2
$\begingroup$

According to literature, dimethyl paraoxon has a reaction rate constant for the aging (spontaneous dealkylation) of acetylcholinesterase of $\pu{0.186 h-1}$, a spontaneous reactivation rate constant of $\pu{1.01 h-1}$, and an inhibition reaction rate constant of $\pu{1.2 \times 10^6 M-1 min-1}$, compared to $\pu{0.022 h-1}$, $\pu{0.022 h-1}$, and $\pu{2.2 \times 10^6 M-1 min-1}$, respectively for paraoxon.[1] It has been shown that the process of aging, at least for the nerve agent tabun, proceeds through cleavage of the $\ce{O-C}$ bond [2], which would presumably mean that a carbocation is generated as an intermediate, and thus, ethyl breakage, rather than methyl, should be more favorable. However, as the referenced paper shows, this is not the case, and methyl paraoxon, rather than paraoxon (with ethyl groups), ages more rapidly, and is also more susceptible to spontaneous reactivation. Furthermore, paraoxon (with ethyl groups) also has a higher inhibition rate constant. Why is this so?

References:

[1] Franz Worek, Horst Thiermann, Ladislaus Szinicz, Peter Eyer, "Kinetic analysis of interactions between human acetylcholinesterase, structurally different organophosphorus compounds and oximes," Biochemical Pharmacology 2004, 68(11), 2237–2248 (doi: https://doi.org/10.1016/j.bcp.2004.07.038).

[2] Eugénie Carletti, He Li, Bin Li, Fredrik Ekström, Yvain Nicolet, Mélanie Loiodice, Emilie Gillon, Marie T. Froment, Oksana Lockridge, Lawrence M. Schopfer, Patrick Masson, Florian Nachon, "Aging of Cholinesterases Phosphylated by Tabun Proceeds through O-Dealkylation," Journal of the American Chemical Society 2008, 130(47), 16011–16020 (doi: https://doi.org/10.1021/ja804941z)

$\endgroup$

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Browse other questions tagged or ask your own question.