Formation of soman (1,2,2-trimethylpropyl methylphosphonofluoridate) via fluoride-induced reactivation of soman-inhibited aliesterase in rat plasma.

After incubation (37 degrees) of rat blood or plasma with the nerve agent soman, (CH3)3C(CH3)C(H)O(CH3)P(O)F (7.7 microM), for 10 min, only a small amount of this organophosphate (7 or 1%, respectively) is left, as determined enzymatically (acetylcholinesterase) and gas chromatographically. Comparison of the results obtained with both analyses shows that this residual soman consists only of its P(-)-isomers. Incubation (25 degrees) at pH 4.8-6.1 of such soman-treated rat blood or plasma with sodium fluoride (2.5 mM) for 0.5 min leads to (i) a substantial increase of the P(-)-soman concentration, and (ii) a (partial) reactivation of the soman-inhibited aliesterase, proportional to the amount of generated P(-)-soman. These results indicate strongly that added fluoride ions regenerate soman by a reversal of the inhibition reaction. From the relationship between percentage of reactivation and increase of soman concentration the aliesterase concentration in rat plasma is calculated as 2.6 microM. Sodium fluoride has a similar effect in blood taken from rats to which soman was administered intravenously. The increase of the P(-)-soman concentration is higher with higher sodium fluoride concentrations and at lower pH values. In accordance with the absence of aliesterase, addition of sodium fluoride does not induce an increase of the P(-)-soman concentration in soman-treated human plasma.