Rates of Reaction of Vicinally Substituted Hydroxamic Acids with Isopropyl Methylphosphonofluoridate (Sarin)¹

The Chemotherapy of Poisoning by Organophosphate Anticholinesterases

“…A number of hydroxamic acids have been tested as antidotes to poisoning by sarin (Askew, 1956;Epstein and Freeman, 1956) and by DFP (Funke, Benoit, and Jacob, 1955) but they were only effective in doses far too high to be of practical significance. Studies of the effect of structure on the direct reactivity of hydroxamic acids with organophosphates showed that the deciding factor was, as with the dihydroxybenzenes, the ionization constant and that the reactivity could be predicted reasonably accurately from the ionization constant alone (Stolberg and Mosher, 1957;Green, Sainsbury, Saville, and Stansfield, 1958). It was also possible to show that for reactivity at physiological pH (7-4), there was an optimum ionization constant equivalent to a pKa of about 8 (Steinberg, Swidler, and Seltzer, 1957).…”

Pharmacological Antagonists of the Anticholinesterase Agents

“…Studies of the reaction rates of various hydroxamic acids with Sarin have been reported (SWIDLER and STEINBERG 1956, STEINBERG and BoLGER 1956, STOLBERG and MosHER 1957, GREEN et al1958, SWIDLER et al 1959. The most rapidly reactive of all thehydroxamic acids seems to be cishexahydrophthalohydroxamic acid (STOLBERG and MosHER 1957).…”

Molecular Catalysis and Interactions in Aqueous Solutions

“…Hackley et al and other workers (7)(8)(9)(10)(11)(12)(13) have found that the reaction of sarin with hydroxamic acids involves a nucleophilic'attack by the hydroximate ion as the rate determining step. The tautomeric form of the ion was proposed to be the reactive species in order to explain the very high activity of these compounds.…”