in equation 20. It should be noted, however, that a recent study showed that above pK a = 9 the corresponding Brønsted plot deviates from linearity for nucleophilic displacements of oximates at the P atom of a variety of OPs, a behavior that was attributed by the authors to an increase in solvation 158 . Yet, the observed break in the linear curve could also be explained by a change in the rate-limiting step of the addition-elimination S N 2 reaction.…”

Alkali‐Metal‐Ion Catalysis and Inhibition in the Nucleophilic Displacement Reaction of Y‐Substituted Phenyl Diphenylphosphinates and Diphenylphosphinothioates with Alkali‐Metal Ethoxides: Effect of Changing the Electrophilic Center from PO to PS

“…[1][2][3][4][5][6][7][8][9][10][11][12] These reactions have been reported to proceed through a concerted mechanism or a stepwise pathway depending on the nature of the nucleophiles and substrates. [2][3][4][5][6][7][8][9][10][11][12] Alkaline ethanolysis of aryl dimethylphosphinates has been concluded to proceed through a pentacoordinate intermediate, its formation being the rate-determining step (RDS) on the basis that s o constants result in significantly better Hammett correlation than s À constants.…”