title: Detoxification of VX and Other V-Type Nerve Agents in Water at 37 °C and pH 7.4 by Substituted Sulfonatocalix[4]arenes.
abstract: Sulfonatocalix[4]arenes with an appended hydroxamic acid residue can detoxify VX and related V-type neurotoxic organophosphonates with half-lives down to 3 min in aqueous buffer at 37 °C and pH 7.4. The detoxification activity is attributed to the millimolar affinity of the calixarene moiety for the positively charged organophosphonates in combination with the correct arrangement of the hydroxamic acid group. The reaction involves phosphonylation of the hydroxamic acid followed by a Lossen rearrangement, thus rendering the mode of action stoichiometric rather than catalytic. Nevertheless, these calixarenes are currently the most efficient low-molecular-weight compounds for detoxifying persistent V-type nerve agents under mild conditions. They thus represent lead structures for novel antidotes that allow treatment of poisonings by these highly toxic chemicals.
authors.affiliation: Fachbereich Chemie-Organische Chemie, Technische Universität Kaiserslautern, Erwin-Schrödinger-Strasse, 67663, Kaiserslautern, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schneider
authors.affiliation: Institut für Pharmakologie und Toxikologie der Bundeswehr, Neuherbergstrasse 11, 80937, München, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Bierwisch
authors.affiliation: Institut für Pharmakologie und Toxikologie der Bundeswehr, Neuherbergstrasse 11, 80937, München, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Koller
authors.affiliation: Institut für Pharmakologie und Toxikologie der Bundeswehr, Neuherbergstrasse 11, 80937, München, Germany.
authors.forename: Franz
authors.identifier: 0000-0003-3531-3616
authors.initials: F
authors.lastname: Worek
authors.affiliation: Fachbereich Chemie-Organische Chemie, Technische Universität Kaiserslautern, Erwin-Schrödinger-Strasse, 67663, Kaiserslautern, Germany. kubik@chemie.uni-kl.de.
authors.forename: Stefan
authors.identifier: 0000-0003-0526-7014
authors.initials: S
authors.lastname: Kubik
keywords: calixarenes; chemical warfare agents; detoxification; hydroxamic acids; scavengers